Hapo

new england journal of medicine
The
established in 1812

may 8, 2008

vol. 358

no. 19

Hyperglycemia and Adverse Pregnancy Outcomes
The HAPO Study Cooperative Research Group*

A BS T R AC T
BACKGROUND

It is controversial whether maternal hyperglycemia less severe than that in diabetes mellitus is associated with increased risks of adverse pregnancy outcomes.
METHODS

A totalof 25,505 pregnant women at 15 centers in nine countries underwent 75-g oral glucose-tolerance testing at 24 to 32 weeks of gestation. Data remained blinded if the fasting plasma glucose level was 105 mg per deciliter (5.8 mmol per liter) or less and the 2-hour plasma glucose level was 200 mg per deciliter (11.1 mmol per liter) or less. Primary outcomes were birth weight above the 90th percentilefor gestational age, primary cesarean delivery, clinically diagnosed neonatal hypoglycemia, and cord-blood serum C-peptide level above the 90th percentile. Secondary outcomes were delivery before 37 weeks of gestation, shoulder dystocia or birth injury, need for intensive neonatal care, hyperbilirubinemia, and preeclampsia.
RESULTS

For the 23,316 participants with blinded data, we calculatedadjusted odds ratios for adverse pregnancy outcomes associated with an increase in the fasting plasma glucose level of 1 SD (6.9 mg per deciliter [0.4 mmol per liter]), an increase in the 1-hour plasma glucose level of 1 SD (30.9 mg per deciliter [1.7 mmol per liter]), and an increase in the 2-hour plasma glucose level of 1 SD (23.5 mg per deciliter [1.3 mmol per liter]). For birth weight above the90th percentile, the odds ratios were 1.38 (95% confidence interval [CI], 1.32 to 1.44), 1.46 (1.39 to 1.53), and 1.38 (1.32 to 1.44), respectively; for cord-blood serum C-peptide level above the 90th percentile, 1.55 (95% CI, 1.47 to 1.64), 1.46 (1.38 to 1.54), and 1.37 (1.30 to 1.44); for primary cesarean delivery, 1.11 (95% CI, 1.06 to 1.15), 1.10 (1.06 to 1.15), and 1.08 (1.03 to 1.12); andfor neonatal hypoglycemia, 1.08 (95% CI, 0.98 to 1.19), 1.13 (1.03 to 1.26), and 1.10 (1.00 to 1.12). There were no obvious thresholds at which risks increased. Significant associations were also observed for secondary outcomes, although these tended to be weaker.
CONCLUSIONS

The members of the Writing Group (Boyd E. Metzger, M.D., Lynn P. Lowe, Ph.D., Alan R. Dyer, Ph.D., NorthwesternUniversity Feinberg School of Medicine, Chicago; Elisabeth R. Trimble, M.D., Queen’s University Belfast, Belfast, Northern Ireland; Udom Chaovarindr, M.D., Rajavithi Hospital, Bangkok, Thailand; Donald R. Coustan, M.D., Women and Infants’ Hospital of Rhode Island–Brown University Medical School, Providence, RI; David R. Hadden, M.D., David R. McCance, M.D., Royal Jubilee Maternity Hospital, Belfast,Northern Ireland; Moshe Hod, M.D., Helen Schneider Hospital for Women, Rabin Medical Center–Sackler Faculty of Medicine, Tel-Aviv University, PetahTiqva, Israel; Harold David McIntyre, M.B., B.S., Jeremy J.N. Oats, M.D., Mater Misericordiae Mothers’ Hospital–University of Queensland, Brisbane, Australia; Bengt Persson, M.D., Ph.D., Karolinska Institute, Stockholm, Sweden; Michael S. Rogers, M.D.,Prince of Wales Hospital–Chinese University of Hong Kong, Hong Kong; and David A. Sacks, M.D., Kaiser Foundation Hospital, Bellflower, CA) of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cooperative Research Group assume responsibility for the overall content and integrity of the article. Address reprint requests to Dr. Metzger at the Northwestern University Feinberg School of Medicine,Endocrinology, 645 N. Michigan Ave., Suite 530-22, Chicago, IL 60611, or at bem@northwestern.edu. *Members of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cooperative Research Group are listed in the Appendix. N Engl J Med 2008;358:1991-2002.
Copyright © 2008 Massachusetts Medical Society.

Our results indicate strong, continuous associations of maternal glucose levels below...