Perinatal & Pediatric
Exposure to gestational diabetes and hypertension in offspring: A triangulation approach Nicole Brunton* Nicole Brunton Heather J. Prior Randy Walld Allison Dart Nathan Nickel Todd A. Duhamel Jonathan McGavock
Background: Exposure to gestational diabetes mellitus (GDM) is associated with increased risk for cardiovascular morbidity including adolescent hypertension. Whether this association represents a causal in utero mechanism remains unclear.
Methods: This study leveraged administrative health data from 418,169 singleton born offspring from 224,963 families in Manitoba, Canada. GDM and adolescent hypertension were determined using ICD codes and validated algorithms. We conducted three complimentary analyses. First, we compared rates of hypertension between offspring exposed to GDM and controls that were exact-matched on birthyear, socioeconomic index, maternal age, parity, residence, and health region using a Poisson model with person-years of the denominator as an offset. Second, we repeated these analyses using paternal type 2 diabetes status as a negative exposure control. Lastly, a sibling analysis compared the incidence of hypertension between siblings discordant for GDM exposure.
Results: Between unrelated families (n=209,461), risk of hypertension was 35% higher in GDM exposed vs unexposed offspring (RR:1.35, 95%CI: 1.19,1.54). After matching on covariates (n=11,612), there was a similar increased risk of hypertension among offspring exposed to GDM (RR:1.41, 95%CI: 1.16,1.72). Among all paternal-offspring pairs (n=145,318), hypertension risk was 1.7-fold higher for offspring whose fathers lived with diabetes (RR:1.70, 95% CI: 1.28, 2.27). The sample was considerably smaller after matching (n=2,022); however, the effect size remained similar, though it was less precise (RR:1.50, 95%CI: 0.96,2.24). There was no difference in risk for hypertension among sibling-pairs discordant for GDM exposure (n=12,204; OR:1.01, 95%CI: 0.83,1.21).
Conclusion: Collectively, these findings suggest that previously documented associations between exposure to GDM and increased risk of offspring hypertension may be due to family-based confounding rather than a direct in utero mechanism.