Associations between community-level patterns of prenatal alcohol and tobacco exposure on brain structure in a non-clinical sample of 6-year-old children: a South African pilot study.

The current small study utilised prospective data collection of patterns of prenatal alcohol and tobacco exposure (PAE and PTE) to examine associations with structural brain outcomes in 6-year-olds and served as a pilot to determine the value of prospective data describing community-level patterns of PAE and PTE in a non-clinical sample of children. Participants from the Safe Passage Study in pregnancy were approached when their child was ∼6 years old and completed structural brain magnetic resonance imaging to examine with archived PAE and PTE data (n = 51 children-mother dyads). Linear regression was used to conduct whole-brain structural analyses, with false-discovery rate (FDR) correction, to examine: (a) main effects of PAE, PTE and their interaction; and (b) predictive potential of data that reflect patterns of PAE and PTE (e.g. quantity, frequency and timing (QFT)). Associations between PAE, PTE and their interaction with brain structural measures demonstrated unique profiles of cortical and subcortical alterations that were distinct between PAE only, PTE only and their interactive effects. Analyses examining associations between patterns of PAE and PTE (e.g. QFT) were able to significantly detect brain alterations (that survived FDR correction) in this small non-clinical sample of children. These findings support the hypothesis that considering QFT and co-exposures is important for identifying brain alterations following PAE and/or PTE in a small group of young children. Current results demonstrate that teratogenic outcomes on brain structure differ as a function PAE, PTE or their co-exposures, as well as the pattern (QFT) or exposure.

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.

Associations between prenatal alcohol and tobacco exposure on Doppler flow velocity waveforms in pregnancy: a South African study.

BACKGROUND: The negative impact of prenatal alcohol and tobacco exposure (PAE and PTE) on fetal development and birth outcomes are well described, yet pathophysiologic mechanisms are less clear. Our aim was to investigate (1) the associations between quantity, frequency and timing (QFT) of PAE and PTE with blood flow velocities in arteries of the fetal-placental-maternal circulation and (2) the extent to which combined effect of QFT of PAE and/or PTE and Doppler flow velocity waveforms (FWV) predict infant birth weight. METHODS: The Safe Passage Study is a cohort based in urban Cape Town, South Africa. Recruitment occurred between 2007 and 2015. Information on QFT of PAE and PTE was collected prospectively at up to 4 occasions during pregnancy using a modified Timeline Follow-Back approach. Ultrasound examinations consisted of Doppler flow velocity waveforms of the uterine, umbilical (UA) and fetal middle cerebral arteries for the pulsatility index (PI) at 20-24 and 34-38 weeks. Exclusion criteria included: twin pregnancies, stillbirths, participants exposed to other drugs. The sample was divided into three groups (controls, PAE and PTE) and included 1396 maternal-fetal-dyads assessed during the second trimester; 1398 assessed during the third trimester. RESULTS: PTE was associated with higher UA PI values in second and third trimesters (p < 0.001), compared to the PAE and control group. The total amount of cigarettes smoked during pregnancy was positively correlated with UA PI values (r = 0.087, p < 0.001). There was a positive correlation between cigarettes smoked per day in trimester one (r = 0.091, p < 0.01), and trimester two (r = 0.075, p < 0.01) and UA PI (in trimester two), as well as cigarettes smoked per day in trimester two (r = 0.058, p < 0.05) and trimester three (r = 0.069, p < 0.05) and the UA PI in trimester three. Generalized additive models indicated that PAE in trimester two, PTE in trimester one and Doppler FWV in trimester three were significant predictors of birth weight in this sample. CONCLUSION: In our study, PTE in trimesters two and three resulted in increased vascular resistance of the placenta. These findings highlight nuance in associations between PAE, PTE and blood flow velocities in arteries of the fetal-placental-maternal circulation and birth weight, suggesting that quantity and timing are important factors in these relationships.

Prenatal Exposure to Tobacco and Alcohol Alters Development of the Neonatal Auditory System.

Prenatal exposures to alcohol (PAE) and tobacco (PTE) are known to produce adverse neonatal and childhood outcomes including damage to the developing auditory system. Knowledge of the timing, extent, and combinations of these exposures on effects on the developing system is limited. As part of the physiological measurements from the Safe Passage Study, Auditory Brainstem Responses (ABRs) and Transient Otoacoustic Emissions (TEOAEs) were acquired on infants at birth and one-month of age. Research sites were in South Africa and the Northern Plains of the U.S. Prenatal information on alcohol and tobacco exposure was gathered prospectively on mother/infant dyads. Cluster analysis was used to characterize three levels of PAE and three levels of PTE. Repeated-measures ANOVAs were conducted for newborn and one-month-old infants for ABR peak latencies and amplitudes and TEOAE levels and signal-to-noise ratios. Analyses controlled for hours of life at test, gestational age at birth, sex, site, and other exposure. Significant main effects of PTE included reduced newborn ABR latencies from both ears. PTE also resulted in a significant reduction of ABR peak amplitudes elicited in infants at 1-month of age. PAE led to a reduction of TEOAE amplitude for 1-month-old infants but only in the left ear. Results indicate that PAE and PTE lead to early disruption of peripheral, brainstem, and cortical development and neuronal pathways of the auditory system, including the olivocochlear pathway.

Within- and between-family transactions of maternal depression and child engagement in the first 2 years of life: Role of prenatal maternal risk and tobacco use.

BACKGROUND: This study examined transactional associations among maternal depression, maternal sensitivity, and child engagement in the context of a low-income, diverse sample with maternal cigarette smoking during pregnancy (MSDP) as a moderator of these transactions. METHODS: A random-intercept cross-lagged panel model was used to investigate within- and between-family variability from infancy to toddlerhood. The sample included 247 mother-child dyads (47% girls; 51% African-American; 178 MSDP, 69 non-MSDP). Assessments were conducted once during each trimester of pregnancy and at 2, 9, 16, and 24 months of child ages. RESULTS: Between-family associations revealed that children exposed to higher levels of sensitive parenting across time had higher behavioral engagement from infancy to toddlerhood. At the within-family level, increased sensitive parenting at 9 months was predictive of increased child engagement at 16 months which in turn predicted increases in sensitive parenting at 24 months. Increased maternal depression was concurrently associated with lower maternal sensitivity at 2 months and lower child engagement at 16 months. Contrary to hypotheses, changes in maternal depression were not associated to changes in parenting or child engagement. These associations did not vary between prenatally smoking and nonsmoking mothers. However, there was significantly higher stability in maternal depression across time among nonsmoking mothers compared to those in the MSDP group. Additionally, increased maternal depression was related to lower-than-expected child engagement at 9 months only for the nonsmoking group. CONCLUSIONS: Results highlight transactional processes at the within-family level and the importance of timing for parent and child effects on transactional processes.

Does early maternal responsiveness buffer prenatal tobacco exposure effects on young children's behavioral disinhibition?

Children with prenatal tobacco exposure (PTE) exhibit early self-regulatory impairments, reflecting a life-course persistent propensity toward behavioral disinhibition. Previously, we demonstrated the protective role of parental responsiveness for reducing the risk of exposure-related disruptive behavior in adolescence. Here, we expanded this line of inquiry, examining whether responsiveness moderates the relation of PTE to a broader set of behavioral disinhibition features in early childhood and testing alternative diathesis-stress versus differential susceptibility explanatory models. PTE was assessed prospectively using interviews and bioassays in the Midwestern Infant Development Study (MIDS). Mother-child dyads (N = 276) were re-assessed at approximately 5 years of age in a preschool follow-up. We quantified maternal responsiveness and child behavioral disinhibition using a combination of directly observed activities in the lab and developmentally sensitive questionnaires. Results supported a diathesis-stress pattern. Children with PTE and less responsive mothers showed increased disruptive behavior and lower effortful control compared with children without PTE. In contrast, exposed children with more responsive mothers had self-regulatory profiles similar to their non-exposed peers. We did not observe sex differences. Findings provide greater specification of the protective role of maternal responsiveness for self-regulation in children with PTE and help clarify mechanisms that may underscore trajectories of exposure-related behavioral disinhibition.

Prenatal exposure to tobacco and marijuana and child autonomic regulation and reactivity: An analysis of indirect pathways via maternal psychopathology and parenting.

We examined a conceptual model for the associations of prenatal exposure to tobacco (PTE) and marijuana with child reactivity/regulation at 16 months of age. We hypothesized that PTE would be associated with autonomic reactivity and regulation that these associations would be indirect via maternal anger/hostility, depression/stress, or harsh parenting assessed at 2 months and that these effects would be most pronounced among children exposed to both tobacco and marijuana (PTME). Participants were 247 dyads (81 PTE, 97 PTME, and 69 nonexposed) who were followed up at 2 (N = 247) and 16 months (N = 238) of child age. Results from model testing indicated an indirect association between PTME and autonomic functioning during the second year of life, which was mediated by harsh parenting during caregiver-infant interactions. This study fills an important gap in the literature on PTE, PTME, and autonomic regulation during the toddler years, highlighting the role of maternal parenting as important intervening variables.

Prenatal tobacco exposure and ADHD symptoms at pre-school age: the Hokkaido Study on Environment and Children's Health.

BACKGROUND: There have been inconsistent findings reported on maternal passive smoking during pregnancy and child risk of ADHD. In this study, ADHD symptoms at pre-school age children in association with prenatal passive and active tobacco smoke exposure determined by maternal plasma cotinine levels in the third trimester were investigated. METHODS: This was a follow-up study of the birth cohort: the Hokkaido Study on Environment and Children's Health. Children whose parents answered Strengths and Difficulties Questionnaire (SDQ) to identify child ADHD symptoms (hyperactivity/inattention and conduct problems) and total difficulties at age 5 years with available maternal plasma cotinine level at the third trimester were included (n = 3216). Cotinine levels were categorized into 4 groups; ≦ 0.21 ng/ml (non-smoker), 0.22-0.51 ng/ml (low-passive smoker), 0.52-11.48 ng/ml (high-passive smoker), and ≧ 11.49 ng/ml (active smoker). RESULTS: Maternal cotinine levels of active smokers were significantly associated with an increased risk of total difficulties (OR = 1.67) and maternal low- and high-passive smoking also increased the risk (OR = 1.11, 1.25, respectively) without statistical significance. Similarly, maternal cotinine levels of active smokers were associated with an increased risk of hyperactivity/inattention (OR = 1.49). Maternal low- and high-passive smoking and active smoking increased the risk of hyperactivity/inattention (OR = 1.45, 1.43, and OR = 1.59, respectively) only in boys. CONCLUSION: Our findings suggested that maternal active smoking during pregnancy may contribute to the increased risk of child total difficulties and hyperactivity/inattention at pre-school age. Pregnant women should be encouraged to quit smoking and avoid exposure to tobacco smoke.

Maternal smoking during pregnancy and academic achievement of offspring over time: A registry data-based cohort study.

Few studies have assessed the cumulative impact of maternal smoking during pregnancy (MSDP) on scholastic outcomes over time. We examined the relations between MSDP and academic achievement in the 4th, 7th and 10th grades using registry data collected at birth, during the neonatal period, and at each grade level from the 2000, LIFECOURSE study birth cohort in Reykjavik, Iceland (N = 1151, girls = 49.3%). Latent growth modeling showed that MSDP influenced Icelandic achievement scores, standardized to a range from 0 to 60, at baseline (ß = -0.04), and over time (ß = -0.05). Likewise, MSDP was negatively associated with standardized mathematics scores at baseline (ß = -0.09) and continued to exert a negative impact on mathematics scores over time (ß = -0.08) after controlling for gender, income, cohabitation, and baseline mathematics and Icelandic achievement scores. Results provide evidence of the persistent negative impact of MSDP on academic achievement in offspring. Findings support the proposition that children whose mothers smoke during the first trimester of pregnancy are, on average, at greater risk for poor scholastic outcomes over time than children whose mothers do not smoke during their first trimester. To our knowledge, this is the first study using a longitudinal cohort design to assess whether the impacts of maternal smoking during pregnancy may persist over time. This study contributes to the current state of knowledge by providing an assessment that focuses on the impact of smoking during pregnancy on academic achievement from childhood into early adolescence.

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

Objective: 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.

Prospective associations between prenatal adversities and borderline personality disorder at 11-12 years.

BACKGROUND: The aetiological pathways to borderline personality disorder (BPD) remain only partly elucidated. Retrospective research indicates that prenatal adversity may be an important early risk factor in the development of BPD. This requires corroboration with prospective longitudinal studies. METHOD: A community sample of 6050 mothers and their children (born between April 1991 and December 1992) were assessed. Maternal anxiety and depression and maternal alcohol and tobacco consumption were assessed during pregnancy (18 and 32 weeks gestation). Postnatal risks, including maladaptive parenting (suboptimal parenting and parent conflict), family adversity, maternal anxiety and depression and maternal alcohol and tobacco consumption, were assessed during early childhood. Internalizing and externalizing symptoms were assessed in late childhood. Trained psychologists interviewed children in late childhood to ascertain the presence of BPD (at least five probable/definite symptoms). RESULTS: In unadjusted analyses, all prenatal risk factors (i.e., maternal alcohol and tobacco consumption and maternal anxiety and depression) were significantly associated with BPD. Following adjustment for sex, birthweight and postnatal exposure to anxiety and depression respectively, maladaptive parenting, family adversity and child's internalizing and externalizing symptoms, prenatal anxiety at 18 weeks gestation [odds ratio (OR) 1.57, 95% confidence interval (CI) 1.18-2.09] and depression at 18 weeks (OR 1.59, 95% CI 1.08-2.32) and 32 weeks (OR 1.57, 95% CI 1.14-2.18) gestation remained significantly associated with BPD. CONCLUSIONS: This study provides prospective evidence of associations between prenatal adversities and BPD at 11-12 years. Prenatal anxiety and depression were independently associated with BPD, suggesting that they may exert direct effects on BPD during the prenatal period. This highlights the importance of programmes to reduce maternal stress during pregnancy.

Prenatal tobacco exposure and infant stress reactivity: role of child sex and maternal behavior.

This study examined the association between prenatal tobacco exposure (PTE) and infant cortisol reactivity at 9 months of infant age. Child sex and maternal parenting behavior were hypothesized moderators. The sample included 217 (148 tobacco-exposed, 69 non-exposed) mother-child dyads. Data used were obtained from pregnancy assessments, mother-infant feeding interactions at 2 months, and salivary cortisol at four time points in response to frustration at 9 months. Results indicated a significant association between PTE and infant cortisol that was moderated by infant sex and maternal intrusiveness. That is, PTE boys had lower cortisol than control boys, but there was no association between PTE and cortisol among girls. There was a significant association between PTE and cortisol among infants of intrusive mothers, but not among infants with non-intrusive mothers. Thus, PTE was associated with cortisol hypo-reactivity such that boys and non-exposed infants experiencing high maternal intrusiveness were at greater risk.

Association of prenatal substance exposure and the development of the amygdala, hippocampus, and parahippocampus.

CONTEXT: Prenatal substance exposure (PSE) can lead to various harmful outcomes for the developing fetus and is linked to many emotional, behavioral, and cognitive difficulties later in life. Therefore, examination of the relationship between the development of associated brain structures and PSE is important for the development of more specific or new preventative methods. OBJECTIVES: Our study's primary objective was to examine the relationship between the physical development of the amygdala, hippocampus, and parahippocampus following prenatal alcohol, tobacco, and prescription opioid exposure. METHODS: We conducted a cross-sectional analysis of the Adolescent Brain and Cognitive Development (ABCD) Study, a longitudinal neuroimaging study that measures brain morphometry from childhood throughout adolescence. Data were collected from approximately 12,000 children (ages 9 and 10) and parents across 22 sites within the United States. Prenatal opioid, tobacco, and alcohol use was determined through parent self-report of use during pregnancy. We extracted variables assessing the volumetric size (mm3) of the amygdala, hippocampus, and parahippocampal gyrus as well as brain volume, poverty level, age, sex, and race/ethnicity for controls within our adjusted models. We reported sociodemographic characteristics of the sample overall and by children who had PSE. We calculated and reported the means of each of the specific brain regions by substance exposure. Finally, we constructed multivariable regression models to measure the associations between different PSE and the demographic characteristics, total brain volume, and volume of each brain structure. RESULTS: Among the total sample, 24.6% had prenatal alcohol exposure, 13.6% had prenatal tobacco exposure, and 1.2% had prenatal opioid exposure. On average, those with prenatal tobacco exposure were found to have a statistically significant smaller parahippocampus. CONCLUSIONS: We found a significant association between prenatal tobacco exposure and smaller parahippocampal volume, which may have profound impacts on the livelihood of individuals including motor delays, poor cognitive and behavioral outcomes, and long-term health consequences. Given the cumulative neurodevelopmental effects associated with PSE, we recommend that healthcare providers increase screening rates, detection, and referrals for cessation. Additionally, we recommend that medical associations lobby policymakers to address upstream barriers to the effective identification of at-risk pregnant individuals, specifically, eliminating or significantly reducing punitive legal consequences stemming from state laws concerning prenatal substance use.

Prenatal Tobacco Exposure and Behavioral Disorders in Children and Adolescents: Systematic Review and Meta-Analysis.

Prenatal tobacco exposure has been implicated in increased risk of the development of behavioral disorders in children and adolescents. The purpose of the current study was to systematically examine the association between prenatal tobacco exposure and diagnoses of Attention Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, and Conduct Disorder in childhood and adolescence. We searched Medline, Psychinfo, ERIC, Proquest, Academic Search Complete, PsychArticles, Psychology and Behavioral Sciences Collection, Web of Science, CINAHL Plus, and Google Scholar databases through October 2022. The authors screened studies and extracted data independently in duplicate. Ten clinical studies examining diagnoses of Attention Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, and Conduct Disorder between the ages of 4 and 18 years old were included. There was insufficient evidence to synthesize outcomes related to Conduct Disorder and Oppositional Defiant Disorder. The meta-analysis found a significant effect of prenatal tobacco exposure in increasing the likelihood of an Attention Deficit/Hyperactivity Disorder diagnosis in childhood and adolescence. Implications for future research are discussed.

Prenatal tobacco and alcohol exposure, white matter microstructure, and early language skills in toddlers from a South African birth cohort.

Introduction: Tobacco and alcohol are the two most common substances used during pregnancy, and both can disrupt neurodevelopment, resulting in cognitive and behavioral deficits including language difficulties. Previous studies show that children with prenatal substance exposure exhibit microstructural alterations in major white matter pathways, though few studies have investigated the impact of prenatal substance exposure on white matter microstructure and language skills during the toddler years. Methods: In this study, 93 children (34 exposed to alcohol and/or tobacco) aged 23 years from the Drakenstein Child Health Study, South Africa, completed Expressive and Receptive Communication assessments from the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and underwent diffusion MRI scans. Diffusion images were preprocessed, and 11 major white matter tracts were isolated. Fractional anisotropy (FA) and mean diffusivity (MD) were extracted for each white matter tract. Linear regression was used to examine differences between the tobacco/alcohol exposed group and unexposed controls for FA, MD, and language scores, as well as relationships between brain metrics and language. There were no significant group differences in language scores or FA. Results: Children with alcohol or tobacco exposure had lower average MD in the splenium of the corpus callosum compared to unexposed controls. Significant interactions between prenatal substance exposure and language scores were seen in 7 tracts but did not survive multiple comparisons correction. Discussion: Our findings show that prenatal alcohol and/or tobacco exposure appear to alter the relationship between white matter microstructure and early language skills in this population of toddlers, potentially laying the basis of language deficits observed later in older children with prenatal substance exposure, which may have implications for learning and interventions.

Clinical and biochemical effects of environmental tobacco smoking on pregnancy outcome.

The effects of environmental tobacco smoke (ETS) are less studied especially on neonates. This study evaluates the clinical and biochemical effects in neonates exposed to ETS during pregnancy. Two hundred pregnant women asked to complete the questioners about their ETS. Ninety from them were enrolled in biochemical assays as two groups according to ETS. The cotinine level determined in saliva and serum of mothers to confirm their tobacco exposure. The routine tracheal suction from the fetus was used to determine the level of neuron specific enolase (NSE), soluble E-cadherin, sApo-1/Fas, nitric oxide (NO) and cotinine. In clinical assessment, the percent of full term babies in non-exposed group (72 %) are higher compared to exposed group (67 %). Apgar score at the first min, admission to intensive care unit (ICU) and morbidity during the first month shows statistical significance increase in exposed compared to non-exposed group (p = 0.03, 0.05, 0.01, respectively). The new born weight in exposed group significantly decreased compared to non-exposed group (2,850 g ± 3.74 vs 2,967.67 g ± 3.34; p = 0.02). In biochemical assessment, NSE and sE-cadherin significantly increased, while NO significantly decreased (p = 0.000) in exposed compared to non-exposed group. There is a positive correlation between level of cotinine and both NSE, sE-cadherin (r = 0.7, 0.9; p = 0.000, 0.006, respectively). To our knowledge, this is the first study link between prenatal tobacco exposure (PTE) and biochemical parameters measured in tracheal suction. PTE will lead to decrease in birth weight most probably by decreasing NO, sFas, and increasing sE-cadherin. While, increased morbidity of neonates in the exposed group could be attributed to cessation of breast feeding and its complication and increased NSE in the studied markers.

Executive functioning, behavioural, emotional, and cognitive difficulties in school-aged children prenatally exposed to methadone.

Aim: The aim of this study was to examine executive function and emotional and behavioural difficulties of children aged between 8 and 10 years who had been prenatally exposed to methadone, compared to non-exposed peers. Methods: Prospective study: third follow-up of an original cohort of 153 children born to methadone-maintained opioid-dependent mothers 2008-2010: previous investigations were at 1-3 days and at 6-7 months of age. Carers completed the Strength and Difficulties Questionnaire (SDQ) and the Behaviour Rating Inventory of Executive Function, Second Edition (BRIEF®2). Results were compared between exposed and non-exposed groups. Results: Carers of 33 of 144 traceable children completed the measures. SDQ responses showed no group differences on subscales of emotional symptoms, conduct problems, or peer relationship problems. A marginally higher proportion of exposed children had a high or very high hyperactivity subscale score. Exposed children scored significantly higher on BRIEF®2 behavioural, emotional, and cognitive regulation indices, and on the global executive composite. After controlling for potentially confounding higher reported maternal tobacco use in the exposed group via regression modelling, the effect of methadone exposure reduced. Interpretation: This study supports evidence that methadone exposure in utero is associated with adverse neurodevelopmental outcomes in childhood. Challenges in studying this population include difficulties with long-term follow-up and controlling for potentially confounding factors. Further investigation of the safety of methadone and other opioids in pregnancy must include consideration of maternal tobacco use.

Contextualizing the impact of prenatal alcohol and tobacco exposure on neurodevelopment in a South African birth cohort: an analysis from the socioecological perspective.

Background: Alcohol and tobacco are known teratogens. Historically, more severe prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) have been examined as the principal predictor of neurodevelopmental alterations, with little incorporation of lower doses or ecological contextual factors that can also impact neurodevelopment, such as socioeconomic resources (SER) or adverse childhood experiences (ACEs). Here, a novel analytical approach informed by a socio-ecological perspective was used to examine the associations between SER, PAE and/or PTE, and ACEs, and their effects on neurodevelopment. Methods: N = 313 mother-child dyads were recruited from a prospective birth cohort with maternal report of PAE and PTE, and cross-sectional structural brain neuroimaging of child acquired via 3T scanner at ages 8-11 years. In utero SER was measured by maternal education, household income, and home utility availability. The child's ACEs were measured by self-report assisted by the researcher. PAE was grouped into early exposure (<12 weeks), continued exposure (>=12 weeks), and no exposure controls. PTE was grouped into exposed and non-exposed controls. Results: Greater access to SER during pregnancy was associated with fewer ACEs (maternal education: ß = -0.293,p = 0.01; phone access: ß = -0.968,p = 0.05). PTE partially mediated the association between SER and ACEs, where greater SER reduced the likelihood of PTE, which was positively associated with ACEs (ß = 1.110,p = 0.01). SER was associated with alterations in superior frontal (ß = -1336.036, q = 0.046), lateral orbitofrontal (ß = -513.865, q = 0.046), caudal anterior cingulate volumes (ß = -222.982, q = 0.046), with access to phone negatively associated with all three brain volumes. Access to water was positively associated with superior frontal volume (ß=1569.527, q = 0.013). PTE was associated with smaller volumes of lateral orbitofrontal (ß = -331.000, q = 0.033) and nucleus accumbens regions (ß = -34.800, q = 0.033). Conclusion: Research on neurodevelopment following community-levels of PAE and PTE should more regularly consider the ecological context to accelerate understanding of teratogenic outcomes. Further research is needed to replicate this novel conceptual approach with varying PAE and PTE patterns, to disentangle the interplay between dose, community-level and individual-level risk factors on neurodevelopment.

Estimating causal and time-varying effects of maternal smoking on youth smoking.

INTRODUCTION: Maternal smoking is a well-known risk factor for youth smoking, yet whether this relationship is causal remains unresolved. This study utilizes propensity score methods for causal inference to robustly account for shared risk factors between maternal and offspring smoking. METHODS: An 8-year longitudinal cohort of 900 adolescents in the Chicago area were followed starting from approximately age 15.6. The effects of maternal lifetime smoking (MLS) and prenatal tobacco exposure (PTE) (among participants reporting MLS) on offspring's past 30-day smoking, daily smoking status and smoking frequency were examined using logistic regression and Poisson regression after nearest-neighbor propensity matching. Age dependency of this relationship was then examined across the age range of 15-25 using time-varying effect modeling. RESULTS: Propensity matching yielded 438 and 132 pairs for MLS and PTE study samples, respectively. MLS demonstrated significant associations with past 30-day smoking (RR 1.09; 95% CI 1.04-1.14), daily smoking (RR 1.08; 95% CI 1.05-1.12), and smoking frequency of offspring (RR 1.32; 95% CI 1.15-1.52), with stable effects across age. Among participants reporting MLS, having PTE showed significant additional effects on daily smoking (RR 1.09; 95% CI 1.02-1.17) and age-dependency that showed significance during young adulthood but not adolescence. CONCLUSION: The relationship between maternal and offspring smoking was not fully accounted for by shared risk factors, suggesting possible causation with PTE having a delayed effect across age. Targeted prevention efforts should be made on maternal smoking-exposed adolescents to mitigate their risks of developing heavy smoking habits in adulthood.

Central white matter integrity alterations in 2-3-year-old children following prenatal alcohol exposure.

BACKGROUND: Prenatal alcohol exposure (PAE) remains a potentially preventable, but pervasive risk factor to neurodevelopment. Yet, evidence is lacking on the impact of alcohol on brain development in toddlers. This study aimed to investigate the impact of PAE on brain white matter integrity in 2-3-year-old children. METHODS: Children (n = 83, 30-37 months old) of the Drakenstein Child Health Study birth cohort, underwent diffusion MRI on a 3 T Siemens scanner during natural sleep. Parameters were extracted in children with PAE (n = 25, 56 % boys) and unexposed controls (n = 58, 62 % boys) using Tract-based Spatial Statistics, and compared by group. The contribution of maternal tobacco smoking to white matter differences was also explored. RESULTS: Children with PAE had altered fractional anisotropy, radial diffusivity and axial diffusivity in brain stem, limbic and association tracts compared to unexposed controls. Notably lower fractional anisotropy was found in the uncinate fasciculus, and lower mean and radial diffusivity were found in the fornix stria terminalis and corticospinal tract (FDR corrected p < 0.05). There was a significant interaction effect of PAE and prenatal tobacco exposure which lowered mean, radial and axial diffusivity in the corticospinal tract significantly in the PAE group but not controls. CONCLUSION: Widespread altered white matter microstructural integrity at 2-3 years of age is consistent with findings in neonates in the same and other cohorts, indicating persistence of effects of PAE through early life. Findings also highlight that prenatal tobacco exposure impacts the association of PAE on white matter alterations, amplifying effects in tracts underlying motor function.