Diagnosing GDM in the first trimester

Amy Carpenter Aquino

December 2019—“If you thought that diagnosing gestational diabetes at 24 to 28 weeks was unsettled, you haven’t seen anything yet.”

That was David B. Sacks, MB, ChB, of the National Institutes of Health, speaking this year in the AACC session on gestational diabetes mellitus (GDM) with his co-presenters who debated the use of the one-step and two-step methods for diagnosing GDM in the second and third trimesters. His talk: “Let’s Not Wait: Diagnosing GDM in the First Trimester.”

“Why do we need to identify gestational diabetes in the first trimester?” asked Dr. Sacks, senior investigator and chief of the clinical chemistry service in the Department of Laboratory Medicine, NIH. “Hyperglycemia in late pregnancy leads to adverse outcomes. It’s thought that women with early gestational diabetes are at higher risk for complications,” Dr. Sacks said, “and it’s also thought that early therapy would be beneficial. This has clearly been shown for pregnant women with preexisting diabetes, and these are women who have diabetes already who became pregnant.”

A study published this year that looked at adverse outcomes in women with preexisting diabetes showed an odds ratio of 3.5 for preeclampsia and cesarean delivery, he said (Alexopoulos AS, et al. JAMA. 019;321[18]:1811–1819).
The odds ratios are increased for all the child adverse outcomes, ranging from about 1.9-fold to almost 27-fold. Most are between a three- and four-fold odds ratio.

The first trimester is when fetal development is most rapid and “when the majority of the fetus’ organ systems are at risk,” yet the current screening recommendation for GDM is at 24 to 28 weeks. “We’re missing almost two-thirds of the pregnancy,” Dr. Sacks said, and there are now recommendations for screening for diabetes early in pregnancy.

Several organizations, among them the American Diabetes Association, American College of Obstetricians and Gynecologists, Diabetes Canada, and World Health Organization, have identified selected populations in which screening should be done early in pregnancy, he said, adding, “The guidelines are very different.” (Johns EC, et al. Trends Endocrinol Metab. 2018;29[11]:743–754.) Diabetes Canada recommends early screening for one population, while ACOG lists nearly a dozen populations.

The ADA and WHO have the same recommendations, which are, for women with risk factors, to evaluate for undiagnosed diabetes at the first prenatal visit (first trimester) using the standard diagnostic criteria: increased hemoglobin A1c, increased fasting glucose, or a two-hour glucose tolerance test, Dr. Sacks said. “If this is positive, the mother is diagnosed with diabetes in pregnancy.” If the result is negative, the mother should be screened for gestational diabetes at 24 to 28 weeks.

Hyperglycemia in pregnancy is divided into two groups: diabetes in pregnancy or GDM, and either one can be type one or two. Diabetes in pregnancy can be diagnosed before the start of pregnancy, even during childhood years, or during pregnancy for the first time.

Women diagnosed with GDM early are more likely to have adverse outcomes. “Maternal outcomes for GDM diagnosed in the first trimester are similar to those with preexisting diabetes,” Dr. Sacks said (Sweeting AN, et al. Diabetes Care. 2016;39[1]:75–81). Similar to the maternal complications, the neonatal complications are significantly higher when the gestational diabetes is diagnosed earlier. “That raises the question as to how we predict gestational diabetes in the first trimester,” Dr. Sacks said.

For biochemical predictors, “People have looked at glucose, either fasting, oral glucose tolerance test, or even continuous glucose monitors. They’ve looked at different kinds of glycated proteins, inflammatory markers, insulin resistance markers, placenta-derived markers, adipocyte-derived markers—the list goes on,” he said. Judging by the literature, most of the evidence has been directed toward fasting plasma glucose and glycated proteins in the first trimester, Dr. Sacks said.

A 2009 study found a progressive increase in adverse maternal and fetal outcomes with increasing fasting plasma glucose in the first trimester (Riskin-Mashiah S, et al. Diabetes Care. 2009;32[9]:1639–1643).

The IADPSG initially recommended a fasting plasma glucose ≥ 92 mg/dL (5.1 mmol/L) in early pregnancy as diagnostic of GDM, Dr. Sacks said, but these criteria were not derived from data in the first half of pregnancy. “The study measured glucose at 24 to 28 weeks, so the diagnosis of gestational diabetes in early pregnancy by fasting glucose or OGTT is not evidence based. There is no evidence at all.”