Highlights
- A nationwide study of over 1.3 million pregnancies found no overall increased risk of gestational diabetes mellitus (GDM) associated with oral corticosteroid (OCS) use.
- The pooled weighted risk ratio (RR) for OCS exposure was 1.01 (95% CI, 0.99-1.03), indicating statistical non-significance for the broad duration of pregnancy.
- A modest, statistically significant increase in risk was identified specifically for exposure between 4 and 6 weeks’ gestation (RR 1.10; 95% CI, 1.03-1.17).
- Subgroup analyses demonstrated that the risk profile remained consistent regardless of maternal age, steroid dosage, duration of treatment, or the specific clinical indication for the medication.
Background: The Challenge of Managing Inflammatory Conditions in Pregnancy
Managing chronic inflammatory and autoimmune conditions—such as asthma, systemic lupus erythematosus (SLE), and rheumatoid arthritis—during pregnancy presents a complex clinical challenge. Oral corticosteroids (OCSs) are indispensable tools in the therapeutic arsenal due to their potent anti-inflammatory and immunosuppressive properties. However, their use is often approached with caution by both patients and clinicians due to concerns regarding metabolic side effects.
Corticosteroids are known to induce insulin resistance and increase hepatic gluconeogenesis, which are physiological pathways that could theoretically trigger or exacerbate gestational diabetes mellitus (GDM). GDM is associated with significant maternal and neonatal complications, including preeclampsia, macrosomia, and long-term metabolic risks for both mother and child. Despite these theoretical risks, high-quality, large-scale evidence regarding the specific association between OCS use and GDM has been limited, leading to potential undertreatment of maternal conditions or unnecessary anxiety regarding steroid therapy.
Study Design: Methodological Rigor in Population-Based Research
To address this evidence gap, Choi et al. conducted a comprehensive, nationwide population-based cohort study in Korea, published in JAMA Internal Medicine. The study analyzed data from pregnancies resulting in live births between 2010 and 2021, leveraging the expansive National Health Insurance Service database. From an initial pool of over 3.8 million pregnancies, 1,325,940 met the eligibility criteria for the final analysis.
The researchers utilized a sequential landmark analysis design, which allowed for a nuanced assessment of OCS exposure in 3-week intervals from the 1st through the 27th week of gestation. This temporal granularity is critical, as metabolic responses to medications can vary significantly depending on the developmental stage of the pregnancy. To minimize confounding by indication and other maternal factors, the study employed propensity score-based overlap weighting. This statistical method balanced the exposed and unexposed groups across a wide range of variables, including maternal comorbidities, concomitant medication use, and healthcare utilization patterns.
Key Findings: Dissecting the Association Between OCS and GDM
Out of the eligible cohort, 79,710 pregnancies (6.0%) involved exposure to oral corticosteroids within the first 27 weeks of gestation. The primary outcome—GDM—was identified using a validated algorithm starting from 20 weeks and 1 day of gestation through delivery.
The Pooled Analysis
The most significant finding for clinical practice was the pooled analysis results. In the raw data, the incidence of GDM was higher in the exposed group (9.50%) compared to the unexposed group (7.36%). However, after rigorous adjustment via overlap weighting, the weighted risk ratio (RR) was 1.01 (95% CI, 0.99-1.03). This result strongly suggests that after accounting for the underlying health status of the mother, OCS use itself does not pose a generalized risk for the development of GDM.
The 4-to-6-Week Window
While most gestational intervals showed no association, the researchers identified a modest but statistically significant increase in risk for women exposed to OCSs specifically between 4 and 6 weeks’ gestation (weighted RR, 1.10; 95% CI, 1.03-1.17). This finding is intriguing from a developmental biology perspective, potentially suggesting a sensitive window for metabolic programming or an early impact on placental development, though the absolute increase in risk remains small.
Subgroup Analyses: Dose, Duration, and Timing
A major strength of this study was its detailed subgroup analysis, which sought to identify if specific patterns of OCS use were more hazardous than others. The researchers examined several factors:
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Maternal Age:
No significant difference in risk was found between younger and older mothers.
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Dosage and Duration:
Neither high-dose therapy nor prolonged duration of OCS use significantly altered the risk of GDM compared to lower doses or shorter courses in the weighted analysis.
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Indication:
Whether the steroid was prescribed for respiratory conditions, dermatological issues, or musculoskeletal disorders, the risk profile remained stable.
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Potency:
The duration of action of the specific corticosteroid (short-acting vs. intermediate/long-acting) did not show a differential effect on GDM risk.
Expert Commentary: Interpreting the Data for Clinical Practice
This study provides much-needed reassurance for obstetricians, rheumatologists, and pulmonologists. The finding that OCSs do not broadly increase the risk of GDM suggests that the metabolic impact of these drugs during pregnancy may be less pronounced than previously feared, or perhaps that the physiological changes of pregnancy interact with corticosteroids in ways that differ from non-pregnant populations.
However, the modest risk increase in the 4-to-6-week window warrants further investigation. While it should not preclude the use of life-saving or condition-stabilizing steroids, it may suggest that clinicians should be particularly mindful of metabolic health in patients requiring steroids in the very early first trimester. It is also important to note that this study focused specifically on oral corticosteroids; the results may not necessarily generalize to high-dose intravenous pulse therapy or long-term, very high-dose regimens used in organ transplantation.
Limitations of the study include its reliance on prescription data, which does not guarantee patient adherence, and the potential for residual confounding inherent in any observational study. Furthermore, while the study used a validated algorithm for GDM, it did not have access to specific laboratory values (such as oral glucose tolerance test results), which might have provided additional depth to the metabolic findings.
Conclusion: A Balanced Approach to Steroid Therapy
The findings by Choi et al. support a shift toward a more confident, evidence-based use of oral corticosteroids during pregnancy when clinically indicated. By demonstrating that the overall risk of gestational diabetes is not significantly elevated, the study empowers clinicians to treat maternal inflammatory conditions effectively, thereby potentially improving overall pregnancy outcomes. The modest risk identified in the early first trimester serves as a reminder for continued vigilance and individualized patient assessment rather than a contraindication to necessary therapy.
References
Choi EY, Cho Y, Oh J, Choi A, Kim H, Shin JY. Oral Corticosteroid Use During Pregnancy and the Risk of Gestational Diabetes. JAMA Intern Med. 2025 Dec 1:e256367. doi: 10.1001/jamainternmed.2025.6367. Epub ahead of print. PMID: 41324930; PMCID: PMC12670261.
