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

Abstract

Background Maternal smoking during pregnancy was reported to be associated with a reduced risk of type 1 diabetes 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. Methods We included 2,995,321 children born in Sweden between 1983 and 2014 and followed them for a diagnosis of type 1 diabetes until 2020 through the National Patient, Diabetes and Prescribed Drug Registers. Apart from conducting a traditional cohort study, we performed a nested case–control study (quasi-experiment) comparing children with type 1 diabetes to their age-matched siblings (or cousins). Information on maternal smoking during pregnancy was retrieved from the Swedish Medical Birth Register. Multivariable adjusted Cox proportional hazards regression and conditional logistic regression were used. Results A total of 18,617 children developed type 1 diabetes, with a median age at diagnosis of 9.4 years. The sibling and cousin comparison design included 14,284 and 7988 of these children, respectively. Maternal smoking during pregnancy was associated with a 22% lower risk of offspring type 1 diabetes in the full cohort (hazard ratio 0.78, 95% confidence interval [CI] 0.75–0.82). The corresponding odds ratio was 0.78 (95% CI 0.69–0.88) in the sibling and 0.72 (95% CI 0.66–0.79) in the cousin comparison analysis. Conclusions This nationwide, family-based study provides support for a protective effect of maternal smoking on offspring type 1 diabetes. Mechanistic studies are needed to elucidate the underlying pathways behind this link.

Maternal factors during pregnancy influencing maternal, fetal, and childhood outcomes

“…Although these data suggest a protective effect of maternal smoking on the risk for offspring to develop type 1 diabetes, mechanistic studies are needed to elucidate the underlying pathways behind this link. Despite these findings, we emphasize that smoking during pregnancy should be strongly advised against since it has severe effects on fetal and childhood health [21].…”

“…Also focusing on the influencing factors on metabolic health, a Swedish nationwide register-based study investigated the association between maternal smoking during pregnancy and type 1 diabetes in the offspring [21]. The cohort consisted of nearly three million children born between the years 1983 and 2014, with follow-up until 2020.…”

Exploring the Causal Relationship Between Modifiable Exposures and Diabetes Mellitus: A Two-Sample Mendelian Randomization Analysis

“…Maternal smoking may also impair pancreatic development or cause epigenetic modifications in offspring [ 62 ]. However, other research has paradoxically shown maternal smoking may reduce type 1 diabetes risk in offspring [ 63 , 64 ]. The mechanisms underlying this discrepancy remain unclear.…”

Maternal smoking during pregnancy and health outcomes in offspring

“…The study by Wei et al [8] provided strong evidence of a lower risk of type 1 diabetes for children exposed to MSDP as compared to unexposed children, by using family-based designs of sibling and cousin comparison analyses. However, this should not preclude the development and implementation of tobacco control policies in pregnant women.…”

“…To control for potential confounders from unmeasured familial background factors, apart from a traditional cohort study design, Wei et al [8] used a family-based, nested case-control study by matching children with type 1 diabetes to their siblings and cousins who were free of diabetes. Sibling and cousin comparisons are quasiexperimental designs, which use design features to help minimise confounding effects from genetic and environmental factors that are shared by family members [9].…”