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Boyd E Metzger, Donald R Coustan, Elisabeth R Trimble, Hyperglycemia and Adverse Pregnancy Outcomes, Clinical Chemistry, Volume 65, Issue 7, 1 July 2019, Pages 937–938, https://doi.org/10.1373/clinchem.2019.303990
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Featured Article: Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, et al., for the HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002.4
Criteria for the diagnosis of gestational diabetes mellitus (GDM)5 based on association of levels of glycemia during pregnancy with subsequent maternal diabetes were first published 55 years ago (1). With adjustments for measurement of glucose in plasma rather than in whole blood and use of enzymatic methods, these criteria remain in use in the US and some other areas. Despite recognition of GDM by various professional organizations in 1979 to 1980, questions remained: (a) Were adverse outcomes attributed to GDM linked to maternal hyperglycemia or to confounding factors such as obesity, maternal age, and less socioeconomic advantage, and (b) did GDM treatment reduce adverse outcomes?
The first question was addressed by the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study, published in the article featured here. The hypothesis was that hyperglycemia in pregnancy, less severe than diabetes, was associated with increased risk of adverse maternal, fetal, and neonatal outcomes independently related to the degree of metabolic disturbance. Eligible women at 15 sites from 9 countries underwent a 75-g, 2-h oral glucose tolerance test (OGTT) at 24 to 32 weeks' gestation, with the target being 28 weeks. Samples were drawn fasting and at 1 h and 2 h after the glucose load. Fasting, 2-h, and random plasma glucose levels at 34 to 37 weeks' gestation were analyzed in local field center laboratories to identify the need for unblinding. Aliquots of the OGTT were analyzed at the central laboratory of the HAPO Study, and these results were used in the analyses reported in the article; 25505 eligible women completed an OGTT. Participants were unblinded with glucose values outside a prespecified range, failure to complete the study usually because of delivery at another hospital, or unanticipated glucose testing for clinical reasons. A total of 23316 women completed the study. Associations of maternal fasting, 1-h, and 2-h 75-g OGTT values with primary study outcomes birth weight above the 90th percentile for gestational age, primary cesarean delivery, clinically diagnosed neonatal hypoglycemia, and cord-blood serum C-peptide above the 90th percentile were continuous. There were no obvious thresholds at which risks increased. Significant associations were also observed for secondary outcomes, although these tended to be weaker.
