Maternal cigarette smoking before or during pregnancy increases the risk of birth congenital anomalies: a population-based retrospective cohort study of 12 million mother-infant pairs

Background The associations of maternal cigarette smoking with congenital anomalies in offspring have been inconsistent. This study aimed to clarify the associations of the timing and intensity of maternal cigarette smoking with 12 subtypes of birth congenital anomalies based on a nationwide large birth cohort in the USA. Methods We used nationwide birth certificate data from the US National Vital Statistics System during 2016–2019. Women reported the average daily number of cigarettes they consumed 3 months before pregnancy and in each subsequent trimester during pregnancy. Twelve subtypes of congenital anomalies were identified in medical records. Poisson regression analysis was used to estimate the risk ratios (RRs) with 95% confidence intervals (CIs) for 12 subtypes of congenital anomalies associated with the timing (i.e., before pregnancy, and during three different trimesters of pregnancy) and intensity (i.e., number of cigarettes consumed per day) of maternal cigarette smoking. Results Among the 12,144,972 women included, 9.3% smoked before pregnancy and 7.0%, 6.0%, and 5.7% in the first, second, and third trimester, respectively. Maternal smoking before or during pregnancy significantly increased the risk of six subtypes of birth congenital anomalies (i.e., congenital diaphragmatic hernia, gastroschisis, limb reduction defect, cleft lip with or without cleft palate, cleft palate alone, and hypospadias), even as low as 1–5 cigarettes per day. The adjusted RRs (95% CIs) for overall birth congenital anomalies (defined as having any one of the congenital malformations above significantly associated with maternal cigarette smoking) among women who smoked 1–5, 6–10, and ≥ 11 cigarettes per day before pregnancy were 1.31 (1.22–1.41), 1.25 (1.17–1.33), and 1.35 (1.28–1.43), respectively. Corresponding values were 1.23 (1.14–1.33), 1.33 (1.24–1.42), 1.33 (1.23–1.43), respectively, for women who smoked cigarettes in the first trimester; 1.32 (1.21–1.44), 1.36 (1.26–1.47), and 1.38 (1.23–1.54), respectively, for women who smoked cigarettes in the second trimester; and 1.33 (1.22–1.44), 1.35 (1.24–1.47), and 1.35 (1.19–1.52), respectively, for women who smoked cigarettes in the third trimester. Compared with women who kept smoking before and throughout pregnancy, women who never smoked had significantly lower risk of congenital anomalies (RR 0.77, 95% CI 0.73–0.81), but women who smoked before pregnancy and quitted during each trimester of pregnancy had no reduced risk (all P > 0.05). Conclusions Maternal smoking before or during pregnancy increased the risk of several birth congenital anomalies, even as low as 1–5 cigarettes per day. Maternal smokers who stopped smoking in the subsequent trimesters of pregnancy were still at an increased risk of birth congenital anomalies. Our findings highlighted that smoking cessation interventions should be implemented before pregnancy.

Maternal smoking during pregnancy and type 1 diabetes in the offspring: A nationwide register-based study with family-based designs

Objectives: Maternal smoking during pregnancy is associated with a reduced risk of type 1 diabetes (T1D) in the offspring. We investigated whether this association is consistent with a causal interpretation by accounting for familial (shared genetic and environmental) factors using family-based, quasi-experimental designs. Design: A nationwide, prospective cohort study and a nested case-control study (quasi-experiment) comparing children with T1D to their age-matched siblings (or cousins). Setting: Swedish national registers. Participants: We included 2,995,321 children born in Sweden between 1983 and 2014. Exposure: Information on maternal smoking during pregnancy was retrieved from the Swedish Medical Birth Register. Main outcome measures: Children were followed for a diagnosis of T1D until 2020 through the National Patient, Diabetes and Prescribed Drug Registers. Results: A total of 18,617 children developed T1D, with a median age at diagnosis of 9.4 years. The sibling and cousin comparison design included 14,284 and 7,988 of these children, respectively. Maternal smoking during pregnancy was associated with a 22% lower risk of offspring T1D in the full cohort (hazard ratio: 0.78, 95% confidence interval [CI]: 0.75 to 0.82) in the multivariable-adjusted model. The corresponding odds ratio was 0.78 (95% CI: 0.69 to 0.88) in the sibling and 0.72 (95% CI: 0.66 to 0.79) in the cousin comparison analysis. Conclusions: This nationwide, family-based study provides support for a protective effect of maternal smoking on offspring T1D. Mechanistic studies are needed to elucidate the underlying pathways behind this link.

Factors Affecting The Outcome of in Vitro Fertilization (IVF)

The high prevalence of infertility motivated researchers to find a solution, henceforth In Vitro Fertilization was invented. Factors that affect the outcome of IVF may include sperm analysis, maternal Body Mass Index (BMI), maternal smoking habits, endometriosis, and maternal age. However, there are ongoing debates about the role of said factors regarding the outcome of IVF. The objective of this research is to analyze those factors. This research is a Case-Control study with an analytical observational design. Data were retrieved from patients’ medical records undergoing IVF in Graha Amerta Fertility Clinic from January 2019-October 2020. First, the Chi-Square Test revealed sperm abnormality (p=0.212), Maternal BMI (p=0.427), endometriosis (p=0.067), meaning there was no connection with the outcome of IVF. Simultaneously, maternal age (p=0.037) showed a connection with the outcome of IVF. From the Binary Logistic Regression Test, maternal age 36-40 years old (p=0.044) affects the outcome of IVF significantly. Concurrently maternal BMI, endometriosis, and sperm abnormality have p value>0.05 meaning it is insignificant to the outcome of IVF. This research concluded that sperm abnormality, maternal BMI, and endometriosis do not affect the outcome of IVF. There was no data about maternal smoking habits. Whilst maternal age affects the outcome of IVF. Conclusion: This research concluded that sperm abnormality, maternal BMI, and endometriosis do not affect the outcome of IVF. There was no data about maternal smoking habits. Whilst maternal age affects the outcome of IVF.

Factors associated with breastfeeding initiation and continuation in Canadian-born and non-Canadian-born women: a multi-centre study

Objective: To identify factors associated with breastfeeding initiation and continuation in Canadian-born and non-Canadian-born women. Design: Prospective cohort of mothers and infants born from 2008–2012: the CHILD Cohort Study. Setting: General community setting in four Canadian provinces. Participants: 3455 pregnant women from Vancouver, Edmonton, Winnipeg, and Toronto between 2008 and 2012. Results: Of 3010 participants included in this study, the majority were Canadian-born (75.5%). Breastfeeding initiation rates were high in both non-Canadian-born (95.5%) and Canadian-born participants (92.7%). The median breastfeeding duration was 10 months in Canadian-born participants and 11 months in non-Canadian-born participants. Among Canadian-born participants, factors associated with breastfeeding initiation and continuation were older maternal age, higher maternal education, living with their partner, and recruitment site. Rooming-in during the hospital stay was also associated with higher rates of breastfeeding initiation, but not continuation at 6-months postpartum. Factors associated with non-initiation of breastfeeding and cessation at 6-months postpartum were maternal smoking, living with a current smoker, cesarean birth, and early-term birth. Among non-Canadian-born participants, maternal smoking during pregnancy was associated with lower odds of breastfeeding initiation, and lower odds of breastfeeding continuation at 6 months, and older maternal age and recruitment site were associated with breastfeeding continuation at 6 months. Conclusions: Although Canadian-born and non-Canadian-born women in the CHILD cohort have similar breastfeeding initiation rates, breastfeeding initiation and continuation are more strongly associated with sociodemographic characteristics in Canadian-born participants. Recruitment site was strongly associated with breastfeeding continuation in both groups and may indicate geographic disparities in breastfeeding rates nationally.

Polymethylation Scores for Prenatal Maternal Smoke Exposure Persist Until Age 15 and Are Detected in Saliva

Background: Prenatal maternal smoking has negative implications for child health. DNA methylation signatures can function as biomarkers of prenatal maternal smoking. However little work has assessed how DNA methylation signatures of prenatal maternal smoking vary across ages, ancestry groups, or tissues. In the Fragile Families and Child Wellbeing study, we tested whether prenatal maternal smoking was associated with salivary polymethylation scores for smoking in participants. We assessed the consistency of associations at ages 9 and 15, their portability across participants from African, European, and Hispanic genetic ancestries and the accuracy of exposure classification using area under the curve (AUC) from receiver operating curve analyses. Results: We created saliva polymethylation scores using coefficients from a meta-analysis of prenatal maternal smoke exposure and DNA methylation in newborn cord blood. In the full sample at age 9 (n=753), prenatal maternal smoke exposure was associated with a 0.52 (95%CI: 0.36, 0.67) standard deviation higher polymethylation score for prenatal smoke exposure The direction and magnitude of the association was consistent when stratified by genetic ancestries. In the full sample at age 15 (n=746), prenatal maternal smoke exposure was associated with a 0.46 (95%CI: 0.3, 0.62) standard deviation higher polymethylation score for prenatal smoke exposure, and the effect size was attenuated among the European and Hispanic genetic ancestry samples. The polymethylation score was reasonably accurate at classifying prenatal maternal smoke exposure (AUC age 9=0.77, P value<0.001, age 15=0.77, P value<0.001). The polymethylation score showed higher classification accuracy than using a single a priori site in the AHRR gene (cg05575921 AUC=0.74, P value=0.03; age 15=0.73, P value=0.01). Conclusions: Prenatal maternal smoking was associated with DNA methylation signatures in saliva samples, a clinically practical tissue. Polymethylation scores for prenatal maternal smoking were portable across genetic ancestries and more accurate than individual DNA methylation sites. DNA polymethylation scores from saliva samples could serve as robust and practical clinical biomarkers of prenatal maternal smoke exposure.

Do Genetic Variants Modify the Effect of Smoking on Risk of Preeclampsia in Pregnancy?

Objective Maternal smoking is associated with as much as a 50% reduced risk of preeclampsia, despite increasing risk of other poor pregnancy outcomes that often co-occur with preeclampsia, such as preterm birth and fetal growth restriction. Researchers have long sought to understand whether this perplexing association is biologically based, or a result of noncausal mechanisms. We examined whether smoking-response genes modify the smoking-preeclampsia association to investigate potential biological explanations. Study Design We conducted a nested case–control study within the Norwegian Mother, Father and Child Birth Cohort (1999–2008) of 2,596 mother–child dyads. We used family-based log-linear Poisson regression to examine modification of the maternal smoking-preeclampsia relationship by maternal and fetal single nucleotide polymorphisms involved in cellular processes related to components of cigarette smoke (n = 1,915 with minor allele frequency ≥10%). We further investigated the influence of smoking cessation during pregnancy. Results Three polymorphisms showed overall (p < 0.001) multiplicative interaction between smoking and maternal genotype. For rs3765692 (TP73) and rs10770343 (PIK3C2G), protection associated with smoking was reduced with two maternal copies of the risk allele and was stronger in continuers than quitters (interaction p = 0.02 for both loci, based on testing 3-level smoking by 3-level genotype). For rs2278361 (APAF1) the inverse smoking-preeclampsia association was eliminated by the presence of a single risk allele, and again the trend was stronger in continuers than in quitters (interaction p = 0.01). Conclusion Evidence for gene–smoking interaction was limited, but differences by smoking cessation warrant further investigation. We demonstrate the potential utility of expanded dyad methods and gene–environment interaction analyses for outcomes with complex relationships between maternal and fetal genotypes and exposures. Key Points