First-Trimester HbA1c Predicts Gestational Diabetes

Measurement of hemoglobin A1c (HbA1c) during the first trimester of pregnancy may aid in early detection of women at risk for gestational diabetes, new research suggests.



The findings, from two prospective ethnically diverse cohorts of nearly 3000 pregnant women, were published online August 16 in Scientific Reports, by Stefanie N. Hinkle, PhD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland, and colleagues.

Among participants, the risk for gestational diabetes increased linearly with first-trimester HbA1c. Moreover, the addition of first-trimester HbA1c to conventional risk factors enhanced gestational diabetes predictive capability, say Hinkle and colleagues.

HbA1c is currently used to diagnose type 2 diabetes and monitor glucose control once diabetes is diagnosed. In pregnancy its use has been limited to screen for overt type 2 diabetes rather than gestational diabetes, they note.

The new findings, however, "suggest potential important clinical utility of HbA1cmeasurement in the first trimester of pregnancy, even among low-risk women. While our findings require replication, gestational diabetes prediction was significantly improved with the inclusion of HbA1c over conventional risk factors suggesting that it could be used to improve early risk-stratification and screening in women with elevated levels. Furthermore, our findings suggest that hyperglycemia even among women without pre-pregnancy diabetes may be important for the development of gestational diabetes," the authors write.

The authors analyzed data from 2334 low-risk pregnancies in nonobese women from the NICHD fetal growth studies — singleton cohort, the primary aim of which was to develop fetal growth standards in healthy mothers. They also included a group of 468 obese women to examine the etiology of gestational diabetes.

The current analysis was based on a nested gestational diabetes case-control study within the cohorts, including 107 women later diagnosed with gestational diabetes (by standard oral glucose tolerance testing [OGTT]) and 214 nongestational diabetes controls, matched by maternal age, race/ethnicity, and gestational week of blood collection. None had an HbA1c of 6.5% or greater at baseline.

Blood specimens were collected and HbA1c measured at enrollment at 8–13 gestational weeks, 16–22 weeks (visit 1), 24–29 weeks (visit 2), and 34–37 weeks (visit 3).

HbA1c was significantly higher among women who later developed gestational diabetes than controls throughout pregnancy (P < .03). Among all the women, HbA1c tended to decrease into the second trimester and then increase around the third trimester. "This is intuitive and in line with the high erythrocyte turnover in pregnancy and the decrease in insulin sensitivity with increasing gestation," Hinkle and colleagues note.

HbA1c at enrollment (8–13 weeks) was significantly and linearly related to gestational diabetes risk (P = .001). Compared with women with median HbA1clevels of 5.2%, those with an HbA1c of 5.7% had a significant 2.73-fold greater risk for gestational diabetes.

The risk did not increase significantly to visit 1, but the change in HbA1c from enrollment to visit 2 was significantly and positively associated with gestational diabetes risk, independent of HbA1c at enrollment (P = .04).

The sensitivity of HbA1c at enrollment for predicting gestational diabetes ranged from 96% among women with an HbA1c of 3.5% to 12% among those with an HbA1c of 6.0%. Specificity ranged from 10% with an HbA1c of 3.5% to 98% at an HbA1c of 6.0%.

"The low sensitivity at higher HbA1c levels suggests that HbA1c may not be a good substitute for a second-trimester OGTT, which tests the acute response to the glucose challenge and how women respond to the increased insulin-resistant environment of late pregnancy," Hinkle and colleagues note.

These data suggest that an optimal HbA1c cutpoint might be 5.1%, which had a sensitivity of 47% and specificity of 79%, they say.

Alternatively, when using an HbA1c of 5.7%, the cutoff used to diagnose prediabetes in nonpregnant adults, the sensitivity was 21% and specificity was 95%. That high specificity "suggests that with this threshold few low-risk women, who otherwise would not receive early screening, would be incorrectly diagnosed by an elevated first-trimester HbA1c level. This presents a unique opportunity for earlier interventions in these women, which would be ideal as gestational diabetes is associated with adverse pregnancy outcomes such as macrosomia."

With the addition of HbA1c at enrollment to the conventional gestational diabetes risk factors of age, race/ethnicity, pre-pregnancy overweight/obesity, family history of diabetes, gestational diabetes in a prior pregnancy, and nulliparity, the area under the curve increased from .59 to .65, a significant improvement in prediction (P = .04).

"While it is plausible that with an earlier intervention these risks might be minimized, future studies evaluating early intervention based on elevated first-trimester HbA1c are essential to determine its utility," the authors conclude.

Source