Gestational Diabetes and Obesity Lead to Macrosomia

Neil Osterweil

June 29, 2010

June 29, 2010 (Orlando, Florida) — Gestational diabetes mellitus (GDM) and obesity alone and together increase the risk for excessively large birth weight infants, reported investigators from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study here at the American Diabetes Association 70th Scientific Sessions.

A new analysis of data from more than 23,000 women in HAPO showed that women who did not have GDM but who were obese had a 13.6% increase in risk for macrosomia (defined as a child weighing 4000 g or more at birth) than nonobese women.

The combination of obesity and GDM was associated with a 20.2% increase in risk for macrosomia, said Boyd Metzger, MD, professor of endocrinology at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

In a separate and newly reported analysis of HAPO data, Dr. Metzger and colleagues found that women with GDM who had a fasting plasma glucose (FPG) level of 4.4 mmol/L or lower tended to have pregnancy outcomes that were similar to those of the entire cohort, suggesting that it might be possible to forgo a 75 g oral glucose tolerance test (OGTT) in pregnant women with FPGs at or below the 4.4 mmol/L threshold.

"The levels of glucose with a risk for adverse pregnancy outcome were statistically very strong, and the number of individuals who qualified for a diagnosis of GDM based on that was around 16%," said Dr. Metzger in an interview with Medscape Diabetes.

"It was surprising that the relationships [between glucose levels] were continuous for all outcomes, and for some of them were very strong despite quite small numbers of outcomes. For example, shoulder dystocia or birth injury, which for obstetricians is a big nightmare, doesn't occur often in absolute terms, but nonetheless the risk of that outcome is linearly associated [with glucose]," he said.

The HAPO study was designed to determine whether maternal hyperglycemia that is less severe than what occurs in diabetes is associated with increased risks for adverse pregnancy outcomes.

Pregnant women at 15 centers in 9 countries underwent 75 g OGTT at 24 to 32 weeks of gestation, and were enrolled if they had an FPG level of 105 mg/dL (5.8 mmol/L) or less, and if their 2-hour plasma glucose level was 200 mg/dL (11.1 mmol/L) or less. The primary outcomes were birth weight above the 90th percentile for gestational age, primary cesarean delivery, clinically diagnosed neonatal hypoglycemia, and cord-blood serum C-peptide level above the 90th percentile. Other outcomes measured were delivery before 37 weeks of gestation, shoulder dystocia or birth injury, need for intensive neonatal care, hyperbilirubinemia, and preeclampsia.

Dr. Metzger and colleagues, who published the initial results of the study in the New England Journal of Medicine (2008;358:1991-2002), found strong and continuous associations of maternal glucose levels with increased birth weight and increased cord-blood serum C-peptide levels.

In the current analyses, presented for the first time in public, the authors found that the prevalence of macrosomia among 17,244 nonobese women with no GDM was 1147 (6.7%), compared with 10.2% for nonobese women with GDM, 13.6% for obese women without GDM, and 20.2% for obese women with GDM.

Using the nonobese, no GDM group as a comparator, the investigators found that the actual percentages of macrosomia were significantly higher among nonobese women with GDM and in obese women without or with GDM (25%, 41%, and 33% higher than predicted, respectively).

In the second analysis, the investigators looked at a subgroup of 11,526 patients (49.4% of the total cohort) who had FPG levels of 4.4 mmol/L or less, and a subgroup of 596 of these women with GDM. They defined GDM using the International Association of Diabetes in Pregnancy Study Groups Consensus Panel recommendations: 1 or more OGTT plasma glucose value of 5.1 mmol/L of more for fasting 1-hour glucose, or of 8.5 mmol/L or more for fasting 2-hour glucose.

They found that among all patients with FPG of 4.4 mmol/L or less, fetal hyperinsulinemia (determined by cord serum C-peptide above the 90th percentile), skinfolds sum above the 90th percentile (also associated with fetal hyperinsulinemia), and preterm delivery were significantly more frequent in the GDM subgroup. There were no significant differences within the subgroup in birth weight above the 90th percentile, clinical hypoglycemia, caesarean section rates, or preeclampsia.

In the subgroup of women with FPGs of 4.4 mmol/L or less and GDM, "the frequencies of outcomes tended to be similar to those of the HAPO cohort overall, and substantially lower than found in the total group of GDM that included those with FPG of 4.4 mmol/L or less," said Dr. Metzger.

The findings of the 2 analyses, and of all the HAPO data, suggest that more consistent standards for diagnosing and managing GDM could improve outcomes for pregnant women with diabetes, said Jacob Friedman, PhD, from the departments of pediatrics, biochemistry, and molecular genetics at the University of Colorado School of Medicine in Denver.

"I think that the continuing story is that the relative risk for adverse perinatal outcomes actually had a much lower threshold than we previously believed, and this keeps being verified by continual analysis of the data, suggesting that our criteria for diagnosing gestational diabetes will change, and hopefully for the better," he said in an interview with Medscape Diabetes.

Dr. Metzger and Dr. Friedman have disclosed no relevant financial relationships.

American Diabetes Association (ADA) 70th Scientific Sessions: Abstracts 154-OR and 160-OR. Presented June 27, 2010.

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