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

BACKGROUND: The 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 FINDINGS: A 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 < 0.001) at an A1c > 6.4%, each relative to an A1c < 5.8%. Among those without previously recognized prepregnancy diabetes and whose A1c was >6.4%, the aRR of SMM or death was 3.25 (95% CI 1.76-6.00; p < 0.001). Study limitations include that selection bias may have incorporated less healthy women tested for A1c, and BMI was unknown for many women. CONCLUSIONS: Our findings indicate that women with an elevated A1c preconception may be at higher risk of SMM or death in pregnancy or postpartum, including those without known prepregnancy DM.

Severe Maternal Morbidity and Infant Mortality in Canada.

BACKGROUND: Severe maternal morbidity (SMM) comprises an array of conditions and procedures denoting an acutely life-threatening pregnancy-related condition. SMM may further compromise fetal well-being. Empirical data are lacking about the relation between SMM and infant mortality. METHODS: This population-based cohort study included 1 892 857 singleton births between 2002 and 2017 in Ontario, Canada, within a universal health care system. The exposure was SMM as an overall construct arising from 23 weeks' gestation up to 42 days after the index delivery. The primary outcome was infant mortality from birth to 365 days. Multivariable modified Poisson regression generated relative risks and 95% confidence intervals (CIs), adjusted for maternal age, income, rurality, world region of origin, diabetes mellitus, and chronic hypertension. RESULTS: Infant mortality occurred among 174 of 19 587 live births with SMM (8.9 per 1000) vs 5289 of 1 865 791 live births without SMM (2.8 per 1000) (an adjusted relative risk of 2.93 [95% CI 2.51-3.41]). Of 19 587 pregnancies with SMM, 4523 (23.1%) had sepsis. Relative to births without SMM, the adjusted odds ratio for infant death from sepsis was 1.95 (95% CI 1.10-3.45) if SMM occurred without maternal sepsis and 6.36 (95% CI 3.50-11.55) if SMM included sepsis. CONCLUSIONS: SMM confers a higher risk of infant death. There is also coupling tendency (concurrent event of interest) between SMM with sepsis and infant death from sepsis. Identification of preventable SMM indicators, as well as the development of strategies to limit their onset or progression, may reduce infant mortality.

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 A1c (HbA1c) 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 HbA1c 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 HbA1c and hemoglobin concentration, and gestational age at HbA1c 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) HbA1c 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 HbA1c, 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 HbA1c. Conclusions and Relevance: These findings suggest that women with prepregnancy diabetes who achieve a reduction in HbA1c 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 HbA1c reduction.