Early-life menstrual characteristics and gestational diabetes in a large US cohort

Background: Associations between early-life menstrual cycle characteristics (MCC) and gestational diabetes (GDM) remain unclear.

Objectives: To evaluate associations between early-life MCCs and GDM in first pregnancy, across pregnancies and its recurrence.

Methods: This analysis included participants from a US-based digital cohort enrolled between 11/2019 and 9/2023 who provided consent, completed relevant surveys, were without diabetes and aged ≥18 at first pregnancy (n = 30,473). Age at menarche [<11 (early), 11-15 (referent), ≥16 (late) years] and time from menarche to cycle regularity [<1 (referent), 1-2, 3-4, ≥5 years, not yet regular, regular after hormones] were self-recalled at enrolment. Additionally, the last three categories were considered prolonged time-to-regularity (PTTR). GDM history was recalled at enrolment for each pregnancy. We restricted to pregnancies of ≥24 weeks with a live birth. We evaluated associations of early-life MCCs with GDM at first pregnancy using modified Poisson regression, across pregnancies using cluster-weighted Poisson generalised estimating equation and GDM recurrence using multinomial logistic regression, adjusted for sociodemographic, early-life factors and age at pregnancy. Missing variables were imputed with multiple imputation by chained equations.

Results: Among 30,473 participants, 20,591 had eligible first pregnancies, of which 5.9% reported GDM. In 17,512 participants with ≥2 pregnancies, 8.3% had GDM once and 3.7% had recurrent GDM. Early menarche (<11 years, vs. 11-15 years) was associated with GDM in first pregnancy (RR 1.34, 95% CI 1.15, 1.57), across pregnancies (RR 1.24, 95% CI 1.10, 1.39) and recurrence (OR 1.51, 95% CI 1.21, 1.89). PTTR was associated with GDM in the first pregnancy (RR 1.22, 95% CI 1.08, 1.38), across pregnancies (RR 1.16, 95% CI 1.05, 1.27) and recurrence (OR 1.19, 95% CI 0.99, 1.43).

Conclusions: Earlier menarche and prolonged time-to-regularity are associated with higher risk of GDM and recurrence, suggesting menstrual characteristics during childhood/adolescence as potential early-life markers for GDM.