Association Between Adverse Early Life Factors and Telomere Length in Middle and Late Life.

Background and Objectives: Telomere length (TL) has been acknowledged as biomarker of biological aging. Numerous investigations have examined associations between individual early life factors and leukocyte TL; however, the findings were far from consistent. Research Design and Methods: We evaluated the relationship between individual and combined early life factors and leukocytes TL in middle and late life using data from the UK Biobank. The early life factors (eg, maternal smoking, breastfeeding, birth weight, and comparative body size and height to peers at age 10) were measured. The regression coefficients (ß) and 95% confidence interval (CI) were applied to assess the link of the early life factors and TL in adulthood. Flexible parametric survival models incorporated age to calculate the relationship between early life factors and life expectancy. Results: Exposure to maternal smoking, lack of breastfeeding, low birth weight, and shorter height compared to peers at age 10 were identified to be associated with shorter TL in middle and older age according to the large population-based study with 197 504 participants. Individuals who experienced more than 3 adverse early life factors had the shortest TL in middle and late life (ß = -0.053; 95% CI = -0.069 to -0.038; p < .0001), as well as an average of 0.54 years of life loss at the age of 45 and 0.49 years of life loss at the age of 60, compared to those who were not exposed to any early life risk factors. Discussion and Implications: Early life factors including maternal smoking, non-breastfed, low birth weight, and shorter height compared to peers at age 10 were associated with shorter TL in later life. In addition, an increased number of the aforementioned factors was associated with a greater likelihood of shorter TL in adulthood, as well as a reduced life expectancy.

Daily snuff use during pregnancy, gestational length and birth weight; register-based study.

BACKGROUND: Snuff is a smokeless source of nicotine that is common in Scandinavia and increasingly used by women of fertile age. Persistent use of snuff during pregnancy has been associated with adverse pregnancy outcomes. Emerging data from the Medical Birth Registry of Norway distinguishes between occasional use and daily use. We provide preliminary estimates of associations between frequency of snuff and gestational length and birth weight. METHODS: Data on snuff use during pregnancies delivered in 2020 and 2021 were available for the west and central regions of Norway. Associations of snuff use with gestational length and birth weight at term (39-41 weeks) were estimated using quantile regression at the 25th, the 50th and the 75th percentiles, with adjustments for mother's age, pre-pregnancy weight, and parity. We compared associations with the pregnancy outcomes according to maternal snuff and cigarette use. RESULTS: 12.4% of 18 042 non-smoking women reported daily use of snuff before pregnancy, and 4.6% reported continuing use during pregnancy, with 1.2% still reporting daily use in the last trimester. Women with daily use through the last trimester delivered babies with a median gestational length reduced by 3.4 days (95% CI: -5.0 to -1.7 days) compared with women who never used snuff. The reduction was even stronger at the 25th percentile of gestational age. The median term birth weight was reduced by 44 g (95% CI: -134 to 46 g). These associations were much weaker for women who quit snuff at some point during pregnancy or used snuff only occasionally. Mothers who smoked daily through the last trimester had a median gestational length reduced by 2.1 days (95% CI: -2.7 to -1.4) and a median term birth weight reduced by 294 g (95% CI: -325 to -262) compared with never-smokers. CONCLUSIONS: Daily snuff use through the last trimester reduced the median gestational length by more than three days. Snuff reduced birth weight, but not as much as smoking, suggesting that the predominant effect of smoking on fetal growth is not through nicotine but through the additional toxic chemicals in cigarettes or by reduced oxygen supply to the fetus.

Associations of preterm birth and neonatal stress exposure with chronic pain in adulthood - Results from the Gutenberg prematurity study.

Although the effect of early childhood stress on central nervous pain processing is well known, studies on the association of prematurity and chronic pain are scarce. This study used data from a single-centre retrospective cohort study followed by a prospective clinical examination and pain assessment. The study was based on data from the local birth registry. Newborns born between 1969 and 2002 who had reached adulthood were eligible .. Using a selection algorithm, a study cohort stratified by gestational age (GA) was recruited. Chronic pain conditions were assessed using questionnaire and standardized pain drawings. Data on the pre-, peri- and postnatal clinical course was assessed from medical records. Multivariable logistic regression analyses were conducted to investigate associations between prematurity and chronic pain with adjustment for age, gender, socioeconomic status, and perinatal stress factors. 427 participants born preterm and full-term were included (age 28.5 ± 8.7 years). Chronic pain conditions were similarly common between groups with different levels of prematurity (GA ≥ 37 weeks: 34.5 %, GA33-36 weeks: 37.6 %, GA32-29 weeks: 25.2 %, GA < 29 weeks: 30.4 %, p = 0.20). In multivariable analyses, no association between low GA and the presence of chronic pain was found (OR = 0.99 (CI95 %: 0.94-1.04, p = 0.63); this was also true for a subanalysis of widespread pain. While neither fetal nutritional status nor perinatal stressors were associated with pain, exposure to maternal but not paternal smoking during pregnancy was associated with increased risk to develop pain (OR = 2.77 (CI95 %: 1.31-5.88, p = 0.008) in adults born preterm and full-term. This study suggests that prematurity by itself does not increase the risk of chronic pain later in life, but provides preliminary evidence for maternal smoking during pregnancy as risk factor.

Influences of Maternal Nutrition and Lifestyle Factors on Early Childhood Oral Health: A Systematic Review of Mechanisms and Intervention Strategies.

BACKGROUND: This systematic review and meta-analysis examined the impact of maternal nutrition and lifestyle factors on early childhood oral health. The review focused on the effects of maternal vitamin D levels and smoking during pregnancy on children's dental health outcomes. METHODS: A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science, yielding 23 that were included for analysis. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The effect estimates were pooled through a random effect model. All analyses were carried out using the R program. RESULTS: Most studies in our systematic review showed a significant association between maternal vitamin D and smoking during pregnancy and childhood dental health outcomes. Meta-analysis revealed a significant association between maternal vitamin D levels and children's dental health (OR = 1.30, 95% CI: 0.49 to 3.45, p < 0.001). Maternal smoking during pregnancy was strongly linked to an increased risk of childhood dental caries (OR = 0.3290, 95% CI: 0.2089-0.4491, p < 0.0001). CONCLUSIONS: These findings underscore the crucial role of maternal health behaviors in shaping children's oral health trajectories. This study emphasizes the need for integrated public health interventions promoting healthier maternal behaviors and early preventive dental care.

Exposure to Smoking as a Predictor of ADHD Subtypes Among Children Within Saudi Arabia: An Observational Study.

Previous studies have found an association between maternal smoking and an increased risk of attention deficit hyperactivity disorder (ADHD) in offspring. However, the prevalence of maternal smoking, secondhand smoke (SHS) exposure during pregnancy, and ADHD in children within the Saudi Arabian context is not well-documented. OBJECTIVE: To explore the prevalence of maternal smoking and SHS exposure during pregnancy among mothers of children diagnosed with ADHD and investigate exposure to smoking as a predictor of ADHD subtypes. METHODS: A cross-sectional study was conducted from December 1, 2022, to February 28, 2023, using an online questionnaire. The study included 217 parents of children aged 4-17 years diagnosed with ADHD and without a family history of the disorder. Data on sociodemographic determinants, academic achievement, ADHD types, and maternal smoking habits during pregnancy were collected. RESULTS: Among the mothers surveyed, 6.4% reported smoking during pregnancy, while 41% were exposed to SHS. The study found a predominance of the combined subtype of ADHD among the children. Logistic regression analysis revealed that families with monthly income <10 000 SR were 2.6 times more likely to have a child with inattentive or hyperactive ADHD (P < 0.03). Male gender was associated with a 46% reduced likelihood of these subtypes (P < 0.03). SHS smoking and active exposure to smoking during pregnancy did not show any significant effect on ADHD. CONCLUSION: The study found that child gender and family income were significantly associated with the distribution of ADHD subtypes, while maternal smoking and SHS exposure during pregnancy did not show a significant association. The high prevalence of SHS exposure emphasizes the need for increased public health awareness and interventions to promote smoke-free environments during pregnancy.

Maternal smoking DNA methylation risk score associated with health outcomes in offspring of European and South Asian ancestry.

Background: Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations. Methods: We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504). Results: Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10-5). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10-33) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10-9) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (-0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (-0.043±0.013 kg, p=0.0011) in the combined cohorts. Conclusions: This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers. Funding: This study was funded by the Canadian Institutes of Health Research Metabolomics Team Grant: MWG-146332.

Maternal smoking during pregnancy and early childhood dental caries in children: a systematic review and meta-analysis.

BACKGROUND: Early childhood dental caries, or ECC, is a significant global oral health concern associated with various adverse outcomes. This systematic review and meta-analysis aimed to investigate the potential link between maternal smoking during pregnancy and the occurrence of dental caries in children. METHOD: Through a comprehensive search of PubMed, Scopus, and Google Scholar databases for studies examining the correlation between maternal smoking during pregnancy and childhood caries, we identified 609 relevant articles up to October 2023. Studies were selected, and data extraction was based on the pre-established eligibility criteria and items. Meta-analysis was executed utilizing Comprehensive Meta-analysis (CMA) with a random effects model, ensuring a robust synthesis of the gathered evidence. RESULT: 7 cohorts and five cross-sectional studies, totaling 12 studies, were included in our analysis. The combined results from the studies revealed a significant association between maternal smoking during pregnancy and an increased risk of dental caries in children (OR = 1.78, 95% CI = 1.55-2.05, I2 = 68.53). Sensitivity analyses confirmed the reliability of our results. However, there were indications of publication bias, as suggested by the funnel plot and Egger's test (P = 0.011) concerning the connection between prenatal smoking and childhood caries. CONCLUSION: This review underscores the association between maternal smoking during pregnancy and childhood dental caries. Nevertheless, confounding variables influence this link, necessitating more large-scale, longitudinal studies with adjusted factors. Additional randomized control trials are needed to validate these findings due to the observed heterogeneity. Future research should investigate the precise reasons behind this association. It is essential to raise awareness among pregnant women about the risks of smoking through educational programs.

New Step in Understanding the Pathogenetic Mechanism of Sudden Infant Death Syndrome: Involvement of the Pontine Reticular Gigantocellular Nucleus.

This study aimed to investigate, for the first time, the potential role of the gigantocellular nucleus, a component of the reticular formation, in the pathogenetic mechanism of Sudden Infant Death Syndrome (SIDS), an event frequently ascribed to failure to arouse from sleep. This research was motivated by previous experimental studies demonstrating the gigantocellular nucleus involvement in regulating the sleep-wake cycle. We analyzed the brains of 48 infants who died suddenly within the first 7 months of life, including 28 SIDS cases and 20 controls. All brains underwent a thorough histological and immunohistochemical examination, focusing specifically on the gigantocellular nucleus. This examination aimed to characterize its developmental cytoarchitecture and tyrosine hydroxylase expression, with particular attention to potential associations with SIDS risk factors. In 68% of SIDS cases, but never in controls, we observed hypoplasia of the pontine portion of the gigantocellular nucleus. Alterations in the catecholaminergic system were present in 61% of SIDS cases but only in 10% of controls. A strong correlation was observed between these findings and maternal smoking in SIDS cases when compared with controls. In conclusion we believe that this study sheds new light on the pathogenetic processes underlying SIDS, particularly in cases associated with maternal smoking during pregnancy.

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.

Maternal smoking cessation in the first trimester still poses an increased risk of attention-deficit/hyperactivity disorder and learning disability in offspring.

Background: Studies have found maternal smoking during pregnancy was linked to attention-deficit/hyperactivity disorder (ADHD) risk. It is unclear if maternal smoking cessation during pregnancy lowers ADHD and learning disability (LD) risk in offspring. This study aimed to explore the associations between maternal smoking cessation during pregnancy and ADHD and LD risk in offspring. Methods: Data from the National Health and Nutrition Examination Survey 1999-2004 (8,068 participants) were used. Logistic regression was used to analyze the associations between maternal smoking and smoking cessation during pregnancy and ADHD and LD risk in offspring. Results: Compared to non-smokers' offspring, maternal smoking during pregnancy increased the risk of ADHD (odds ratios [OR] = 2.07, 95% confidence interval [CI]: 1.67-2.56) and LD (OR = 1.93, 95% CI: 1.61-2.31) in offspring, even if mothers quit smoking later (ORADHD = 1.91, 95%CIADHD: 1.38-2.65, ORLD = 1.65, 95%CILD: 1.24-2.19). Further analysis of the timing of initiation of smoking cessation during pregnancy revealed that, compared to non-smokers' offspring, maternal quitting smoking in the first trimester still posed an increased risk of ADHD (OR = 1.72, 95% CI: 1.41-2.61) and LD (OR = 1.52, 95% CI: 1.06-2.17) in offspring. Maternal quitting smoking in the second or third trimester also had a significantly increased risk of ADHD (OR = 2.13, 95% CI: 1.26-3.61) and LD (OR = 1.82, 95% CI: 1.16-2.87) in offspring. Furthermore, maternal smoking but never quitting during pregnancy had the highest risk of ADHD (OR = 2.17, 95% CI: 1.69-2.79) and LD (OR = 2.10, 95% CI: 1.70-2.58) in offspring. Interestingly, a trend toward a gradual increase in the risk-adjusted OR for ADHD and LD risk was observed among the three groups: maternal quitting smoking in the first trimester, maternal quitting smoking in the second or third trimester, and maternal smoking but never quitting. Conclusion: Maternal smoking cessation in the first trimester still poses an increased risk of ADHD and LD in offspring. Furthermore, it seems that the later the mothers quit smoking during pregnancy, the higher the risk of ADHD and LD in their offspring. Therefore, early intervention of maternal smoking in preconception and prenatal care is vital for offspring neurodevelopment.

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.

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.

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.

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.

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.

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.

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.

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.