Prenatal Cigarette Exposure Research Articles

Effects of Prenatal Electronic Cigarette Exposure On Foetal Development: a Review of the Literature.

Since their market launch in 2007, e-cigarettes gained popularity and were considered a relatively safe alternative to traditional cigarettes. Pregnant women and women of childbearing age in particular are increasingly turning to e-cigarettes. Little is known about the effects of prenatal exposure on the affected foetus. This paper aims to provide an overview of the current research on the effects of prenatal e-cigarette exposure on the foetus. Since studies in humans are lacking to date, this review refers only to animal and in vitro analyses. The PubMed and Web of Science databases were used for an extensive literature search. The search yielded N = 17 significant research papers. Possible sequelae resulting from prenatal exposure to traditional cigarettes were also seen in prenatal exposure to e-cigarettes. Prenatal e-cigarette exposure was found to be associated with increased DNA methylation overall, resulting in lower gene expression. This could adversely impact the development of affected children, especially in case of those genes relevant to their development. In mice, for example, this greatly reduced the cell vitality of neural and stem cells and increased cell death. Further, prenatal exposure to e-cigarettes resulted in numerous developmental disorders, such as malformations of facial morphology and lower birth weight. Moreover, in animal models the animals suffered from a deterioration of their short-term memory. Activity and cognitive flexibility increased, while anxiety behaviour decreased. It is clear that more research and especially studies of humans are needed on this issue. In addition, there is a need for more intense education of prenatal care professionals as well as women of childbearing age and during pregnancy.

The effects of prenatal cigarette and e-cigarette exposure on infant neurobehaviour: A comparison to a control group

BackgroundInfant neurobehaviour provides an insight into the development of the central nervous system during infancy, with behavioural abnormalities highlighting a cause for concern. Research has demonstrated that prenatal exposure to cigarettes leads to deficits within neurobehavioural development, along with negative birth outcomes detrimental to subsequent development. With the growing use of e-cigarettes amongst pregnant women, this study explores how prenatal e-cigarette exposure compares to prenatal cigarette exposure.MethodsEighty-three infants were involved in the study, either exposed prenatally to cigarettes or e-cigarettes or not exposed to either. Differences were assessed between these three groups for birth outcomes and scores on the Neonatal Behavioural Assessment Scale (NBAS) at one month of age.FindingsBoth cigarette and e-cigarette exposed infants had a significantly greater number of abnormal reflexes (p = ·001; p = ·002). For both self-regulation and motor maturity, cigarette exposed infants performed significantly worse (p = ·010; p = ·002), with e-cigarette exposed infants having decreased motor maturity (p = ·036) abilities and marginally decreased for self-regulation (p = ·057). Birth outcomes, namely birthweight, gestation and head circumference, did not differ for e-cigarette exposed infants compared with infants who were not prenatally exposed to nicotine. Cigarette exposed infants had a significantly lower birthweight (p = ·021) and reduced head circumference (p = ·008) in comparison to non-exposed infants.InterpretationTo our knowledge, this is the first research study assessing a neurological outcome as a result of e-cigarette exposure. Findings of this have potentially important implications for public health policies regarding the safety and use of e-cigarettes throughout pregnancy.FundingThis research was funded by a doctoral training partnership scholarship via the ESRC, ES/P000762/1.

Infant neurobehavioural consequences of prenatal cigarette exposure: A systematic review and meta-analysis.

AimPrenatal exposure to cigarettes leads to alterations in brain development during pregnancy. This has an impact on postnatal psychological and behavioural processes, affecting an infant's neurobehavioural profile with little known about which aspects are affected. The evidence was synthesised to assess the effects of prenatal cigarette smoke exposure on neurobehavioural outcomes within the first year of life.MethodsSix databases were searched (Web of Science Core Collections, MEDLINE, PsycINFO, CINAHL, EBSCOhost eBook Collection and OpenGrey) in November 2018. Eligible studies (n = 17) had to include a measure of prenatal cigarette exposure and a neurobehavioural assessment ≤1 year of age.ResultsIn the first year of life, specific areas of neurobehavioural functioning are related to prenatal cigarette exposure with eight out of 10 areas of neurobehaviour having significant medium (negative affect, attention, excitability, irritability and orientation) or small (muscle tone, regulation and difficult temperament) pooled effect sizes. Only lethargy and stress did not show any significant pooled effects.ConclusionPrenatal cigarette exposure affects a significant range of behaviours during the first year of life.

Prenatal electronic cigarette exposure decreases brain glucose utilization and worsens outcome in offspring hypoxic-ischemic brain injury.

It has been shown that prenatal nicotine and tobacco smoke exposure can cause different neurobehavioral disorders in the offspring. We hypothesize that prenatal exposure to nicotine-containing electronic cigarette (e-Cig) vapor can predispose newborn to enhanced sensitivity to hypoxic-ischemic (HI) brain injury and impaired motor and cognitive functions. In this study, pregnant CD1 mice were exposed to e-Cig vapor (2.4% nicotine). Primary cortical neurons isolated from e-Cig exposed fetus were exposed to oxygen-glucose deprivation followed by reoxygenation (OGD/R) to mimic HI brain injury. Cell viability and glucose utilization were analyzed in these neurons. HI brain injury was induced in 8-9-day-old pups. Short-term brain injury was evaluated by triphenyltetrazolium chloride staining. Long-term motor and cognitive functions were evaluated by open field, novel object recognition, Morris water maze, and foot fault tests. Western blotting and immunofluorescence were done to characterize glucose transporters in offspring brain. We found that e-Cig exposed neurons demonstrated decreased cell viability and glucose utilization in OGD/R. Prenatally e-Cig exposed pups also had increased brain injury and edema 24hr after HI brain injury. Further, in utero e-Cig exposed offspring with HI brain injury displayed impaired memory, learning, and motor coordination at adolescence. Additionally, the expression of glucose transporters decreased in e-Cig exposed offspring brain after HI brain injury. These results indicate that reduced glucose utilization can contribute to prenatal e-Cig exposure induced worsened HI brain injury in offspring. This study is instrumental in elucidating the possible deleterious effects of e-Cig use in the general population.

Comparison of Safety and Efficacy of Methadone vs Morphine for Treatment of Neonatal Abstinence Syndrome

Although opioids are used to treat neonatal abstinence syndrome (NAS), the best pharmacologic treatment has not been established. To compare the safety and efficacy of methadone and morphine in NAS. In this randomized, double-blind, intention-to-treat trial, term infants from 8 US newborn units whose mothers received buprenorphine, methadone, or opioids for pain control during pregnancy were eligible. A total of 117 infants were randomized to receive methadone or morphine from February 9, 2014, to March 6, 2017. Mothers who declined randomization could consent to data collection and standard institutional treatment. Infants were assessed with the Finnegan Neonatal Abstinence Scoring System every 4 hours and treated with methadone or placebo every 4 hours or morphine every 4 hours. Infants with persistently elevated Finnegan scores received dose increases. Infants who exceeded a predetermined opioid dose received phenobarbital. Dose reductions occurred every 12 to 48 hours when signs of NAS were controlled with therapy, stopping at 20% of the original dose. The primary end point was length of hospital stay (LOS). The secondary end points were LOS attributable to NAS and length of drug treatment (LOT). A total of 183 mothers consented to have their infants in the study; 117 infants required treatment. Because 1 parent withdrew consent, data were analyzed on 116 infants (mean [SD] gestational age, 39.1 [1.1] weeks; mean [SD] birth weight, 3157 [486] g; 58 [50%] male). Demographic variables and risk factors were similar except for more prenatal cigarette exposure in infants who received methadone. Adjusting for study site and maternal opioid type, methadone was associated with decreased mean number of days for LOS by 14% (relative number of days, 0.86; 95% CI, 0.74-1.00; P = .046), corresponding to a difference of 2.9 days; 14% reduction in LOS attributable to NAS (relative number of days, 0.86; 95% CI, 0.77-0.96; P = .01), corresponding to a difference of 2.7 days; and 16% reduction in LOT (relative number of days, 0.84; 95% CI, 0.73-0.97; P = .02), corresponding to a difference of 2.3 days. Methadone was also associated with reduced median LOS (16 vs 20 days, P = .005), LOS attributable to NAS (16 vs 19 days, P = .005), and LOT (11.5 vs 15 days, P = .009). Study infants had better short-term outcomes than 170 nonrandomized infants treated with morphine per standard institutional protocols. With use of weight- and sign-based treatment for NAS, short-term outcomes were better in infants receiving methadone compared with morphine. Assessment of longer-term outcomes is ongoing. ClinicalTrials.gov Identifier: NCT01958476.

Prenatal and postnatal cigarette and cannabis exposure: Effects on Secretory Immunoglobulin A in early childhood

AimsSecretory Immunoglobulin A (SIgA) plays a critical role in immune functioning by preventing pathogens from adhering to epithelial mucosa. Most infectious agents enter the body via mucosal surfaces, thus SIgA serves in the defense against respiratory, intestinal, and urinogenitary infections, as well as periodontal disease and caries. This study examined the possibility that pre- and postnatal exposure to cigarette and cannabis is associated with individual differences in Secretory Immunoglobulin A (SIgA) levels in early childhood. MethodsParticipants were 50 mother/infant (29 boys; 35% Caucasian) dyads recruited at their first prenatal appointment in a large northeastern community hospital in the United States. Repeated assessments of pre- and postnatal cigarette and cannabis were conducted beginning in the first trimester of pregnancy, using multiple methods (i.e., saliva, meconium, self-report). Infants were grouped into those prenatally exposed to either cigarette only (n = 19), cigarette and cannabis (n = 19), or with no prenatal substance exposure (n = 12). At age 5 years, the children's saliva was collected and assayed for SIgA. ResultsThere were group differences in SIgA levels as a function of prenatal exposure to cigarette and cannabis – children in the cigarette only and the cigarette and cannabis groups had higher SIgA levels compared to the non-exposed children. Children who experienced the combination of postnatal exposure to cigarette and cannabis had higher levels of SIgA, even after accounting for prenatal exposures and other covariates relevant to immune system functioning. ConclusionsPrenatal and postnatal exposure to cigarette and cannabis may be associated with hyperactivity of mucosal immunity in early childhood. Links between cigarette and cannabis exposure and health problems in early childhood may be partially explained by prenatal and postnatal exposure-related changes in mucosal immunity.

Effects of prenatal alcohol and cigarette exposure on offspring substance use in multiplex, alcohol-dependent families.

Prenatal exposures to alcohol, cigarettes, and other drugs of abuse are associated with numerous adverse consequences for affected offspring, including increased risk for substance use and abuse. However, maternal substance use during pregnancy appears to occur more often in those with a family history of alcohol dependence. Utilizing a sample that is enriched for familial alcohol dependence and includes controls selected for virtual absence of familial alcohol dependence could provide important information on the relative contribution of familial risk and prenatal exposures to offspring substance use. A sample of multigenerational families specifically ascertained to be at either high or low risk for developing alcohol dependence (AD) provided biological offspring for a longitudinal prospective study. High-risk families were selected based on the presence of 2 alcohol-dependent sisters. Low-risk families were selected on the basis of minimal first and second-degree relatives with AD. High-risk (HR=99) and Low-risk offspring (LR=110) were assessed annually during childhood and biennially in young adulthood regarding their alcohol, drug, and cigarette use. At the first childhood visit, mothers were interviewed concerning their prenatal use of substances. High-risk mothers were more likely to use alcohol, cigarettes, and other drugs during pregnancy than low-risk control mothers, and to consume these substances in greater quantities. Across the sample, prenatal exposure to alcohol was associated with increased risk for both offspring cigarette use and substance use disorders (SUD), and prenatal cigarette exposure was associated with increased risk for offspring cigarette use. Controlling for risk status by examining patterns within the HR sample, prenatal cigarette exposure remained a specific predictor of offspring cigarette use, and prenatal alcohol exposure was specifically associated with increased risk for offspring SUD. Women with a family history of SUD are at increased risk for substance use during pregnancy. Both familial loading for alcohol dependence and prenatal exposure to alcohol or cigarettes are important risk factors in the development of offspring substance use. An inadequate assessment of family history may obscure important interactions between familial risk and prenatal exposures on offspring outcomes.

Physiological Regulation at 9 Months of Age in Infants Prenatally Exposed to Cigarettes.

The primary purpose of this study was to examine the association between prenatal cigarette exposure and physiological regulation at 9 months of age. Specifically, we explored the possibility that any association between prenatal cigarette exposure and infant physiological regulation was moderated by postnatal environmental tobacco smoke (ETS) exposure or infant gender. We evaluated whether male infants with prenatal cigarette exposure or infants who were also exposed to ETS after birth had the highest levels of physiological dysregulation. Respiratory sinus arrhythmia (RSA) was obtained from 206 (142 exposed and 64 nonexposed) infants during a baseline period and during procedures designed to elicit both positive and negative affect. There was a significant suppression of RSA during the negative affect task for nonexposed infants but not for exposed infants. Postnatal ETS exposure did not moderate this association; however, gender did moderate this association such that boys with prenatal cigarette exposure had a significant increase in RSA rather than the suppression seen among both nonexposed boys and girls. These results provide additional support for the idea that boys are particularly vulnerable to the effects of prenatal cigarette exposure.

Molecular mechanisms of maternal cannabis and cigarette use on human neurodevelopment

Prenatal development is highly sensitive to maternal drug use due to the vulnerability for disruption of the fetal brain with its ongoing neurodevelopment, resulting in lifelong consequences that can enhance risk for psychiatric disorders. Cannabis and cigarettes are the most commonly used illicit and licit substances, respectively, among pregnant women. Although the behavioral consequences of prenatal cannabis and cigarette exposure have been well-documented in epidemiological and clinical studies, only recently have investigations into the molecular mechanisms associated with the developmental impact of early drug exposure been addressed. This article reviews the literature relevant to long-term gene expression disturbances in the human fetal brain in relation to maternal cannabis and cigarette use. To provide translational insights, we discuss animal models in which protracted molecular consequences of prenatal cannabis and cigarette exposure can be better explored and which enable future evaluation of epigenetic pathways, such as DNA methylation and histone modification, that could potentially maintain abnormal gene regulation and related behavioral disturbances. Altogether, this information may help to address the current gaps of knowledge regarding the impact of early drug exposure that set in motion lifelong molecular disturbances that underlie vulnerability to psychiatric disorders.

Anger, hostility, and aggression as predictors of persistent smoking during pregnancy.

We examined the role of anger, hostility, and aggression, in addition to depression and stress, in predicting persistent smoking during pregnancy in a low-income sample. The sample consisted of 270 pregnant women (189 smokers, 81 nonsmokers) recruited into a prospective study of prenatal cigarette exposure in the first trimester. Persistent pregnancy smoking was defined as self-reporting daily smoking in at least two trimesters, a positive salivary cotinine level in at least two trimesters, or infant meconium positive for nicotine and/ or its metabolites. Persistent smokers reported higher prenatal stress and negative affect symptoms (depression, anger, hostility, aggression) than nonpersistent smokers or nonsmokers. However, in the context of model testing, maternal anger, hostility, and aggression each accounted for unique variance in persistent smoking, whereas symptoms of depression and stress did not. To date, interventions for pregnant low-income smokers have been largely ineffective. The current results suggest that anger management interventions may be particularly effective for low-income persistent pregnant smokers and may be more likely to prevent relapse than depression-focused interventions.

Physiological regulation in cigarette exposed infants: An examination of potential moderators

The primary purpose of this study was to examine pathways from prenatal cigarette exposure to physiological regulation at 2 months of age. Specifically, we explored the possibility that any association between prenatal cigarette exposure and infant physiological regulation was moderated by fetal growth, prenatal or postnatal environmental tobacco smoke (ETS) exposure or maternal depressive symptomatology during pregnancy. We evaluated whether exposed infants who were also exposed to ETS after birth, were small for gestational age (SGA) or had mothers with higher depressive symptoms during pregnancy had the highest levels of physiological dysregulation. Respiratory sinus arrhythmia (RSA) was obtained from 234 (166 exposed and 68 nonexposed) infants during sleep. As expected, cigarette-exposed infants had significantly lower RSA than nonexposed infants. This association was not moderated by prenatal or postnatal ETS exposure, or maternal depressive symptomatology during pregnancy. However, small for gestational age status did moderate this association such that nonexposed infants who were not small for gestational age had a significantly higher RSA than nonexposed small for gestational age infants and exposed infants. These findings provide additional evidence that prenatal cigarette exposure is directly associated with dysregulation during infancy.

Prenatal cigarette exposure and infant learning stimulation as predictors of cognitive control in childhood

Prenatal exposures to neurotoxins and postnatal parenting practices have been shown to independently predict variations in the cognitive development and emotional-behavioral well-being of infants and children. We examined the independent contributions of prenatal cigarette exposure and infant learning stimulation, as well as their inter-relationships in predicting variations in the proficiency of executive attention, a core element of cognitive control and self-regulation. Participants were an ethnic-racially, socio-economically diverse sample of 249 children followed from birth in the Project on Human Development in Chicago Neighborhoods. We obtained histories of prenatal exposure to alcohol, cigarettes, and other drugs, and we assessed socio-economic status and learning stimulation during a home visit when the participants were infants. In childhood we utilized the Attention Networks Test to assess the proficiency of executive attention during two home visits, one year apart. Accounting for age, SES, prenatal alcohol exposure, and baseline performance, we found that prenatal cigarette exposure impaired the speed of executive attention. Infant learning stimulation mitigated these effects, and predicted better accuracy of executive attention as well, suggestive of both protective and health promoting effects. Effect sizes for these relations, whether examined independently or by their inter-relationships, were comparable to if not greater in magnitude than the effects of age on speed and accuracy, highlighting the importance of these very early experiences in shaping the proficiency of self-regulation. Since executive attention is central to cognitive control and self-regulation, previously described relations between prenatal cigarette exposure, parenting practices, and some forms of childhood psychopathology may be contingent on how early learning stimulation contributes to the proficiency of executive attention through direct and indirect effects. Furthermore, considering the prolonged developmental trajectory of executive attention, interventions to support provision of learning stimulation may mitigate poor outcomes for some at-risk children by promoting development of more proficient executive attention.

Infant Birth Outcomes Among Substance Using Women: Why Quitting Smoking During Pregnancy is Just as Important as Quitting Illicit Drug Use

Poor birth outcomes are associated with illicit drug use during pregnancy. While prenatal cigarette exposure has similar effects, cessation of illicit drug use during pregnancy is often prioritized over cessation of smoking. The study goal was to examine the impact of pregnancy tobacco use, relative to use of illicit drugs, on birth outcomes. Women were recruited at entry to prenatal care, with background and substance use information collected during pregnancy. Urine drug screens were performed during pregnancy, and the final sample (n = 265) was restricted to infants who also had biologic drug testing at delivery. Participants were classified by pregnancy drug use: no drugs/no cigarettes, no drugs/cigarette use, illicit drugs/no cigarettes, and illicit drugs/cigarette use. Groups differed significantly on infant birthweight, but not gestational age at delivery after control for confounders including background and medical factors. Among women who smoked, the adjusted mean birthweight gain was 163 g for those not using hard illicit drugs, while marijuana use had no effect on birth weight beyond the effect of smoking cigarettes. Women who used hard illicit drugs and did not smoke had an adjusted mean birthweight gain of 317 g over smokers. Finally, women who refrained from hard illicit drugs and smoking had a birthweight gain of 352 g. Among substance using pregnant women, smoking cessation may have a greater impact on birthweight than eliminating illicit drug use. Intervention efforts should stress that smoking cessation is at least as important to improving pregnancy outcomes as abstaining from illicit drug use.

P13 Association of prenatal and postnatal smoking and alcohol consumption on birth weight in the white British population in Bradford: preliminary findings from the born in Bradford study

BackgroundExposure to cigarette smoke and heavy alcohol consumption has been known to influence birth weight and risk of being small for gestational age. Despite this knowledge, very little exploration of...

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.

Developmental alterations of the prefrontal cerebral cortex in sudden unexplained perinatal and infant deaths

The aim of this study was to investigate the developmental patterns of the human prefrontal cortex involved in breathing control in a wide cohort of fetal and infant death victims, aged from the 22(nd) gestational week to 10 months of life, and to evaluate whether morpho-functional disorders are present in this specific cortical area in victims of sudden unexplained death. A further aim was to determine whether prenatal absorption of nicotine could also affect the maturational processes of the prefrontal cortex. A pronounced radial organization of the cerebral wall was evident from the 26(th) gestational week. By 36 gestational weeks this columnar structure disappeared, coinciding with the formation of a laminar cyto-architecture. The mature cortex, observable from the 4(th) month of life, was organized horizontally into six laminae. In 33% of the sudden death victims the prefrontal cortex showed morphological alterations with anomalous laminar patterns and delayed neuronal maturation. A significant correlation with prenatal cigarette exposure was found.

The association between prenatal exposure to cigarettes and cortisol reactivity and regulation in 7-month-old infants.

We examined the association between prenatal exposure to cigarettes and adrenocortical responses to stress in 7-month-old infants. Cortisol levels were assessed twice prior to and twice following affect-eliciting procedures in 111 (59 exposed and 52 nonexposed) infants. Cortisol reactivity was defined as the difference between the peak poststressor cortisol level and the pretask cortisol level. Higher values indicated higher cortisol reactivity. Exposed infants had higher peak cortisol reactivity than nonexposed infants. There were no differences in pretask cortisol levels. Maternal hostility mediated the association between cigarette exposure and peak cortisol reactivity. Furthermore, infant gender moderated this association such that exposed boys had significantly higher peak cortisol reactivity than nonexposed infants or exposed girls. These findings provide additional evidence that prenatal cigarette exposure is associated with dysregulation during infancy and that early adverse, nonsocial experiences may have relatively long-lasting effects on cortisol reactivity in infants.

Volumetric MRI Study of Brain in Children With Intrauterine Exposure to Cocaine, Alcohol, Tobacco, and Marijuana

The objective of this study was to use volumetric MRI to study brain volumes in 10- to 14-year-old children with and without intrauterine exposure to cocaine, alcohol, cigarettes, or marijuana. Volumetric MRI was performed on 35 children (mean age: 12.3 years; 14 with intrauterine exposure to cocaine, 21 with no intrauterine exposure to cocaine) to determine the effect of prenatal drug exposure on volumes of cortical gray matter; white matter; subcortical gray matter; cerebrospinal fluid; and total parenchymal volume. Head circumference was also obtained. Analyses of each individual substance were adjusted for demographic characteristics and the remaining 3 prenatal substance exposures. Regression analyses adjusted for demographic characteristics showed that children with intrauterine exposure to cocaine had lower mean cortical gray matter and total parenchymal volumes and smaller mean head circumference than comparison children. After adjustment for other prenatal exposures, these volumes remained smaller but lost statistical significance. Similar analyses conducted for prenatal ethanol exposure adjusted for demographics showed significant reduction in mean cortical gray matter; total parenchymal volumes; and head circumference, which remained smaller but lost statistical significance after adjustment for the remaining 3 exposures. Notably, prenatal cigarette exposure was associated with significant reductions in cortical gray matter and total parenchymal volumes and head circumference after adjustment for demographics that retained marginal significance after adjustment for the other 3 exposures. Finally, as the number of exposures to prenatal substances grew, cortical gray matter and total parenchymal volumes and head circumference declined significantly with smallest measures found among children exposed to all 4. CONCLUSIONS; These data suggest that intrauterine exposures to cocaine, alcohol, and cigarettes are individually related to reduced head circumference; cortical gray matter; and total parenchymal volumes as measured by MRI at school age. Adjustment for other substance exposures precludes determination of statistically significant individual substance effect on brain volume in this small sample; however, these substances may act cumulatively during gestation to exert lasting effects on brain size and volume.

Environmental influences that affect attention deficit/hyperactivity disorder

Three independent complex segregation analyses found that the cause of Attention Deficit/Hyperactivity Disorder (ADHD) was the presence of major genes interacting with environmental influences. In order to identify potential environmental risk factors for ADHD in the Paisa community--a very well described, genetically isolated group--we randomly selected a sample of 486 children between 6 and 11 years of age. This group included 200 children with ADHD (149 males and 51 females) and 286 healthy controls (135 males and 151 females). The ADHD DSM-IV diagnosis was obtained using the DICA and BASC evaluation instruments, and the children's mothers or grandmothers filled out a questionnaire on each child's exposure to prenatal, neonatal, and early childhood risk factors. The data were analyzed using cross tabulation and stepwise logistic multiple-regression analyses. Cross tabulation associated ADHD with a variety of factors, including miscarriage symptoms, premature delivery symptoms, maternal respiratory viral infection, moderate to severe physical illness in the mother during gestation, prenatal cigarette and alcohol exposure, neonatal seizures, asphyxia or anoxia, severe neonatal illness, mild speech retardation, moderate brain injury, and febrile seizures (odds ratio >or= 2, P < 0.05). Stepwise logistic multiple-regression analysis also uncovered a block of variables, including male gender, maternal illnesses, prenatal alcohol exposure, mild speech retardation, febrile seizures, and moderate brain injury (odds ratio >or= 2.0, P < 0.05). Future studies on the risk of developing ADHD must include these environmental factors as covariates.

Effects of maternal smoking in pregnancy on prenatal brain development. The Generation R Study

Nicotine, as has been shown in animal studies, is a neuroteratogen, even in concentrations that do not cause growth retardation. In humans, there is only indirect evidence for negative influences of nicotine on brain development from studies on the association between maternal smoking in pregnancy and behavioural and cognitive development in the offspring. We investigated the associations of maternal smoking in pregnancy with foetal head growth characteristics in 7042 pregnant women. This study was embedded in the Generation R Study, a population-based prospective cohort study from foetal life until adulthood. Maternal smoking was assessed by questionnaires in early, mid- and late pregnancy. Head circumference, biparietal diameter, transcerebellar diameter and atrial width of lateral ventricles were repeatedly measured by ultrasound. When mothers continued to smoke during pregnancy, foetal head circumference showed a growth reduction of 0.13 mm [95% confidence interval (CI): -0.18, -0.09] per week compared to foetuses of mothers who never smoked during pregnancy. Biparietal diameter of foetuses with smoking mothers grew 0.04 mm (95% CI: -0.05, -0.02) less per week than that of foetuses of nonsmoking mothers. Atrial width of lateral ventricle was 0.12 mm (95% CI: -0.22, -0.02) smaller and transcerebellar diameter was 0.08 mm (95% CI: -0.15, -0.00) smaller if mothers smoked, but growth per week of these characteristics was not affected by maternal smoking in pregnancy. In conclusion, continuing to smoke during pregnancy leads to reduced growth of the foetal head. Further research should focus on the causal pathway from prenatal cigarette exposure via brain development to behavioural and cognitive functions.