Prepregnancy hemoglobin A1c and risk of maternal complications

Canadian researchers say that prepregnancy elevated levels of hemoglobin A1C—even below thresholdsfor diabetes mellitus (DM)—may increase risk of severe maternal morbidity. The findings are from a population-based cohort study published in PLoS Medicine.1

The main cohort included 31,225 women aged 16 to 50 with a hospital live birth or stillbirth from 2007 to 2015 who had an A1c measured within 90 days before conception. Of thecohort noted, 90% (28,075) had no known prepregnancy DM.

Cut-points used to diagnose diabetes were A1c < 5.8% for normal, 5.8% to 6.4% for prediabetes, and > 6.4% for DM.

The main outcome was severe maternal morbidity or maternal mortality from 23 weeks’ gestation up to 42 days postpartum. Poisson regression was used to generate relative risks, with adjustment for maternal age, multifetal pregnancy, world region of origin, and tobacco/drug dependence.

Severe maternal morbidity or death occurred in 682 births, with a relative risk (RR) of 1.16 (95% confidence interval [CI] 1.14 to 1.19; P < 0.001) per 0.5 increase in A1c and 1.16, (95% CI 1.13 to 1.18; P < 0.001) after adjusting for the covariates. The adjusted RR was increased among those with and without prepregnancy DM (1.11, 95% CI 1.07-1.14; P < 0.001 and 1.15, 95% CI 1.02 to 1.29; P < 0.001, respectively).

The adjusted RRs for body mass index and chronic hypertension and prepregnancy serum creatinine were 1.15, 95% CI 1.11 to 1.20; P < 0.001 and 1.11, 95% CI 1.04 to 1.18; P = 0.002, respectively.

Looking at specific A1c levels, the authors found that in women with a preconception level of 5.8% to 6.4%, the adjusted RR for severe maternal morbidity or death was 1.31 (95% CI 1.06 to 1.62; P = 0.01), for A1c > 6.4% it was 2.84 (95% CI 2.31 to 3.49; P < 0.001), each relative to an A1c < 5.8%. In women with an A1c of > 6.4% who did not have prepregnancy DM, the adjusted RR for severe maternal morbidity or mortality was 3.25 (95% CI 1.76 to 6.00; P < 0.001).

The authors said this research “underscores the importance of identifying women with any degree of prepregnancy hyperglycemia, given their higher risk of severe maternal morbidity.”

They noted that their approach was novel, in that they bundled indicators of SMM [severe maternal morbidity] into those likely, possibly, and unlikely to be related to preconception A1C.

“Not all indicators have the same association with A1c,” they concluded, “which may direct future research and potential initiatives to reduce SMM.”

Reference

1. Davidson AJF, Park AL, Berger H, Aoyama K, Harel Z, Cook JL, et al. Risk of severe maternal morbidity or death in relation to elevated hemoglobin A1c preconception, and in early pregnancy: A population-based cohort study. PLoS Med. 17(5):e1003104. https://doi.org/10.1371/journal.pmed.1003104.