Fetal Growth Associated with Maternal Rheumatoid Arthritis and Juvenile Idiopathic Arthritis

Abstract

Introduction: Patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are at a twice-higher risk of developing adverse pregnancy outcomes, such as preterm births and infants with a low birth weight. We aimed to evaluate fetal growth among patients with and without rheumatoid arthritis and juvenile idiopathic arthritis (RA and JIA). Materials and Methods: We conducted a population-based cohort study in Denmark from 2008-2018, which included 503,491 singleton pregnancies. Among them, 2206 were pregnancies of patients with RA and JIA. We linked several nationwide databases and clinical registries in Denmark to achieve our aim. First, we used the International Classification of Diseases-10 codes to identify pregnant patients with RA and JIA from the National Patient Registry. Next, we obtained fetal biometric measurements gathered from second-trimester fetal ultrasound scans and birthweights through the Fetal Medicine Database. Finally, we computed a fetal growth gradient between the second trimester and birth, using the mean difference in the Z-score distances for each fetal growth indicator. We also calculated the risk of small for gestational age (SGA). All outcomes were compared between pregnant individuals with and without RA and JIA, adjusted for confounders. Results: Maternal RA and JIA were not associated with a reduction in the estimated fetal weight (EFW) at 18 to 22 weeks of gestational age [adjusted mean EFW Z-score difference of 0.05 (95% CI 0.01, 0.10)]. We observed reduced mean Z-score differences in the weight gradient from the second trimester to birth among offspring of patients with RA and JIA who used corticosteroids [-0.26 (95% CI -0.11, -0.41)] or sulfasalazine [-0.61 (95% CI -0.45, -0.77)] during pregnancy. Maternal RA and JIA were also associated with SGA [aOR of 1.47 (95% CI 1.16, 1.83)] and the risk estimates were higher among corticosteroid [aOR 3.44 (95% CI 2.14, 5.25)] or sulfasalazine [(aOR 2.28 (95% CI 1.22, 3.88)] users. Conclusions: Among pregnant patients with RA and JIA, fetal growth restriction seemed to occur after 18 to 22 weeks of gestational age. The second half of pregnancy may be a vulnerable period for optimal fetal growth in this population.

Keywords: autoimmune disease; fetal growth; high-risk pregnancies; juvenile idiopathic arthritis; maternal fetal medicine; rheumatoid arthritis.

Figure 1

Flowchart of patient selection from linked clinical registries. Legends: DFMD: Danish Fetal Medicine Database; DCRS: Danish Civil Registration System; DMBR: Danish Medical Birth Registry; DNPR: Danish National Patient Registry; NPR: National Prescription Registry; RA: rheumatoid arthritis; JIA: juvenile idiopathic arthritis. * Incomplete records: pregnancy and birth records without gestational ages, lack of second-trimester fetal ultrasound information, lack of birthweights.

Figure 2

Proportion of antirheumatic therapy uptake at any time before and after second-trimester fetal ultrasound during pregnancy. CCS: corticosteroids; NSAIDs: Non-steroidal anti-inflammatory drugs; HCQ: hydroxychloroquine; SSZ: sulfasalazine.

Figure 3

Weight gradient of offspring born to patients with RA and JIA between second trimester and at birth. * Adjusted for maternal age, maternal body mass index, smoking status, income status, race, parity, birth year, pre-pregnancy hypertension, pre-pregnancy diabetes, and co-medication use during pregnancy.

Figure 4

Head circumference gradient of offspring born to patients with RA and JIA between second trimester and at birth. * Adjusted for maternal age, maternal body mass index, smoking status, income status, race, parity, birth year, pre-pregnancy hypertension, pre-pregnancy diabetes, and co-medication use during pregnancy.