The new england journal of medicinen engl j med nejm.org1Early versus Second-Trimester Screening and Treatment for Diabetes in PregnancyMichael F. Greene, M.D.
After a decades-long debate regarding the use-fulness of universal screening for and treatment of gestational diabetes mellitus, two large random-ized, controlled trials of screening in the second trimester that were published in the Journal in 20051 and 20092
clearly showed that such screenng and treatment reduced morbidity related to gestational diabetes, when diagnosed, among both mothers and their offspring. Universal second-trimester screening for gestational diabetes has long been recommended by the American College of Obstetricians and Gynecologists and the Amer-ican Diabetes Association.
Many of the complications associated with untreated gestational diabetes, such as excessive fetal growth, birth injury, preeclampsia, and neo-natal hypoglycemia, are known to occur more commonly among women with higher glucose levels within the normal range than among those with lower levels.
The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, a large observational study involving women whose oral glucose-tolerance test (OGTT) results did not in-dicate gestational diabetes, showed continuous associations of maternal glucose level with several adverse pregnancy outcomes, with no “thresh-old” effect.3Increasing maternal body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) and maternal age are strong-ly associated with the probability of both gesta-tional diabetes and type 2 diabetes in the gen-eral population.
Data regarding U.S. births in 2020 show that 57% of all mothers were either overweight, with a BMI of 25 to less than 30 (27% of mothers), or obese, with a BMI of 30 or greater (30% of mothers).4 The average age of U.S. mothers rose steadily between 1990 and 2019, apparently plateauing thereafter.4 These trends parallel those for the rise in the incidence of diagnosed diabetes in the United States.5 The conf luence of these trends has resulted in calls from professional societies for screening for hyperglycemia early in pregnancy in women at particularly high risk — in addition to standard screening in the second trimester (24 to 28 weeks’ gestation) to identify and treat women with ges-tational diabetes and undiagnosed type 2 diabetes — to further reduce the risk of adverse pregnancy outcomes.6,7 To date, a single random-ized clinical trial of early screening and treatment for gestational diabetes involving 900 women with obesity (the Early Gestational Diabetes Screen-ing in the Gravid Obese Woman [EGGO] trial) did not show a reduction in morbidity.8Simmons et al.9 now report in the Journal the results of a randomized, controlled trial con-ducted at 17 hospitals in Australia, Austria, India, and Sweden. Women 18 years of age or older with a singleton pregnancy at 4 weeks’ to 19 weeks 6 days’ gestation and at least one risk factor for hyperglycemia in pregnancy were administered a World Health Organization (WHO)–standard 2-hour 75-g OGTT before 20 weeks’ gestation.
Women who met the WHO criteria for gestational diabetes were randomly assigned in a 1:1 ratio to receive either immediate treatment for gestational diabetes or deferred or no treatment, de-pending on the results of a second OGTT at 24 to 28 weeks’ gestation (control). Randomization was stratified according to hospital and according to the OGTT results (higher or lower range of ab-The New England Journal of Medicine Downloaded from nejm.org at OREBRO on May 24, 2023. For personal use only. No other uses without permission. Copyright © 2023 Massachusetts Medical Society. All rights reserved.
The new england journal of medicinen engl j med nejm.org2normal glycemic levels on early OGTT). The clinic and trial staff and women were unaware of the OGTT results.
Management of care for all the women included education, dietary advice, and instructions on how to measure capillary blood glucose levels. Criteria for pharmacotherapy and other intensification of treatment were consis-tent with those in previous trials. Obstetrical management was performed according to local practice.The trial had three prespecified primary out-comes, for which the results were assessed hier-archically. After assessment of the initial screen-ing results, 802 women underwent randomization, of whom 98.9% were included in the final analy-sis. The baseline characteristics of the women in the trial groups were similar. The women had a mean maternal age of 32 years, a mean BMI of 32 at the first visit, and a mean glycated hemo-globin level of 5.2%. Slightly less than 22% of the women were primigravid, 48% had a family history of diabetes, 19% had a history of poly-cystic ovary syndrome, and 36% had a history of gestational diabetes in a previous pregnancy, and the initial OGTT was performed at a mean of 15.6 weeks’ gestation. The percentage of women with a history of larger babies was higher in the control group than in the intervention group (19% vs. 13%), as was the percentage of women with a his-tory of chronic hypertension (6.9% vs. 3.5%).An adverse neonatal outcome event (the first primary outcome, a composite of birth at <37 weeks, birth weight of ≥4500 g, birth trauma, neonatal respiratory distress warranting treat-ment, phototherapy, stillbirth or neonatal death, or shoulder dystocia) occurred in 24.9% of the infants born to women in the intervention group and in 30.5% of those born to women in the control group, for an adjusted relative risk of 0.82 (95% confidence interval, 0.68 to 0.98).
This difference with respect to the primary outcome was driven by a lower percentage of infants with re-spiratory distress among the women in the in-tervention group than among those in the control group; it is important to note that the incidence of serious adverse respiratory events (three events) did not differ between the trial groups. No ma-terial between-group differences were observed with respect to pregnancy-related hypertension (the second primary outcome) and neonatal lean body mass (the third primary outcome).With few exceptions, the secondary outcomes also appeared to be similar in the trial groups. The apparent difference in the percentage of women with perineal injury (0.8% in the inter-vention group and 3.6% in the control group) is difficult to reconcile with the very similar results in the two trial groups with respect to neonatal birth weight (3258 g in the intervention group and 3343 g in the control group) and percentage of infants with shoulder dystocia (2.9% and 3.0%, respectively).
Not surprisingly, women in the intervention group were more likely to be treated with antihyperglycemic pharmacotherapy.This well-conducted trial provides much need-ed information regarding the benefits and harms of screening for and treating gestational diabetes in early pregnancy.
The modest benefits observed — coupled with the negative results of the EGGO trial — call into question current recommenda-tions for early screening and treatment among high risk women.
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