Prenatal Tobacco Exposure Research Articles

Smoking in Pregnancy and Fetal Growth: The Case for More Intensive Assessment.

Many studies on prenatal tobacco exposure (PTE) effects have relied on single item retrospective measures of PTE. However, it is unclear how these single item measures may relate to more intensive maternal self-reports and to biological markers of maternal use and/or fetal exposure. It is also unclear whether these measures may be more valid predictors of fetal growth (gestational age, birthweight, head circumference, and birth length). Data were obtained from 258 women during their pregnancy. PTE was assessed by four methods: a single item question, a calendar-based self-report measure from each trimester of pregnancy, maternal salivary cotinine assays, and nicotine and metabolites in infant meconium. We hypothesized that the more intensive measures and biological assays would account for additional variance in birth outcomes, above and beyond the single item measure. The single item self-report measure was not related to fetal growth. However, the more intensive calendar based self-report measure and the biological assays of PTE (ie, maternal salivary assays and infant meconium) were significant predictors of poor fetal growth, even with the single item measure in the model. The negative effects of PTE on important child outcomes may be greatly underestimated in the literature as many studies use single item self-report measures to ascertain PTE. Whereas more intensive self-report measures or biological assays may be cost prohibitive in large scale epidemiological studies, using a combination of measures when possible should be considered given their superiority both identifying prenatal smokers and predicting poor fetal growth. The present work underscores the importance of measurement issues when assessing associations between PTE and fetal growth. Results suggest that we may be greatly underestimating the negative effects of prenatal smoking on fetal growth and other important child outcomes if we rely solely on restricted single item self-report measures of prenatal smoking. Researchers should consider more intensive prospective self-report measures and biological assays as viable and superior alternatives to single item self-report measures.

Prenatal tobacco exposure, birthweight, and offspring psychopathology

Although prenatal tobacco exposure (PTE) is associated with several adverse offspring mental health outcomes, mechanisms remain unclear. We test whether associations between PTE and offspring psychopathology are explained by birthweight, one of the earliest-occurring outcomes of PTE. The analysis focuses on 238 offspring from a family study of depression with (1) collected prenatal histories and (2) at least one clinical interview in adulthood to assess psychiatric problems. Exposure was categorized by maternal smoking of ≥10 cigarettes daily/nearly daily; diagnostic outcomes were confirmed by clinicians using the best-estimate procedure, blind to exposure. After adjusting for potential confounders, PTE was associated with 0.7lb(9%) lower birthweight (p=0.0002), increased rates of disruptive behavior disorders [males: OR=2.66(1.15,6.16), and (trend) substance use disorders [females: OR=2.23(0.98,5.09)], and decreased rates of mood disorders (males: OR=0.42(0.17,0.98)]. Birthweight was not independently associated with diagnoses and did not mediate the association between exposure and psychopathology. Maternal smoking has long-term adverse consequences for offspring. Although birthweight cannot be manipulated, smoking is a modifiable risk factor. Thus, cessation efforts focused on pregnant women may not only improve maternal wellbeing, but also mitigate adverse proximal (e.g., birthweight) and long-term (psychopathology) outcomes in offspring.

Prenatal tobacco exposure, maternal postnatal nicotine dependence and adolescent risk for nicotine dependence: Birth cohort study

AimsThe goals of this study are to determine if there is (a) a threshold effect for prenatal tobacco exposure (PTE) on adolescent risk for nicotine dependence, and (b) an additive effect of PTE and maternal postnatal nicotine dependence on adolescent risk for nicotine dependence. MethodsPregnant women were recruited in their 4th or 5th gestational month and asked about cigarette use during the first trimester. Mothers reported on third trimester cigarette use at delivery. Sixteen years post-partum, mothers and offspring reported on current levels of cigarette use (N=784). Nicotine dependence was assessed in both using a modified Fagerström questionnaire. ResultsBased on the results of a threshold analysis for PTE, four groups were created: threshold PTE only (10+ cigarettes per day), maternal nicotine postnatal dependence with no-low PTE (0–<10 cigarettes per day), threshold PTE+maternal postnatal nicotine dependence, and a referent group with no-low PTE and no maternal postnatal nicotine dependence. Adolescents in the PTE-only group and the PTE+maternal postnatal nicotine dependence group were significantly more likely to be at risk for nicotine dependence than the offspring from the referent group. However, there was no evidence for an additive effect of maternal postnatal nicotine dependence, and maternal nicotine dependence was not a significant predictor of adolescent risk for nicotine dependence in regression models including prenatal tobacco exposure. ConclusionsBivariate analysis revealed a threshold effect for PTE of 10 cigarettes per day. In multivariate analysis, PTE remained significantly related to risk for offspring nicotine dependence, after controlling for maternal postnatal nicotine dependence and other covariates associated with adolescent cigarette use.

Assessment of tobacco, alcohol and cannabinoid metabolites in 645 meconium samples of newborns compared to maternal self-reports

Prenatal psychoactive substance exposure has significant impact on neonatal health and child development and the development of reliable biomarkers is critical. Meconium presents several advantages for detecting prenatal exposure to psychoactive substances, as it is easy to collect and provides a broad time frame of exposure (third trimester). The aim of our study was to compare the prevalence of alcohol, tobacco and/or cannabis use during the third trimester of pregnancy (using maternal self-reports) with the results of meconium testing of their metabolites in newborns (cotinine, ethyl-glucuronide (EtG) and cannabinoid metabolites).Among all deliveries (993) that occurred in all maternities in Rouen (Normandy) during a defined time period (5 consecutive weeks in August, 2010 and August, 2011), 724 mothers were included and 645 meconium samples were collected. Maternal self-reports, using the Addiction Severity Index (5th edition), and meconium samples were collected within 72 h of delivery.Cotinine detection appears highly correlated to maternal self-reports (Kappa value: 0.79; [95%CI: 0.73–0.85]). Moreover, detection in meconium seems more accurate in the prediction of neonatal consequences of prenatal tobacco exposure as compared to maternal self-reports. In contrast, we have found a lower concordance between maternal self-reports and meconium testing for EtG and cannabinoid metabolites (Kappa value: 0.13; [95%CI: 0.04–0.22] and: 0.30; [95%CI: −0.03–0.63], respectively); however the total number of EtG- and cannabinoid-positive meconium samples was small. Interestingly, meconium samples with the highest levels of EtG mainly corresponded to negative maternal self-reports. Fetal exposure to alcohol, tobacco or cannabis may also considerably differ as displayed in our pairs of dizygotic twins. Finally, a polyconsumption of these psychoactive substances was not frequently observed according to meconium testing.In conclusion, cotinine detection appears as a valuable meconium biomarker. EtG measurement in meconium samples seems interesting if there is any risk of high fetal exposure, whereas assessment of prenatal cannabis exposure, using meconium testing, needs to be improved.

Tobacco Exposure and Conditional Weight-for-Length Gain by 2 Years of Age.

To prospectively examine dose-response and timing effects of prenatal (PTE) and postnatal tobacco exposure on obesity risk assessed by conditional weight-for-length gain (CWFLG), by 2 years of age. CWFLG over the first 2 years of life was examined for 117 PTE and 57 nonexposed children. Repeated assessments of PTE were conducted beginning in the first trimester of pregnancy, using multiple methods. PTE or postnatal exposure status was not predictive of CWFLG. However, there was a dose-response association and an association with fetal exposure ascertained by infant meconium positive for nicotine and metabolites. PTE is related to restricted growth at birth, yet associated with accelerated CWFLG by 2 years of age, a measure that controls for birthweight differences. Results highlight the importance of examining dose-response and timing of exposure associations, along with the importance of obesity risk-reduction interventions within the first 2 years of life among PTE children.

Does MAOA increase susceptibility to prenatal stress in young children?

BackgroundWe previously demonstrated a gene-by-prenatal-environment interaction whereby the monoamine oxidase A gene (MAOA) modified the impact of prenatal tobacco exposure (PTE) on adolescent disruptive behavior (DB), with the MAOA risk genotype varying by sex. We extend this work by examining whether this mechanism is evident with another common adversity, prenatal stress exposure (PSE), and whether sex differences are present earlier in development in closer proximity to exposure. MethodsParticipants were 281 mothers and their 285 children derived from a prenatal cohort with in-depth prospective measures of PSE and PTE. We assessed DB at age 5 via dimensional developmentally-sensitive measurement. Analyses were stratified by sex based on prior evidence for sex differences. ResultsConcurrent stress exposure predicted DB in children (β=0.310, p=0.001), while main effects of prenatal exposures were seen only in boys. We found a three-way interaction of MAOA×PSE×sex on DB (β=0.813, p=0.022). Boys with MAOA-H had more DB as a function of PSE, controlling for PTE (β=0.774, p=0.015), and as a function of PTE, controlling for PSE (β=0.362, p=0.037). Boys with MAOA-L did not show this susceptibility. MAOA did not interact with PSE (β=−0.133, p=0.561) nor PTE (β=−0.144; p=0.505) in predicting DB in girls. Examination of gene-environment correlation (rGE) showed a correlation between paternal MAOA-L and daughters' concurrent stress exposure (r=−0.240, p=0.013). DiscussionFindings underscore complex mechanisms linking genetic susceptibility and early adverse exposures. Replication in larger cohorts followed from the pregnancy through adolescence is suggested to elucidate mechanisms that appear to have varying developmental expression.

M31 - Gene Expression In Blood of Children And Adolescents: Influence of Environmental Stressors On Major Depressive Disorder

Background Studies investigating major depressive disorder (MDD) in childhood and adolescence are relevant to understand relative contributions from either genetic and environmental factors on MDD, since early stages of disease have less influence of illness exposure. We aimed to investigate peripheral mRNA expression of 12 genes related to HPA axis (NR3C1, FKBP5), inflammation (TNF, TNFR1, TNFR2, IL1B), neurodevelopment (DISC1, PDE4B, QKI), and neurotransmission (SLC1A4, GLUL, COMT) in blood of children and adolescents with MDD and to test if history of childhood maltreatment (CM) or prenatal alcohol (PA) and tobacco (PT) exposure (environmental stressors that influences psychiatry disorders risk) could affect MDD via gene expression. Methods mRNA levels in whole blood were compared among 20 children and adolescents with MDD diagnosis (MDD group), 48 subjects without MDD diagnosis but with high levels of depressive symptoms (DS group) and 61 healthy controls (HC group). We also performed a mediation model in which CM/PA/PT exposure was the independent variable, MDD was the outcome and gene expression was the intermediary variable. Results NR3C1, TNF, TNFR1 and IL1B expression levels were significantly lower in MDD group compared to the other groups. The direct effects of CM, PA and PT exposure on MDD were not significant. Moreover, there was not an indirect effect of PA or PT exposure on MDD. However, there was an indirect effect on the aggregation of these four genes expressions, mediating the relationship between CM and MDD. Discussion In the largest study investigating gene expression in children with MDD, we demonstrated that the NR3C1, TNF, TNFR1 and IL1B expression are related to the MDD and conjunctly mediated the effect of history of CM on risk of developing the disorder, supporting a role of glucocorticoids and inflammation as possible effectors of environmental distress on this disorder.

Urban Young Adults’ Adaptive Functioning

Research on the association between prenatal substance exposures and adaptive functioning among young adults is limited, with inconsistent conclusions. In a prospective longitudinal study of 138 urban young adults, prenatal substance exposures were identified at birth from maternal self-report, urine screens, and/or infant meconium. At follow-up between ages 18 and 24 years, masked interviewers assessed level of adaptive functioning, a composite indicator comprising five domains: education, housing, adolescent pregnancy, arrest history, and employment. A significant negative association was found between prenatal tobacco exposure and adaptive functioning, particularly among females with heavier exposure. This association with heavier, but not lighter, prenatal tobacco exposure is consistent with a neuroteratologic explanation, but other, non-biological explanations cannot be ruled out. No statistically significant associations were observed between prenatal cocaine, marijuana, or low-moderate alcohol exposure and young adult adaptive functioning.

DNA methylation and substance-use risk: a prospective, genome-wide study spanning gestation to adolescence.

Epigenetic processes have been implicated in addiction; yet, it remains unclear whether these represent a risk factor and/or a consequence of substance use. Here, we believe we conducted the first genome-wide, longitudinal study to investigate whether DNA methylation patterns in early life prospectively associate with substance use in adolescence. The sample comprised of 244 youth (51% female) from the Avon Longitudinal Study of Parents and Children (ALSPAC), with repeated assessments of DNA methylation (Illumina 450k array; cord blood at birth, whole blood at age 7) and substance use (tobacco, alcohol and cannabis use; age 14–18). We found that, at birth, epigenetic variation across a tightly interconnected genetic network (n=65 loci; q<0.05) associated with greater levels of substance use during adolescence, as well as an earlier age of onset amongst users. Associations were specific to the neonatal period and not observed at age 7. Key annotated genes included PACSIN1, NEUROD4 and NTRK2, implicated in neurodevelopmental processes. Several of the identified loci were associated with known methylation quantitative trait loci, and consequently likely to be under significant genetic control. Collectively, these 65 loci were also found to partially mediate the effect of prenatal maternal tobacco smoking on adolescent substance use. Together, findings lend novel insights into epigenetic correlates of substance use, highlight birth as a potentially sensitive window of biological vulnerability and provide preliminary evidence of an indirect epigenetic pathway linking prenatal tobacco exposure and adolescent substance use.

Refining the Understanding of the Effects of Prenatal Methamphetamine and Tobacco Exposure on the Developing Brain

Refining the Understanding of the Effects of Prenatal Methamphetamine and Tobacco Exposure on the Developing Brain

Sex-Specific Alterations of White Matter Developmental Trajectories in Infants With Prenatal Exposure to Methamphetamine and Tobacco

Methamphetamine is a common illicit drug used worldwide. Methamphetamine and/or tobacco use by pregnant women remains prevalent. However, little is known about the effect of comorbid methamphetamine and tobacco use on human fetal brain development. To investigate whether microstructural brain abnormalities reported in children with prenatal methamphetamine and/or tobacco exposure are present at birth before childhood environmental influences. A prospective, longitudinal study was conducted between September 17, 2008, and February 28, 2015, at an ambulatory academic medical center. A total of 752 infant-mother dyads were screened and 139 of 195 qualified neonates were evaluated (36 methamphetamine/tobacco exposed, 32 tobacco exposed, and 71 unexposed controls). They were recruited consecutively from the community. Prenatal methamphetamine and/or tobacco exposure. Quantitative neurologic examination and diffusion tensor imaging performed 1 to 3 times through age 4 months; diffusivities and fractional anisotropy (FA) assessed in 7 white matter tracts and 4 subcortical brain regions using an automated atlas-based method. Of the 139 infants evaluated, 72 were female (51.8%); the mean (SE) postmenstrual age at baseline was 41.5 (0.27) weeks. Methamphetamine/tobacco-exposed infants showed delayed developmental trajectories on active muscle tone (group × age, P < .001) and total neurologic scores (group × age, P = .01) that normalized by ages 3 to 4 months. Only methamphetamine/tobacco-exposed boys had lower FA (group × age, P = .02) and higher diffusivities in superior (SCR) and posterior corona radiatae (PCR) (group × age × sex, P = .002; group × age × sex, P = .01) at baseline that normalized by age 3 months. Only methamphetamine/tobacco- and tobacco-exposed girls showed persistently lower FA in anterior corona radiata (ACR) (group, P = .04; group × age × sex, P = .01). Tobacco-exposed infants showed persistently lower axial diffusion in the thalamus and internal capsule across groups (P = .02). Prenatal methamphetamine/tobacco exposure may lead to delays in motor development, with less coherent fibers and less myelination in SCR and PCR only in male infants, but these abnormalities may normalize by ages 3 to 4 months after cessation of stimulant exposure. In contrast, persistently less coherent ACR fibers were observed in methamphetamine/tobacco- and tobacco-exposed girls, possibly from increased dendritic branching or spine density due to epigenetic influences. Persistently lower diffusivity in the thalamus and internal capsule of all tobacco-exposed infants suggests aberrant axonal development. Collectively, prenatal methamphetamine and/or tobacco exposure may lead to delayed motor development and white matter maturation in sex- and regional-specific manners.

Tobacco exposure and maternal psychopathology: Impact on toddler problem behavior

Prenatal exposure to tobacco has consistently predicted later problem behavior for children. However, little is known about developmental mechanisms underlying this association. We examined a conceptual model for the association between prenatal tobacco exposure and child problem behavior in toddlerhood via indirect paths through fetal growth, maternal depression, and maternal aggressive disposition in early infancy and via maternal warmth and sensitivity and infant negative affect in later infancy. The sample consisted of 258 mother–child dyads recruited during pregnancy and assessed periodically at 2, 9, and 16months of child age. Pathways via maternal depression and infant negative affect to toddler problem behavior were significant. Further, combined tobacco and marijuana exposure during pregnancy and reduced fetal growth also demonstrated important associations with infant negative affect and subsequent problem behavior. These results highlight the importance of considering the role of maternal negative affect and poor fetal growth as risk factors in the context of prenatal exposure.

Prenatal Maternal Smoking and Increased Risk for Tourette Syndrome and Chronic Tic Disorders

We assessed the role of prenatal maternal smoking in risk for Tourette syndrome and chronic tic disorder (TS/CT) and pediatric-onset obsessive-compulsive disorder (OCD). In an analysis of 73,073 singleton pregnancies from the Danish National Birth Cohort, we calculated incidence rates (IR) per 1,000 person-year for TS/CT and OCD. We then determined crude and adjusted hazard ratios and 95% CIs associated with prenatal maternal smoking, considering smoking as a dichotomous (yes/no) variable or a stratified variable (no smoking, light smoking, and heavy smoking [≥10 cigarettes/day]). Additional analyses examined the effect of maternal smoking on risk for TS/CT with other comorbid psychiatric conditions. In final adjusted analyses, heavy smoking was associated with a 66% increased risk for TS/CT (adjusted hazard ratio= 1.66, 95% CI= 1.17-2.35). In addition, heavy smoking was associated with a 2-fold increased risk for TS/CT with comorbid attention-deficit/hyperactivity disorder (ADHD), and both light and heavy smoking were associated with a more than2-fold increased risk for TS/CT with any non-ADHDpsychiatric comorbidity. Our parallel analyses of pediatric-onset OCD were likely underpowered but showed similar relationships. Prenatal maternal smoking was associated with increased risk for TS/CT as well as TS/CT with comorbid psychiatric conditions, even after adjustment for several important variables, including maternal psychiatric history, socioeconomic status, and partner smoking. Our findings point to a pathway linking prenatal tobacco exposure and altered brain development to TS/CT.

Prenatal Tobacco Exposure Shortens Telomere Length in Children.

Preliminary evidence suggests a possible association between prenatal tobacco exposure and telomere length in children. This study was conducted to investigate whether maternal smoking during pregnancy was associated with telomere shortening in their children and whether prenatal and childhood exposure to environmental tobacco had any impact on this association. This is a population-representative study on the association between prenatal tobacco exposure and telomere length in children. Ninety-eight Hong Kong Chinese children aged under 15 years with prenatal tobacco exposure and 98 age- and gender-matched controls were recruited from a population health study with stratified random sampling. Telomere length in children with prenatal tobacco exposure was significantly shorter than in those with no exposure (mean T/S ratio = 24.9 [SD = 8.58] in exposed vs. 28.97 [14.15] in control groups; P = 0.02). A negative dose-response relationship was observed between the T/S ratio and tobacco exposure duration: the longer the duration of maternal smoking in pregnancy, the shorter the child's telomere length. The association between the child's telomere length and prenatal tobacco exposure remained significant after considering the influence of family socioeconomic status and exposure to environmental tobacco smoke during pregnancy and childhood. Prenatal tobacco exposure was associated with telomere shortening in children. As this may impose significant health impacts through fetal genetic programming, more efforts should be made to reduce fetal tobacco exposure by educating pregnant women to not smoke and motivating smokers to quit in early pregnancy. As reflected by telomere shortening, prenatal tobacco exposure in children can cause premature aging and increased health risks, which we suggest is entirely preventable. Not smoking during pregnancy or quitting smoking is critical to improving the health outcome of our future generations as prenatal tobacco exposure may affect children's biological programming.

Prenatal Tobacco Exposure in High-Risk Pregnancies

INTRODUCTION: Maternal cigarette smoking is one of the most hazardous environmental exposures during pregnancy and understanding its health consequences is complicated by method of ascertainment of exposure. There are two primary methods of assessing smoking behavior: self-report and biological assay. Few studies have characterized the potential discrepancy between these two methods. METHODS: Subjects participated in prospective observational studies of the perinatal course of mental illness at the Emory Women's Mental Health Program. Participants' tobacco exposure was ascertained by weekly self-report and assay of urine levels of nicotine and cotinine at one or more time points during pregnancy. We compared self-report and objective measures collected in the same week to determine if a patient “under-reported” (denied) smoking during the pregnancy. RESULTS: In a sample of 804 pregnant women, relying upon urine assay, the overall prevalence of active and passive smoking was 10.3% and 0.6%, respectively. By self-report, the prevalence of smoking was 14.8%, 8.6% and 8.0% in the first, second and third trimesters, respectively. The prevalence of under-reporting smoking during pregnancy was overall 2.4%, and among 83 active smokers confirmed by positive biomarkers, 23% denied cigarette smoking on one or more occasions. CONCLUSION: In our study, approximately one in four pregnant women denied cigarette smoking when biomarkers identified them as current smokers. Though the sample consists of women with a psychiatric history, this suggests that self-report of cigarette exposure may not be sufficient to identify at-risk pregnancies in a broader population. Efforts should be aimed at decreasing barriers to patient disclosure.

Risk Factors for Childhood Obesity in the First 1,000 Days: A Systematic Review.

Mounting evidence suggests that the origins of childhood obesity and related disparities can be found as early as the "first 1,000 days"-the period from conception to age 2 years. The main goal of this study is to systematically review existing evidence for modifiable childhood obesity risk factors present from conception to age 2 years. PubMed, Embase, and Web of Science were searched for studies published between January 1, 1980, and December 12, 2014, of childhood obesity risk factors present during the first 1,000 days. Prospective, original human subject, English-language research with exposure occurrence during the first 1,000 days and with the outcome of childhood overweight or obesity (BMI ≥85th percentile for age and sex) collected between age 6 months and 18 years were analyzed between December 13, 2014, and March 15, 2015. Of 5,952 identified citations, 282 studies met inclusion criteria. Several risk factors during the first 1,000 days were consistently associated with later childhood obesity. These included higher maternal pre-pregnancy BMI, prenatal tobacco exposure, maternal excess gestational weight gain, high infant birth weight, and accelerated infant weight gain. Fewer studies also supported gestational diabetes, child care attendance, low strength of maternal-infant relationship, low SES, curtailed infant sleep, inappropriate bottle use, introduction of solid food intake before age 4 months, and infant antibiotic exposure as risk factors for childhood obesity. Modifiable risk factors in the first 1,000 days can inform future research and policy priorities and intervention efforts to prevent childhood obesity.

Developmental pathways from prenatal tobacco and stress exposure to behavioral disinhibition

Prenatal tobacco exposure (PTE) and prenatal stress exposure (PSE) both have been linked to externalizing behavior, although their effects generally have been considered in isolation. Here, we aimed to characterize the joint or interactive roles of PTE and PSE in early developmental pathways to behavioral disinhibition, a profile of cognitive and behavioral under-control that presages severe externalizing behavior. As part of a prospective, longitudinal study, 296 children were assessed at a mean age of 5years. Exposures were assessed via repeated interviews across the prenatal period and bioassays of cotinine were obtained. Behavioral disinhibition was assessed using temperament measures in infancy, performance-based executive control tasks and measures of disruptive and inattentive behavior. PSE was associated with a higher probability of difficult temperament in infancy. Each exposure independently predicted poorer executive control at age 5years. Difficult temperament and executive control difficulties in turn predicted elevated levels of disruptive behavior, although links from PTE and PSE to parent-reported attention problems were less robust. Children who experienced these prenatal exposures in conjunction with higher postnatal stress exposure showed the lowest executive control and highest levels of disruptive behavior. Findings highlight the compounding adverse impact of PTE and PSE on children's behavioral trajectories. Given their high concordance, prenatal health campaigns should target these exposures in tandem.

A meta-analysis provides evidence that prenatal smoking exposure decreases age at menarche.

Since studies of association between prenatal tobacco exposure and age at menarche have reported inconsistent results so far, we conducted a meta-analysis to examine this association. In total 36 relevant articles (1995-2014) were identified, 17 of which satisfied the inclusion criteria and were used in the analysis. Nearly one month decrease (-0.092 [95%CI:-0.160, -0.024] year) in age at menarche was found in women who were exposed to tobacco in utero. The meta-regression analysis showed that average year of birth in the cohorts might significantly influence association between maternal smoking and daughter's age at menarche. Based on results obtained from 5 studies where age at menarche was treated as a categorical variable, maternal smoking status during pregnancy increased a risk for daughters to have menarche earlier than at 11 years old by 15%.

Prenatal tobacco exposure predicts child's internalizing behavior

Prenatal tobacco exposure predicts child's internalizing behavior

Commentary on Leung et al. (2015): Inequalities in mental health begin in utero--the case of prenatal tobacco exposure.

Tobacco smoking in pregnancy is arguably the most important preventable cause of adverse pregnancy outcomes and a number of childhood developmental problems. Recent findings suggest a very early effect of socio-economic disadvantage and that public health research ought to refocus on a ‘womb to tomb’ perspective...