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The effect of maternal pre-/early-pregnancy BMI and pregnancy smoking and alcohol on congenital heart diseases: a parental negative control study.

ABSTRACT: Congenital heart diseases (CHDs) are the most common congenital anomaly. The causes of CHDs are largely unknown. Higher prenatal body mass index (BMI), smoking and alcohol consumption are associated with increased risk of CHDs. Whether these are causal is unclear. Seven European birth cohorts including 232,390 offspring (2,469 CHD cases [1.1%]) were included. We applied negative exposure paternal control analyses to explore the intrauterine effects of maternal BMI, smoking and alcohol consumption during pregnancy, on offspring CHDs and CHD severity. We used logistic regression and combined estimates using a fixed-effects meta-analysis. Analyses of BMI categories resulted in similar increased odds of CHD in overweight (mothers OR: 1.15 (1.01, 1.31) and fathers 1.10 (0.96, 1.27)) and obesity (mothers OR: 1.12 (0.93, 1.36) and fathers 1.16 (0.90, 1.50)). The association of mean BMI with CHD was null. Maternal smoking was associated with increased odds of CHD (OR: 1.11 (0.97, 1.25)) but paternal smoking was not (OR: 0.96 (0.85, 1.07)). The difference increased when removing offspring with genetic/chromosomal defects (mothers OR: 1.15 (1.01, 1.32) and fathers 0.93 (0.83, 1.05)). The positive association with maternal pregnancy smoking appeared to be driven by non-severe CHD cases (OR: 1.22 (1.04, 1.44)). Associations with maternal (OR: 1.16 (0.52, 2.58)) and paternal (OR: 1.23 (0.74, 2.06)) moderate/heavy pregnancy alcohol consumption were similar. We found evidence of an intrauterine effect for maternal smoking on offspring CHDs, but no evidence for higher maternal BMI or alcohol consumption. Our findings provide further support for why smoking cessation is important during pregnancy.

SUBMITTER: Taylor K

PROVIDER: S-EPMC7654878 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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The effect of maternal pre-/early-pregnancy BMI and pregnancy smoking and alcohol on congenital heart diseases: a parental negative control study.

Taylor Kurt K Elhakeem Ahmed A Nader Johanna Lucia Thorbjørnsrud JLT Yang Tiffany T Isaevska Elena E Richiardi Lorenzo L Vrijkotte Tanja T de Moira Angela Pinot AP Murray Deirdre M DM Finn Daragh D Mason Dan D Wright John J Oddie Sam S Roeleveld Nel N Harris Jennifer R JR Nybo Andersen Anne-Marie AM Caputo Massimo M Lawlor Deborah A DA

medRxiv : the preprint server for health sciences 20201104

<h4>Background</h4>Congenital heart diseases (CHDs) are the most common congenital anomaly. The causes of CHDs are largely unknown. Higher prenatal body mass index (BMI), smoking and alcohol consumption are associated with increased risk of CHDs. Whether these are causal is unclear.<h4>Methods and results</h4>Seven European birth cohorts including 232,390 offspring (2,469 CHD cases [1.1%]) were included. We applied negative exposure paternal control analyses to explore the intrauterine effects o ...[more]

PMID: 33173887

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Project description:BackgroundThe importance of the maternal-infant dyad in the genesis of nonalcoholic fatty liver disease (NAFLD) is of increasing interest. The Avon Longitudinal Study of Parents and Children (ALSPAC) showed that at age 24, 1 in 5 had NAFLD measured by transient elastography and controlled attenuation parameter (CAP). Our aim was to investigate the association between breastfeeding duration and maternal pre-pregnancy BMI on offspring NAFLD in young adulthood.Methods4021 participants attended clinic for FibroScan and CAP measurement using Echosens 502 Touch®. 440 participants with Alcohol Use Disorders were excluded. Offspring of 100 non-singleton pregnancies were excluded. 2961 valid CAP measurements for NAFLD were analysed. Exposures of interest were breastfeeding of any duration, ≥6months exclusive breastfeeding, and maternal pre-pregnancy BMI. Multivariable regression models estimated the odds of NAFLD at 24 years. We performed a paternal negative control test to explore residual confounding in the analyses of pre-pregnancy BMI.FindingsThere was a modest inverse association of exclusive and non-exclusive breastfeeding ≥6 months having a protective effect on NAFLD in offspring (OR 0·92 [95%CI 0·66-1·27] and OR 0·90 [0·67-1·21] respectively).The odds of offspring NAFLD in overweight pre-pregnancy maternal BMI and paternal BMI was OR 2·09 [1·62-2·68] and OR 1·33 [95%CI 1·07-1·65] respectively, with the ratio of effect sizes OR 1·57 [1·11-2·22]. Similarly, odds of offspring NAFLD with obese pre-pregnancy maternal BMI and paternal BMI was OR 2·66 [1·71-4·14] and OR 1·35 [0·91-2·00] respectively, with the ratio of effect sizes OR 1·98 [1·05-3·74].InterpretationHigher maternal pre-pregnancy BMI was associated with offspring NAFLD, having accounted for shared parental confounding. We did not replicate previous work that found a strong association between breastfeeding and NAFLD.FundingMedical Research Council UK, Alcohol Research UK, David Telling Charitable Trust.

Project description:BackgroundPrior studies suggested that maternal smoking before and during pregnancy could be associated with increased risks of congenital heart diseases (CHDs) in offspring. However, the results were inconsistent, and the existence of a causal relationship was not confirmed. Our study aimed to estimate the associations of maternal active and passive smoking during the pre-pregnancy/early-pregnancy period with CHDs as well as its common phenotypes in offspring.MethodsThis study was based on data from a prospective cohort study conducted in Central China. A total of 49 158 eligible pregnant women between the 8th and 14th weeks of gestation were invited to join the cohort and were planned to be followed up until 3 months postpartum. The exposure of interest was maternal smoking status, including active and passive smoking status in 3 months before pregnancy as well as in early pregnancy. Self-reported maternal smoking status was ascertained via an in-person interview after recruitment. CHDs were diagnosed by pediatric cardiologists and classified according to ICD-10. Multivariable Poisson regression models were used to estimate the relative risks (RRs) with 95% confidence intervals (CIs) of all CHDs and their common phenotypes associated with maternal smoking status, adjusting for potential confounding factors identified by directed acyclic graphs.ResultsCHDs were diagnosed in 564 children. After adjusting for potential confounding factors and comparing with the unexposed groups, CHDs incidence was 165% higher (adjusted RR = 2.65; 95% CI = 1.76-3.98) in offspring exposed to maternal active smoking in 3 months before pregnancy, 69% higher (adjusted-RR = 1.69; 95% CI = 1.39-2.05) in offspring exposed to maternal passive smoking in 3 months before pregnancy, 133% higher (adjusted RR = 2.33; 95% CI = 1.46-3.70) for offspring exposed to maternal active smoking in early pregnancy, and 98% higher (adjusted-RR = 1.98; 95% CI = 1.56-2.51) for offspring exposed to maternal passive smoking in early pregnancy. More specifically, the offspring exposed to maternal active smoking in early pregnancy had the highest risk of Tetralogy of Fallot (adjusted RR = 9.84; 95% CI = 2.49-38.84). These findings were recapitulated in analyses that further adjusted for other behaviour variables apart from the characteristic being assessed and were also confirmed by sensitivity analyses.ConclusionsOur findings add to the existing body of evidence that implicates maternal pre-pregnancy/early-pregnancy smoking as a significant risk factor for CHDs and their select phenotypes.

Dataset Information

The effect of maternal pre-/early-pregnancy BMI and pregnancy smoking and alcohol on congenital heart diseases: a parental negative control study.

Publications

The effect of maternal pre-/early-pregnancy BMI and pregnancy smoking and alcohol on congenital heart diseases: a parental negative control study.

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