WEDNESDAY, May 23, 2012 (MedPage Today) — Gestational diabetes is often blamed for larger babies, but maternal weight may have a much greater impact on infant birth weight than glycemia, according to a new study.

Among women without gestational diabetes, the significant metabolic predictors of having a large-for-gestational-age infant included body mass index (BMI) before and weight gain during pregnancy up to the time of a glucose tolerance, reported Jill Hamilton, MD, from the Hospital for Sick Children in Toronto, and colleagues online in CMAJ.

The authors also found that leptin and C-reactive protein emerged as significant negative predictors for birth weight and large-for-gestational-age infants. Historically, leptin, a hormone involved in the regulation of body fat, has increased with BMI, so the negative association is "striking and a testimony to the complexity of issues surrounding control of birth weight," wrote Edmond Ryan, MD, of the University of Alberta in Edmonton, Canada, in an accompanying CMAJ commentary.

Hamilton's group explained that "this emerging concept regarding the relative importance of maternal obesity versus glycemia may hold implications for the current debate regarding the lowering of diagnostic thresholds for gestational diabetes on antepartum glucose tolerance testing."

In fact, the National Institutes of Health is slated to hold a consensus conference on gestational diabetes in October. One of the issues that requires better definition is the respective contributions of maternal weight and glucose levels.

The researchers conducted the current analysis within the context of an ongoing prospective cohort study. Patients were recruited when they were late in the second trimester or early in the third trimester, and all underwent a 3-hour, 100-g oral glucose tolerance test.

Women in the current analysis had either gestational impaired glucose tolerance or normal glucose tolerance; women with gestational diabetes were excluded. Also, the study population was restricted to white, Asian, and South Asian women because ethnicity-specific centiles of birth weight have been established for these groups in Canada, the authors explained.

Obstetric outcomes were assessed at delivery. Multiple linear regression analysis of infant birth weight was done with adjustment for the following covariates:

  • Length of gestation
  • Infant sex
  • Maternal demographics
  • Maternal smoking status
  • Glucose tolerance status
  • Insulin adipokines (leptin)
  • Inflammatory proteins (C-reactive protein)

Finally, the analysis adjusted for pre-pregnancy BMI and weight gain during pregnancy up to the time of the oral glucose tolerance test.

Among 472 women, 22 percent had gestational impaired glucose tolerance. The infants had a mean birth weight of almost 8 lbs. and 68 were considered large for gestational age at delivery.

BMI before pregnancy varied across the groups and was highest in the top tertile of birth weight. At delivery, this top tertile had the longest length of gestation and the largest proportion of cesarean delivery.

Length of gestation, male sex, pre-pregnancy BMI, and weight gain during pregnancy up to the time of the oral glucose tolerance test all were associated with higher birth weight.

Another significant predictor of having a larger baby was Asian ethnicity versus white so the group then repeated the analysis for white women only. The same predictors emerged for large-for-gestational-age infants. Also, being a former smoker versus never smoking also reached significance.

The authors highlighted three take-home points from this study. First, maternal adiposity was the strongest determinant of infant birth weight and having a baby with excessive weight. They suggested that shared genetic factors may apply to maternal adiposity and fetal growth.

Second, leptin and C-reactive protein were significant negative predictors of both birth weight and having a large-for-gestational-age baby, which speaks to the relative contributions of obesity-related circulating factors. "These factors may play a role in attenuating the pro-macrosomia effects of maternal adiposity," the authors wrote.

Finally, gestational impaired glucose tolerance was an independent predictor of birth weight, but its impact was relatively modest compared with pre-pregnancy BMI and weight gain during pregnancy. However, glucose tolerance was not a significant independent predictor of having a large-for-gestational-age infant.

The study did have some limitations. The authors did not evaluate the high-molecular weight form of adiponectin, which may be the specific maternal mediator that affects fetal growth. Also, pre-pregnancy weight was self-reported by patients and may have been subject to bias. Finally, weight gain during pregnancy was not determined across the total length of gestation.

The authors' recommendation that clinicians target maternal obesity is a sound one, wrote Ryan. A recent meta-analysis showed that a healthy, calorie-controlled diet to reduce excess weight gain during pregnancy is safe for mother and baby, and can improve pregnancy outcomes compared with exercise alone or a combination of the two.

Indeed, targeting weight issues in pregnancy may be a more efficient use of healthcare resources rather than lowering the threshold for what constitutes gestational diabetes, Ryan added.