Maternal cocaine use and mother-infant interactions: Direct and moderated associations

This study examined the associations between prenatal cocaine exposure and quality of mother-infant play interactions at 13 months of infant ages. We investigated whether maternal psychological distress and infant reactivity mediated or moderated this association. Participants consisted of 220 (119 cocaine exposed and 101 non-cocaine exposed) mother-infant dyads participating in an ongoing longitudinal study of prenatal cocaine exposure. Results indicated that mothers who used cocaine during pregnancy displayed higher negative affect and lower sensitivity toward their infant during play interactions at 13 months, and that their infants were less responsive toward them. Contrary to hypothesis, this association was not mediated by maternal psychological distress or by infant reactivity. However, results for both the cocaine and non-cocaine exposed infants were supportive of a transactional model where lower maternal sensitivity at 1 month was predictive of higher infant reactivity at 7 months, which in turn was predictive of lower maternal warmth/sensitivity at 13 months, controlling for potential stability in maternal behavior. Results also indicated that as hypothesized, infant reactivity moderated the association between maternal cocaine use during pregnancy and maternal warmth/sensitivity at 13 months of age. Cocaine-using mothers who experienced their infants as being more reactive in early infancy were less warm/sensitive toward them in later infancy. Results have implications for parenting interventions that may be targeted toward improving maternal sensitivity among cocaine-using mothers with more reactive infants.     

Effects of Prenatal Exposure to Sheesha Smoke: Response of Juvenile Rats to Novel Environment

Abstract

The traditional tobacco smoking known as sheesha, hubble-bubble, or hoaka is a process by which a tobacco-fruit mixture is drawn through a long tube, then passed through a water trap, before its inhalation by the smoker. Recently sheesha has gained substantial popularity among pregnant woman as a safer alternative to cigarette smoking. The aim of the present work is to examine the effect of prenatal exposure to sheesha smoke on growth and locomotor activities of juvenile rats. Two-day-pregnant rats were exposed daily to sheesha smoke for 10 minutes up to day 18 pregnancy. The effect of sheesha smoke on gestation period, progeny number, and body weight was determined. The ambulatory and stereotype behavior of offspring were measured at the age of 30 days. Results show that passive exposure to sheesha smoke during pregnancy had no effects on the gestational period, number of pups, birth weight, and body weight growth. The total ambulatory activity of exposed rats was 21.1% lower than that of matched control, P = .08. The decline rate of ambulatory activity in exposed rats was 27.6% lower than that of nonexposed, P = .09. The total stereotype movements in exposed rats were 26% lower than that of nonexposed, P = .029. The decline rate of the stereotype movements in the exposed rats was 10-fold lower than that of nonexposed, P = .00006. It was concluded that prenatal exposure to sheesha smoke lowers the response of rats tc novel environments.     

Exposure to environmental tobacco smoke during pregnancy in rats yields less effect on indices of brain cell number and size than does postnatal exposure

While there is evidence that human perinatal exposure to environmental tobacco smoke (ETS) can result in an increased risk of respiratory disorders and sudden infant death syndrome, evidence linking ETS exposure to neurodevelopmental handicaps is suggestive but less compelling. We previously noted that postnatal ETS exposure, rather than prenatal exposure, resulted in reduced concentration of hindbrain DNA and increased protein/DNA ratio when rat brain tissue was studied at 9 weeks postnatal age. We have now evaluated the effects of ETS exposure during pregnancy on brain development by assaying brain tissue at term. ETS exposure had no detectable effects on regional brain concentrations of DNA, protein and cholesterol or on protein/DNA and cholesterol/DNA ratios. While ETS exposure during pregnancy also had no detectable effects on the weights of the individual fetuses or on the weights of various organs, certain regions of the fetal skeleton demonstrated accelerated ossification. The findings of this study are contrasted to the developmental effects of both nicotine and ETS in Rhesus macaques. Additional studies designed specifically to assess the risk of prenatal ETS exposure on brain development in non-human primates and other precocial species are warranted.     

Antenatal maternal anxiety is related to HPA-axis dysregulation and self-reported depressive symptoms in adolescence: a prospective study on the fetal origins of depressed mood.

Depressive symptomatology can proceed from altered hypothalamic-pituitary-adrenocortex (HPA)-axis function. Some authors stress the role that early life stress (ELS) may play in the pathophysiology of depressive symptoms. However, the involvement of the HPA-axis in linking prenatal ELS with depressive symptoms has not been tested in a prospective-longitudinal study extending until after puberty in humans. Therefore, we examined whether antenatal maternal anxiety is associated with disturbances in HPA-axis regulation and whether the HPA-axis dysregulation mediates the association between antenatal maternal anxiety and depressive symptoms in post-pubertal adolescents. As part of a prospective-longitudinal study, we investigated maternal anxiety at 12-22, 23-32, and 32-40 weeks of pregnancy (wp) with the State Trait Anxiety Inventory (STAI). In the 14-15-year-old offspring (n=58) HPA-axis function was measured through establishing a saliva cortisol day-time profile. Depressive symptoms were measured with the Children's Depression symptoms Inventory (CDI). Results of regression analyses showed that antenatal exposure to maternal anxiety at 12-22 wp was in both sexes associated with a high, flattened cortisol day-time profile (P=0.0463) which, in female adolescents only, was associated with depressive symptoms (P=0.0077). All effects remained after controlling for maternal smoking, birth weight, obstetrical optimality, maternal postnatal anxiety and puberty phase. Our prospective study demonstrates, for the first time, the involvement of the HPA-axis in the link between antenatal maternal anxiety/prenatal ELS and depressive symptoms for post-pubertal female adolescents.     

Effects of prenatal cocaine exposure on behavior during the early postnatal period

Offspring of Sprague-Dawley dams injected SC with 40 mg/kg/3 cc cocaine HCl daily from gestational days 8-20, pair-fed dams injected with the vehicle alone and nontreated control dams were examined behaviorally during the early postnatal period. No significant differences were observed among the treatment conditions in maternal weight gain during pregnancy, duration of pregnancy, or number of live male and female pups/litter. Offspring body weights at birth and weaning, physical maturation and reflex development were not significantly affected by prenatal cocaine exposure. In contrast, neonates exposed prenatally to cocaine were observed to exhibit significant deficits in learning of an odor/milk association that nontreated offspring learned and retained for a 24 hr period. On postnatal day 12, cocaine offspring exhibited an increase in locomotor activity and attenuated wall climbing precipitated by footshock, in the absence of any alteration in sensitivity to footshock. Given that wall climbing has been previously shown to be strongly related to levels of catecholamine activity at this age, these data suggest the possibility that there may be some attenuation in catecholaminergic function in pups exposed gestationally to cocaine. The results of this study provide evidence that prenatal cocaine exposure may have an impact upon behavioral and cognitive function even during the early postnatal period. More work is needed to fully characterize the range of alterations observed and the neural mechanisms underlying these early exposure effects.     

An animal model of cigarette smoke-induced in utero growth retardation

Maternal/fetal genetic constitution and environmental factors are vital to delivery of a healthy baby. In the United States (US), a low birth weight (LBW) baby is born every minute and a half. LBW, defined as weighing less than 5.5 lbs at birth, affects nearly 1 in 12 infants born in the US with resultant costs for the nation of more than 15 billion dollars annually. Infant birth weight is the single most important factor affecting neonatal mortality. Various environmental and genetic risk factors for LBW have been identified. Several risks are preventable, such as cigarette smoking during pregnancy. Over one million babies are exposed prenatally to cigarette smoke accounting for over 20% of the LBW incidence in the US. Cigarette smoke exposure in utero results in a variety of adverse developmental outcomes with intrauterine growth restriction and infant LBW being the most well documented. However, the mechanisms underlying the causes of LBW remain poorly understood. The purpose of this study was: (1) to establish an animal model of cigarette smoke-induced in utero growth retardation and LBW using physiologically relevant inhalation exposure conditions which simulate "active" and "passive" tobacco smoke exposures, and (2) to determine whether particular stages of development are more susceptible than others to the adverse effects of in utero smoke exposure on embryo/fetal growth. Pregnant C57BL/6J mice were exposed to cigarette smoke during three periods of gestation: pre-/peri-implantation (gestational days [gds] 1-5), post-implantation (gds 6-18), and throughout gestation (gds 1-17). Reproductive and fetal outcomes were assessed on gd 18.5. Exposure of dams to mainstream/sidestream cigarette smoke, simulating "active" maternal smoking, resulted in decreases in fetal weight and crown-rump length when exposed throughout gestation (gds 1-17). Similar results were seen when dams were exposed only during the first 5 days of gestation (pre-/peri-implantation period gds 1-5). Exposure of dams from the post-implantation period through gestation (gds 6-18) did not result in reduced fetal weight, although a significant reduction in crown-rump length remained evident. Interestingly, maternal sidestream smoke exposure, simulating exposure to environmental tobacco smoke (ETS), during the pre-/peri-implantation period of development also produced significant decreases in fetal weight and crown-rump length. Collectively, results from the present study confirm an association between prenatal exposure to either "active" or "passive" cigarette smoke and in utero growth retardation. The data also identify a period of susceptibility to in utero cigarette smoke exposure-induced growth retardation and LBW during pre-/peri-implantation embryonic development.     

12- and 24-month neurobehavioural follow-up of children prenatally exposed to marihuana, cigarettes and alcohol

The motor, mental, and language development plus the home environment was examined in 217 twelve-month and 153 twenty-four-month-old children for whom prenatal exposure to marijuana, alcohol and cigarettes was previously ascertained. With this low-risk sample multiple regression analysis was used to assess the association between outcome measures and prenatal drug exposure while adjusting for potential confounding factors. Prenatal exposure to marijuana was uniquely positively associated with a series of items evaluating the child's attitudes and interests that reflect a cognitive factor. Moderate levels of alcohol were significantly associated with lower mental scores at 24 months of age. Prenatal maternal cigarette smoking was significantly associated with lower mental scores at 12 months of age and altered responses on auditory items at 12 and 24 months. However, at 24 months, the strong relationship of postnatal environmental factors with cognitive outcomes and with prenatal maternal smoking resulted in loss of significant, unique predictive power for maternal smoking. Based on the present work and supplemented by previously reported data pertaining to maternal attitudes during pregnancy and neonatal behaviour, a transactional interpretation is presented.     

Birth to age 7 growth of children prenatally exposed to drugs: a prospective cohort study

Prenatal exposure to cocaine, alcohol, and cigarettes has been linked to decreased birth weight and length. Unclear, however, is whether growth deficits persist into childhood. Women who were pregnant, African-American, not HIV-positive, and who delivered singleton infants were extensively screened throughout pregnancy for cocaine, alcohol, cigarette, and other illicit drug use. Of the approximately 1100 eligible subjects, 665 families were located at a 7-year postbirth follow-up and 540 participated. After appropriate control for potential confounders and prenatal exposures, prenatal exposure to cocaine, alcohol, and cigarettes each independently predicted birth weight and length. At age 7, prenatal cocaine exposure was significantly related to height deficits after accounting for other prenatal exposures and significant confounders. Children at age 7 exposed to cocaine in utero were up to 1 in. shorter and twice as likely to fall below the 10th percentile in height as the control children after accounting for other significant confounders including other prenatal exposures. Maternal age moderated the relation between prenatal exposures and child growth. Children born to women over 30 and exposed to cocaine were up to 2 in. shorter and four times more likely to have clinically significant height deficits at age 7. Children of older women and exposed to moderate-to-high levels of alcohol prenatally were up to 14 lb lighter and five times more likely to fall below the 10th percentile in weight. Similar growth restriction was not associated with prenatal exposures for children born to younger mothers. These outcomes add to the growing body of literature detailing long-term effects of prenatal drug exposure, suggesting differential effects for cocaine and alcohol, and indicating that maternal age may moderate these effects. Mechanisms for growth restriction and failure of catch-up under conditions of prenatal exposures are presented, suggesting further study of these developmental outcomes.     

Four-year language outcomes of children exposed to cocaine in utero

A large cohort of children exposed to cocaine in utero (n=189) were followed prospectively from birth to 4 years of age and compared to nonexposed children (n=185) on the Clinical Evaluation of Language Fundamentals-Preschool (CELF-P), a measure of receptive and expressive language abilities. Children exposed to cocaine in utero performed more poorly on the expressive and total language measures than nonexposed children after controlling for confounding variables, including prenatal exposure to alcohol, marijuana, and tobacco, as well as medical and sociodemographic variables. Children exposed to cocaine had more mild receptive language delays than nonexposed children and were less likely to have higher expressive abilities. Also, maternal factors such as language ability, performance IQ, race, and education correlated with child language abilities. Prenatal cigarette and marijuana exposure were related to deficits in specific language skills. Children placed in adoptive or foster care who were cocaine exposed demonstrated superior language skills compared to children exposed to cocaine who remained in biological relative or mother's care. These findings support a cocaine-specific effect on language skills in early childhood that may be modified with an enriched environment.     

Growth from birth to early adolescence in offspring prenatally exposed to cigarettes and marijuana.

Weight, height, and head circumference were examined in children from birth to early adolescence for whom prenatal exposure to marijuana and cigarettes had been ascertained. The subjects were from a low-risk, predominantly middle-class sample participating in an ongoing longitudinal study. The negative association between growth measures at birth and prenatal cigarette exposure was overcome, sooner in males than females, within the first few years, and by the age of six, the children of heavy smokers were heavier than control subjects. Pre and postnatal environmental tobacco smoke did not have a negative effect upon the growth parameters; however, the choice of bottle-feeding or shorter duration of breast-feeding by women who smoked during pregnancy appeared to play an important positive role in the catch-up observed among the infants of smokers. Prenatal exposure to marijuana was not significantly related to any growth measures at birth, although a smaller head circumference observed at all ages reached statistical significance among the early adolescents born to the heavy marijuana users.     

Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development

Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual’s lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development.     

Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge.

Prenatal exposure to infections represents a risk factor for the emergence of neuropsychiatric disorders in later life, including schizophrenia and autism. However, it remains essentially unknown whether this association is primarily attributable to prenatal and/or postnatal maternal effects on the offspring. Here, we addressed this issue by dissecting the relative contributions of prenatal inflammatory events and postnatal maternal factors in an animal model of prenatal viral-like infection. Pregnant mice were exposed to the inflammatory agent polyriboinosinic-polyribocytidilic acid (PolyI:C; 5 mg/kg, i.v.) or vehicle treatment on gestation day 9, and offspring born to PolyI:C- and vehicle-treated dams were cross fostered to surrogate rearing mothers that had either experienced inflammatory or sham treatment during pregnancy. We demonstrate that a variety of dopamine- and glutamate-related pharmacological and neuroanatomical disturbances emerge after prenatal immune challenge regardless of whether neonates were raised by vehicle- or PolyI:C-exposed surrogate mothers. However, the adoption of prenatal control animals to immune-challenged surrogate mothers was also sufficient to induce specific pharmacological and neuroanatomical abnormalities in the fostered offspring. Multiple schizophrenia-related dysfunctions emerging after prenatal immune challenge are thus mediated by prenatal but not postnatal maternal effects on the offspring, but immunological stress during pregnancy may affect postpartum maternal factors in such a way that being reared by an immune-challenged surrogate mother can confer risk for distinct forms of psychopathology in adult life.     

Gender and alcohol moderate prenatal cocaine effects on teacher-report of child behavior

Prenatal cocaine exposure has been associated with behavior problems at school age. However, the correspondence between use of cocaine and alcohol during pregnancy is often high, making appropriate allocation of variance and control for other exposures and their interactions difficult. Additionally, gender-specific effects are not typically reported. The purpose of the current study was to determine the degree to which gender-specific effects of prenatal cocaine exposure on teacher-reported child externalizing behavior problems were evident when evaluated in relation to prenatal alcohol exposure. Subjects were singleton infants of mothers who were prospectively evaluated during pregnancy. At age seven, 499 children (214 exposed prenatally to cocaine) were evaluated in our laboratory and teacher reports were solicited. Analyses stratified by gender and prenatal alcohol exposure status, and controlled for significant pre- and postnatal confounders, revealed that among boys with prenatal alcohol exposure, those with persistent cocaine exposure throughout pregnancy had significantly higher levels of Delinquent Behavior compared to boys with no cocaine exposure. Boys with any prenatal cocaine exposure were twice as likely as unexposed boys to have clinically significant Externalizing Behavior scores. However, no association was found between prenatal cocaine exposure and scores on Externalizing Behavior and specific syndromes for boys with no prenatal alcohol exposure. Among girls with no prenatal alcohol exposure, those with persistent cocaine exposure had significantly higher levels of Externalizing Behaviors and Aggressive Behaviors compared to girls with no prenatal cocaine exposure after control for confounding, and were almost five times as likely to have clinically significant Externalizing Behavior scores. However, for girls with prenatal alcohol exposure, no association between prenatal cocaine exposure and scores on Externalizing Behavior and specific syndromes was found after control for confounding. The current findings support gender- and alcohol-moderated effects of prenatal cocaine exposure on school-age teacher-reported child behavior problems. These findings are similar to what we have reported for independent parent-reported behavioral evaluation.     

From in utero and childhood exposure to parental smoking to childhood cancer: a possible link and the need for action.

The objective of the present work is to critically summarize published studies and reassess the state of knowledge on a highly controversial topic: the potential association between prenatal exposure to passive smoking as well as maternal active smoking and postnatal exposure to environmental tobacco smoke (ETS) and enhanced incidence of childhood cancer. Elements to be considered include the substantial proportion of pregnant women who remain smokers, the widespread nature of exposure to ETS during pregnancy as well as during childhood, the known toxicology of tobacco smoke, and in particular sidestream smoke, characterized by a rich carcinogen content, the specific metabolism of foetuses and new-borns and finally the amount of epidemiologic data already available. We conducted a thorough review of the literature to identify studies either exclusively dealing with the effects of passive smoking on the occurrence of childhood cancers or more generally etiologic studies of cancer, be it overall or site-specific. We identified close to 50 publications presenting pertinent results from epidemiological investigations and about 50 more on mechanisms and metabolism, smoking in pregnancy and exposure to ETS as well as selected reviews and commentaries. Collaborative epidemiological studies were conducted in the United Kingdom (UK), USA, Sweden, Netherlands and internationally (France, Italy). In addition, other studies were also available from the USA, UK, Canada, Australia, Sweden, Italy, Denmark and People's Republic of China. The vast majority were case-control studies dealing with all cancers, leukaemia and lymphomas, central nervous system (CNS) tumours, Wilms' tumour, retinoblastoma, neuroblastoma, hepatoblastoma, rhabdomyosarcoma, bone and soft tissues tumours, germ cell tumours, as well as specific histological types of leukaemias, lymphomas or CNS tumours. No strong association between maternal smoking in pregnancy and/or exposure to ETS and childhood cancer is found. Yet, several studies found slightly increased relative risks, generally smaller than 1.5, i.e. the order of magnitude associated with some recognized hazards of exposure to ETS (1.2 to 1.3 for adult lung cancer and cardiovascular diseases). Tumours most often found associated with maternal smoking in pregnancy or ETS exposure are childhood brain tumours and leukaemia-lymphoma, with risks up to two or greater in selected studies. In a few studies, risks associated with paternal smoking are higher than the maternal ones. This evidence from human studies coupled with demonstration of genotoxic effects on the foetus of exposure to metabolites of tobacco smoke, and demonstrable presence of adducts should lead to strong recommendations aiming at fully protecting foetuses, new-borns and infants from tobacco smoke.     

The impact of maternal smoking on fast auditory brainstem responses

Deficits in auditory processing have been posited as one of the underlying neurodevelopmental consequences of maternal smoking during pregnancy that leads to later language and reading deficits. Fast auditory brainstem responses were used to assess differences in the sensory processing of auditory stimuli among infants with varying degrees of prenatal cigarette exposure. Maternal report of consumption of cigarettes and blood samples were collected in the hospital to assess exposure levels and participants were then seen at 6-months. To participate in the study, all infants had to pass the newborn hearing exam or a clinically administered ABR and have no known health problems. After controlling for participant age, maternal smoking during pregnancy was negatively related to latency of auditory brainstem responses. Of several potential covariates, only perinatal complications and maternal alcohol use were also related to latency of the ABR responses and maternal smoking level accounted for significant unique variance after controlling for these factors. These results suggest that the relationship between maternal smoking may lead to disruption in the sensory encoding of auditory stimuli.     

Melamine in prenatal and postnatal organs in rats

Melamine can be transferred to fetus in utero through placenta and to infant ex utero by breast feeding. In this study, we characterized the pharmacokinetics of melamine in prenatal and postnatal organs in rats. Single bolus of melamine was administered to pregnant rats at different gestational stages and to infants at different postnatal stages. Distribution of melamine in maternal serum was about 30% higher in late pregnancy than that in early pregnancy; and it was 2 folds higher in postnatal serum in early infants in young adulthood. Distribution of melamine in all postnatal organs was higher than that in prenatal organs. Postnatal kidneys in early infants had the highest maximum concentration and the lowest clearance of melamine than the other postnatal organs. It may relate to the high vulnerability to the toxicity of melamine in this population.     

Influence of prenatal cocaine exposure on full-term infant neurobehavioral functioning

This study investigated infant neurobehavioral functioning during the newborn period in 334 full-term, African American neonates (187 cocaine exposed, 147 non-cocaine exposed) enrolled prospectively at birth, with documentation of drug exposure status through maternal interview and urine and meconium toxicology assays. Infants were assessed using the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) during the newborn period (0–6 postnatal days). Findings from multivariate profile analyses support a consistent, modest effect of prenatal cocaine exposure on neurobehavioral functioning in full-term neonates. All of the BNBAS cluster scores, with the exception of abnormal reflexes, were similarly affected, sharing a common slope (D=−0.14; 95% CI=−0.27, −0.003; P=.046) representing a −0.14 point difference between cocaine-exposed and non-cocaine-exposed infants after controlling for prenatal exposure to alcohol, tobacco, and marijuana (ATM); maternal age, education, employment, primigravida status, and prenatal care visits; and infant sex and postnatal age in days. Fetal growth was also related to neurobehavioral functioning and, in part, mediated the relationship between cocaine exposure and the BNBAS cluster scores. Cocaine exposure during each trimester similarly influenced infant neurobehavioral profiles, with cocaine-associated deficits most pronounced in infants with exposure in all three trimesters. Results from qualitative and quantitative urine and meconium bioassay indicators further substantiated these results. Findings, while significant, represent modest effect sizes in full-term infants.     

Effects of prenatal cocaine exposure on infant reactivity and regulation

The purpose of this study was to examine the role of prenatal cocaine exposure and associated risk factors on infant reactivity and regulation at 7 months of infant age. Participants consisted of 167 mother-infant dyads participating in an ongoing longitudinal study of prenatal cocaine exposure, who completed the arm restraint procedure at the 7-month assessment (87 cocaine exposed, 80 non-cocaine exposed). We hypothesized that cocaine exposed infants would display higher arousal or reactivity and lower regulation during a procedure designed to arouse anger/frustration. Results indicated that cocaine exposed infants were more reactive to increases in the level of stress from trial 1 to trial 2 but exhibited no change in the number of regulatory strategies as stress increased, unlike the control group infants. Infant birth weight moderated the association between cocaine exposure and infant regulation. Among cocaine exposed infants, those with lower birth weight displayed higher reactivity compared to those with higher birth weight. Contrary to expectations, there were no indirect effects between cocaine exposure and infant reactivity/regulation via environmental risk, parenting, or birth weight. Results are supportive of a teratological model of prenatal cocaine exposure for infant reactivity/regulation in infancy.     

Prenatal Tobacco Exposure and Brain Morphology: A Prospective Study in Young Children

It is well known that smoking during pregnancy can affect offspring health. Prenatal tobacco exposure has been associated with negative behavioral and cognitive outcomes in childhood, adolescence, and young adulthood. These associations between prenatal tobacco exposure and psychopathology in offspring could possibly be explained by the influence of prenatal tobacco exposure on brain development. In this prospective study, we investigated the association between prenatal tobacco exposure, behavioral and emotional functioning and brain morphology in young children. On the basis of age and gender, we matched 113 children prenatally exposed to tobacco with 113 unexposed controls. These children were part of a population-based study in the Netherlands, the Generation R Study, and were followed from pregnancy onward. Behavioral and emotional functioning was assessed at age 6 with the Child Behavior Checklist. We assessed brain morphology using magnetic resonance imaging techniques in children aged 6–8 years. Children exposed to tobacco throughout pregnancy have smaller total brain volumes and smaller cortical gray matter volumes. Continued prenatal tobacco exposure was associated with cortical thinning, primarily in the superior frontal, superior parietal, and precentral cortices. These children also demonstrated increased scores of affective problems. In addition, thickness of the precentral and superior frontal cortices was associated with affective problems. Importantly, brain development in offspring of mothers who quit smoking during pregnancy resembled that of nonexposed controls (no smaller brain volumes and no thinning of the cortex). Our findings suggest an association between continued prenatal tobacco exposure and brain structure and function in school-aged children.