Oral corticosteroids confer little to no GDM risk for expectant mothers

Exposure to oral corticosteroids during pregnancy is not associated with the risk of gestational diabetes mellitus (GDM), except for a modest increase during an early exposure window, as shown in a study from South Korea.

The pooled estimate for the crude risk of GDM in relation to OCS exposure from gestational weeks 1 through 27 indicated an increase (risk ratio [RR], 1.29, 95 percent confidence interval [CI], 1.26–1.32), but this risk increase was attenuated to null following adjustments for covariates (weighted RR, 1.01, 95 percent CI, 0.99–1.03). [JAMA Intern Med 2025;doi:10.1001/jamainternmed.2025.6367]

When OCS exposure was assessed by 3-week intervals, only exposure during the 4–6-week interval was associated with a heightened risk of GDM (weighted RR, 1.10, 95 percent CI, 1.03–1.17).

The findings were consistent in subgroups defined by maternal age, indication, duration of action, dosage, timing, or duration of exposure.

“These [data provide reassurance to] clinicians managing chronic inflammatory or autoimmune conditions during pregnancy, when corticosteroid therapy may be essential for maternal and foetal wellbeing,” according to the investigators.

Concerns about the use of corticosteroids during pregnancy have been raised due to the drug’s well-known effect on glucose metabolism, including peripheral insulin resistance promotion, hepatic gluconeogenesis stimulation, and pancreatic β-cell function impairment. [Diabetes Metab Res Rev 2014;30:96-102; JAMA Netw Open 2024;7:e2423563]

“However, our findings indicate that, in the context of pregnancy, [the mentioned] effects may not translate into clinically meaningful adverse metabolic outcomes. It is possible that the degree or duration of corticosteroid exposure during pregnancy is insufficient to overwhelm the adaptive metabolic mechanisms that maintain maternal–foetal glucose homeostasis,” the investigators explained.

As for the modestly elevated risk of GDM occurring between 4 and 6 weeks’ gestation, the investigators postulated that OCS exposure during early pregnancy, even for a short period, may disrupt the pancreas’ ability to adapt, causing early insulin resistance. “This underscores the importance of considering early gestational exposures and highlights the need for further research into mechanisms underlying GDM development during this vulnerable period.”

Nevertheless, when considering OCS use during pregnancy, physicians should prioritize maternal disease control while maintaining vigilance in monitoring glucose metabolism, particularly in women with pre-existing risk factors, they said.

The analysis included 1,325,940 pregnancies resulting in live birth, of which 79,710 (6 percent) were exposed to OCS between 1 and 27 weeks of gestation. Compared with unexposed women, those with OCS exposure during pregnancy were more likely to have comorbidities including asthma (7.2 percent vs 2.2 percent), immune-mediated inflammatory disease (2.5 percent vs 0.4 percent), and migraine (8.1 percent vs 5.4 percent).