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CORK Bibliography: Prenatal Drug Exposure

66 citations. October 2006 to present

Prepared: September 2007

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.

Al Mamun A; Lawlor DA; Alati R; O'Callaghan MJ; Williams GM; Najman JM. Does maternal smoking during pregnancy have a direct effect on future offspring obesity? Evidence from a prospective birth cohort study. American Journal of Epidemiology 164(4): 317-325, 2006. (38 INC refs.)

The authors used a population-based birth cohort of 3,253 children (52% males) born in Brisbane, Australia, between 1981 and 1984 to prospectively examine whether maternal smoking during pregnancy was associated with offspring overweight and obesity. The authors compared mean body mass indexes (weight (kg)/height (m)(2)) and levels of overweight and obesity at age 14 years among offspring by patterns of maternal smoking (never smoked, smoked before and/or after pregnancy but not during pregnancy, or smoked during pregnancy). Adolescent body mass index and prevalences of overweight and obesity were greater in offspring whose mothers had smoked during pregnancy than in those whose mothers had never smoked. Body mass index and levels of overweight and obesity among adolescent offspring whose mothers stopped smoking during pregnancy but smoked at other times in the child's life were similar to those among offspring whose mothers had never smoked. These results were independent of a range of potentially confounding factors and suggest a direct effect of maternal smoking during pregnancy on adolescent overweight and obesity. They provide yet another incentive for pregnant women to be persuaded not to smoke and for young women to be encouraged to never take up smoking.

Al Mamun A; O'Callaghan FV; Alati R; O'Callaghan M; Najman JM; Williams GM et al. Does maternal smoking during pregnancy predict the smoking patterns of young adult offspring? A birth cohort study. Tobacco Control 15(6): 452-457, 2006. (32 refs.)

Objective: To examine the association between maternal smoking during pregnancy and the development of smoking behaviour patterns among young adult offspring. Method: Data were from the Mater- University of Queensland Study of Pregnancy (MUSP), a birth cohort of 7223 mothers and children enrolled in Brisbane, Australia, in 1981. The development of smoking behaviours (early or late onset, or combination of onset and prevalence patterns) among offspring at age 21 years with different patterns of maternal smoking (never smoked, smoked before or after pregnancy but not during pregnancy, or smoked during pregnancy) were compared. Maternal smoking information was derived from the prospectively collected data from the beginning of pregnancy until the child was 14 years of age. Analyses were restricted to the 3058 mothers and children whose smoking status was reported. Results: The proportion of young adults who smoked regularly, either with early onset or late onset, was greater among those whose mothers had smoked during pregnancy compared with those whose mothers had never smoked. The smoking patterns among those adolescent offspring whose mothers stopped smoking during pregnancy, but who then smoked at other times during the child's life, were similar to those whose mothers had never smoked. This association was robust to adjustment for a variety of potential covariates. Conclusions: The findings provide some evidence for a direct effect of maternal smoking in utero on the development of smoking behaviour patterns of offspring and provide yet another incentive to persuade pregnant women not to smoke.

Alati R; Al Mamun A; Williams GM; O'Callaghan M; Najman JM; Bor W. In utero alcohol exposure and prediction of alcohol disorders in early adulthood: A birth cohort study. Archives of General Psychiatry 63(9): 1009-1016, 2006. (31 refs.)

Context: Little is known about the contribution of fetal alcohol exposure to the development of alcohol disorders in early adulthood. Objective: To examine the independent effect of maternal alcohol use during early vs late periods in pregnancy on the time of onset of alcohol disorders in offspring. Design: Follow-up study of the Mater-University of Queensland Study of Pregnancy and Its Outcomes (MUSP), a population-based birth cohort study commenced in Brisbane, Australia, in 1981 and designed to examine the association of maternal alcohol exposure with the onset of alcohol disorders. Mothers and children were followed up at birth, 6 months, and 5, 14, and 21 years after the initial interview. Maternal alcohol use was assessed before pregnancy, in early and late pregnancy, and at the 5- and 14-year follow-up visits. Alcohol disorders in early adulthood were assessed at age 21 years using the lifetime version of the Composite International Diagnostic Interview-computerized version. Setting: Population-based birth cohort study. Participants: A subsample of 2138 participants for whom complete data were available at the 21-year follow-up. Main Outcome Measure: Onset of alcohol disorder from adolescence to 21 years of age. Results: In utero alcohol exposure of 3 or more glasses was associated with alcohol disorders. The fully adjusted odds ratios (95% confidence intervals) of developing early-onset alcohol disorders at age 21 years were 2.95 (1.62-5.36) for those exposed to maternal drinking in early pregnancy and 1.35 (0.69-2.63) for those exposed in late pregnancy. There was also a strong association between alcohol exposure in early pregnancy and late-onset alcohol disorders (odds ratio, 3.29 [95% confidence interval, 1.74-6.24]). Conclusions: Our results provide support for a biological origin of adult alcohol disorders and suggest that the association is not explained solely by maternal drinking or smoking during childhood and adolescence or other intervening factors. Further research is needed to understand the mechanisms underlying the association.

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; Reynolds EW; Hansen WF. Marijuana use, adolescent pregnancy, and alteration in newborn behavior: How complex can it get? (editorial). Journal of Pediatrics 149(6): 742-745, 2006. (40 refs.)

Barros MCD; Guinsburg R; Peres CD; Mitsuhiro S; Chalem E; Laranjeira RR. Exposure to marijuana during pregnancy alters neurobehavior in the early neonatal period. Journal of Pediatrics 149(6): 781-787, 2006. (37 refs.)

Objective: To assess the neurobehavior of full-term neonates of adolescent mothers exposed to marijuana during pregnancy. Study design: This prospective cross-sectional study included full-term infants within 24 to 72 hours of life born to adolescent mothers at a single center in Brazil. Data on sociodemographic and obstetrical and neonatal characteristics were collected. The mothers underwent the Composite International Diagnostic Interview, and the infants were assessed with the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS). Maternal hair and neonatal meconium were analyzed. Neonates exposed in utero to tobacco, alcohol, cocaine, and/or any other drugs except marijuana were excluded. Results: Of 3685 infants born in the study hospital, 928 (25%) were born to adolescent mothers. Of these, 561 infants met the inclusion criteria and were studied. Marijuana exposure was detected in 26 infants (4.6%). Infants exposed (E) or not exposed (NE) to marijuana differed in the following NNNS variables: arousal (E, 4.05 +/- 1.19 vs NE, 3.68 +/- 0.70), regulation (E, 5.75 +/- 0.62 vs NE, 6.04 +/- 0.72), and excitability (E, 3.27 +/- 1.40 vs NE, 2.40 +/- 1.57). After controlling for confounding variables, the effect of marijuana exposure on these scores remained significant. Conclusions: Marijuana exposure during pregnancy alters the neurobehavioral performance of term newborn infants of adolescent mothers.

Batty GD; Der G; Deary IJ. Effect of maternal smoking during pregnancy on offspring's cognitive ability: Empirical evidence for complete confounding in the US National Longitudinal Survey of Youth. Pediatrics 118(3): 943-950, 2006. (30 refs.)

BACKGROUND. Numerous studies have reported that maternal cigarette smoking during pregnancy is related to lower IQ scores in the offspring. Confounding is a crucial issue in interpreting this association. METHODS. In the US National Longitudinal Survey of Youth 1979, IQ was ascertained serially during childhood using the Peabody Individual Achievement Test, the total score for which comprises results on 3 subtests: mathematics, reading comprehension, and reading recognition. Maternal IQ was assessed by using the Armed Forces Qualification Test. There were 5578 offspring ( born to 3145 mothers) with complete information for maternal smoking habits, total Peabody Individual Achievement Test score, and covariates. RESULTS. The offspring of mothers who smoked >= 1 pack of cigarettes per day during pregnancy had an IQ score ( Peabody Individual Achievement Test total) that was, on average, 2.87 points lower than children born to nonsmoking mothers. Separate control for maternal education (0.27-IQ-point decrement) and, to a lesser degree, maternal IQ (1.51-IQ-point decrement) led to marked attenuation of the maternal-smoking-offspring-IQ relation. A similar pattern of results was seen when Peabody Individual Achievement Test subtest results were the outcomes of interest. The only exception was the Peabody Individual Achievement Test mathematics score, in which adjusting for maternal IQ essentially led to complete attenuation of the maternal-smoking-offspring-IQ gradient (0.66-IQ-point decrement). The impact of controlling for physical, behavioral, and other social indices was much less pronounced than for maternal education or IQ. CONCLUSIONS. These findings suggest that previous studies that did not adjust for maternal education and/or IQ may have overestimated the association of maternal smoking with offspring cognitive ability.

Bech BH; Autrup H; Nohr EA; Henriksen TB; Olsen J. Stillbirth and slow metabolizers of caffeine: Comparison by genotypes. International Journal of Epidemiology 35(4): 948-953, 2006. (31 refs.)

Background: Cytochrome P4501A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) are key enzymes in the metabolism of caffeine. The polymorphism of these genes facilitates the detection of fast and slow metabolizers, and if caffeine is causally related to stillbirth, we expect slow metabolizers to have a higher risk of stillbirth at any given intake of caffeine. Gluthatione S-transferase alpha 1 (GSTA1) may also be active in the metabolism of caffeine as it conjugates glutathione to aromatic amines. Our study, therefore, included analyses of the association between GSTA1 and stillbirth. Methods A nested case non-case study among women who participated in the Danish National Birth Cohort: 142 cases of singleton stillbirths and 157 controls of singleton live births. Results: Slow oxidizer status (CYP1A2), slow acetylator status (NAT2), and low activity of GSTA1 were not individually associated with the risk of stillbirth [odds ratio (OR) = 1.06, 95% confidence interval (95% CI) 0.67-1.67, OR = 0.95, 95% CI 0.60-1.51, and OR = 1.42, 95% CI 0.88-2.28, respectively]. We did, however, observe that subjects with a combination of slow CYP1A2, slow NAT2, and low GSTA1 genes had almost a 2-fold risk of stillbirth compared with subjects with other combinations of genotypes. Conclusions: We found no link between any single genotype and the risk of stillbirth. An association between a combination of genotypes and stillbirth was discovered. Caffeine may be causally related to stillbirth, but larger studies using Mendelian randomization are needed to verify this.

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.

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.

Box D; Cochran D. Safe reduction in administration of naloxone to newborn infants: An observational study. Acta Paediatrica 95(9): 1083-1086, 2006. (12 refs.)

Background: Naloxone, a specific opiate antagonist, is widely used during neonatal resuscitation to reverse possible opiate-induced respiratory depression. Aim: To determine the frequency with which naloxone is administered when resuscitation guidelines are conscientiously followed and to document any effect on respiratory morbidity. Methods: Perinatal data including naloxone administration and respiratory morbidity were collected retrospectively, and compared with prospectively collected data following the introduction of "Good Practice" guidelines. Results: There were 500 deliveries in the retrospective arm of the study and 1000 deliveries in the prospective arm. Although a similar proportion of women received opiates in labour in the two periods of study, there was a marked reduction in the use of naloxone when the guidelines were introduced ( 11% of opiate-exposed deliveries compared to 0.2%). There was no significant effect on respiratory morbidity with the change in practice. Conclusion: Naloxone is rarely needed to reverse the effects of opiates in newborn infants, and its use can be curtailed by following current resuscitation guidelines without increasing respiratory morbidity.

Brook DW; Zhang CS; Rosenberg G; Brook JS. Maternal cigarette smoking during pregnancy and child aggressive behavior. American Journal on Addictions 15(6): 450-456, 2006. (44 refs.)

This study's objective was to examine the association between maternal smoking during pregnancy and childhood aggressive behavior in African-American and Puerto Rican children, as well as the relationship between maternal unconventional behavior, low maternal affection, and offspring aggression. Participants consisted of African-American and Puerto Rican children (N = 203; mean age = 8.6, SD = 0.87) and their mothers living in an inner city community. An interview consisting of a structured questionnaire was administered to the mothers and their children. Scales with adequate psychometric properties were adapted from previous validated measures. They included maternal smoking during pregnancy, maternal education, unconventionality, and warmth. Controlling for demographic factors, maternal unconventional behavior, and low maternal warmth, maternal smoking during pregnancy was associated with having offspring who were aggressive. Maternal unconventionality and warmth were independently related to childhood aggression. Although causal limitations are noted, it may be that a decrease in smoking during pregnancy is associated with a reduction in aggression in the offspring.

Cambria S; Manganaro R; Mami C; Marseglia L; Gemelli M. Hyperexcitability syndrome in a newborn infant of chocoholic mother. American Journal of Perinatology 23(7): 421-422, 2006. (11 refs.)

We present a case of hyperexcitability syndrome observed in a neonate born to a mother who was a heavy user of cocoa and chocolate during pregnancy and lactation. The infant presented jitteriness, irritability, inconsolable crying, excessive sucking, and sleeping difficulties almost immediately after birth. The infant underwent extensive diagnostic studies, but none of the usual causes for its symptoms were identified. The symptoms resolved after the interruption of maternal chocolate consumption. We hypothesize that the heavy exposure to chocolate could be responsible for the hyperexcitability syndrome.

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.

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.

Cruz RP. The greatest source of wealth: Washington State's response to prenatal substance abuse. Gonzaga Law Review 41: 1-27, 2006. (248 legal refs.)

It has been over thirty years since President Nixon declared war on drugs, naming drug abuse "public enemy number one in the United States." This paper discusses the medical and economic impact of prenatal substance abuse. It will present the various policies a number of states have adopted to address the problem, and most importantly, will discuss Washington's current policy, critique the proposed revision to this policy, and argue the need for earlier intervention. Part II of this paper identifies the damaging health effects of in utero drug exposure to a fetus. An overwhelming amount of medical research demonstrates that exposing a fetus to chemical substances could have irreparable and, in some cases, deadly health consequences. Part III examines the various state responses to the problem. More specifically, it discusses state initiatives that have taken a more punitive approach, including criminal and civil commitment statutes, along with child welfare laws recognizing a newborn's positive toxicology result as evidence of parental neglect. Part IV will detail both Washington's current policy and its proposal to take a minimal involvement approach to prenatal substance abuse. It will critique both degrees of state initiatives, discussing the economic and social impact of both a punitive approach and a minimal involvement approach. In Part V, the author discusses the importance of early intervention - the necessity of offering prenatal care and drug treatment services on a voluntary basis at the earliest possible time when an expectant mother is suspected of abusing substances.

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.

Dinehart LHB; Dice JL; Dobbins DR; Claussen AH; Bono KE. Proximal variables in families of children prenatally exposed to cocaine and enrolled in a center- or home-based intervention. Journal of Early Intervention 29(1): 32-47, 2006. (55 refs.)

The present study examined proximal variables in families of children prenatally exposed to cocaine and enrolled in a large-scale intervention program. Fifty-six high-risk families of children enrolled in the center-based (n = 30) or home-based (n = 26) intervention of the Linda Ray Intervention Program were interviewed. Four proximal variables were assessed: (a) quality of the caregiving environment, (b) family's regularity and predictability of daily routines, (c) caregiver's perception of the family's adequacy of resources, and (d) frequency and intensity of caregiver's experience with daily hassles. Results suggested that families of children enrolled in the center-based condition had more predictable daily routines than families of home-based participants. A family's adequacy of resources influenced the quality of the caregiving environment. Families with adequate resources were more likely to provide daily routines. Caregivers with fewer years of education were less able to establish and maintain daily routines which predicted, in part, a poorer caregiving environment.

Doggett C; Burrett S; Osborn DA. Home visits during pregnancy and after birth for women with an alcohol or drug problem. (review). Cochrane Database of Systemic Reviews 4(article no. CD004456), 2005. (111 refs.)

Background: One potential method of improving outcome for pregnant or postpartum women with a drug or alcohol problem is with home visits. Objectives: To determine the effects of home visits during pregnancy and/or after birth for pregnant women with a drug or alcohol problem. Search strategy We searched the Cochrane Pregnancy and Childbirth Trials Register (30 April 2004), CENTRAL (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to April 2004), EMBASE (1980 to week 16, 2004), CINAHL (1982 to April 2004), PsycINFO (1974 to April 2004), citations from previous reviews and trials, and contacted expert informants. Selection criteria Studies using random or quasi-random allocation of pregnant or postpartum women with a drug or alcohol problem to home visits. Trials enrolling high-risk women of whom more than 50% were reported to use drugs or alcohol were also eligible. Data collection and analysis assessments of trials were performed independently by all review authors. Statistical analyses were performed using fixed and random effects models where appropriate. Main results: Six studies (709 women) compared home visits after birth with no home visits. None provided a significant antenatal component of home visits. The visitors included community health nurses, pediatric nurses, trained counsellors, paraprofessional advocates, midwives and lay African-American women. Most studies had methodological limitations, particularly large losses to follow up. There were no significant differences in continued illicit drug use (2 studies, 248 women; relative risk (RR) 0.95, 95% confidence interval (CI) 0.75 to 1.20), continued alcohol use (RR 1.08, 95% CI 0.83 to 1.41) failure to enrol in a drug treatment program (2 studies, 211 women; RR 0.45 95% CI 0.10 to 1.94). There was no significant difference in the Bayley MDI (3 studies, 199 infants; weighted mean difference 2.89, 95% CI -1.17 to 6.95) or Psychomotor Index (WMD 3.14, 95% CI -0.03 to 6.32). Other outcomes reported by one study only included breastfeeding at six months (RR 1.00, 95% CI 0.81 to 1.23), incomplete six-month infant vaccination schedule (RR 1.07, 95% CI 0.58 to 1.96), non-accidental injury and non-voluntary foster care (RR 0.16, 95% CI 0.02 to 1.23), failure to use postpartum contraception (RR 0.41, 95% CI 0.20 to 0.82), child behavioural problems (RR 0.46, 95% CI 0.21 to 1.01), and involvement with child protective services (RR 0.38, 95% CI 0.20 to 0.74). Authors' conclusions: There is insufficient evidence to recommend the routine use of home visits for women with a drug or alcohol problem. Further large, high-quality trials are needed, and women's views on home visiting need to be assessed. Not enough information on home visiting in pregnancy and after the birth for women with an alcohol or drug problem. Women with an alcohol or drug problem in pregnancy are at increased risk of miscarriage, low birthweight babies, infections and postnatal depression, and the babies of withdrawal symptoms or impaired development. Home visits by individuals or teams of health professionals or trained lay people are aimed at improving health and social outcomes for mothers and babies. A review of trials found evidence that home visits after the birth increased the engagement of these women in drug treatment services but there were insufficient data to say if this improved the health of the baby or mother. Further research is needed, with visits starting during pregnancy.

Doris JL; Meguid V; Thomas M; Blatt S; Eckenrode J. Prenatal cocaine exposure and child welfare outcomes. Child Maltreatment 11(4): 326-337, 2006. (41 refs.)

This study examines the relationship between prenatal cocaine exposure and child welfare outcomes. Seventy-six infants positive for cocaine at birth were matched to 76 negative infants. With prenatal care and maternal use of alcohol and tobacco controlled, cocaine-exposed infants had significant decrements in birth weight, length, head circumference, and depressed 5-min Apgar scores. This confirmed the health risk of prenatal cocaine exposure for the sample. Three-year follow-up data were obtained from the State Central Register and foster care records. Adjusting for prior maternal involvement with child welfare services the study groups did not differ in incidents of child maltreatment or foster care placement. These findings suggest that prenatal cocaine exposure is not a marker for abusive parenting. However, from the perspective of a cumulative risk model, the identification of cocaine-exposed infants at birth can form the starting point for the development of appropriate diagnostic and follow-up services for mother and child.

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.

George L; Granath F; Johansson ALV; Anneren G; Cnattingius S. Environmental tobacco smoke and risk of spontaneous abortion. Epidemiology 17(5): 500-505, 2006. (25 refs.)

Background: Studies of exposure to environmental tobacco smoke (ETS) and risk of spontaneous abortion are limited to a few studies of self-reported exposure, and the results have been inconsistent. The aim of this study was to investigate risk of early spontaneous abortion related to ETS and active smoking as defined by plasma cotinine levels. Methods: We conducted a population-based case-control study in Uppsala County, Sweden, between January 1996 and December 1998. Cases were 463 women with spontaneous abortion at 6 to 12 completed weeks of gestation, and controls were 864 pregnant women matched to cases according to the week of gestation. Exposure status was defined by plasma cotinine concentrations: nonexposed, < 0.1 ng/mL; ETS-exposed, 0.1-15 ng/mL; and exposed to active smoking, > 15 ng/mL. Multivariable analysis was used to estimate the relative risk of spontaneous abortion associated with exposure to ETS and active smoking. Results: Nineteen percent of controls and 24% of cases were classified as having been exposed to ETS. Compared with nonexposed women, risk of spontaneous abortion was increased among both ETS-exposed women (adjusted odds ratio = 1.67; 95% confidence interval = 1.17-2.38) and active smokers (2.11; 1.36-3.27). We could not show a differential effect of exposure to ETS or active smoking between normal and abnormal fetal karyotype abortions. Conclusions: Nonsmoking pregnant women exposed to ETS may be at increased risk of spontaneous abortion. Given the high prevalence of ETS exposure, the public health consequences of passive smoking regarding early fetal loss may be substantial.

Gilliland FD; Islam T; Berhane K; Gauderman WJ; McConnell R; Avol E et al. Regular smoking and asthma incidence in adolescents. American Journal of Respiratory and Critical Care Medicine 174(10): 1092-1100, 2006. (47 refs.)

Rationale: Although involuntary exposure to maternal smoking during the in utero period and to secondhand smoke are associated with occurrence of childhood asthma, few studies have investigated the role of active cigarette smoking on asthma onset during adolescence. Objectives: To determine whether regular smoking is associated with the new onset of asthma during adolescence. Methods: We conducted a prospective cohort study among 2,609 children with no lifetime history of asthma or wheezing who were recruited from fourth- and seventh-grade classrooms and followed annually in schools in 12 southern California communities. Regular smoking was defined as smoking at least seven cigarettes per day on average over the week before and 300 cigarettes in the year before each annual interview. Incident asthma was defined using new cases of physician-diagnosed asthma. Measurements and Main Results: Regular smoking was associated with increased risk of new-onset asthma. Children who reported smoking 300 or more cigarettes per year had a relative risk (RR) of 3.9 (95% confidence interval [95% Cl], 1.7-8.5) for new-onset asthma compared with nonsmokers. The increased risk from regular smoking was greater in nonallergic than in allergic children. Regular smokers who were exposed to maternal smoking during gestation had the largest risk from active smoking (RR, 8.8; 95% Cl, 3.2-24.0). Conclusions: Regular smoking increased risk for asthma among adolescents, especially for nonallergic adolescents and those exposed to maternal smoking during the in utero period.

Glantz MD; Chambers JC. Prenatal drug exposure effects on subsequent vulnerability to drug abuse. (review). Development and Psychopathology 18(3): 893-922, 2006. (253 refs.)

Research has shown that both prenatal alcohol and tobacco exposure are associated with increased risk of significant adverse medical, developmental, and behavioral outcomes including substance abuse. Research on the outcomes of prenatal exposure to illicit drugs (PNDE) has also found increased physical and behavioral problems for gestationally drug-exposed children. However, a clear picture has not emerged on whether the consequences of PNDE are independent from those associated with having a substance abusing parent and whether PNDE increases vulnerability to drug abuse. Because of its typical co-occurrence with factors inherent in having a drug-abusing parent, PNDE is at least a marker of significant increased risk for a range of negative outcomes including greater vulnerability to substance abuse. Although a review of the relevant research literatures indicates that the direct consequences of PNDE appear to be generally both subtle and nonglobal, PNDE does appear to have negative developmental and behavioral outcomes, and there is evidence that it is a modest direct contributor to increased substance abuse vulnerability.

Huijbregts SCJ; Seguin JR; Zelazo PD; Parent S; Japel C; Tremblay RE. Interrelations between maternal smoking during pregnancy, birth weight and sociodemographic factors in the prediction of early cognitive abilities. Infant and Child Development 15(6): 593-607, 2006. (40 refs.)

Maternal prenatal smoking, birth weight and sociodemographic factors were investigated in relation to cognitive abilities of 1544 children (aged 3.5 years) participating in the Quebec Longitudinal Study of Children's Development. The Peabody Picture Vocabulary Test (PPVT) was used to assess verbal ability, the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) block design test to assess visuospatial ability, and the Visually Cued Recall (VCR) task to assess short-term memory. Prenatal smoking was related to performance on the WPPSI-R, the PPVT, and the VCR, although it did not independently predict any cognitive ability after maternal education was taken into account. Birth weight was a more robust predictor of all outcome measures and independently predicted VCR-performance. Birth weight interacted significantly with family income and maternal education in predicting visuospatial ability, indicating a greater influence of birth weight under relatively poor socio-economic conditions. Parenting and family functioning mediated associations between maternal education/family income and cognitive task performance under different birth weight conditions, although there were indications for stronger effects under relatively low birth weight. We conclude that investigations of moderating and mediating effects can provide insights into which children are most at risk of cognitive impairment and might benefit most from interventions.

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.

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.

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.

Knopik VS; Heath AC; Jacob T; Slutske WS; Bucholz KK; Madden PAF et al. Maternal alcohol use disorder and offspring ADHD: Disentangling genetic and environmental effects using a children-of-twins design. Psychological Medicine 36(10): 1461-1471, 2006. (56 refs.)

Background. Children of alcoholics are significantly more likely to experience high-risk environmental exposures, including prenatal substance exposure, and are more likely to exhibit externalizing problems [e.g. attention deficit hyperactivity disorder (ADHD)]. While there is evidence that genetic influences and prenatal nicotine and/or alcohol exposure play separate roles in determining risk of ADHD, little has been done on determining the joint roles that genetic risk associated with maternal alcohol use disorder (AUD) and prenatal risk factors play in determining risk of ADHD. Method. Using a children-of-twins design, diagnostic telephone interview data from high-risk families (female monozygotic and dizygotic twins concordant or discordant for AUD as parents) and control families targeted from a large Australian twin cohort were analyzed using logistic regression models. Results. Offspring of twins with a history of AUD, as well as offspring of non-AUD monozygotic twins whose co-twin had AUD, were significantly more likely to exhibit ADHD than offspring of controls. This pattern is consistent with a genetic explanation for the association between maternal AUD and increased offspring risk of ADHD. Adjustment for prenatal smoking, which remained significantly predictive, did not remove the significant genetic association between maternal AUD and offspring ADHD. Conclusions. While maternal smoking during pregnancy probably contributes to the association between maternal AUD and offspring ADHD risk, the evidence for a significant genetic correlation suggests: (i) pleiotropic genetic effects, with some genes that influence risk of AUD also influencing vulnerability to ADHD; or (ii) ADHD is a direct risk-factor for AUD.

LaGasse LL; Hammond J; Liu J; Lester BM; Shankaran S; Bada H et al. Violence and delinquency, early onset drug use, and psychopathology in drug-exposed youth at 11 years. Annals of the New York Academy of Sciences: Resilience in Children 1094: 313-318, 2006. (11 refs.)

In this first study of violence and resilience in 517 youth exposed to cocaine and other drugs during pregnancy, we identified specific links between four types of violence and delinquency, drug use, and psychopathology in early adolescence. Further, positive and interpersonal attributes promoted resilience in the face of exposure to violence and other risks. This study provides new evidence for the impact of violence as well as resilience against disruptive forms of psychopathology and behavior.

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.

Lawson CC; LeMasters GK. Regarding "Caffeine metabolism, genetics, and perinatal outcomes: A review of exposure assessment considerations during pregnancy" (letter). Annals of Epidemiology 16(9): 733-733, 2006. (3 refs.)

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.

Lyttle T. Stop the injustice: A protest against the unconstitutional punishment of pregnant drug-addicted women. New York University Journal of Legislation and Public Policy 9: 781-815, 2005. (237 legal refs.)

SUMMARY: Beginning in the late 1970s, an innovative prosecutorial strategy arose: states began prosecuting pregnant women because of their criminal behavior and its effects on their unborn and newborn children. ... In Robinson v. California, the Supreme Court established the principle that it is cruel and unusual punishment to punish an individual solely for his or her status as a drug offender. ... The punishment of drug-addicted women for their behavior during pregnancy is closer to the context of Robinson v. California than Powell v. Texas. Unlike the defendant in Powell, who committed the illegal act of being drunk in public, drug addiction during pregnancy is not an affirmative "act" but rather an involuntary addictive behavior. ... While the actions of these women could potentially endanger their fetuses, the women who are not drug addicts but use drugs during pregnancy are nevertheless still protected by the Constitution's Cruel and Unusual Punishment Clause, as the State is unlawfully punishing them for their status as drug users, which Robinson prohibits. ... The reasons behind a pregnant woman's drug use are numerous and should not be reduced to the assumption that the woman simply does not care about her fetus. ... In addition to the principles laid out in Robinson, punishing women for their behavior during pregnancy is precluded by the Cruel and Unusual Punishment Clause's principle of equality. Part I provides an overview of states' strategies for prosecuting pregnant drug-addicted women. States have primarily used child abuse, neglect, endangerment, controlled substance, homicide, and manslaughter statutes to punish pregnant drug-addicted women for allegedly exposing their fetuses to potential harm. Part II explores the constitutional and policy arguments most frequently made against criminalizing maternal substance abuse. Part III analyzes the Eighth Amendment argument against punishing pregnant drug-addicted women, including a brief overview of the origins of the Eighth Amendment, the purpose of the Amendment, and the Supreme Court's interpretation of the Cruel and Unusual Punishment Clause. Part III then builds on this information, applying it to the prosecution of pregnant drug-addicted women.

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.

Morrow CE; Culbertson JL; Accornero VH; Xue LH; Anthony JC; Bandstra ES. Learning disabilities and intellectual functioning in school-aged children with prenatal cocaine exposure. Developmental Neuropsychology 30(3): 905-931, 2006. (59 refs.)

Risk for developing a learning disability (LD) or impaired intellectual functioning by age 7 was assessed in full-term children with prenatal cocaine exposure drawn from a cohort of 476 children born full term and enrolled prospectively at birth. Intellectual functioning was assessed using the Wechsler Intelligence Scale for Children-Third Edition (Wechsler, 199 1) short form, and academic functioning was assessed using the Wechsler Individual Achievement Test (WIAT; Wechsler, 1993) Screener by examiners blind to exposure status. LDs were categorized based on ability-achievement discrepancy scores, using the regression-based predicted achievement method described in the WIAT manual. The sample in this report included 409 children (212 cocaine-exposed, 197 non-cocaine-exposed) from the birth cohort with available data. Cumulative incidence proportions and relative risk values were estimated using STATA software (Statacorp, 2003). No differences were found in the estimate of relative risk for impaired intellectual functioning (IQ below 70) between children with and without prenatal cocaine exposure (estimated relative risk=.95; 95% confidence interval [CI] =0.65, 1.39;p=.79). The cocaine-exposed children had 2.8 times greater risk of developing a LD by age 7 than non-cocaine-exposed children (95% CI=1.05,7.67;p=.038; IQ >= 70 cutoff). Results remained stable with adjustment for multiple child and caregiver covariates, suggesting that children with prenatal cocaine exposure are at increased risk for developing a learning disability by age 7 when compared to their non-cocaine-exposed peers.

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.

Munafo MR; Wileyto EP; Murphy MFG; Collins BN. Maternal smoking during late pregnancy and offspring smoking behaviour. Addictive Behaviors 31(9): 1670-1682, 2006. (29 refs.)

We explored the influence of maternal smoking during late pregnancy on the likelihood of smoking among offspring in adolescence and adulthood, using birth cohort data collected in the United Kingdom as part of the 1958 National Child Development Study. Longitudinal analysis indicated that maternal smoking during late pregnancy was associated with an increased likelihood of being a non-smoker at 16-year, 23-year and 33-year follow-up. This association differed between male and female offspring, with women showing no significant association and men showing an increased likelihood of being a non-smoker. There did not appear to be any association between maternal smoking during late pregnancy and cigarette consumption among offspring who reported smoking for either sex. These results are inconsistent with some previous reports that maternal smoking during pregnancy increases the likelihood of smoking among female offspring, although the observation of a moderating effect of sex on smoking behaviour is consistent with several previous reports. We discuss possible mechanisms for this association, and suggest factors that may account for the observed sex differences in this association, and the discrepancy between our results and some previous reports.

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.

Perreira KM; Cortes KE. Race/ethnicity and nativity differences in alcohol and tobacco use during pregnancy. American Journal of Public Health 96(9): 1629-1636, 2006. (47 refs.)

Objectives. We examined race/ethnicity and nativity correlates of prenatal substance use. Methods. Using data on a nationally representative cohort of pregnant women in US cities (N=4185), we evaluated the relative importance of socioeconomic status, paternal health behaviors, social support, and maternal stress and health history in explaining variations in prenatal substance use by race/ethnicity and nativity. Results. Maternal stress and health history appeared to fully explain differences in alcohol use by nativity, but these and other factors could not explain differences in prenatal smoking. For all races/ethnicities, paternal health behaviors were most strongly associated with maternal substance use. Except among Black women, socioeconomic background bore little relation to prenatal substance use after adjustment for more proximal risk factors (e.g., paternal and maternal health behaviors). Social support was most protective among Hispanic women. Conclusions. Foreign-born immigrant women are at equal risk of prenatal alcohol use compared with similarly situated US-born women and should not be overlooked in the design of interventions for at-risk women. Furthermore, the inclusion of fathers and the development of social support structures for at-risk women can strengthen interventions.

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.

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.

Rassool GH; Villar-Luis M. Reproductive risks of alcohol and illicit drugs: An overview. Journal of Addictions Nursing 17(4): 211-213, 2006. (16 refs.)

Some studies suggest that alcohol and illicit substance abuse has an adverse effect on behavior, sexual performance, and reproduction. The aim of the paper is to present an overview of the effects of substance abuse and its risks for reproduction. Alcohol abuse is associated with high-risk behaviors and individuals who abuse alcohol are at risk for sexually transmitted infections and unwanted pregnancy. The primary concern of alcohol misuse in pregnancy is its teratogenic potential result that can in fetal alcohol syndrome and potential miscarriage. Cocaine is associated with perinatal complications and spontaneous abortion following maternal abuse during pregnancy and other risky behaviors. Cannabis also is associated with perinatal complications such as miscarriage, intrauterine growth restrictions, abruptio placentae, pre-term delivery, and neurobehavioral abnormalities. A preventative approach needs to be implemented in order to reduce the risks associated with substance abuse and to provide minimal interventions at primary and community care settings.

Rauh VA; Garfinkel R; Perera FP; Andrews HF; Hoepner L; Barr DB et al. Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Pediatrics 118(6): e1845-e1859, 2006. (89 refs.)

OBJECTIVE. The purpose of this study was to investigate the impact of prenatal exposure to chlorpyrifos on 3-year neurodevelopment and behavior in a sample of inner-city minority children. METHODS. As part of an ongoing prospective cohort study in an inner-city minority population, neurotoxicant effects of prenatal exposure to chlorpyrifos were evaluated in 254 children through the first 3 years of life. This report examined cognitive and motor development at 12, 24, and 36 months (measured with the Bayley Scales of Infant Development II) and child behavior at 36 months (measured with the Child Behavior Checklist) as a function of chlorpyrifos levels in umbilical cord plasma. RESULTS. Highly exposed children (chlorpyrifos levels of > 6.17 pg/g plasma) scored, on average, 6.5 points lower on the Bayley Psychomotor Development Index and 3.3 points lower on the Bayley Mental Development Index at 3 years of age compared with those with lower levels of exposure. Children exposed to higher, compared with lower, chlorpyrifos levels were also significantly more likely to experience Psychomotor Development Index and Mental Development Index delays, attention problems, attention-deficit/hyperactivity disorder problems, and pervasive developmental disorder problems at 3 years of age. CONCLUSIONS. The adjusted mean 36-month Psychomotor Development Index and Mental Development Index scores of the highly and lower exposed groups differed by only 7.1 and 3.0 points, respectively, but the proportion of delayed children in the high-exposure group, compared with the low-exposure group, was 5 times greater for the Psychomotor Development Index and 2.4 times greater for the Mental Development Index, increasing the number of children possibly needing early intervention services.

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.

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.

Schmitz M; Denardin D; Silva TL; Pianca T; Hutz MH; Faraone S et al. Smoking during pregnancy and attention-deficit/hyperactivity disorder, predominantly inattentive type: A case-control study. Journal of the American Academy of Child and Adolescent Psychiatry 45(11): 1338-1345, 2006. (56 refs.)

Objective: Few previous studies assessed specifically attention-deficit/hyperactivity disorder, predominantly inattentive subtype (ADHD-I) in nonreferred samples. This study investigated the association between ADHD-I and prenatal exposure to nicotine. Method: In a case-control study performed between September 2002 and April 2005, we assessed a nonreferred Brazilian sample of 100 children and adolescents with ADHD-I and 100 non-ADHD controls (6-18 years old). Cases and controls, matched by gender and age, were screened using teacher reports in the Swanson, Nolan, and Pelham-IV (SNAP-IV) scale. They were systematically evaluated through structured diagnostic interviews. Prenatal exposure to nicotine and potential confounding factors were evaluated by direct interview with mothers. Results: Adjusting for confounding factors (maternal ADHD, oppositional defiant disorder, birth weight, and alcohol use during pregnancy), children whose mothers smoked 1 0 cigarettes per day during pregnancy presented a significantly higher odds ratio for ADHD-I than children who were not exposed to nicotine during pregnancy (odds ratio 3.44; 95% confidence interval 1.17-10.06). Dimensional analyses showed significantly higher inattentive scores in subjects whose mothers smoked >= 10 cigarettes per day than in others after adjusting for confounding factors (p =.002). Conclusions: In a nonreferred sample, the authors expanded to ADHD-I previous findings documenting the association between prenatal exposure to nicotine and broadly defined ADHD in clinical samples.

Shankaran S; Das A; Bauer CR; Bada H; Lester B; Wright L et al. Fetal origin of childhood disease: Intrauterine growth restriction in term infants and risk for hypertension at 6 years of age. Archives of Pediatrics & Adolescent Medicine 160(9): 977-981, 2006. (36 refs.)

Objective: To examine the association between intrauterine growth restriction (IUGR) status at birth among full-term infants, exposure to substance use during pregnancy, and risk of hypertension at 6 years of age. Design: Prospective evaluation of high-risk children. Setting: Four centers of the National Institute of Child Health and Human Development Neonatal Research Network. Participants: One thousand three hundred eighty-eight infants (600 cocaine exposed, 781 nonexposed, and 7 indeterminate, matched by gestational age, race, and sex), were enrolled at these sites. Nine hundred fifty children (415 exposed, 535 nonexposed) were followed up for 6 years. Intervention: Right arm blood pressure was measured using the Dinamap portable adult/pediatric monitor with appropriate cuff size. Main Outcome Measure: Blood pressure levels. Hypertension was defined as either systolic or diastolic blood pressure higher than the 95th percentile for sex, age, and height. Results: Eight hundred ninety-one children had blood pressure data at 6 years of age: 516 were born at full term; 144 (28%) of the 516 children had a diagnosis of IUGR at birth. At 6 years of age, 93 (19%) of 516 children had hypertension. Of 144 children with IUGR, 35 (24%) had hypertension as compared with 58 (16%) of 372 children without IUGR (P <.05). Twenty percent of cocaine-exposed children had hypertension as compared with 16% of nonexposed children (P=.20). Intrauterine growth restriction status at birth was significantly associated with hypertension (relative risk, 1.8 [95% confidence interval, 1.2-2.7]) when multivariable Poisson regression analysis was performed adjusting for site; maternal race, education, and tobacco, marijuana, alcohol, and cocaine use during pregnancy; and child's current body mass index (calculated as weight in kilograms divided by height in meters squared). Conclusion: In term infants, IUGR is linked to risk of hypertension in early childhood, which may be a marker for adult cardiovascular disease.

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.

Sheinkopf SJ; Lagasse LL; Lester BM; Liu J; Seifer R; Bauer CR et al. Prenatal cocaine exposure: Cardiorespiratory function and resilience. Annals of the New York Academy of Sciences: Resilience in Children 1094: 354-358, 2006. (8 refs.)

Cardiac vagal tone (VT) was studied as a resilience factor in children prenatally exposed to cocaine and nonexposed controls (n = 550). A cumulative risk index was derived and used to classify children as high versus low risk. VT was measured during mildly stressful observations at 1 and 36 months of age. Children were classified as having consistently high, consistently low, or fluctuating VT. Risk and VT interacted to predict adaptive behaviors. For high-risk children, low VT was related to higher ratings of adaptive behaviors. This finding suggests that regulatory functioning, as indexed by VT, may be 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.

Singh SP; Razani-Boroujerdi S; Pena-Philippides JC; Langley RJ; Mishra NC; Sopori ML. Early postnatal exposure to cigarette smoke impairs the antigen-specific T-cell responses in the spleen. Toxicology Letters 167(3): 231-237, 2006. (40 refs.)

Annually, approximately two million babies are exposed to cigarette smoke in utero and postnatally through cigarette smoking of their mothers. Exposure to mainstream cigarette smoke is known to impair both innate and adaptive immunities, and it has been hypothesized that the effects of in utero exposure to cigarette smoke on children's health might primarily stem from the adverse effects of cigarette smoke on the immune system. To simulate the environment that babies from smoking mothers encounter, we examined the effects of prenatal mainstream and postnatal sidestream cigarette smoke on spleen cell responses. Results show that postnatal exposure of newborn Balb/c mouse pups to sidestream cigarette smoke through the first 6 weeks of life strongly suppresses the antibody response of spleen cells to the T-cell-dependent antigen, sheep red blood cells. The reduction in the antibody response seen within 6 weeks of postnatal smoke exposure is much quicker than the published data on the time 25 weeks) required to establish reproducible immunosuppression in adult rats and mice. Moreover, the immumosuppression is not associated with significant changes in T-cell numbers or subset distribution. While the postnatal exposure to cigarette smoke did not affect the mitogenic response of T and B cells, the exposure inhibited the T cell receptor-mediated rise in the intracellular calcium concentration. These results suggest that the early postnatal period is highly sensitive to the immunosuppressive effects of environmental tobacco smoke, and the effects are causally associated with impaired antigen-mediated signaling in T cells.

Smith LM; LaGasse LL; Derauf C; Grant P; Shah R; Arria A et al. The infant development, environment, and lifestyle study: Effects of prenatal methamphetamine exposure, polydrug exposure, and poverty on intrauterine growth. Pediatrics 118(3): 1149-1156, 2006. (45 refs.)

OBJECTIVE. Methamphetamine use among pregnant women is an increasing problem in the United States. Effects of methamphetamine use during pregnancy on fetal growth have not been reported in large, prospective studies. We examined the neonatal growth effects of prenatal methamphetamine exposure in the multicenter, longitudinal Infant Development, Environment and Lifestyle study. DESIGN/ METHOD. The Infant Development, Environment and Lifestyle study screened 13 808 subjects at 4 clinical centers: 1618 were eligible and consented, among which 84 were methamphetamine exposed, and 1534 were unexposed. Those who were methamphetamine exposed were identified by self-report and/ or gas chromatography-mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Those who were unexposed denied amphetamine use and had a negative meconium screen. Both groups included prenatal alcohol, tobacco, or marijuana use, but excluded use of opiates, LSD, PCP or cocaine only. Neonatal parameters included birth weight and gestational age in weeks. One-way analysis of variance and linear-regression analyses were conducted on birth weight by exposure. The relationship of methamphetamine exposure and the incidence of small for gestational age was analyzed using multivariate logistic-regression analyses. RESULTS. The methamphetamine exposed group was 3.5 times more likely to be small for gestational age than the unexposed group. Mothers who used tobacco during pregnancy were nearly 2 times more likely to have small-for-gestational-age infants. In addition, less maternal weight gain during pregnancy was more likely to result in a small-for-gestational-age infant. Birthweight in the methamphetamine exposed group was lower than the unexposed group. CONCLUSIONS. These findings suggest that prenatal methamphetamine use is associated with fetal growth restriction after adjusting for covariates. Continued follow-up will determine if these infants are at increased risk for growth abnormalities in the future.

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.

Suzuki K; Nakai K; Hosokawa T; Oka T; Okamura K; Sakai T. Association of maternal smoking during pregnancy and infant neurobehavioral status. Psychological Reports 99(1): 97-106, 2006. (26 refs.)

The association of maternal smoking during pregnancy with neurobehavioral status was examined in 344 Japanese infants. Based on a questionnaire, their mothers were classified into three groups, Nonsmokers, Exsmokers, and Smokers. The Neonatal Behavioral Assessment Scale was administered three days after birth. Among the three groups, on the seven clusters and their 28 behavioral subscales there were no significant differences. The infants of Smokers had lower scores than those of Exsmokers and Nonsmokers on two behavioral items, general tone and peak of excitement. General tone remained significant after adjustment for covariates.

Vuijk P; van Lier PAC; Huizink AC; Verhulst FC; Crijnen AAM. Prenatal smoking predicts non-responsiveness to an intervention targeting attention-deficit/hyperactivity symptoms in elementary schoolchildren. Journal of Child Psychology and Psychiatry and Allied Disciplines 47(9): 891-901, 2006. (46 refs.)

Background: Some evidence suggests that prenatal exposure to maternal smoking contributes to the etiology of Attention-Deficit/Hyperactivity Disorder (ADHD). The present study tested an intervention targeting disruptive behavior to establish whether exposure to maternal smoking during pregnancy predicts intervention failure in elementary schoolchildren. Methods: Five hundred and eight elementary schoolchildren were followed from ages 7 to 11. At ages 8 and 9, they were randomly assigned to a control condition, or to a two-year universal classroom-based intervention targeting disruptive behavior. Measures included maternal reports of smoking during pregnancy, teacher-rated symptoms of ADHD from ages 7 to 9 years, and children's self-report of experimentation with smoking at ages 10 and 11 years. Results: At age 7, prenatally exposed children had higher ADHD symptom scores. The intervention did not affect the course of their ADHD symptoms and the probability of early-onset experimentation with smoking. Among non-exposed children, the intervention positively affected the course of ADHD symptoms, and reduced the probability of early-onset experimentation with smoking. Conclusions: Prenatally exposed children are most prone to follow a path of high levels of ADHD symptoms and associated elevated risk for early-onset experimentation with smoking, which is unreceptive to a universal preventive intervention. In these children, the developmental course of ADHD symptoms seems to have been influenced by their prenatal exposure to maternal smoking. Future research should further explore whether prenatal smoking is a proxy measure that indexes another risk factor, or a causal factor for adverse developmental outcomes.

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.

Yanai J; Ben-Shaanan TL; Haimovitch H; Katz S; Kazma M. Mechanism-based approaches for the reversal of drug neurobehavioral teratogenicity. Annals of the New York Academy of Sciences. Cellular and molecular mechanisms of drugs of abuse and neurotoxicity. 1074: 659-671, 2006. (62 refs.)

Understanding the mechanism of neurobehavioral teratogenicity is the primary prerequisite for reversal of the defect. Progress in such studies can be best achieved if the investigation focuses on behaviors related to a specific brain region and innervation. Our model focused on teratogen-induced deficits in hippo camp us-related eight-arm and Morris maze behaviors. Different "cholinergic" teratogens, mainly heroin, induced both pre- and postsynaptic hyperactivity in the hippocampal cholinergic innervation that terminated in desensitization of Protein Kinase C (PKC) isoforms to cholinergic receptor stimulation. Understanding this mechanism enabled its reversal with a pharmacological therapy-nicotine infusion. Studies by others provided similar findings by targeting the deficits respective to the model investigated. Consistently, destruction of the A10-septal dopaminergic pathways that downregulate the septohippocampal cholinergic innervation ameliorated maze performance. Grafting of embryonic differentiated cholinergic cells or neural progenitors similarly reversed the biochemical/molecular alterations and the resulting deficits. Reversal therapies offer a model for the understanding of neurobehavioral teratogenicity and, clinically, offer a model for potential treatment of these deficits. Whereas neural progenitor grafting appears to be the most effective treatment, pharmacological reversal with nicotine infusion seems to possess the most feasible and immediate therapy for neurobehavioral birth defects produced by various teratogens, including drugs. This is true even though the effect of pharmacological therapies is diffuse, affecting multiple areas of the brain.