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First trimester HbA1c may predict gestational diabetes risk in low-risk women

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August 17, 2018

Cuilin Zhang
Cuilin Zhang

In healthy, pregnant women, a first trimester HbA1c measurement better predicted gestational diabetes risk vs. analysis of conventional risk factors, suggesting the test could improve early risk stratification, according to study findings published in Scientific Reports.

“Gestational diabetes is a common pregnancy complication and has adverse short-term and long-term health implications on both women and their children,” Cuilin Zhang, MD, PhD, of the Epidemiology Branch at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIHCD) in Rockville, Maryland, told Endocrine Today. “It is critical to prevent gestational diabetes. The current gestational diabetes screening and diagnosis tests are not implemented until late in the second trimester, which may leave limited time for intervention to be effective. As such, identifying women at high risk early in pregnancy becomes important.”

In a secondary analysis of a case-control study, Zhang and colleagues analyzed data from 100 women with gestational diabetes (37.9% Hispanic; 57.4% aged 25 to 34 years) each matched with two healthy controls matched by maternal age, race and gestational week of blood collection (n = 211; 40% Hispanic; 56% aged 25 to 35 years), all participating in the NIHCD Fetal Growth Studies-Singleton Cohort, an analysis of low-risk pregnancies among women with both normal weight and obesity. All women underwent standard care, which included an oral glucose tolerance test (OGTT) and blood samples collected at enrollment (8 to 13 weeks gestation) and three additional study visits at weeks 16 to 22, 24 to 29 and 34 to 37. Researchers measured HbA1c at all four timepoints for women with gestational diabetes and one of the two matched controls, and at enrollment and the first study visit for the second matched controls. Researchers examined the prospective association between first trimester HbA1c and gestational diabetes risk and change between HbA1c in the first and second trimesters and gestational diabetes risk. Researchers then used receiver-operator characteristics (ROC) curves to evaluate the predictive ability of HbA1c for a diagnosis of gestational diabetes, estimating the sensitivity and specificity of first trimester HbA1c by each 0.1% HbA1c increase from 3.5% to 6%. Researchers also estimated the value of using HbA1c for the prediction of gestational diabetes above and beyond conventional risk factors, such as maternal age, race, prepregnancy weight, family history of diabetes and prior gestational diabetes.

At enrollment, 15% of cases and 2.4% of controls had HbA1c at least 5.7%, the cutoff for prediabetes, but less than 6.4%. Median HbA1c for the cohort was 5.2%.

Researchers found that HbA1c measurements in cases were higher vs. controls throughout pregnancy (P < .03); however, regardless of gestational diabetes status, HbA1c tended to decrease in the second trimester before increasing in the third trimester.

Compared with women who had a median HbA1c of 5.2%, women with first trimester HbA1c 5.7% were 2.73 times more likely to develop gestational diabetes in the third trimester (95% CI, 1.59-4.66). Additionally, change in HbA1c between enrollment and visit 2 was positively associated with gestational diabetes risk independent of the enrollment HbA1c value (P = .04). Results were similar in sensitivity analyses excluding women who smoked or who obesity, prior gestational diabetes or a hematologic disorder.

In sensitivity and specificity analyses, researchers observed that the optimal HbA1c cutpoint was at 5.1%, where the sensitivity was 47% (95% CI, 34-60) and the specificity was 79% (95% CI, 62-88). At an HbA1c of 5.7%, sensitivity was 21% (95% CI, 8-36) and specificity was 95% (95% CI, 91-99) for prediction of gestational diabetes, the researchers wrote.

“We observed a significant improvement in [gestational diabetes] prediction with the inclusion of first trimester HbA1c over conventional risk factors alone,” the researchers wrote. “Thus, even in this cohort of low-risk women without pre-existing medical conditions, HbA1c measured in the first trimester improved [gestational diabetes] prediction.”

The researchers noted the findings suggest that hyperglycemia, even among women without pre-pregnancy diabetes, may be important for the development of gestational diabetes. – by Regina Schaffer

Disclosures: The authors report no relevant financial disclosures.

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