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CORK Bibliography: Prenatal Drug Exposure



105 citations. September 2011 to present

Prepared: September 2012



Abbott LC; Winzer-Serhan UH. Smoking during pregnancy: Lessons learned from epidemiological studies and experimental studies using animal models. (review). Critical Reviews in Toxicology 42(4): 279-303, 2012. (229 refs.)

Numerous epidemiological studies in the human population clearly indicate that smoking while pregnant has deleterious effects on fetal development as well as long-term adverse consequences on postnatal development and maturation of several organ systems. Low birth weight, sudden infant death syndrome (SIDS), behavioral disorders including attention deficit hyperactivity disorder (ADHD), externalizing and internalizing behavioral problems and conduct disorders in children have all been linked to prenatal exposure to tobacco smoke. The major pharmacologically active chemical found in tobacco smoke is nicotine, and prenatal exposure to nicotine has been shown to have significant effect on the development of multiple organ systems, including the nervous, respiratory, and cardiovascular systems. In this review, we define mainstream and sidestream smoke, summarize the major classes of compounds found in cigarette smoke, and describe how use of laboratory animal models can be used to assess mechanisms of toxicity and risk in the human population in general. We then discuss the association with smoking during pregnancy and the occurrence of reduced lung function, low birth weight, the incidence of congenital structural malformations, SIDS, ADHD, cognitive impairment, and mood disorders in children, and review pertinent experimental studies using a variety of animal models of developmental nicotine exposure, including, rats, mice, monkeys, lambs, and pigs that have increased our understanding of the pathophysiology of these disorders.

Copyright 2012, Informa HealthCare


Adams EK; Markowitz S; Kannan V; Dietz PM; Tong VT; Malarcher AM. Reducing prenatal smoking: The role of state policies. American Journal of Preventive Medicine 43(1): 34-40, 2012. (33 refs.)

Background: Maternal smoking causes adverse health outcomes for both mothers and infants and leads to excess healthcare costs at delivery and beyond. Even with substantial declines over the past decade, around 23% of women enter pregnancy as a smoker and though almost half quit during pregnancy, half or more quitters resume smoking soon after delivery. Purpose: To examine the independent effects of higher cigarette taxes and prices, smokefree policies, and tobacco control spending on maternal smoking prior to, during, and after a pregnancy during a period in which states have made changes in such policies. Methods: Data from pooled cross-sections of women with live births during 2000-2005 in 29 states plus New York City (n = 225,445) were merged with cigarette price data inclusive of federal, state, and local excise taxes, full or partial bans on smoking in public places, and tobacco control spending. Probit regression models using a mixed panel, state fixed effects, and time indicators were used to assess effect of policies on smoking (during 3 months before pregnancy); quitting by last 3 months of pregnancy; and having sustained quitting at the time of completing the postpartum survey. Results: Multivariate analysis indicated that a $1.00 increase in taxes and prices increases third-trimester quits by between 4 and 5 percentage points after controlling for the other policies and covariates. Implementing a full private worksite smoking ban increases quits by the third trimester by an estimated 5 percentage points. Cumulative spending on tobacco control had no effect on pregnancy smoking rates overall. Association of tobacco control policies with maternal smoking varied by age. Conclusions: States can use multiple tobacco control policies to reduce maternal smoking. Combining higher taxes with smokefree policies particularly can be effective.

Copyright 2012, Elsevier Science


Akuete K; Oh SS; Thyne S; Rodriguez-Santana JR; Chapela R; Meade K et al. Ethnic variability in persistent asthma after in utero tobacco exposure. Pediatrics 128(3): E623-E630, 2011. (53 refs.)

BACKGROUND: The effects of in utero tobacco smoke exposure on childhood respiratory health have been investigated, and outcomes have been inconsistent. OBJECTIVE: To determine if in utero tobacco smoke exposure is associated with childhood persistent asthma in Mexican, Puerto Rican, and black children. PATIENTS AND METHODS: There were 295 Mexican, Puerto Rican, and black asthmatic children, aged 8 to 16 years, who underwent spirometry, and clinical data were collected from the parents during a standardized interview. The effect of in utero tobacco smoke exposure on the development of persistent asthma and related clinical outcomes was evaluated by logistic regression. RESULTS: Children with persistent asthma had a higher odds of exposure to in utero tobacco smoke, but not current tobacco smoke, than did children with intermittent asthma (odds ratio [OR]: 3.57; P = .029). Tobacco smoke exposure from parents in the first 2 years of life did not alter this association. Furthermore, there were higher odds of in utero tobacco smoke exposure in children experiencing nocturnal symptoms (OR: 2.77; P = .048), daily asthma symptoms (OR: 2.73; P = .046), and emergency department visits (OR: 3.85; P = .015) within the year. CONCLUSIONS: Exposure to tobacco smoke in utero was significantly associated with persistent asthma among Mexican, Puerto Rican, and black children compared with those with intermittent asthma. These results suggest that smoking cessation during pregnancy may lead to a decrease in the incidence of persistent asthma in these populations.

Copyright 2011, American Academy of Pediatrics


Alverson CJ; Strickland MJ; Gilboa SM; Correa A. Maternal smoking and congenital heart defects in the Baltimore-Washington Infant Study. (editorial). Obstetrical & Gynecological Survey 66(7): 408-409, 2011. (2 refs.)


Antonopoulos CN; Sergentanis TN; Papadopoulou C; Andrie E; Dessypris N; Panagopoulou P et al. Maternal smoking during pregnancy and childhood lymphoma: A meta-analysis. International Journal of Cancer 129(11): 2694-2703, 2011. (50 refs.)

Results from epidemiological studies exploring the association between childhood lymphoma and maternal smoking during pregnancy have been contradictory. This meta-analysis included all published cohort (n = 2) and case-control (n = 10) articles; among the latter, the data of the Greek Nationwide Registry for Childhood Hematological Malignancies study were updated to include all recently available cases (-2008). Odds ratios (ORs), relative risks and hazard ratios were appropriately pooled in three separate analyses concerning non-Hodgkin lymphoma (NHL, n = 1,072 cases), Hodgkin lymphoma (HL, n = 538 cases) and any lymphoma (n = 1,591 cases), according to data availability in the included studies. An additional meta-regression analysis was conducted to explore dose-response relationships. A statistically significant association between maternal smoking (any vs. no) during pregnancy and risk for childhood NHL was observed (OR = 1.22, 95% confidence interval, CI: 1.03-1.45, fixed effects model), whereas the risk for childhood HL was not statistically significant (OR = 0.90, 95 CI: 0.66-1.21, fixed effects model). The analysis on any lymphoma did not reach statistical significance (OR = 1.10, 95 CI = 0.96-1.27, fixed effects model), possibly because of the case-mix of NHL to HL. No dose-response association was revealed in the meta-regression analysis. In conclusion, this meta-analysis points to a modest increase in the risk for childhood NHL, but not HL, among children born by mothers smoking during pregnancy. Further investigation of dose-response phenomena in the NHL association, however, warrants accumulation of additional data.

Copyright 2011, Wiley-Blackwell


Ayer JG; Belousova E; Harmer JA; David C; Marks GB; Celermajer DS. Maternal cigarette smoking is associated with reduced high-density lipoprotein cholesterol in healthy 8-year-old children. European Heart Journal 32(19): 2446-2453, 2011. (47 refs.)

Aims: Smoking in pregnancy is common. Its effects on lipoprotein levels and arterial structure in childhood are not well characterized. We aimed to determine the effects of maternal smoking in pregnancy on lipoprotein levels and arterial wall thickness in healthy pre-pubertal children. Methods and results A community-based longitudinal study with prospective ascertainment of exposure to smoking in pregnancy and environmental tobacco smoke (ETS) since birth and then lipoprotein and arterial measurements at age 8 years. In 616 newborn infants (gestation >36 weeks and birth weight >2.5 kg) data were collected prospectively by questionnaire on smoking in pregnancy and ETS exposure in childhood. At age 8-years, 405 of the children had measurements of lipoproteins, blood pressure (BP) and carotid intima-media thickness. Children born to mothers who smoked in pregnancy had lower HDL cholesterol [1.32 vs. 1.50 mmol/L, 95% confidence interval (CI) for difference -0.28 to -0.08, P = 0.0005], higher triglycerides (1.36 vs. 1.20 mmol/L, 95% CI for ratio 1.01-1.30, P = 0.04) and higher systolic BP (102.1 vs. 99.9 mmHg, 95% CI for difference 0.6-3.8, P = 0.006). After adjustment for maternal passive smoking, post-natal ETS exposure, gender, breast feeding duration, physical inactivity, and adiposity, smoking in pregnancy remained significantly associated with lower HDL cholesterol (difference -0.22 mmol/L, 95% CI -0.36 to -0.08, P = 0.003) but not with higher systolic BP. Neither smoking in pregnancy nor post-natal ETS exposure was associated with alterations of carotid artery wall thickness. Conclusion Smoking in pregnancy is independently associated with significantly lower HDL cholesterol in healthy 8-year-old children.

Copyright 2011, Oxford University Press


Bakker H; Jaddoe VWV. Cardiovascular and metabolic influences of fetal smoke exposure. (review). European Journal of Epidemiology 26(10): 763-770, 2011. (118 refs.)

Many epidemiological studies showed associations of low birth weight with cardiovascular disease, type 2 diabetes and obesity. The associations seem to be consistent and stronger among subjects with a postnatal catch up growth. It has been suggested that developmental changes in response to adverse fetal exposures might lead to changes in the fetal anatomy and physiology. These adaptations may be beneficial for short term, but may lead to common diseases in adulthood. Maternal smoking during pregnancy is one of the most important adverse fetal exposures in Western countries, and is known to be associated with a 150-200 g lower birth weight. An accumulating body of evidence suggests that maternal smoking during pregnancy might be involved in pathways leading to both low birth weight and common diseases, including cardiovascular disease, type 2 diabetes and obesity, in adulthood. In this review, we discuss epidemiological studies focused on the associations of maternal smoking with fetal growth and development and cardiovascular and metabolic disease in later life. We also discuss potential biological mechanisms, and challenges for future epidemiological studies.

Copyright 2011, Springer


Bakker R; Kruithof C; Steegers EAP; Tiemeier H; Mackenbach JP; Hofman A et al. Assessment of maternal smoking status during pregnancy and the associations with neonatal outcomes. Nicotine & Tobacco Research 13(12): 1250-1256, 2011. (22 refs.)

Single assessment of smoking during pregnancy may lead to misclassification due to underreporting or failure of smoking cessation. We examined the percentage of mothers who were misclassified in smoking status based on single assessment, as compared with repeated assessment, and whether this misclassification leads to altered effect estimates for the associations between maternal smoking and neonatal complications. This study was performed in 5,389 mothers participating in a prospective population-based cohort study in the Netherlands. Smoking status was assessed 3 times during pregnancy using questionnaires. Information on birth weight and neonatal complications was obtained from hospital records. For categorizing mothers per smoking status, Cohen's Kappa coefficient was .86 (p < .001) between single and repeated assessments. Of all mothers who reported nonsmoking or first trimester-only smoking in early pregnancy, 1.7% (70 of 4,141) and 33.7% (217 of 643), respectively, were reclassified to continued smoking based on repeated assessment. Younger, shorter lower educated mothers who had non-European ethnicity experienced more stress, consumed more alcohol, and did not use folic acid supplements had higher risk of underreporting their smoking status or failure of smoking cessation. Marginal differences were found on the associations of maternal smoking with neonatal complications between single or repeated assessment. Our results suggest that single assessment of smoking during pregnancy leads to underestimation of the continued smoking prevalence, especially among mothers who reported quitting smoking in first trimester. However, this underestimation does not materially change the effect estimates for the associations between maternal smoking and neonatal outcomes.

Copyright 2011, Oxford University Press


Barros MCM; Mitsuhiro SS; Chalem E; Laranjeira RR; Guinsburg R. Prenatal tobacco exposure is related to neurobehavioral modifications in infants of adolescent mothers. Clinics 66(9): 1597-1603, 2011. (36 refs.)

INTRODUCTION: Prenatal tobacco exposure interferes with neonatal outcomes. OBJECTIVE: To determine the neonatal neurobehavioral effects of in utero tobacco exposure. METHODS: This prospective cross-sectional study included healthy, term, with birth weight appropriate for gestacional age neonates without exposure to alcohol, drugs, or infections, born to adolescent mothers without psychiatric disorders or post-traumatic stress. Infants were classified according to in utero tobacco exposure, as identified by the Composite International Diagnostic Interview administered to mothers. Neurobehavior was assessed by the Neonatal Intensive Care Unit Network Neurobehavioral Scale. Both tools were administered between 24 and 72 hours after birth. Neurobehavioral outcomes were compared between exposed and non-exposed infants by ANOVA. The associations between neurobehavioral scores and number of cigarettes smoked were studied by linear correlation. RESULTS: During the study, 928 newborns of adolescent mothers were born, and 388 were included in the study. Of these, 23 were exposed to tobacco, and 365 neonates were not exposed. There were no differences between the groups in gestational age, birth weight, post-natal age at the exam, or time between last feeding and exam. Exposed neonates showed higher scores on arousal (p = 0.004), excitability (p = 0.003), and stress/abstinence signals (p = 0.019) and a lower score on regulation (p = 0.025). After adjusting for the type of anesthesia, mode of delivery, gender, age at neurologic exam, exam duration and time between last feeding and exam, differences in arousal and excitability remained significant. The mean number of cigarettes consumed daily was positively correlated with lethargy (p = 0.013) and inversely with attention (p = 0.043). CONCLUSIONS: Neonates exposed in utero to tobacco showed worse neurobehavioral performance between 24 and 48 hours of life.

Copyright 2011, Hospital Clinicas, University of Sao Paulo


Bekkers MBM; Brunekreef B; Smit HA; Kerkhof M; Koppelman GH; Oldenwening M et al. Early-life determinants of total and HDL cholesterol concentrations in 8-year-old children: The PIAMA Birth Cohort Study. PLoS ONE 6(9): e25533, 2011. (28 refs.)

Background: Adult cholesterol concentrations might be influenced by early-life factors, such as breastfeeding and birth weight, referred to as "early programming". How such early factors exert their influence over the life course is still poorly understood. Evidence from studies in children and adolescents is scarce and conflicting. We investigated the influence of 6 different perinatal risk factors on childhood total and HDL cholesterol concentrations and total-to-HDL cholesterol ratio measured at 8 years of age, and additionally we studied the role of the child's current Body Mass Index (BMI). Methods: Anthropometric measures and blood plasma samples were collected during a medical examination in 751 8-year-old children participating in the prospective Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study. Linear and logistic regression were performed to estimate associations of total and HDL cholesterol concentrations with breastfeeding, birth weight, infant weight gain, maternal overweight before pregnancy, gestational diabetes and maternal smoking during pregnancy, taking into account the child's current BMI. Results: Linear regressions showed an association between total-to-HDL cholesterol ratio and maternal pre-pregnancy overweight (beta = 0.15, Confidence Interval 95% (CI): 0.02, 0.28), rapid infant weight gain (beta = 0.13, 95% CI: 0.01, 0.26), and maternal smoking during pregnancy (beta = 0.14, 95% CI: 0.00, 0.29). These associations were partly mediated by the child's BMI. Conclusion: Total-to-HDL cholesterol ratio in 8-year-old children was positively associated with maternal pre-pregnancy overweight, maternal smoking during pregnancy and rapid infant weight gain.

Copyright 2011, Public Library of Science


Bogdanovic G; Ljuca D; Ostrvica E; Babovic A; Nevacinovic E. Human mature placenta in relation to cigarettes smoking during pregnancy. Healthmed 6(2): 703-710, 2012. (33 refs.)

Introduction: Cigarettes smoking during pregnancy is understood as ante partum (maternal) cause of fetal hypoxia and fetoplacental respiratory insufficiency. It is linked to a number of complications of the pregnancy and increased perinatal morbidity and mortality. The objective of the study was to research whether morphological changes, which could cause disorder of the pregnancy course and fetal growth and development, occur in the placenta of the pregnant women who smoked cigarettes during the entire pregnancy. Patients and methods: Prospective research was carried out in the Gynecology-Obstetrics Clinic of the University Clinical Centre Tuzla and Histology and Embryology Institute of the Medical School of the University in Tuzla. Sixty (60) human mature placentas were analyzed by histo-morphological and quantitative stereological methods. The placentas were divided into two groups, depending on the cigarettes smoking in pregnancy: a) 30 placentas of the pregnant women who smoked more that 15 cigarettes a day during the entire pregnancy (examinee group) and b) 30 placentas of the pregnant women who did not smoke during pregnancy (control group). Placenta volume (V-p) and body weight of the newborn were measured at birth. Volume density (V-v) and total volume (V) of the terminal villi, other villi, perivillous fibrinoid and intervillous space were calculated and compared in both examinee groups. Results. In the placentas of pregnant smokers absolute volume of fibrinoid ((x) over bar =30,15 cm(3); (x) over bar =18,61 cm(3); p<0,01) and other villi (<(x)over bar>=110,62 cm(3); (x) over bar =86,82 cm(3); p<0,05) is significantly higher; and significantly smaller body weight of the newborn at birth (<(x)over bar>=3010,01 g; (x) over bar =3424,33 g; p<0,05). Total volume of the placentas, terminal villi and intervillous space is not significantly different in relation to cigarettes smoking during pregnancy. Conclusion. The result of our quantitative analysis shows that in one cm(3) of the placenta of the pregnant women smokers changes of volume and spatial distribution of the placental parenchyma occur. Because of that fetomaternal exchange of substances is insufficient and body weight of the newborn is decreased, so the placentas of pregnant smokers functionally do not satisfy the needs of normal growth and development of fetus.

Copyright 2012, Drunpp-Sarajevo


Booij L; Benkelfat C; Leyton M; Vitaro F; Gravel P; Levesque ML et al. Perinatal effects on in vivo measures of human brain serotonin synthesis in adulthood: A 27-year longitudinal study. European Neuropsychopharmacology 22(6): 419-423, 2012. (25 refs.)

There is an increasing evidence that prenatal and early postnatal stressors have life long impacts on physical and mental health problems. Animal studies have shown that this could include enduring changes to brain serotonin neurotransmission. In the present study, we tested whether perinatal adversity in humans has a long-term impact on brain serotonin neurotransmission in adulthood. Twenty-six healthy males, recruited from a 27-year longitudinal study, underwent a positron emission tomography scan with the tracer alpha-[C-11]methyl-L-tryptophan (C-11-AMT), as an index of serotonin synthesis capacity. The trapping constant is taken as a proxy for the regional 5-HT synthesis. Birth complications, especially a delivery where the fetus showed signs of physiological distress, predicted lower C-11-AMT trapping in the hippocampus and medial orbitofrontal cortex. Lower C-11-AMT trapping in the medial orbitofrontal cortex was also predicted by maternal smoking and lower birth weight. There were no effects of childhood or recent adversity. This is the first human study reporting associations between perinatal adversity and adult C-11-AMT trapping in the hippocampus and medial orbitofrontal cortex. The associations suggest that limbic serotonin pathways may be particularly vulnerable to environmental challenges during the period when they undergo the most prominent neurodevelopmental changes. In combination with other risk factors, perinatal stressors may contribute to increased vulnerability for psychiatric disorders in which serotonin plays a major role.

Copyright 2012, Elsevier Science


Bublitz MH; Stroud LR. Maternal smoking during pregnancy and offspring brain structure and function: Review and agenda for future research. (review). Nicotine & Tobacco Research 14(4): 388-397, 2012. (41 refs.)

Maternal smoking during pregnancy (MSDP) has been associated with long-term neurobehavioral and cognitive deficits in offspring. Animal models demonstrate alterations in brain structure and function following prenatal nicotine exposure. However, few studies have assessed the relationship between MSDP and brain development in humans. Therefore, the aims of this review are (a) to synthesize findings from the small number of human studies investigating effects of MSDP on offspring brain development and (b) to outline an agenda for future research in this nascent area. We searched MEDLINE and Psychinfo databases for human studies of MSDP and offspring brain structure and/or function. Eleven studies meeting our search criteria were identified; 6 studies investigated effects of MSDP on brain structure; 5 examined effects on brain function. Across studies, MSDP was associated with decreased volume/thickness of the cerebellum and corpus callosum, increased auditory brainstem responses, and lack of coordination across brain regions during information and auditory processing. Results from the small number of human studies revealed effects of MSDP on brain structure and function, highlighting potential neural pathways linking MSDP and offspring neurobehavioral and cognitive deficits. Given the limited amount of research in this area, we propose an agenda for future research. Gold standard studies would utilize longitudinal designs, integrated biological and maternal report measures of MSDP, and repeated measures of brain structure/function and neurobehavioral deficits across key developmental periods.

Copyright 2012, Oxford University Press


Buckingham-Howes S; Oberlander SE; Kim EM; Black MM. Prenatal drug exposure and peer victimization in early adolescence: Testing childhood anxiety/depression and aggression as possible mediators. Journal of Developmental And Behavioral Pediatrics 33(5): 416-422, 2012. (38 refs.)

Objective: Children who are prenatally exposed to drugs may be at risk for emotion dysregulation, including childhood anxiety/depression and aggression, potentially increasing their risk for peer victimization. The objectives of this study were to investigate how prenatal drug exposure relates to adolescent peer victimization and the mediating effects of childhood anxiety/depression and aggression. Methods: Seventy-six prenatally drug exposed (PDE) and 38 nonexposed (NE) adolescent-caregiver dyads followed since birth and middle childhood, respectively, participated in an evaluation during adolescence. In middle childhood, caregivers reported on their child's anxiety/depression and aggression, and children reported on violence exposure. In adolescence, caregivers and adolescents responded to a parallel single-item measure of peer victimization. Analyses were conducted using multivariate linear and logistic regression models, adjusting for covariates, including violence exposure. Results: One-third (33.3%, n = 35) of the sample endorsed peer victimization: 40.8% PDE and 17.6% NE, p = .01. In middle childhood, PDE youth had more aggressive behaviors (11.92 vs 7.45, p < .01) and anxiety/depression symptoms (3.43 vs 1.76, p < .01) than NE youth. Anxious/depressed behavior during childhood mediated the association between prenatal drug exposure and adolescent peer victimization. Aggression was not a significant mediator. Conclusions: The consequences of prenatal drug exposure extend into adolescence. Prenatal drug exposure may interfere with emotion regulation, resulting in anxious/depressed behavior during childhood and significantly increasing the risk for peer victimization during adolescence, even in the presence of violence exposure. Strategies to reduce anxious/depressed behavior among children with a history of prenatal drug exposure may reduce adolescent peer victimization.

Copyright 2012, Lippincott, Williams & Wilkins


Buscicchio G; Piemontese M; Gentilucci L; Ferretti F; Tranquilli AL. The effects of maternal caffeine and chocolate intake on fetal heart rate. Journal of Maternal-Fetal & Neonatal Medicine 25(5): 528-530, 2012. (19 refs.)

Objective: The aim of our study was to analyze the effects of caffeine and chocolate (70% cocoa) on fetal heart rate (FHR). Study design: Fifty pregnant women with uncomplicated gestation, matched for age and parity, underwent computerized FHR recording before and after the consumption of caffeine and then, after one week, before and after 70% cocoa chocolate intake. Computerized cardiotocography (cCTG) parameters were expressed as mean and SD. The differences were tested for statistical significance using the paired t-test, with significance at p < 0.05. Results: The number of uterine contraction peaks, the number of small and large accelerations (10 and 15 beats per minute for 15 seconds), the duration of episodes of high variation and the short-term FHR variation were significantly higher (p < 0.001) after maternal coffee intake. The number of large accelerations, the duration of episodes of high variation and the short-term FHR variation were significantly higher (p < 0.001) after maternal consumption of chocolate, whilst no effect of cocoa was found during contractions. Conclusions: Our results suggest that maternal intake of both caffeine and 70% cocoa have a stimulating action on fetal reactivity. This finding is likely due to the pharmacological action of theobromine, a methilxanthine present in coffee and in chocolate. The correlation between maternal caffeine intake and increased uterine contraction peaks is likely due to the effect of caffeine on the uterine muscle.

Copyright 2012, Informa HealthCare


Chang L; Cloak CC; Jiang CS; Hoo A; Hernandez AB; Ernst TM. Lower glial metabolite levels in brains of young children with prenatal nicotine exposure. Journal of Neuroimmune Pharmacology 7(1, special issue): 243-252, 2012. (38 refs.)

Many pregnant women smoke cigarettes during pregnancy, but the effect of nicotine on the developing human brain is not well understood, especially in young children. This study aims to determine the effects of prenatal nicotine exposure (PNE) on brain metabolite levels in young (3-4 years old) children, using proton magnetic resonance spectroscopy (H-1 MRS). Twenty-six children with PNE and 24 nicotine-unexposed children (controls) were evaluated with a structured examination, a battery of neuropsychological tests, and MRI/H-1 MRS (without sedation). Concentrations of N-acetyl compounds (NA), total creatine (tCR), choline-containing compounds (CHO), myo-inositol (MI), and glutamate+glutamine (GLX) were measured in four brain regions. Children with PNE had similar performance to controls on neuropsychological testing. However, compared to controls, the PNE group had lower MI (repeated measures ANOVA-p=0.03) and tCr levels (repeated measures ANOVA-p=0.003), especially in the basal ganglia of the girls (-19.3%, p=0.01). In contrast, GLX was elevated in the anterior cingulate cortex of the PNE children (+9.4%, p=0.03), and those with the highest GLX levels had the poorest performance on vocabulary (r=-0.67; p<0.001) and visual motor integration (r=-0.53; p=0.01). The amount of prenatal nicotine exposure did not correlate with metabolite concentrations. These findings suggest that PNE may lead to subclinical abnormalities in glial development, especially in the basal ganglia, and regionally specific changes in other neurometabolites. These alterations were not influenced by the amount of nicotine exposure prenatally. However, the effects of PNE on energy metabolism may be sex specific, with greater alterations in girls.

Copyright 2012, Springer


Chen XG; Abdulhamid I; Woodcroft K. Maternal smoking during pregnancy, polymorphic CYP1A1 and GSTM1, and lung-function measures in urban family children. Environmental Research 111(8): 1215-1221, 2011. (65 refs.)

Purpose: Understanding the interplay between genes and in-utero tobacco exposure in affecting child lung development is of great significance. In this study, we tested the hypothesis that tobacco-related lung-function reduction in children differs by maternal polymorphic genes Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase Mu 1 (GSTM1). Materials and methods: Data were collected among 370 children (6-10 years old, 81.6% African-Americans) and their biological mothers visiting a large children's hospital. Study hypotheses were tested using multiple regression method. Results: Among the study sample, 143 mothers smoked throughout pregnancy and 72 smoked on a daily basis. Spirometric measures (mean +/- SD) included were: forced vital capacity(FVC)=1635 +/- 431 mL, forced expiratory volume in the first 1 s (FEV(1))=1440 +/- 360 mL, percent FEV(1)/FVC ratio=89 +/- 12, and forced expiratory flow between the 25% and 75% of PVC (FEF(25-75))=1745 +/- 603 mL In addition to a tobacco effect on FVC (-131 mL, 95% Cl: -245, -17) and FEV(1)/FVC ratio (42, 95% Cl: 1,83), regression analysis controlling for covariates indicated that for the subsample of children whose mothers were CYP1A1*2A homozygous, maternal daily smoking was associated with -734 mL (95% Cl: -1206, -262) reductions in FEV(1) and -825 mL (95% Cl: -909, -795) reductions in PVC; reduced smoking was still associated with -590 mL (95% CI: -629, -551) reductions in PVC. For children of mothers with GSTM1 deletion, persistent daily smoking was associated with -176 mL (95% CI: -305, -47) reductions in FVC. Discussion and conclusions: Maternal smoking during pregnancy was significantly associated with lung-function reduction in children, particularly for those whose mothers possessed the polymorphic CYP1A1*2A and GSTM1 deletion.

Copyright 2011, Elsevier Science


Cirillo PM; Cohn BA; Krigbaum NY; Lee M; Brazil C; Factor-Litvak P. Effect of maternal coffee, smoking and drinking behavior on adult son's semen quality: Prospective evidence from the Child Health and Development Studies. Journal of Developmental Origins of Health and Disease 2(6, special issue): 375-386, 2011. (37 refs.)

Fetal exposure to caffeine is associated with adverse pregnancy outcomes. Animal and human studies suggest that caffeine may have effects on the developing reproductive system. Here we report on mothers' smoking, coffee and alcohol use, recorded during pregnancy, and semen quality in sons in the age group of 38-47 years. Subjects were a subset of the Child Health and Development Studies, a pregnancy cohort enrolled between 1959 and 1967 in the Kaiser Foundation Health Plan near Oakland, California. In 2005, adult sons participated in a follow-up study (n = 338) and semen samples were donated by 196 participants. Samples were analyzed for sperm concentration, motility and morphology according to the National Cooperative Reproductive Medicine Network (Fertile Male Study) Protocol. Mean sperm concentration was reduced by approximately 16 million sperms for sons with high prenatal exposure (5 cups of maternal coffee use per day) compared with unexposed sons (P-value for decreasing trend = 0.09), which translates to a proportionate reduction of 25%. Mean percent motile sperm decreased by approximately 7 points (P-value = 0.04), a proportionate decline of 13%, and mean percent sperm with normal morphology decreased by approximately 2 points (P-value = 0.01), a proportionate decline of 25%. Maternal cigarette and alcohol use were not associated with son's semen quality. Adjusting for son's contemporary coffee, alcohol and cigarette use did not explain the maternal associations. Findings for son's coffee intake and father's prenatal coffee, cigarette and alcohol use were non-significant and inconclusive. These results contribute to the evidence that maternal coffee use during pregnancy may impair the reproductive development of the male fetus.

Copyright 2011, Cambridge University Press


Cleary BJ; Eogan M; O'Connell MP; Fahey T; Gallagher PJ; Clarke T et al. Methadone and perinatal outcomes: A prospective cohort study. Addiction 107(8): 1482-1492, 2012. (51 refs.)

Aims: Methadone use in pregnancy has been associated with adverse perinatal outcomes and neonatal abstinence syndrome (NAS). This study aimed to examine perinatal outcomes and NAS in relation to (i) concomitant drug use and (ii) methadone dose. Design: Prospective cohort study. Setting Two tertiary care maternity hospitals. Participants: A total of 117 pregnant women on methadone maintenance treatment recruited between July 2009 and July 2010. Measurements: Information on concomitant drug use was recorded with the Addiction Severity Index. Perinatal outcomes included pre-term birth (<37 weeks' gestation), small-for-gestational-age (<10th centile) and neonatal unit admission. NAS outcomes included: incidence of medically treated NAS, peak Finnegan score, cumulative dose of NAS treatment and duration of hospitalization. Findings: Of the 114 liveborn infants 11 (9.6%) were born pre-term, 49 (42.9%) were small-for-gestational-age, 56 (49.1%) had a neonatal unit admission and 29 (25.4%) were treated medically for NAS. Neonates exposed to methadone-only had a shorter hospitalization than those exposed to methadone and concomitant drugs (median 5.0 days versus 6.0 days, P = 0.03). Neonates exposed to methadone doses =80 mg required higher cumulative doses of morphine treatment for NAS (median 13.2 mg versus 19.3 mg, P = 0.03). The incidence and duration of NAS did not differ between the two dosage groups. Conclusions: The incidence and duration of the neonatal abstinence syndrome is not associated with maternal methadone dose, but maternal opiate, benzodiazepine or cocaine use is associated with longer neonatal hospitalization.

Copyright 2012, Society for the Study of Addiction to Alcohol and Other Drugs


Cornelius MD; Goldschmidt L; De Genna NM; Larkby C. Long-term effects of prenatal cigarette smoke exposure on behavior dysregulation among 14-year-old offspring of teenage mothers. Maternal and Child Health Journal 16(3): 694-705, 2012. (87 refs.)

In this prospective study, we examined the long-term effects of prenatal cigarette smoke exposure (PCSE) on behavioral dysregulation (BD) in the offspring of adolescent mothers. The adolescent mothers (mean age = 16; range = 12-18; 70% African American) were interviewed about their tobacco use during pregnancy. Offspring were followed to age 14 years (n = 318). Indices of BD outcomes included aggression, rule breaking, externalizing, social problems, attention, distractibility and activity. Multiple measures and multiple informants were used for each construct. Regression analyses were conducted to test if PCSE predicted the BD outcomes, adjusting for demographic and maternal psychological characteristics, and for prenatal exposure to other substances. Independent effects of PCSE were found. Exposed offspring had more aggressive, social, and externalizing problems on both the maternal report and the adolescent self-report measures. They were more active, had more attention problems and greater difficulty with distraction and task orientation. Most PCSE effects were found from first trimester exposure and from exposure to as few as 10 cigarettes per day. These results are consistent with previous findings in this cohort when offspring were 6 and 10 years old, demonstrating that the effects of prenatal cigarette smoke exposure can be identified early and persist into adolescence.

Copyright 2012, Springer


Crane JMG; Keough M; Murphy P; Burrage L; Hutchens D. Effects of environmental tobacco smoke on perinatal outcomes: A retrospective cohort study. (editorial). Obstetrical & Gynecological Survey 66(10): 597-598, 2011. (5 refs.)

The relationship between maternal cigarette smoking during pregnancy and obstetric complications is well established. Previous studies suggest a dose-response relationship with increasing risks for complications associated with increased number of cigarettes smoked and duration of smoking during pregnancy. Little data are available for the risks of adverse pregnancy outcomes among nonsmoking women following exposure to environmental tobacco smoke (ETS; secondhand smoke). A number of meta-analyses have found that ETS reduces mean birth weight and may increase the risk of low birth weight but does not seem to affect gestational age or the rate of preterm birth. There is little or no information on other adverse perinatal outcomes. This retrospective cohort study investigated the effects of ETS on perinatal outcomes in a population of nonsmoking women with singleton pregnancies. The participants were identified using the Newfoundland and Labrador Provincial Perinatal Database. Perinatal outcomes were compared between women with self-reported exposure to ETS (n = 1202; 11.1%) and those with no exposure (n = 10,560; 89.9%). Multiple logistic regression models were used to compare outcomes between the 2 groups, adjusting for maternal age, parity, partnered status, work status, level of education, body mass index, alcohol use, illicit drug use, and gestational age at delivery. The primary study outcome measures were birth weight, head circumference, birth length, and stillbirth. Secondary outcomes examined were prelabor rupture of membranes, gestational age at delivery (including preterm birth < 37 weeks and < 34 weeks of gestation), Apgar score, endotracheal intubation for resuscitation, neonatal intensive care unit admission, congenital anomalies, respiratory distress syndrome, intraventricular hemorrhage, necrotising enterocolitis, neonatal bacterial sepsis, jaundice, and neonatal metabolic abnormalities. Independent risk factors associated with exposure to ETS included lower mean birth weight (adjusted odds ratio [aOR], -53.7 g; 95% confidence interval [CI], -98.4 to -8.9 g), smaller head circumference (aOR, -0.24 cm; 95% CI, -0.39 to -0.08 cm), shorter birth length (aOR, -0.29 cm; 95% CI, -0.51 to -0.07 cm), stillbirth (aOR, 3.35; 95% CI, 1.16-9.72), trends toward preterm birth < 34 weeks (aOR, 1.87; 95% CI, 1.00-3.53), and neonatal sepsis (aOR, 2.96; 95% CI, 0.99-8.86); all P values were <= 0.05. These findings show an association between exposure of nonsmoking pregnant women to ETS with several adverse perinatal outcomes, including reduced birth weight, smaller head circumferences, stillbirth, and shorter birth length.

Copyright 2011, Lippincott, Williams & Wilkins


Delsing C; Van Den Wittenboer E; Liu AJW; Peek MJ; Quinton A; Mongelli M et al. The relationship between maternal opiate use, amphetamine use and smoking on fetal growth. Australian & New Zealand Journal of Obstetrics & Gynaecology 51(5): 446-451, 2011. (35 refs.)

Background: Opiate and amphetamine use during pregnancy is frequently associated with cigarette smoking. The negative effects on fetal growth from nicotine combined with opiates or amphetamines during pregnancy are not well documented. Aims: To investigate the relationship between maternal opiate or amphetamine use and smoking on fetal growth. Methods: A retrospective study was performed comparing pregnancies affected with either opiates or amphetamines with individually matched controls. All mothers smoked cigarettes during pregnancy. The outcome measures included changes in fetal abdominal circumference, head circumference and femur length during the second half of pregnancy and weight, length and head circumference at birth. Results: There were 91 opiate- and 37 amphetamine-affected pregnancies. Deviations from normative data only became apparent from the third trimester. The proportion of infants with a gestation-adjusted birthweight below the 10th percentile was not significantly different in the opiate group compared to their controls 35 (38%). However, there was a significant difference in proportions in the amphetamine group and their controls ( P < 0.001). We then compared antenatal growth patterns between the amphetamine group and their controls. Amphetamine-exposed fetuses showed comparable growth parameters in the second trimester but significantly larger head and abdominal circumferences and longer femoral lengths in the third trimester than their respective controls ( P < 0.05 for all). Conclusions: When combined with cigarette smoking, opiates had no observed independent effect on birth parameters. Unexpectedly, in the amphetamine group, the negative effects of smoking on growth were altered in late pregnancy.

Copyright 2011, Wiley-Blackwell


D'Onofrio BM; Van Hulle CA; Goodnight JA; Rathouz PJ; Lahey BB. Is maternal smoking during pregnancy a causal environmental risk factor for adolescent antisocial behavior? Testing etiological theories and assumptions. Psychological Medicine 42(7): 1535-1545, 2012. (60 refs.)

Background. Although many studies indicate that maternal smoking during pregnancy (SDP) is correlated with later offspring antisocial behavior (ASB), recent quasi-experimental studies suggest that background familial factors confound the association. The present study sought to test alternative etiological hypotheses using multiple indices of adolescent ASB, comparing differentially exposed siblings, and testing assumptions in the sibling-comparison design. Method. The study examined the association between maternal SDP and adolescent-reported ASB, criminal convictions and membership in a group of individuals with early-starting and chronic ASB among 6066 offspring of women from the National Longitudinal Survey of Youth, a representative sample of women in the USA. The analyses controlled for statistical covariates and examined associations while comparing differentially exposed siblings. Results. At the population level, each additional pack of cigarettes per day predicted greater mean adolescent-reported ASB symptoms [ratio of means 1.15, 95% confidence interval (CI) 1.08-1.22], odds of being in the top 10% of ASB [odds ratio (OR) 1.34, 95% CI 1.10-1.65], hazard of a criminal conviction [hazard ratio (HR) 1.51, 95% CI 1.34-1.68] and odds of chronic ASB (OR 1.57, 95% CI 1.25-1.99). SDP robustly predicted most assessments of ASB while controlling for measured covariates. When siblings exposed to differing levels of SDP were compared, however, all of the associations were attenuated and were not statistically significant : adolescent-reported mean ASB (ratio of means 0.86, 95% CI 0.74-1.01), high ASB (OR 0.67, 95% CI 0.41-1.12), criminal conviction (HR 0.98, 95% CI 0.66-1.44) and chronic ASB (OR 0.80, 95% CI 0.46-1.38). Conclusions. The results strongly suggest that familial factors account for the correlation between SDP and offspring adolescent ASB, rather than a putative causal environmental influence of SDP.

Copyright 2012, Cambridge University Press


Dorea JG. Co-exposure and confounders during neurodevelopment: We need them in the bigger picture of secondhand smoke exposure during pregnancy. (editorial). Environmental Research 111(8): 1332-1333, 2011. (10 refs.)


Downard CD; Grant SN; Maki AC; Krupski MC; Matheson PJ; Bendon RW et al. Maternal cigarette smoking and the development of necrotizing enterocolitis. Pediatrics 130(1): 78-82, 2012. (18 refs.)

Background: The maternal variables that affect fetal development and correlate with necrotizing enterocolitis (NEC), the most common gastrointestinal emergency in premature infants, are not well defined. We hypothesized that maternal risk factors were the primary determinant of future development of NEC. Methods: Patients with NEC were identified from an established NICU database and were control-matched with 2 neonates treated at the same institution. The medical records of each patient during the NICU admission as well as the prenatal and delivery record of the patient's mother were reviewed. Perinatal data, including maternal smoking, maternal hypertension, maternal BMI, maternal gestational diabetes, conduct of labor and type of delivery, Apgar scores, types of feedings, and placental pathology, were examined, with P < .05 deemed significant. Results: A total of 73 neonates diagnosed with NEC and 146 matched controls were identified. Medical records for each subject and their mothers were reviewed (438 records total). Maternal cigarette smoking was significantly associated with the future development of NEC (P = .02). Maternal gestational diabetes, maternal hypertension, formula feeding, and pathologic chorioamnionitis or uteroplacental insufficiency did not correlate with NEC. Conclusions: These data identified maternal cigarette smoking as the only risk factor that is associated with the development of NEC in premature infants. Our data imply that smoking delivers toxins and nicotine to the uterine microenvironment that can affect microvascular development and may predispose the fetus to future NEC.

Copyright 2012, American Academy of Pediatrics


Duijts L. Fetal and infant origins of asthma. (review). European Journal of Epidemiology 27(1): 5-14, 2012. (170 refs.)

Previous studies have suggested that asthma, like other common diseases, has at least part of its origin early in life. Low birth weight has been shown to be associated with increased risks of asthma, chronic obstructive airway disease, and impaired lung function in adults, and increased risks of respiratory symptoms in early childhood. The developmental plasticity hypothesis suggests that the associations between low birth weight and diseases in later life are explained by adaptation mechanisms in fetal life and infancy in response to various adverse exposures. Various pathways leading from adverse fetal and infant exposures to growth adaptations and respiratory health outcomes have been studied, including fetal and early infant growth patterns, maternal smoking and diet, children's diet, respiratory tract infections and acetaminophen use, and genetic susceptibility. Still, the specific adverse exposures in fetal and early postnatal life leading to respiratory disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life, and their epigenetic mechanisms may underlie the complex associations of low birth weight with respiratory disease in later life. New well-designed epidemiological studies are needed to identify the specific underlying mechanisms. This review is focused on specific adverse fetal and infant growth patterns and exposures, genetic susceptibility, possible respiratory adaptations and perspectives for new studies.

Copyright 2012, Springer


Duijts L; Jaddoe VWV; van der Valk RJP; Henderson JA; Hofman A; Raat H et al. Fetal exposure to maternal and paternal smoking and the risks of wheezing in preschool children: The Generation R Study. Chest 141(4): 876-885, 2012. (37 refs.)

Background: Previous studies have suggested that fetal smoke exposure is associated with increased risks of wheezing during childhood. The underlying pathways are unknown. We examined the associations of parental smoking during pregnancy with wheezing in preschool children and whether these associations are explained by postnatal smoke exposure or small for gestational age at birth. Methods: This study was embedded in a population-based prospective cohort study. Parental smoking was prospectively assessed by questionnaires. Wheezing was reported at 1 to 4 years. Small for gestational age at birth was available from registries. The analyses were based on 4,574 subjects. Results: Maternal smoking during the first trimester only was not associated with wheezing. Continued maternal smoking in pregnancy was associated with the risk of wheezing at 1 to 4 years (P for trends <.05). The strongest effect estimates were observed for frequent wheezing (four or more episodes of wheezing per year) until age 3 years (OR [95% CI]: age 1,1.64 [1.12-2.40]; age 2, 1.64 [1.01-2.64]; age 3, 2.19 [1.24-3.86]). Among children of nonsmoking mothers, fetal exposure to paternal smoking was not consistently associated with the risks of wheezing. The associations of continued maternal smoking during pregnancy with wheezing symptoms were independent of postnatal smoke exposure or small for gestational age at birth. Conclusions: Fetal exposure to continued maternal smoking is associated with increased risks of wheezing in preschool children. Further research is needed to explore the effects of paternal smoking. Diminishing maternal smoking before conception or in early pregnancy is likely to have the greatest impact on reducing childhood wheezing.

Copyright 2012, American College of Chest Physicians


Durante AS; Ibidi SM; Lotufo JPB; Carvallo RMM. Maternal smoking during pregnancy: Impact on otoacoustic emissions in neonates. International Journal of Pediatric Otorhinolaryngology 75(9): 1093-1098, 2011. (33 refs.)

Objectives: To determine the effect of maternal smoking during pregnancy on transient evoked otoacoustic emissions levels in neonates. Methods: This was a cross-sectional study investigating neonates in the maternity ward of a university hospital in the city of Sao Paulo, Brazil. A total of 418 term neonates without prenatal or perinatal complications were evaluated. The neonates were divided into two groups: a study group, which comprised 98 neonates born to mothers who had smoked during pregnancy; and a control group, which comprised 320 neonates born to mothers who had not. In order to compare the two ears and the two groups in terms of the mean overall response and the mean transient evoked otoacoustic emissions in response to acoustic stimuli delivered at different frequencies, we used analysis of variance with repeated measures. Results: The mean overall response and the mean frequency-specific response levels were lower in the neonates in the study group (p < 0.001). The mean difference between the groups was 2.47 dB sound pressure level (95% confidence interval: 1.47-3.48). Conclusions: Maternal smoking during pregnancy had a negative effect on cochlear function, as determined by otoacoustic emissions testing. Therefore, pregnant women should be warned of this additional hazard of smoking. It is important that smoking control be viewed as a public health priority and that strategies for treating tobacco dependence be devised.

Copyright 2011, Elsevier Science


Ekblad M; Gissler M; Lehtonen L; Korkeila J. Relation of prenatal smoking exposure and use of psychotropic medication up to young adulthood. American Journal of Epidemiology 174(6): 681-690, 2011. (33 refs.)

The study objective was to determine the relation of prenatal smoking exposure to the use of psychotropic medication up to young adulthood by using population-based longitudinal register data consisting of all singletons born in Finland from 1987 to 1989 (n = 175,869). Information on maternal smoking was assessed during antenatal care and received from the Finnish Medical Birth Register. Information on the children's psychotropic medication (1994-2007) was received from the Drug Prescription Register, and the children's psychiatric diagnoses related to outpatient (1998-2007) and inpatient (1987-2007) care were derived from the Finnish Hospital Discharge Register. A total of 15.3% (n = 26,083) of the children were exposed to prenatal smoking. The incidence of psychotropic medication use was 8.3% in unexposed children, 11.3% in children exposed to < 10 cigarettes per day (adjusted odds ratio = 1.36, 95% confidence interval: 1.29, 1.43), and 13.6% in children exposed to > 10 cigarettes per day (odds ratio = 1.63, 95% confidence interval: 1.53, 1.74). The exposure was significantly associated with the risk for all medication use and for both single- and multiple-drug consumption even after adjustment (e.g., mothers' severe psychiatric illnesses). These findings show that exposure to smoking during pregnancy is linked to both mild and severe psychiatric morbidity.

Copyright 2011, Oxford University Press


El Marroun H; Hudziak JJ; Tiemeier H; Creemers H; Steegers EAP; Jaddoe VWV et al. Intrauterine cannabis exposure leads to more aggressive behavior and attention problems in 18-month-old girls. Drug and Alcohol Dependence 118(2-3): 470-474, 2011. (25 refs.)

Background: The development of the fetal endocannabinoid receptor system may be vulnerable to maternal cannabis use during pregnancy and may produce long-term consequences in children. In this study, we aimed to determine the relationship between gestational cannabis use and childhood attention problems and aggressive behavior. Methods: Using a large general population birth cohort, we examined the associations between parental prenatal cannabis and tobacco use and childhood behavior problems at 18 months measured using the Child Behavior Checklist in N=4077 children. Substance use was measured in early pregnancy. Results: Linear regression analyses demonstrated that gestational exposure to cannabis is associated with behavioral problems in early childhood but only in girls and only in the area of increased aggressive behavior (B = 2.02; 95% CI: 0.30-3.73; p = 0.02) and attention problems (B = 1.04; 95% CI: 0.46-1.62; p < 0.001). Furthermore, this study showed that long-term (but not short term) tobacco exposure was associated with behavioral problems in girls (B = 1.16; 95% Cl: 0.20-2.12; p = 0.02). There was no association between cannabis use of the father and child behavior problems. Conclusions: Our results suggest that intrauterine exposure to cannabis is associated with an increased risk for aggressive behavior and attention problems as early as 18 months of age in girls, but not boys. Further research is needed to explore the association between prenatal cannabis exposure and child behavior at later ages. Our data support educating future mothers about the risk to their babies should they smoke cannabis during pregnancy.

Copyright 2011, Elsevier Science


Ellingson JM; Rickert ME; Lichtenstein P; Langstrom N; D'Onofrio BM. Disentangling the relationships between maternal smoking during pregnancy and co-occurring risk factors. Psychological Medicine 42(7): 1547-1557, 2012. (64 refs.)

Background. Maternal smoking during pregnancy (SDP) has been studied extensively as a risk factor for adverse offspring outcomes and is known to co-occur with other familial risk factors. Accounting for general familial risk factors has attenuated associations between SDP and adverse offspring outcomes, and identifying these confounds will be crucial to elucidating the relationship between SDP and its psychological correlates. Method. The current study aimed to disentangle the relationship between maternal SDP and co-occurring risk factors (maternal criminal activity, drug problems, teen pregnancy, educational attainment, and cohabitation at childbirth) using a population-based sample of full- (n = 206 313) and half-sister pairs (n = 19 363) from Sweden. Logistic regression models estimated the strength of association between SDP and co-occurring risk factors. Bivariate behavioral genetic models estimated the degree to which associations between SDP and co-occurring risk factors are attributable to genetic and environmental factors. Results. Maternal SDP was associated with an increase in all co-occurring risk factors. Of the variance associated with SDP, 45% was attributed to genetic factors and 53% was attributed to unshared environmental factors. In bivariate models, genetic factors accounted for 21% (non-drug-, non-violence-related crimes) to 35% (drug-related crimes) of the covariance between SDP and co-occurring risk factors. Unshared environmental factors accounted for the remaining covariance. Conclusions. The genetic factors that influence a woman's criminal behavior, substance abuse and her offspring's rearing environment all influence SDP. Therefore, the intergenerational transmission of genes conferring risk for antisocial behavior and substance misuse may influence the associations between maternal SDP and adverse offspring outcomes.

Copyright 2012, Cambridge University Press


England LJ; Kim SY; Shapiro-Mendoza CK; Wilson HG; Kendrick JS; Satten GA; Lewis CA et al. Maternal smokeless tobacco use in Alaska Native women and singleton infant birth size. Acta Obstetricia et Gynecologica Scandinavica 91(1): 93-103, 2012. (12 refs.)

Objective. To examine the effects of maternal prenatal smokeless tobacco use on infant birth size. Design. A retrospective medical record review of 502 randomly selected deliveries. Population and Setting. Singleton deliveries to Alaska Native women residing in a defined geographical region in western Alaska, 19972005. Methods. A regional medical center's electronic records were used to identify singleton deliveries. Data on maternal tobacco exposure and pregnancy outcomes were abstracted from medical records. Logistic models were used to estimate adjusted mean birthweight, length and head circumference for deliveries to women who used no tobacco (n=121), used smokeless tobacco (n=237) or smoked cigarettes (n=59). Differences in mean birthweight, length and head circumference, 95% confidence intervals and p-values were calculated using non-users as the reference group. Main Outcome Measures. Infant birthweight, crownheel length and head circumference. Results. After adjustment for gestational age and other potential confounders, the mean birthweight of infants of smokeless tobacco users was reduced by 78g compared with that of infants of non-users (p=0.18) and by 331g in infants of smokers (p<0.01). No association was found between maternal smokeless tobacco use and infant length or infant head circumference. Conclusions. We found a modest but non-significant reduction in the birthweight of infants of smokeless tobacco users compared with infants of tobacco non-users. Because smokeless tobacco contains many toxic compounds that could affect other pregnancy outcomes, results of this study should not be construed to mean that smokeless tobacco use is safe during pregnancy.

Copyright 2012, Wiley-Blackwell


Farber HJ. Promoting tobacco to women of reproductive age harms fetuses. (editorial). Chest 141(4): 839-840, 2012. (13 refs.)


Fisher PA; Kim HK; Bruce J; Pears KC. Cumulative effects of prenatal substance exposure and early adversity on foster children's HPA-axis reactivity during a psychosocial stressor. International Journal of Behavioral Development 36(1): 29-35, 2012. (40 refs.)

Dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis stress response has been reported among individuals with prenatal substance exposure and those with early adversity exposure. However, few researchers have examined the combined effects of these risk factors. Patterns of HPA reactivity among maltreated foster children with and without prenatal substance exposure (N = 53; ages 9-12 years) were examined using the Trier Social Stress Test for Children. Area under the curve with respect to increase (AUC(I)) analyses revealed that prenatal substance exposure or physical abuse significantly increased the likelihood of a negative AUC(I) (i.e., little or no HPA reactivity). Among children with prenatal substance exposure and physical abuse, 85% exhibited a negative AUC(I). The results underscore the importance of addressing this combined risk.

Copyright 2012, Sage Publications


Fisher PA; Lester BM; DeGarmo DS; Lagasse LL; Lin H; Shankaran S et al. The combined effects of prenatal drug exposure and early adversity on neurobehavioral disinhibition in childhood and adolescence. Development and Psychopathology 23(3, special issue): 777-788, 2011. (54 refs.)

The negative effects of prenatal substance exposure on neurobiological and psychological development and of early adversity are clear, but little is known about their combined effects. In this study, multilevel analyses of the effects of prenatal substance exposure and early adversity on the emergence of neurobehavioral disinhibition in adolescence were conducted. Neurobehavioral disinhibition has previously been observed to occur frequently in multiproblem youth from high-risk backgrounds. In the present study, neurobehavioral disinhibition was assessed via behavioral dysregulation and poor executive function composite measures. Data were drawn from a prospective longitudinal investigation of prenatal substance exposure that included 1,073 participants followed from birth through adolescence. The results from latent growth modeling analyses showed mean stability but significant individual differences in behavioral dysregulation and mean decline with individual differences in executive function difficulties. Prior behavioral dysregulation predicted increased executive function difficulties. Prenatal drug use predicted the emergence and growth in neurobehavioral disinhibition across adolescence (directly for behavioral dysregulation and indirectly for executive function difficulties via early adversity and behavioral dysregulation). Prenatal drug use and early adversity exhibited unique effects on growth in behavioral dysregulation; early adversity uniquely predicted executive function difficulties. These results are discussed in terms of implications for theory development, social policy, and prevention science.

Copyright 2011, Cambridge University Press


Florek E; Piekoszewski W; Basior A; Merritt AT; Mazela J; Lechowicz W et al. Effect of maternal tobacco smoking or exposure to second-hand smoke on the levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine of mother and the first urine of newborn. Journal of Physiology and Pharmacology 62(3): 377-383, 2011. (36 refs.)

Tobacco smoking during pregnancy is associated with a variety of negative consequences not only for the mother, but also for the developing fetus. Many studies have shown that carcinogens contained in tobacco smoke permeate across the placenta, and are found in fetus. The aim of the study was to determine the prenatal exposure to tobacco-specific carcinogenic N-nitrosamines on the basis of measurements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine of smoking and second-hand smoke (SHS) exposed women and in the first urine of their newborns. A questionnaire documenting demographics and socio-economical data, smoking habits and exposure to SHS was completed by 121 delivering women near or at term. Maternal concentrations of cotinine and NNAL were measured in urine of the mother and the first urine of her newborn infant by liquid chromatography tandem mass spectrometry (LC/MS/MS). The mean concentration of cotinine was 439.2 ng/mg creatinine and NNAL concentration in urine of smoking women was 74.0 pg/mg creatinine, and for her newborn 78.6 pg/mg creatinine. Among mothers exposed to SHS, cotinine and NNAL mean concentration were 23.1 ng/mg creatinine, and 26.4 pg/mg creatinine. In newborns of SHS exposed mothers during pregnancy the mean concentration of NNAL was 34.1 pg/mg creatinine, respectively. Active tobacco smoking as well as passive exposure to smoking during pregnancy is an important source of tobacco specific N-nitrosamines to the fetuses as evidenced by increased concentrations of this carcinogen. Determination of NNAL in maternal urine samples can be a useful biomarker of prenatal exposure of newborn to carcinogenic nitrosamines.

Copyright 2011, Polish Physiological Society


Frye CA; Paris JJ; Osborne DM; Kippin TE. Prenatal stress alters progestogens to mediate susceptibility to sex-typical, stress-sensitive disorders, such as drug abuse: A review. (review). Frontiers in Psychiatry 2: e-52, 2011

Maternal-offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well understood. Our hypothesis is that allopregnanolone, during gestation, plays a particularly vital role in mitigating effects of stress on the developing fetus and may mediate, in part, alterations apparent throughout the lifespan. Specifically, altered balance between glucocorticoids and progestogens during critical periods of development (stemming from psychological, immunological, and/or endocrinological stressors during gestation) may permanently influence behavior, brain morphology, and/or neuroendocrine-sensitive processes. 5alpha-reduced progestogens are integral in the developmental programming of sex-typical, stress-sensitive, and/or disorder-relevant phenotypes. Prenatal stress (PNS) may alter these responses and dysregulate allopregnanolone and its normative effects on stress axis function. As an example of a neurodevelopmental, neuropsychiatric, and/or neurodegenerative process, this review focuses on responsiveness to drugs of abuse, which is sensitive to PNS and progestogen milieu. This review explores the notion that allopregnanolone may effect, or be influenced by, PNS, with consequences for neurodevelopmental-, neuropsychiatric-, and/or neurodegenerative- relevant processes, such as addiction.

Copyright 2011, Frontiers Media


Geerts CC; Bots ML; van der Ent CK; Grobbee DE; Uiterwaal CSPM. Parental smoking and vascular damage in their 5-year-old children. Pediatrics 129(1): 45-54, 2012. (42 refs.)

BACKGROUND: The relation between smoke exposure in early life, the prenatal period in particular, and the vascular development of young children is largely unknown. METHODS: Data from the birth cohort participating in the WHISTLER-Cardio study were used to relate the smoking of parents during pregnancy to subsequent vascular properties in their children. In 259 participating children who turned 5 years of age, parental smoking data were updated and children's carotid artery intimamedia thickness (CIMT) and arterial wall distensibility were measured by using ultrasonography. RESULTS: Children of mothers who had smoked throughout pregnancy had 18.8 mu m thicker CIMT (95% confidence interval [CI] 1.1, 36.5, P = .04) and 15% lower distensibility (95% CI -0.3, -0.02, P = .02) after adjustment for child's age, maternal age, gender, and breastfeeding. The associations were not found in children of mothers who had not smoked in pregnancy but had smoked thereafter. The associations were strongest if both parents had smoked during pregnancy, with 27.7 mu m thicker CIMT (95% CI 0.2, 55.3) and 21% lower distensibility (95% CI -0.4, -0.03). CONCLUSION: Exposure of children to parental tobacco smoke during pregnancy affects their arterial structure and function in early life.

Copyright 2012, American Academy of Pediatrics


Goetzinger KR; Cahill AG; Macones GA; Odibo AO. The relationship between maternal body mass index and tobacco use on small-for-gestational-age infants. American Journal of Perinatology 29(3): 153-158, 2012. (22 refs.)

We sought to estimate the association between prepregnancy body mass index (BMI) and small-for-gestational-age (SGA) neonates and to determine if there is a synergistic effect of tobacco use on SGA across all BMI strata. We performed a retrospective cohort study of 65,104 patients seen for second-trimester ultrasound. BMI was categorized into underweight, normal weight, overweight, and obese. SGA was defined as birth weight < 10th percentile and < 5th percentile. Univariable and multivariable logistic regression analyses were used to evaluate the association between BMI and SGA. Stratified analyses and tests for effect modification were performed to evaluate for a potential synergistic effect between tobacco use and abnormal prepregnancy BMI on SGA. After controlling for potential confounders, underweight BMI was associated with an increased risk for SGA < 10th percentile (adjusted odds ratio [aOR] 1.8, 95% confidence interval [Cl] 1.5 to 2.1), while overweight (aOR 0.7, 95% Cl 0.7 to 0.8) and obese BMIs (aOR 0.6, 95% Cl 0.5 to 0.7) were associated with a decreased risk of SGA. There was no effect modification of tobacco use on the risk of SGA across all BMI categories. Although both tobacco and underweight BMI are independently associated with SGA, there was no evidence of synergism. Continued emphasis on both smoking cessation and maintenance of normal prepregnancy BMI remains paramount to decreasing the incidence of SGA.

Copyright 2012, Thieme Medical Publishers


Goldschmidt L; Cornelius MD; Day NL. Prenatal cigarette smoke exposure and early initiation of multiple substance use. Nicotine & Tobacco Research 14(6): 694-702, 2012. (45 refs.)

Earlier studies have shown a relation between prenatal cigarette smoke exposure (PCSE) and offspring initiation of tobacco use. No prior study has examined the association between PCSE and early initiation of multiple substances (EIMS) including marijuana and alcohol in addition to tobacco. We investigated the association between PCSE and multiple substance use during adolescence. Pregnant women attending an urban prenatal clinic were selected to participate in the prospective longitudinal study based on their substance use. This study is based on the 16-year follow-up phase and consists of 579 mother-offspring dyads. The women were of lower socioeconomic status, 54% were Black, and 53% reported smoking cigarettes. 52% of the offspring were female. EIMS is a measure of the number of substances initiated prior to age 16 by the adolescents; it ranged from 0 (no initiation, N = 166) to 3 (all, N = 162). Adolescents exposed to tobacco during first trimester of gestation were 1.4 times more likely to initiate multiple substances by age 16 than the nonexposed group. PCSE was a significant predictor of EIMS after controlling for other prenatal exposures, home environment, and demographic characteristics, using ordinal polytomous logistic regression. Other risk factors of EIMS were maternal and adolescent depression, less strict and less involved parenting, offspring attention problems, and lack of participation in a youth club. There is a significant relation between PCSE and adolescent's EIMS.

Copyright 2012, Oxford University Press


Gorog K; Pattenden S; Antova T; Niciu E; Rudnai P; Scholtens S et al. Maternal smoking during pregnancy and childhood obesity: Results from the CESAR Study. Maternal and Child Health Journal 15(7): 985-992, 2011. (40 refs.)

Childhood obesity is a worldwide public health concern. Recent studies from high income countries have demonstrated associations between maternal smoking during pregnancy and children's excess body weight. We examine associations between maternal smoking during pregnancy and children's overweight or obesity, in six countries in the less affluent Central/Eastern European region. Questionnaire data were analysed, for 8,926 singleton children aged 9-12 years. Country-specific odds ratios for effects of maternal smoking during pregnancy on being overweight, and on obesity, were estimated using logistic regression. Heterogeneity between country-specific results, and mean effects (allowing for heterogeneity) were estimated. Positive associations between maternal smoking and overweight were seen in all countries but Romania. While not individually statistically significant, the mean odds ratio was 1.26 (95% CI 1.03-1.55), with no evidence of between-country heterogeneity. Obese children were few (2.7%), and associations between obesity and maternal smoking during pregnancy were more heterogeneous, with odds ratios ranging from 0.71 (0.32-1.57) in Poland to 5.49 (2.11-14.30) in Slovakia. Between-country heterogeneity was strongly related to average persons-per-room, a possible socioeconomic indicator, with stronger associations where households were less crowded. Estimates of dose-response relationships tended to be small and non-significant, even when pooled. Our results provide evidence of a link between maternal smoking in pregnancy and childhood overweight. Associations with obesity, though strong in some countries, were less consistent. Maternal smoking may confer an addition to a child's potential for obesity, which is more likely to be realised in affluent conditions.

Copyright 2011, Springer


Graziotti AL; Hammond J; Messinger DS; Bann CM; Miller-Loncar C; Twomey JE et al. Maintaining participation and momentum in longitudinal research involving high-risk families. Journal of Nursing Scholarship 44(2): 120-126, 2012. (16 refs.)

Purpose: The purpose of the current study was to identify and describe strategies available to optimize retention of a high-risk research cohort and assist in the recovery of study participants following participant dropout. Design and Methods: The Maternal Lifestyle Study (MLS), which investigated the effects of prenatal substance exposure (cocaine or opiates) on child outcome, is a prospective longitudinal follow-up study that extended from birth through 15 years of age. Retention strategies to maximize participation and factors that might negatively impact compliance were examined over the course of five follow-up phases. Findings: At the conclusion of the 15-year visits, MLS had successfully maintained compliance at 76%. Retention rates did not differ by exposure group. Conclusions: Maintaining ongoing participation of enrolled study subjects is a critical element of any successful longitudinal study. Strategies that can be used to reengage and maintain participants in longitudinal research include persistence, flexibility with scheduling, home visits, long-distance trips, increased incentives, and development of a computerized tracking system. Establishing rapport with families and ensuring confidentiality contributed to overall participant retention. The use of multiple tracking techniques is essential. Clinical Relevance: Researchers are challenged to maintain participants in longitudinal studies to ensure the integrity of their research.

Copyright 2012, Wiley-Blackwell


Gunnerbeck A; Wikstrom AK; Bonamy AKE; Wickstrom R; Cnattingius S. Relationship of maternal snuff use and cigarette smoking with neonatal apnea. Pediatrics 128(3): 503-509, 2011. (38 refs.)

BACKGROUND: Maternal smoking is associated with disturbed cardiorespiratory control in the infant. Despite lacking knowledge of whether the harmful effects of smoking are caused by combustion products in tobacco smoke or by nicotine, it has been argued that nicotine-replacement therapy during pregnancy is safer than smoking. OBJECTIVE: The goal of this study was to investigate if the disturbances in cardiorespiratory control associated with maternal smoking are also seen in infants prenatally exposed to snuff. We hypothesized that prenatal nicotine exposure (via moist snuff) causes disturbances in autonomic control and thereby increases the risk of apnea in the newborn. METHODS: In a nationwide Swedish cohort study, we studied associations between maternal tobacco use during pregnancy and neonatal apnea. Of 609 551 live-born singleton infants, 7599 were born to snuff-using mothers, 41 391 and 16 928 were born to light (1-9 cigarettes per day) and heavy (>= 10 cigarettes per day) smokers, respectively. Logistic regression was used to calculate odds ratios, using 95% confidence intervals. RESULTS: Compared with infants of nontobacco users, infants with prenatal exposure to snuff were at an increased risk of apnea even after adjustment for differences in gestational age (odds ratio: 1.96 [ 95% confidence interval: [1.30-2.96]) Smoking was associated with increased risk of apnea before, but not after, adjusting for gestational age. CONCLUSIONS: Snuff use during pregnancy is associated with a higher risk of neonatal apnea than smoking. Maternal use of snuff or nicotine-replacement therapy cannot be regarded as an alternative to smoking during pregnancy.

Copyright 2011, American Academy of Pediatrics


Haltigan JD; Lambert BL; Seifer R; Ekas NV; Bauer CR; Messinger DS. Security of attachment and quality of mother-toddler social interaction in a high-risk sample. Infant Behavior & Development 35(1): 83-93, 2012. (70 refs.)

The quality of children's social interactions and their attachment security with a primary caregiver are two widely studied indices of socioemotional functioning in early childhood. Although both Bowlby and Ainsworth suggested that the parent-child interactions underlying the development of attachment security could be distinguished from other aspects of parent-child interaction (e.g., play), relatively little empirical research has examined this proposition. The aim of the current study was to explore this issue by examining concurrent relations between toddler's attachment security in the Strange Situation Procedure and quality of mother-child social interaction in a high-risk sample of toddlers characterized by prenatal cocaine exposure and low levels of maternal education. Analyses of variance suggested limited relations between attachment security and quality of social interaction. Further research examining the interrelations among various components of the parent-child relationship is needed.

Copyright 2012, Elsevier Science


Hauck FR; Tanabe KO; Moon RY. Racial and ethnic disparities in infant mortality. (review). Seminars in Perinatology 35(4): 209-220, 2011. (96 refs.)

Racial and ethnic disparities in infant mortality in the United States seem to defy all attempts at elimination. Despite national priorities to eliminate these disparities, black infants are 2.5 times more likely to die in infancy compared with non-Hispanic white infants. This disparity is largely related to the greater incidence among black infants of prematurity and low birth weight, congenital malformations, sudden infant death syndrome, and unintentional injuries. This greater incidence, in turn, is related to a complex interaction of behavioral, social, political, genetic, medical, and health care access factors. Thus, to influence the persistent racial disparity in infant mortality, a highly integrated approach is needed, with interventions adapted along a continuum from childhood through the periods of young adulthood, pregnancy, postpartum and beyond. The content and methodologies of these interventions need to be adapted to the underlying behaviors, social influences, and technology and access issues they are meant to address. [Note: The association of both alcohol and drug use with increased risks for infant mortality is referenced.]

Copyright 2011, WB Saunders


Hernandez-Martinez C; Val VA; Subias JE; Sans JC. A longitudinal study on the effects of maternal smoking and secondhand smoke exposure during pregnancy on neonatal neurobehavior. Early Human Development 88(6): 403-408, 2012. (55 refs.)

Maternal smoking during pregnancy is one of the most modifiable causes of morbidity and mortality for both pregnant women and their fetuses. The long-term effects of prenatal exposure to smoke on child behavior and development have been the subject of more extensive research than have the short-term effects. Therefore, the aim of this work is to examine the effects of smoke exposure during pregnancy on neonatal behavior, including in our study a group of mothers exposed to secondhand smoke. The behavior of 282 healthy full-term newborns was assessed using the Neonatal Behavior Assessment Scale (NBAS) at 48-72 h of life. Sixty-two mothers smoked during pregnancy (no mother smoked more than 15 cig/day) and 17 were exposed to secondhand smoke. After adjusting for socio-demographic and obstetric factors, both newborns whose mothers smoked and those whose mothers were exposed to secondhand smoke showed significantly lower scores in the habituation cluster than non-smoking mothers. Exposure to secondhand smoke was also related to lower motor system cluster scores as well as some supplementary items and the newborns of smoking mothers showed significantly lower scores in the state regulation cluster and in some items of the state organization cluster than the newborns of non-smoking mothers. We conclude that active and passive smoking during pregnancy affects several aspects of neurobehavioral development, regardless of socio-demographic, obstetric and pediatric factors.

Copyright 2012, Elsevier Science


Herschl LC; Highland KB; McChargue DE. Prenatal exposure to testosterone interacts with lifetime physical abuse to predict anger rumination and cognitive flexibility among incarcerated methamphetamine users. American Journal on Addictions 21(4): 363-369, 2012. (56 refs.)

The present pilot study hypothesized that degree of exposure to prenatal testosterone interacts with a history of lifetime physical abuse (LPA) to predict the cognitive (anger rumination) and behavioral (intimate partner and interpersonal violence) components of aggression within incarcerated methamphetamine (MA) users. In addition, we hypothesized that the degree of exposure to prenatal testosterone interacts with LPA to predict cognitive flexibility (Stroop Color-Word performance). Male inmate MA users (N = 60) completed neuropsychological and paper/pencil tests. Hand photocopies were also obtained to index prenatal testosterone exposure. Five covariate-adjusted moderation models were tested using anger rumination, intimate partner violence (IPV) perpetration, interpersonal violence perpetration (before and while incarcerated), and Stroop Color-Word T-score as the criteria, prenatal testosterone exposure as the predictor, and LPA as the moderator. Results indicated that, in individuals with a history of LPA, exposure to higher levels of prenatal testosterone exposure predicted greater anger rumination, lower Stroop Color-Word test T-scores, and lower frequencies of IPV perpetration. Findings were not significant in individuals without a history of LPA. This research suggests that biochemical and psychosocial vulnerabilities influence anger rumination and cognitive flexibility, which may render incarcerated MA users at greater risk to relapse or recidivate upon release from prison.

Copyright 2012, Wiley-Blackwell


Hesselink AE; van Poppel MN; van Eijsden M; Twisk JWR; van der Wal MF. The effectiveness of a perinatal education programme on smoking, infant care, and psychosocial health for ethnic Turkish women. Midwifery 28(3): 306-313, 2012. (42 refs.)

Objective: antenatal programmes might be effective in preventing unhealthy lifestyles, poor maternal infant care practices, and poor psychosocial health in ethnic minority women, but there are few evidence-based interventions. For this reason an antenatal education programme, called 'Happy Mothers, Happy Babies' (HMHB) was systematically designed for ethnic Turkish women in the Netherlands. Design: in a non-randomised trial Turkish women attending HMHB (HMHB group) were compared with those receiving care as usual (control group). Setting: Parent-Child Centres, which provide integrated maternity and infant care. Participants: in both the HMHB (n=119) and the control (n=120) group, questionnaires were administered by ethnic Turkish interviewers at three (T0) and eight (T1) months of pregnancy, and two (T2) and six (T3) months after birth. Findings: at baseline, women in the HMHB group had significantly lower educational levels, were less frequently in paid employment, had less knowledge about smoking, and showed more often mildly depressive symptoms. Adjusted analyses showed that HMHB was effective in improving knowledge about smoking (OR=2.73; 95% CI 1.40, 5.31), intention to engage in prevention of sudden infant death syndrome (SIDS) (OR=8.08; 95% CI 3.34, 19.56) and short-term SIDS prevention behaviour (OR=2.22; 95% CI= 1.18, 4.19). However, no intervention effect was found for smoking during pregnancy, SIDS prevention behaviour on the long term, soothing behaviour, serious depressive symptoms, and parent-child attachment. Key conclusions: although we could not demonstrate intervention effects on all outcome measures, the HMHB programme appears to be highly welcome, and reaches an underserved minority group at increased risk for adverse perinatal outcomes. Implications for practice: the HMHB programme is one of the first systematically developed antenatal interventions for ethnic minority women. The programme can be used as a basic antenatal programme, and as a screening opportunity for women who smoke or show serious depressive symptoms.

Copyright 2012, Elsevier Science


Howe LD; Matijasevich A; Tilling K; Brion MJ; Leary SD; Smith GD et al. Maternal smoking during pregnancy and offspring trajectories of height and adiposity: Comparing maternal and paternal associations. International Journal of Epidemiology 41(3): 722-732, 2012. (34 refs.)

Background: Maternal smoking during pregnancy is associated with reduced offspring birth length and has been postulated as a risk factor for obesity. Causality for obesity is not established. Causality is well-supported for birth length, but evidence on persistence of height deficits is inconsistent. Methods: We examined the association between maternal smoking during pregnancy and trajectories of offspring height (0-10 years, N 9424), ponderal index (PI) (0-2 years, N 9321) and body mass index (BMI) (2-10 years, N 8887) in the Avon Longitudinal Study of Parents and Children. To strengthen inference, measured confounders were controlled for, maternal and partner smoking associations were compared, dose-response and associations with post-natal smoking were examined. Results: Maternal smoking during pregnancy was associated with shorter birth length, faster height growth in infancy and slower growth in later childhood. By 10 years, daughters of women who smoke during pregnancy are on average 1.11 cm (SE 0.27) shorter after adjustment for confounders and partner smoking; the difference is 0.22 cm (SE 0.22) for partner's smoking. Maternal smoking was associated with lower PI at birth, faster PI increase in infancy, but not with BMI changes 2-10 years. Associations were stronger for maternal than partner smoking for PI at birth and PI changes in infancy, but not for BMI changes after 2 years. A similar dose-response in both maternal and partner smoking was seen for BMI change 2-10 years. Conclusion: Maternal smoking during pregnancy has an intrauterine effect on birth length, and possibly on adiposity at birth and changes in height and adiposity in infancy. We do not find evidence of a specific intrauterine effect on height or adiposity changes after the age of 2 years.

Copyright 2012, Oford University Press


Hudak ML; Tan RC. Neonatal drug withdrawal. (review). Pediatrics 129(2): article E540-E560, 2012. (165 refs.)

Maternal use of certain drugs during pregnancy can result in transient neonatal signs consistent with withdrawal or acute toxicity or cause sustained signs consistent with a lasting drug effect. In addition, hospitalized infants who are treated with opioids or benzodiazepines to provide analgesia or sedation may be at risk for manifesting signs of withdrawal. This statement updates information about the clinical presentation of infants exposed to intrauterine drugs and the therapeutic options for treatment of withdrawal and is expanded to include evidence-based approaches to the management of the hospitalized infant who requires weaning from analgesics or sedatives.

Copyright 2012, American Academy of Pediatrics


Huizink AC. Prenatal substance use, prenatal stress and offspring behavioural outcomes: Considerations for future studies. Nordic Journal of Psychiatry 66(2): 115-122, 2012. (58 refs.)

Background: Numerous studies have been conducted in which the most common forms of maternal substance use during pregnancy (smoking, drinking or using cannabis) and maternal stress during pregnancy and her offspring's developmental or behavioural outcome have been the focus of interest. These studies seem to suggest that any perturbation caused by maternal substance use or maternal stress during fetal development may have (enduring) effects on offspring behaviour. However, recent developments in research methodology used to examine these associations question whether these prenatal influences actually cause altered offspring outcomes. Aims: This review provides a short overview of previous studies in this field of research, some methodological issues particularly involved in studies that focus on the association between maternal substance use or stress during pregnancy and offspring's outcomes. Furthermore, it introduces several new approaches that have been applied recently to test these associations. Results: Studies that applied these designs to disentangle prenatal influences from associated or inherited factors consistently show an effect of prenatal substance use exposure on birth weight, but yield little evidence for causal effects on behaviour. In contrast, prenatal stress may have a causal effect on some aspects of behaviour, although only one study thus far has been able to differentiate heritable factors from environmental factors.

Copyright 2012, Informa HealthCare


Ingersoll KS; Hettema JE; Cropsey KL; Jackson JP. Preconception markers of dual risk for alcohol and smoking exposed pregnancy: Tools for primary prevention. Journal of Women's Health 20(11): 1627-1633, 2011. (36 refs.)

Objective: Effective preconception primary prevention strategies are needed for women who are at dual risk for alcohol and smoking exposed pregnancies. The current study seeks to identify risk factors that can be used to target intervention strategies at women who are at dual risk. Methods: During a 2-year period from January 2007 through December 2009, 109 women at dual risk for alcohol exposed pregnancy (AEP) and smoking exposed pregnancy (SEP) and 108 women at risk only for AEP were recruited from central Virginia cities. All participants completed a battery of instruments, including assessments of sexual, smoking, and alcohol history and current behavior in each area. Results: Several factors differentiated women at dual risk for SEP/AEP vs. AEP alone, including lower educational level and employment, higher frequency of sexual intercourse, less use of contraception, and higher frequency of alcohol use and mental disorders. Conclusions: Several measurable factors differentiate SEP/AEP women, and these factors could be used to efficiently target primary prevention. The increased severity of women at dual risk of SEP/AEP on a variety of factors demonstrates the importance of preconception prevention efforts for these women.

Copyright 2011, Mary Ann Liebert Inc


Ino T; Shibuya T; Saito K; Ohtani T. Effects of maternal smoking during pregnancy on body composition in offspring. Pediatrics International 53(6): 851-857, 2011. (34 refs.)

Background: The aim of the present cross-sectional study was to use objective methods to assess the association between maternal smoking and body composition in offspring. Methods: A total of 2508 grade 4 school children were enrolled; all underwent lifestyle disease and passive smoking screening. Children were classified into four groups according to their urinary cotinine level and maternal smoking status during or before pregnancy. Items measured on lifestyle disease screening were compared among the four groups. Results: Only degree of obesity (DO) and body mass index (BMI) were significantly associated with maternal smoking during pregnancy. The prevalence of both DO > 20% and DO > 30%, and BMI > 22% and BMI > 25% was highest in children of mothers who smoked during pregnancy. These children had a tendency toward shorter height and increased weight although it was not statistically significant. There were no significant differences between maternal smoking status and lipid profile among groups. Confounders such as food, exercise and sleep were able to be eliminated. Conclusion: Maternal smoking during pregnancy may be an independent risk factor of changing body composition in offspring, that is, shorter height and increased weight.

Copyright 2011, Wiley-Blackwell


Irner TB; Teasdale TW; Nielsen T; Vedal S; Olofsson M. Substance use during pregnancy and postnatal outcomes. Journal of Addictive Diseases 31(1): 19-28, 2012. (40 refs.)

Substance exposure in utero has been associated with physical birth defects and increased risk of regulatory and neuropsychological difficulties. The aims of this study were to describe women who use substances and are in treatment with respect to the type and number of substances used during pregnancy, as well as their background, and to examine the effect substance use has on gestational age, birth weight, and the development of neonatal abstinence syndrome at birth. A sample of 161 pregnant women and their 163 newborn children were included. The results indicate that the children whose mothers continued to use substances throughout their pregnancies were born at a lower gestational age (Chi-Square = 15.1(2), P < .01); children exposed to poly-substances in utero were more affected than those exposed to only alcohol and those with no substance exposure. The same children were more vulnerable to the development of neonatal abstinence syndrome at birth (Chi-Square = 51.7(2), P < .001). Newborns who were exposed primarily to alcohol in utero were at a significant risk of being born with low birth weight (Chi-Square = 8.8(2), P < .05) compared with those exposed to other types of substances. More than 50% of the mothers ceased using any substances (with the exception of tobacco) by birth, indicating that the treatment program did have an interventional effect on the mothers. The mothers' ability to either cease or decrease the use of substances during pregnancy appears to have direct positive effect on their newborns.

Copyright 2012, Taylor & Francis


Jansson LM; Di Pietro JA; Elko A; Williams EL; Milio L; Velez M. Pregnancies exposed to methadone, methadone and other illicit substances, and poly-drugs without methadone: A comparison of fetal neurobehaviors and infant outcomes. Drug and Alcohol Dependence 122(3): 213-219, 2012. (39 refs.)

Background: It is suspected that there is a continuum of impairment among prenatally drug-exposed infants, such that opioid and/or poly-drug exposure confers the highest risk for adverse neonatal outcomes than other classes of substances or single substance exposures. Suitable control groups are difficult to identify. This study compared fetal neurobehavioral development and infant outcomes in offspring of three groups of pregnant women in drug treatment. Exposure groups include: Methadone + other illicit substances (MM + Poly) and two groups currently abstinent for poly drug exposures: Methadone only (MM/A) and Non-Methadone (NM/A). Methods: Forty-nine women (19 MM + Poly, 18 MM/A, and 12 NM/A) underwent fetal monitoring at 36 weeks gestation at peak and trough levels of methadone (MM + Poly; MM/A) or at comparable morning and afternoon times (NM/A). Fetal heart rate (FHR), heart rate variability (FHRV) and motor activity (FM) data were collected. Infant measures included birth outcomes and Neonatal Abstinence Syndrome (NAS) assessment. Results: As compared to the NM/A group, cardiac measures were decreased in methadone-exposed fetuses at peak levels. FHR was significantly more suppressed in the MM + Poly group: FM was significantly lower in the MM/A vs. the NM/A group at both peak and trough, indicative of more persistent exposure effects. The MM + Poly group delivered I week earlier and required NAS pharmacological treatment twice as often as the MM/A group. Conclusions: Results support the notion that poly-drug exposure may potentiate the effects of methadone on the fetus and infant and highlights the need for intensified treatment for methadone-maintained women who abuse other substances.

Copyright 2012, Elsevier Science


Jansson LM; Velez M. Neonatal abstinence syndrome. (review). Current Opinion in Pediatrics 24(2): 252-258, 2012. (55 refs.)

Purpose of review This review will discuss the complex nature of maternal and other factors that can affect the infant's display of neonatal abstinence syndrome (NAS), clinical presentation and treatment of NAS, and the impact of recent findings on future directions for research. Recent findings: NAS has traditionally been described as a constellation of signs/symptoms displayed by the neonate upon withdrawal of gestational opioid exposure; however, recent research has advanced our understanding of this disorder. Other psychoactive substances, such as increasingly prescribed serotonin reuptake inhibitors, may produce an independent or synergistic discontinuation syndrome. The wide variability in NAS presentation has generated interest in the interplay of prenatal and postnatal environmental and genetic factors that may moderate or mediate its expression. Finally, recent advances in the treatment of opioid-dependent pregnant women have suggested buprenorphine as an alternative treatment to methadone during pregnancy, largely due to reduced NAS severity in exposed neonates. Summary: Physicians should be aware of the complexity of the maternal, fetal, and infant factors that combine to create the infant's display of NAS, and incorporate these aspects into comprehensive assessment and care of the dyad. Further research regarding the pathophysiology and treatment of NAS is warranted.

Copyright 2012, Lippincott, Williams & Wilkins


Jarosz M; Wierzejska R; Siuba M. Maternal caffeine intake and its effect on pregnancy outcomes. European Journal of Obstetrics & Gynecology and Reproductive Biology 160(2): 156-160, 2012. (33 refs.)

Objective: Estimation of the maternal caffeine intake during pregnancy and its influence on pregnancy duration, birthweight and Apgar score of the newborn. Study design: The research was conducted on pregnant women who gave birth at the Clinic of Obstetrics, Gynaecology and Oncology, 2nd Faculty of Medicine, Medical University of Warsaw. It covered unifetal pregnancies without diseases (N = 509). Research data were collected by direct questionnaire supplemented with data from patients' records. Statistical analysis employed a multivariate logistic regression model and a non-parametric Spearman's rank correlation coefficient. Results: 98.4% of pregnant women consume no more than 300 mg of caffeine per day. Pregnant women who smoke and older women consume more caffeine than non-smokers and younger women [beta 1.95 (95% CI: 1.02-2.88)] and [beta 0.68 (95% CI: 0.05-1.3)] respectively. There is no association between maternal caffeine intake during pregnancy and the risk of premature birth, the birthweight or the Apgar score of newborns. Conclusion: Caffeine intake of no more than 300 mg per day during pregnancy does not affect pregnancy duration and the condition of the newborn.

Copyright 2012, Elsevier Science


Jones D; Yates L; Stephens S; Dunstan H; Richardson JL; James D et al. Preliminary data on exposure to mephedrone in pregnancy. (meeting abstract). Clinical Toxicology 49(3): 213, 2011. (0 refs.)


Joya X; Gomez-Culebras M; Callejon A; Friguls B; Puig C; Ortigosa S et al. Cocaine use during pregnancy assessed by hair analysis in a Canary Islands cohort. BMC Pregnancy and Childbirth 12: article 2, 2012. (39 refs.)

Background: Drug use during pregnancy is difficult to ascertain, and maternal reports are likely to be inaccurate. The aim of this study was to estimate the prevalence of illicit drug use among pregnant women by using maternal hair analysis. Methods: A toxicological analysis of hair was used to detect chronic recreational drug use during pregnancy. In 2007, 347 mother-infant dyads were included from the Hospital La Candelaria, Santa Cruz de Tenerife, Canary Islands (Spain). Data on socioeconomic characteristics and on substance misuse during pregnancy were collected using a structured questionnaire. Drugs of abuse: opiates, cocaine, cannabinoids and amphetamines were detected in maternal hair by immunoassay followed by gas chromatography-mass spectrometry for confirmation and quantitation. Results: Hair analysis revealed 2.6% positivity for cocaine and its metabolites. Use of cocaine during pregnancy was associated with unusual behaviour with potentially harmful effects on the baby. Conclusions: The results of the study demonstrate significant cocaine use by pregnant women in Canary Islands. The data should be used for the purpose of preventive health and policy strategies aimed to detect and possibly to avoid in the future prenatal exposure to drugs of abuse.

Copyright 2012, BioMed Central


Kelly L; Dooley J; Cromarty H; Minty B; Morgan A; Madden S et al. Narcotic-exposed neonates in a First Nations population in northwestern Ontario: Incidence and implications. Canadian Family Physician 57(11): E441-E447, 2011. (13 refs.)

Objective To document the incidence of neonatal abstinence syndrome (NAS) and the rate of narcotic use during pregnancy in northwestern Ontario, where narcotic abuse is a growing social and medical problem. Design Retrospective chart review. Setting The Sioux Lookout Meno Ya Win Health Centre catchment area in northwestern Ontario. Participants Mothers and neonates for the 482 live births that took place in the 18-month study period (January 2009 to June 2010). Main outcome measures Maternal drug use and neonatal outcomes were documented. Results The incidence of narcotic (oxycodone) abuse during pregnancy increased from a low of 8.4% at the beginning of the study period to a high of 17.2% by mid-2010. Narcotic-using mothers were more likely to also use nicotine and alcohol, to have premature deliveries, and to be episodic users. Narcotic-exposed neonates experienced NAS 29.5% of the time; daily maternal use was associated with a higher rate of NAS (66.0%). While all infants roomed in with their mothers, exposed infants were more likely to require transfer to a tertiary care nursery. Infants with severe NAS were treated with oral morphine and had significantly longer hospital stays compared with the entire cohort (4.5 vs 1.5 days, P = .004). Narcotic abuse during pregnancy in our region is not currently associated with increased rates of HIV or hepatitis C infection, as intravenous route of administration is less common at present than intranasal and oral ingestion. Conclusion Narcotic abuse during pregnancy is a considerable problem in First Nations communities in northwestern Ontario. Community-based initiatives need to be developed to address this issue, and medical and nursing staff need to develop surveillance, assessment, and therapeutic responses. Passive neonatal addiction and withdrawal result from maternal narcotic use during pregnancy. Rates of opioid use among pregnant Canadian women are unknown.

Copyright 2011, College of Family Physicians, Canada


Klimentopoulou A; Antonopoulos CN; Papadopoulou C; Kanavidis P; Tourvas AD; Polychronopoulou S et al. Maternal smoking during pregnancy and risk for childhood leukemia: A nationwide case-control study in Greece and meta-analysis. Pediatric Blood & Cancer 58(3): 344-351, 2012. (56 refs.)

Background: Maternal smoking during pregnancy has been often implicated in the development of childhood leukemia with ambiguous results. Hence, we conducted a meta-analysis aiming to summarize current evidence and quantify any tentative impact.

Copyright 2012, Wiley Periodicals


Kvalvik LG; Nilsen RM; Skjaerven R; Vollset SE; Midttun O; Ueland PM et al. Self-reported smoking status and plasma cotinine concentrations among pregnant women in the Norwegian Mother and Child Cohort Study. Pediatric Research 72(1): 101-107, 2012. (32 refs.)

Introduction: Underreporting of smoking in epidemiologic studies is common and may constitute a validity problem, leading to biased association measures. In this prospective study, we validated self-reported tobacco use against nicotine exposure assessed by plasma cotinine in the Norwegian Mother and Child Cohort Study (MoBa). Methods: The study was based on a subsample of 2,997 women in the MoBa study who delivered infants during the period 2002-2003. Self-reported tobacco use (test variable) and plasma cotinine concentrations (gold standard) were assessed at approximately gestational week 18. Results: Daily smoking was reported by 9% of the women, occasional smoking by 4%, and nonsmoking by 86% of the women. Sensitivity and specificity for self-reported smoking status were calculated using a cotinine cut-off estimated from the study population (30 nmol/l). Plasma cotinine concentrations >= 30 nmol/l were found in 94% of self-reported daily smokers, 66% of occasional smokers, and 2% of nonsmokers. After the numbers of self-reported nonsmokers with cotinine concentrations above the cut-off limit were added, the daily smoking prevalence increased from 9 to 11%. The sensitivity and specificity for self-reported daily smoking, using 30 nmol/l as the cut-off concentration, were 82 and 99%, respectively. Discussion: These findings suggest that self-reported tobacco use is a valid marker for tobacco exposure in the MoBa cohort.

Copyright 2012, Nature Publishing


Ladhani NNN; Shah PS; Murphy KE. Prenatal amphetamine exposure and birth outcomes: A systematic review and metaanalysis. American Journal of Obstetrics and Gynecology 205(3): 219.e1, 2011. (21 refs.)

OBJECTIVE: The aim of this study was to systematically review the relationship between amphetamine exposure in pregnancy and birth outcomes. STUDY DESIGN: Electronic databases were searched to identify relevant studies. Data from included studies were extracted by 2 reviewers. Summary odds ratio (OR) and confidence intervals (CIs) were calculated using the random effects model. RESULTS: Ten studies were included. Significant increases in unadjusted risks of preterm birth (OR, 4.11; 95% CI, 3.05-5.55), low birth-weight (OR, 3.97; 95% CI, 2.45-6.43), and small for gestational age (OR, 5.79; 95% CI, 1.39-24.06) were identified among women ex-posed to amphetamines in pregnancy. The mean birth-weight was significantly lower among amphetamine-exposed pregnancies (mean difference, -279 g; 95% CI, -485 to -74 g). Two studies provided adjusted estimates on different outcomes, and their results were consistent with the findings from the unadjusted data. CONCLUSION: Amphetamine exposure in pregnancy is associated with adverse birth outcomes and should be identified by physicians providing antenatal care.

Copyright 2011, Elsevier Science


LaGasse LL; Derauf C; Smith LM; Newman E; Shah R; Neal C et al. Prenatal methamphetamine exposure and childhood behavior problems at 3 and 5 years of age. Pediatrics 129(4): 681-688, 2012. (45 refs.)

Objective: We evaluated behavior problems in children who were prenatally exposed to methamphetamine (MA) at ages 3 and 5 years. Methods: The Infant Development, Environment, and Lifestyle study, a prospective, longitudinal study of prenatal MA exposure and child outcome, enrolled subjects postpartum in Los Angeles, California; Honolulu, Hawaii; Des Moines, Iowa; and Tulsa, Oklahoma. Prenatal exposure was determined by maternal self-report and/or meconium results. Exposed and comparison groups were matched on race, birth weight, public health insurance, and education. Mothers in the comparison group denied use and had a negative meconium screen for amphetamines. Prenatal exposures to tobacco, alcohol, or marijuana occurred in both groups. At ages 3 and 5 years, 330 children (166 exposed and 164 comparison) were assessed for behavior problems by using the caregiver report on the Child Behavior Checklist. General linear mixed models were used to determine the effects of prenatal methamphetamine exposure, including heavy exposure (>= 3 days per week), age, and the interaction of exposure and age on behavior problems with adjustment for other drugs of abuse and environmental risk factors. Results: methamphetamine exposure was associated with increased emotional reactivity and anxious/depressed problems at both ages and externalizing and attention-deficit/hyperactivity disorder problems by age 5 years. Heavy exposure was related to attention problems and withdrawn behavior at both ages. There were no effects of MA on the internalizing or total behavior problems scales. Conclusions: This first report of behavior problems in patients as young as 3 years associated with methamphetamine exposure identifies an important public health problem. Continued follow-up can inform the development of preventive intervention programs.

Copyright 2012, American Academy of Pediatrics


Land TG; Landau AS; Manning SE; Purtill JK; Pickett K; Wakschlag L et al. Who underreports smoking on birth records: A Monte Carlo predictive model with validation. PLoS ONE 7(4): e-article 34853, 2012. (28 refs.)

Background: Research has shown that self-reports of smoking during pregnancy may underestimate true prevalence. However, little is known about which populations have higher rates of underreporting. Availability of more accurate measures of smoking during pregnancy could greatly enhance the usefulness of existing studies on the effects of maternal smoking offspring, especially in those populations where underreporting may lead to underestimation of the impact of smoking during pregnancy. Methods and Findings: In this paper, we develop a statistical Monte Carlo model to estimate patterns of underreporting of smoking during pregnancy, and apply it to analyze the smoking self-report data from birth certificates in the state of Massachusetts. Our results illustrate non-uniform patterns of underreporting of smoking during pregnancy among different populations. Estimates of likely underreporting of smoking during pregnancy were highest among mothers who were college-educated, married, aged 30 years or older, employed full-time, and planning to breastfeed. The model's findings are validated and compared to an existing underreporting adjustment approach in the Maternal and Infant Smoking Study of East Boston (MISSEB). Conclusions: The validation results show that when biological assays are not available, the Monte Carlo method proposed can provide a more accurate estimate of the smoking status during pregnancy than self-reports alone. Such methods hold promise for providing a better assessment of the impact of smoking during pregnancy.

Copyright 2012, Public Library of Science


Levine TP; Lester B; Lagasse L; Shankaran S; Bada HS; Bauer CR et al. Psychopathology and special education enrollment in children with prenatal cocaine exposure. Journal of Developmental And Behavioral Pediatrics 33(5): 377-386, 2012. (61 refs.)

Objective: This study evaluated how enrollment in special education services in 11-year-old children relates to prenatal cocaine exposure (PCE), psychopathology, and other risk factors. Methods: Participants were 498 children enrolled in The Maternal Lifestyle Study, a prospective, longitudinal, multisite study examining outcomes of children with PCE. Logistic regression was used to examine the effect of PCE and psychopathology on enrollment in an individualized education plan (IEP; a designation specific to children with special education needs), with environmental, maternal, and infant medical variables as covariates. Results: PCE, an interaction of PCE and oppositional defiant disorder, child attention-deficit hyperactivity disorder, parent-reported internalizing behaviors, and teacher-reported externalizing behaviors, predicted enrollment in an IEP. Other statistically significant variables in the model were male gender, low birth weight, being small for gestational age, white race, caregiver change, low socioeconomic status, low child intelligence quotient, caregiver depression, and prenatal marijuana exposure. Conclusions: PCE increased the likelihood of receiving an IEP with adjustment for covariates. Psychopathology also predicted this special education outcome, in combination with and independent of prenatal cocaine exposure.

Copyright 2012, Lippincott, Williams & Wilkins


Li L; Zhu GQ; Meng T; Shi JY; Wu J; Xu X et al. Biological and epidemiological evidence of interaction of infant genotypes at Rs7205289 and maternal passive smoking in cleft palate. American Journal of Medical Genetics. Part A 155A(12): 2940-2948, 2011. (49 refs.)

The noncoding SNP rs7205289, located in the microRNA-140 gene has been associated with cleft palate risk. MiR-140 was found to regulate zebrafish palatal development in vivo and its expression level be reduced by environmental smoke exposure in vitro. Therefore, we sought to investigate whether the A allele of rs7205289 and maternal smoke exposure during the first trimester might contribute to cleft palate risk by regulating microRNA-140. We used in situ hybridization to explore the microRNA-140 expression pattern. A luciferase reporting system and Western blot were used to validate the target of microRNA-140. Mouse palatal mesenchymal cells (MPMC) were transfected with microRNA-140 expression vectors, or treated with cigarette smoke extract. In addition, we performed a hospital-based case control study in 169 patients with nonsyndromic cleft palate and 306 unaffected controls. We demonstrated microRNA-140 expression in mouse palatal shelves from embryonic days 12 to 15. Pdgfra was the target of microRNA-140 in MPMC. When these cells were transfected with the minor allele vector or exposed to cigarette smoke extract, they showed a decrease in microRNA-140 expression. Epidemiological analyses showed that infants with CA/AA genotypes and exposed to maternal passive smoking during pregnancy had evidence of synergistic interaction in contributing to cleft palate risk. We concluded that infants with CA/AA genotypes at rs7205289 and maternal passive smoking during the first trimester may synergistically contribute to cleft palate risk by decreasing microRNA-140 during palatal development.

Copyright 2011, Wiley-Blackwell


Lim R; Sobey CG. Maternal nicotine exposure and fetal programming of vascular oxidative stress in adult offspring. (editorial). British Journal of Pharmacology 164(5): 1397-1399, 2011. (23 refs.)

Despite the well-known harmful effects, many women continue to smoke throughout pregnancy. Consequently, nicotine replacement therapy (NRT) - which has been developed as a pharmacotherapy for smoking cessation - has been used as an alternative to smoking during pregnancy. However, like cigarette smoking, NRT results in biologically significant levels of nicotine crossing the placenta, leading to both fetal and neonatal exposure to nicotine, and yet, NRT safety during pregnancy has not been extensively evaluated. There is now evidence from studies in rats that maternal nicotine exposure throughout gestation results in fetal programming of vascular oxidative stress in the offspring during adulthood. This phenomenon involves vascular dysfunction mediated by reactive oxygen species in association with decreased superoxide dismutase activity and increased Nox2-NADPH oxidase expression in the vascular wall. If this phenomenon also occurs in humans, either smoking or NRT use during pregnancy may represent a novel risk factor for the unborn that results in accelerated cardiovascular disease in their adulthood.

Copyright 2011, Wiley-Blackwell


Machaalani R; Say M; Waters KA. Effects of cigarette smoke exposure on nicotinic acetylcholine receptor subunits alpha 7 and beta 2 in the sudden infant death syndrome (SIDS)// brainstem. Toxicology and Applied Pharmacology 257(3): 396-404, 2011. (57 refs.)

It is postulated that nicotine, as the main neurotoxic constituent of cigarette smoke, influences SIDS risk through effects on nicotinic acetylcholine receptors (nAChRs) in brainstem nuclei that control respiration and arousal. This study compared alpha 7 and beta 2 nAChR subunit expression in eight nuclei of the caudal and rostral medulla and seven nuclei of the pons between SIDS (n = 46) and non-SIDS infants (n = 14). Evaluation for associations with known SIDS risk factors included comparison according to whether infants had a history of exposure to cigarette smoke in the home, and stratification for sleep position and gender. Compared to non-SIDS infants, SIDS infants had significantly decreased alpha 7 in the caudal nucleus of the solitary tract (cNTS), gracile and cuneate nuclei, with decreased beta 2 in the cNTS and increased beta 2 in the facial. When considering only the SIDS cohort: 1-cigarette smoke exposure was associated with increased alpha 7 in the vestibular nucleus and increased beta 2 in the rostral dorsal motor nucleus of the vagus, rNTS and Cuneate, 2-there was a gender interaction for alpha 7 in the gracile and cuneate, and beta 2 in the cNTS and rostral arcuate nucleus, and 3-there was no effect of sleep position on alpha 7, but prone sleep was associated with decreased beta 2 in three nuclei of the pons. In conclusion, SIDS infants demonstrate differences in expression of alpha 7 and beta 2 nAChRs within brainstem nuclei that control respiration and arousal, which is independent on prior history of cigarette smoke exposure, especially for the NTS, with additional differences for smoke exposure (beta 2), gender (alpha 7 and beta 2) and sleep position (beta 2) evident.

Copyright 2011, Elsevier Science


Machado JD; Filho PVM; Petersen GO; Chatkin JM. Quantitative effects of tobacco smoking exposure on the maternal-fetal circulation. BMC Pregnancy and Childbirth 11: 24, 2011. (23 refs.)

Background: Despite the existence of various published studies regarding the effects of tobacco smoking on pregnancy, and especially in regards to placental blood flow and vascular resistance, some points still require clarification. In addition, the amount of damage due to tobacco smoking exposure that occurs has not been quantified by objective means. In this study, we looked for a possible association between flow resistance indices of several arteries and the levels of urinary cotinine and the concentration of carbon monoxide in the exhaled air (COex) of both smoking and non-smoking pregnant women. We also looked for a relationship between those findings and fetal growth and birth weight. Methods: In a prospective design, thirty pregnant smokers and thirty-four pregnant non-smokers were studied. The volunteers signed consent forms, completed a self-applied questionnaire and were subjected to Doppler velocimetry. Tobacco smoking exposure was quantified by subject provided information and confirmed by the measurement of urinary cotinine levels and by the concentration of carbon monoxide in the exhaled air (COex). The weight of newborns was evaluated immediately after birth. Results: Comparing smoking to non-smoking pregnant women, a significant increase in the resistance index was observed in the uterine arteries (P = 0.001) and umbilical artery (P = 0.001), and a decrease in the middle cerebral artery (P = 0.450). These findings were associated with progressively higher concentrations of COex and urinary cotinine. A decrease in the birth weight was also detected (P < 0.001) in association with a progressive increase in the tobacco exposure of the pregnant woman. Conclusions: In pregnant women who smoke, higher arterial resistance indices and lower birth weights were observed, and these findings were associated with increasing levels of tobacco smoking exposure. The values were significantly different when compared to those found in non-smoking pregnant women. This study contributes to the findings that smoking damage during pregnancy is dose-dependent, as demonstrated by the objective methods for measuring tobacco smoking exposure.

Copyright 2011, BioMedical Central


Mackay DF; Nelson SM; Haw SJ; Pell JP. Impact of Scotland's smoke-free legislation on pregnancy complications: Retrospective cohort study. PLoS Medicine 9(3): e-article 1001175, 2012. (28 refs.)

Background: Both active smoking and environmental tobacco smoke exposure are associated with pregnancy complications. In March 2006, Scotland implemented legislation prohibiting smoking in all wholly or partially enclosed public spaces. The aim of this study was to determine the impact of this legislation on preterm delivery and small for gestational age. Methods and Findings: We conducted logistic regression analyses using national administrative pregnancy data covering the whole of Scotland. Of the two breakpoints tested, 1 January 2006 produced a better fit than the date when the legislation came into force (26 March 2006), suggesting an anticipatory effect. Among the 716,941 eligible women who conceived between August 1995 and February 2009 and subsequently delivered a live-born, singleton infant between 24 and 44 wk gestation, the prevalence of current smoking fell from 25.4% before legislation to 18.8% after legislation (p<0.001). Three months prior to the legislation, there were significant decreases in small for gestational age (-4.52%, 95% CI -8.28, -0.60, p = 0.024), overall preterm delivery (-11.72%, 95% CI -15.87, -7.35, p<0.001), and spontaneous preterm labour (-11.35%, 95% CI -17.20, -5.09, p = 0.001). In sub-group analyses, significant reductions were observed among both current and never smokers. Conclusions: Reductions were observed in the risk of preterm delivery and small for gestational age 3 mo prior to the introduction of legislation, although the former reversed partially following the legislation. There is growing evidence of the potential for tobacco control legislation to have a positive impact on health.

Copyright 2012, Public Library Science


Mahar I; Bagot RC; Davoli MA; Miksys S; Tyndale RF; Walker CD et al. Developmental hippocampal neuroplasticity in a model of nicotine replacement therapy during pregnancy and breastfeeding. PLoS ONE 7(5): e-article 37219, 2012. (66 refs.)

Rationale: The influence of developmental nicotine exposure on the brain represents an important health topic in light of the popularity of nicotine replacement therapy (NRT) as a smoking cessation method during pregnancy. Objectives: In this study, we used a model of NRT during pregnancy and breastfeeding to explore the consequences of chronic developmental nicotine exposure on cerebral neuroplasticity in the offspring. We focused on two dynamic lifelong phenomena in the dentate gyrus (DG) of the hippocampus that are highly sensitive to the environment: granule cell neurogenesis and long-term potentiation (LTP). Methods: Pregnant rats were implanted with osmotic mini-pumps delivering either nicotine or saline solutions. Plasma nicotine and metabolite levels were measured in dams and offspring. Corticosterone levels, DG neurogenesis (cell proliferation, survival and differentiation) and glutamatergic electrophysiological activity were measured in pups. Results: Juvenile (P15) and adolescent (P41) offspring exposed to nicotine throughout prenatal and postnatal development displayed no significant alteration in DG neurogenesis compared to control offspring. However, NRT-like nicotine exposure significantly increased LTP in the DG of juvenile offspring as measured in vitro from hippocampal slices, suggesting that the mechanisms underlying nicotine-induced LTP enhancement previously described in adult rats are already functional in pups. Conclusions: These results indicate that synaptic plasticity is disrupted in offspring breastfed by dams passively exposed to nicotine in an NRT-like fashion.

Copyright 2012, Public Library of Science


Massey SH; Neiderhiser JM; Shaw DS; Leve LD; Ganiban JM; Reiss D. Maternal self concept as a provider and cessation of substance use during pregnancy. Addictive Behaviors 37(8): 956-961, 2012. (41 refs.)

Objective: Maternal substance use during pregnancy is a common modifiable risk factor for poor birth outcomes, and is associated with long term psychological risks to offspring. As self concept is known to affect substance use behaviors in non-pregnant women, we hypothesized that self concept as a provider may be particularly salient to cessation of use during pregnancy. To isolate psychological processes specific to pregnancy from those associated with the transition to parenthood, we examined birth mothers who made adoption placements participating in the Early Growth and Development Study. Methods: We obtained lifetime and pregnancy substance use history and psychological measures at 3 to 4 months postpartum from 693 women recruited from the Northwest, Southwest, and Mid-Atlantic regions of the United States. Life history calendar and computer-assisted personal interviewing methods were used to minimize reporting bias. Using logistic regression, we assessed the association of self concept as an adequate provider with cessation of substance use during pregnancy, controlling for sociodemographic variables, depressive symptoms experienced during pregnancy, past year antisocial behaviors, family history of substance abuse, timing of pregnancy recognition, timing of initiation of prenatal care, and emotional adjustment to the adoption decision. Results: More positive self-concept as an adequate provider was independently associated with cessation of substance use and earlier initiation of prenatal care during pregnancy [OR = 1223; 95% C.I. (1.005-1.489); B(SE) = .201(.100)]. Familial substance abuse, depressive symptoms, and antisocial behaviors during pregnancy, were also independent predictors, and more strongly associated with cessation [OR = .531:95% C.I. (.375-.751); B(SE) = -.634 (.178)], [OR. 940; 95% C.I. (.906-.975); B(SE) = -.062 (.019)]. [OR=.961; 95% C.I. (.927-.996); B(SE) = -.040 (.018)]. Conclusions: Enhancing maternal identity as a provider for the fetus during pregnancy, along with treatment of depression, may improve motivation to stop substance use.

Copyright 2012, Elsevier Science


Mateja WA; Nelson DB; Kroelinger CD; Ruzek S; Segal J. The association between maternal alcohol use and smoking in early pregnancy and congenital cardiac defects. Journal of Women's Health 21(1): 26-34, 2012. (51 refs.)

Background: Alcohol use is an extremely prevalent but preventable risk factor among women seeking to become pregnant. Many women continue to use alcohol in the early stages of pregnancy before they are aware they are pregnant. Research is unclear about the role of maternal alcohol use during pregnancy and congenital cardiac defects, one of the leading types of birth defects in the United States. Methods: Data from the Pregnancy Risk Assessment Monitoring Survey (PRAMS) were used to examine maternal alcohol use and its association with congenital cardiac defects. Various measures of alcohol use in the 3 months prior to pregnancy, as well as smoking and other risk factors for congenital cardiac defects, were linked to birth certificate data for nine states over a 10-year period (1996-2005). In this case-control study, cases included infants with a congenital cardiac defect indicated on the birth certificate, and the control group consisted of healthy, normal weight infants with no indication of a congenital abnormality on their birth certificate. Complex samples logistic regression models were used to study the relationships between several measures of alcohol use, including binge drinking and binge drinking on more than once occasion, and the interaction between alcohol use and smoking with the odds of congenital cardiac defects. Results: A significant increase in congenital cardiac defects was found among mothers who reported binge drinking more than once in the 3 months prior to pregnancy compared to mothers who did not report binge drinking (adjusted odds ratio [aOR] 2.99, 95% confidence interval [CI] 1.19-7.51). There was a significant interaction between any binge drinking or binge drinking more than once and cigarette use, which corresponded to a substancial increase in congenital cardiac defects (aOR 12.65, 95% CI 3.54-45.25 and aOR 9.45, 95% CI 2.53-35.31, respectively). Conclusions: Multiple episodes of maternal binge drinking in early pregnancy may increase the odds of congenital cardiac defects, and we found this relationship was more dramatic when combined with maternal smoking.

Copyright 2012, Mary Ann Liebert


Meghea CI; Rus D; Rus IA; Holtrop JS; Roman L. Smoking during pregnancy and associated risk factors in a sample of Romanian women. European Journal of Public Health 22(2): 229-233, 2012. (31 refs.)

Background: Smoking during pregnancy is one of the most modifiable risk factor for poor birth outcomes. This study assesses the prevalence and correlates of smoking during pregnancy. Methods: A questionnaire was applied to pregnant women in two urban clinics in Romania to assess smoking prevalence, attitudes and knowledge about smoking, and other risks poorly documented in Romania, such as depressive symptoms, stress and social support. The response rate was > 80% and the valid sample comprised of 916 women. Descriptive statistics and logistic regressions were used to estimate the prevalence of smoking and other risk factors and to identify correlates of smoking during pregnancy. Results: Approximately 15% of the women continued smoking during pregnancy, and 26% of all women said they smoked prior to pregnancy, but quit upon finding out they were pregnant. Depressive symptoms and stress were not associated with smoking during pregnancy. Women with no social support had higher odds of continued smoking vs. non-smoking (OR = 2.3, P < 0.01), and vs. quitting (OR = 2.3, P < 0.05). Roma women had 5.2 times the odds (P < 0.01) of continued smoking vs. non-smoking. Lack of awareness about the benefits of quitting smoking and about the risks of smoking light cigarettes were associated with continued smoking during pregnancy. Conclusions: Smoking was common in a sample of Romanian pregnant women. Smoking cessation programs in Romania should include components to raise the awareness about the risks of smoking during pregnancy and the benefits of quitting at any time during pregnancy. More targeted interventions are needed in Roma communities.

Copyright 2012, Oxford University Press


Milidou I; Henriksen TB; Jensen MS; Olsen J; Sondergaard C. Nicotine replacement therapy during pregnancy and infantile colic in the offspring. Pediatrics 129(3): E652-E658, 2012. (36 refs.)

Objective: To investigate the associations between use of nicotine replacement therapy (NRT) and smoking during pregnancy and infantile colic in the offspring. Methods: We used data from maternal interviews (from pregnancy and at 6 months post partum) from the Danish National Birth Cohort (1996-2002). We included 63 128 live-born singletons with complete information on nicotine exposure during pregnancy and infantile colic symptoms as recorded at 6 months of age. Results: A total of 46 660 infants (73.9%) were unexposed to nicotine during pregnancy; 207 (0.3%) were exposed to NRT, 15 016 (23.8%) were exposed to smoking, and 1245 (2.0%) to both. A total of 4974 (7.9%) infants fulfilled Wessel's modified criteria for infantile colic. Prenatal nicotine exposure was associated with elevated risk for infantile colic in the offspring. Compared with the unexposed, NRT users had an adjusted odds ratio (OR) (95% confidence interval) of 1.6 (1.02.5; P = .03), smokers had OR = 1.3 (1.2-1.4), and women who both smoked and used NRT had OR = 1.6 (1.3-1.9). Partners' smoking was not associated with infantile colic after adjustment for maternal smoking. Conclusions: We corroborated the association between smoking and infantile colic after adjustment for several possible confounders in a large cohort study. Moreover, we found that infants exposed to NRT prenatally had an increased risk for infantile colic of the same magnitude as those exposed to tobacco smoke. Thus, nicotine may play a role in the pathogenesis of infantile colic.

Copyright 2012, American Academy of Pediatrics


Milne E; Greenop KR; Scott RJ; Bailey HD; Attia J; Dalla-Pozza L et al. Parental prenatal smoking and risk of childhood acute lymphoblastic leukemia. American Journal of Epidemiology 175(1): 43-53, 2012. (30 refs.)

The association between parental smoking and risk of childhood acute lymphoblastic leukemia (ALL) was investigated in an Australian population-based case-control study that included 388 cases and 868 controls aged <15 years, recruited from 2003 to 2006. Both of the child's parents provided information about their smoking habits for each year from age 15 years to the child's birth. Data were analyzed by logistic regression. Maternal smoking was not associated with risk of childhood ALL, but the odds ratio for paternal smoking of >= 15 cigarettes per day around the time of the child's conception was 1.35 (95% confidence interval: 0.98, 1.86). The associations between parental smoking risk of childhood ALL did not differ substantially by immunophenotypic or cytogenetic subtype. Meta-analyses of paternal smoking, including results from the Australian Study of Causes of Acute Lymphoblastic Leukemia in Children and those of previous studies, produced summary odds ratios of 1.15 (95% confidence interval: 1.06, 1.24) for any paternal smoking around the time of the child's conception and 1.44 (95% confidence interval: 1.24, 1.68) for smoking >= 20 cigarettes per day at that time. Study results suggest that heavier paternal smoking around the time of conception is a risk factor for childhood ALL. Men should be strongly encouraged to cease smoking, particularly when planning to start a family.

Copyright 2012, Oxford University Press


Minnes S; Lang A; Singer L. Prenatal tobacco, marijuana, stimulant, and opiate exposure: Outcomes and practice implications. Addiction Science & Clinical Practice 6(1): unpaginated, 2011

Abuse of drugs by pregnant women both in the United States and worldwide has raised many questions regarding the effects of prenatal drug exposure on the developing fetus and subsequent child outcomes. Studies using the neurobehavioral teratology model have been undertaken to determine specific prenatal drug effects on cognitive and behavioral development. Here we summarize the findings of studies that have investigated the developmental effects of prenatal exposure to tobacco, marijuana, stimulants, and opiates. These studies consider the timing and amount of prenatal exposure; other drug exposures; maternal characteristics; and other health, nutritional, and environmental factors. We review treatment options for pregnant, substance-dependent women and therapeutic interventions for exposed children.

Public Domain


Monshouwer K; Huizink AC; Harakeh Z; Raaijmakers QAW; Reijneveld SA; Oldehinkel AJ et al. Prenatal smoking exposure and the risk of behavioral problems and substance use in adolescence: The TRAILS Study. European Addiction Research 17(6): 342-350, 2011. (50 refs.)

Aims: To study the prospective relationship between maternal smoking during pregnancy (MSP) and behavioral problems, heavy alcohol use, daily smoking, and ever use of cannabis in the offspring, and to assess the role of confounding and mediating factors in a systematic way. Methods: Population-based cohort study of 2,230 respondents, starting in 2001 when respondents were around the age of 11 years, and two follow-up measurements at intervals of about 2.5 years (response rates of 96.0 and 81.4%). Results: Almost one third of the respondents' mothers had smoked tobacco during pregnancy. These respondents were at an increased risk for all outcomes except internalizing problems (significant odds ratios ranged from 1.40 to 2.97). The successive models showed that the potential confounding factors reduced the strength of all relationships. In the full model, the strongest relationship was found for mothers who smoked more than 10 cigarettes a day during pregnancy and daily smoking in early adolescence (odds ratio: 1.56), but none of the relationships were statistically significant. Conclusions: MSP is a marker for future behavioral outcomes in the offspring, but reducing the prevalence of MSP is unlikely to make a meaningful contribution to the prevention of these problems in adolescents.

Copyright 2011, Karger


Motlagh MG; Sukhodolsky DG; Landeros-Weisenberger A; Katsovich L; Thompson N; Scahill L et al. Adverse effects of heavy prenatal maternal smoking on attentional control in children With ADHD. Journal of Attention Disorders 15(7): 593-603, 2011. (84 refs.)

Objective: Exposure to heavy maternal cigarette smoking in pregnancy and severe maternal psychosocial stress during pregnancy appear to be important risk factors for the development of ADHD. This study aimed to determine whether these perinatal risk factors were associated with neuropsychological deficits commonly seen in ADHD. Method: We examined the effect of these two risk factors on measures of attentional control, motor inhibition, visual-motor integration, and fine motor coordination in a group of 81 children with ADHD, aged from 8 to 18 years. The neuropsychological battery included the Connors' Continuous Performance Test (CPT), the Stroop Color-Word Interference Test, the Beery Visual-Motor Integration Test, and the Purdue Pegboard Test. Results: Heavy maternal smoking during pregnancy was associated with slower reaction times (p < .002), and reaction time variability (p < .007) on the CPT. Conclusions: This study suggests a persistent negative effect of heavy prenatal maternal smoking on attentional control in children with ADHD. Future studies should examine the neurobiological basis and determine the degree to which inherited genetic susceptibility factors contribute to this finding.

Copyright 2011, Sage Publications


Ortega-Garcia JA; Gutierrez-Churango JE; Sanchez-Sauco MF; Martinez-Aroca M; Delgado-Marin JL; Sanchez-Solis M et al. Head circumference at birth and exposure to tobacco, alcohol and illegal drugs during early pregnancy. Child's Nervous System 28(3): 433-439, 2012. (29 refs.)

We aimed to assess the effects of exposure to tobacco smoke, alcohol and illegal drugs during early pregnancy on the head circumference (HC) at birth of otherwise healthy neonates. A follow-up study from the first trimester of pregnancy to birth was carried out in 419 neonates. An environmental reproductive health form was used to record data of substance exposure obtained during the first obstetric visit at the end of the first trimester. A multiple linear regression model was created for this purpose. Alcohol intake during pregnancy and medical ionizing radiation exposure were the most significant predictors of HC. The mothers' alcohol consumption increased with the mothers' and fathers' education level, net family income and fathers' alcohol consumption. In contrast, maternal smoking decreased with increasing mothers' and fathers' education level and net family income. About 13% of the surveyed embryos were exposed to illegal drugs. Mild to moderate alcohol consumption diminishes the at-birth HC of theoretically healthy newborns in a linear form. There was no threshold dose. We perceived a need for increasing the awareness, and for training, of health care professionals and parents, in regard to risks of alcohol consumption and for recommending abstinence of these substances in both parents during pregnancy. It should also be remembered that medical ionizing radiation should be performed only during the first half of the cycle in fertile women. We think that our study has an important social impact as it affords data for implementing policies for promoting "healthy pregnancies".

Copyright 2012, Springer


Ortigosa S; Friguls B; Joya X; Martinez S; Marinoso ML; Alameda F et al. Feto-placental morphological effects of prenatal exposure to drugs of abuse. Reproductive Toxicology 34(1): 73-79, 2012. (63 refs.)

The aim of the study was to find morphological changes in the feto-placental unit due to prenatal exposure to drugs of abuse. A blind histomorphometric study was performed using 225 placentas. Based on meconium testing, the fetuses were classified as exposed or unexposed to opiates, cocaine, cannabis or alcohol. To establish prenatal tobacco exposure, cotinine in cord blood was analyzed. At the microscopic level a non statistically significant reduction of placental vascularization was observed in cocaine, opiates and alcohol using mothers. In addition, alcohol-consuming mothers did not present with larger placental vessel diameter than controls. Prenatal use of cocaine and tobacco was associated with a decrease in newborn weight and length. Furthermore, tobacco use was associated with a higher rate of previous abortions. In conclusion, placentas from mothers using tobacco, cocaine, opiates or alcohol during pregnancy present vasculature changes that may explain the adverse perinatal outcomes in their newborns.

Copyright 2012, Elsevier Science


Parrish DE; von Sternberg K; Velasquez MM; Cochran J; Sampson M; Mullen PD. Characteristics and factors associated with the risk of a nicotine exposed pregnancy: Expanding the CHOICES preconception counseling model to tobacco. Maternal and Child Health Journal 16(6): 1224-1231, 2012. (32 refs.)

The preconception counseling model tested in the CDC funded Project CHOICES efficacy trial to reduce the risk of an alcohol-exposed pregnancy (AEP) could be extended to smokers to prevent a nicotine-exposed pregnancy (NEP), when pharmacotherapy can be provided safely and disclosure of these risk behaviors is more likely. The CHOICES model, which incorporates motivational interviewing, encourages reduction of AEP risk by decreasing risky drinking or using effective contraception; in the efficacy trial, most women chose both options. We conducted a secondary analysis of the CHOICES epidemiologic survey data (N = 2,672) (Project CHOICES Research Group in Am J Prev Med 23(3), 166-173, 2002) to identify the prevalence of risk of NEP and the factors associated with this risk using logistic regression modeling procedures. Conducted in six settings with women at risk for AEP, the percentage of AEP was 12.5% (333/2,672) among women of childbearing age (18-44). A total of 464 of the 2,672 (17.4%) were at risk for NEP. Among women at-risk of an unplanned pregnancy (n = 1,532), the co-occurrence of AEP and NEP risk was more prevalent (16.3%) than AEP risk alone (5.5%) or NEP risk alone (14.0%). In the multivariable model, statistically significant correlates for NEP risk included lifetime drug use, prior alcohol/drug treatment, drug use in the last 6 months, being married or living with a partner, having multiple sexual partners in the last 6 months, physical abuse in the last year, and lower levels of education. These findings suggest that preconception counseling for NEP could be combined with a program targeting AEP.

Copyright 2012, Springer


Piper BJ; Corbett SM. Executive function profile in the offspring of women that smoked during pregnancy. Nicotine & Tobacco Research 14(2): 191-199, 2012. (58 refs.)

Smoking tobacco during pregnancy results in exposure to the fetal neuroteratogen nicotine. The current study evaluated if the offspring of smokers show abnormalities in maternal ratings of executive function, prevalence of Attention Deficit Hyperactivity Disorder (ADHD), and academic performance. A secondary objective was to determine the utility of online data collection. Mothers (N = 357) completed the parent form of the Behavioral Rating Inventory of Executive Function (BRIEF) and provided information about smoking during pregnancy. The internal consistency of the BRIEF when administered electronically was quite satisfactory (Cronbach's alpha = .98). As anticipated, ADHD was more frequently diagnosed in the offspring of women that smoked at least 10 cigarettes/day (odds ratio [OR] = 2.64, 95% CI = 1.22-5.71). Higher (i.e., more problematic) ratings relative to unexposed children (p < .01) were only identified on the total BRIEF score, the Metacognition Index, and on the Initiate, Plan/Organize, and Monitor scales among children exposed to >= 10 cigarettes/day. Nicotine-exposed children were also more likely to perform less well than their classmates in math (OR = 2.78, 95% CI = 1.59-4.87) and reading (OR = 2.00, 95% CI = 1.10-3.63), and these academic effects were independent of maternal education levels. This report provides preliminary evidence that the BRIEF has adequate psychometric properties when administered electronically and that mothers who smoke have offspring with lower executive function proficiency. These findings contribute to a larger literature that indicates that smoking during pregnancy results in adverse reproductive outcomes and, possibly, subtle but enduring deficits in prefrontal function.

Copyright 2012, Oxford University Press


Quesada O; Gotman N; Howell HB; Funai EF; Rounsaville BJ; Yonkers KA. Prenatal hazardous substance use and adverse birth outcomes. Journal of Maternal-Fetal & Neonatal Medicine 25(8): 1222-1227, 2012. (30 refs.)

Objective: Assess the relative effects of a variety of illicit and licit drugs on risk for adverse birth outcomes. Methods: We used data from two large prospective investigations, and a novel analytic method, recursive partitioning class analysis to identify risk factors associated with preterm birth and delivering a small for gestational age infant. Results: Compared to cocaine and opiate non-users, cocaine users were 3.53 times as likely (95% CI: 1.65-7.56; p = 0.001) and opiate users 2.86 times as likely (95% CI: 1.11-7.36; p = 0.03) to deliver preterm. The odds of delivering a small for gestational age infant for women who smoked more than two cigarettes daily was 3.74, (95% CI: 2.47-5.65; p < 0.0001) compared to women who smoked two or less cigarettes daily and had one previous child. Similarly, less educated, nulliparous women who smoked two or fewer cigarettes daily were 4.12 times as likely (95% CI: 2.04-8.34; p < 0.0001) to have a small for gestational age infant. Conclusions: Among our covariates, prenatal cocaine and opiate use are the predominant risk factors for preterm birth; while tobacco use was the primary risk factor predicting small for gestational age at delivery. Multi-substance use did not substantially increase risk of adverse birth outcomes over these risk factors.

Copyright 2012, Informa Healthcare


Robison RG; Kumar R; Arguelles LM; Hong XM; Wang GY; Apollon S et al. Maternal smoking during pregnancy, prematurity and recurrent wheezing in early childhood. Pediatric Pulmonology 47(7): 666-673, 2012. (43 refs.)

Background: Prenatal maternal smoking and prematurity independently affect wheezing and asthma in childhood. Objective We sought to evaluate the interactive effects of maternal smoking and prematurity upon the development of early childhood wheezing. Methods: We evaluated 1,448 children with smoke exposure data from a prospective urban birth cohort in Boston. Maternal antenatal and postnatal exposure was determined from standardized questionnaires. Gestational age was assessed by the first day of the last menstrual period and early prenatal ultrasound (preterm < 37 weeks gestation). Wheezing episodes were determined from medical record extraction of well and ill/unscheduled visits. The primary outcome was recurrent wheezing, defined as = 4 episodes of physician documented wheezing. Logistic regression models and zero inflated negative binomial regression (for number of episodes of wheeze) assessed the independent and joint association of prematurity and maternal antenatal smoking on recurrent wheeze, controlling for relevant covariates. Results: In the cohort, 90 (6%) children had recurrent wheezing, 147 (10%) were exposed to in utero maternal smoke and 419 (29%) were premature. Prematurity (odds ratio [OR] 2.0; 95% confidence interval [CI], 1.33.1) was associated with an increased risk of recurrent wheezing, but in utero maternal smoking was not (OR 1.1, 95% CI 0.52.4). Jointly, maternal smoke exposure and prematurity caused an increased risk of recurrent wheezing (OR 3.8, 95% CI 1.88.0). There was an interaction between prematurity and maternal smoking upon episodes of wheezing (P = 0.049). Conclusions: We demonstrated an interaction between maternal smoking during pregnancy and prematurity on childhood wheezing in this urban, multiethnic birth cohort.

Copyright 2012, Wiley-Blackwell


Sachiyo K; Kumiko A; Keiko N; Kaori K; Sonomi O. Effect of passive smoking using maternal and neonatal salivary cotinine measurements. Nursing Research 61(2): 148-152, 2012. (18 refs.)

Background: In Japan, the rate of passive smoking among pregnant women is 52.7%, and smokers are usually their husbands (80.8%). Fetal environmental tobacco smoke has been measured using cotinine levels in maternal and neonatal hair, urine, or umbilical cord blood. However, using saliva from neonates immediately after birth has not been explored among noninvasive methods. Objective: The aims of this study were to (a) determine the relationship between fathers' smoking status during pregnancy and neonatal and maternal salivary cotinine immediately after delivery and (b) evaluate the potential use of salivary cotinine measurements immediately after birth to determine the exposure of the neonates to passive smoke. Method: A cross-sectional survey design was used. The participants were 34 pairs of nonsmoking mothers and their neonates who had visited for a health check-up at a general hospital in Tokyo. Saliva samples were collected from mothers and their neonates within 24 hours of delivery. All samples were analyzed using an enzyme-linked immunosorbent assay. Information about maternal age, neonate's birth weight, and smoking status of the father were obtained by interview and questionnaire. Results: Salivary cotinine levels in neonates and mothers with indoor-smoking fathers were significantly higher compared with those in neonates and mothers with nonsmoking and outdoor-smoking fathers. A very strong positive correlation was observed between neonatal and maternal cotinine levels. Conclusion: Smoking indoors by the father affected the mother and neonate. Salivary cotinine measurement is a feasible method to evaluate passive exposure of neonates to tobacco smoke.

Copyright 2012, Lippinocott, Williams & Wilkins


Sarkola T; Gissler M; Kahila H; Autti-Ramo I; Halmesmaki E. Alcohol and substance abuse identified during pregnancy: Maternal morbidity, child morbidity and welfare interventions. Acta Paediatrica 101(7): 784-790, 2012. (26 refs.)

Aim: To study the relations between postnatal maternal morbidity, child morbidity and welfare interventions in families with prenatal alcohol or substance abuse. Methods: A register-based longitudinal retrospective cohort study. The exposed cohort included 638 children born to 524 women followed-up during pregnancy for alcohol or substance abuse 19922001. Non-exposed children (n = 1914) born to control women were matched for maternal age, parity, number of foetuses, month of birth and delivery hospital of the index child. Perinatal and follow-up data of both cohorts were collected from national registers until 2007. Results: Postnatal maternal abuse-related healthcare utilization and use of medication were associated with child out-of-home care. Significant differences were in particular observed in the categories of maternal mental and behavioural disorders caused by psychoactive substance use as well as injury and poisoning. Maternal inpatient care for mental and behavioural disorders peaked at the time of child out-of-home care. Maternal abuse-related healthcare utilization was associated with early child healthcare utilization and use of medication for mental and behavioural disorders. These associations were largely explained by the association with child out-of-home care. Conclusions: Postnatal maternal abuse-related morbidity is associated with significant early child morbidity, use of medication and timing of out-of-home care.

Copyright 2012, Wiley-Blackwell


Seybold DJ; Broce M; Siegel E; Findley J; Calhoun BC. Smoking in pregnancy in West Virginia: Does cessation/reduction improve perinatal outcomes? Maternal and Child Health Journal 16(1): 133-138, 2012. (31 refs.)

To determine if pregnant women decreasing/quitting tobacco use will have improved fetal outcomes. Retrospective analysis of pregnant smokers from 6/1/2006-12/31/2007 who received prenatal care and delivered at a tertiary medical care center in West Virginia. Variables analyzed included birth certificate data linked to intervention program survey data. Patients were divided into four study groups: < 8 cigarettes/day-no reduction, < 8 cigarettes/day-reduction, more than 8 cigarettes/day-no reduction, and amore than 8 cigarettes/day-reduction. Analysis performed using ANOVA one-way test for continuous variables and Chi-square for categorical variables. Inclusion criteria met by 250 patients. Twelve women (4.8%) quit smoking; 150 (60%) reduced; 27 (10.8%) increased; and 61 (24.4%) had no change. Comparing the four study groups for pre-term births (< 37 weeks), 25% percent occurred in more than 8 no reduction group while 10% occurred in more than8 with reduction group (P = 0.026). The high rate of preterm birth (25%) in the non-reducing group depended on 2 factors: (1) more than 8 cigarettes/day at beginning and (2) no reduction by the end of prenatal care. Finally, there was a statistically significant difference in birth weights between the two groups: more than 8 cigarettes/day with no reduction (2,872.6 g) versus < 8 cigarettes/day with reduction (3,212.4 g) (P = 0.028). Smoking reduction/cessation lowered risk of pre-term delivery (< 37 weeks) twofold. Encouraging patients who smoke more than 8 cigarettes/day during pregnancy to decrease/quit prior to delivery provides significant clinical benefit by decreasing the likelihood of preterm birth. These findings support tobacco cessation efforts as a means to improve birth outcome.

Copyright 2012, Springer


Shah R; Diaz SD; Arria A; LaGasse LL; Derauf C; Newman E et al. Prenatal methamphetamine exposure and short-term maternal and infant medical outcomes. American Journal of Perinatology 29(5): 391-400, 2012. (37 refs.)

Objective: Examine maternal and infant medical outcomes of prenatal exposure to methamphetamine (MA). Study Design: Four hundred and twelve mother-infant pairs (204 MA-exposed and 208 unexposed matched comparisons) were enrolled in the Infant Development, Environment and Lifestyle (IDEAL) study. Exposure was determined by maternal self-report during this pregnancy and/or positive meconium toxicology. Maternal interviews assessed prenatal drug use, pregnancy course, and sociodemographic information. Medical chart reviews provided medical history, obstetric complications, infant outcomes, and discharge placement. Results: MA-using mothers were more likely to be poor, to have a psychiatric disorder/emotional illness and less prenatal care, and to be less likely to breast-feed their infant than comparison mothers. After adjusting for covariates, MA-exposed infants were more likely to exhibit poor suck, to have smaller head circumferences and length, to require neonatal intensive care unit (NICU) admission, and to be referred to child protective services (CPS). Several outcomes previously reported from studies that lacked adequate control groups or adjustment for covariates were not significantly different in this study. Conclusion: Prenatal MA exposure is associated with maternal psychiatric disorder/emotional illness, poor suck, NICU admission, and CPS involvement, and MA-exposed infants were less likely to be breast-fed; however, the absence of many serious complications, such as fetal distress, chronic hypertension, preeclampsia, placenta previa, abruptio placentae, and cardiac defects, suggests confounding variables influenced prior studies.

Copyright 2012, Thieme Medical Publishing


Singer LT; Moore DG; Fulton S; Goodwin J; Turner JJD; Min MO et al. Neurobehavioral outcomes of infants exposed to MDMA (Ecstasy) and other recreational drugs during pregnancy. Neurotoxicology and Teratology 34(3): 303-310, 2012. (55 refs.)

3,4-methylenedioxymethamphetamine (MDMA) or "Ecstasy" is one of the most widely used illicit recreational drugs among young adults. MDMA is an indirect monoaminergic agonist and reuptake inhibitor that primarily affects the serotonin system. Preclinical studies in animals have found prenatal exposure related to neonatal tremors and long-term learning and memory impairments. To date, there are no prospective studies of the sequelae of prenatal exposure to MDMA in humans, despite concerns about its potential for harmful effects to the fetus. The present study is the first to prospectively identify MDMA-using women during pregnancy and to document patterns and correlates of use with neonatal and early infancy outcomes of offspring. All mothers and infants were prospectively recruited through the Case Western Reserve University (CWRU) and University of East London (UEL) Drugs and Infancy Study (DAISY) that focused on recreational drug use in pregnant women. Women were interviewed about substance use prior to and during pregnancy and infants were seen at 1 and 4 months using standardized, normative assessments of neonatal behavior, and cognitive and motor development, including the NICU Network Neurobehavioral Scale (NNNS), the Bayley Mental and Motor Development Scales (MDI, PDI), and the Alberta Infant Motor Scales (AIMS). The sample was primarily middle class with some university education and in stable partner relationships. The majority of women recruited had taken a number of illicit drugs prior to or during pregnancy. Group differences between those polydrug using women who had specifically used MDMA during pregnancy (n = 28) and those who had not (n = 68) were assessed using chi-square and t-tests. MDMA and other drug effects were assessed through multiple regression analyses controlling for confounding variables. Women who used MDMA during pregnancy had fewer prior births and more negative sequelae associated with their drug use, including more health, work, and social problems. MDMA exposed infants differed in sex ratio (more male births) and had poorer motor quality and lower milestone attainment at 4 months, with a dose-response relationship to amount of MDMA exposure. These findings suggest risk to the developing infant related to MDMA exposure and warrant continued follow-up to determine whether early motor delays persist or resolve.

Copyright 2012, Elsevier Science


Singh SP; Gundavarapu S; Pena-Philippides JC; Rir-sima-ah J; Mishra NC; Wilder JA et al. Prenatal secondhand cigarette smoke promotes Th2 polarization and impairs goblet cell differentiation and airway mucus formation. Journal of Immunology 187(9): 4542-4552, 2011. (74 refs.)

Parental, particularly maternal, smoking increases the risk for childhood allergic asthma and infection. Similarly, in a murine allergic asthma model, prenatal plus early postnatal exposure to secondhand cigarette smoke (SS) exacerbates airways hyper-activity and Th2 responses in the lung. However, the mechanism and contribution of prenatal versus early postnatal SS exposure on allergic asthma remain unresolved. To identify the effects of prenatal and/or early postnatal SS on allergic asthma, BALB/c dams and their offspring were exposed gestationally and/or 8-10 wk postbirth to filtered air or SS. Prenatal, but not postnatal, SS strongly increased methacholine and allergen (Aspergillus)-induced airway resistance, Th2 cytokine levels, and atopy and activated the Th2-polarizing pathway GATA3/Lck/ERK1/2/STAT6. Either prenatal and/or early postnatal SS downregulated the Th1-specific transcription factor T-bet and, surprisingly, despite high levels of IL-4/IL-13, dramatically blocked the allergen-induced mucous cell metaplasia, airway mucus formation, and the expression of mucus-related genes/proteins: Muc5ac, gamma-aminobutyric acid A receptors, and SAM pointed domain-containing Ets-like factor. Given that SS/nicotine exposure of normal adult mice promotes mucus formation, the results suggested that fetal and neonatal lung are highly sensitive to cigarette smoke. Thus, although the gestational SS promotes Th2 polarization/allergic asthma, it may also impair and/or delay the development of fetal and neonatal lung, affecting mucociliary clearance and Th1 responses. Together, this may explain the increased susceptibility of children from smoking parents to allergic asthma and childhood respiratory infections.

Copyright 2011, American Association of Immunologists


Siqveland T; Smith L; Moe V. The impact of optimality on maternal sensitivity in mothers with substance abuse and psychiatric problems and their infants at 3 months. Infant Behavior & Development 35(1): 60-70, 2012. (69 refs.)

The main aim of this study was to investigate the predictive validity of four different optimality indexes, as well as infant perinatal status, in relation to maternal sensitivity in interaction at 3 months. The four optimality indexes comprised items related to substance abuse, psychiatric condition, relational experience and socioeconomic status (SES). Maternal sensitivity in mother-infant interaction was assessed in two different groups of mothers. One group consisted of mothers with substance abuse and psychiatric problems who underwent treatment during pregnancy. The other group of mothers had neither substance abuse nor psychiatric problems. The expectant mothers were interviewed in the third trimester of pregnancy. Medical records and meconium were obtained from the infants at birth. Three months after birth, maternal sensitivity in mother-infant interaction was assessed. Altogether 79 mother-infant dyads participated in the study. The mothers' optimality associated with relational experiences, as well as the infants' perinatal status were found to predict maternal sensitivity in mother-infant interaction at 3 months. The SES index was also significantly related to maternal sensitivity. The relation between group and maternal sensitivity was mediated by the mothers' optimality associated with relational experiences. This study points to the importance of addressing the mothers' own relational experiences and their current representations of motherhood during treatment, in order to support and enhance maternal sensitivity.

Copyright 2012, Elsevier Science


Smith LM; Paz MS; LaGasse LL; Derauf C; Newman E; Shah R et al. Maternal depression and prenatal exposure to methamphetamine: Neurodevelopmental findings from the infant development, environment, and lifestyle (ideal) study. Depression and Anxiety 29(6): 515-522, 2012. (48 refs.)

Background: Maternal depression is associated with a higher incidence of behavioral problems in infants, but the effects of maternal depression as early as 1 month are not well characterized. The objective of this study is to determine the neurobehavioral effects of maternal depression on infants exposed and not exposed to methamphetamine (MA) using the NICU Network Neurobehavioral Scale (NNNS). Methods: Four hundred twelve mother-infant pairs were enrolled (MA = 204) and only biological mothers with custody of their child were included in the current analysis. At the 1-month visit (n = 126 MA-exposed; n = 193 MA-unexposed), the Beck Depression Inventory-II (BDI-II) was administered, and the NNNS was administered to the infant. Exposure was identified by self-report and/or gas chromatography/mass spectroscopy confirmation of amphetamine and metabolites in newborn meconium. Unexposed subjects were matched, denied amphetamine use, and had negative meconium screens. General Linear Models tested the effects of maternal depression and prenatal MA exposure on NNNS, with significance accepted at P < .05. Results: The MA group had an increased incidence of depression-positive diagnosis and increased depression scores on the BDI-II. After adjusting for covariates, MA exposure was associated with increased arousal and handling scores, and a decreased ability to self-regulate. Maternal depression was associated with higher autonomic stress and poorer quality of movement. No additional differences were observed in infants whose mothers were both depressed and used MA during pregnancy. Conclusions: Maternal depression is associated with neurodevelopmental patterns of increased stress and decreased quality of movement, suggesting maternal depression influences neurodevelopment in infants as young as 1 month.

Copyright 2012, Wiley-Blackwell


Sucharew H; Khoury JC; Xu YY; Succop P; Yolton K. NICU Network Neurobehavioral Scale (NNNS) profiles predict developmental outcomes in a low-risk sample. Paediatric And Perinatal Epidemiology 26(4): 344-352, 2012. (22 refs.)

Background: Latent profile analysis (LPA) has been used previously to classify neurobehavioral responses of infants prenatally exposed to cocaine and other drugs of abuse. The objective of this study was to define NICU Network Neurobehavioral Scale (NNNS) profile response patterns in a cohort of infants with no known cocaine exposure or other risks for neurobehavior deficits, and determine whether these profiles predict neurobehavioral outcomes in these low-risk infants. Methods: NNNS exams were performed on 355 low-risk infants at approximately 5 weeks after birth. LPA was used to define discrete profiles based on the standard NNNS summary scales. Associations between the infant profiles and neurobehavioral outcomes at one to three years of age were examined. Results: Twelve of the 13 summary scales were used and three discrete NNNS profiles identified: social/easy going infants (44%), hypotonic infants (24%), and high arousal/difficult infants (32%). Statistically significant associations between NNNS profiles and later neurobehavioral outcomes were found for psychomotor development and externalizing behaviors. Hypotonic infants had both lower psychomotor development and lower externalizing scores compared to the other two profiles. Conclusions: Three distinct profiles of the NNNS summary scores were identifiable using LPA among infants with no known cocaine exposure. These profile patterns were associated with early childhood neurobehavioral outcome, similar to findings reported in a study of infants with substantial cocaine exposure, demonstrating the utility of this profiling technique in both exposed and unexposed populations.

Copyright 2012, Wiley-Blackwell


Suter MA; Aagaard K. What changes in DNA methylation take place in individuals exposed to maternal smoking in utero? (editorial). Epigenomics 4(2): 115-118, 2012. (21 refs.)


Thiering E; Bruske I; Kratzsch J; Thiery J; Sausenthaler S; Meisinger C et al. Prenatal and postnatal tobacco smoke exposure and development of insulin resistance in 10 year old children. International Journal of Hygiene and Environmental Health 214(5): 361-368, 2011. (34 refs.)

In this study, we evaluated the association between prenatal and postnatal exposure to environmental tobacco smoke and the development of insulin resistance in 10 year old children. Fasting blood samples were collected from 470 children participating in two prospective birth cohorts. Of those 276 were selected population based and enriched with 194 children exceeding the 85th percentile of body mass index in this age group. Children already having diabetes type 1 or 2 at the age of 10 years were excluded. Fasting blood insulin and glucose levels and calculated HOMA index for insulin resistance assessment were analysed using generalised additive models. Potential confounders were adjusted for. Insulin resistance was increased by 24% in children frequently exposed to environmental tobacco smoke during childhood (MR(adj) = 1.24, p = 0.001), while glucose levels were not. Exclusion of prenatally exposed children did not attenuate the association (MR(adj) = 1.25, p = 0.006). After stratification, the effect sizes were identical within overweight children and the population based sample of children. Insulin resistance and fasting insulin levels were increasing with increasing numbers of cigarettes smoked in children's home. Maternal smoking during the third trimester of pregnancy increased children's insulin levels (MR(adj) = 1.19, p = 0.037), and even more so, if children were exclusively breastfed after birth (MR(adj) = 1.31, p = 0.016). Increased mean ratios were found for smoking of a third person in addition to maternal smoking. Positive dose-dependent associations and independent effects of postnatal exposure suggest involvement of environmental tobacco smoke in the risk for development of insulin resistance in children.

Copyright 2011, Elsevier Science


Unger A; Jagsch R; Bawert A; Winklbaur B; Rohrmeister K; Martin PR et al. Are male neonates more vulnerable to neonatal abstinence syndrome than female neonates? Gender Medicine 8(6): 355-364, 2011. (45 refs.)

Background: Prior studies have shown an increased vulnerability among males to adverse outcomes during the postnatal period. Most children exposed to opioids and other medications in utero develop neonatal abstinence syndrome (NAS), yet individual predisposition for NAS is poorly understood. Objective: This investigation examined the role of neonatal sex in the postnatal period for neonates exposed to standardized opioid maintenance treatment in utero with a focus on NAS regarding severity, medication requirements, and duration. Methods: This was a secondary analysis of data collected in a prospective randomized, double-blind, double-dummy, multicenter trial (MOTHER study) that examined the comparative safety and efficacy of methadone and buprenorphine during pregnancy. A total of 131 neonates born to opioid-dependent women randomized at 6 US sites (n = 74) and 1 European site (n = 37) were analyzed. Sex-based differences in birth weight, length, head circumference, NAS duration, NAS severity, and treatment parameters of full-term neonates were assessed. Results: Males had a significantly higher birth weight (P = 0.027) and head circumference (P = 0.017) compared with females, with no significant sex difference in rates of preterm delivery. No significant sex-related differences were found for NAS development, severity, or duration, or medication administered, and there were no significant differences in concomitant drug consumption during pregnancy (P = 0.959). Conclusions: This unique prospective study shows similar postnatal vulnerability for both sexes, suggesting that factors other than sex are the major determinants of clinically significant NAS.

Copyright 2011, Elsevier Science


Unger A; Jagsch R; Jones H; Arria A; Leitich H; Rohrmeister K et al. Randomized controlled trials in pregnancy: Scientific and ethical aspects. Exposure to different opioid medications during pregnancy in an intra-individual comparison. Addiction 106(7): 1355-1362, 2011. (34 refs.)

Background: Chronic medical conditions such as opioid dependence require evidence-based treatment recommendations. However, pregnant women are under-represented in clinical trials. We describe the first within-subject comparison of maternal and neonatal outcomes for methadone-versus buprenorphine-exposed pregnancies. Although methadone is the established treatment of pregnant opioid-dependent women, recent investigations have shown a trend for a milder neonatal abstinence syndrome (NAS) under buprenorphine. However, it is not only the choice of maintenance medication that determines the occurrence of NAS; other factors such as maternal metabolism, illicit substance abuse and nicotine consumption also influence its severity and duration and represent confounding factors in the assessment of randomized clinical trials. Case series description Three women who were part of the European cohort of a randomized, double-blind multi-center trial with a contingency management tool [the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study], each had two consecutive pregnancies and were maintained on either methadone or buprenorphine for their first and then the respective opposite, still-blinded medication for their second pregnancy. Birth measurements, the total neonatal abstinence score, the total amounts of medication used to treat NAS and the days of NAS treatment duration were assessed. Results: Both medications were effective and safe in reducing illicit opioid relapse and avoiding preterm labor. Methadone maintenance yielded to a significantly higher neonatal birth weight. Data patterns suggest that buprenorphine exposure was associated with lower neonatal abstinence syndrome (NAS) scores. Findings from this unique case series are consistent with earlier reports using between-group analyses. Conclusions: Buprenorphine has the potential to become an established treatment alternative to methadone for pregnant opioid-dependent women. Under special consideration of ethical boundaries, psychopharmacological treatment during pregnancy must be addressed as an integral part of clinical research projects in order to optimize treatment for women and neonates.

Copyright 2011, Society for the Study of Addiction


van den Berg G; van Eijsden M; Vrijkotte TGM; Gemke RJBJ. Educational inequalities in perinatal outcomes: The mediating effect of smoking and environmental tobacco exposure. PLoS ONE 7(5): e-article 37002, 2012. (45 refs.)

Objective: Socioeconomic status (SES) is adversely associated with perinatal outcomes. This association is likely to be mediated by tobacco exposure. However, previous studies were limited to single perinatal outcomes and devoted no attention to environmental tobacco exposure. Therefore, this study aimed firstly to explain the role of maternal smoking in the association between maternal education and preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA), and secondly to explain whether environmental tobacco smoke mediates these associations further. Study Design: This study was nested in a population-based cohort study in the Netherlands, the Amsterdam Born Children and their Development (ABCD) study. Analyses were done in a sample of 3821 pregnant women of Dutch origin, using logistic regression analysis. Results: Least educated women, who were more often smoking and exposed to environmental tobacco smoke, had a significantly higher risk of PTB (OR 1.95 [95% CI: 1.19-3.20]), LBW (OR 2.41 [95% CI: 1.36-4.27]) and SGA (OR 1.90 [95% CI 1.32-2.74]) than highly educated women. The mediating effect of smoking in the least educated women was 43% for PTB, 55% for LBW and 66% for SGA. Environmental tobacco smoke did not explain these associations further. After adjustment for maternal smoking, the association between lower maternal education and pregnancy outcomes was no longer significant. Conclusions: Smoking explains to a considerable extent the association between lower maternal education and adverse perinatal outcomes. Therefore, tobacco-interventions in lower educated women should be primarily focussed on maternal smoking to reduce PTB, LBW, and SGA. Additional attention to environmental tobacco exposure does not seem to reduce educational inequalities in perinatal outcomes.

Copyright 2012, Public Library of Science


van der Zee B; de Beaufort I; Temel S; de Wert G; Denktas S; Steegers E. Preconception care: An essential preventive strategy to improve children's and women's health. Journal of Public Health Policy 32(3): 367-379, 2011. (53 refs.)

Reproductive health has improved little in the last few decades. The Netherlands, particularly in large cities, has relatively high perinatal death rates compared with other European countries. Lack of improvement in reproductive outcomes despite improved quality of and better access to prenatal care strongly suggests that prenatal care alone is insufficient. We discuss how preconception care offers new strategies for improving reproductive health, how it usefully connects the life course of the affected individual and many health-care disciplines, and the benefits of combining a top-down policy structure and bottom-up organisation around caregivers. Given the likely benefits and cost savings calculated for the Netherlands, we conclude that failing to facilitate preconception care would reflect a breakdown of both professional and governmental responsibilities.

Copyright 2011, Palgrave Macmillan Ltd


van Vonderen JJ; Siew ML; Hooper SB; de Boer MA; Walther FJ; te Pas AB. Effects of naloxone on the breathing pattern of a newborn exposed to maternal opiates. Acta Paediatrica 101(7): e309-e312, 2012. (11 refs.)

Aim: To give new insights into how an infant responded to naloxone, given after acquiring a maternal opiate by recording the breathing pattern directly after birth. Method: A respiratory recording is presented of an infant during resuscitation in the delivery room after receiving naloxone for respiratory depression, resulting from maternal remifentanyl use. Results: The infant was born apneic and bradycardic. Normal resuscitation manoeuvres had no effect on the respiratory drive. Directly after administration of naloxone, a tachypneic breathing pattern with sporadic expiratory breaking manoeuvres was observed. Conclusion: The immediate tachypnoea is most likely a direct effect of the naloxone causing an immediate rebound response after the release of the opiate-induced inhibition of the respiratory drive.

Copyright 2012, Wiley-Blackwell


Veid J; Karttunen V; Myohanen K; Myllynen P; Auriola S; Halonen T et al. Acute effects of ethanol on the transfer of nicotine and two dietary carcinogens in human placental perfusion. Toxicology Letters 205(3): 257-264, 2011. (61 refs.)

Many mothers use, against instructions, alcohol during pregnancy. Simultaneously mothers are exposed to a wide range of other environmental chemicals. These chemicals may also harm the developing fetus, because almost all toxic compounds can go through human placenta. Toxicokinetic effects of ethanol on the transfer of other environmental compounds through human placenta have not been studied before. It is known that ethanol has lytic properties and increases the permeability and fluidity of cell membranes. We studied the effects of ethanol on the transfer of three different environmental toxins: nicotine, PhIP (2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine) and NDMA (N-nitrosodimethylamine) in placental perfusion. We tested in human breast cancer adenocarcinoma cell line MCF-7 whether ethanol affects ABCG2/BCRP, which is also the major transporter in human placenta. We found that the transfer of ethanol is comparable to that of antipyrine, which points to passive diffusion as the transfer mechanism. Unexpectedly, ethanol had no statistically significant effect on the transfer of the other studied compounds. Neither did ethanol inhibit the function of ABCG2/BCRP. These experiments represent only the effects of acute exposure to ethanol and chronic exposure remains to be studied.

Copyright 2011, Elsevier Science


Wojtyla A; Gozdziewska M; Paprzycki P; Bilinski P. Tobacco-related foetal origin of adult diseases hypothesis: Population studies in Poland. Annals of Agricultural and Environmental Medicine 19(1): 117-128, 2012. (150 refs.)

Epidemiological studies in Poland show that tobacco smoking by adolescents at reproductive age is still frequently observed. This concerns both boys and girls. The study was based on all-Polish population studies of health behaviours of adolescents aged 14-24 (Youth Behavioural Polish Survey - YBPS) conducted in 2011, and the Pregnancy-related Assessment Monitoring Survey (PrAMS). More than 12% of pregnant women do not discontinue smoking in association with becoming pregnant and expose the foetus to tobacco smoke, despite being aware of the hazardous effect of smoking on the health of the mother and child. Smoking in pregnancy is mainly observed among mothers with a low education level and those aged under 23. According to the Baker's Foetal Origins of Adult Health and Diseases Hypothesis, exposure of the foetus to the components of tobacco smoke results in many perturbations in the form of a lower birth weight, prematurity, worse state of neonates after birth, and higher susceptibility to contacting civilization diseases at the age of adulthood. The results of studies confirm some observations. Polish studies clearly confirmed a lower birth weight of babies delivered by mothers who smoke; however, earlier termination of pregnancy and worse status of neonates after birth were not observed. According to the Baker's hypothesis, a lower birth weight of babies delivered by smoking mothers during the further life cycle exposes the offspring to the risk of contracting civilization diseases. The efforts undertaken by public health authorities should be biased towards education of the population at reproductive age about the hazardous effect of smoking on the health of the foetus and the offspring born. Women at reproductive age should be encouraged to discontinue smoking in association with the planning of pregnancy and in pregnancy.

Copyright 2012, Institute of Agricultural Medicine, Poland


Zabaneh R; Smith LM; LaGasse LL; Derauf C; Newman E; Shah R et al. The effects of prenatal methamphetamine exposure on childhood growth patterns from birth to 3 years of age. American Journal of Perinatology 29(3): 203-210, 2012. (39 refs.)

We examined the effects of prenatal methamphetamine (MA) exposure on growth parameters from birth to age 3 years. The 412 subjects included (n = 204 exposed) were enrolled at birth in the Infant Development, Environment and Lifestyle study, a longitudinal study assessing the effects of prenatal MA exposure on childhood outcomes. Individual models were used to examine the effects of prenatal MA exposure on weight, head circumference, height, and weight-for-length growth trajectories. After adjusting for covariates, height trajectory was lower in the exposed versus the comparison children (p = 0.021) over the first 3 years of life. Both groups increased height on average by 2.27 cm per month by age 3 years. In term subjects, MA exposure was also associated with a lower height trajectory (p = 0.034), with both the exposed and comparison groups gaining 2.25 cm per month by age 3 years. There was no difference in weight, head circumference, or weight-for-length growth trajectories between the comparison and the exposed groups. Children exposed prenatally to MA have a modest decrease in height growth trajectory during the first 3 years of life with no observed difference in weight, head circumference, or weight-for-length trajectories.

Copyright 2012, Thieme Medical Publishing