Hemoglobin A1c Remains the Strongest Predictor of Negative Outcomes in Type 1 Diabetes Pregnancies

HbA1c (Hemoglobin A1c) is still the most reliable biomarker to determine adverse pregnancy outcomes in women with type 1 diabetes, shows a new study published in Diabetes Care.

In this study, U.K. researchers conducted a secondary analysis of the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT). The study compared HbA1c, continuous glucose monitoring (CGM) metrics, and biochemical markers glycated CD59, 1,5-anhydroglucitol, fructosamine, and glycated albumin at 12, 24 and 34 weeks gestation to predict negative pregnancy outcomes, including preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, and admission to a neonatal intensive care unit.

The study, which included 157 women (mean age 32 years, 25.5 BMI, mostly European or Mediterranean), found that while HbA1c was consistently associated with determining suboptimal pregnancy outcomes across the board, continuous glucose monitoring metrics and some alternative laboratory markers were found to be on target at 24 weeks gestation, but not enough to substantially increase the prediction of pregnancy outcomes as compared to HbA1c and glucose monitoring metrics time in range (TIR) and time above range (TAR).

Continuous glucose monitoring metrics predicted more outcomes during the first trimester and with laboratory markers (area under the ROC curve generally <0.7) during the third trimester. Time in range (TIR) (63–140 mg/dL [3.5–7.8 mmol/L]) and time above range (TAR) (>140 mg/dL [>7.8 mmol/L]) were the most consistently predictive continuous glucose monitoring metrics.

“HbA1c was consistently associated with [determining] pregnancy outcomes, suggesting that despite the known limitations of HbA1c for assessing antenatal glycemia, it is still a critically important biomarker for obstetric and neonatal health outcomes. While other laboratory biomarkers demonstrated some promise, none were able to significantly increase the area under the ROC (receiver operating characteristic) curve, showing, at best, comparable prediction to HbA1c alone,” researchers wrote.

Type 1 diabetes in pregnancy is associated with maternal hyperglycemia with some women developing preeclampsia and requiring an assisted birth or operative delivery. Preterm deliveries are more common under these conditions and newborns can be large for gestational age (birth weight greater than 90th centile) or have neonatal hypoglycemia.

Complications associated with a type 1 diabetes pregnancy are well documented. Complications can be prevented or lessened by controlling blood sugar levels, but assessing maternal glycemia is not a straightforward process, the authors say. “Gestational changes in red cell turnover and serum protein concentrations raise concerns about the validity of HbA1c as a glycemic marker. HbA1c measurements typically reflect glycemia over the preceding 2–3 months, which is also less suitable for intensive monitoring of 1–2 weekly glucose patterns during pregnancy,” the authors wrote.

Options for assessing glycemia in pregnancy include laboratory markers glycated CD59 (gCD59), 1,5-anhydroglucitol, fructosamine, glycated albumin and the use of continuous glucose monitoring metrics, which is commonly used in pregnant women with type 1 diabetes.

There were several limitations associated with this study, including the exclusion of women with HbA1c of less than 6.5% (48 mmol/mol) or greater than 10.0% (86 mmol/mol) at baseline. Excluding this group may have reduced the strength of association between glycemic markers and pregnancy outcomes. Plus, continuous glucose monitoring metrics and glycemic biomarkers were only measured at three time points. More frequent measurements, or using continuous glucose monitoring for more than six days, or throughout the pregnancy, may have found more associations with obstetric and neonatal outcomes.

Future studies should focus on identifying specific factors associated with negative outcomes in type 1 diabetes pregnancies, the authors wrote.

Reference

Claire L. Meek, Diana Tundidor, Denice S. Feig, Jennifer M. Yamamoto, et al. “Novel Biochemical Markers of Glycemia to Predict Pregnancy Outcomes in Women With Type 1 Diabetes,” Diabetes Care. March 2021. doi.org/10.2337/dc20-2360