Association of Improved Periconception Hemoglobin A_1c With Pregnancy Outcomes in Women With Diabetes

Abstract

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 PARTICIPANTSThis population-based cohort study was completed in all of Ontario, Canada, from 2007 to 2018. Included were births among women with prepregnancy diabetes whose HbA 1c 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 MEASURESThe 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 HbA 1c 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. RESULTSA 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 RELEVANCEThese 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.

Association of change in haemoglobin A1c with adverse perinatal outcomes in women with pregestational diabetes

“…24 In a recent study using population-based data from Canada using an analytical approach similar to the current analysis, Davidson et al demonstrated that every incremental decrease in HbA 1c by 6 mmol/mol (0.5%) during pregnancy was associated with a reduced risk of congenital anomalies and preterm birth, as well as maternal outcomes including severe maternal morbidity, preeclampsia, and death. 20,32 Prior studies have also documented an association between an early pregnancy or periconceptional HbA 1c and increased risk of fetal and infant death. 6 Taken together these findings suggest that repeated HbA 1c assessments can be clinically valuable data points for both clinical management and risk stratification.…”

“…25 We analysed change in HbA 1c as a continuous measure given validated clinical thresholds for change in HbA 1c have not been defined for pregnancy. As recommended by national guidelines and recent analyses conducted in pregnancy 19,20 we evaluated HbA 1c as an absolute percentage of total haemoglobin using standards set by the International Federation of Clinical Chemistry 26 and with an assay that is currently certified by the US National Glycohaemoglobin Standardization Program with methods and reagents as having documented traceability to the Diabetes Control and Complications Trial Reference Method. 27 The primary outcomes were an LGA infant at birth (>90th percentile birthweight) and neonatal hypoglycaemia.…”

“…19 Whether a change in HbA 1c during at least two time points in pregnancy in response to clinical interventions to achieve glycaemic control affects the risk of adverse perinatal outcomes at delivery remains to be fully answered. 20 Our objective was to assess whether a net decline in HbA 1c from early to late pregnancy was associated with improved perinatal outcomes at delivery, in particular infants born LGA or with neonatal hypoglycaemia among women with pregestational diabetes. We hypothesized that improved glycaemic control as measured by HbA 1c at two time points in early (<20 weeks) and late pregnancy (≥20 weeks) would decrease the risk of adverse perinatal outcomes.…”

“…Recently, professional societies, including the American Diabetes Association (ADA), have set a target for preconception HbA 1c <48 mmol/mol (6.5%) and pregnancy HbA 1c <42 mmol/mol (6.0%) to optimize pregnancy outcomes 19 . Whether a change in HbA 1c during at least two time points in pregnancy in response to clinical interventions to achieve glycaemic control affects the risk of adverse perinatal outcomes at delivery remains to be fully answered 20 …”

Clinical analysis of 2860 cases of diabetes in pregnancy: a single-center retrospective study

“…For every 1% increase in the HbA1c level, the risk of adverse pregnancy outcomes increases by 3.8 to 7.3%. Davidson et al [ 12 ] found that for every 0.5% decrease in the HbA1c level, the risks of fetal and fetal heart malformations were reduced by 1 and 11%, respectively. In pregnant women with diabetes, maternal hyperglycemia can lead to fetal hyperglycemia.…”