Maternal hypoglycemia, hyperglycemia increases risk to fetus

HAPO researchers call for re-evaluation of gestational diabetes treatment criteria.

Issue: August 2007

CHICAGO — More pregnant women and their infants may be at risk for adverse outcomes associated with gestational diabetes than previously thought, according to results from the Hyperglycemia and Adverse Pregnancy Outcome, or HAPO, study presented at the American Diabetes Association 67th Annual Scientific Sessions.

“We found that the risk for having a large baby, a first-time cesarean delivery, low blood glucose levels in the newborn requiring treatment and high insulin levels in the baby that may signal problems ahead all increased as blood glucose levels during pregnancy increased,” Boyd E. Metzger, MD, professor of medicine, division of endocrinology, Northwestern University, Feinberg School of Medicine, Chicago, said in a press release.

This relationship persisted across the entire range of blood glucose levels examined in 23,325 pregnant women.

HAPO study

The HAPO study was an international, prospective analysis that took place at 15 centers in nine countries over seven years.

At 28 weeks, the researchers acquired three blood samples from each pregnant woman: a morning fasting blood glucose, an oral glucose tolerance test with one sample taken one hour after drinking 75 g of glucose and then another sample taken one hour later.

At delivery, the researchers measured cord blood for serum C-peptide and plasma glucose. One and two hours after birth; they measured neonatal plasma glucose.

The study was blinded, except when values exceeded predefined cutoff points and the pregnant women required treatment. In these cases, the women were removed from the study and treated.

Results from the fasting blood glucose test ranged from 75 mg/dL to 105 mg/dL. The chance of the infant having macrosomia increased four to six times the spread from the lowest to highest blood glucose results seen in the study. Additionally, the chance of a high insulin level at delivery increased by as much as 10 times the range of the mother’s levels. About 5% of women with the lowest fasting plasma glucose levels (<75 mg/dL) gave birth to infants with macrosomia. Similarly, 27% of women who had the highest fasting levels (>100 mg/dL) had children with macrosomia (OR=6.6; 95% CI, 4.6-9.6).

Increased blood glucose also signaled a greater likelihood that the infant would be above the 90th percentile for total skinfolds (mothers with lowest glucose levels, 5.4%, vs. highest, 28%; OR=1.52; 95% CI, 1.4-1.59).

The researchers concluded that maternal glucose is strongly associated with fetal adiposity. Infants of women with the highest glucose levels were 10 times more likely to be born with high insulin levels. The same infants were about five times more likely to have hypoglycemia.

“Low blood glucose levels in a newborn that require treatment are thought to be a consequence of exposure to higher than normal blood glucose levels in the mother, leading to a more difficult transition from the womb to surviving independently — a classical medical problem in newborns of mothers with known diabetes,” Metzger said.

Call for consensus criteria

Many problems that infants develop are a result of high insulin levels. Hopefully, current and future research will determine which problems are related to this condition, Metzger said. HAPO researchers cannot independently determine exactly where along the range of blood glucose the effects of higher levels are clinically important or which should be considered abnormal values. Ultimately, the decision concerning application of the study results requires the collective input from the broader medical community, according to Metzger.

“It is probable that the level of maternal blood glucose at which a diagnosis of gestational diabetes is made will soon be lowered based on the findings of this study,” he said.

There are no current guidelines for physicians to make a diagnosis of gestational diabetes related to fetal outcomes. Metzger recommended a consensus translation for diagnostic recommendations. A consensus group is scheduled to meet in June 2008. – by Katie Kalvaitis

For more information:
Metzger BE. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) highlights. Presented at: the American Diabetes Association 67th Annual Scientific Sessions; June 22-26, 2007; Chicago.