Improved Periconception A1C Linked to Reduction in Adverse Pregnancy Outcomes

A reduction in glycated hemoglobin (A1C) may result in improved perinatal and maternal outcomes among women with prepregnancy diabetes, according to results of a cohort study published in JAMA Network Open.

Women with diabetes and elevated preconception A1C levels have greater risks of developing a severe maternal morbidity (SMM), and their infants are more prone to congenital anomalies, researchers explained. These conditions can include cardiac malformations, preterm birth, and death.

Although preconception interventions promoting glycemic control are believed to lower these risks, “it is not known whether improved glycemic control between the pre-conception and early pregnancy to mid-pregnancy periods can reduce the risk of adverse perinatal and maternal outcomes,” the authors wrote.

To determine if a net decrease in A1C from preconception to the first half of pregnancy (early pregnancy to mid-pregnancy) is associated with a lower risk of mother and infant adverse outcomes, researchers conducted a population-based cohort study of women giving birth in Ontario, Canada, between 2007 and 2018. Existing data sets were used for the study and linked using unique coded identifiers.

All women with prepregnancy diabetes who had a live birth or stillbirth in an Ontario hospital from 21 weeks’ gestation onward were included in the study. Those who did not have their A1C measured within 90 days of preconception and between conception and 21 weeks’ gestation were excluded.

Twenty-one weeks marks a typical starting point for defining a stillbirth; “most in utero sonographic screening for structural anomalies is completed by this gestational age,” authors wrote.

SMM was defined as a composite outcome made up of roughly 40 indicators arising in pregnancy, during labor, or post partum.

A total of 3459 pregnancies of women with prepregnancy diabetes were included in the final analyses. Mean (SD) maternal age was 32.6 (5) years, and A1C was measured at a mean (SD) of 44.4 (25.5) days prior to conception and at 13.5 (5.4) weeks’ gestation in early pregnancy to mid-pregnancy. Sixty-five pregnancies (1.9%) resulted in a stillbirth or live birth with death at less than 28 days.

Over one-third of births recorded were to immigrant women, while “the rate of chronic hypertension was 7.9%, and 16.5% of women had a preconception hemoglobin concentration less than 12 g/dL.”

Analyses revealed:

• Mean A1C decreased from 7.2% (1.6%) preconception to 6.4% (1.1%) in early pregnancy to mid-pregnancy.
• There were 497 pregnancies (14.4%) with a congenital anomaly, with an adjusted relative risk (aRR) of 0.94 (95% CI, 0.89-0.98) per 0.5% net decrease in A1C, including for cardiac anomalies (237 infants; aRR, 0.89; 95% CI, 0.84-0.95).
• Risk of preterm birth was also reduced per 0.5% net decrease in A1C (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 A1C.
• Women with a 2% absolute net change in A1C from preconception to early pregnancy to mid-pregnancy had an absolute risk of an infant congenital anomaly of 12% (95% CI, 14.0%-17.4%), in contrast to a 15.6% absolute risk (95% CI, 10.4%-13.8%) with a 0 net decrease in A1C.

Overall, improvement in periconception A1C was most strongly associated with a reduced risk of adverse perinatal and maternal outcomes in women whose preconception A1C was higher than 6.4%.

“These results emphasize the importance of improved glycemic control prior to, and soon after, conception,” researchers wrote. “The benefits of improved A1C may translate not only into a reduced risk of congenital anomalies, but also preterm birth and SMM.”

Lack of data on induced abortions or miscarriages and prepregnancy body mass index marks a limitation to the study. Information on diet, insulin, and type of diabetes was also not included in the study.

“There are several evidence-based recommendations for improving periconception glycemic control. A1C reduction can be achieved by lifestyle changes and access to glucose lowering medications, both of which are mediated by improved access to health care, pregnancy planning information, and advocacy,” the authors concluded. Future studies ought to be conducted to determine the best combination of factors that can lead to periconception A1C reductions.

Reference

Davidson AJF, Park AL, Berger H, et al. Association of improved periconception hemoglobin A1C with pregnancy outcomes in women with diabetes. JAMA Netw Open. Published online December 23, 2020. doi: 10.1001/jamanetworkopen.2020.30207