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CORK Bibliography: Prenatal Drug Exposure

118 citations. January 2007 to present

Prepared: September 2008

Abrahams RR; Kelly SA; Payne S; Thiessen PN; Mackintosh J; Janssen PA. Rooming-in compared with standard care for newborns of mothers using methadone or heroin. Canadian Family Physician 53: 1723-1730, 2007. (18 refs.)

OBJECTIVE To evaluate the effect of rooming-in (rather than standard nursery care) on the incidence and severity of neonatal abstinence syndrome among opioid-exposed newborns and on the proportion of mothers who retain custody of their babies at hospital discharge. DESIGN Retrospective cohort study. SETTING Lower mainland in southwestern British Columbia. PARTICIPANTS We selected 32 women in the city of Vancouver known to have used heroin or methadone during pregnancy between October 2001 and December 2002. Comparison groups were a historical cohort of 38 women in Vancouver and a concurrent cohort of 36 women cared for in a neighbouring community hospital. MAIN OUTCOME MEASURES Need for treatment with morphine, number of days of treatment with morphine, and whether babies were discharged in the custody of their mothers. RESULTS Rooming-in was associated with a significant decrease in need for treatment of neonatal abstinence syndrome compared with the historical cohort (adjusted relative risk [RR] 0.40, 95% confidence interval [CI] 0.20 to 0.78) and the concurrent cohort (adjusted RR 0.39, 95% CI 0.20 to 0.75). Rooming-in was also associated with shorter newborn length of stay in hospital compared with both comparison groups. Newborns who roomed in at BC Women's Hospital were significantly more likely to be discharged in the custody of their mothers than babies in the historical cohort (RR 2.23, 95% CI 1.43 to 3.98) or the concurrent cohort (RR 1.15 to 2.53) were. CONCLUSION Rooming-in might ease opioid-exposed newborns' transition to extrauterine life and promote more effective mothering.

Accornero VH; Amado AJ; Morrow CE; Xue LH; Anthony JC; Bandstra ES. Impact of prenatal cocaine exposure on attention and response inhibition as assessed by continuous performance tests. Journal of Developmental and Behavioral Pediatrics 28(3): 195-205, 2007. (61 refs.)

Objective: This study examined the influence of prenatal cocaine exposure on attention and response inhibition measured by continuous performance tests (CPTs) at ages 5 and 7 years. Methods: The baseline sample consisted of 253 cocaine-exposed and 223 non-cocaine-exposed children enrolled prospectively at birth and assessed comprehensively through age 7 years in the longitudinal Miami Prenatal Cocaine Study. This report includes a subsample of 415 children (219 cocaine-exposed, 196 non-cocaine-exposed) who completed at least one CPT assessment at ages 5 and/or 7 years. Prenatal cocaine exposure was measured by maternal self-report and maternal and infant bioassays. Deficits in attention and response inhibition are estimated in relation to prenatal cocaine exposure using generalized estimating equations within the general linear model. Results: Results indicate cocaine-associated increases in omission errors at ages 5 and 7 as well as increases in response times for target tasks (i.e., slower reaction times) and decreased consistency in performance at age 7. There were no demonstrable cocaine-associated deficits in commission errors. Estimates did not change markedly with statistical adjustment for selected prenatal and postnatal covariates. Conclusion: Evidence supports cocaine-associated deficits in attention processing through age 7 years.

Askew JP. Zolpidem addiction in a pregnant woman with a history of second-trimester bleeding. Pharmacotherapy 27(2): 306-308, 2007. (7 refs.)

Whether zolpidem crosses the placenta in humans is unknown. A 30-year-old Caucasian woman with a history of zolpidem abuse underwent spontaneous vaginal delivery at 38 weeks' gestation. Total fetal exposure to zolpidem was unknown, but it was estimated to be at least 1000 mg over at least 1 month. Typical peak plasma concentrations after a single 5- and 10-mg dose of zolpidem are 29-113 ng/ml (mean 59 ng/ml) and 58-272 ng/ml (mean 121 ng/ml), respectively Cord blood was sampled for zolpidem, with a result of 41 ng/ml. Despite the presence of zolpidem in the cord blood sample, the neonate was active and alert after normal delivery. No withdrawal symptoms were noted, and the mother and neonate were discharged home after 48-hour observation. This case report indicates that zolpidem crosses the human placenta, as was exemplified with cord blood sampling. The drug should therefore be used during pregnancy only if clearly necessary.

Bada HS; Langer J; Twomey J; Bursi C; Lagasse L; Bauer CR et al. Importance of stability of early living arrangements on behavior outcomes of children with and without prenatal drug exposure. Journal of Developmental and Behavioral Pediatrics 29(3): 173-182, 2008. (43 refs.)

Objective: We evaluated whether living arrangements of children with or without prenatal drug exposure would be associated with their behavior outcomes and adaptive functioning. Methods: A total of 1388 children with or without prenatal cocaine or opiate exposure were enrolled in a longitudinal cohort study at I month of age, were seen at intervals, tracked over time for their living situation, and evaluated for behavior problems and adaptive functioning at 3 years of age. The Child Behavior Checklist and Vineland Adaptive Behavior Scales were administered. Using multiple regression models, we determined the factors that would predict behavior problems and adaptive functioning. Results: Of the children enrolled, 1092 children were evaluated. Total and externalizing behavior problems T scores of children in relative care were lower (better) than those in parental care; externalizing behavior scores were lower than those in nonrelative care (p < .05). Total behavior problem scores increased 2.3 and 1.3 points, respectively, with each move per year and each year of Child Protective Services involvement. Compared to children in nonrelative care, those in parental or relative care had higher (better) scores in the Vineland Adaptive Behavior Scales total composite (p < .023), communication (p < .045), and daily living (p < .001). Each caretaker change was associated with a decrease of 2.65 and 2.19 points, respectively, in communication and daily living scores. Conclusion: Children's living arrangements were significantly associated with childhood behavior problems and adaptive functioning. The instability of living situation was also a significant predictor of these outcomes. While family preservation continues to be the goal of the child welfare system, expediting decision toward permanency remains paramount once children are placed in faster care.

Bennett DS; Bendersky M; Lewis M. Children's cognitive ability from 4 to 9 years old as a function of prenatal cocaine exposure, environmental risk, and maternal verbal intelligence. Developmental Psychology 44(4): 919-928, 2008. (81 refs.)

This study examined the effects of prenatal cocaine exposure, environmental risk, and maternal verbal intelligence on children's cognitive ability. Gender and age were examined as moderators of potential cocaine exposure effects. The Stanford-Binet IV intelligence test was administered to 23 1 children (91 cocaine exposed, 140 unexposed) at ages 4, 6, and 9 years. Neonatal medical risk and other prenatal exposures (alcohol, cigarettes, and marijuana) were also examined for their unique effects on child IQ. Mixed models analysis indicated that prenatal cocaine exposure interacted with gender, as cocaine-exposed boys had lower composite IQ scores. Age at assessment did not moderate this relation, indicating that cocaine-exposed boys had lower IQs across this age period. A stimulating home environment and high maternal verbal IQ also predicted higher composite IQ scores. Cocaine-exposed boys had lower scores on the Abstract[Visual Reasoning subscale, with trends for lower scores on the Short-Term Memory and Verbal Reasoning subscales, as exposure effects were observed across domains. The findings indicate that cocaine exposure continues to place children at risk for mild cognitive deficits into preadolescence. Possible mechanisms for the Exposure X Gender interaction are discussed.

Bennett D; Bendersky M; Lewis M. Preadolescent health risk behavior as a function of prenatal cocaine exposure and gender. Journal of Developmental and Behavioral Pediatrics 28(6): 467-472, 2007. (37 refs.)

Objective: To examine the effect of prenatal cocaine exposure on health risk behaviors during preadolescence. Methods: The present study examined prenatal cocaine exposure, gender, and environmental risk as predictors of self-reported substance use, aggression, and a disregard for safety precautions on the Youth Risk Behavior Survey in a sample of 10.5 year olds (n = 154, including 60 who were prenatally exposed to cocaine). Results: Gender tended to moderate the effects of prenatal cocaine exposure because exposure effects were found for boys but not girls. Boys who were prenatally exposed to cocaine reported engaging in more high-risk behavior. In examining individual outcomes, cocaine exposed boys had the highest scores for aggression, substance use, and a disregard for safety precautions, although these differences were significant only for the composite health risk behavior measure. Conclusions: The findings extend earlier work showing that prenatal cocaine exposure places boys at risk for problems of inhibitory control, emotional regulation, and antisocial behavior. Research is needed to examine whether the effects of prenatal cocaine on health risk behaviors persist into adolescence, when such behaviors tend to increase.

Beratis NG; Asimacopoulou A; Varvarigou A. Association of secondary sex ratio with smoking and parity. Fertility and Sterility 89(3): 662-667, 2008. (51 refs.)

Objective: To assess the sex ratio in offspring of smoking and nonsmoking mothers in relationship to parity. Design: Prospective study. Setting: University hospital. Patient(s): The authors studied 2,108 term singleton neonates born between 1993 and 2002, 665 from smoking mothers and 1,443 from nonsmoking mothers. Intervention(s): A prospective recording of maternal age, parity and smoking status, and gender of neonates delivered over a 10-year period. Main Outcome Measure(s): Secondary sex ratio in regard to maternal smoking and parity. Result(s): The offspring sex ratio in the total sample studied was 1.09; in the offspring of smoking and nonsmoking mothers, it was 1.26 and 1.03, respectively, a statistically significant difference. In the offspring of smoking women who had parity 1, 2, and >= 3, it was 1.47, 1.35, and 0.92, whereas in those of nonsmoking women, it was 1.04, 1.00, and 1.03, respectively (the differences of the parity 1 and 2 groups between the offspring of smoking and nonsmoking mothers were statistically significant). Logistic regression analysis showed that the possibility of a boy being delivered by a mother who smoked was significantly greater in primiparous women than in women who had parity 3, independent of the maternal age. Conversely, parity did not affect significantly the sex ratio in the offspring of nonsmoking women. Conclusion(s): The findings suggest that among women who smoked, significantly more male than female offspring are born from primiparous women, whereas women who had parity 3 gave birth to more female offspring; F biparous women give birth to significantly more male offspring, but the offspring sex ratio declined with the number of cigarettes when the mothers smoked >= 10 cigarettes per day.

Bergsjo P; Bakketeig LS; Lindmark G. Maternal smoking does not affect fetal size as measured in the mid-second trimester. Acta Obstetricia et Gynecologica Scandinavica 86(2): 156-160, 2007. (21 refs.)

Background. Cigarette smoking during pregnancy is causally related to birthweight, but we do not know whether fetal growth restriction is a continuous process or, if not, at what stage of pregnancy it affects weight gain. Material and methods. A random sample of para 1 and 2 mothers, drawn from the population of pregnant women in Bergen and Trondheim, Norway, and Uppsala, Sweden, were examined by a detailed questionnaire concerning smoking habits, menstrual history and pregnancy dating, and subjected to morphometric sonography of their fetuses in or around week 17. Of the 547 study participants, 31.9% were smokers. Gestational age was primarily determined by the last menstrual period [LMP], except in those with irregular cycles, and in 30 cases (6.6% of those with regular cycles) in whom the biparietal diameter [BPD]-determined age deviated > 14 days from the LMP-based date. Results. The analysis did not reveal any statistically significant differences between the fetuses of non-smokers, light smokers (0-9 cigarettes per day) and heavy (10 + cigarettes per day) smokers, regarding BPD, mean abdominal diameter [MAD] femur length [FL], and a 'body contour index': [BPD + FL] divided by MAD. Conclusion. Tobacco-induced fetal growth restriction probably begins after gestational week 17.

Binder T; Vavrinkova B. Prospective randomised comparative study of the effect of buprenorphine, methadone and heroin on the course of pregnancy, birthweight of newborns, early postpartum adaptation and course of the neonatal abstinence syndrome (NAS) in women followed up in the outpatient department. Neuroendocrinology Letters 29(1): 80-86, 2008. (13 refs.)

OBJECTIVE: The aim of the study was to evaluate the effect of substitution therapy in heroin addicted pregnant women on the course of pregnancy, perinatal outcomes and course of the neonatal abstinence syndrome. DESIGN OF THE STUDY. A five-year randomised prospective comparative study METHODS: The study was carried out in the period of 2002-2007. The group of patients included 147 i.v. heroin-addicted pregnant women. All of them were outpatients of our Perinatal Care Unit. Their daily dose of heroin was approximately lg. Later, 30 women were disqualified from the study for breaking the randomised criteria engagement. The substitution therapy in women who agreed to undergo it, started during the 1. trimester of pregnancy. Finally, 47 heroin, 32 methadone and 38 buprenorphine addicted women were enrolled in the study. Birthweight of newborns was compared with the national birthweight tables. Severity and duration of neonatal abstinence syndrome (NAS) were evaluated by Finnegan's score scale. RESULTS: None of the women delivered before the end of 34(th) gestational week. We did not encounter any perinatal death or developmental defect. The lowest birthweight, the highest number of newborns with IUGR and the most numerous placental changes were found in the group of heroin-addicted women. The differences compared to the two groups receiving substitution therapy were statistically significant (p < 0.05). The severity and course of NAS were the most severe (p < 0.001) in newborns of women from the methadone group.

Bono KE; Sheinberg N; Scott KG; Claussen AH. Early intervention for children prenatally exposed to cocaine. Infants and Young Children 20(1): 26-37, 2007. (59 refs.)

This article brings together information from our experience of providing research-based intervention to more than 600 children who were prenatally exposed to cocaine and from the research literature on the effects of prenatal cocaine exposure. Based on our experience and this literature, it is now clear that there are no large negative independent effects of cocaine exposure and that there is no "crack baby" syndrome. However, many of these children who have been exposed to cocaine are at risk for poor developmental outcomes, particularly in the area of language development, primarily because of the environmental factors that are associated with parental substance abuse. As our intervention research shows, early intervention can be effective in ameliorating some of this risk. Suggestions are made regarding programmatic steps that should be taken next to further improve program effectiveness and enhance the knowledge base.

Brion MJA; Leary SD; Lawlor DA; Smith GD; Ness AR. Modifiable maternal exposures and offspring blood pressure: A review of epidemiological studies of maternal age, diet, and smoking. (review). Pediatric Research 63(6): 593-598, 2008. (67 refs.)

Prenatal programming of adult disease is well established in animals. In humans the impact of common in utero exposures on long-term offspring health is less clear. We reviewed epidemiology studies of modifiable maternal exposures and offspring blood pressure (BP). Three maternal exposures were identified for review and meta-analyzed where possible: smoking during pregnancy, diet, and age at childbirth. Meta-analysis suggested there was a modest association between higher offspring BP and prenatal exposure to smoke (confounder-adjusted beta=0.62 mm Hg, 95% confidence interval: 0.19-1.05, I-2=16.4%). However, the level of confounder adjustment varied between studies, which in some studies attenuated the association to the null. There was no strong evidence that any component of maternal diet during pregnancy (maternal protein, energy, calcium, and various other nutrients) influences offspring BP. The results of studies of maternal age varied and there was strong evidence of heterogeneity in the pooled analysis. The association with maternal age, if present, was modest (confounder-adjusted beta=0.09 mm Hg/y, 95% confidence interval: -0.03 to 0.21, I-2=89.8%). In sum, there is little empirical evidence that the maternal exposures reviewed program offspring BP. Other components of offspring health may be more susceptible to effects of programming in utero.

Browne ML; Bell EM; Druschel CM; Gensburg LJ; Mitchell AA; Lin AE et al. Maternal caffeine consumption and risk of cardiovascular malformations. Birth Defects Research. Part A: Clinical and Molecular Teratology 79(7): 533-543, 2007. (36 refs.)

Background: The physiologic effects and common use of caffeine during pregnancy call for examination of maternal caffeine consumption and risk of birth defects. Epidemiologic studies have yielded mixed results, but such studies have grouped etiologically different defects and have not evaluated effect modification. Methods: The large sample size and precise case classification of the National Birth Defects Prevention Study allowed us to examine caffeine consumption and specific cardiovascular malformation (CVM) case groups. We studied consumption of caffeinated coffee, tea, soda, and chocolate to estimate total caffeine intake and separately examined exposure to each caffeinated beverage. Smoking, alcohol, vasoactive medications, folic acid supplement use, and infant gender were evaluated for effect modification. Maternal interview reports for 4,196 CVM case infants overall and 3,957 control infants were analyzed. Results: We did not identify any significant positive associations between maternal caffeine consumption and CVMs. For tetralogy of Fallot, nonsignificant elevations in risk were observed for moderate (but not high) caffeine intake overall and among nonsmokers (ORs of 1.3 to 1.5). Risk estimates for both smoking and consuming caffeine were less than the sum of the excess risks for each exposure. We observed an inverse trend between coffee intake and risk of atrial septal defect; however, this single significant pattern of association might have been a chance finding. Conclusions: Our study found no evidence for an appreciable teratogenic effect of caffeine with regard to CVMs.

Burke KD. Substance-exposed newborns: Hospital and child protection responses. Children and Youth Services Review 29(12): 1503-1519, 2007. (49 refs.)

Recent federal legislation mandates that newborns identified as prenatally substance-exposed be reported to local child protective agencies. However, the legislation does not outline methods of identifying such newborns. A number of methods of identifying substance-exposed newborns exist, including maternal self-report, urine tests of either mother or newborn, and meconium testing, each with its own benefits and drawbacks. Alcohol poses special challenges, as it is arguably as damaging to newborns as illegal substances, but it is treated differently by the medical profession and by child protective agencies than are illegal substances. There is inconsistency in the reporting by hospitals to child protective agencies, in terms of substances and maternal characteristics. This paper calls for hospitals to develop formal protocols for ascertaining prenatal substance exposure, including establishing objective criteria that both identifies a newborn as substance-exposed and dictates under what circumstances a newborn should be brought to the attention of child protective services. The child protective response is also seemingly inconsistent, and the system should develop appropriate responses for this population of newborns and their families.

Burns L; Mattick RP; Wallace C. Smoking patterns and outcomes in a population of pregnant women with other substance use disorders. Nicotine & Tobacco Research 10(6): 969-974, 2008. (38 refs.)

Using a retrospective cross-sectional study design, we examined smoking patterns and associated neonatal outcomes in infants born to women with a diagnosis of a substance use disorder in pregnancy. Antenatal and birth admissions were linked to midwives data on pregnancy care, services, and outcomes over a 5-year period (1998-2002). Birth admissions were flagged as positive for drug use where a birth admission or any pregnancy admission for that birth involved a cannabis-, opioid-, stimulant-, or alcohol-related ICD-10AM code. There were 4,346 live births to women with a substance-related diagnosis in pregnancy. Women with a substance-related diagnosis (the drug group) had an adjusted odds ratio for smoking during pregnancy of 10.8 (95% CI=9.9-11.7) relative to women without a substance-related diagnosis (the non-drug group). Women in the drug group also were heavier smokers; 26% smoked 1-10 cigarettes/day and 56% smoked more than 10 cigarettes/day compared with 8% in both groups in the non-drug group. Relative to the drug group, the adjusted odds ratio for quitting smoking during pregnancy in the non-drug group was 3.1 (95% CI=2.3-4.3). Among women in the drug group, any smoking significantly increased the risk of poor fetal growth, prematurity, and admission to the special care nursery. In conclusion, innovative and effective strategies for tobacco cessation should target pregnant women as a high priority. Further research should identify the models of tobacco cessation most suited to women who also use other substances during pregnancy.

Button TMM; Maughan B; McGuffin P. The relationship of maternal smoking to psychological problems in the offspring. Early Human Development 83(11): 727-732, 2007. (28 refs.)

There is strong evidence for an association between maternal smoking in pregnancy and psychological problems in offspring. The problems most frequently associated are attention problems, hyperactivity, and conduct problems, although there is some evidence for an association with substance use problems as well. The nature of this association is unclear, but it is likely the result of a number of different mechanisms. Animal studies provide evidence for a causal relationship, in which exposure to nicotine has detrimental effects on foetal development. Other studies suggest that factors that correlate with maternal prenatal smoking may be the real risk factors for behavioural problems, although evidence that the associations remain after controlling for such risks goes some way to dispel this as the only explanation. Finally, maternal prenatal smoking may index underlying psychological problems in the mother that are inherited by the offspring. In all likelihood, a combination of these mechanisms may contribute to observed relationships between prenatal smoking and offspring psychological problems. Now that the association is well established, future research needs to focus more strongly on disentangling underlying mechanisms. Although animal studies demonstrate a casual retationship, it appears from other research that this may not be the whole story in human samples. Furthermore, the relationship may only exist under certain conditions (i.e. against a certain genetic background), and this possibility warrants further examination, particularly in relation to other genetic risks, and outcomes other than ADHD. Application of the children-of-twins design may also cast further light on the processes involved.

Carter S; Paterson J; Gao WZ; Lusitini L. Maternal smoking during pregnancy and behaviour problems in a birth cohort of 2-year-old Pacific children in New Zealand. Early Human Development 84(1): 59-66, 2008. (47 refs.)

Aim: The present study investigated associations between maternal smoking during pregnancy and child behaviour problems in a cohort of Pacific Islands two-year-old children in New Zealand. Study design: Data were gathered as part of the Pacific Islands Families (PIF) Study. Mothers of a cohort of 1398 Pacific infants born in South Auckland, New Zealand were interviewed when their children were six-weeks, 12 and 24 months of age. Within the context of a wider interview, data regarding cigarette smoking during pregnancy was obtained from 1038 biological mothers at the six-week interview and reports of child behaviour using the Child Behaviour Checklist were gathered when the children were 24 months old. Results: The prevalence rates of clinically relevant cases were higher in children of smokers compared to non-smokers for internalising (22.6% versus 15.2%), externalising (9.6% versus 5.7%) and total problem scores (20% versus 12.4%). Following adjustment for potential confounding factors, smoking was associated with a moderately increased prevalence of total behaviour problems (OR=1.75, 95% CI=(1.12, 2.74); p=0.015). For internalising scores, the effects of smoking appeared to be raised for children of non-partnered mothers (OR=3.35, 95% CI=(1.29, 8.67); p=0.013). For externalising scores, smoking appeared to have a greater detrimental effect on girls (OR=237, 95% CI=(1.12, 5.04); p=0.024). Conclusions: Findings indicate there are significant effects of prenatal tobacco exposure on problem behaviour among young children. Smoking is a modifiable factor worthy of increased early preventive efforts.

Cepeda EE; Ostrea EM. 50 years ago in The Journal of Pediatrics - Narcotic withdrawal symptoms in the newborn infant resulting from maternal addiction. (editorial). Journal of Pediatrics 152(6): 776-776, 2008. (1 refs.)

Chang L; Alicata D; Ernst T; Volkow N. Structural and metabolic brain changes in the striatum associated with methamphetamine abuse. Addiction 102(Supplement 1): 16-32, 2007. (64 refs.)

Aims: To review structural, chemical and metabolic brain changes, particularly those in the basal ganglia, in individuals who used methamphetamine, as well as in children with prenatal methamphetamine exposure. Methods Magnetic resonance imaging (MRI) and positron emission tomography (PET) studies that evaluated brain structural, chemical and metabolite changes in methamphetamine subjects, or children with prenatal methamphetamine exposure, were reviewed and summarized. Relevant pre-clinical studies that provided insights to the interpretations of these imaging studies were also reviewed. Results: In adults who used methamphetamine, MRI demonstrates enlarged striatal volumes, while MR spectroscopy shows reduced concentrations of the neuronal marker N-acetylasparate and total creatine in the basal ganglia. In contrast, children with prenatal methamphetamine exposure show smaller striatal structures and elevated total creatine. Furthermore, PET studies consistently showed reduced dopamine transporter (DAT) density and reduced dopamine D-2 receptors in the striatum of methamphetamine subjects. PET studies also found lower levels of serotonergic transporter density and vesicular monoamine transporter (VMAT2) across striatal subregions, as well as altered brain glucose metabolism that correlated with severity of psychiatric symptoms in the limbic and orbitofrontal regions. Conclusion: Neuroimaging studies demonstrate abnormalities in brain structure and chemistry convincingly in individuals who used methamphetamine and in children with prenatal methamphetamine exposure, especially in the striatum. However, many important questions remain and larger sample sizes are needed to validate these preliminary observations. Furthermore, longitudinal studies are needed to evaluate the effects of treatment and abstinence on these brain changes and to determine whether imaging, and possibly genetic, markers can be used to predict treatment outcome or relapse.

Chaplin TM; Fahy T; Sinha R; Mayes LC. Young children's emotional arousal and self-regulation in a frustrating task: Effects of gender and prenatal cocaine exposure. (meeting abstract). Journal of Women's Health & Gender-based Medicine 16(8): 1114-1114, 2007. (0 refs.)

Chiriboga CA; Kuhn L; Wasserman GA. Prenatal cocaine exposures and dose-related cocaine effects on infant tone and behavior. Neurotoxicology and Teratology 29(3): 323-330, 2007. (53 refs.)

Background: In experimental models, prenatal cocaine exposure has been found to perturb monoaminergic development. In humans, numerous studies have sought clinical correlates, but few have focused on dose-related effects, especially as regards neurologic function beyond the neonatal period. Objective: To assess whether prenatal cocaine exposure has adverse effects on infant neurologic, developmental and behavioral outcomes and whether any effects are dose-dependent. Design/Methods: Infants (398) were enrolled at birth from an urban hospital. Drug exposure was ascertained with biomarkers in hair (n=395), urine (n = 170) and meconium (n = 109). Children were followed prospectively and 286 (72%) were evaluated blind to drug exposure at 6 months of age with the Bayley scales, Fagan Scale of Infant Intelligence and a standardized neurological examination. Results: Certain neurological findings increased significantly by the amount of cocaine detected in maternal hair, e.g. abnormality of tone, as indicated by extensor posture was detected among 28% of cocaine-unexposed infants, 43% of infants exposed to lower and 48% exposed to higher cocaine levels in maternal hair (p<0.009). Persistent fisting increased in a similar dose-dependent manner. These associations persisted in adjusted analyses. Prenatal cocaine exposure was not associated with developmental scores (mental, motor or novelty preference) but was associated with lower orientation scores in adjusted analyses. Conclusions: At 6 months of age, prenatal cocaine exposure was associated with abnormalities of tone and posture and with lower orientation scores. Perturbations in monoaminergic systems by cocaine exposure during fetal development may explain the observed neurological and behavioral symptoms. Whether such findings in infancy increase the risk of later neurobehavioral problems requires further study.

Chotro MG; Arias C; Laviola G. Increased ethanol intake after prenatal ethanol exposure: Studies with animals. (review). Neuroscience and Biobehavioral Reviews 31(2): 181-191, 2007. (119 refs.)

This review analyses the most relevant studies in which ethanol intake was measured after prenatal exposure to the drug. Despite the variety in methodology, in most such studies this prenatal experience induced a higher consumption of ethanol. Several variables that may affect the expression of this phenomenon are discussed, such as gender, age at testing, period of ethanol exposure, ethanol dose and conditions during the test. The mechanisms proposed in all these studies to explain the increased ethanol intake effect are also discussed. Some of these mechanisms are related to the teratological effects of the drug on the neurochemical systems involved in the reinforcing effects of abuse drugs, as well as on the regulatory systems of stress response. Another explanation of this phenomenon is also proposed in terms of associative learning. Specifically, the increased ethanol intake effect may be the result of a conditioned preference for ethanol acquired by the fetus when exposed to the drug during the last days of gestation.

Coleman T. Recommendations for the use of pharmacological smoking cessation strategies in pregnant women. CNS Drugs 21(12): 983-993, 2007. (49 refs.)

Maternal smoking during pregnancy causes significant fetal morbidity and is a public health problem, as 36% of women in the UK and 11% of those in the US smoke during pregnancy. Behavioural support for smoking cessation, provided outside of routine antenatal care, is effective for promoting smoking cessation by pregnant women, but relatively few pregnant women access such support. Effective pharmacological aids to smoking cessation, which have been trialled in nonpregnant populations, include nicotine replacement therapy (NRT), bupropion and varenicline; however, there is very little evidence to justify the use of these drugs in pregnancy. Also, for safety reasons, it is doubtful that definitive trials investigating the effectiveness of either bupropion or varenicline for smoking cessation will be conducted in pregnant women in the foreseeable future. In the short to medium term, research information relating to the use of these drugs in pregnancy is, therefore, likely to be derived from observational studies that are more difficult to interpret than clinical trials. This article assesses the evidence for the effectiveness and safety of using NRT, bupropion and varenicline for smoking cessation during pregnancy. The principle recommendations made are that NRT may be safer than smoking in pregnancy, and pregnant women who have unsuccessfully tried to stop smoking without pharmacotherapy may consider using NRT in subsequent quit attempts after informed discussion with their doctor. There is no evidence, however, that NRT is actually effective for smoking cessation in pregnancy. With currently available evidence, bupropion and varenicline cannot be recommended in pregnancy for smoking cessation.

Cornelius MD; Goldschmidt L; DeGenna N; Day NL. Smoking during teenage pregnancies: Effects on behavioral problems in offspring. Nicotine & Tobacco Research 9(7): 739-750, 2007. (104 refs.)

We prospectively examined the relationship between prenatal tobacco exposure (PTE) and child behavior in a birth cohort of 357 offspring of teenage mothers. PTE was defined as any exposure across pregnancy and, in separate analyses, exposure within each trimester. Outcomes included measures of behavior problems, activity, and attention. On average, the children were 6.4 years of age, 48% were females, and 69% were Black. Data on maternal tobacco and other substance use were collected prenatally and postnatally: 46% of the mothers smoked in the first trimester and 58(% smoked 6 years later. Child urinary cotinine measured exposure to environmental tobacco smoke (ETS). Stepwise multiple regressions were run. PTE predicted significantly increased offspring activity; impulsivity; and aggression, externalizing, and total behavior problems in step 1. PTE remained a significant predictor of increased activity when maternal psychological characteristics, home environment, and ETS were added. The results were similar when PTE was examined by trimesters, although later pregnancy tobacco exposure predicted the most behavioral outcomes. In the final model, PTE (all three trimesters) and PTE (second trimester) were significant predictors of increased activity and attention problems, respectively. Other predictors of child behavior included maternal anxiety, depression, hostility, and home environment. ETS was not a significant predictor of child behavior when PTE was considered. Smoking during pregnancy among adolescents is a significant predictor of increased activity and attention problems in their offspring after controlling for covariates in the prenatal and current environments. Smoking cessation interventions are recommended for this population to avoid the effects of PTE on the offspring of pregnant adolescents. This is particularly important because these mothers will likely become pregnant again and many will increase their level of tobacco use as they mature.

da Veiga PV; Wilder RP. Maternal smoking during pregnancy and birthweight: A propensity score matching approach. Maternal and Child Health Journal 12(2): 194-203, 2008. (30 refs.)

There is accumulated evidence of the existence of a deleterious effect of smoking on birth outcomes. Understanding the effect of smoking on pregnancy is a critical issue because of the public policy implications for dissuading maternal smoking. We explore this issue by using the propensity score method and compare that with parametric estimators. First we estimate the treatment effect of smoking during pregnancy on different birth outcomes, by race. Then, we extend the method to the case of the multi-treatment "intensity of smoking." The deleterious effect of smoking is found robust to the different estimation methods used.

de Chazeron I; Llorca PM; Ughetto S; Coudore F; Boussiron D; Perriot J et al. Occult maternal exposure to environmental tobacco smoke exposure. Tobacco Control 16(1): 64-65, 2007. (6 refs.)

Background: Environmental tobacco smoke ( ETS) is a recognised air pollutant. Its harmful effects have been found to be implicated in health disorders, including unfavourable pregnancy outcomes. The discrepancy between self-reported emvironmental tobacco smoke exposure and cotinine levels in pregnant non-smokers in France was examined. Method: Plasma cotinine was determined by a CPG- SM method on women who had answered a self-questionnaire describing their habits and environment during pregnancy. Results: Of 698 pregnant women reported as non-smokers, 305 ( 43.7%) claimed not to be exposed to ETS, yet 196 of these ( 64.3%) had plasma cotinine levels above the limit of detection. Conclusion: Self-reported data on ETS exposure in pregnant women therefore underestimate actual exposure. However, cotinine assay cab rectify this misclassification. An accurate identification of this risk factore will help to change attitudes towards ETS and avert its adverse effects on mother and fetus.

Derauf C; LaGasse LL; Smith LM; Grant P; Shah R; Arria A et al. Demographic and psychosocial characteristics of mothers using methamphetamine during pregnancy: Preliminary results of the Infant Development, Environment, and Lifestyle Study (IDEAL). American Journal of Drug and Alcohol Abuse 33(2): 281-289, 2007. (20 refs.)

This study describes the psychological characteristics and caretaking environments of 131 women enrolled in the first longitudinal study of prenatal methamphetamine (MA) exposure and child development. Prenatal MA use was associated with lower maternal perceptions on quality of life, greater likelihood of substance use among family and friends, increased risk for ongoing legal difficulties, and a markedly increased likelihood of developing a substance abuse disorder. Our preliminary findings suggest that MA using women are more likely to have multiple, intertwined psychosocial risks that may result in maladaptive parenting and caregiving. These factors may impact the developmental outcomes of affected children.

Diaz-Gomez NM; Mendoza C; Gonzalez-Gonzalez NL; Barroso F; Jimenez-Sosa A; Domenech E et al. Maternal smoking and the vitamin D-parathyroid hormone system during the perinatal period. Journal of Pediatrics 151(6): 618-623, 2007. (36 refs.)

Objective: To evaluate the effect of smoking on the vitamin D-parathyroid hormone (PTH) system during the perinatal period. Study design: Sixty-one healthy women with singleton pregnancies and their newborns participated in a cohort study. We compared serum PTH and BsmI polymorphism of the vitamin D receptor gene, 25 hydroxyvitamin D (25(OH)D), 1,25 dihydroxyvitamin D, calcium, phosphorus, and bone alkaline phosphatase (bALP) in a smoking group (n = 32) versus a non-smoking group (n = 29), controlling for lifestyle confounders. The mothers were examined at 30 to 32 weeks and 38 to 40 weeks of pregnancy, and the infants were examined at 2 to 3 days of postnatal life. Results: Mothers who smoked and their newborns showed decreased serum PTH (30-32 weeks, 26.9 +/- 10.7 pg/mL versus 37.1 +/- 19.5 pg/mL; 38-40 weeks, 32.2 +/- 13.5 pg/mL versus 46.2 +/- 21.9 pg/mL, P =.005; newborns, 43.4 +/- 21.8 versus 64.1 +/- 34.2 pg/mL, P = .02) and increased phosphorus. Newborns of mothers who smoked also had significantly lower anthropometric measurements and serum 25(OH)D (14.2 +/- 6.2 ng/mL versus 22.3 +/- 11.3 ng/mL, P = .009). In addition, pregnant women who smoked had lower bALP (30-32 weeks, 31 +/- 15 U/L versus 44 +/- 29 U/L; 38-40 weeks, 55 +/- 32 U/L versus 97 +/- 62 U/L, P = .005). Conclusions: Smoking during pregnancy negatively influences calcium-regulating hormones, leading to relative hypoparathyroidism in both the mother and their newborns.

Diego M; Field T; Hernandez-Reif M; Vera Y; Gil K; Gonzalez-Garcia A. Caffeine use affects pregnancy outcome. Journal of Child & Adolescent Substance Abuse 17(2): 41-49, 2007. (18 refs.)

A sample of 750 women were interviewed during pregnancy on their depression and anxiety symptoms, substance use and demographic variables. A subsample was seen again at the neonatal stage (n = 152), and their infants were observed for sleep-wake behavior. Symptoms of depression and anxiety were related to caffeine use. Mothers who consumed more caffeine also smoked more often, were younger, were less educated, reported less sleep effectiveness and more obstetric complications. Their newborns were lower birthweight, they spent less time in REM sleep and they showed more stress behaviors including hiccups, tremors and jerkiness.

Donnelly JC; Cooley SM; Walsh TA; Sarkar R; Durnea U; Geary MP. Illegal drug use, smoking and alcohol consumption in a low-risk Irish primigravid population. Journal of Perinatal Medicine 36(1): 70-72, 2008. (10 refs.)

To evaluate the prevalence of illegal drug use, smoking and alcohol consumption in Irish primigravidas, we interviewed 1011 women at their booking visit. A total of 23.5% (235) of women had used illegal drugs prior to their first pregnancy, 28.9% were ex-smokers and 27.9% were still smoking during pregnancy. A total of 53.9% admitted to drinking alcohol during pregnancy. Smokers are 2.8 times more likely to have used drugs in the past than non-smokers. Level of alcohol consumption appears to be a significant predictor of drug use.

D'Onofrio BM; Van Hulle CA; Waldman ID; Rodgers JL; Harden KP; Rathouz PJ et al. Smoking during pregnancy and offspring externalizing problems: An exploration of genetic and environmental confounds. Development and Psychopathology 20(1): 139-164, 2008. (80 refs.)

Previous studies have documented that smoking during pregnancy (SDP) is associated with offspring externalizing problems, even when measured covariates were used to control for possible confounds. However, the association may be because of nonmeasured environmental and genetic factors that increase risk for offspring externalizing problems. The current project used the National Longitudinal Survey of Youth and their children, ages 4-10 years, to explore the relations between SDP and offspring conduct problems (CPs), oppositional defiant problems (ODPs), and attention-deficit/hyperactivity problems (ADHPs) using methodological and statistical controls for confounds. When offspring were compared to their own siblings who differed in their exposure to prenatal nicotine, there was no effect of SDP on offspring CP and ODP. This suggests that SDP does not have a causal effect on offspring CP and ODP. There was a small association between SDP and ADHP, consistent with a causal effect of SDP, but the magnitude of the association was greatly reduced by methodological and statistical controls. Genetically informed analyses suggest that unmeasured environmental variables influencing both SDP and offspring externalizing behaviors account for the previously observed associations. That is, the current analyses imply that important unidentified environmental factors account for the association between SDP and offspring externalizing problems, not teratogenic effects of SDP.

England LJ; Grauman A; Qian C; Wilkins DG; Schisterman EF; Yu KF et al. Misclassification of maternal smoking status and its effects on an epidemiologic study of pregnancy outcomes. Nicotine & Tobacco Research 9(10): 1005-1013, 2007. (25 refs.)

Reliance on self-reported smoking status among pregnant women can result in exposure misclassification. We used data from the Calcium for Preeclampsia Prevention trial, a randomized study of nulliparous women conducted from 1992 to 1995, to characterize tobacco exposure misclassification among women who reported at study enrollment that they had quit smoking. Urinary cotinine concentration was used to validate quit status, and factors associated with exposure misclassification and the effects of misclassification on associations between smoking and pregnancy outcomes were evaluated using logistic regression. Of 4,289 women enrolled, 508 were self-reported smokers and 771 were self-reported quitters. Of 737 self-reported quitters with a valid cotinine measurement, 21.6% had evidence of active smoking and were reclassified as smokers. Women who reported having quit smoking during pregnancy were more likely to be reclassified than women who reported quitting before pregnancy (p <.001). Among smokers, factors independently associated with misclassification of smoking status included fewer cigarettes smoked per day and fewer years smoked. After reclassification the odds ratio for a small-for-gestationalage birth among smokers decreased by 14%, and the smoking-related reduction in birth weight decreased by 15%. Effects of misclassification on the association with hypertensive disorders of pregnancy were present but less dramatic. In conclusion, use of self-reported smoking status collected at the time of study enrollment resulted in the introduction of bias into our study of smoking and pregnancy outcomes. The potential for this type of bias should be considered when conducting and interpreting epidemiologic studies of smoking and pregnancy outcomes.

Fleming P; Blair PS. Sudden Infant Death Syndrome and parental smoking. Early Human Development 83(11): 721-725, 2007. (21 refs.)

Prenatal exposure to tobacco smoke is a major risk factor associated with Sudden Infant Death Syndrome (SIDS) and the risk has increased despite continued advice against this practice. Evidence from the UK suggests the prevalence of maternal smoking during pregnancy has risen amongst SIDS mothers (from 50% to 80%) when the rate amongst expectant mothers in the general population has fatten (from 30% to 20%) confirming pooled estimates from recent studies of a fourfold risk. An additional risk from postnatal exposure has also been identified; increasing with the number of smokers in the household or the daily hours the infant is subjected to a smoke-fitted environment. Exposure may lead to a complex range of effects upon normal physiological and anatomical development in fetal and postnatal life that places infants at greatly increased risk of SIDS. Recent legislation prohibiting smoking in public places needs to emphasise the adverse effects of tobacco smoke exposure to infants and amongst pregnant women.

Forrester MB; Merz RD. Risk of selected birth defects with prenatal illicit drug use, Hawaii, 1986-2002. Journal of Toxicology and Environmental Health. Part A, Current Issues 70(1): 7-18, 2007. (50 refs.)

The literature on the association between prenatal illicit drug use and birth defects is inconsistent. The objective of this study was to determine the risk of a variety of birth defects with prenatal illicit drug use. Data were derived from an active, population-based adverse pregnancy outcome registry. Cases were all infants and fetuses with any of 54 selected birth defects delivered during 1986 - 2002. The prenatal methamphetamine, cocaine, or marijuana use rates were calculated for each birth defect and compared to the prenatal use rates among all deliveries. Among all deliveries, the prenatal use rate was 0.52% for methamphetamine, 0.18% for cocaine, and 0.26% for marijuana. Methamphetamine rates were significantly higher than expected for 14 (26%) of the birth defects. Cocaine rates were significantly higher than expected for 13 (24%) of the birth defects. Marijuana rates were significantly higher than expected for 21 (39%) of the birth defects. Increased risk for the three drugs occurred predominantly among birth defects associated with the central nervous system, cardiovascular system, oral clefts, and limbs. There was also increased risk of marijuana use among a variety of birth defects associated with the gastrointestinal system. Prenatal uses of methamphetamine, cocaine, and marijuana are all associated with increased risk of a variety of birth defects. The affected birth defects are primarily associated with particular organ systems.

Garcia-Algar O; Felipe A; Puig C; Monleon T; Pacifici R; Pichini S. Fetal exposure to cocaine and infections during the first 18 months of life in infants from a mediterranean city. Acta Paediatrica 96(5): 762-763, 2007. (5 refs.)

Aim: The incidence of infections during the first 18 months of life was investigated in 36 infants prenatally exposed to cocaine and in 72 non-exposed controls from Barcelona, Spain. Methods: Fetal exposure to cocaine was ascertained by meconium analysis, infections by structured questionnaire. Results: A higher incidence of infections, if excluding those acquired in utero, was not found in exposed infants versus non-exposed infants of similar demographical and socioeconomic characteristics. Conclusions: A possible role for life style factor in those cases where increased infections are associated with fetal exposure to cocaine is hypothesized.

Gunes T; Koklu E; Yikilmaz A; Ozturk MA; Akcakus M; Kurtoglu S; Coskun A; Koklu S. Influence of maternal smoking on neonatal aortic intima-media thickness, serum IGF-I and IGFBP-3 levels. European Journal of Pediatrics 166(10): 1039-1044, 2007. (41 refs.)

Epidemiological studies have reported associations between a range of cardiovascular risk factors such as smoking and intima-media thickness (IMT). Some reports indicate that the maternal tobacco smoking causes disturbances of the endocrine status of the foetus. There are several potential mechanisms by which insulin-like growth factor I (IGF-I) could modify atherosclerotic processes either locally or in a systemic manner. The aim of this study was to investigate the influence of maternal smoking on neonatal aortic IMT (aIMT), serum IGF-I and IGF-binding protein-3 (IGFBP-3) levels. Aortic intima-media thickness was measured in 28 neonates whose mothers smoked during the pregnancy and 28 control neonates. Mean and weight-adjusted aIMT were significantly greater in the neonates whose mothers smoked (0.455 +/- 0.009 mm and 0.151 +/- 0.005 mm/kg, respectively) than in controls (0.403 +/- 0.029 mm and 0.118 +/- 0.014 mm/kg, respectively). Birth-weight of newborns whose mothers smoked was less than that of the controls. The decreases in serum IGF-I and IGFBP-3 observed in the infants whose mothers smoked were non-significant. Mean aIMT was negatively associated with birth-weight and IGF-I level. In conclusion, neonates whose mothers smoked have significantly increased aIMT. It might play a role in the pathogenesis of atherosclerosis in adult life.

Helmbrecht GD; Lewis KM; Ebert A. Pregnancy complicated by opiate addiction and fetal growth restriction. Journal of Addiction Medicine 2(1): 17-21, 2008. (12 refs.)

This case describes recovery of fetal growth restriction in utero after treatment for opiate addiction with the long-acting agent methadone. It is followed by discussions by an addiction medicine specialist followed by a maternal-fetal medicine specialist.

Helmbrecht GD; Thiagarajah S. Management of addiction disorders in pregnancy. Journal of Addiction Medicine 2(1): 1-16, 2008. (155 refs.)

In this article, we will review the prevalence of addiction disorders in pregnancy and the impact that it has on perinatal morbidity and mortality. We will then review effective screening techniques and propose a management scheme for achieving short-term abstinence leading to the ultimate goal of long-term recovery. The various medical and obstetric complications unique to this patient population will be discussed as well as the specific adverse effects of substance abuse on placentation and the developing fetus. Finally, medications proven efficacious in the treatment of addiction disorders will be reviewed in the context of their use in the pregnant population.

Herrmann M; King K; Weitzman M. Prenatal tobacco smoke and postnatal secondhand smoke exposure and child neurodevelopment. (review). Current Opinion in Pediatrics 20(2): 184-190, 2008. (112 refs.)

Purpose To review the recent scientific literature examining the association of prenatal tobacco and postnatal secondhand smoke exposure and child neurodevelopment. Recent findings Low birth weight and decreased in-utero brain growth are two of multiple potential etiologic pathways proposed as mediating the effects of prenatal tobacco smoke exposure on child neurodevelopment. These negative effects of prenatal exposure have been consistently demonstrated in animal models, and in humans have been found as early as the newborn period. The literature on both prenatal and postnatal exposure is remarkably consistent in showing associations with increased rates of behavior problems, including irritability, oppositional defiant behavior, conduct disorders and attention deficit hyperactivity disorder. A more rudimentary literature also suggests deficits in intelligence quotient. Recent studies have focused on elucidating the complex interaction among tobacco exposure, genetics and environmental factors. Questions still remain about the relative roles of prenatal vs. postnatal exposure and the potential role of genetic and social confounders, limiting the ability to infer a causal nature to these associations at this time. The consistency of findings across studies is, however, highly suggestive of a causal relationship between environmental tobacco exposure and adverse behavioral and cognitive outcomes in children. Summary Prenatal tobacco and postnatal secondhand smoke exposure is consistently associated with problems in multiple domains of children's neurodevelopment and behavior.

Huijbregts SCJ; Warren AJ; de Sonneville LMJ; Swaab-Barneveld H. Hot and cool forms of inhibitory control and externalizing behavior in children of mothers who smoked during pregnancy: An exploratory study. Journal of Abnormal Child Psychology 36(3): 323-333, 2008. (73 refs.)

This study examined whether children exposed to prenatal smoking show deficits in "hot" and/or "cool" executive functioning (EF). Hot EF is involved in regulation of affect and motivation, whereas cool EF is involved in handling abstract, decontextualized problems. Forty 7 to 9-year-old children (15 exposed to prenatal smoking, 25 non-exposed) performed two computerized tasks. The Sustained Attention Dots (SA-Dots) Task (as a measure of "cool" inhibitory control) requires 400 non-dominant hand and 200 dominant hand responses. Inhibitory control of the prepotent response is required for dominant hand responses. The Delay Frustration Task (DeFT) (as a measure of "hot" inhibitory control) consists of 55 simple maths exercises. On a number of trials delays are introduced before the next question appears on the screen. The extent of response-button pressing during delays indicates frustration-induced inhibitory control. Prenatally exposed children showed poorer inhibitory control in the DeFT than non-exposed children. A dose-response relationship was also observed. In addition, prenatally exposed children had significantly higher (dose-dependent) conduct problem- and hyperactivity-inattention scores. There were no significant group differences in inhibitory control scores from the SA-Dots. These results indicate that children exposed to prenatal smoking are at higher risk of hot but not cool executive function deficits.

Hussain T; Ewer AK. Maternal methadone may cause arrhythmias in neonates. (editorial). Acta Paediatrica 96(5): 768-769, 2007. (11 refs.)

Methadone treatment is a well recognised cause of QT interval lengthening in adults. In this case report, we present for the first time, clinically significant QT interval lengthening in a neonate secondary to maternal methadone treatment. Neonatal paediatricians should be aware of this important and potentially serious clinical phenomenon. Conclusion: Bradycardia, tachycardia or an irregular heart rate in an infant born to a mother on methadone treatment should not be ignored and a 12-lead electrocardiogram should be performed. Furthermore, there is also a need for a prospective study of QTc intervals in infants born to mothers receiving methadone.

Huuskonen P; Storvik M; Reinisalo M; Honkakoski P; Rysa J; Hakkola J; Pasanen M. Microarray analysis of the global alterations in the gene expression in the placentas from cigarette-smoking mothers. Clinical Pharmacology and Therapeutics 83(4): 542-550, 2008. (47 refs.)

The effects of maternal cigarette smoking on the transcriptome of human full-term placentas were investigated by a microarray analysis. QPCR was performed for a selected set of metabolizing genes. Differentially expressed genes were selected by fold change (+/- 1.5-fold) and analysis of variance (P<0.05) between the control and smoker groups. The expression of 174 probe sets was affected significantly. Chronic cigarette smoking induced the expression of CYP1A1. A trend toward a decrease in the expression of several steroid hormone-metabolizing enzymes, including CYP19A1, was detected. The expression of phase II enzymes was not altered, and no enriched categories were observed among the regulated genes, except for aryl hydrocarbon receptor (AhR)-CYP1A1. The unaltered expression of phase II enzymes may result in an increase in the levels of active metabolites and elevated oxidative chemical stress in the placenta and the fetus. On the basis of our results, it seems that cigarette smoke acts as a hormone disrupter in the placenta.

Hytinantti T; Kahila H; Renlund M; Jarvenpaa AL; Halmesmaki E; Kivitie-Kallio S. Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero. Acta Paediatrica 97(8): 1040-1044, 2008. (14 refs.)

Aim: To study the neonatal outcome of infants exposed to buprenorphine in utero. Methods: We prospectively followed 54 buprenorphine-using pregnant women and their 58 infants. Urinary buprenorphine and norbuprenorphine concentrations in the mothers were measured prior to delivery, and in the infants during the first 3 days of life. The Finnegan score was used to evaluate neonatal abstinence syndrome. Other medical problems as well as social outcomes were recorded. Results: All infants had buprenorphine in their urine. A total of 38 infants required 20 +/- 10 days (range 7-48 days) of morphine treatment for neonatal abstinence syndrome. The length of hospital stay for all infants was 25 +/- 19 days (range 3-125 days). The infants' highest urinary norbuprenorphine concentrations across their first 3 days of life correlated with the length of hospital stay and duration of morphine treatment (both p < 0.05). The mean birth weight and mean head circumference (n = 58) were below average (mean -0.7 standard deviation [SD] and mean -0.5 SD, respectively). Eleven infants were discharged home, 19 infants were placed in foster care and 28 infants were discharged with their mothers to Mother and Child homes or to other institutions. Conclusion: Maternal buprenorphine use at the time of birth may cause neonatal abstinence syndrome, requiring long-term hospitalization. Multiple social problems require a multidisciplinary team approach.

Infante-Rivard C. Caffeine intake and small-for-gestational-age birth: Modifying effects of xenobiotic-metabolising genes and smoking. Paediatric and Perinatal Epidemiology 21(4): 300-309, 2007. (45 refs.)

The relationship between caffeine consumption and small-for-gestational-age (SGA) birth remains uncertain. However, factors that can influence caffeine metabolism, such as genetic polymorphisms, have not been considered, while other similar factors such as smoking and ethnicity have not always been fully accounted for in the interpretation of results. A case-control study was carried out comprising 493 cases and 472 controls. Cases were newborns whose birthweight was below the 10th percentile according to gestational age and sex, based on national norms, and controls were at or above the 10th percentile. Caffeine consumption from beverages was estimated for each pregnancy trimester. Maternal and newborn variants in the CYP1A2 and CYP2E1 genes involved in the metabolism of caffeine were determined. Contrasting consumption >= 300 mg/day with a lower level, or using caffeiwne as a continuous measure, while adjusting for smoking and nausea, showed no increased risk for SGA. However, when stratifying for cigarette smoking, caffeine odds ratios (for the continuous and dichotomous measures) in the first trimester were statistically heterogeneous, suggesting a greater risk among non-smokers. Using birthweight as the outcome and caffeine as a continuous measure, a small 38 g [95% confidence interval -68, -8] decrement for every 100 mg of daily caffeine was observed in the third trimester. The studied polymorphisms did not modify the effect of caffeine. Caffeine consumption is unlikely to be a major risk factor for SGA or low birthweight in pregnant women.

Jackson DJ; Batiste E; Rendall-Mkosi K. Effect of smoking and alcohol use during pregnancy on the occurrence of low birthweight in a farming region in South Africa. Paediatric and Perinatal Epidemiology 21(5): 432-440, 2007. (38 refs.)

The aim of this case-control study was to determine the risk factors for low birthweight in a farming region in South Africa, with particular attention to maternal alcohol use and smoking, both independently and in combination. Data collection was via structured postpartum interviews and review of antenatal and delivery records. The study setting was a regional referral hospital in a farming region. The study subjects were 200 infants with birthweight < 2500g (cases) and 200 unmatched control infants of normal weight born during the same period as the cases. The outcome measure was low birthweight, i.e. infant birthweight < 2500 g. Results showed the contribution of term low birthweight (as a measure of intrauterine growth retardation) to the total low-birthweight incidence was almost 50%, indicating a substantial intrauterine growth retardation component in this population. Sociodemographic factors were not as predictive of low birthweight in this predominantly low income population. Smoking (adjusted OR 2.67, [95% CI 1.69, 4.20]) was the strongest life style-related predictor of low birthweight. The alcohol low-birthweight relationship was not significant when adjusted for smoking status (crude OR 2.15, [95% CI 1.37, 3.39]; adjusted OR 1.32, [95% CI 0.80, 2.20]). However, there appeared to be an interaction with combined use of these two substances during pregnancy that increased the risk of low birthweight (adjusted OR increased to 4.24, [95% CI 1.01, 17.76]. It is clear that life style factors such as smoking and drinking are contributing to the occurrence of low birthweight in the target region. A comprehensive health promotion programme needs to be implemented as an integral part of antenatal and family planning services, to reduce smoking and drinking by women in this community.

Jaddoe VWV; de Ridder MAJ; van den Elzen APM; Hofman A; Uiterwaal CSPM; Witteman JCM. Maternal smoking in pregnancy is associated with cholesterol development in the offspring: A 27-years follow-up study. Atherosclerosis 196(1): 42-48, 2008. (29 refs.)

Objective: To examine the associations of maternal smoking in pregnancy with development of cholesterol levels from childhood to adulthood. Methods: Total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol were measured annually from 1975 to 1993 and in 2002 in 350 subjects aged 5-19 years at baseline who participate in a prospective cohort study. Pregnancy and birth data were obtained through questionnaires sent to the parents. Results: Children of mothers who smoked in pregnancy showed a higher annual change in total cholesterol of 0.12 mmol/l per 10 years (95% confidence interval (CI): 0, 0.23) compared to children whose mothers did not smoke in pregnancy. Larger effect estimates were found in children with moderate overweight (0.39 mmol/l per 10 years (95% CI: 0.14, 0.63). HDL-cholesterol and LDL-cholesterol showed tendencies towards a decrease and increase, respectively, in children of mothers who smoked in pregnancy compared to children whose mothers did not smoke in pregnancy. Adjustment for potential confounders did not materially change the effect estimates. Conclusion: This study suggests for the first time that maternal smoking in pregnancy is associated with an increased rise in total cholesterol levels and a tendency towards an adverse lipoprotein profile in the offspring

Jauniaux E; Burton GJ. Morphological and biological effects of maternal exposure to tobacco smoke on the feto-placental unit. Early Human Development 83(11): 699-706, 2007. (84 refs.)

Active and passive maternal smoking has a damaging effect in every trimester of human pregnancy. Cigarette smoke contains scores of toxins which exert a direct effect on the placental and fetal cell proliferation and differentiation and can explain the increased risk of miscarriage, fetal growth restriction (FGR) stillbirth, preterm birth and placental abruption reported by epidemiological studies. In the placenta, smoking is associated from early in pregnancy, with a thickening of the trophobtastic basement membrane, an increase in collagen content of the villous mesenchyme and a decrease in vascularisation. These anatomical changes are associated with changes in placental enzymatic and synthetic functions. In particular, nicotine depresses active amino-acid (AA) uptake by human placental. villi and trophoblast invasion and cadmium decreases the expression and activity of 11 beta-hydroxysteroid dehydrogenase type 2 which is causally linked to FGR. Maternal smoking also dysregulates trophoblast expression of molecules that govern cellular responses to oxygen tension. In the fetus, smoking is associated with a reduction of weight, fat mass and most anthropometric parameters and as in the placenta with alterations in protein metabolism and enzyme activity. These alterations are the results of a direct toxic effect on the fetal cells or an indirect effect through damage to, and/or functional disturbances of the placenta. In particular, smoking interferes strongly with the fetal brain and pancreas biological parameters and induces chromosomal instability, which is associated with an increase in the risk of cancer, especially childhood malignancies.

Jessup MA. Organizational change in a perinatal treatment setting: Integration of clinical practice and policies on tobacco and smoking cessation. Journal of Psychoactive Drugs 39(4): 461-472, 2007. (84 refs.)

Perinatal smoking presents serious health risks to the fetus, mother, and child. Despite extensive evidence of risk and high rates of smoking among in-treatment perinatal women substance abusers, tobacco-related practice and policy change has not been widely transferred for application in drug abuse treatment programs for pregnant and parenting women: This qualitative study investigated the process of change and the resultant adoption of clinical policy and treatment innovation in a residential drug abuse treatment program that converted from tobacco-tolerant to tobacco-free with provision of smoking cessation services. Informed by the Organizational Readiness for Change Model, staff interviews and data analysis were conducted to examine program characteristics affecting adoption. An organizational climate of openness to change and the program's clarity of mission, expressed in perinatal-specific motivators for change, influenced the adoption of tobacco-related clinical practice and policy. Re-allocation of time, previously occupied by smoking behaviors, allowed for added promotion of maternal-child interaction and positive role-modeling for children.

Jobe AH. Maternal smoking disrupts fetal and neonatal calcium metabolism. (editorial). Journal of Pediatrics 151(6): 2A-2A, 2007. (0 refs.)

Julvez J; Ribas-Fito N; Torrent M; Forns M; Garcia-Esteban R; Sunyer J. Maternal smoking habits and cognitive development of children at age 4 years in a population-based birth cohort. International Journal of Epidemiology 36(4): 825-832, 2007. (44 refs.)

Background: Active maternal smoking during pregnancy has been associated with a higher risk of behavioural disorders in children, but a few cohort studies measuring smoking data prospectively have studied its specific effects on the cognitive abilities of pre-schoolers. Method: A birth cohort was set up in Menorca Island in 1997 within the Asthma Multicenter Infants Cohort Study. A total of 420 (87% of those eligible) children had complete data for final analyses at age 4 years. Interviewer-administered questionnaires were completed by mothers during the third trimester of pregnancy and then every year up to age 4 years of their child. A standardized version of the McCarthy Scales of Children's Abilities (MCSA) was used to evaluate the child's motor and cognitive capabilities. Multivariable regressions were used with MCSA`s assessed outcomes adjusting for: home location, maternal alcohol consumption, mother's social class and level of education during pregnancy, parity, marital status, father's education level, child's gender, birth weight and height, breastfeeding duration, passive smoking, school season, age during test administration and evaluator (psychologist). Results: A high global consistency in maternal smoking habits was found (total agreement= 88.7%). Maternal social class and education level were inversely associated with maternal smoking behaviour. Maternal smoking during pregnancy (in cig./day) was associated with a decrease (in points) of children's global cognitive score [beta=-0.60, (95% CI: -1.10; -0.09)]; as wen as global cognitive sub-areas like verbal score [beta = -0.59, (95% CI: -1.11; -0.07)]; quantitative score [beta=-0.57, (95% CI: -1.08; -0.06)]; executive function score [beta = -0.71, (95% CI: -1.23; -0.20)]; and working memory score [beta=-0.46, (95% CI: -0.92; -0.01)]. Conclusion: Our findings suggest an association with maternal smoking during pregnancy and lowered cognitive development in children at age 4 years.

Kable JA; Coles CD; Lynch ME; Platzman K. Physiological responses to social and cognitive challenges in 8-year olds with a history of prenatal cocaine exposure. Developmental Psychobiology 50(3): 251-265, 2008. (76 refs.)

Cocaine-exposed infants have been found to have altered arousal responses but little is known about such responses in later childhood. Physiological responses to stressors were used to assess the arousal modulation of school-aged, cocaine-exposed children (n = 73) and two contrast groups, socioeconomically-matched controls (n = 58) and children with behavioral disturbance (n = 35). The behaviorally disturbed group had the highest heart rate across conditions but demonstrated a pattern of hyporesponsiveness to the stressors. They had the smallest decrement in skin conductance response at baseline and the least recovery of skin conductance response following exposure to stressors. Cocaine-exposed children demonstrated greater acceleratory responses to the stressors as indexed by their skin conductance level and were intermediate between the socioeconomically-matched controls and children with behavioral disturbance in recovery of skin conductance response following stressors. Altered arousal responses associated with prenatal cocaine exposure persisted into middle childhood but were different from those found in behaviorally disturbed children.

Kahila H; Kivitie-Kallio S; Halmesmaki E; Valanne L; Autti T. Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine. Acta Radiologica 48(2): 228-231, 2007. (16 refs.)

Purpose: To evaluate the brains of newborns exposed to buprenorphine prenatally. Material and Methods: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. Results: Neither structural abnormalities nor abnormalities in signal intensity were recorded. Conclusion: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process.

Koren G; Hutson J; Gareri J. Novel methods for the detection of drug and alcohol exposure during pregnancy: Implications for maternal and child health. Clinical Pharmacology and Therapeutics 83(4): 631-634, 2008. (31 refs.)

Despite extensive evidence of fetal and neonatal risk, a large number of pregnant women are involved in excessive alcohol and drug abuse, such as with cocaine, methamphetamine, opioids, and cannabinoids.

Latzin P; Frey U; Roiha HL; Baldwin DN; Regamey N; Strippoli MPF; Swiss Pediatric Respiratory Research Group. Prospectively assessed incidence, severity, and determinants of respiratory symptoms in the first year of life. Pediatric Pulmonology 42(1): 41-50, 2007. (39 refs.)

Respiratory symptoms are common in infancy. Nevertheless, few prospective birth cohort studies have studied the epidemiology of respiratory symptoms in normal infants. The aim of this study was to prospectively obtain reliable data on incidence, Severity and determinants of common respiratory symptoms (including cough and wheeze) in normal infants and to determine factors associated with these symptoms. In a prospective population-based birth cohort, we assessed respiratory symptoms during the first year of life by weekly phone calls to the mothers. Poisson regression was used to examine the association between symptoms and various risk factors. In the first year of life, respiratory symptoms occurred in 181/195 infants (93%), more severe symptoms in 89 (46%). The average infant had respiratory symptoms for 4 weeks and 90% had symptoms for less than 12 weeks (range 0 to 23). Male sex, higher birth weight, maternal asthma, having older siblings and nursery care were associated with more, maternal hay fever with fewer respiratory symptoms. The association with prenatal maternal smoking decreased with time since birth. This study provides reliable data on the frequency of cough and wheeze during the first year of life in healthy infants; this may help in the interpretation of published hospital and community-based studies. The apparently reduced risk in children of mothers with hayfever but no asthma, and the decreasing effect of prenatal smoke exposure over time illustrate the complexity of respiratory pathology in the first year of life.

Leon AEC; Michienzi K; Ma CX; Hutchison AA. Serum caffeine concentrations in preterm neonates. American Journal of Perinatology 24(1): 39-47, 2007. (20 refs.)

Caffeine therapy reduces apnea of prematurity, promotes successful extubation from invasive positive-pressure ventilation, and decreases the incidence of bronchopulmonary dysplasia. The recommended dosing for caffeine is a loading dose of 20 mg/kg followed by a 5 mg/kg/d maintenance dose. However, controversy exists about the optimal dosing regimen and data on serum caffeine concentrations in extremely immature infants are scant. We determined serum caffeine concentrations similar to 7 days after starting therapy with a 20 or 25 mg/kg loading dose and a 6 mg/kg/d maintenance dose in 154 infants with a mean gestational age of 29 weeks. The 25th to 75th percentile range for the serum caffeine concentrations with the two dosing regimens was equivalent, similar to 18 to 23 mg/L. Within the first 14 postnatal days, the serum caffeine concentrations were not dependent on postmenstrual age, weight, or postnatal age, and were in a range that is safe and therapeutic. This latter observation remained valid over the ranges of clinical and laboratory assessments of renal and hepatic functions that are usually found in practice. Routine measurement of steady-state serum caffeine concentrations in infants 24 to 35 weeks gestational age is not required in the absence of ongoing apnea/hypopnea or signs compatible with toxicity.

Lewis BA; Kirchner HL; Short EJ; Minnes S; Weishampel P; Satayathum S et al. Prenatal cocaine and tobacco effects on children's language trajectories. Pediatrics 120(1): E78-E85, 2007. (37 refs.)

OBJECTIVE. The objective of this study was to examine the effects of prenatal cocaine and polydrug exposure on language development of preschool children using a prospective longitudinal model, controlling for confounders. METHODS. Children who were exposed to cocaine in utero (n = 209) and nonexposed children (n = 189) were followed prospectively at birth and at 1, 2, 4, and 6 years of age and were compared on receptive, expressive, and total language scores across time using random coefficient models, controlling for confounders. RESULTS. A significant, stable effect of cocaine exposure on language development was observed over time for all language domains, with cocaine exposure related to poorer language performance. Cigarette exposure was related to lower receptive language scores. Environmental influences on language scores were also observed. Both the cocaine-exposed and nonexposed children declined in language performance over time. CONCLUSIONS. Prenatal cocaine exposure has a stable negative effect on language skills during the first 6 years of life. Both cocaine-exposed and nonexposed children showed decreased language growth over time; however, cocaine-exposed children demonstrated linguistic deficits compared with nonexposed peers and did not catch up. Cigarette and environmental influences were also noted.

Loopez P; Bermejo AM; Tabernero MJ; Fernaandez P; Alvarez I. Determination of cocaine and heroin with their respective metabolites in meconium by gas chromatography-mass spectrometry. Journal of Applied Toxicology 27(5): 464-471, 2007. (26 refs.)

The analysis of meconium specimens is a relatively accurate method for the detection of fetal exposure to drugs. The purpose of this study was to develop and validate a method for meconium sample preparation for a gas chromatography-mass spectrometry (GC-MS) confirmation of meconium extracts for cocaine, benzoylecgonine, codeine, morphine and 6-monoacetylmorphine. The analytes were initially extracted from the matrix by methanol. Subsequently a solid-phase extraction with Waters Oasis(R) HLB cartridges was applied. Analytes were determined in GC-MS single monitoring mode. The method was validated in the range 40-2000 ng g(-1) using 0.5 g of meconium per assay. The detector response was linear over the studied range, and limits of quantitation and detection were found to be acceptable. Intra- and inter-batch coefficients of variation oscillated between 2.54% and 20.5%, and mean relative errors were in the range 0.79%-19.9%. The recoveries were higher than 42.1% in all cases. Finally the method was applied to analysis of meconium in newborns to assess fetal exposure to cocaine and opiates.

Lozano J; Garcia-Algar O; Vall O; de la Torre R; Scaravelli G; Pichini S. Biological matrices for the evaluation of in utero exposure to drugs of abuse (review). Therapeutic Drug Monitoring 29(6): 711-734, 2007. (111 refs.)

In recent years, the evaluation of in utero exposure to drugs of abuse has been achieved by testing biological matrices coming from the fetus or newborn (eg, meconium, fetal hair, cord blood, neonatal urine), the pregnant or nursing mother (eg, hair, blood, oral fluid, sweat, urine, breast milk), or from both the fetus and the mother (placenta, amniotic fluid). Overall, these matrices have the advantage of noninvasive collection (with the exception of amniotic fluid) and early detection of exposure from different gestational periods. Matrices such as amniotic fluid, meconium, fetal hair, and maternal hair provide a long historical record of prenatal exposure to certain drugs and can account for different periods of gestation: amniotic fluid from the early pregnancy, meconium for the second and third trimester of gestation, fetal hair for the third, and finally maternal hair (when long enough) for the whole pregnancy. Placenta may reveal the passage of a substance from the mother to the fetus. Cord blood and neonatal urine are useful for determining acute exposure to drugs of abuse in the period immediately previous to delivery. Drug detection in maternal blood, oral fluid, and sweat accounts only for acute consumption that occurred in the hours previous to collection and gives poor information concerning fetal exposure. Different immunoassays were used as screening methods for drug testing in the above-reported matrices or as unique analytical investigation tools when chromatographic techniques coupled to mass spectrometry were not commonly available. However, in the last decade, both liquid and gas chromatography-mass spectrometric methodologies have been routinely applied after appropriate extraction of drugs and their metabolites from these biological matrices.

Lozano J; Garcia-Algar O; Marchei E; Vall O; Monleon T; Di Giovannandrea R et al. Prevalence of gestational exposure to cannabis in a Mediterranean city by meconium analysis. Acta Paediatrica 96(12): 1734-1737, 2007. (6 refs.)

Aim: To investigate the prevalence of in utero exposure to cannabis in a cohort of 974 mother-infants dyads from Barcelona (Spain). Methods: A validated gas chromatographic-mass spectrometric assay was used for meconium analysis. Results: Prenatal exposure to cannabis was detected in 5.3% newborns; however, only 1.7% of the participating mothers disclosed gestational drug use. Ethnicity was not associated with cannabis use, nor were the maternal features or newborns somatometry. A significantly higher percentage of cannabis using mothers had a managerial professional job versus nonusers. Conclusions: Meconium analysis is especially important to identify neonates who have been exposed to cannabis in utero, which appear normal at birth and therefore may not be recognized. Timely detection of these newborns at risk provides the basis for appropriate treatment and adequate medical and social follow-up.

Lumeng JC; Cabral HJ; Gannon K; Heeren T; Frank DA. Pre-natal exposures to cocaine and alcohol and physical growth patterns to age 8 years. Neurotoxicology and Teratology 29(4): 446-457, 2007. (53 refs.)

Two hundred and two primarily African American/Caribbean children (classified by maternal report and infant meconium, as 38 heavier, 74 lighter and 89 not cocaine-exposed) were measured repeatedly from birth to age 8 years to assess whether there is an independent effect of pre-natal cocaine exposure on physical growth patterns. Children with fetal alcohol syndrome identifiable at birth were excluded. At birth, cocaine and alcohol exposures were significantly and independently associated with lower weight, length and head circumference in cross-sectional multiple regression analyses. The relationship over time of pre-natal exposures to weight, height, and head circumference was then examined by multiple linear regression using mixed linear models including covariates: child's gestational age, gender, ethnicity, age at assessment, current caregiver, birth mother's use of alcohol, marijuana and tobacco during the pregnancy and pre-pregnancy weight (for child's weight) and height (for child's height and head circumference). The cocaine effects did not persist beyond infancy in piecewise linear mixed models, but a significant and independent negative effect of pre-natal alcohol exposure persisted for weight, height, and head circumference. Catch-up growth in cocaine-exposed infants occurred primarily by 6 months of age for all growth parameters, with some small fluctuations in growth rates in the preschool age range but no detectable differences between heavier versus unexposed nor lighter versus unexposed thereafter. reserved.

MacArthur AC; McBride ML; Spinelli JJ; Tamaro S; Gallagher RP; Theriault G et al. Risk of childhood leukemia associated with parental smoking and alcohol consumption prior to conception and during pregnancy: the cross-Canada childhood leukemia study. Cancer Causes and Control 19(3): 283-295, 2008. (45 refs.)

Objective As part of a larger case-control study, the authors evaluated risk of childhood leukemia relative to parental self-reported smoking and alcohol consumption. Methods Children 0-14 years of age diagnosed with leukemia between 1990 and 1994 were ascertained through population-based sources at the time of diagnosis. For each participating case, an age, gender, and area-matched control was randomly selected from provincial government health insurance rolls. Risk factor information was obtained through personal interviews with each child's parents. Conditional logistic regression models were used to examine risk of leukemia associated with parental smoking and drinking. Results Maternal alcohol consumption prior to conception (OR = 1.37, 95% CI, 0.99-1.90) and during pregnancy (OR = 1.39, 95% CI, 1.01-1.93) was associated with an excess risk of childhood leukemia, with a positive dose-response trend for increasing weekly consumption (p< 0.05). Similar results were observed for children diagnosed with acute lymphoblastic leukemia (ALL). Odds ratios for maternal cigarette smoking before and during pregnancy were consistently elevated above one, but not statistically significant. No relationship was observed with paternal drinking or smoking in the perinatal period. Conclusion Our study suggests that maternal alcohol drinking before or during pregnancy may contribute to an increased risk of childhood leukemia.

Malik S; Cleves MA; Honein MA; Romitti PA; Botto LD; Yang SP et al. Maternal smoking and congenital heart defects. Pediatrics 121(4): e810-e816, 2008. (52 refs.)

OBJECTIVES. In a population-based case-control study, we investigated the association between congenital heart defects and maternal smoking. METHODS. The National Birth Defects Prevention Study enrolled 3067 infants with nonsyndromic congenital heart defects and their parents and 3947 infants without birth defects and their parents. Affected infants had >= 1 of the following defects: conotruncal, septal, anomalous pulmonary venous return, atrioventricular septal defects, and left-sided or right-sided obstructive heart defects. Mothers of case and control infants were asked if they smoked during the periconceptional period, defined as 1 month before pregnancy through the first trimester. Maternal home and workplace exposure to tobacco smoke during the same period was also determined. Logistic regression was used to compute odds ratios and 95% confidence intervals while controlling for potential confounders. RESULTS. Case infants were more likely to be premature and have lower birth weight than control infants. Women who smoked anytime during the month before pregnancy to the end of the first trimester were more likely to have infants with septal heart defects than women who did not smoke during this time period. This association was stronger for mothers who reported heavier smoking during this period. This relation was independent of potential confounding factors, including prenatal vitamin use, alcohol intake, maternal age, and race or ethnicity. Women who smoked >= 25 cigarettes per day were more likely than nonsmoking mothers to have infants with right-sided obstructive defects. There was no increased risk of congenital heart defects with maternal exposure to environmental tobacco smoke. CONCLUSIONS. Maternal smoking during pregnancy was associated with septal and right-sided obstructive defects. Additional investigation into the timing of tobacco exposure and genetic susceptibilities that could modify this risk will provide a more precise evidence base on which to build clinical and public health primary prevention strategies.

Marin SJ; Coles R; Urry FM; McMillin GA. Confirmation of cannabinoids in meconium using two-dimensional gas chromatography with mass spectrometry detection. Journal of Chromatography B 858(1-2): 59-64, 2007. (14 refs.)

Meconium has become the specimen of choice for determining fetal exposure to drugs of abuse, but its physical complexity can cause interferences from matrix effects. A new method to determine 9-carboxy-11-nor-Delta(9)-THC (9-THCA) and 11-hydroxy-Delta(9)-THC (11-OH-THC) using two-dimensional (2D) GC-MS was developed to reduce interferences and carryover. The method was validated using 70 spiked samples prepared in drug-free meconium and 46 residual patient specimens that were confirmed to contain cannabinoids. Ten patient specimens that failed to confirm due to interferences using the previous GC-MS method were analyzed using the new 2D method and 9-THCA was quantitated in all ten samples. The 2D GC-MS method improved chromatography which significantly reduced interferences and carryover when compared to the previous GC-MS method.

Mayes L; Snyder PJ; Langlois E; Hunter N. Visuospatial working memory in school-aged children exposed in utero to cocaine. Child Neuropsychology 13(3): 205-218, 2007. (70 refs.)

Objective: Among the neurocognitive impairments reported as associated with prenatal cocaine exposure, slower response time, and less efficient learning in school-aged children are common to findings from several laboratories. This study presents performance data on a spatial working memory task in 75 prenatally cocaine exposed (CE) and 55 nondrug-exposed (NDE) 8- to 10-year-old children. Methods: Children were administered a novel neuropsychological measure of immediate-and short-term memory for visuospatial information, the Groton Maze Learning Test (c) (GMLT), a computer-based hidden maze learning test that consists of a "timed chase test" (a simple measure of visuomotor speed), eight learning trials followed by a delayed recall trial after an 8-minute delay and a reverse learning trial. Performance is expressed as correct moves per second and number of errors per trial. Results: Across all trials, the cocaine-exposed group showed significantly slower correct moves per second and made significantly more errors. There were no significant main effects for amounts of alcohol, tobacco, or marijuana exposure. After an 8-minute delay and compared to the eighth trial, cocaine-exposed children showed less consolidation in learning compared to nonexposed children. When asked to complete the maze in reverse, cocaine-exposed children showed a greater decrement in performance (decreased correct moves per second and increased errors) compared to the eighth learning trial. Conclusions: Children exposed in utero to cocaine exhibit a possible impairment in procedural learning and diminished efficiency in creating and accessing an internal spatial map to master the hidden maze.

Menegaux F; Ripert M; Hemon D; Clavel J. Maternal alcohol and coffee drinking, parental smoking and childhood leukaemia: A French population-based case-control study. Paediatric and Perinatal Epidemiology 21(4): 293-299, 2007. (21 refs.)

We investigated the role of maternal alcohol and coffee drinking during pregnancy and that of parental smoking in the aetiology of childhood leukaemia. A French, population-based, case-control study was conducted, comparing 472 [407 acute lymphoblastic leukaemia (ALL) and 62 acute myeloblastic leukaemia] cases of childhood acute leukaemia (AL) and 567 population controls, frequency-matched with cases on age, gender and region of residence. Both case and control mothers filled in a comprehensive self-administered standardised questionnaire, eliciting detailed data on maternal alcohol and coffee consumption during pregnancy and parental smoking before, during and after pregnancy. Maternal alcohol consumption of more than 1 drink per day was related to ALL (OR = 2.8 [95% CI 1.8, 5.9]). While maternal coffee consumption was not significantly related to AL (OR = 1.4 [95% CI 0.9, 2.3]), highest intake of coffee (more than 3 cups per day) during pregnancy was associated with AL in children whose mothers were non-smokers (OR = 1.9 [95% CI 1.0, 3.5]). No association with parental smoking, either maternal or paternal, was observed with AL. The present results suggest a possible role of the highest consumption of alcohol by the mother during pregnancy in the aetiology of childhood AL.

Milner AD; Rao H; Greenough A. The effects of antenatal smoking on lung function and respiratory symptoms in infants and children. Early Human Development 83(11): 707-711, 2007. (42 refs.)

We highlight evidence demonstrating antenatal smoking exposure is an important risk factor for increased respiratory symptoms and lung function abnormalities in infants and children. Epidemiological. studies have demonstrated an excess both of wheezing in the first two years after birth and asthma and persistent wheezing in older children. Lung function testing in children exposed to antenatal smoking has demonstrated a reduction in airway function. Antenatal exposure of nicotine to animal models results in pulmonary hypoplasia, fewer but larger alveoli and altered airway morphology. Pulmonary function testing, however, has not demonstrated that infant tung volume is affected by antenatal smoking exposure, other than due to the expected effect of smoking on somatic growth, but there is an adverse effect on airway development. There is no evidence that antenatal smoking exposure increases bronchial hyperreactivity, rather it may be associated with a diminished response to both bronchoconstrictors; and bronchodilators in infants.

Minnes S; Singer LT; Kirchner HL; Satayathum S; Short EJ; Min M et al. The association of prenatal cocaine use and childhood trauma with psychological symptoms over 6 years. Archives of Women's Mental Health 11(3): 181-192, 2008. (55 refs.)

The use of cocaine and other drugs during pregnancy may have serious public health consequences. The objective of this study was to determine if the use of cocaine prenatally identifies women for ongoing risk of psychological symptoms. Four hundred and two women (207 cocaine using [C], 195 non-cocaine using [NC]) were assessed for rates of clinically elevated psychological symptoms shortly after childbirth, 6.5 months and 1, 2, 4 and 6 years after using the Brief Symptom Inventory (BSI). Generalized estimating equation modeling (GEE) was used to compare psychological symptom severity, controlling for confounding factors including early childhood trauma. Results indicated that women identified as having used cocaine during pregnancy had clinically elevated psychological distress (OR = 1.76, 95%CI = 1.15-2.71, p = 0.01), psychoticism (OR = 1.97, 95%CI = 1.41-2.76, p = 0.001), interpersonal sensitivity (OR = 2.34; 95%CI = 1.65-3.34; p < 0.0001) and phobic anxiety (OR = 1.86; 95%CI = 1.24-2.79) across all assessments compared to NC women. Childhood emotional abuse was also independently associated with psychological distress. Women who use cocaine during pregnancy should be recognized as at very high risk of ongoing clinically elevated psychological symptoms and should receive early and regular assessments and intervention for mental health and substance use problems.

Mongraw-Chaffin ML; Cohn BA; Cohen RD; Christianson RE. Maternal smoking alcohol consumption and caffeine consumption during pregnancy in relation to a son's risk of persistent cryptorchidism: A prospective study in the child health and development studies cohort 1959-1967. American Journal of Epidemiology 167(3): 257-261, 2008. (34 refs.)

The Child Health and Development Studies is a >= 40-year follow-up of 20,754 pregnancies occurring between 1959 and 1967 in California. There were 84 cases of undescended testes at birth persisting to at least age 2 years among 7,574 liveborn sons whose mothers were interviewed in early pregnancy. Cases were matched to three controls on birth year and race. Compared with mothers of controls, mothers of cryptorchid boys consumed more caffeine during pregnancy (odds ratio = 1.4, 95% confidence interval: 1.1, 1.9 for an interquartile range equivalent to three cups of coffee per day) but were not more likely to smoke or drink alcohol when all behaviors were considered together. Other maternal and perinatal risk factors were not significantly associated with persistent cryptorchidism and did not confound the association with caffeine.

Mulvihill AO; Cackett PD; George ND; Fleck BW. Nystagmus secondary to drug exposure in utero. British Journal of Ophthalmology 91(5): 613-615, 2007. (11 refs.)

Aim: To report the occurrence of nystagmus in children exposed to opiates and/or benzodiazepines during pregnancy, and to describe the associated ocular and systemic findings. Methods: Clinical examination and casenote review of 14 children with nystagmus whose mothers had misused opiates and/or benzodiazepines during pregnancy. Results: Twelve children were exposed to opiates during pregnancy, of whom nine had also been exposed to benzodiazepines. Two children were exposed to benzodiazepines alone. In the primary position, the nystagmus was a fine horizontal pendular type in 10 (71.4%) children and was a fine horizontal jerk nystagmus in the other 4 (28.6%) children. The onset of the nystagmus probably occurred in the first 6 months of life in all cases. The mean binocular best-corrected logarithm of the minimum angle of resolution visual acuity was 0.59 (20/80). Electroretinogram and visual evoked potential examinations were found to be normal in the three children tested. Nine (64.3%) children had developmental delay and at least 7 (50%) had delayed visual maturation. Six children had microcephaly and two had bilateral optic nerve hypoplasia. None of the children had a specific neurological diagnosis or seizure disorder. Conclusion: This study strongly supports a teratogenic association between exposure to controlled drugs in utero and infantile nystagmus. Furthermore, the nystagmus and associated clinical features seem to be particularly associated with combined use of opiates and benzodiazepines. Exposure to opiates and/or benzodiazepines during pregnancy should be considered in the differential diagnosis of infantile nystagmus.

Murphy CR; Bell EF; Sato Y; Klein JM. Periventricular leukomalacia and prenatal methamphetamine exposure: A case report. American Journal of Perinatology 2007(24): 2, 2007. (10 refs.)

Periventricular leukomalacia (PVL) is a complication of prematurity that carries a high risk of long-term neurologic morbidity. We report the first case, to our knowledge, of unexpected PVL associated with in utero methamphetamine exposure in a 30-week gestation premature infant with a benign hospital course, who subsequently developed cerebral palsy by 24 months of life.

Neuman RJ; Lobos E; Reich W; Henderson CA; Sun LW; Todd RD. Prenatal smoking exposure and dopaminergic genotypes interact to cause a severe ADHD subtype. Biological Psychiatry 61(12): 1320-1328, 2007. (63 refs.)

Background: In utero exposure to smoking and alcohol are common risk factors that have been associated with attention-deficit/hyperactivity disorder (ADHD) in human beings and animal models. Furthermore, molecular studies have focused on the association between ADHD and DNA polymorphisms in dopamine pathway-related genes. We examined the joint effects of genetic and prenatal substance exposures on DSM-IV and population-defined subtypes of ADHD. Methods: Logistic regression was used to assess the relationship between ADHD subtypes, DAT1 and DRD4 polymorphisms, and prenatal substance exposures in a birth-record sample of male and female twin pairs, aged 7-19 years. Results: Interactions between prenatal exposure to smoking and variations in the DAT1 and DRD4 loci were observed in children with either the DSM-IV or population-defined ADHD combined subtypes. The odds of a diagnosis of DSM-IV combined subtype was 2.9 times greater in twins who had inherited the DAT1 440 allele and who were exposed, than in unexposed twins without the risk allele. The OR was 2.6 in the population-defined subtype. Odds ratios for the DRD4 seven-repeat allele were 3.0 (2.8) in the population-defined (DSM-IV) combined ADHD subtypes. The OR for exposed children with both alleles was 9.0 (95% confidence interval = 2.0-41.5) for the population-defined combined subtypes. Conclusions: Results indicate that smoking during pregnancy is associated with specific subtypes of ADHD in genetically susceptible children.

Oei J; Lui K. Management of the newborn infant affected by maternal opiates and other drugs of dependency. (review). Journal of Paediatrics and Child Health 43(1-2): 9-18, 2007. (126 refs.)

Illicit drug use during pregnancy is common and probably underestimated in the majority of published studies. The infant exposed to opiates or other drugs of dependency during intrauterine development is at risk for post-natal withdrawal as well as to long-term problems that are associated with drug-effects and often, adverse social circumstances. This article examines the early management of the infant and mother for detection and monitoring of drug-exposure, pharmacological intervention for withdrawal and the management of associated, particularly infective and psychosocial, problems. Practical concerns surrounding these issues are discussed and further research on psychosocial intervention to improve long-term outcome are much needed.

Oken E; Levitan EB; Gillman MW. Maternal smoking during pregnancy and child overweight: systematic review and meta-analysis. International Journal of Obesity 32(2): 201-210, 2008. (85 refs.)

Objective: Perform a systematic review of studies reporting on the association between maternal prenatal cigarette smoking and child overweight. Design: Meta-analysis of observational studies. Data sources: Medline search and review of reference lists among studies published through June 2006. Review methods: Included studies reported an association between maternal smoking during pregnancy and risk of overweight among children at least 2 years of age. We did not include in the meta-analysis studies that provided only a continuous measure of adiposity, although those studies are discussed separately. Results: Based on results of 84 563 children reported in 14 observational studies, children whose mothers smoked during pregnancy were at elevated risk for overweight (pooled adjusted odds ratio (OR) 1.50, 95% CI: 1.36, 1.65) at ages 3-33 years, compared with children whose mothers did not smoke during pregnancy. The pooled estimate from unadjusted odds ratios (OR 1.52, 95% CI: 1.36, 1.69) was similar to the adjusted estimate, suggesting that sociodemographic and behavioral differences between smokers and nonsmokers did not explain the observed association. Although we observed evidence for publication bias, simulating a symmetric set of studies yielded a similar estimate (OR 1.40, 95% CI: 1.26, 1.55). Conclusions: Prenatal smoking exposure appears to increase rates of overweight in childhood. In parts of the world undergoing the epidemiologic transition, the continuing increase in smoking among young women could contribute to spiraling increases in rates of obesity-related health outcomes in the 21 st century.

Paus T; Nawazkhan I; Leonard G; Perron M; Pike GB; Pitiot A et al. Corpus callosum in adolescent offspring exposed prenatally to maternal cigarette smoking. Neuroimage 40(2): 435-441, 2008. (60 refs.)

Teratogens, such as alcohol or anti-epileptic drugs, affect the size of the corpus callosum. Here we report findings obtained in a case-control study that investigated possible effects of teratogens contained in cigarette smoke on the size and structural properties of this structure. We recruited and scanned with magnetic resonance imaging a total of 408 adolescents (12 to 18 years of age); a subsample of 300 adolescents is considered in this report. Cases (n=146) were exposed to maternal cigarette smoking during pregnancy; non-exposed controls (n=154) were matched to cases by maternal education. We measured the size of corpus callosum (CC) and its sections (corrected for brain size), as well as mean values of magnetization-transfer ratio (MTR) in each CC section. Corpus callosum, and especially its posterior part, was smaller in the exposed vs. non-exposed female adolescents; no significant effects were found in males. Exposed and non-exposed subjects did not differ in the MTR-based index of myelination in either gender in any CC section. Given the lack of exposure effect on the myelination index, this finding might reflect a lower number of inter-hemispheric connections in female offspring of mothers who smoked during pregnancy.

Pettersson A; Akre O; Richiardi L; Ekbom A; Kaijser M. Maternal smoking and the epidemic of testicular cancer: A nested case-control study. International Journal of Cancer 120(9): 2044-2046, 2007. (18 refs.)

For no apparent reason, the incidence of testicular cancer has increased to epidemic proportions in many countries. Pregnancy smoking has been suggested to be a cause. Previous analytical studies have been negative, but the inherent difficulties in retrospective assessment of this exposure have led to no definite conclusion. We have conducted a population-based case-control study on 192 cases of testicular germ-cell cancer -- born in Sweden in 1973 onwards and aged >= 15 at cancer diagnosis -- and 494 matched controls, where data on maternal smoking were collected during pregnancy. We found no association with testicular cancer for maternal smoking during pregnancy (OR, 0.91; 95% CI, 0.64-1.30), and there was no evidence of a dose-response effect. We conclude that the epidemic rise in testicular cancer in many populations is not due to the surge in smoking among women.

Pollard I. Neuropharmacology of drugs and alcohol in mother and fetus. Seminars in Fetal & Neonatal Medicine 12(2): 106-113, 2007. (35 refs.)

Epidemiological evidence suggests that an adverse prenatal environment can have profound long-term health consequences throughout postnatal Life. This chapter discusses the underlying mechanisms implicated in the consumption of mood-altering recreational drugs and teratogenicity in the fetus. The way metabolic parameters in pregnancy influence the pharmacokinetic characteristics of drugs and alcohol and the developmental stage of neurotoxicity are reviewed. The general underlying mechanisms that link multifaceted interactions between drug characteristics, gene polymorphisms, dietary deficiencies, changed endocrine indices and fetal programming are outlined, with specific examples throughout the text. As developmental injury is of significant social concern, the final section questions whether society provides adequate support for making appropriate and informed lifestyle choices to alleviate preventable transgenerational harm.

Post A; Gilljam H; Bremberg S; Galanti MR. Maternal smoking during pregnancy: a comparison between concurrent and retrospective self-reports. Paediatric and Perinatal Epidemiology 22(2): 155-161, 2008. (24 refs.)

Retrospective reports of smoking in pregnancy are of importance for clinical or scientific purposes. Careful analyses of stability and accuracy of recalled behaviour are, therefore, needed. In 1998, the mothers of 2369 pre-teens born in Sweden retrospectively reported their smoking behaviour during the first trimester of the index pregnancy. We matched these reports with those recorded by midwives at the beginning of the index pregnancy, using information from the Swedish Medical Birth Registry. Using this registry as gold standard, the sensitivity and specificity of the retrospective reports containing any smoking were 83.9% and 92.8% respectively, but the sensitivity was low for daily smoking, 56.0%. Of the 222 discordant reports, 19.0% were due to mothers recalling daily smoking which was not reported at the time of pregnancy, and 42% were due to failure to recall smoking reported at the time of pregnancy, while the remaining 39% retrospectively reported occasional smoking, whereas they were registered as non-daily smokers when pregnant. Retrospective recall of pregnancy smoking is fairly stable over time.

Pulsifer MB; Butz AM; Foran MO; Belcher HME. Prenatal drug exposure: Effects on cognitive functioning at 5 years of age. Clinical Pediatrics 47(1): 58-65, 2008. (37 refs.)

The goal of this cross-sectional study was to compare cognitive functioning at age 5 years in prenatal drug-exposed children with nondrug-exposed children from a comparable inner-city environment. Children with prenatal drug exposure scored significantly lower on measures of language, school readiness skills, impulse control, and visual attention span/sequencing than controls matched for age and socioeconomic status. Intelligence, visual-motor, manual dexterity, and sustained attention scores were not significantly different between groups. The total sample scored significantly below the normative mean on standardized measures of intelligence, language, school readiness, visual-motor skills, impulse control, and sustained attention, with 40% scoring at least I standard deviation below the mean (IQ < 85) on a measure of intelligence. Findings suggest that children with prenatal drug exposure are at increased risk for learning and attention problems and are in need of close developmental surveillance and possible intervention to support school success and improve behavioral outcome.

Ramlau-Hansen CH; Thulstrup AM; Storgaard L; Toft G; Olsen J; Bonde JP. Is prenatal exposure to tobacco smoking a cause of poor semen quality? A follow-up study. American Journal of Epidemiology 165(12): 1372-1379, 2007. (18 refs.)

A few studies indicate that exposure to maternal smoking during fetal life decreases semen quality in adult life, but the results are inconsistent and retrospectively collected smoking data were used in most studies. From a Danish pregnancy cohort established in 1984-1987, 347 of 5,109 sons were selected according to their exposure to tobacco smoke in fetal life. From February 2005 to January 2006, a semen sample from the 347 men was analyzed for conventional semen characteristics according to standardized criteria by using a mobile laboratory. The authors found an inverse association between maternal smoking during pregnancy and total sperm count (p = 0.002). Men exposed to more than 19 cigarettes daily during pregnancy had approximately 19% lower semen volume (p = 0.04), 38% lower total sperm count (p = 0.11), and 17% lower sperm concentration (p = 0.47) compared with unexposed men. The odds ratio for oligospermia was 2.16 (95% confidence interval: 0.68, 6.87) among exposed men compared with the unexposed. No associations were found for sperm motility or morphology. These results indicate that prenatal exposure to tobacco smoke may have an adverse effect on semen quality and, if these associations are causal, they could explain some of the reported differences between populations and secular changes in semen quality.

Rao H; Wang J; Giannetta J; Korczykowski M; Shera D; Avants BB et al. Altered resting cerebral blood flow in adolescents with in utero cocaine exposure revealed by perfusion functional MRI. Pediatrics 120(5): E1245-E1254, 2007. (54 refs.)

OBJECTIVES. Animal studies have clearly demonstrated the effects of in utero cocaine exposure on neural ontogeny, especially in dopamine-rich areas of cerebral cortex; however, less is known about how in utero cocaine exposure affects longitudinal neurocognitive development of the human brain. We used continuous arterial spin-labeling perfusion functional MRI to measure the effect of in utero cocaine exposure on resting brain function by comparing resting cerebral blood flow of cocaine-exposed adolescents with non-cocaine-exposed control subjects. PATIENTS AND METHODS. Twenty-four cocaine-exposed adolescents and 25 matched non-cocaine-exposed control subjects underwent structural and perfusion functional MRI during resting states. Direct subtraction, voxel-wise general linear modeling, and region-of-interest analyses were performed on the cerebral blood flow images to compare the resting cerebral blood flow between the 2 groups. RESULTS. Compared with control subjects, cocaine-exposed adolescents showed significantly reduced global cerebral blood flow. The decrease of cerebral blood flow in cocaine-exposed adolescents was observed mainly in posterior and inferior brain regions, including the occipital cortex and thalamus. After adjusting for global cerebral blood flow, however, a significant increase in relative cerebral blood flow in cocaine-exposed adolescents was found in anterior and superior brain regions, including the prefrontal, cingulate, insular, amygdala, and superior parietal cortex. Furthermore, the functional modulations by in utero cocaine exposure on all of these regions except amygdala cannot be accounted for by the variation in brain anatomy. CONCLUSIONS. In utero cocaine exposure may reduce global cerebral blood flow, and this reduction may persist into adolescence. The relative increase of cerebral blood flow in anterior and superior brain regions in cocaine-exposed adolescent participants suggests that compensatory mechanisms for reduced global cerebral blood flow may develop during neural ontogeny. Arterial spin-labeling perfusion MRI may be a valuable tool for investigating the long-term effects of in utero drug exposure.

Rayburn WF. Maternal and fetal effects from substance use. Clinics in Perinatology 34(4): 559-+, 2007. (19 refs.)

Drug use is most prevalent in the reproductive age population. Among women aged 15 to 44, almost 90% have used alcohol, approximately 44% have used marijuana, and at least 14% have used cocaine. Even though a reduction in substance use may occur during pregnancy, some women may not alter their drug use patterns until pregnancy is diagnosed. For these reasons, a large number of fetuses are exposed to illicit substances in utero. Patient interviews and urine toxicologic testing at the initial prenatal visit and at delivery suggest that substance use during pregnancy ranges from 0.4% to 27%, depending on the population surveyed. This finding is not surprising, as more than one third of the total adult population interviewed admitted to some illicit drug use. Care of substance-using pregnant women is complex, difficult, and often demanding. Providers must be aware of their unique psychologic and social needs, and the related legal and ethical ramifications surrounding pregnancy. In addition, relating specific substances to perinatal outcome is difficult, as concurrent use of multiple substances is frequent and many users are members of economically disadvantaged segments of society in which unfavorable perinatal outcomes are more common than in other segments of society. It is also very difficult to follow neonatal outcomes in such pregnancies and to analyze research data. This article discusses a variety of issues related to pregnancies complicated by substance use. Identification of substance use, perinatal pharmacology and teratogenic risks, limitations with reported investigations, treatment approaches, and comprehensive perinatal management are reviewed.

Richardson GA; Goldschmidt L; Larkby C. Effects of prenatal cocaine exposure on growth: A longitudinal analysis. Pediatrics 120(4): e1017-e1027, 2007. (58 refs.)

OBJECTIVE. There has been a limited amount of research on the long-term effects of prenatal cocaine exposure on growth of the infant, and there has been no use of longitudinal growth models. We investigated the effects of prenatal cocaine exposure on offspring growth from 1 through 10 years of age by using a repeated-measures growth-curve model. METHODS. Women were enrolled from a prenatal clinic and interviewed at the end of each trimester of pregnancy about their cocaine, crack, alcohol, marijuana, tobacco, and other drug use. Fifty percent of the women were white, and 50% were black. Follow-up assessments occurred at 1, 3, 7, and 10 years of age. RESULTS. Cross-sectional analyses showed that children exposed to cocaine during the first trimester (n = 99) were smaller on all growth parameters at 7 and 10 years, but not at 1 or 3 years, than the children who were not exposed to cocaine during the first trimester (n = 125). The longitudinal analyses indicated that the growth curves for the 2 groups diverged over time: children who were prenatally exposed to cocaine grew at a slower rate than children who were not exposed. These analyses controlled for other factors associated with child growth. CONCLUSIONS. To our knowledge, this is the first study of the long-term effects of prenatal cocaine exposure to conduct longitudinal growth-curve analyses using 4 time points in childhood. Children who were exposed to cocaine during the first trimester grew at a slower rate than those who were not exposed. These findings indicate that prenatal cocaine exposure has a lasting effect on child development.

Rodriguez A; Miettunen J; Henriksen TB; Olsen J; Obel C; Taanila A et al. Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: Evidence from three prospective pregnancy cohorts. International Journal of Obesity 32(3): 550-557, 2008. (44 refs.)

Objectives: We examine whether pregnancy weight (pre-pregnancy body mass index (BMI) and/or weight gain) is related to core symptoms of attention deficit hyperactivity disorder (ADHD) in school-age offspring. Design: Follow-up of prospective pregnancy cohorts from Sweden, Denmark and Finland within the Nordic Network on ADHD. Methods: Maternal pregnancy and delivery data were collected prospectively. Teachers rated inattention and hyperactivity symptoms in offspring. High scores were defined as at least one core symptom rated as 'severe' and two as 'present' (approximately 10% of children scored in this range). Logistic regression and latent class analyses were used to examine maternal pregnancy weight in relation to children's ADHD core symptoms. Results: Teacher rated 12 556 school-aged children. Gestational weight gain outside of the Institute of Medicine guidelines was not related to ADHD symptoms (below recommendations: odds ratio (OR): 0.96; 95% confidence interval (CI): 0.81, 1.14; above recommendations: OR: 0.98; 95% CI: 0.82, 1.16). To examine various patterns of pre-pregnancy BMI and weight gain, we used latent class analysis and found significant associations between classes that included pre-pregnancy overweight or obesity and a high ADHD symptom score in offspring, ORs ranged between 1.37 (95% CI: 1.07, 1.75) and 1.89 (95% CI: 1.13, 3.15) adjusted for gestational age, birth weight, weight gain, pregnancy smoking, maternal age, maternal education, child gender, family structure and cohort country of origin. Children of women who were both overweight and gained a large amount of weight during gestation had a 2-fold risk of ADHD symptoms (OR: 2.10, 95% CI: 1.19, 3.72) compared to normal-weight women. Conclusions: We show for the first time that pre-pregnancy BMI is associated with ADHD symptoms in children. Our results are of public health significance if the associations are causal and will then add ADHD symptoms in offspring to the list of deleterious outcomes related to overweight and obesity in the prenatal period.

Rogers-Adkinson DL; Stuart SK. Collaborative services: Children experiencing neglect and the side effects of prenatal alcohol exposure. Language, Speech and Hearing Services in Schools 38(2): 149-156, 2007. (62 refs.)

Purpose: The purpose of this article is to provide critical knowledge regarding children who are served by the child welfare system and how these children's specialized needs affect speech-language services. Specifically, the structure of social services system models is presented, with an emphasis on the cultural and systemic interactions between services providers and families. In addition, the role of special education for children who have experienced abuse, neglect, and prenatal drug or alcohol exposure is presented, with an emphasis on social services and special education legal issues. Method: This article provides a critical analysis of the research literature to date regarding effective tools for providing collaborative intervention to children who are experiencing fetal alcohol syndrome disorder or abuse and/or neglect. Clinical implications: This article provides suggestions about the collaborative roles that speech-language pathologists should integrate into treatment milieu when delivering therapy to children with histories of abuse, neglect, and prenatal drug or alcohol exposure.

Salihu HM; Sharma PP; Getahun D; Hedayatzadeh M; Peters S; Kirby RS et al. Prenatal tobacco use and risk of stillbirth: A case-control and bidirectional case-crossover study. Nicotine & Tobacco Research 10(1): 159-166, 2008. (39 refs.)

We sought to estimate the association between prenatal smoking and stillbirth in a longitudinal cohort using two study designs: a case-control study and a bidirectional case-crossover study. The analysis was conducted using the Missouri maternally linked cohort dataset from 1978 through 1997. In the case-control study, each mother contributed only one birth to the analysis. For the bidirectional crossover design, analysis was restricted to women who gave birth to at least one stillbirth, and the controls comprised all live births before and after the stillbirth. The independent association between prenatal smoking and stillbirth was computed using nonconditional (case-control design) and conditional (bidirectional case-crossover design) logistic regression. Prenatal smoking decreased from 29.7% in 1978 to 21.2% by 1997 (p <.001). The absolute risk of stillbirth was greater among smokers (7.7/1000) than nonsmokers (5.3/1000), p <.001. In the case-control design, the risk of stillbirth was 34% greater among smokers than nonsmokers (OR=1.34, 95% CI 1.26-1.43). For each 10-unit increase in the number of cigarettes consumed per day prenatally, the likelihood of stillbirth rose by about 14% (p.001). In the bidirectional case-crossover design, the association between stillbirth and smoking during pregnancy was confirmed, although the magnitude of the relationship was smaller (OR=1.20, 95% CI 1.03-1.39). In conclusion, we found prenatal smoking to be a risk factor for stillbirth even after minimizing the influence of known and unknown sources of confounding as well as changes in temporal trend in prenatal smoking.

Salihu HM; Wilson RE. Epidemiology of prenatal smoking and perinatal outcomes. Early Human Development 83(11): 713-720, 2007. (58 refs.)

During the previous two decades smoking among pregnant women in the developed world declined by about 60-75%. Nevertheless, prenatal smoking remains a common habit and accounts for a significant proportion of fetal morbidity and mortality through both a direct (fetal) and an indirect (placental) effect. The most important smoking-induced placental. pathology is placental abruption with reported risk estimates ranging from 1.4 to 4.0. It is almost a consensus that prenatal smoking is a causative factor for placental abruption. Although the evidence is less compelling, smoking mothers are at an increased risk for placenta previa and placenta-previa-accreta combination. There is no association between maternal smoking and the syndrome of idiopathic uterine bleeding. The relationship between maternal smoking and fetal growth is causal, and includes significant reduction in growth of head circumference, abdominal circumference and femur length, with the largest reduction in size observed for femur length. Prenatal smoking is associated with a 20-30% higher likelihood for stillbirth, a 40% elevation in the risk for infant mortality and a 2-fold increase in the incidence of SIDS. Conclusion: Despite a temporal decline in maternal smoking, it still accounts for significant feto-infant morbidity and mortality, and efforts to discourage prenatal smoking need to be intensified.

Salisbury AL; Lester BM; Seifer R; LaGasse L; Bauer CR; Shankaran S et al. Prenatal cocaine use and maternal depression: Effects on infant neurobehavior. Neurotoxicology and Teratology 29(3): 331-340, 2007. (72 refs.)

Objective: The present study examined the impact of both perinatal maternal depression and cocaine use on infant neurobehavior at I month of age in a large, multi-site study. Methods: Infant neurobehavior was examined in 1053 infants at I month of age using the NICU Network Neurobehavioral Scale (NNNS). Mothers were interviewed using The Addiction Severity Index to determine present and past psychiatric history. Four groups were derived from the total sample: 385 prenatally cocaine-exposed infants, 76 whose mothers reported current postpartum depression (DEP/COC) and 309 without current postpartum depression (nonDEP/COC); 668 infants were not exposed to cocaine, 104 whose mothers reported current postpartum depression (DEP/nonCOC), 564 without current postpartum depression (nonDEP/nonCOC). A 2x2 Analysis of Covariance was used with covariates (birthweight, maternal age, SES, nicotine, alcohol, and research site) to examine infant neurobehavior in these four conditions. Secondary analyses were conducted to examine the effects of amount and timing of prenatal cocaine exposure. Results: DEP group by COC exposure status interactions were significant; there was only a DEP effect in the nonCOC infants. Infants in the nonCOC/DEP group had poorer self-regulation and more stress signs, excitability, and arousal than infants in the other groups. Conclusions: Postpartum maternal depression has negative effects on infant neurobehavior at I month of age. Prenatal cocaine exposure may serve to suppress or buffer the effects of postpartum depression on infant neurobehavior. Maternal mood could explain some of the inconsistencies found in the prenatal cocaine exposure literature.

Sasaki S; Sata F; Katoh S; Saijo Y; Nakajima S; Washino N et al. Adverse birth outcomes associated with maternal smoking and polymorphisms in the N-nitrosamine-metabolizing enzyme genes NQO1 and CYP2E1. American Journal of Epidemiology 167(6): 719-726, 2008. (46 refs.)

Maternal smoking during pregnancy can result in both pregnancy complications and reduced size of the fetus and neonate. Among women who smoke, genetic susceptibility to tobacco smoke also is a likely causative factor in adverse pregnancy outcomes. A prospective cohort study was conducted among 460 pregnant women who delivered live singletons in Sapporo, Japan, from 2002 to 2005. Multiple linear regression models were used to estimate associations of maternal smoking and polymorphisms in two genes encoding N-nitrosamine-metabolizing enzymes-NAD(P)H: quinone oxidoreductase 1 (NQO1) and cytochrome P-450 2E1 (CYP2E1)-with birth size. Among infants born to smokers with the NQO1 homozygous wild-type allele, birth weight, birth length, and birth head circumference were significantly reduced (p < 0.01 for each factor). For the homozygous wild-type CYP2E1 allele, birth weight was lower by an estimated 195 g (standard error, 55; p < 0.001) among smokers. These genotypes did not confer adverse effects among women who had never smoked or who quit smoking during the first trimester. The adverse effects of maternal smoking on infant birth size may be modified by maternal genetic polymorphisms in N-nitrosamine-metabolizing enzymes among Japanese subjects. These results may help in directing smoking cessation interventions during pregnancy, especially among susceptible women.

Schempf AH. Illicit drug use and neonatal outcomes: A critical review. Obstetrical & Gynecological Survey 62(11): 749-757, 2007. (88 refs.)

Although the neonatal consequences of tobacco and alcohol exposure are well established, the evidence related to prenatal illicit drug use is less consistent despite prevalent views to the contrary. The many social, psychosocial, behavioral, and biomedical risk factors for adverse birth outcomes associated with illicit drug use complicate the evaluation of neonatal effects. Placing emphasis on recent research, this review summarizes the epidemiologic literature on the neonatal impact of marijuana, opiate, and cocaine use. Of these drugs, cocaine use is most consistently related to fetal growth decrements and dose-response effects have been observed. However, studies to date have largely failed to control for associated social, psychosocial, and contextual factors. Additional recommendations for future research are provided. It is likely that interventions will need to address the factors surrounding drug use to greatly improve neonatal outcomes (e.g., social circumstances, poor nutrition, stress, infections).

Schmid JMP; Kuehni CE; Strippoli MPF; Roiha HL; Pavlovic R; Latzin P; Swiss Pediatric Respiratory Research Group. Maternal tobacco smoking and decreased leukocytes, including dendritic cells, in neonates. Pediatric Research 61(4): 462-466, 2007. (22 refs.)

Maternal smoking in pregnancy is associated with respiratory diseases in the offspring, possibly due to prenatal influences on the developing immune system. We investigated whether maternal smoking in pregnancy was associated with cord blood leukocyte numbers, including precursor dendritic cells, adjusting for concomitant factors. In a prospective healthy birth cohort study, total leukocyte counts were reduced in neonates of smoking mothers [10.7 (8.4-13.0), n = 14] compared with nonexposed infants [14.7 (13.7-15.7), n = 74, p = 0.002] [geometric mean cells X 10(3)/mu L (95% confidence interval)]. All leukocyte subsets were decreased, most prominently segmented neutrophils [4.3 (2.8-5.7) versus 6.2 (5.5-6.8), p = 0.021], lymphocytes [3.8 (2.9-4.8) versus 5.0 (4.5-5.6), p = 0.036], and myeloid precursor dendritic cells [12.7 cells/mu L (9.1-17.8) versus 18.3 (15.8-21.2), p = 0.055]. These differences persisted after adjustment for possible confounders. Predictors of myeloid precursor dendritic cell numbers in multivariable models were maternal smoking (-5.1 cells/mu L, p = 0.042), age (-0.5 cells/mu L/y, p = 0.035), and, marginally, asthma (+8.1 cells/mu L, p = 0.075). The decrease of all leukocytes in neonates of smoking mothers could be clinically significant and suggests a decreased cell production, increased peripheral recruitment, or retention in bone marrow. Given the importance of dendritic cells in early immune responses, their decrease might reflect an impact of maternal smoking on the developing fetal immune system.

Schuetze P; Eiden RD. The association between prenatal exposure to cigarettes and infant and maternal negative affect. Infant Behavior & Development 30(3): 387-398, 2007. (70 refs.)

This study examined the association between prenatal exposure to cigarettes and infant and maternal negative affect. Participants were 115 mother-infant dyads (69 prenatally exposed to cigarettes and 46 nonexposed). Infant and maternal negative affect were both assessed during the neonatal period (2-4 weeks of age) and again at 7 months of infant age. Results indicated that only prenatal exposure to cigarettes predicted infant negative affect. Infants who were prenatally exposed to more cigarettes had higher levels of negative affect at both time points. Furthermore, regression analyses indicated that both infant and maternal negative affect during the neonatal period predicted maternal negative affect at 7 months of age. These results highlight the importance of considering the reciprocal relationship between infant and maternal behavior when examining developmental outcomes among infants prenatally exposed to cigarettes.

Shankaran S; Lester BM; Das A; Bauer CR; Bada HS; Lagasse L et al. Impact of maternal substance use during pregnancy on childhood outcome. Seminars in Fetal & Neonatal Medicine 12(2): 143-150, 2007. (42 refs.)

The impact of maternal substance abuse is reflected in the 2002-2003 National Survey on Drug Use and Health. Among pregnant women in the 15-44 age group, 4.3%, 18% and 9.8% used illicit drugs, tobacco and alcohol, respectively. Maternal pregnancy complications following substance use include increases in sexually transmitted disorders, placental abruption and HIV-positive status. Effects on the neonate include a decrease in growth parameters and increases in central nervous system and autonomic nervous system signs and in referrals to child protective agencies. In childhood, behavioral and cognitive effects are seen after prenatal cocaine exposure; tobacco and alcohol have separate and specific effects. The ongoing use of alcohol and tobacco by the caretaker affects childhood behavior. Therefore, efforts should be made to prevent and treat behavioral problems as well as to limit the onset of drug use by adolescent children born to women who use drugs during pregnancy.

Shea AK; Steiner M. Cigarette smoking during pregnancy. (review). Nicotine & Tobacco Research 10(2): 267-278, 2008. (118 refs.)

Maternal smoking during pregnancy is associated with several adverse developmental outcomes in the offspring. These include preterm delivery, spontaneous abortion, growth restriction, increased risk of sudden infant death syndrome (SIDS), as well as long-term behavioral and psychiatric disorders. However, the underlying physiological mechanisms for these ill-effects are not fully understood. The aim of this paper is to review the animal and human data to date, linking in utero smoke exposure to negative neurodevelopmental outcomes. It is known that nicotine from cigarette smoke exerts its effects by affecting placental vasculature, and also by nicotinic acetylcholine receptor binding in fetal membranes. Thus, subsequent consequences involve a cascade of events causing not only dysregulation of the nicotinic and muscarinic, but also catecholaminergic and serotonergic neurotransmitter systems. These observations provide some insight into how smoking can impair neurodevelopment, but the long-term neurotransmitter involvement in dysregulation of emotion and attention awaits further elucidation. It is important that pregnant women are warned of the detrimental effects of smoking, and encouraged to abstain for healthy fetal development.

Sheinkopf SJ; Lagasse LL; Lester BM; Liu J; Seifer R; Bauer CR et al. Vagal tone as a resilience factor in children with prenatal cocaine exposure. Development and Psychopathology 19(3): 649-673, 2007. (82 refs.)

Studies have investigated the potential effects of prenatal cocaine exposure (CE) on children's development. However, few studies have examined predictors of resilient outcomes in this population. We examined vagal tone (VT) as a resilience factor in prenatal CE. Utilizing data from the Maternal Lifestyle Study, a cumulative risk index was derived for children with and without prenatal CE. Presence of CE and other prenatal drugs was summed with postnatal risks in infancy to Yield a 15-item risk index. Preschool cognitive outcomes, problem behaviors, and adaptive behaviors were measured. VT was assessed during an infant exam at I month and toy exploration at 36 months. We included children with complete physiologic data (217 CE. 333 non-CE). Children were classified having consistently high, consistently low, or fluctuating. VT at 1 and 36 months. Children were also classified as high versus low risk. High-risk children had lower IQ scores. more problem behaviors, and lower ratings of adaptive behaviors than low-risk children. A significant risk by VT-stability interaction indicated that for high-risk children, those with stable low VT had higher ratings of adaptive behaviors at 36 months. This is consistent with theory linking reduced VT during tasks to adaptive regulation and indicates that such regulatory functioning may serve as a protective factor in prenatal CE.

Shi M; Christensen K; Weinberg C; Romitti P; Bathum L; Lozada A et al. Orofacial cleft risk is increased with maternal smoking and specific detoxification-gene variants. American Journal of Human Genetics 80(1): 76-90, 2007. (45 refs.)

Maternal smoking is a recognized risk factor for orofacial clefts. Maternal or fetal pharmacogenetic variants are plausible modulators of this risk. In this work, we studied 5,427 DNA samples, including 1,244 from subjects in Denmark and Iowa with facial clefting and 4,183 from parents, siblings, or unrelated population controls. We examined 25 single-nucleotide polymorphisms in 16 genes in pathways for detoxification of components of cigarette smoke, to look for evidence of gene-environment interactions. For genes identified as related to oral clefting, we studied gene-expression profiles in fetal development in the relevant tissues and time intervals. Maternal smoking was a significant risk factor for clefting and showed dosage effects, in both the Danish and Iowan data. Suggestive effects of variants in the fetal NAT2 and CYP1A1 genes were observed in both the Iowan and the Danish participants. In an expanded case set, NAT2 continued to show significant overtransmission of an allele to the fetus, with a final P value of .00003. There was an interaction between maternal smoking and fetal inheritance of a GSTT1-null deletion, seen in both the Danish ( P p) and Iowan (P = .002) studies, with a Fisher's combined P value of <.001, which remained significant after correction .03 for multiple comparisons. Gene-expression analysis demonstrated expression of GSTT1 in human embryonic craniofacial tissues during the relevant developmental interval. This study benefited from two large samples, involving independent populations, that provided substantial power and a framework for future studies that could identify a susceptible population for preventive health care.

Silvani P; Camporesi A. Drug-induced pulmonary hypertension in newborns: A review. Current Vascular Pharmacology 5(2): 129-133, 2007. (59 refs.)

Persistent pulmonary hypertension (PPHN) is a disease characterised by the disruption of the transition from fetal to neonatal circulation with the persistence of high pulmonary vascular resistances and right-to left shunting. This condition, occurring in about 1-2 newborns per 1000 live births, causes severe hypoxemia. Despite significant improvements in treatment, the mortality of PPHN varies from 10 to 20 % of affected newborns. Pulmonary hypertension is frequently observed in some cardiac malformation and in congenital diaphragmatic hernia, in meconium aspiration syndrome, neonatal sepsis, podalic presentation and male sex. Maternal risk factors are tobacco smoking, cesarean section, low socioeconomic conditions, diabetes and urinary infections. Another predisposing condition is antenatal or postnatal exposure to some drugs. The medications involved in drug-induced pulmonary hypertension and the mechanisms involved are reviewed.

Simard JF; Rosner BA; Michels KB. Exposure to cigarette smoke in utero: Comparison of reports from mother and daughter. Epidemiology 19(4): 628-633, 2008. (23 refs.)

Background: Smoking during pregnancy has been associated with asthma, obesity, and decreased cognitive functioning in the offspring. To study the role of in utero smoking exposure in offsprings' adult health outcomes, it may be necessary to rely upon reports by the offspring themselves. Methods: We studied 34,949 mother-daughter pairs participating in the Nurses' Health Study II for whom data on the daughter's early passive cigarette smoke exposure had been obtained from both mother and daughter. We calculated sensitivity and specificity of daughter's early exposure to smoke (using mother's report as the gold standard), as well as K statistics. Mother and daughter reports were also analyzed as risk factors for asthma and birthweight to demonstrate face validity. Results: Sensitivity of daughters' reported prenatal exposure ranged from 74% to 85%, while specificity was between 90% and 95% (k = 0.72-0.81). Daughter's reported childhood exposure as a proxy for mother's report of smoking during pregnancy had a sensitivity of 89% and specificity of 88%. Results were similar for daughter's report of father's smoking during her childhood. Maternal smoking during pregnancy is consistently associated with reductions in offspring birthweight, and with asthma risk in offspring. The daughter's risk of being very low (<1500 g) or low birthweight (<2500 g) or of having asthma were similar when exposure was defined according to mother's report, daughter's report of fetal smoke exposure, and daughter's report of mother's smoking during childhood. Conclusions: Daughter's report of mother's smoking prenatally and in childhood are good proxy measures for mother's own report of smoking during pregnancy.

Smith DK; Johnson AB; Pears KC; Fisher PA; DeGarmo DS. Child maltreatment and foster care: Unpacking the effects of prenatal and postnatal parental substance use. Child Maltreatment 12(2): 150-160, 2007. (71 refs.)

Parental substance use is a well-documented risk for children. However, little is known about specific effects of prenatal and postnatal substance use on child maltreatment and foster care placement transitions. In this study, the authors unpacked unique effects of (a) prenatal and postnatal parental alcohol and drug use and (b) material and paternal substance use as predictors of child maltreatment and foster care placement transitions in a sample of 117 maltreated foster care children. Models were tested with structural equation path modeling. Results indicated that prenatal maternal alcohol use predicted child maltreatment and that combined prenatal maternal alcohol and drug use predicted foster care placement transitions. Prenatal maternal alcohol and drug use also predicted postnatal paternal alcohol and drug use, which in turn predicted foster care placements. Findings highlight the potential integrative role that maternal and paternal substance use has on the risk for child maltreatment and foster care.

Smith LM; LaGasse LL; Derauf C; Grant P; Shah R; Arria A et al. Prenatal methamphetamine use and neonatal neurobehavioral outcome. Neurotoxicology and Teratology 30(1): 20-28, 2008. (49 refs.)

Background: Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. How prenatal MA exposure affects neonatal neurobehavior is unknown. Objective: To examine the neurobehavioral effects of prenatal MA exposure. Design: The Infant Development, Environment and Lifestyle (IDEAL) study screened 13,808 subjects and 1632 were eligible and consented. 166 (n = 74 exposed) were enrolled in a longitudinal follow-up. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. The NICU Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life. Analyses conducted on NNNS summary scores included exposure group effects, heavy MA use effects, association with frequency of use by trimester, and dose-response relationships with amphetamine metabolites. Results: After adjusting for covariates, exposure to MA was associated with increased physiological stress. Heavy MA use was related to lower arousal, more lethargy, and increased physiological stress. First trimester MA use was related to elevated stress abstinence. Third trimester use was related to poorer quality of movement. Higher level of amphetamine metabolites in meconium was associated with increased CNS stress. Conclusions: Prenatal MA exposure was associated with neurobehavioral patterns of decreased arousal, increased stress, and poor quality of movement. The dose-response relationships may represent neurotoxic effects from MA.

Steinhausen HC; Blattmann B; Pfund F. Developmental outcome in children with intrauterine exposure to substances. European Addiction Research 13(2): 94-100, 2007. (38 refs.)

The developmental outcome of children born to Swiss substance-dependent mothers in a residential treatment program was studied in a sample of 61 children ranging from infancy to preadolescence (mean age = 5.10, SD = 3.10 years) by use of age-appropriate tests of intelligence. A large list of biological and psychosocial risk factors was tested for associations with outcome in the children. The mean profile of test findings across all age ranges was significantly lower than population norms and there was an excess of children with subnormal intellectual functioning. Performance IQ was associated negatively only with intrauterine substance exposure, but with none of the other risk factors. Among the various substances, predominantly heroin or methadone were responsible for this association when controls for nicotine or cannabis consumption were made. The study provides further evidence that intrauterine exposure to heroin and methadone negatively affects the developmental outcome in the offspring of substance-dependent mothers.

Street K; Whitlingum G; Gibson P; Cairns P; Ellis M. Is adequate parenting compatible with maternal drug use? A 5-year follow-up. Child Care Health and Development 34(2): 204-206, 2008. (2 refs.)

Introduction: This prospective, cohort study compares child protection outcomes over the first 5 years of life in a group of children born to self-declared drug-using mothers recruited during pregnancy (cases) and a group of children matched for gestational age, chronological age, maternal neighbourhood and place of delivery whose mothers made no such declaration of problematic drug use (controls). Methodology We monitored local child protection registers to identify cohort members who came to the attention of the local authority. Results Of the 71 original cases and 142 original controls, 55 (77%) and 96 (68%) remained in the area enrolled in local schools at 5 years of age. In total, 26 (47.3%) of the case children were subject to child protection procedures compared with 18 (18.8%) of the control children. This risk difference of 28.5% (95% CI 13.2% to 43.9%) has increased marginally since our previous report in this journal of child protection outcomes at 18 months of age (32% vs. 7%). However, the level of intervention deemed necessary to protect the child has increased significantly with six cases (compared with one control child) taken into the care of the local authority. Conclusions: Despite early maternal intentions and multiple supportive interventions, 27% of children born to women with significant substance abuse problems in our area required child protection during the pre-school years. Child protection risk assessment procedures need to weigh problematic maternal drug use heavily. Intervention studies with child welfare outcomes are needed to identify the most effective harm reduction strategies and inform public debate on how we can minimize child abuse related to substance misuse.

Strohsnitter WC; Hatch EE; Hyer M; Troisi R; Kaufman RH; Robboy SJ et al. The association between in utero cigarette smoke exposure and age at menopause. American Journal of Epidemiology 167(6): 727-733, 2008. (24 refs.)

Menopause onset, on average, occurs earlier among women who smoke cigarettes than among women who do not smoke. Prenatal smoke exposure may also influence age at menopause through possible effects on follicle production in utero. Smoking information was obtained from the mothers of 4,025 participants in the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project, a US study begun in 1975 to examine the health effects of prenatal diethylstilbestrol exposure. Between 1994 and 2001, participants provided information on menopausal status. Cox proportional hazards modeling compared the probability of menopause among participants who were and were not prenatally exposed to maternal cigarette smoke. Participants prenatally exposed to maternal cigarette smoke were more likely than those unexposed to be postmenopause (hazard ratio = 1.21, 95% confidence interval: 1.02, 1.43). The association was present among only those participants who themselves had never smoked cigarettes (hazard ratio = 1.38, 95% confidence interval: 1.10, 1.74) and was absent among active smokers (hazard ratio = 1.03, 95% confidence interval: 0.81, 1.31). In this cohort of participants predominantly exposed to diethylstilbestrol, results suggest that prenatal exposure to maternal cigarette smoke may play a role in programming age at menopause. The possibility that active cigarette smoking modifies this effect is also suggested.

Sun AP; Freese MP; Fitzgerald M. An exploratory study of drug-exposed infants: Case substantiation and subsequent child maltreatment. Child Welfare 86(3): 33-50, 2007. (23 refs.)

This study explores factors related to drug-exposed infants' case substantiation and subsequent child maltreatment. Child protective services computerized administrative data (from January 1998 to October 2001) were obtained from an urban Nevada county. The data included 457 drug-exposed infant cases. Chi-square, t-test, oneway ANOVA, and logistic regression were used to analyze the data. Results indicate that: (1) drug-exposed infant case substantiation was related to the type of drug exposure and the unit to which the case was assigned, but not to the mother's ethnicity; and (2) subsequent maltreatment among drug-exposed infants was related to the mother's age and prior parental alcohol abuse, but not to the type of drug exposure, nor to the initial drug-exposed infant status of case substantiation. Implications for child welfare practice and research are discussed.

Suzuki K; Tanaka T; Kondo N; Minai J; Sato M; Yamagata Z. Is maternal smoking during early pregnancy a risk factor for all low birth weight infants? Journal of Epidemiology 18(3): 89-96, 2008. (31 refs.)

Background: Low birth weight (LBW) infants do not form a homogeneous group; LBW can be caused by prematurity or poor fetal growth manifesting as small for gestational age (SGA) infants or intrauterine growth retardation. We aimed to clarify the relationship of maternal smoking with both SGA and preterm LBW infants. Methods: The study population comprised pregnant women who registered at the Koshu City between January 1, 1995, and December 31, 2000, and their children. We performed multivariate analyses using multiple logistic regression models to clarify the relationship of maternal smoking during pregnancy with the SGA outcome and preterm birth in LBW infants. Results: In this study period, 1,329 pregnant women responded to questionnaires, and infant data were collected from 1,100 mothers (follow-up rate: 82.8%). The number of LBW infants was 81 (7.4%). In this cohort, maternal smoking during early pregnancy was associated with LBW and the SGA outcome. Maternal smoking during early pregnancy was a risk factor for LBW with SGA outcome and for LBW with full-term birth. However, it was not a risk factor for LBW with appropriate weight for gestational age (AGA) and LBW with preterm birth. Conclusion: These results suggested that LBW with AGA and LBW with preterm birth were associated with other risk factors that were not considered in this study, such as periodontal disease. For the prevention of LBW, not only abstinence from smoking during pregnancy but also other methods such as establishing a clinical setting should be adopted.

Tebow G; Sherrill DL; Lohman IC; Stern DA; Wright AL; Martinez FD et al. Effects of parental smoking on interferon gamma production in children. Pediatrics 121(6): e1563-e1569, 2008. (27 refs.)

OBJECTIVES. Environmental tobacco smoke is associated with several negative health outcomes in children, including an increased susceptibility to infections. One of the postulated mechanisms for these effects is the impairment of the immune system function and/ or development. Yet, it remains unknown whether cumulative exposure to parental smoking is associated with altered immune responses in childhood and whether these effects are independent of in utero exposure to maternal smoking. In a population-based birth cohort, we sought to determine the relation of parental smoking, as assessed prospectively since pregnancy, to the child's interferon gamma and interleukin 4 production at 11 years of age. PATIENTS AND METHODS. We used data on 512 children and their parents from the Tucson Children's Respiratory Study cohort. Information on maternal and paternal smoking was collected prospectively by questionnaire, and pack-years for mother, father, and both parents combined were assessed prospectively between the prenatal period and year 11. At age 11 years, children's interferon gamma and interleukin 4 production from mitogen-stimulated peripheral blood mononuclear cells was measured. RESULTS. Children of parents who smoked between the prenatal period and year 11 were more likely to be in lower quartiles of interferon gamma production than children of nonsmoking parents. In addition, maternal, paternal, and parental pack-years showed significant inverse dose-response relationships with interferon gamma production in the child. These dose-response relationships with interferon gamma remained significant for both paternal and parental pack-years among children of mothers who did not smoke during pregnancy, suggesting the existence of specific postnatal effects of environmental tobacco smoke exposure. In contrast, no significant effects of parental smoking were found on interleukin 4 production. CONCLUSIONS. Interferon gamma responses of school-aged children are impacted by parental smoking.

Topley J; Windsor D; Williams R. Behavioural, developmental and child protection outcomes following exposure to Class A drugs in pregnancy. Child Care, Health and Development 34(1): 71-76, 2008. (11 refs.)

Background: The long-term consequences of intrauterine exposure to Class A drugs are still relatively undocumented, and much of the literature relates to the North American experience, where cocaine use predominates. In Britain, heroin and amphetamine use is more common and, within Britain, patterns of drug use vary. Clearly the long-term educational and welfare needs of these children will be enhanced if the behavioural, developmental and child-care outcomes are known. This study attempts to explore some of these issues. Methods The developmental, behavioural and child protection outcomes in a group of 62 children exposed to Class A drugs in utero were investigated when the children were in full-time schooling. Results: Seventy-four per cent (46/62) of the children at the time of the study had no educational or behavioural problems, and 11 (17.7%) were receiving extra support in school. No child had a statement of special educational need. Twelve (19.3%) were reported to have behaviour and concentration problems, and in four cases, this was attributed to poor-quality parenting at the time of the study. Three of the 12 children had fetal alcohol syndrome. Twenty-six (42%) children were placed on the Child Protection Register, and care orders or residence orders were granted for 22 (35.5%) of those who were placed on the register. All of the 22 children went into substitute care at some stage. Of these children, nine were adopted and 10 were placed permanently with other family members. Ten of the 62 (16.1%) children at the time of the study were of concern to professionals for child protection reasons, and four of them were on the Child Protection Register. Conclusions: This study suggests we can be reasonably optimistic about the developmental and behavioural outcomes for children exposed to Class A drugs in utero. Over 50% required an intervention by social services, and 31% were in substitute care at the time of the study. There were continuing child protection concerns in 16% at school entry.

Toro R; Leonard G; Lerner JV; Lerner RM; Perron M; Pike GB et al. Prenatal exposure to maternal cigarette smoking and the adolescent cerebral cortex. Neuropsychopharmacology 33(5): 1019-1027, 2008. (75 refs.)

Smoking during pregnancy is associated with long-term consequences on offspring behavior. We measured thickness of the cerebral cortex using magnetic resonance images obtained in 155 adolescents exposed in utero to maternal smoking and compared them with 159 non-exposed subjects matched by maternal education. Orbitofrontal, middle frontal, and parahippocampal cortices were thinner in exposed, as compared with non-exposed, individuals; these differences were more pronounced in female adolescents. In exposed females, the thickness of the orbitofrontal cortex correlated negatively with a self-rated assessment of caring, one of the components of a model of positive youth development. These findings provide evidence of the long-term impact of prenatal environment on a neural substrate of cognition and social behavior.

Triche EW; Hossain N; Paidas MJ. Genetic influences on smoking cessation and relapse in pregnant women. (review). Journal of Obstetrics and Gynaecology 28(2): 155-160, 2008. (79 refs.)

Cigarette smoking during pregnancy continues to be a significant public health concern. Maternal smoking during pregnancy has been associated with low birth weight(< 2500 g), fetal growth restriction, placental problems, pre-term delivery and spontaneous abortion. Mothers who smoke during pregnancy are twice as likely to give birth to low birth weight infants, and smoking during pregnancy is estimated to be responsible for 20-30% of all low birth weight infants. Smoking during pregnancy not only affects placental function, thus causing obstetrical complications, but nicotine also crosses the placenta and acts as a neuroteratogen. This in turn, elevates the risk of cognitive and auditory processing deficits, and has also been found to be negatively associated with long-term consequences on offspring behaviour. In addition, smoking has negative long-term health consequences for both mother and child, including respiratory conditions, cancer and cardiovascular problems. This review provides insight into the genetic influences on smoking behaviour in pregnant women. In particular, the roles of genes in the neuro transmitter pathways are highlighted. It also emphasises the need for further research in this area, and provides rationale for the importance of focusing on pregnant women who are highly motivated to quit when researching smoking behaviours in women.

Trksak GH; Glatt SJ; Mortazavi F; Jackson D. A meta-analysis of animal studies on disruption of spatial navigation by prenatal cocaine exposure. (review). Neurotoxicology and Teratology 29(5): 570-577, 2007. (102 refs.)

Water-maze testing has been used to assess prenatal cocaine (PCOC)-induced deficits in behavioral studies of spatial navigation and memory abilities. Effects of PCOC in acquisition or in probe trials over water-maze testing days were rarely detected. Despite an absence of effects of PCOC when data were collapsed over multiple days, there was a potential difference when examined during the first day of acquisition training, characterized by a PCOC-associated decrease in learning efficiency but not capacity. Here, we review studies of PCOC-related changes in day-1 water-maze acquisition training and examine the relationship between experimental methodologies and PCOC-treatment procedures and the variability in effect size estimates across studies. The results revealed a significant increase in latencies to goal platform on acquisition training day-1 in PCOC-exposed offspring vs. controls (effect size: r=0.44). Significant effects attributable to variations in the PCOC-treatment procedures across studies were also identified. The moderating variable of PCOC "dose" was significant as lower doses of PCOC exposure yielded larger treatment effects. "Duration" of PCOC exposure was not significant, although a trend for greater effects was observed in studies that employed longer daily treatment schedules or schedules administered in later gestational periods. This analysis identified a consistent difference in acquisition training day-1 of water-maze testing in PCOC-exposed offspring indicating a PCOC-induced deficiency in spatial learning. These findings of impaired spatial learning efficiency are of particular interest given clinical scenarios involving acutely impaired spatial memory and related learning in PCOC-exposed children that highlight the potential consequences in classroom learning.

Twomey JE. Partners of perinatal substance users: Forgotten, failing, or fit to father? American Journal of Orthopsychiatry 77(4): 563-572, 2007. (66 refs.)

The role fathers play in families affected by perinatal substance use largely has been unexamined. It is difficult to reconcile this peripheral role assigned to the fathers of substance-exposed infants as the importance of fathers in the lives of children and of partners in the lives of substance-using women has become better appreciated. In this article, case presentations of families in which both parents were substance users illustrate the complexities and diverse trajectories of relationships between perinatal substance users and their children's fathers. An examination of families' lives can be used to better understand the challenges they face, stimulate further discussion about how partners of perinatal substance users can be conceptualized as fathers, and consider the impact they have in the lives of their children and their children's mothers. Discussion of case studies can yield increased knowledge about the role of fathers in the lives of families affected by perinatal substance abuse. This will lead to better-informed treatment interventions, research, and public policy.

Vahidnia F; Eskenazi B; Jewell N. Maternal smoking, alcohol drinking, and febrile convulsion. Seizure 17(4): 320-326, 2008. (21 refs.)

Background: Previous studies have suggested that maternal cigarette smoking and alcohol drinking during pregnancy may increase risk for febrile convulsion during childhood. We evaluated the relationship of maternal smoking, alcohol drinking, and their interaction on febrile convulsion. Method: Pregnant women (n = 10, 108) enrolled in the Child Health and Development Studies in California between 1959 and 1966 were interviewed about their habits during pregnancy and febrile convulsions of the child were ascertained soon after an event. Results: Febrile convulsions were reported in 2.9% of children of mothers who both smoked and drank alcohol, 2.0% for children of mothers who smoked but did not drink, 1.5% for children of mothers who drank but did not smoke and 2.1% of children of mothers who neither smoked nor drank. After adjusting for covariates, children of smokers who did not drink and children of drinkers who did not smoke did not have a significant hazard for febrile convulsion, compared to children of non-smokers nondrinkers. However, children of smokers who drank had a 30% increased hazard of febrile convulsion (95% Cl = 1.0, 1.9). The interaction term for smoking and alcohol drinking was significant in the multivariable model (p = 0.02). Conclusion: These results suggest that children of mothers who both smoke and drink alcohol during pregnancy may have a higher risk for febrile convulsions.

Walhovd KB; Moe V; Slinning K; Due-Tonnessen P; Bjornerud A; Dale AM et al. Volumetric cerebral characteristics of children exposed to opiates and other substances in utero. Neuroimage 36(4): 1331-1344, 2007. (54 refs.)

Morphometric cerebral characteristics were studied in children with prenatal poly-substance exposure (n = 14) compared to controls (n = 14) without such exposure. Ten of the substance-exposed children were born to mothers who used opiates (heroin) throughout the pregnancy. Groups were compared across 16 brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, lateral ventricles, inferior lateral ventricles, and the 3rd and 4th ventricles. In addition, continuous measurement of thickness across the entire cortical mantle was performed. Volumetric characteristics were correlated with ability and questionnaire assessments 2 years prior to scan. Compared to controls, the substance-exposed children had smaller intracranial and brain volumes, including smaller cerebral cortex, amygdala, accumbens area, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, and inferior lateral ventricles, and thinner cortex of the right anterior cingulate and lateral orbitofrontal cortex. Pallidum and putamen appeared especially reduced in the subgroup exposed to opiates. Only volumes of the right anterior cingulate, the right lateral orbitofrontal cortex and the accumbens area, showed some association with ability and questionnaire measures. The sample studied is rare and hence small, so conclusions cannot be drawn with certainty. Morphometric group differences were observed, but associations with previous behavioral assessment were generally weak. Some of the volumetric differences, particularly thinner cortex in part of the right lateral orbitofrontal cortex, may be moderately involved in cognitive and behavioral difficulties more frequently experienced by opiate and polysubstance-exposed children.

Weiss SJ; Jonn-Seed MS; Harris-Muchell C. The contribution of fetal drug exposure to temperament: Potential teratogenic effects on neuropsychiatric risk. (review). Journal of Child Psychology and Psychiatry 48(8): 773-784, 2007. (137 refs.)

Background: Preliminary evidence indicates that fetal drug exposure may be associated with alterations in temperament. However, studies often do not dissociate the potential effects of drug exposure from other perinatal or environmental factors that could influence temperament phenotypes. Methods: High risk children (n = 120) were followed from birth to 6 months of age to determine the effects of fetal drug exposure on temperament, after controlling for the child's gender, gestational age, medical morbidity, ethnicity, and maltreatment as well as the mother's stress, income adequacy, and quality of caregiving. Methods included medical chart review, questionnaires, and videotapes of mother-child interaction. Results: Preliminary analyses indicated that fetal drug exposure was associated with both distractibility and intensity of children's responses to the environment at 6 months of age. After adjusting for potentially confounding variables, drug exposure accounted for 12% of the variance in distractibility but was not a significant predictor in the regression model for intensity. Conclusions: Findings suggest that drug-exposed children may experience difficulty sustaining their focus of attention and be more easily distracted by environmental stimuli than non-drug-exposed children. Results converge with previous research to implicate cortical hyperarousal, stemming from teratogenic effects on the dopaminergic system during fetal development.

Wigle DT; Arbuckle TE; Walker M; Wade MG; Liu SL; Krewski D. Environmental hazards: Evidence for effects on child health. (review). Journal of Toxicology and Environmental Health. Part B, Critical Reviews 10(1/2): 3-39, 2007. (359 refs.)

The human fetus, child, and adult may experience adverse health outcomes from parental or childhood exposures to environmental toxicants. The fetus and infant are especially vulnerable to toxicants that disrupt developmental processes during relatively narrow time windows. This review summarizes knowledge of associations between child health and development outcomes and environmental exposures, including lead, methylmercury, polychlorinated biphenyls (PCBs), dioxins and related polyhalogenated aromatic hydrocarbons (PHAHs), certain pesticides, environmental tobacco smoke (ETS), aeroallergens, ambient air toxicants (especially particulate matter [PM] and ozone), chlorination disinfection by-products (DBPs), sunlight, power-frequency magnetic fields, radiofrequency (RF) radiation, residential proximity to hazardous waste disposal sites, and solvents. The adverse health effects linked to such exposures include fetal death, birth defects, being small for gestational age (SGA), preterm birth, clinically overt cognitive, neurologic, and behavioral abnormalities, subtle neuropsychologic deficits, childhood cancer, asthma, other respiratory diseases, and acute poisoning. Some environmental toxicants, notably lead, ionizing radiation, ETS, and certain ambient air toxicants, produce adverse health effects at relatively low exposure levels during fetal or child developmental time windows. For the many associations supported by limited or inadequate epidemiologic evidence, major sources of uncertainty include the limited number of studies conducted on specific exposure-outcome relationships and methodologic limitations. The latter include (1) crude exposure indices, (2) limited range of exposure levels, (3) small sample sizes, and (4) limited knowledge and control of potential confounders. Important knowledge gaps include the role of preconceptual paternal exposures, a topic much less studied than maternal or childhood exposures. Large longitudinal studies beginning before or during early pregnancy are urgently needed to accurately measure and assess the relative importance of parental and childhood exposures and evaluate relatively subtle health outcomes such as neuropsychologic and other functional deficits. Large case-control studies are also needed to assess the role of environmental exposures and their interactions with genetic factors in relatively uncommon outcomes such as specific types of birth defects and childhood cancers. There is also an urgent need to accelerate development and use of biomarkers of exposure and genetic susceptibility in epidemiologic studies. This review supports the priority assigned by international agencies to relationships between child health and air quality (indoor and outdoor), lead, pesticides, water contaminants, and ETS. To adequately address such priorities, governments and agencies must strengthen environmental health research capacities and adopt policies to reduce parental and childhood exposures to proven and emerging environmental threats.

Wilbur MB; Marani JE; Appugliese D; Woods R; Siegel JA; Cabral HJ et al. Socioemotional effects of fathers' incarceration on low-income, urban, school-aged children. Pediatrics 120(3): E678-E685, 2007. (49 refs.)

OBJECTIVE. The goal was to evaluate whether children of incarcerated fathers are more likely to report or exhibit behavioral symptoms than their equally disadvantaged peers without an incarcerated father. METHODS. During an ongoing longitudinal study of intrauterine cocaine exposure involving 102 children (50% male and 89% black) from urban, low- income homes, questions regarding incarceration of the child's father were asked of the child's primary caregiver at each visit during school age. Children were administered the Children's Depression Inventory between the ages of 6 and 11 years, and their primary caregivers completed the Child Behavior Checklist. In addition, the children's teachers completed the Teacher Report Form. Children's Depression Inventory, Child Behavior Checklist, and Teacher Report Form data obtained at the oldest available age after the first report of paternal incarceration were analyzed. RESULTS. In bivariate analyses, children whose fathers were in jail had higher Children's Depression Inventory total scores compared with children without incarcerated fathers, indicating more depressive symptoms. This finding was robust in multivariate analyses after adjustment for children's age, gender, prenatal cocaine and alcohol exposure, and school- age violence exposure. Teachers reported higher Teacher Report Form externalizing scores for children whose fathers were in jail, after adjustment for age, gender, prenatal cocaine and marijuana exposure, and school- age violence exposure. CONCLUSIONS. Children of incarcerated fathers reported more depressive symptoms and their teachers noted more externalizing behaviors, after controlling for other biopsychosocial risks. Interventions targeted to ameliorate the distress of children with incarcerated fathers should be considered.

Winklbaur B; Kopf N; Ebner N; Jung E; Thau K; Fischer G. Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence: A knowledge synthesis for better treatment for women and neonates. (review). Addiction 103(9): 1429-1440, 2008. (134 refs.)

Aims: Through a novel synthesis of the literature and our own clinical experience, we have derived a set of evidence-based recommendations for consideration as guidance in the management of opioid-dependent pregnant women and infants. Methods PubMed literature searches were carried out to identify recent key publications in the areas of pregnancy and opioid dependence, neonatal abstinence syndrome (NAS) prevention and treatment, multiple substance abuse and psychiatric comorbidity. Results Pregnant women dependent on opioids require careful treatment to minimize harm to the fetus and neonate and improve maternal health. Applying multi-disciplinary treatment as early as possible, allowing medication maintenance and regular monitoring, benefits mother and child both in the short and the long term. However, there is a need for randomized clinical trials with sufficient sample sizes. Recommendations: Opioid maintenance therapy is the recommended treatment approach during pregnancy. Treatment decisions must encompass the full clinical picture, with respect to frequent complications arising from psychiatric comorbidities and the concomitant consumption of other drugs. In addition to standardized approaches to pregnancy, equivalent attention must be given to the treatment of NAS, which occurs frequently after opioid medication. Conclusion: Methodological flaws and inconsistencies confound interpretation of today's literature. Based on this synthesis of available evidence and our clinical experience, we propose recommendations for further discussion.

Winklbaur B; Kopf N; Ebner N; Jung E; Thau K; Fischer G. Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence: A knowledge synthesis for better treatment for women and neonates. (review). Addiction 103(9): 1429-1440, 2008. (134 refs.)

Aims: Through a novel synthesis of the literature and our own clinical experience, we have derived a set of evidence-based recommendations for consideration as guidance in the management of opioid-dependent pregnant women and infants. Methods: PubMed literature searches were carried out to identify recent key publications in the areas of pregnancy and opioid dependence, neonatal abstinence syndrome (NAS) prevention and treatment, multiple substance abuse and psychiatric comorbidity. Results Pregnant women dependent on opioids require careful treatment to minimize harm to the fetus and neonate and improve maternal health. Applying multi-disciplinary treatment as early as possible, allowing medication maintenance and regular monitoring, benefits mother and child both in the short and the long term. However, there is a need for randomized clinical trials with sufficient sample sizes. Recommendations: Opioid maintenance therapy is the recommended treatment approach during pregnancy. Treatment decisions must encompass the full clinical picture, with respect to frequent complications arising from psychiatric comorbidities and the concomitant consumption of other drugs. In addition to standardized approaches to pregnancy, equivalent attention must be given to the treatment of NAS, which occurs frequently after opioid medication. Conclusion: Methodological flaws and inconsistencies confound interpretation of today's literature. Based on this synthesis of available evidence and our clinical experience, we propose recommendations for further discussion.

Xue F; Willett WC; Rosner BA; Forman MR; Michels KB. Parental characteristics as predictors of birthweight. Human Reproduction 23(1): 168-177, 2008. (78 refs.)

BACKGROUND: Previous studies provided conflicting results on the relevance of parental characteristics for offspring's size at birth. The objective of this study was to investigate parental predictors of birthweight. METHODS: In this cross-sectional study, 34 063 women in the Nurses' Mother's Cohort were queried about parental characteristics during the pregnancy with and birthweight of their nurse daughter. RESULTS: The predictive linear regression model of birthweight included 13 factors and the majority of the predictive power came from parental anthropometric factors. In the adjusted analysis, daily consumption of each additional glass of milk was associated with an increase of similar to 6 g in birthweight (P for trend = 0.01) and daily consumption of each additional cup of coffee was associated with a decrease of similar to 10 g in birthweight (P for trend < 0.0001). Drinking 1-2, 3-4 and 5+ cups of coffee daily was associated with a 28% [95% confidence interval (CI) 0.12, 0.47], 30% (95% CI 0.10, 0.55) and 63 % (95 % CI 0.25, 1.12) increase, respectively, in the odds of intrauterine growth restriction when compared with non-drinkers. CONCLUSIONS: The present study confirmed several previously reported determinants of birthweight. Maternal dietary intake of milk and coffee during pregnancy may influence fetal growth.

Yamaguchi ET; Cardoso MMSC; Torres MLA; de Andrade AG. Drug abuse during pregnancy. (review) [Portuguese]. Revista de Investigacion Clinica 35(Supplement 1): 44-47, 2008. (41 refs.)

Background: Despite the fact that it has being a growing problem worldwide, very few works and papers have been published on drug use during pregnancy. Objectives: To objectively address the most commonly abused drugs (alcohol, cocaine, marijuana, and tobacco) by women of a reproductive age. Methods: A literature review (MEDLINE, LILACS) of the most recent papers on drug abuse by women of reproductive age was carried out. Results: The primary consequences of drug abuse both for the mother and the infant are described. Conclusions: This is a little discussed major public health issue which requires the involvement of a multidisciplinary team. The publication of a greater number of papers on the problem is necessary in order to establish the best strategy for addressing intervention in this population.