HAPO Study Reveals Maternal Hyperglycemia Associated with Pregnancy Complications
Feinberg School Researchers at the Helm of International Study
Feinberg School of Medicine researchers have played a lead role in an international study that shows an association between maternal hyperglycemia and the risk of pregnancy complications. Boyd Metzger, MD, the Tom D. Spies Professor of Metabolism and Nutrition at the Feinberg School, is the principal investigator for the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, which explored the association between maternal hyperglycemia less than that in diabetes mellitus and adverse pregnancy outcomes. The results of this study have now been reported in “Hyperglycemia and Adverse Pregnancy Outcomes,” in the May 8 issue of the New England Journal of Medicine. Dr. Metzger led a team of investigators that also includes the Feinberg School’s Alan R. Dyer, PhD, professor of preventive medicine and principal investigator of the HAPO Data Coordinating Center, and Lynn P. Lowe, PhD, research assistant professor of preventive medicine, and project manager for the HAPO Study. Sharon Dooley, MD, professor of obstetrics and gynecology, was principal investigator of the clinical center that enrolled participants at the Northwestern site of the HAPO study.
The HAPO study report notes that, although overt diabetes mellitus during pregnancy is associated with significantly increased risk of adverse prenatal outcomes, the risks associated with hyperglycemia that is less severe than diagnostic diabetes have been uncertain. No uniform, international standards exist to ascertain and diagnose gestational diabetes mellitus. In addition, the extent to which adverse outcomes associated with gestational diabetes mellitus may be explained by confounders such as obesity or advanced maternal age is unclear. This study was conducted in an effort to clarify the risks of adverse outcomes associated with various degrees of maternal hyperglycemia less severe than in overt diabetes mellitus.
A total of 23,316 pregnant women from 15 centers in nine countries participated in and completed the HAPO study. The women, none of whom had received treatment for diabetes before the current pregnancy, underwent a standard glucose tolerance test using a 75-gram dose of glucose between 24 and 32 weeks of gestation (the target time of testing was 28 weeks). Height, weight, and blood pressure were measured at the test visit. Data concerning maternal alcohol use, history of diabetes and hypertension among first-degree family members, and demographic characteristics were collected with a standardized questionnaire. Data were blinded if the fasting plasma glucose level was 105 milligrams per deciliter (mg/dL) or less and the two-hour plasma glucose level was 200 mg/dL or less. Primary outcomes were birth weight above the 90th percentile for gestational age, primary cesarean delivery, clinical diagnosis of neonatal hypoglycemia, and umbilical cord blood serum C-peptide level above the 90th percentile. Secondary outcomes were delivery before 37 weeks of gestation, shoulder dysphasia or birth injury, need for intensive neonatal care, hyperbilirubinemia, and preeclampsia.
The researchers calculated adjusted odds ratios of adverse pregnancy outcomes associated with an increase in the fasting plasma glucose level of 1 standard deviation (SD) (6.9 mg/dL ), an increase in the one-hour plasma glucose level of 1 SD (30.9 mg/dL), and an increase in the two-hour plasma glucose level of 1 SD (23.5 mg/dL). For birth weight above the 90th percentile, the odds ratios were 1.38, 1.46, and 1.38, respectively; for cord-blood serum C-peptide level above the 90th percentile, 1.55, 1.46, and 1.37; for primary cesarean delivery, 1.11, 1.10, and 1.08; and for neonatal hypoglycemia, 1.08, 1.13, and 1.10. Significant associations were also observed for secondary outcomes.
These results indicate that women with high blood sugar without clinically diagnosed diabetes face an increased risk of complications. “We found strong independent associations between the mother’s blood sugar levels during oral glucose tolerance tests at 28 weeks of gestation and pregnancy outcomes,” says Dr. Metzger. “But because the relationship between the mother’s blood glucose level and risk tend to be continuous, it is not immediately obvious where the risk reaches the point where treatments should begin.” Dr. Metzger notes that the results of the HAPO study were discussed at the annual meeting of the American Diabetes Association, held in early June.
“Those of us who care for pregnant women are grateful for the HAPO study and its implications on the role of hyperglycemia,” says Dr. Dooley. “We will be watching with interest to see if new guidelines for clinical care emerge from this important study.”