Pregnancies among patients with rheumatoid arthritis were associated with higher rates of preterm birth and small-for-gestational-age infants compared with matched pregnancies from the French general population, according to a prospective multicenter study published in RMD Open. Preterm birth occurred in 16% of rheumatoid arthritis pregnancies vs 8% of matched controls, while small-for-gestational-age birth below the 10th percentile occurred in 21% vs 11%, respectively.
Researchers analyzed 100 pregnancies among 90 patients with rheumatoid arthritis (RA) enrolled in the French Groupe de Recherche sur la Grossesse et les maladies Rares prospective observational cohort prior to 12 weeks of gestation. From December 2015 to June 2021, 124 pregnancies among 111 patients with RA were enrolled with researchers prospectively collected maternal characteristics, disease activity, treatment exposure, obstetric history, and pregnancy outcomes.
For comparison with the general population, 90 RA pregnancies that met French National Perinatal Survey eligibility criteria were matched with 359 pregnancies from the 2016 and 2021 surveys. Matching was based on maternal age group, parity, geographic region, and singleton vs multiple pregnancy. The comparison included births at 22 weeks of gestation or later with birth weights of at least 500 g. Outcomes between the matched groups were evaluated using univariate analyses.
Mean maternal age was 34 years, and 53 of 92 pregnancies (58%) occurred among nulliparous patients. During pregnancy, glucocorticoid exposure occurred in 46% of pregnancies, conventional synthetic disease-modifying antirheumatic drug exposure in 25%, and biologic disease-modifying antirheumatic drug exposure in 39%. Moderate or high RA activity was documented at least once in 27% of the 78 pregnancies with at least one available disease-activity measurement.
Compared with matched controls, patients with RA had about twice the odds of preterm birth and small-for-gestational-age birth below the 10th percentile. Small-for-gestational-age birth below the third percentile occurred in 6% of RA pregnancies vs 2% of controls, corresponding to about three times the odds. No statistically significant differences were observed in gestational diabetes, cesarean delivery, macrosomia, congenital malformations, or neonatal transfer to intensive care or a neonatology department. Among 14 preterm births, 9 were spontaneous, and 5 were iatrogenic; 1 occurred before 32 weeks of gestation.
Because small-for-gestational-age and preterm births were more frequent among patients with RA than among those in the general population, researchers used multilevel mixed-effects logistic regression within the RA cohort to identify factors independently associated with each outcome. The models included random intercepts at the clinical-center and patient levels to account for within-center and within-patient correlation. Disease activity, body mass index, and treatment exposure classes were retained in the models, and multiple imputation was used for missing explanatory variables.
In multivariable analysis, nulliparity was associated with small-for-gestational-age birth. Maternal age and systemic glucocorticoid exposure at doses of at least 10 mg/day during pregnancy were independently associated with preterm birth; glucocorticoid exposure was associated with nearly five times the odds. This exposure was defined as any reported systemic daily dose meeting that threshold during pregnancy for RA treatment. Available data did not permit reliable estimates of treatment duration or cumulative glucocorticoid exposure.
RA disease activity measured by the Disease Activity Score in 28 joints using C reactive protein and tumor necrosis factor inhibitor exposure were not associated with increased odds of small-for-gestational-age or preterm birth. However, disease-activity measurements were missing for substantial proportions of pregnancies, particularly for trimester-specific assessments. Researchers also noted that glucocorticoid exposure could reflect more severe or refractory disease that was not fully captured by the available disease-activity measures.
The researchers identified a relatively small sample size, potential selection bias toward more complex or severe cases because patients were managed in tertiary centers, incomplete disease-activity data, potential disease-activity misclassification, and residual confounding as limitations.
The French Groupe de Recherche sur la Grossesse et les maladies Rares study received funding from patient associations, professional societies, public and institutional sources, research foundations, the ORRICK Society, and an unrestricted UCB grant. Assistance Publique–Hôpitaux de Paris provided logistical and administrative support. The study reports that its funder had no role in study design, data collection, analysis, interpretation, or manuscript preparation. Full disclosures can be found in the published study.
Source: RMD Open
