Association of improved periconception hemoglobin A1c with pregnancy outcomes in women with diabetes

Importance — Prepregnancy diabetes is associated with higher perinatal and maternal morbidity, especially if periconception glycemic control is suboptimal. It is not known whether improved glycemic control from preconception to early pregnancy and midpregnancy periods can reduce the risk of adverse perinatal and maternal outcomes.

Objective — To determine whether a net decline in glycated hemoglobin A_1c (HbA_1c) from preconception to the first half of pregnancy is associated with a lower risk of adverse outcomes for mother and child.

Design, Setting, and Participants — This population-based cohort study was completed in all of Ontario, Canada, from 2007 to 2018. Included were births among women with prepregnancy diabetes whose HbA1c was measured within 90 days preconception and again from conception through 21 weeks completed gestation (early pregnancy to midpregnancy). Statistical analysis was performed from July to September 2020.

Exposures — Net decrease in HbA_1c from preconception to early pregnancy and midpregnancy.

Main Outcomes and Measures — The main outcome was a congenital anomaly from birth to age 1 year. Other outcomes included preterm birth or perinatal mortality among offspring as well as severe maternal morbidity (SMM) or death among mothers. Adjusted relative risks (aRRs) were calculated per 0.5% absolute net decline in HbA1c from preconception up to early pregnancy and midpregnancy, adjusting for maternal age at conception, preconception HbA_1c and hemoglobin concentration, and gestational age at HbA_1c measurement.

Results — A total of 3459 births were included, with a mean (SD) maternal age of 32.6 (5.0) years at conception. Overall, the mean (SD) HbA_1c decreased from 7.2% (1.6%) preconception to 6.4% (1.1%) in early pregnancy to midpregnancy. There were 497 pregnancies (14.4%) with a congenital anomaly, with an aRR of 0.94 (95% CI, 0.89-0.98) per 0.5% net decrease in HbA_1c, including for cardiac anomalies (237 infants; aRR, 0.89; 95% CI, 0.84-0.95). The risk was also reduced for preterm birth (847 events; aRR, 0.89; 95% CI, 0.86-0.91). SMM or death occurred among 191 women (5.5%), with an aRR of 0.90 (95% CI, 0.84-0.96) per 0.5% net decrease in HbA_1c.

Conclusions and Relevance — These findings suggest that women with prepregnancy diabetes who achieve a reduction in HbA_1c may have improved perinatal and maternal outcomes. Further study is recommended to determine the best combination of factors, such as lifestyle changes and/or glucose-lowering medications, that can influence periconception HbA_1c reduction.