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Fetal sex and the natural history of maternal risk of diabetes during and after pregnancy


Context — It has recently emerged that carrying a male fetus is associated with poorer maternal beta-cell function in pregnancy and an increased risk of gestational diabetes mellitus (GDM). Beta-cell dysfunction is the central pathophysiologic defect underlying both GDM and subsequent postpartum progression to type 2 diabetes (T2DM).

Objective — To determine whether fetal sex influences the natural history of maternal risk of diabetes after delivery and in a subsequent pregnancy.

Design — Retrospective cohort study.

Setting — Population-based administrative databases in Ontario, Canada.

Patients — All women with a singleton live-birth first pregnancy between April 2000 and March 2010  (n=642,987).

Exposure — Fetal sex (313,280 delivered a girl; 329,707 delivered a boy).

Main Outcome Measure — Development of T2DM or a second pregnancy. Glucose tolerance in each  pregnancy was classified as either GDM or non-GDM.

Results — The population was followed for a median of 3.8 years. Carrying a boy yielded a higher risk of GDM in both the first pregnancy (OR=1.03, 95% CI 1.0002-1.054) and second pregnancy (OR=1.04, 38 1.01-1.08). For women with GDM in the first pregnancy, the likelihood of developing T2DM before a second pregnancy was higher if they delivered a girl (OR=1.07, 95% CI 1.01-1.12). Recurrence of GDM was not affected by fetal sex (p=0.7). However, amongst women with a non-GDM first pregnancy while carrying a girl, having a boy in their second pregnancy predicted an increased risk of GDM (OR=1.07, 42 1.01-1.14).

Conclusions — Fetal sex is a previously-unrecognized factor that is associated with maternal diabetic risk  both after delivery and in a subsequent pregnancy.



Retnakaran R, Shah BR. J Clin Endocrinol Metab. 2015; 100(7):2574-80. Epub 2015 May 20.

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