Association between maternal pregestational diabetes mellitus and spina bifida: A population-based case-control study, Finland, 2000-2014

Background Maternal pregestational diabetes mellitus (PGDM) is a known risk factor for neural tube defects. We examined the association between maternal PGDM and spina bifida in the offspring using PGDM status from medical records in Finland. Methods We conducted a nationally representative, multiregistry, population-based case-control study in Finland. Cases were included if they were live or stillborn infants and diagnosed with spina bifida and delivered between years 2000 and 2014 in Finland. Controls were Finnish infants without spina bifida or other major structural birth defects and delivered during the same time period as cases. Clinical and demographic data were obtained by linking multiple national health registers and census. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (CI) for PGDM were estimated using logistic regression analysis. Interaction by maternal obesity was examined. Results Our study included 181 spina bifida cases (61% isolated) and 876,672 controls. Overall, 2.2% percent of all case, and 0.5% of control mothers, had PGDM during pregnancy. Maternal PGDM was significantly associated with an increased odds of spina bifida (adjusted OR 4.35; 95% CI 1.37, 13.82). A similar association was found in our subanalysis on isolated spina bifida cases (adjusted OR 4.41; 95% CI 1.07, 18.24). There was no significant interaction by maternal obesity. Conclusions Maternal PGDM was positively associated with spina bifida in Finland, and maternal obesity did not modify this effect. We lacked information on maternal PGDM for electively terminated and spontaneously aborted cases; results should be interpreted with caution.