Treating gestational diabetes early in pregnancy without waiting for confirmation of a repeat oral glucose-tolerance test (OGTT) improved neonatal outcomes, the TOBOGM randomized trial showed.
For women first diagnosed before 20 weeks’ gestation, immediate treatment significantly reduced the composite incidence of adverse neonatal outcomes — preterm birth, birth trauma, high birth weight, respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia — to a rate of 24.9% compared with 30.5% among those whose treatment depended on confirmation as usual after repeat OGTT at 24 to 28 weeks’ gestation.
Maternal outcomes, however, didn’t improve with the earlier intervention, David Simmons, MD, of Western Sydney University in Australia, and colleagues reported in the New England Journal of Medicine.
The findings were also presented at the International DIP Symposium on Diabetes, Hypertension, Metabolic Syndrome & Pregnancy: Innovative Approaches in Maternal Offspring Health in Thessaloniki, Greece.
The confluence of rising maternal age and overweight and obesity among women — the two strongest risk factors for gestational diabetes — has led professional societies to call for screening high risk women for hyperglycemia early in pregnancy along with standard screening in the second trimester, noted an accompanying editorial.
“This well-conducted trial provides much needed information regarding the benefits and harms of screening for and treating gestational diabetes in early pregnancy,” wrote Michael F. Greene, MD, of Massachusetts General Hospital and Harvard Medical School, both in Boston.
However, the only prior randomized trial of early screening and treatment for gestational diabetes in a high risk group of women with obesity (the EGGO trial) showed no impact on combined maternal and neonatal outcomes, although underpowered with only 69 gestational diabetes cases.
Against that backdrop, the “modest benefits observed” in TOBOGM “call into question current recommendations for early screening and treatment among high risk women,” Greene argued.
The researchers acknowledged that the 95% confidence interval around the estimated difference in neonatal adverse outcomes was compatible with anywhere from a 1.2 to a 10.1 percentage-point reduction in risk.
And it was driven by fewer infants with respiratory distress in the intervention group, which was unexpected, according to Simmons and colleagues. “[A]lthough respiratory distress is known to occur more frequently in infants born to women with gestational diabetes, its incidence was not shown to be lower in other trials of treatment for gestational diabetes that had been diagnosed at 24 to 28 weeks’ gestation.”
Greene also emphasized that there was no difference in incidence of serious adverse respiratory events between groups in the TOBOGM trial (three events for both).
The trial included 802 women with a mean age of 32 seen at 17 hospitals in Australia, Austria, India, and Sweden. The women all had a singleton pregnancy at 4 weeks’ to 19 weeks 6 days’ gestation, at least one risk factor for hyperglycemia in pregnancy (prior gestational diabetes, BMI >30, age ≥40, first-degree relative with diabetes, previous macrosomia, polycystic ovary syndrome, or non-European ancestry), and met World Health Organization (WHO) criteria for gestational diabetes on a 2-hour 75-g OGTT (done at 15.6 week’s gestation on average).
They were randomly assigned to receive immediate treatment for gestational diabetes or to deferred decision on treatment based on repeat oral glucose-tolerance test (OGTT) at 24 to 28 weeks’ gestation. The immediate treatment group were more likely than the delayed group to get insulin (58.1% vs 41.4%) or metformin (23.6% vs 10.4%).
One-third of the early gestational diabetes cases didn’t have it on repeat OGTT in the second trimester, as expected from prior studies.
“This finding raises questions about whether criteria that had been established for OGTT at 24 to 28 weeks’ gestation can be applied to testing early in pregnancy, particularly if there is a potential for harm, such as an increase in the number of small-for-gestational-age births among women who had received early treatment,” the researchers noted.
Glycemia is known to vary as pregnancy progresses during the first trimester, which makes setting diagnostic criteria a challenge, they added. The Glycemic Observation and Metabolic Outcomes in Mothers and Offspring (GO MOMs) observational study is underway to evaluate use of continuous glucose monitoring between 10 and 14 weeks’ gestation.
After the first primary outcome of neonatal events in TOBOGM, hierarchical assessment of the second primary endpoint — pregnancy-related hypertension — showed no impact of early treatment (10.6% vs 9.9%, adjusted mean difference 0.7 percentage points, 95% CI −1.6 to 2.9). The third primary, neonatal lean body mass, likewise didn’t differ between groups significantly (2.86 vs 2.91 kg).
Serious adverse events associated with screening and treatment were similar between groups as well.
Limitations of the trial mentioned by the researchers included “the nonstandardized approach to treatment for gestational diabetes and the use of treatment targets that had been established for the third trimester of pregnancy and had not been tested in early pregnancy.” Also, recruitment of women with risk factors for hyperglycemia meant that the results may not be applicable to broad screening of women without these risk factors. The trial also included limited numbers of Black or Hispanic women, “few of whom live in the trial recruitment countries.”
The trial was supported by the National Health and Medical Research Council, the Region Örebro Research Committee, Medical Scientific Fund of the Mayor of Vienna, the South Western Sydney Local Health District Academic Unit, and a Western Sydney University Ainsworth Trust Grant.
Simmons disclosed relationships with Abbott Diabetes Care.
Greene disclosed employment by the New England Journal of Medicine as associate editor.
New England Journal of Medicine
Source Reference: Simmons D, et al “Treatment of gestational diabetes mellitus diagnosed early in pregnancy” N Engl J Med 2023; DOI: 10.1056/NEJMoa2214956.
New England Journal of Medicine
Source Reference: Greene MF “Early versus second-trimester screening and treatment for diabetes in pregnancy” N Engl J Med 2023; DOI: 10.1056/NEJMe2304543.