Prenatal Tobacco Exposure Research Articles

The Influence of DNA Repair Genes and Prenatal Tobacco Exposure on Risk of Childhood Acute Lymphoblastic Leukemia-A Gene-Environment Interaction Study.

Acute lymphoblastic leukemia (ALL) is the most common type of cancer among children. Tobacco exposure during gestation has been investigated as a potential risk factor, but its role remains undefined. Given tobacco's toxicological profile as a DNA damaging agent, we examined the impact of DNA repair gene variability as a source of vulnerability to tobacco exposure risk for ALL. Leveraging demographic and genotype data from two large California-based ALL epidemiology studies, we used logistic regression, MinimumP (MinP) statistical method and permutation tests to examine interactions between DNA repair genes and prenatal tobacco exposure. We found statistically significant interactions between prenatal tobacco exposure and DNA repair genes RECQL (minP= 1.00x 10-4, FDR-P value = 1.86x 10-2) and TDG (minP= 1.00x 10-4, FDR-P value = 1.86 x 10-2) regarding childhood ALL risk. Notable interactions in the homologous recombination pathway were observed among Latino children, while non-Latino White children displayed significant interactions in the base excision repair and nucleotide excision repair pathways. Our study highlights the significance of DNA repair genes and pathways when evaluating environmental exposure to tobacco smoke, suggesting that genetic variability within these pathways could impact vulnerability in the development of childhood ALL. This study highlights the significant impact of genetic variation interacting with prenatal tobacco exposure on ALL risk. Further research is needed to understand these interactions and their implications for ALL etiology. Expanding studies to other gene-environment interactions will aid in developing targeted prevention, diagnosis, and treatment strategies for pediatric oncology.

Prenatal risk factors for child executive function at 3–5 years of age: the roles of maternal mood, substance use, and socioeconomic adversity in a prospective cohort study

BackgroundA growing body of literature links prenatal mood and substance use to children's cognitive and behavioral development. The relative contribution of these risk factors on children's executive function (EF) in the context of socioeconomic adversities needs further evaluation. To address this gap, we investigated the role of prenatal maternal anxiety and depression on childhood EF, specifically inhibitory control and working memory, within the context of socioeconomic adversities and prenatal substance use. We hypothesized that higher maternal mood symptoms, higher persistent prenatal drinking and smoking, and lower socioeconomic status would be associated with lower EF skills during early childhood.MethodsWe used data from 334 mother–child dyads followed prospectively through pregnancy and the offspring’s childhood. Prenatal maternal depression and anxiety were assessed via standardized questionnaires. Prenatal alcohol and tobacco consumption were assessed via a timeline follow-back interview. The EF touch battery assessed child inhibitory control and working memory at 3–5 years of age (4.76 ± 0.58 years, 171 females). Separate linear regression models were used to estimate the association of prenatal tobacco, alcohol, anxiety, and depression exposure with our two components of child EF, inhibitory control and working memory, while adjusting for gestational age, sex, and age at assessment. The following variables were also included as covariates: maternal educational achievement, employment status, parity, and household crowding index.ResultsChildren of mothers with high trait anxiety scores had reduced inhibitory control compared to children of mothers without trait anxiety or depression (β = -0.12, 95% CI:-0.22,-0.01). Children of mothers in the moderate to high continuous smoking group showed lower inhibitory control (β = − 0.19, 95% CI:-0.38,-0.01) compared to children of mothers in the none smoking group. Additionally, lower maternal education and higher household crowding were each associated with reduced inhibitory control. We found no significant association between prenatal maternal depression, anxiety, or socioeconomic factors with working memory.ConclusionsThese results underscore the need for comprehensive context-specific intervention packages, including mental health support for women to promote healthy inhibitory control development in children.

High Prevalence of Tobacco Consumption among Pregnant Women in a Southern European City (Seville): A Challenge for the Health System.

The prevalence of prenatal tobacco exposure remains high in many countries, particularly in southern Europe. The aims of this study were to estimate the prevalence of smoking among pregnant women in a southern Spanish city (Seville) and to identify the associated sociodemographic and obstetric characteristics. In a descriptive, cross-sectional study, a random sample of pregnant women who were scheduled to undergo a morphology scan at their public referral hospital in their 20th week of gestation were interviewed in person. At the start of pregnancy, 38.2% of the pregnant women were smokers. In the twentieth week, 19.1% continued to smoke, and the same percentage had quit. The prevalence of smoking in pregnant women was higher among those with a low level of education (60% among pregnant women with no studies and 30.4% in those with primary education) and among those who had had abortions (38.5%). Pregnant smokers with obesity were the least likely to have given up smoking during pregnancy. Women with a lower educational level should be a prime target for cross-sectoral interventions aimed at preventing prenatal tobacco exposure. Implementation of support measures for providing effective clinical advice in preconception and prenatal care regarding healthy lifestyles is particularly needed.

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

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. 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. 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. 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.

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.

Longitudinal mapping of cortical change during early adolescence associated with prenatal tobacco and/or alcohol exposure in the Adolescent Brain Cognitive Development Study.

The effects of prenatal alcohol (PAE) and tobacco exposure (PTE) on adolescent neuroanatomical development are typically evaluated cross-sectionally. It is unclear if observed effects persist throughout life or reflect different developmental trajectories. To determine how PAE and PTE are associated with cortical structure and development across two timepoints in early adolescence. Observational, longitudinal analyses of data within the Adolescent Brain Cognitive Development Study. 21 study sites in the United States. 5,417 youth participants, aged ~9-12 years old. PAE and PTE based on caregiver (self) reports of alcohol/tobacco use during pregnancy, before and after pregnancy recognition. Cortical thickness (mm) and cortical surface area (mm2) measured approximately 2 years apart in early adolescence, across 68 bilateral cortical regions. At baseline data collection, youth participants were ~9.9 years old (SD=0.6). At the second neuroimaging appointment, youth participants were ~11.9 years old (SD=0.6). When modelling cortical thickness, we controlled for individuals' whole-brain volume; when modelling cortical surface area, individuals' total surface area. Cortical thickness generally declined with age. Cortical surface area either expanded or contracted with age, depending on region. PAE had minimal effects on cortical structure (main effects) and development (PAE×Age interactions). PTE had robust effects on cortical thickness and was associated with faster rates of cortical thinning in several regions within the frontal lobe. Post hoc analyses on (1) the effects of PTE for those who continued tobacco use after pregnancy recognition and (2) the effects of PTE in those who did not also use alcohol revealed weaker effects. PTE had robust effects on neuroanatomical structure and longitudinal development, particularly cortical thickness. Analyzing developmental cortical trajectories informs how PTE and/or PAE not only affects cortical structure but how it develops long after those prenatal exposures occurred. Future analyses involving cotinine biomarkers of PTE would enhance the temporal resolution of the ABCD Study®'s PTE-related queries of tobacco use before and after learning of the pregnancy.

Prenatal Cannabis and Tobacco Co-Exposure and Its Association with Behavioural Outcomes in Middle Childhood: Co-exposition prénatale au cannabis et au tabac et son association avec les résultats comportementaux au cours de l'enfance intermédiaire.

Cannabis legalization has triggered an increase in prenatal cannabis use. Given that tobacco is commonly co-used with cannabis, determining outcomes associated with prenatal cannabis and tobacco co-exposure is crucial. While literature exists regarding the individual effects of prenatal cannabis and tobacco exposure on childhood behaviour, there is a gap regarding their combined use, which may have interactive effects. Therefore, we investigated whether prenatal cannabis and tobacco co-exposure was associated with greater externalizing and internalizing problems in middle childhood compared to prenatal exposure to either substance alone or no exposure. Baseline data from the Adolescent Brain Cognitive Development (ABCD) Study (collected in children ages 9-11) were used to explore differences in externalizing and internalizing scores derived from the Childhood Behavior Checklist across four groups: children with prenatal cannabis and tobacco co-exposure (CT, n = 290), children with prenatal cannabis-only exposure (CAN, n = 225), children with prenatal tobacco-only exposure (TOB, n = 966), and unexposed children (CTL, n = 8,311). We also examined if the daily quantity of tobacco exposure modulated the effect of cannabis exposure on outcomes. Adjusting for covariates, a 2 × 2 ANCOVA revealed significant main effects for prenatal cannabis (p = 0.03) and tobacco exposure (p < 0.001), and a significant interaction effect on externalizing scores (p = 0.032); no significant main effects or interactions were found for internalizing scores. However, interactions between daily quantity of cannabis and tobacco exposure significantly predicted both externalizing and internalizing scores (p < 0.01). These findings indicate that co-exposure is associated with greater externalizing problems than exposure to either substance alone, which did not differ from each other. Further, greater tobacco exposure may amplify the negative effect of cannabis exposure on both externalizing and internalizing behaviours in children. These findings underscore the need for interventions that target cannabis and tobacco co-use in pregnant women to circumvent their adverse impact on middle childhood behaviour.

Spline linear mixed‐effects models for causal mediation analysis with longitudinal data

SummaryOften, causal mediation analysis is of interest when both the mediator and the final outcome are repeatedly measured, but limited work has been done for this situation (as opposed to where only the mediator is repeatedly measured). Available methods are primarily based on parametric models and tend to be sensitive to model assumptions. This article presents semiparametric, continuous‐time models to provide a flexible and robust approach to causal mediation analysis for longitudinal data, which allows these data to be unbalanced or irregular. Specifically, the method uses spline linear mixed‐effects models for the mediator and for the final outcome, with a two‐step approach to model‐fitting in which a predicted mediator is used as a covariate in the final outcome model. The models allow flexible functions for both the mean and individual response functions for each outcome. We derive estimated natural direct and indirect effects as a function of time using an extended mediation formula and sequential ignorability assumption. In simulation studies, we compare properties of estimated direct and indirect effects, and a delta method estimate of the standard error of the latter, under alternative approaches for predicting the mediator. The approach is illustrated using harmonised data from two cohort studies to examine attention as a mediator of the effect of prenatal tobacco exposure on externalising behaviour in children.

Perinatal risk factors and subclinical hypomania: A prospective community study

BackgroundPerinatal risk factors are implicated in the development of psychopathology, but their role in bipolar disorder (BD) and hypomania is unclear. Using data from a prospective community cohort, this is the first study to investigate the association between a range of perinatal risk factors, hypomanic symptoms, and ‘high-risk’ for BD in the general population. MethodsParent report of perinatal events were available for 26,040 eighteen-month-olds from the Twins Early Development Study. Subsequent self-report hypomania was measured at ages 16 (Hypomania Checklist-16; N = 2943) and 26 (Mood Disorders Questionnaire; N = 7748). Participants were categorised as ‘high-risk’ for BD using established classifications. Linear and logistic regressions were conducted within a generalised estimating equations framework to account for relatedness in the sample. ResultsPrenatal alcohol exposure (β = 0.08, SE = 0.04, p = .0002) and number of alcohol units consumed (β = 0.09, SE = 0.02, p < .0001) were associated with hypomanic symptoms at age 16, and number of alcohol units (OR = 1.13, 95 % CI:1.06–1.21, p = .0003) and maternal stress (OR = 1.68, 95 % CI:1.21–2.34, p = .002) were associated with ‘high-risk’ for BD age 16. Prenatal tobacco exposure (β = 0.10, SE = 0.04, p < .0001) and number of cigarettes smoked (β = 0.10, SE = 0.01, p < .0001) were associated with hypomanic symptoms and ‘high-risk’ for BD at age 26, although these result were attenuated controlling for parental psychiatric history. LimitationsFamilial confounding could not be fully adjusted for. Rater reports include some biases. ConclusionsThese findings show perinatal risk factors to be associated with subclinical hypomania and ‘high-risk’ for BD. Future work should explore the mechanisms underlying these longitudinal associations, which could shed light on prevention and intervention efforts.

Prenatal tobacco and tobacco-cannabis co-exposure: Relationship with attention and memory in middle childhood

We examined associations between prenatal tobacco exposure (with and without cannabis exposure) and children's performance on laboratory measures of sustained attention, attentional set shifting, and working memory in middle childhood (9–12 years of child age). Participants were recruited in the first trimester of pregnancy and oversampled for prenatal tobacco exposure; with a smaller sample (n = 133; n = 34 non-substance exposed, n = 37 exposed to tobacco only, n = 62 co-exposed) invited (oversampled for co-exposure) to participate in the middle-childhood assessment (M age = 10.6, SD = 0.77; 68% Black, 20% Hispanic). Results for sustained attention indicated lower attention (percent hits) at the first epoch for tobacco only exposed compared to non-exposed and co-exposed; a trend (p = .07) towards increases in impulsive responding across time (a total of 8 epochs) for tobacco exposed (with and without cannabis) compared to non-exposed children; and a significant association between higher number of cigarettes in the first trimester and greater increases in impulsive responding across epochs. However, children prenatally exposed to tobacco (with and without cannabis) demonstrated greater short-term memory compared to children not prenatally exposed, and this difference was driven by higher scores for children prenatally co-exposed to tobacco and cannabis compared to those who were non-exposed. Overall, results suggest that prenatal tobacco exposure, especially in the first trimester, may increase risk for impulsive responding on tasks requiring sustained attention, and that co-use of cannabis did not exacerbate these associations. The higher short-term memory scores among children who were co-exposed compared to non-exposed are perplexing and need replication, particularly in studies with larger sample sizes and samples exposed only to cannabis to examine this more closely.

Early-life tobacco exposure is causally implicated in aberrant RAG-mediated recombination in childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, yet few environmental risk factors have been identified. We previously found an association between early-life tobacco smoke exposure and frequency of somatic deletions of 8 leukemia driver genes among childhood ALL patients in the California Childhood Leukemia Study. To expand analysis genome-wide and examine potential mechanisms, we conducted tumor whole-genome sequencing in 35 ALL patients, including 18 with high prenatal tobacco exposure and 17 with low exposure as determined by established epigenetic biomarkers. High tobacco exposure patients had significantly more structural variants (P < .001) and deletions (P = .001) genome-wide than low exposure patients. Investigation of off-target RAG recombination revealed that 41% of deletions in the high tobacco exposure patients were putatively RAG-mediated (full RAG motif identified at one or both breakpoints) compared with only 21% in the low exposure group (P = .001). In a multilevel model, deletions in high tobacco exposure patients were 2.44-fold (95% CI:1.13-5.38) more likely to be putatively RAG-mediated than deletions in low exposure patients. No point mutational signatures were associated with prenatal tobacco exposure. Our findings suggest that early-life tobacco smoke exposure may promote leukemogenesis by driving development of somatic deletions in pre-leukemic lymphocytes via off-target RAG recombination.

Identifying Risk Factors for Attention-Deficit/Hyperactivity Disorder (ADHD): a Public Health Concern and Opportunity.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders with significant individual and societal negative impacts of the disorder continuing into adulthood (Danielson et al. inJournal of Clinical Child and Adolescent Psychology, in press; Landes and London in Journal of Attention Disorders 25:3-13, 2021). Genetic and environmental risk (e.g., modifiable exposures such as prenatal tobacco exposure and child maltreatment) for ADHD is likely multifactorial (Faraone et al. in Neuroscience & Biobehavioral Reviews 128:789-818, 2021). However, the evidence for potentially modifiable contextual risks is spread across studies with different methodologies and ADHD criteria limiting understanding of the relationship between early risk factors and later childhood ADHD. Using common methodology across six meta-analyses (Bitsko et al. in Prevention Science, 2022; Claussen et al. in Prevention Science 1-23,2022; Dimitrov et al. in Prevention Science, 2023; Maher et al. in Prevention Science, 2023; Robinson, Bitskoet al. in Prevention Science, 2022; So et al. in Prevention Science, 2022) examining 59 risk factors for childhood ADHD, the papers in this special issue use a public health approach to address prior gaps in the literature. This introductory paper provides examples of comprehensive public health approaches focusing on policy, systems, and environmental changes across socio-ecological contexts to improve health and wellbeing through prevention, early intervention, and support across development using findings from these meta-analyses. Together, the findings from these studies and a commentary by an author independent from the risk studies have the potential to minimize risk conditions, prioritize prevention efforts, and improve the long-term health and wellbeing of children and adults with ADHD.

Mediating Effect of Tobacco Dependence on the Association Between Maternal Smoking During Pregnancy and Chronic Obstructive Pulmonary Disease: Case-Control Study.

Maternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. This study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). This case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was <0.7 in a postbronchodilator pulmonary function test according to the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Logistic regression was used to examine the correlation between MSDP and COPD, adjusting for age, sex, BMI, educational attainment, place of residence, ethnic background, occupation, childhood passive smoking, residential fine particulate matter, history of childhood pneumonia or bronchitis, average annual household income, and medical history (coronary heart disease, hypertension, and diabetes). Mediation analysis examined TD as a potential mediator in the link between MSDP and COPD risk. The significance of the indirect effect was assessed through 1000 iterations of the "bootstrap" method. The study included 5943 participants (2991 with COPD and 2952 controls). Mothers of the COPD group had higher pregnancy smoking rates (COPD: n=305, 10.20%; controls: n=211, 7.10%; P<.001). TD was more prevalent in the COPD group (COPD: n=582, 40.40%; controls: n=478, 33.90%; P<.001). After adjusting for covariates, MSDP had a significant effect on COPD (β=.097; P<.001). There was an association between MSDP and TD (β=.074; P<.001) as well as between TD and COPD (β=.048; P=.007). Mediation analysis of TD in the MSDP-COPD association showed significant direct and indirect effects (direct: β=.094; P<.001 and indirect: β=.004; P=.03). The indirect effect remains present in the smoking population (direct: β=.120; P<.001 and indirect: β=.002; P=.03). This study highlighted the potential association between MSDP and the risk of COPD in offspring, revealing the mediating role of TD in this association. These findings contribute to a deeper understanding of the impact of prenatal tobacco exposure on lung health, laying the groundwork for the development of relevant prevention and treatment strategies.

Prenatal tobacco, tobacco-cannabis coexposure, and child emotion regulation: The role of child autonomic functioning and sensitive parenting.

Prenatal tobacco exposure (PTE) and tobacco-cannabis coexposure (PTCE) co-occur with negative maternal emotional functioning (termed prenatal risks) and together increase risk for child regulatory problems at early school age (ESA). Little is known about developmental processes in early childhood that may mediate this association. We examined two hypothesized mediational processes linking prenatal risks to ESA emotion regulation (ER) and lability-negativity; parasympathetic functioning at toddler age and chronic risk reflected by continued postnatal maternal negative emotional functioning (i.e., depression, anger/hostility, and emotion dysregulation) and substance exposure. Congruent with differential susceptibility theory, we examined interactions between sensitive parenting and toddler parasympathetic functioning predicting ESA ER. Finally, we explored the role of child sex as a moderator. Mothers (N = 247; 53% male infants; 51% Black, 31% White, 19% Hispanic, and 8% other or mixed race) were recruited in the first trimester of pregnancy into one of three groups: PTE (n = 81), PTCE (n = 97), and no substance exposure (n = 69) matched on age and education. Substance exposure was assessed using multiple methods, maternal negative emotional functioning via self-reports, parenting with observations, and child ER using teacher, maternal, and lab assessor reports. Results supported a chronic risk pathway with less support for a parasympathetic pathway. Toddlers who demonstrated respiratory sinus arrhythmia withdrawal to frustration were susceptible to the positive context of sensitive parenting in predicting higher ER. Results emphasize the importance of chronicity of postnatal risks including substance exposure and evaluating the differential impact of positive environments for children with substance exposure. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Impact of in utero tobacco exposure on fetal growth: Amount of exposure and second trimester fetal growth measurements

BackgroundResearch reveals small and inconsistent findings linking prenatal tobacco exposure and early fetal growth, but failure to consider confounding and amount of exposure many explain inconsistencies. GoalTo examine whether fetal growth effects following exposure to tobacco are evident in the second trimester, specific to certain growth parameters, and dose dependent. MethodsParticipants were pregnant women (64 smokers, 100 controls) with no other drug use. Available data included background/medical information and ultrasound measurements coded as percentiles. ResultsControlling for background differences, 10+ cig/day predicted a 10+ percentile point reduction in estimated fetal weight, femur length, head circumference, and biparietal diameter compared to non-exposed controls. Exposure to <10 cig/day predicted significant reduction in only biparietal diameter. Exposure was unrelated to abdominal circumference. ConclusionsResults demonstrate utility of considering amount of exposure when examining/quantifying fetal growth effects, and suggest even reduction in early pregnancy smoking may positively benefit aspects of fetal development.

In Utero Exposure to Alcohol and Tobacco and Electroencephalogram Power During Childhood

Prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) are risk factors associated with adverse neurobehavioral and cognitive outcomes. To quantify long-term associations of PAE and PTE with brain activity in early and middle childhood via electroencephalography (EEG). This cohort study included participants enrolled in the Safe Passage Study (August 2007 to January 2015), from which a subset of 649 participants were followed up in the Environmental Influences on Child Health Outcomes Program. From September 2018 through November 2022, EEG recordings were obtained at ages 4, 5, 7, 9, or 11 years. Data were analyzed from November 2022 to November 2023. Maternal self-reported consumptions of alcohol and tobacco during pregnancy were captured at the recruitment interview and at up to 3 visits during pregnancy (20-24, 28-32, and ≥34 weeks' gestation). Classifications of PAE (continuous drinking, quit-early drinking, and nondrinking) and PTE (continuous smoking, quit-early smoking, and nonsmoking) were previously obtained. EEG band powers (theta, alpha, beta, gamma) were extracted from the EEG recordings. Linear regression models were used to estimate the associations of PAE and PTE with EEG estimates. The final sample included 649 participants (333 [51.3%] female) aged 4, 5, 7, 9, or 11 years. Children whose mothers were in the quit-early drinking cluster had increased alpha power (0.116 [95% CI, 0.023 to 0.209] μV2; P = .02) compared with individuals without PAE. The magnitude of this increase was approximately double for children exposed to continuous drinking (0.211 [95% CI, 0.005 to 0.417] μV2; P = .04). Children whose mothers were in the continuous smoking cluster had decreased beta power (-0.031 [95% CI, -0.059 to -0.003] μV2; P = .03) and gamma power (-0.020 [95% CI, -0.039 to -0.000] μV2; P = .04) compared with the nonsmoking cluster. In exploratory sex-stratified models, male participants in the quit-early PAE cluster had greater EEG power in the alpha band (0.159 [95% CI, 0.003 to 0.315] μV2; P = .04) compared with those with no PAE, and the difference was approximately double for male participants with continuous PAE (0.354 [95% CI, 0.041 to 0.667] μV2; P = .03). Male participants in the continuous PTE cluster had decreased beta (-0.048 [95% CI, -0.090 to - 0.007] μV2; P = .02) and gamma (-0.032 [95% CI, -0.061 - 0.002] μV2; P = .04) power compared with those with no PTE. These findings suggest that even low levels of PAE and PTE were associated with long-term alterations of brain activity.

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.

Prenatal tobacco exposure associations with physical health and neurodevelopment in the ABCD cohort.

To investigate the strength and reproducibility of the teratogenic impact of prenatal tobacco exposure (PTE) on child physical health and neurodevelopmental outcomes, in the context of intersecting sociodemographic and other prenatal correlates, and test if early postnatal health mediates PTE associations with childhood outcomes. Among 9-10-year-olds (N = 8,803) in the Adolescent Brain Cognitive Development Study, linear mixed-effect models tested PTE associations with birth and childhood outcomes of physical health, cognitive performance, and brain structure, controlling for confounding sociodemographic and prenatal health correlates. Mediation analysis tested the extent to which health at birth explained the associations between PTE and childhood outcomes. PTE was reported by 12% of mothers (8% [n = 738] pre-knowledge of pregnancy only, and 4% [n = 361] pre- and post-knowledge of pregnancy). PTE was highest for children with a risk for passive smoke exposure. Overall, children with any PTE had shorter breastfeeding durations than those without PTE, and PTE following knowledge of pregnancy was associated with being small for gestational age having lower birth weight, and obesity and lower cortical volume and surface area in childhood. Among children from high-parent education households, any PTE was related to lower cognitive performance, which was partially mediated by duration of breastfeeding. PTE was linked to poorer health indicators at birth and neurodevelopmental outcomes at age 9-10 years in a large community cohort, independent of sociodemographic factors. Efficacious interventions for smoking-cessation during pregnancy are still needed and should incorporate support for breastfeeding to promote healthier development. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Gastroschisis Associated Intestinal Dysmotility: What Can We Do?

The cause of gastroschisis is not fully known, but risk factors like prenatal tobacco exposure, maternal infection and maternal drug use are often associated. When gastroschisis occurs with intestinal dysmotility, the enteric interstitial cells of Cajal (ICC) implicate the dysmotility and may ultimately impact the growth of an infant. Furthermore, neonates experience growth weight failure when not taking any enteral feedings secondary to dysmotility. We had a case of an infant with gastroschisis and intestinal atresia who had a prolonged course of feeding intolerance and abdominal distention after his bowel resection. His growth was preserved because of careful management of total parenteral nutrition (TPN) via a judicious nutrition plan.

Gene-Environment Analyses Reveal Novel Genetic Candidates with Prenatal Tobacco Exposure in Relation to Risk for Childhood Acute Lymphoblastic Leukemia.

Associations between maternal tobacco exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL) have yielded mixed results. This may be due to biases in self-reported smoking or other differences in individual-level risk factors. We utilized a biological marker of maternal tobacco exposure to evaluate the association between maternal tobacco exposure during pregnancy, genetics, and subsequent childhood ALL risk in two large population-based studies of childhood ALL in California. Maternal exposure to tobacco smoke was assessed with a validated methylation marker (cg05575921) of the aryl hydrocarbon receptor repressor (AHRR) gene in newborn dried blood spots. We adjusted for sex, birthweight, gestational age, mode of delivery, year of birth, AHRR quantitative trait locus (mQTL) rs77111113, and a polygenetic risk score for childhood ALL. We additionally adjusted for principal components in a gene-environment interaction testing method that incorporates gene-only and environment-only effects along with interactions. AHRR hypomethylation overall was not associated with childhood ALL. In gene-environment interaction testing, several genetic variants displayed significant interaction with AHRR hypomethylation and childhood ALL. Our results suggest that novel candidates in PTPRK and DPP6 may play a role in tobacco-related leukemogenesis. Further research is necessary to better understand the effects of tobacco and these variants on childhood ALL risk. Despite the lack of an overall "main effect," tobacco exposure during pregnancy affects childhood ALL risk depending on specific genetic variants.