[pronut-hiv] Maternal Hyperglycemia Linked to Adverse Pregnancy Outcomes

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Maternal Hyperglycemia Linked to Adverse Pregnancy Outcomes

May 7, 2008 " Maternal glucose levels below the range indicating diabetes are associated with increased birth weight and increased cord-blood serum C-peptide levels, according to the results of a study reported in the May 8 issue of the New England Journal of Medicine.
"It is controversial whether maternal hyperglycemia less severe than that [seen] in diabetes mellitus is associated with increased risks of adverse pregnancy outcomes," write Boyd E. Metzger, MD, from Northwestern University Feinberg School of Medicine, Chicago, Illinois, and colleagues from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cooperative Research Group. "There are no uniform international standards for the ascertainment and diagnosis of gestational diabetes mellitus. In addition, the extent to which adverse outcomes associated with gestational diabetes mellitus may be explained by confounders (including obesity, advanced maternal age, or associated medical complications) is unclear."
At 15 centers in 9 countries, 25,505 pregnant women underwent 75-g oral glucose tolerance testing at 24 to 32 weeks of gestation. If the fasting plasma glucose level was 105 mg/dL (5.8 mmol/L) or less and the 2-hour plasma glucose level was 200 mg/dL (11.1 mmol/L) or less, data remained blinded. 
The main endpoints 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; secondary endpoints were delivery before 37 weeks of gestation, shoulder dystocia or birth injury, need for intensive neonatal care, hyperbilirubinemia, and preeclampsia.
Adjusted odds ratios (ORs) for adverse pregnancy outcomes were calculated for the 23,316 women, based on increases in fasting plasma glucose level of 1 SD (6.9 mg/dL [0.4 mmol/L]), increases in the 1-hour plasma glucose level of 1 SD (30.9 mg/dL [1.7 mmol/L]), and increases in the 2-hour plasma glucose level of 1 SD (23.5 mg/dL [1.3 mmol/L]). 
For birth weight above the 90th percentile, ORs were 1.38 (95% confidence interval [CI], 1.32 - 1.44), 1.46 (95% CI, 1.39 - 1.53), and 1.38 (95% CI, 1.32 - 1.44) for fasting, 1-hour, and 2-hour glucose levels, respectively. For cord-blood serum C-peptide level above the 90th percentile, ORs were 1.55 (95% CI, 1.47 - 1.64), 1.46 (95% CI, 1.38 - 1.54), and 1.37 (95% CI, 1.30 - 1.44), respectively. 
For primary cesarean delivery, ORs were 1.11 (95% CI, 1.06 - 1.15), 1.10 (95% CI, 1.06 - 1.15), and 1.08 (95% CI, 1.03 - 1.12); and for neonatal hypoglycemia, they were 1.08 (95% CI, 0.98 - 1.19), 1.13 (95% CI, 1.03 - 1.26), and 1.10 (95% CI, 1.00 - 1.12), respectively. 
There were no clear thresholds at which risks dramatically increased. Although significant associations were also seen for secondary endpoints, they were not as strong as for the main endpoints.
"Our results indicate strong, continuous associations of maternal glucose levels below those diagnostic of diabetes with increased birth weight and increased cord-blood serum C-peptide levels," the study authors write. "Lack of clear thresholds for risk and the fact that the four primary outcomes are not necessarily of equal clinical importance make direct translation of our results into clinical practice challenging. However, our findings of significant associations between adverse outcomes and higher levels of maternal glucose within what is currently considered a nondiabetic range indicate the need to reconsider current criteria for diagnosing and treating hyperglycemia during pregnancy."
Limitations of this study include a lack of data on nutritional status and gestational weight gain of the participants; the effect of some confounders, such as previous gestational diabetes mellitus, maternal body mass index, or previous macrosomia, on clinical decisions such as the choice of route of delivery; and observational design preventing causal inferences.
In an accompanying editorial, Jeffrey L. Ecker, MD, and Michael F. Greene, MD, from HarvardMedicalSchooland Massachusetts GeneralHospitalin Boston, call HAPO an "elegantly designed, very large, international study."
"Whether treating mild degrees of hyperglycemia would increase the risk for poor fetal growth and attendant complications should be carefully determined before such treatment is implemented at lower glucose thresholds," write Dr. Ecker and Dr. Greene. "Finally, there is the possibility that the associations of mild carbohydrate intolerance with adverse outcomes during pregnancy are just that â associations that are not causally mediated. Until trials show clinical benefits from expanding the diagnostic criteria for 'gestational diabetes,' we would not favor any change."
The Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Research Resources, the American Diabetes Association, Diabetes UK, Kaiser Permanente Medical Center, KK Women's and Children's Hospital, Mater Mother's Hospital, Novo Nordisk, the Myre Sim Fund of the Royal College of Physicians of Edinburgh, and the Howard and Carol Bernick Family Foundation supported this study. Three authors have disclosed no relevant financial relationships with Novo Nordisk and/or Takeda.
N Engl JMed.2008;358:1991-2002, 2061-2063.