Maternal Smoking during Pregnancy and its effects on Neural Tube Defects.

Objectives: Maternal smoking is a potent teratogen among congenital malformations, however its role in the development of Neural Tube Defects (NTDs) is still unclear. In this systematic review, we intend to further investigate the interaction of smoking during pregnancy and the incidence of NTDs. Materials & Methods: This article was written according to PRISMA criteria from February 2015 and August 2022. After examining the four stages of PRISMA criteria, we selected clinical articles. These articles were selected from PubMed, Scopus and Google scholar (for results follow-up) databases. We gathered NTDs effect and types, smoking type and habit of parents, from neonates. Results: Eventually, 8 articles were included by two separated authors, Smoking was associated with an increase NTDs in the population of pregnant mothers and also among children whose fathers smoked. The main side effects that were considered to be the cause of NTDs besides smoking were alcohol and BMI (18.5-24.9). Smoking also affects the level of folic acid as a substance with an essential role that affects the closure of the neural tube. folic acid available to infants changing along with the level of other blood elements such as zinc, that necessary prevent for NTDs condition. Conclusion: Parental smoking can be considered as one of the strong teratogens in the occurrence of NTDs. Smoking, whether active or passive by the mother, or by the father, is associated with the occurrence of NTDs, In order to reduce the prevalence this disorder, we advise pregnant mothers and neonate's fathers to quit smoking.

The association of maternal smoking around birth with chronic respiratory diseases in adult offspring: A Mendelian randomization study.

INTRODUCTION: Maternal smoking during pregnancy disturbs fetal lung development, and induces in their offspring childhood respiratory diseases. Whether it has a continued impact on offspring adult lung health and exerts a casual effect of chronic respiratory diseases (CRDs), remains uncertain. We seek to determine the causal relationships between maternal smoking around birth and offspring adult CRDs, using summary data from previously described cohorts. METHODS: Mendelian randomization (MR) study was used to analyze the genome-wide associations of maternal smoking around birth and offspring adult CRDs, including respiratory insufficiency, chronic obstructive pulmonary disease (COPD), related respiratory insufficiency, emphysema, COPD, COPD hospital admissions, early onset of COPD, later onset of COPD, asthma, idiopathic pulmonary fibrosis (IPF), lung cancer (LC), small cell lung carcinoma (SCLC), and lung squamous cell carcinoma (LUSC). RESULTS: After removing single-nucleotide polymorphisms (SNPs) associated with smoking by the offspring, maternal smoking around birth was associated with increased risk of offspring adult respiratory diseases (OR=1.14; 95% CI: 1.013-1.284; p=0.030), respiratory insufficiency (OR=2.413; 95% CI: 1.039-5.603; p=0.040), COPD (OR=1.14; 95% CI: 1.013-1.284; p=0.003), and asthma (OR=1.336; 95% CI: 1.161-1.538; p<0.001). Besides, maternal smoking during pregnancy was associated with a greater risk of LUSC (OR=1.229; 95% CI: 0.992-1.523; p=0.059) than the risk of IPF (OR=1.001; 95% CI: 0.999-1.003; p=0.224), LC (OR=1.203; 95% CI: 0.964-1.501; p=0.103), or SCLC (OR=1.11; 95% CI: 0.77-1.601; p=0.577). CONCLUSIONS: In this MR analysis, maternal smoking around birth caused a strong risk factor for the offspring to develop lung problems and CRDs in adulthood. The policy related to smoking cessation for mothers during pregnancy should be encouraged.

Maternal risk factors for congenital vertebral formation and mixed defects: A population-based case-control study.

Background: The etiology and risk factors of congenital vertebral anomalies are mainly unclear in isolated cases. Also, there are no reports on the risk factors for different subgroups of vertebral anomalies. Therefore, we assessed and identified potential maternal risk factors for these anomalies and hypothesized that diabetes, other chronic diseases, smoking, obesity, and medication in early pregnancy would increase the risk of congenital vertebral anomalies. Methods: All cases with congenital vertebral anomalies were identified in the Finnish Register of Congenital Malformations from 1997 to 2016 for this nationwide register-based case-control study. Five matched controls without vertebral malformations were randomly selected. Analyzed maternal risk factors included maternal age, body mass index, parity, smoking, history of miscarriages, chronic diseases, and prescription drug purchases in early pregnancy. Results: The register search identified 256 cases with congenital vertebral malformations. After excluding 66 syndromic cases, 190 non-syndromic malformations (74 formation defects, 4 segmentation defects, and 112 mixed anomalies) were included in the study. Maternal smoking was a significant risk factor for formation defects (adjusted odds ratio 2.33, 95% confidence interval 1.21-4.47). Also, pregestational diabetes (adjusted odds ratio 8.53, 95% confidence interval 2.33-31.20) and rheumatoid arthritis (adjusted odds ratio 13.19, 95% confidence interval 1.31-132.95) were associated with mixed vertebral anomalies. Conclusion: Maternal pregestational diabetes and rheumatoid arthritis were associated with an increased risk of mixed vertebral anomalies. Maternal smoking increases the risk of formation defects and represents an avoidable risk factor for congenital scoliosis. Level of evidence: III.

A Comprehensive Look at the Development of Asthma in Children.

Asthma, a prevalent chronic respiratory condition affecting millions of children globally, presents a significant health challenge. This review critically examines the developmental pathways of asthma in children, focusing on genetic, environmental, and early-life determinants. Specifically, we explore the impact of prenatal and postnatal factors such as maternal smoking, nutrition, respiratory infections, and allergen exposure on asthma development. Our analysis highlights the intricate interplay of these influences and their contribution to childhood asthma. Moreover, we emphasize targeted strategies and interventions to mitigate its burden, including genetic counseling for at-risk families, environmental modifications to reduce triggers, and early-life immunomodulation. By delving into these preventive measures and interventions, our review aims to provide actionable insights for healthcare professionals in developing tailored strategies to address the complexities of childhood asthma. In summary, this article offers a detailed examination of asthma development in children, aiming to enhance understanding and inform efforts to reduce its burden through targeted interventions.

Maternal smoking, consumption of alcohol, and caffeinated beverages during pregnancy and the risk of childhood brain tumors: a meta-analysis of observational studies.

BACKGROUND: We conducted this meta-analysis to investigate the potential association between maternal smoking, alcohol and caffeinated beverages consumption during pregnancy and the risk of childhood brain tumors (CBTs). METHODS: A thorough search was carried out on PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Internet to identify pertinent articles. Fixed or random effects model was applied to meta-analyze the data. RESULTS: The results suggested a borderline statistically significant increased risk of CBTs associated with maternal smoking during pregnancy (OR 1.04, 95% CI 0.99-1.09). We found that passive smoking (OR 1.12, 95% CI 1.03-1.20), rather than active smoking (OR 1.00, 95% CI 0.93-1.07), led to an increased risk of CBTs. The results suggested a higher risk in 0-1 year old children (OR 1.21, 95% CI 0.94-1.56), followed by 0-4 years old children (OR 1.12, 95% CI 0.97-1.28) and 5-9 years old children (OR 1.11, 95% CI 0.95-1.29). This meta-analysis found no significant association between maternal alcohol consumption during pregnancy and CBTs risk (OR 1.00, 95% CI 0.80-1.24). An increased risk of CBTs was found to be associated with maternal consumption of caffeinated beverages (OR 1.16, 95% CI 1.07-1.26) during pregnancy, especially coffee (OR 1.18, 95% CI 1.00-1.38). CONCLUSIONS: Maternal passive smoking, consumption of caffeinated beverages during pregnancy should be considered as risk factors for CBTs, especially glioma. More prospective cohort studies are warranted to provide a higher level of evidence.

Morphological and clinical findings in placentas and newborns with a history of tobacco, alcohol, and other substance abuse during pregnancy.

BACKGROUND: Exposure to toxins during pregnancy is the main modifiable behavior that affects the placenta and, consequently, the fetus. In particular, smoking is a recognized risk factor for negative outcomes. Our study pretended to examine gross and microscopic placental features in women who reported exposure to tobacco, alcohol, or other psychoactive substances. METHODS: In this observational case-control study, we collected 706 placentas to assess precise substance exposure histological-interaction features of in the placenta. We examined gross and microscopic placental features, and then recorded maternal and newborn clinical conditions. RESULTS: We found that 4.8% of mothers admitted to consumption of some type of (harmful) substance. The most common pre-existing maternal condition was obesity (20.3%); predominant complications included amniotic infection (32.3%), urinary tract infection (14.5%) and hypertensive disorders of pregnancy (14.5%). In newborns, we discovered positive associations as respiratory distress syndrome. Macroscopically, exposed mothers had heavier placentas, more true knots, and single umbilical artery; microscopically, they were more likely to exhibit fetal vascular malperfusion (FVM). CONCLUSIONS: Until our present study, no research linked umbilical cord defects to toxic substance exposure; our study results do confirm association with adverse outcomes in neonates and alterations in the neuro-cardio-placental circuit through FVM. IMPLICATIONS: The results are confirming the importance of this modifiable risk factor and how its presence may potentially affect the course of pregnancy, as well as the health of both mother and child.

Stress-Induced Changes in Nucleocytoplasmic Localization of Crucial Factors in Gene Expression Regulation.

This study investigates the toxic effect of harmful materials, unfiltered by the placenta, on neonatal umbilical cord (UC) vessels, focusing on stress-induced adaptations in transcriptional and translational processes. It aims to analyze changes in pathways related to mRNA condensate formation, transcriptional regulation, and DNA damage response under maternal smoking-induced stress. UC vessels from neonates born to smoking (Sm) and nonsmoking mothers (Ctr) were examined. Immunofluorescence staining and confocal microscopy assessed the localization of key markers, including Transcription Complex Subunit 1 (CNOT1) and the largest subunit of RNA polymerase II enzyme (RPB1). Additionally, markers of DNA damage response, such as Poly(ADP-ribose) polymerase-1, were evaluated. In Sm samples, dissolution of CNOT1 granules in UC vessels was observed, potentially aiding stalled translation and enhancing transcription via RPB1 assembly and translocation. Control vessels showed predominant cytoplasmic RPB1 localization. Despite adaptive responses, Sm endothelial cells exhibited significant damage, indicated by markers like Poly(ADP-ribose) polymerase-1. Ex vivo metal treatment on control vessels mirrored Sm sample alterations, emphasizing marker roles in cell survival under toxic exposure. Maternal smoking induces specific molecular adaptations in UC vessels, affecting mRNA condensate formation, transcriptional regulation, and DNA damage response pathways. Understanding these intricate molecular mechanisms could inform interventions to improve neonatal health outcomes and mitigate adverse effects of toxic exposure during pregnancy.

Exploring a Potential Interaction Between the Effect of Specific Maternal Smoking Patterns and Comorbid Antenatal Depression in Causing Postpartum Depression.

Purpose: To explore a potential interaction between the effect of specific maternal smoking patterns and the presence of antenatal depression, as independent exposures, in causing postpartum depression (PPD). Methods: This case-control study of participants with singleton term births (N = 51220) was based on data from the 2017-2018 Pregnancy Risk Assessment Monitoring System. Multivariable log-binomial regression models examined the main effects of smoking patterns and self-reported symptoms of antenatal depression on the risk of PPD on the adjusted risk ratio (aRR) scale and tested a two-way interaction adjusting for covariates selected in a directed acyclic graph (DAG). The interaction effects were measured on the additive scale using relative excess risk due to interaction (RERI), the attributable proportion of interaction (AP), and the synergy index (SI). Causal effects were defined in a counterfactual framework. The E-value quantified the potential impact of unobserved/unknown covariates, conditional on observed covariates. Results: Among 6841 women in the sample who self-reported PPD, 35.7% also reported symptoms of antenatal depression. Out of 3921 (7.7%) women who reported smoking during pregnancy, 32.6% smoked at high intensity (≥10 cigarettes/day) in all three trimesters and 36.6% had symptoms of antenatal depression. The main effect of PPD was the strongest for women who smoked at high intensity throughout pregnancy (aRR 1.65; 95% CI: 1.63, 1.68). A synergistic interaction was detected, and the effect of all maternal smoking patterns was augmented, particularly in late pregnancy for Increasers and Reducers. Conclusion: Strong associations and interaction effects between maternal smoking patterns and co-occurring antenatal depression support smoking prevention and cessation interventions during pregnancy to lower the likelihood of PPD.

Maternal smoking during pregnancy increases the risk of gut microbiome-associated childhood overweight and obesity.

Childhood obesity is linked to maternal smoking during pregnancy. Gut microbiota may partially mediate this association and could be potential targets for intervention; however, its role is understudied. We included 1,592 infants from the Canadian Healthy Infants Longitudinal Development Cohort. Data on environmental exposure and lifestyle factors were collected prenatally and throughout the first three years. Weight outcomes were measured at one and three years of age. Stool samples collected at 3 and 12 months were analyzed by sequencing the V4 region of 16S rRNA to profile microbial compositions and magnetic resonance spectroscopy to quantify the metabolites. We showed that quitting smoking during pregnancy did not lower the risk of offspring being overweight. However, exclusive breastfeeding until the third month of age may alleviate these risks. We also reported that maternal smoking during pregnancy significantly increased Firmicutes abundance and diversity. We further revealed that Firmicutes diversity mediates the elevated risk of childhood overweight and obesity linked to maternal prenatal smoking. This effect possibly occurs through excessive microbial butyrate production. These findings add to the evidence that women should quit smoking before their pregnancies to prevent microbiome-mediated childhood overweight and obesity risk, and indicate the potential obesogenic role of excessive butyrate production in early life.

Perinatal factors as risk factors of bipolar disorder onset in young adulthood: a 22-year birth cohort.

BACKGROUND: Bipolar disorder (BD) is a leading cause of disability-adjusted life years in young adults. Complications during prenatal periods have been associated with BD previously. The study aims to examine the association between perinatal factors and BD in order to prevent the risk of developing BD. METHODS: 3,794 subjects from the 1993 Pelotas population-based birth cohort study were included. We assessed 27 initial variables at birth and modelled BD onset at 18 and 22 years. We performed bivariate analysis, using binomial logistic regression models. The variables with p-value smaller than 0.05 were included into a multiple regression with confounding variables. RESULTS: Maternal smoking was associated with a 1.42-fold increased risk of BD at 18 or 22 years old (95% CI: 1.091-1.841), and maternal passive exposure to tobacco with a 1.43-fold increased risk (95% CI: 1.086-1.875). No association was found between other perinatal factors and BD after controlling for confounding factors. CONCLUSION: The results of this cohort corroborate with previous findings in the literature that already indicate the negative outcomes of maternal smoking during pregnancy. They may now be linked to other studies to target these factors for preventing the development of BD.

Maternal smoking around birth and its influence on offspring allergic diseases: A mendelian randomization study.

Objective: The influence of maternal smoking around birth (MSAB) on offspring allergic diseases, specifically childhood asthma (CA), allergic rhinitis (AR), allergic conjunctivitis (AC), and atopic dermatitis (AD) remains incompletely understood. We performed a rigorous mendelian randomization (MR) study to obtain the unconfounded association between MSAB and allergic diseases in offspring with and without adjustment for the effect of breastfeeding. Methods: Utilizing publicly available information of MSAB, breastfeeding, CA, AR, AC, and AD from large-scale genome-wide association studies (GWAS), we performed a two-sample mendelian randomization (TSMR) analysis to assess the respective causal relationship of MSAB and breastfeeding to allergic diseases in offspring. To get a reliable conclusion, MR Egger regression, weighted median, and inverse variance weighted (IVW) were employed to estimate the causality, with IVW as the primary analysis. Multivariate MR (MVMR) analysis was used to assess the effect of MSAB on allergic diseases after adjusting for breastfeeding's impact. Sensitivity analysis was conducted using the Cochran Q test, MR-Egger, and leave-one-out approaches to ensure the reliability and stability of results. Results: The TSMR analysis demonstrated MSAB increased the risks of CA (PIVW = 0.013, OR: 1.018, 95%CI: 1.004 to 1.033) and AD (PIVW = 0.006, OR: 8.293, 95%CI: 1.815 to 37.884) in offspring. Conversely, breastfeeding decreased the risk of CA (PIVW <0.001, OR: 0.946, 95%CI: 0.918 to 0.974). MSAB still increased the risks of CA (P = 0.0497, OR: 1.013, 95%CI: 1.000017 to 1.026) and AD (P = 0.003, OR: 13.800, 95%CI: 2.490 to 269.246) after adjusting for breastfeeding. We observed no strong indication of a negative causality between MSAB and AC and AR. Conclusion: Our findings provided robust evidence of the adverse effects of MSAB on offspring. We emphasized the urgency of smoking cessation around birth and the importance of breastfeeding even in smoking mothers.

Maternal smoking, nutritional factors at different life stage, and the risk of incident type 2 diabetes: a prospective study of the UK Biobank.

BACKGROUND: This study aims to investigate potential interactions between maternal smoking around birth (MSAB) and type 2 diabetes (T2D) pathway-specific genetic risks in relation to the development of T2D in offspring. Additionally, it seeks to determine whether and how nutritional factors during different life stages may modify the association between MSAB and risk of T2D. METHODS: This study included 460,234 participants aged 40 to 69 years, who were initially free of T2D from the UK Biobank. MSAB and breastfeeding were collected by questionnaire. The Alternative health eating index(AHEI) and dietary inflammation index(DII) were calculated. The polygenic risk scores(PRS) of T2D and pathway-specific were established, including ß-cell function, proinsulin, obesity, lipodystrophy, liver function and glycated haemoglobin(HbA1c). Cox proportion hazards models were performed to evaluate the gene/diet-MSAB interaction on T2D. The relative excess risk due to additive interaction (RERI) were calculated. RESULTS: During a median follow-up period of 12.7 years, we identified 27,342 cases of incident T2D. After adjustment for potential confounders, participants exposed to MSAB had an increased risk of T2D (HR=1.11, 95%CI:1.08-1.14), and this association remained significant among the participants with breastfeeding (HR= HR=1.10, 95%CI: 1.06-1.14). Moreover, among the participants in the highest quartile of AHEI or in the lowest quartile of DII, the association between MSAB and the increased risk of T2D become non-significant (HR=0.94, 95%CI: 0.79-1.13 for AHEI; HR=1.09, 95%CI:0.99-1.20 for DII). Additionally, the association between MSAB and risk of T2D became non-significant among the participants with lower genetic risk of lipodystrophy (HR=1.06, 95%CI:0.99-1.14), and exposed to MSAB with a higher genetic risk for ß-cell dysfunction or lipodystrophy additively elevated the risk of T2D(RERI=0.18, 95%CI:0.06-0.30 for ß-cell function; RERI=0.16, 95%CI:0.04-0.28 for lipodystrophy). CONCLUSIONS: This study indicates that maintaining a high dietary quality or lower dietary inflammation in diet may reduce the risk of T2D associated with MSAB, and the combination of higher genetic risk of ß-cell dysfunction or lipodystrophy and MSAB significantly elevate the risk of T2D in offspring.

Improvements in lung function following vitamin C supplementation to pregnant smokers are associated with buccal DNA methylation at 5 years of age.

BACKGROUND: We previously reported in the "Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function" randomized clinical trial (RCT) that vitamin C (500 mg/day) supplementation to pregnant smokers is associated with improved respiratory outcomes that persist through 5 years of age. The objective of this study was to assess whether buccal cell DNA methylation (DNAm), as a surrogate for airway epithelium, is associated with vitamin C supplementation, improved lung function, and decreased occurrence of wheeze. METHODS: We conducted epigenome-wide association studies (EWAS) using Infinium MethylationEPIC arrays and buccal DNAm from 158 subjects (80 placebo; 78 vitamin C) with pulmonary function testing (PFT) performed at the 5-year visit. EWAS were performed on (1) vitamin C treatment, (2) forced expiratory flow between 25 and 75% of expired volume (FEF25-75), and (3) offspring wheeze. Models were adjusted for sex, race, study site, gestational age at randomization (≤ OR > 18 weeks), proportion of epithelial cells, and latent covariates in addition to child length at PFT in EWAS for FEF25-75. We considered FDR p < 0.05 as genome-wide significant and nominal p < 0.001 as candidates for downstream analyses. Buccal DNAm measured in a subset of subjects at birth and near 1 year of age was used to determine whether DNAm signatures originated in utero, or emerged with age. RESULTS: Vitamin C treatment was associated with 457 FDR significant (q < 0.05) differentially methylated CpGs (DMCs; 236 hypermethylated; 221 hypomethylated) and 53 differentially methylated regions (DMRs; 26 hyper; 27 hypo) at 5 years of age. FEF25-75 was associated with one FDR significant DMC (cg05814800), 1,468 candidate DMCs (p < 0.001), and 44 DMRs. Current wheeze was associated with 0 FDR-DMCs, 782 candidate DMCs, and 19 DMRs (p < 0.001). In 365/457 vitamin C FDR significant DMCs at 5 years of age, there was no significant interaction between time and treatment. CONCLUSIONS: Vitamin C supplementation to pregnant smokers is associated with buccal DNA methylation in offspring at 5 years of age, and most methylation signatures appear to be persistent from the prenatal period. Buccal methylation at 5 years was also associated with current lung function and occurrence of wheeze, and these functionally associated loci are enriched for vitamin C associated loci. Clinical trial registration ClinicalTrials.gov, NCT01723696 and NCT03203603.

Secondhand Smoke Exposure and Risk of Dementia in Nonsmokers: A Population-Based Cohort Study.

BACKGROUND: Large population-based prospective studies are necessary to provide clarification on the associations of panoramic secondhand smoking burden, including prenatal and postnatal secondhand smoke (SHS) exposure, with the risk of developing dementia. METHODS: Our study comprised a sample of 353,756 dementia-free individuals from the UK Biobank who were nonsmokers had data on the exposure of maternal smoking as well as SHS exposure in daily life, which was quantified in terms of hours per week (h/week) and whether they lived with household smokers. Multivariable Cox regression models were utilized to analyze the independent and joint associations of maternal smoking and daily life SHS exposure with dementia risk. RESULTS: During a median follow-up of 11.8 years, 4,113 participants developed dementia. Compared with those who lived in the environment without smokers, multivariable-adjusted hazard ratios (HRs) (95% CIs) were 1.11 (1.02, 1.20) and 1.31 (1.13, 1.52) for those who exposed to SHS for >0 but ≤4 h/week and >4 h/week, respectively, and was 1.25 (1.13, 1.39) for those who lived with smokers in the household. A positive history of maternal smoking was associated with a modestly higher risk of dementia (HR = 1.07; 95% CI: 1.01, 1.15). Furthermore, compared with participants with neither history of maternal smoking nor exposure to SHS, a particularly higher risk of dementia was observed among those with both exposures (HR = 1.48; 95% CI: 1.18, 1.86). Additionally, the HR (95% CI) was 1.32 (1.10, 1.59) when comparing participants with a history of maternal smoking who lived with smokers in their households with those who had neither exposures. CONCLUSIONS: Having a history of maternal smoking, longer exposure to SHS, and living with smokers in the household were each associated with an increased risk of developing dementia. Individuals who were simultaneously exposed to maternal smoking and SHS or lived with household smokers had a particularly higher dementia risk.

The causal impact of maternal smoking around birth on offspring ADHD: A two-sample Mendelian randomization study.

BACKGROUND: The previous literature highlights a relationship between maternal smoking around birth (MSAB) and offspring attention-deficit/hyperactivity disorder (ADHD). These studies have focused on the causal effects of MSAB on offspring ADHD. METHOD: A Mendelian randomization analysis was conducted using summary statistics. Data on MSAB were obtained from a recent study including 391,992 participants. ADHD data were obtained from six sources for 246,888 participants. The present study used five methods to examine the causal impact from outcomes on exposures. The inverse variance weighted (IVW) was the main method of analysis, while the other four methods were supplementary methods. RESULT: The IVW revealed that MSAB was a risk factor for offspring ADHD (OR: 2.54; 95 % confidence interval [CI]: 1.61-4.00, p = 6.04 × 10-5). Concerning ADHD in both sexes, MSAB was associated with females (OR = 3.96, 95 % CI: 1.99-7.90, p = 8.98 × 10-5) and males (OR = 3.74, 95 % CI: 1.74-5.72, p = 1.48 × 10-4). In different diagnosis periods for ADHD, MSAB increased the risk of childhood (OR = 3.63, 95 % CI: 2.25-5.87, p = 1.31 × 10-7), late-diagnosed (OR = 2.99, 95 % CI: 1.74-5.14, p = 7.33 × 10-5), and persistent (OR = 4.77, 95 % CI: 1.88-12.14, p = 1.03 × 10-3) ADHD. The final analysis did not reveal heterogeneity. CONCLUSIONS: A causal impact of MSAB on offspring ADHD was observed. These findings highlight the need for careful consideration of prenatal exposure (MSAB) during the assessment of offspring ADHD. Additionally, it can provide targeted guidance for prenatal interventions. Future studies should analyze the effects of different doses of maternal smoking on ADHD.

Inequality in smoking and related risk factors for smoking in expectant mothers - a nationwide Danish register-based study.

AIMS: Foetuses exposed to smoking during pregnancy are disadvantaged due to numerous adverse obstetric outcomes. This study aimed to examine 1) inequality in maternal smoking between subgroups of pregnant women and 2) significant risk factors of maternal smoking. METHODS: Data were collected from Danish registries. Trends in maternal smoking within each study period, T1 (2000-2002) and T2 (2014-2016), were investigated by Poisson regression calculating prevalence proportion ratios, and trends between study periods were studied by adding an interaction term. The significance of risk factors for maternal smoking (low age, low education, living alone and having a moderate/severe mental health condition) were studied by interaction analysis on the additive scale. RESULTS: The prevalence of maternal smoking decreased from 21% in 2000 to 7% in 2016. Decreases were found in all subgroups of maternal age, cohabitation status, educational level and mental health condition. However, large differences in smoking prevalence between subgroups were found, and inequality in maternal smoking increased from 2000 to 2016. The probability of maternal smoking increased with the addition of risk factors, and positive additive interactions were found for almost all combinations of multiple risk factors. CONCLUSIONS: Our results provide knowledge on risk factors and increasing levels of inequality in maternal smoking which points to a need for targeted interventions in relation to maternal smoking for subgroups of pregnant women in future smoking cessation programmes and in antenatal care.

Cotinine concentrations in maternal serum and amniotic fluid during pregnancy and risk of testicular germ cell cancer in the offspring: A prospective nested case-control study.

Maternal smoking in pregnancy may increase the risk of testicular germ cell cancer (TGCC) in offspring, but current evidence remains inconclusive. We performed a nested case-control study using cotinine measurements in maternal serum and amniotic fluid as a biomarker for tobacco exposure during pregnancy. A total of 654 males with maternal serum (n = 359, ncases/controls = 71/288) and/or amniotic fluid (n = 295, ncases/controls = 66/229) samples were included. Data on TGCC diagnoses and relevant covariates were derived from nationwide Danish health registries. Cotinine was quantified by liquid chromatography tandem mass spectrometry. An adapted cox regression model estimated the risk of TGCC considering active and inactive tobacco use defined according to cotinine concentrations of <, ≥15 ng/ml. Overall, the concentrations of cotinine were comparable in maternal serum and amniotic fluid (medianserum/amniotic fluid : 2.1/2.6 ng/ml). A strong statistically significant correlation was detected in 14 paired samples (Spearman rho: 0.85). Based on maternal serum cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC in offspring (HR 0.88, 95% CI 0.51; 1.52). Similarly, based on amniotic fluid cotinine concentrations, exposure to active tobacco use was not associated with risk of TGCC (HR 1.11, 95% CI 0.64; 1.95). However, different risks were observed for seminomas and nonseminomas in both matrices, but none were statistically significant. Our findings did not provide convincing evidence supporting that exposure to tobacco during pregnancy is associated with TGCC.

Early life exposures contributing to accelerated lung function decline in adulthood - a follow-up study of 11,000 adults from the general population.

Background: We aimed to assess whether exposure to risk factors in early life from conception to puberty continue to contribute to lung function decline later in life by using a pooled cohort comprising approx. 11,000 adults followed for more than 20 years and with up to three lung function measurements. Methods: Participants (20-68 years) in the ECRHS and NFBC1966 cohort studies followed in the periods 1991-2013 and 1997-2013, respectively, were included. Mean annual decline in maximum forced expired volume in 1 s (FEV1) and forced vital capacity (FVC) were main outcomes. Associations between early life risk factors and change in lung function were estimated using mixed effects linear models adjusted for sex, age, FEV1, FVC and height at baseline, accounting for personal smoking. Findings: Decline in lung function was accelerated in participants with mothers that smoked during pregnancy (FEV1 2.3 ml/year; 95% CI: 0.7, 3.8) (FVC 2.2 ml/year; 0.2, 4.2), with asthmatic mothers (FEV1 2.6 ml/year; 0.9, 4.4) (FEV1/FVC 0.04 per year; 0.04, 0.7) and asthmatic fathers (FVC 2.7 ml/year; 0.5, 5.0), and in women with early menarche (FVC 2.4 ml/year; 0.4, 4.4). Personal smoking of 10 pack-years contributed to a decline of 2.1 ml/year for FEV1 (1.8, 2.4) and 1.7 ml/year for FVC (1.3, 2.1). Severe respiratory infections in early childhood were associated with accelerated decline among ever-smokers. No effect-modification by personal smoking, asthma symptoms, sex or cohort was found. Interpretation: Mothers' smoking during pregnancy, parental asthma and early menarche may contribute to a decline of FEV1 and FVC later in life comparable to smoking 10 pack-years. Funding: European Union's Horizon 2020; Research Council of Norway; Academy of Finland; University Hospital Oulu; European Regional Development Fund; Spanish Ministry of Science and Innovation; Generalitat de Catalunya.

Impact of Maternal Smoking, Offspring Smoking, and Genetic Susceptibility on Crohn's Disease and Ulcerative Colitis.

BACKGROUND AND AIMS: The long-term impact of maternal smoking during pregnancy (MSDP) on adult offspring's risk of Crohn's disease (CD) and ulcerative colitis (UC) remains uncertain. Our study aims to investigate the individual and combined effects of early life exposure (MSDP), offspring personal behavior (smoking), and genetic risk on the development of CD and UC in adult offspring. METHODS: We conducted a prospective cohort study using UK Biobank data, including 334,083 participants recruited between 2006-2010, with follow-up until December 31, 2021. Multivariable Cox regression models were used to evaluate the associations of genetic factors, maternal and personal smoking, and their combination with CD and UC. RESULTS: Participants exposed to MSDP had an 18% increased risk of CD compared to those without MSDP (hazard ratio (HR) = 1.18, 95% confidence interval (CI) = 1.01-1.39). However, no significant association was found between MSDP and the UC risk (HR = 1.03, 95%CI = 0.92-1.16). Personal smoking increased the risk of CD and UC, and had a numerically amplified effect with MSDP. Participants with high genetic risk and MSDP had a 2.01-fold (95%CI = 1.53-2.65) and a 2.45-fold (95%CI = 2.00-2.99) increased risk of CD and UC, respectively, compared to participants without MSDP and with low genetic risk. CONCLUSIONS: Our prospective cohort study provides evidence that MSDP increases the risk of CD in adult offspring, whereas no evidence supports their causal association. Additionally, smoking and genetic susceptibility had a numerically amplified effect with MSDP on CD and UC, but the interaction lacked statistical significance.

Early Life Factors and Polycystic Ovary Syndrome in a Swedish Birth Cohort.

Polycystic ovary syndrome (PCOS) is a medical condition with important consequences for women's well-being and reproductive outcomes. Although the etiology of PCOS is not fully understood, there is increasing evidence of both genetic and environmental determinants, including development in early life. We studied a population of 977,637 singleton women born in in Sweden between 1973 and 1995, followed sometime between the age 15 and 40. The incidence of PCOS was measured using hospital register data during 2001-2012, complemented with information about the women's, parents' and sisters' health and social characteristics from population and health care registers. Cox regression was used to study how PCOS is associated with intergenerational factors, and a range of early life characteristics. 11,594 women in the study sample were diagnosed with PCOS during the follow-up period. The hazard rate for PCOS was increased 3-fold (HR 2.98, 95% CI 2.43-3.64) if the index woman's mother had been diagnosed with PCOS, and with 1.5-fold (HR 1.51, 95% CI 1.39-1.63) if their mother had diabetes mellitus. We found associations of PCOS with lower (<7) one-minute Apgar score (HR 1.19, 95% CI 1.09-1.29) and with post-term birth (HR 1.19, 95% CI 1.13-1.26). Furthermore, heavy (10+ cigarettes/day) maternal smoking (HR 1.30, 95% CI 1.18-1.44) and maternal obesity (HR 1.90, 95% CI 1.62-2.36) were strongly associated with PCOS. This study finds support for the heritability and fetal origins of PCOS. Risk of PCOS could be reduced by further emphasizing the importance of maternal and early life health.