Fetal Growth Associated with Maternal Rheumatoid Arthritis and Juvenile Idiopathic Arthritis.

Abstract

Background: Prior studies indicated that women with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are at twice higher risk of developing adverse pregnancy outcomes, this include preterm births and infants with low birth weight. A wide knowledge gap exists in our current understanding of how RA and JIA affect fetal growth during pregnancy. Objective: We aimed to evaluate fetal growth among patients with RA/JIA by comparing fetal growth indicators of offspring born to this population, compared to individuals without RA/JIA. We hypothesized that fetal growth among patients with RA/JIA is reduced, compared to individuals without RA/JIA. Study Design: We conducted a population-based cohort study in Denmark from 2008-2018 which included 503,491 individuals with singleton pregnancies. Among them, 2,206 were patients with RA and JIA. We linked several nationwide databases and clinical registries in Denmark to achieve our aim. Through the Danish Fetal Medicine Database (DFMD), we obtained fetal biometric measurements gathered from second trimester fetal ultrasound scans. We used International Classification of Diseases (ICD)-10 codes to identify pregnant patients with RA/JIA from the Danish National Patient Registry and linked them to the DFMD, other variables of interest were obtained from different Danish clinical registries. Next, we computed fetal growth gradient between second trimester and birth, using the mean difference in Z-score distances for each fetal growth indicator. We also estimated the risk of small for gestational age (SGA), all outcomes were compared between pregnant individuals with and without RA/JIA and adjusted for confounders. Results: Maternal RA and JIA was not associated with a reduction of estimated fetal weight (EFW) at mid-pregnancy [adjusted mean EFW Z-score difference of 0.05 (95% CI 0.01, 0.10; p=0.022)], but lower birth weights were observed among offspring [adjusted mean Z-score difference of -0.08 (95% CI -0.13, -0.04; p<0.001)]. We observed reduced mean Z-score differences in weight gradient from second trimester to birth among offspring of patients with RA/JIA who also used corticosteroids [-0.26 (95% CI -0.11, -0.41; p<0.001)], and sulfasalazine [-0.61 (95% CI -0.45, -0.77; p<0.001)] during pregnancy. Maternal RA/JIA was also associated with SGA [aOR of 1.47 (95% CI 1.16, 1.83; p<0.001)]. Similarly, the risk estimates were higher among corticosteroid [aOR 3.44 (95% CI 2.14, 5.25; p<0.001)] and sulfasalazine [(aOR 2.28 (95% CI 1.22, 3.88; p=0.005) users. Conclusion: Among pregnant patients with RA/JIA, fetal growth restriction may be most apparent after 18 to 22 weeks of gestational age. Closer antenatal monitoring around this period should be considered for this population.