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Comprehensive Assessment of the Associations between Maternal Diabetes and Structural Birth Defects in Offspring: A Phenome-Wide Association Study.

Jeremy M. Schraw,P. Langlois,P. Lupo

Published 2020 in Annals of Epidemiology

ABSTRACT

PURPOSE Our objective was to comprehensively evaluate risk of a broad range of birth defects among offspring of women with diabetes, overall and stratified by pre-gestational versus gestational diagnosis, using the phenome-wide association (PheWAS) methodology. METHODS We performed a registry linkage study of all livebirths (>6,500,000) and birth defects cases (>290,000) in Texas, 1999-2015. We ascertained diabetes from birth and fetal death certificates. We calculated prevalence rate ratios (PRR) for phenotypes with ≥10 cases among exposed offspring (N=130). RESULTS Diabetes was associated with prevalence of any defect (PRR 1.40, 95% confidence interval [CI] 1.38-1.42), multiple defects (PRR 1.86, 95% CI 1.81-1.91), and 60 specific phenotypes, including novel (hypospadias, mitral stenosis) and previously reported phenotypes (renal a-/dysgenesis, spinal anomalies). Pre-gestational diabetes was a stronger risk factor for any defect (PRR 2.00, 95% CI 1.93-2.07), multiple defects (PRR 3.27, 95% CI 3.11-3.44), and the 60 specific phenotypes evaluated. Gestational diabetes was associated with any defect (PRR 1.21, 95% CI 1.19-1.23) and 47 specific birth defects phenotypes, although associations were weaker than for pregestational diabetes. CONCLUSIONS The PheWAS is an efficient way to identify risk factors for disease using population-based registry data. Pre-gestational diabetes is associated with a broader range of phenotypes than previously reported. Because diabetes is diagnosed in 1% of women prior to pregnancy and 6-9% during pregnancy, our results highlight a significant public health concern.

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