Risk of severe maternal morbidity or death in relation to elevated hemoglobin A1c preconception, and in early pregnancy: A population-based cohort study

Abstract

BackgroundThe relation between prepregnancy average glucose concentration and a woman's risk of severe maternal morbidity (SMM) is unknown. The current study evaluated whether an elevated preconception hemoglobin A1c (A1c) is associated with SMM or maternal death among women with and without known prepregnancy diabetes mellitus (DM). Methods and findingsA population-based cohort study was completed in Ontario, Canada, where there is universal healthcare. The main cohort included 31,225 women aged 16-50 years with a hospital live birth or stillbirth from 2007 to 2015, and who had an A1c measured within 90 days before conception, including 28,075 women (90%) without known prepregnancy DM. The main outcome was SMM or maternal mortality from 23 weeks' gestation up to 42 days postpartum. Relative risks (RRs) were generated using modified Poisson regression, adjusting for the main covariates of maternal age, multifetal pregnancy, world region of origin, and tobacco/ drug dependence. The mean maternal age was 31.1 years. Overall, SMM or death arose among 682 births (2.2%). The RR of SMM or death was 1.16 (95% CI 1.14-1.19; p < 0.001) per 0.5% increase in A1c and 1.16 (95% CI 1.13-1.18; p < 0.001) after adjusting for the main covariates. The adjusted relative risk (aRR) was increased among those with (1.11, 95% CI 1.07-1.14; p < 0.001) and without (1.15, 95% CI 1.02-1.29; p < 0.001) known prepregnancy diabetes, and upon further adjusting for body mass index (BMI) (1.15, 95% CI 1.11-1.20; p < 0.001), or chronic hypertension and prepregnancy serum creatinine (1.11, 95% CI 1.04-1.18; p = 0.002). The aRR of SMM or death was 1.31 (95% CI 1.06-1.62; p = 0.01) in those with a preconception A1c of 5.8%-6.4%, and 2.84 (95% CI 2.31-3.49; p <

Association of Improved Periconception Hemoglobin A1c With Pregnancy Outcomes in Women With Diabetes

“…Although structural variants of hemoglobin, such as hemoglobin S, were known to interfere with older generations of HbA 1c assays, this is unlikely to be the case in the past 15 years. 1 HbA 1c minimally decreases in the first and second trimester of pregnancy, 2 because of the decreased lifespan and enhanced production of red cells. 13 However, these effects were largely mitigated herein by controlling for preconception HbA 1c and the gestational age of HbA 1c measurement.…”

“…It is a typical starting point for defining a stillbirth, and most in utero sonographic screening for structural anomalies is completed by this gestational age. 12 HbA 1c tends to change by less than 0.2% between conception and 21 weeks , 2 preceding the potential physiological decline in HbA 1c that occurs by early pregnancy to midpregnancy. 13 , 14 If a woman had more than 1 HbA 1c test in the preconception period, the earliest test was used; and if she had more than 1 HbA 1c test in the early pregnancy to midpregnancy period, then the latest was used.…”

Differences in Hemoglobin A1c during Pregnancy between Non-Hispanic Black versus White Women with Prepregnancy Diabetes

“…Over 1 in 3 infants born to women with pregestational diabetes will experience an adverse outcome related to maternal dysglycemia, including large-for-gestational age and neonatal hypoglycemia (6,7). Pregnant women with pregestational diabetes and poor glycemic control are at greater risk of preeclampsia, severe maternal morbidity, and death (8,9). Non-Hispanic Black women are at higher risk of many of these adverse perinatal outcomes compared to non-Hispanic White women (10).…”

“…6,7 Pregnant women with pregestational diabetes and poor glycemic control are at greater risk of preeclampsia, severe maternal morbidity, and death. 8,9 Non-Hispanic Black women are at higher risk of many of these adverse perinatal outcomes compared with non-Hispanic White women. 10 Strict glycemic control as measured by hemoglobin A1c (HbA1c) is associated with a decreased risk of adverse perinatal outcomes.…”

Gestational and pregestational diabetes in pregnant women with cystic fibrosis

“…Furthermore, women with more significant diabetic nephropathy (baseline macroalbuminuria, eGFR < 60 ml/min) at the start of pregnancy and poorly controlled HTN during pregnancy can have permanent kidney decline and in the worst cases progression to kidney failure [75] . Finally, diabetes has long been recognized as a risk factor for increased maternal mortality in both type 1 and type 2 diabetes [68] , [76] , [77] . Treatment of diabetes in pregnancy can also be complicated by hypoglycemia, which occurs more often with the stringent glucose targets in pregnancy and fluctuating insulin resistance including period of insulin sensitization at the end of first trimester [78] , [79] .…”