The influence of maternal body mass index, maternal diabetes mellitus, and maternal smoking during pregnancy on the risk of childhood-onset type 1 diabetes mellitus in the offspring: Systematic review and meta-analysis of observational studies.

There is emerging evidence that events occurring before and shortly after birth may be important in determining the risk of childhood-onset type 1 diabetes mellitus (T1DM). We aimed to summarize and synthesize the associations between maternal body mass index (BMI), maternal diabetes mellitus (DM), and maternal smoking during pregnancy and the risk of childhood-onset T1DM in the offspring by performing a systematic review and meta-analysis of observational studies. A random effects model was used to generate the summary risk estimates. The PubMed and Web of Science databases were searched to identify relevant observational studies. Twenty one observational studies were included in the present meta-analysis. Compared with offspring of mothers with normal weight, offspring of women with overweight or obesity were at an increased risk of developing childhood-onset T1DM (overweight: relative risk [RR] 1.09, 95% confidence interval [CI], 1.03-1.15; obesity: RR 1.25, 95% CI, 1.16-1.34; per 5 kg m-2 increase in BMI: RR 1.10, 95% CI, 1.06-1.13). No association was found for maternal underweight (RR 0.92, 95% CI, 0.75-1.13). Maternal DM was associated with an increased risk of childhood-onset T1DM (RR 3.26, 95% CI, 2.84-3.74). Regarding the type of maternal DM, the greatest risk of T1DM in the offspring appeared to be conferred by maternal T1DM (RR 4.46, 95% CI, 2.89-6.89), followed by maternal gestational diabetes mellitus (RR 1.66, 95% CI, 1.16-2.36), and lastly by maternal type 2 diabetes mellitus (RR 1.11, 95% CI, 0.69-1.80). Additional analysis of studies comparing maternal versus paternal T1DM within the same population revealed that offspring of fathers with T1DM had a 1.5 times higher risk of developing childhood-onset T1DM than offspring of mothers with T1DM (RR 9.58, 95% CI, 6.33-14.48 vs. RR 6.24, 95% CI, 5.52-7.07). Furthermore, a reduced risk of childhood-onset T1DM was observed in infants born to mothers who smoked during pregnancy compared with infants born to mothers who did not smoke during pregnancy (RR 0.79, 95% CI, 0.71-0.87). In summary, our findings add further evidence that early-life events or environmental factors may play a role in modulating infants' risk of developing T1DM later in life.