Effects Of Prenatal Tobacco Exposure Research Articles

Influence of perinatal and childhood exposure to tobacco and mercury in children's gut microbiota.

Early life determinants of the development of gut microbiome composition in infants have been widely investigated; however, if early life pollutant exposures, such as tobacco or mercury, have a persistent influence on the gut microbial community, its stabilization at later childhood remains largely unknown. In this exposome-wide study, we aimed at identifying the contribution of exposure to tobacco and mercury from the prenatal period to childhood, to individual differences in the fecal microbiome composition of 7-year-old children, considering co-exposure to a width of established lifestyle and clinical determinants. Gut microbiome was studied by 16S rRNA amplicon sequencing in 151 children at the genus level. Exposure to tobacco was quantified during pregnancy through questionnaire (active tobacco consumption, second-hand smoking -SHS) and biomonitoring (urinary cotinine) at 4 years (urinary cotinine, SHS) and 7 years (SHS). Exposure to mercury was quantified during pregnancy (cord blood) and at 4 years (hair). Forty nine other potential environmental determinants (12 at pregnancy/birth/infancy, 15 at 4 years and 22 at 7 years, such as diet, demographics, quality of living/social environment, and clinical records) were registered. We used multiple models to determine microbiome associations with pollutants including multi-determinant multivariate analysis of variance and linear correlations (wUnifrac, Bray-Curtis and Aitchison ß-diversity distances), single-pollutant permutational multivariate analysis of variance adjusting for co-variates (Aitchison), and multivariable association model with single taxa (MaAsLin2; genus). Sensitivity analysis was performed including genetic data in a subset of 107 children. Active smoking in pregnancy was systematically associated with microbiome composition and ß-diversity (R2 2-4%, p < 0.05, Aitchison), independently of other co-determinants. However, in the adjusted single pollutant models (PERMANOVA), we did not find any significant association. An increased relative abundance of Dorea and decreased relative abundance of Akkermansia were associated with smoking during pregnancy (q < 0.05). Our findings suggest a long-term sustainable effect of prenatal tobacco exposure on the children's gut microbiota. This effect was not found for mercury exposure or tobacco exposure during childhood. Assessing the role of these exposures on the children's microbiota, considering multiple environmental factors, should be further investigated.

Demystifying the impact of prenatal tobacco exposure on the placental immune microenvironment: Avoiding the tragedy of mending the fold after death.

Prenatal tobacco exposure (PTE) correlates significantly with a surge in adverse pregnancy outcomes, yet its pathological mechanisms remain partially unexplored. This study aims to meticulously examine the repercussions of PTE on placental immune landscapes, employing a coordinated research methodology encompassing bioinformatics, machine learning and animal studies. Concurrently, it aims to screen biomarkers and potential compounds that could sensitively indicate and mitigate placental immune disorders. In the course of this research, two gene expression omnibus (GEO) microarrays, namely GSE27272 and GSE7434, were included. Gene set enrichment analysis (GSEA) and immune enrichment investigations on differentially expressed genes (DEGs) indicated that PTE might perturb numerous innate or adaptive immune-related biological processes. A cohort of 52 immune-associated DEGs was acquired by cross-referencing the DEGs with gene sets derived from the ImmPort database. A protein-protein interaction (PPI) network was subsequently established, from which 10 hub genes were extracted using the maximal clique centrality (MCC) algorithm (JUN, NPY, SST, FLT4, FGF13, HBEGF, NR0B2, AREG, NR1I2, SEMA5B). Moreover, we substantiated the elevated affinity of tobacco reproductive toxicants, specifically nicotine and nitrosamine, with hub genes through molecular docking (JUN, FGF13 and NR1I2). This suggested that these genes could potentially serve as crucial loci for tobacco's influence on the placental immune microenvironment. To further elucidate the immune microenvironment landscape, consistent clustering analysis was conducted, yielding three subtypes, where the abundance of follicular helper T cells (p < 0.05) in subtype A, M2 macrophages (p < 0.01), neutrophils (p < 0.05) in subtype B and CD8+ T cells (p < 0.05), resting NK cells (p < 0.05), M2 macrophages (p < 0.05) in subtype C were significantly different from the control group. Additionally, three pivotal modules, designated as red, blue and green, were identified, each bearing a close association with differentially infiltrated immunocytes, as discerned by the weighted gene co-expression network analysis (WGCNA). Functional enrichment analysis was subsequently conducted on these modules. To further probe into the mechanisms by which immune-associated DEGs are implicated in intercellular communication, 20 genes serving as ligands or receptors and connected to differentially infiltrating immunocytes were isolated. Employing a variety of machine learning techniques, including one-way logistic regression, LASSO regression, random forest and artificial neural networks, we screened 11 signature genes from the intersection of immune-associated DEGs and secretory protein-encoding genes derived from the Human Protein Atlas. Notably, CCL18 and IFNA4 emerged as prospective peripheral blood markers capable of identifying PTE-induced immune disorders. These markers demonstrated impressive predictive power, as indicated by the area under the curve (AUC) of 0.713 (0.548-0.857) and 0.780 (0.618-0.914), respectively. Furthermore, we predicted 34 potential compounds, including cyclosporine, oestrogen and so on, which may engage with hub genes and attenuate immune disorders instigated by PTE. The diagnostic performance of these biomarkers, alongside the interventional effect of cyclosporine, was further corroborated in animal studies via ELISA, Western blot and immunofluorescence assays. In summary, this study identifies a disturbance in the placental immune landscape, a secondary effect of PTE, which may underlie multiple pregnancy complications. Importantly, our research contributes to the noninvasive and timely detection of PTE-induced placental immune disorders, while also offering innovative therapeutic strategies for their treatment.

Prenatal tobacco exposure on brain morphometry partially mediated poor cognitive performance in preadolescent children.

To evaluate whether prenatal tobacco exposure (PTE) is related to poorer cognitive performance, abnormal brain morphometry, and whether poor cognitive performance is mediated by PTE-related structural brain differences. The Adolescent Brain Cognitive Development study dataset was used to compare structural MRI data and neurocognitive (NIH Toolbox®) scores in 9-to-10-year-old children with (n=620) and without PTE (n=10,989). We also evaluated whether PTE effects on brain morphometry mediated PTE effects on neurocognitive scores. Group effects were evaluated using Linear Mixed Models, covaried for socio-demographics and prenatal exposures to alcohol and/or marijuana, and corrected for multiple comparisons using the false-discovery rate (FDR). Compared to unexposed children, those with PTE had poorer performance (all p-values <0.05) on executive function, working memory, episodic memory, reading decoding, crystallized intelligence, fluid intelligence and overall cognition. Exposed children also had thinner parahippocampal gyri, smaller surface areas in the posterior-cingulate and pericalcarine cortices; the lingual and inferior parietal gyri, and smaller thalamic volumes (all p-values <0.001). Furthermore, among children with PTE, girls had smaller surface areas in the superior-frontal (interaction-FDR-p=0.01), precuneus (interaction-FDR-p=0.03) and postcentral gyri (interaction-FDR-p=0.02), while boys had smaller putamen volumes (interaction-FDR-p=0.02). Smaller surface areas across regions of the frontal and parietal lobes, and lower thalamic volumes, partially mediated the associations between PTE and poorer neurocognitive scores (p-values <0.001). Our findings suggest PTE may lead to poorer cognitive performance and abnormal brain morphometry, with sex-specific effects in some brain regions, in pre-adolescent children. The poor cognition in children with PTE may result from the smaller areas and subcortical brain volumes.

The impact of prenatal alcohol and/or tobacco exposure on brain structure in a large sample of children from a South African birth cohort.

Neuroimaging studies have emphasized the impact of prenatal alcohol exposure (PAE) on brain development, traditionally in heavily exposed participants. However, less is known about how naturally occurring community patterns of PAE (including light to moderate exposure) affect brain development, particularly in consideration of commonly occurring concurrent impacts of prenatal tobacco exposure (PTE). Three hundred thirty-two children (ages 8 to 12) living in South Africa's Cape Flats townships underwent structural magnetic resonance imaging. During pregnancy, their mothers reported alcohol and tobacco use, which was used to evaluate PAE and PTE effects on their children's brain structure. Analyses involved the main effects of PAE and PTE (and their interaction) and the effects of PAE and PTE quantity on cortical thickness, surface area, and volume. After false-discovery rate (FDR) correction, PAE was associated with thinner left parahippocampal cortices, while PTE was associated with smaller cortical surface area in the bilateral pericalcarine, left lateral orbitofrontal, right posterior cingulate, right rostral anterior cingulate, left caudal middle frontal, and right caudal anterior cingulate gyri. There were no PAE × PTE interactions nor any associations of PAE and PTE exposure on volumetrics that survived FDR correction. PAE was associated with reduction in the structure of the medial temporal lobe, a brain region critical for learning and memory. PTE had stronger and broader associations, including with regions associated with executive function, reward processing, and emotional regulation, potentially reflecting continued postnatal exposure to tobacco (i.e., second-hand smoke exposure). These differential effects are discussed with respect to reduced PAE quantity in our exposed group versus prior studies within this geographical location, the deep poverty in which participants live, and the consequences of apartheid and racially and economically driven payment practices that contributed to heavy drinking in the region. Longer-term follow-up is needed to determine potential environmental and other moderators of the brain findings here and assess the extent to which they endure over time.

Prenatal tobacco exposure and risk of asthma and allergy outcomes in childhood.

Harmful effects of prenatal tobacco exposure and possible interaction with 17q12-21 genetic variants have been shown for some asthma outcomes in childhood, whereas findings related to allergy outcomes are more inconsistent. This study aimed to examine the effect of prenatal tobacco exposure and relation to 17q12-21 genotype on a wide array of asthma and allergy-related outcomes in early childhood. Prenatal tobacco exposure was determined by maternal smoking during the third trimester (yes/no) in 411 children from the phenotyped Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) birth cohort with clinical follow-up to age 7 years. The rs7216389 single nucleotide polymorphism was used as main representative of the 17q12-21 locus. Asthma end-points included asthma diagnosis, exacerbations, episodes with troublesome lung symptoms and lower respiratory tract infections, spirometry, plethysmography, bronchial responsiveness to methacholine, exercise and cold dry air. Allergy-related endpoints included aeroallergen sensitisation, allergic rhinitis, fractional exhaled nitric oxide, blood eosinophil count and urine eosinophil protein X levels. Statistical analyses were done using Cox regression, linear regression, logistic regression and quasi-Poisson regression. Prenatal tobacco exposure increased the risk of asthma (adjusted hazard ratio (aHR) 2.05, 95% CI 1.13-3.73; p=0.02), exacerbations (aHR 3.76, 95% CI 2.05-6.91; p<0.001), number of LRTIs (adjusted incidence rate ratio 1.87, 95% CI 1.34-2.55; p<0.001), and was associated with decreased spirometry indices (forced expiratory volume in 1 s (FEV1) adjusted mean difference (aMD) -0.07 L, 95% CI -0.13- -0.005 L, p=0.03; maximal mid-expiratory flow aMD -0.19 L·s-1, -0.34- -0.04 L·s-1, p=0.01) and increased bronchial responsiveness to methacholine (provocative dose of methacholine causing a 20% drop in FEV1 adjusted geometric mean ratio 0.55, 95% CI 0.31-0.96; p=0.04). In contrast, there was no association with any allergy-related end-points. The effect on asthma depended on 17q12-21 genotype with an increased risk only among children without risk alleles. Prenatal tobacco exposure was associated with asthma dependent on 17q12-21 genotype and with exacerbations, lung function and bronchial responsiveness, but not with any allergy-related outcomes. This suggests that tobacco exposure in utero leads to adverse lung developmental/structural effects rather than susceptibility to develop allergy and type 2 inflammation.

Prenatal second-hand smoke exposure and newborn telomere length

Cigarette smoking is associated with shorter telomere lengths in adults, but evidence on the effect of prenatal tobacco exposure is limited. We aimed to investigate the association between prenatal second-hand smoke exposure and newborn telomere length. We recruited 762 mother-newborn pairs from Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) between November 2013 and March 2015. Information on second-hand smoke exposure was obtained via questionnaires. Relative telomere length was measured in DNA extracted from umbilical cord blood. We used linear regression to assess the associations between prenatal second-hand smoke exposure and newborn telomere length. In the fully adjusted model, prenatal second-hand smoke exposure was associated with 9.7% shorter newborn telomere length (percent difference: -9.7%; 95% confidence interval (CI): -15.0, -4.0). The estimate for boys was lower (percent difference: -10.9%; 95% CI: -18.6, -2.5) than that for girls (percent difference: -8.5%; 95% CI: -15.8, -0.5), but the interaction term between newborn sex and prenatal second-hand smoke was not significant (P = 0.751). This study demonstrated that prenatal second-hand smoke exposure may be a preventable risk factor for accelerated biological aging in the intrauterine stage, and further suggested possible sex differences in the susceptibility to prenatal second-hand smoke.

High Maternal Circulating Cotinine During Pregnancy is Associated With Persistently Shorter Stature From Birth to Five Years in an Asian Cohort.

Self-reported maternal active smoking has been associated with reduced offspring birth length and shorter stature in early and late childhood. To use circulating cotinine as an objective biomarker to investigate the association between smoking and environmental tobacco smoke (ETS) exposure in pregnancy and longitudinal measures of offspring length/height from birth to 60 months. In 969 maternal-offspring dyads from the GUSTO cohort, maternal plasma cotinine at 26-28 weeks' gestation was measured by LC/MS/MS and categorized into four groups: Group 1: cotinine <0.17 ng/mL (the assay's detection limit) and no ETS exposure; Group 2: cotinine <0.17 ng/mL but self-reported ETS; Group 3: cotinine 0.17-13.99 ng/mL (ETS or light smoking); Group 4: cotinine ≥14 ng/mL (active smoking). Adjusting for infant sex, gestational age at birth, ethnicity, maternal age, education, parity, BMI, and height, Group 4 offspring were shorter at birth [z-score β = -0.42 SD units (SDs) (95% CI = -0.77 to -0.06)] than Group 1 offspring. Group 4 offspring continued to be shorter at older ages, with similar effect sizes at 3 months [-0.57 SDs (-0.95 to -0.20)], 36 months [-0.53 SDs (-0.92 to -0.15)], 48 months [-0.43 SDs (-0.81 to -0.04)], and 60 months [-0.57 SDs (-0.96 to -0.17)]. Associations were particularly marked in boys. No significant differences in stature were observed in Groups 2 or 3 compared with Group 1. This Asian longitudinal study associated high prenatal cotinine with persistently shorter stature in offspring from birth and into early childhood, whilst low prenatal cotinine levels and ETS exposure showed no such association. Little is known about the long-term effects of prenatal tobacco exposure on offspring stature in Asia where passive smoking is common. This study has used an objective biomarker to reveal that the association of prenatal tobacco exposure with offspring length/height mainly occurs at a high maternal cotinine level of greater than 14 ng/mL in pregnancy, consistent with active smoking, but no significant associations were found with lower cotinine levels, consistent with passive smoking. Encouraging women to quit smoking prior to or during pregnancy may avert the long-term negative impact on their child's height despite appreciable prenatal ETS exposure.

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, 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.

Mediating Role of Stress Reactivity in the Effects of Prenatal Tobacco Exposure on Childhood Mental Health Outcomes

Prenatal tobacco exposure, through maternal smoking during pregnancy, has been associated with adverse mental health outcomes in childhood. However, the mechanisms by which prenatal tobacco exposure compromises mental health later in life are unclear. We hypothesized that sensitized reactivity to stressful life events in early childhood mediates the effect of prenatal tobacco exposure on mental health outcomes in middle childhood, after accounting for earlier mental health outcomes. Data were from 12,308 mothers and their children drawn from the Avon Longitudinal Study of Parents and Children, a large prospective population-based study. Mothers' self-reports of smoking during pregnancy, mothers' ratings of their child's reactivity to stressful life events, and teachers' and mothers' ratings of the Strengths and Difficulties Questionnaire assessing 5 domains of mental health outcomes were measured. A positive association was found between prenatal tobacco exposure and stress reactivity between the ages of 2 and 6. In turn, stress reactivity was positively associated with peer (isolation), hyperactivity, conduct, and emotional problems (but not prosocial behaviors) between the ages of 7 and 11, after accounting for the mental health outcome at age 4 and other confounders. Heightened stress reactivity in preschool ages mediated the effect of prenatal tobacco exposure on adverse mental health outcomes between the ages of 7 and 11. Interventions to assist children exposed to tobacco smoke during gestation in coping with stressful life events may help mitigate psychiatric symptoms in this population.

Early Hits and Long-Term Consequences: Tracking the Lasting Impact of Prenatal Smoke Exposure on Telomere Length in Children

We examined the association between telomere length and prenatal tobacco exposure (PTE) in 104 children aged 4 to 14 years. Salivary telomere length (STL) was determined from salivary DNA using quantitative polymerase chain reaction. Of the children, 18% had maternal reported PTE. Mean STL was significantly lower among children with PTE (6.4 vs 7.5, P < .05). Findings extend the literature demonstrating the negative long-term effects of PTE to include a cellular marker of aging linked to multiple negative health outcomes.

Theory of Mind Development is Impaired in 4-year-old Children with Prenatal Exposure to Maternal Tobacco Smoking.

Theory of Mind (ToM) is an important component of social cognition. Deficits in ToM are found in various neurodevelopmental disorders and social and environmental factors have been found to influence ToM development. Little previous research has focused on effects of exposure to toxins; this report examines the impact of tobacco. Department of Psychiatry, University of Colorado School of Medicine, between April 2006 - August 2012. 101 children, 18 with prenatal exposure to tobacco, underwent ToM testing at 40 (n=89) and 48 (n=77) months of age. Test questions received dichotomous pass/fail scores and percentage of correct responses was utilized as the primary dependent variable. At 40 months of age children were rarely able to correctly answer false belief questions and there were no significant differences according to prenatal tobacco exposure. At 48 months of age, there was a significant effect of prenatal tobacco exposure with non-exposed 48-month-olds correctly answering 45±40.6% of content false belief questions correctly, compared to 13.9±25.3% for 48-month-olds with prenatal tobacco exposure (F=4.79, df= 1,73, p=.032). ToM abilities are rapidly developing between 40 and 48 months of age. Prenatal exposure to tobacco is associated with impairment at 48 but not 40 months of age. This finding supports consideration of nicotinic mechanisms as contributors to early development of social cognition.

Maternal prenatal smoking and offspring emotional problems: No moderating effect of maternal or child 5‐HTTLPR genotype

In a recent paper, Cents and others (2012) demonstrated a novel interaction effect of a polymorphism in the serotonin transporter gene (5-HTTLPR) and maternal prenatal smoking on offspring emotional (internalizing) problems at age 3 in a sample of 1,529 Dutch mother-child dyads. The 5-HTTLPR polymorphism has previously been shown to moderate effects of stressful life-events and childhood maltreatment on depression (Karg and others, 2011). Cents and others (2012) extended those findings to the period of fetal life using maternal prenatal smoking as the environmental risk factor, and offspring emotional problems at age 3 as the outcome measure. Cents and others (2012) did not find a significant main effect of the 5- HTTLPR genotype or maternal prenatal smoking on offspring emotional problems, but detected an interaction effect. Having the short allele of the 5-HTTLPR polymorphism in combination with maternal smoking during pregnancy was associated with increased emotional problems at age 3 as rated by the mother. A similar interaction was observed for maternal 5-HTTLPR genotype and this effect was independent of the child’s genotype, suggesting that maternal serotonin levels influence fetal development. The interactions remained significant after correction for maternal educational level, maternal psychopathology, and age and sex of the child. Maternal rater bias was controlled for by alternatively using paternal ratings of offspring emotional problems which showed comparable results. Moreover, when Cents and others (2012) repeated the analyses using paternal prenatal smoking as a predictor instead of maternal prenatal smoking, no interaction with 5-HTTLPR was observed, providing additional support for a direct effect of prenatal tobacco exposure as opposed to confounding effects.

Subcortical and Cortical Structural Central Nervous System Changes and Attention Processing Deficits in Preschool-Aged Children with Prenatal Methamphetamine and Tobacco Exposure

Objective: To examine the independent contributions of prenatal methamphetamine exposure (PME) and prenatal tobacco exposure (PTE) on brain morphology among a sample of nonalcohol-exposed 3- to 5-year-old children followed prospectively since birth. Study Design: The sample included 20 children with PME (19 with PTE) and 15 comparison children (7 with PTE), matched on race, birth weight, maternal education and type of insurance. Subcortical and cortical volumes and cortical thickness measures were derived through an automated segmentation procedure from T1-weighted structural magnetic resonance images obtained on unsedated children. Attention was assessed using the computerized Conners’ Kiddie Continuous Performance Test Version 5 (K-CPT™ V.5). PME effects on subcortical and cortical brain volumes and cortical thickness were tested by general linear model with type III sum of squares, adjusting for PTE, prenatal marijuana exposure, age at time of scan, gender, handedness, pulse sequence and total intracranial volume (for volumetric outcomes). A similar analysis was done for PTE effects on subcortical and cortical brain volumes and thickness, adjusting for PME and the above covariates. Results: Children with PME had significantly reduced caudate nucleus volumes and cortical thickness increases in perisylvian and orbital-frontal cortices. In contrast, children with PTE showed cortical thinning in perisylvian and lateral occipital cortices and volumetric increases in frontal regions and decreases in anterior cingulate. PME was positively related and caudate volume was inversely related to K-CPT reaction time by inter-stimulus interval, a measure of the ability to adjust to changing task demands, suggesting that children with PME may have subtle attentional deficits mediated by caudate volume reductions. Conclusions: Our results suggest that PME and PTE may have distinct differential cortical effects on the developing central nervous system. Additionally, PME may be associated with subtle deficits in attention mediated by caudate volume reductions.

Effects of prenatal cigarette smoke exposure on neurobehavioral outcomes in 10-year-old children of adolescent mothers

In this prospective study, adolescent mothers (mean age = 16; range = 12–18; 70% African-American) were interviewed about their tobacco use during pregnancy. When their children were ten, mothers reported on their child's behavior and the children completed a neuropsychological battery. We examined the association between prenatal cigarette smoke exposure (PCSE) and offspring neurobehavioral outcomes on data from the 10-year phase ( n = 330). Multivariate regression analyses were conducted to test if PCSE predicted neurobehavioral outcomes, adjusting for demographic characteristics, maternal psychological characteristics, prenatal exposure to other substances, and exposure to environmental tobacco smoke. Independent effects of PCSE were found. Exposed offspring had more delinquent, aggressive, and externalizing behaviors (CBCL). They were more active (Routh, EAS, and SNAP) and impulsive (SNAP) and had more problems with peers (SNAP). On the Stroop test, deficits were observed on the more complex interference task that requires both selective attention and response inhibition. The significant effects of PCSE on neurobehavioral outcomes were found for exposure to as few as 10 cigarettes per day. Most effects were found from first trimester PCSE exposure. These results are consistent with results from an earlier assessment when the children were age 6, demonstrating that the effects of prenatal tobacco exposure can be identified early and are consistent through middle childhood.

Effects of prenatal tobacco, alcohol and marijuana exposure on processing speed, visual–motor coordination, and interhemispheric transfer

Deficits in motor control are often reported in children with prenatal alcohol exposure (PAE). Less is known about the effects of prenatal tobacco exposure (PTE) and prenatal marijuana exposure (PME) on motor coordination, and previous studies have not considered whether PTE, PAE, and PME interact to affect motor control. This study investigated the effects of PTE, PAE, and PME as well as current drug use on speed of processing, visual–motor coordination, and interhemispheric transfer in 16-year-old adolescents. Data were collected as part of the Maternal Health Practices and Child Development Project. Adolescents (age 16, n = 320) participating in a longitudinal study of the effects of prenatal substance exposure on developmental outcomes were evaluated in this study. The computerized Bimanual Coordination Test (BCT) was used to assess each domain of function. Other important variables, such as demographics, home environment, and psychological characteristics of the mother and adolescent were also considered in the analyses. There were significant and independent effects of PTE, PAE, and PME on processing speed and interhemispheric transfer of information. PTE and PME were associated with deficits in visual–motor coordination. There were no interactions between PAE, PTE, and PME. Current tobacco use predicted deficits in speed of processing. Current alcohol and marijuana use by the offspring were not associated with any measures of performance on the BCT.

Addiction in Pregnancy

ABSTRACT Substance abuse in pregnancy has increased over the past three decades in the United States, resulting in approximately 225,000 infants yearly with prenatal exposure to illicit substances. Routine screening and the education of women of child bearing age remain the most important ways to reduce addiction in pregnancy. Legal and illegal substances and their effect on pregnancy discussed in this review include opiates, cocaine, alcohol, tobacco, marijuana, and amphetamines. Most literature regarding opiate abuse is derived from clinical experience with heroin and methadone. Poor obstetric outcomes can be up to six times higher in patients abusing opiates. Neonatal care must be specialized to treat symptoms of withdrawal. Cocaine use in pregnancy can lead to spontaneous abortion, preterm births, placental abruption, and congenital anomalies. Neonatal issues include poor feeding, lethargy, and seizures. Mothers using cocaine require specialized prenatal care and the neonate may require extra supportive care. More than 50% of women in their reproductive years use alcohol. Alcohol is a teratogen and its effects can include spontaneous abortion, growth restriction, birth defects, and mental retardation. Fetal alcohol spectrum disorder can have long-term sequelae for the infant. Tobacco use is high among pregnant women, but this can be a time of great motivation to begin cessation efforts. Long-term effects of prenatal tobacco exposure include spontaneous abortion, ectopic pregnancy, placental insufficiency, low birth weight, fetal growth restriction, preterm delivery, childhood respiratory disease, and behavioral issues. Marijuana use can lead to fetal growth restriction, as well as withdrawal symptoms in the neonate. Lastly, amphetamines can lead to congenital anomalies and other poor obstetric outcomes. Once recognized, a multidisciplinary approach can lead to improved maternal and neonatal outcomes.

Developmental consequences of prenatal tobacco exposure.

This paper reviews results from published, in press, and conference proceedings from 2007 and 2008 that link in-utero tobacco exposure to neurodevelopmental outcomes in exposed offspring. Prenatal tobacco exposure (PTE) affected speech processing, levels of irritability and hypertonicity, attention levels, ability to self-regulate, need to be handled, and response to novelty preference in infants. In early childhood, PTE effects were mostly behavioral outcomes including activity and inattention and externalizing behaviors, including conduct disorder and antisocial behavior. In adolescents, PTE predicted increased attention deficit hyperactivity disorder, modulation of the cerebral cortex and white matter structure, and nicotine addiction. Several studies found moderating effects with PTE and genetic susceptibilities including dopamine transporter, serotonergic synaptic function, and monomine oxidase pathways. Other studies suggested that environmental and genetic factors might be more important than the direct teratological effects of PTE. The majority of studies reviewed were prospective and tobacco exposure was quantified biologically. Most demonstrated a direct association between PTE and neurodevelopmental outcomes. More work is needed to examine multifactorial influences. Effects of PTE on the offspring appear to be moderated by genetic variability, neurobehavioral disinhibition, and sex.

Effects of Prenatal Tobacco Exposure on Gene Expression Profiling in Umbilical Cord Tissue

Maternal smoking doubles the risk of delivering a low birth weight infant. The purpose of this study was to analyze differential gene expression in umbilical cord tissue as a function of maternal smoking, with an emphasis on growth-related genes. We recruited 15 pregnant smokers and 15 women who never smoked during pregnancy to participate. RNA was isolated from umbilical cord tissue collected and snap frozen at the time of delivery. Microarray analysis was performed using the Affymetrix GeneChip Scanner 3000. Six hundred seventy-eight probes corresponding to 545 genes were differentially expressed (i.e. had an intensity ratio > +/- 1.3 and a corrected significance value p < 0.005) in tissue obtained from smokers versus nonsmokers. Genes important for fetal growth, angiogenesis, or development of connective tissue matrix were upregulated among smokers. The most highly upregulated gene was CSH1, a somatomammotropin gene. Two other somatomammotropin genes (CSH2 and CSH-L1) were also upregulated. The most highly downregulated gene was APOBEC3A; other downregulated genes included those that may be important in immune and barrier protection. Validation of the three somatomammotropin genes showed a high correlation between qPCR and microarray expression. We conclude that maternal smoking may be associated with altered gene expression in the offspring.

Smoking during teenage pregnancies: Effects on behavioral problems in offspring

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