Rheumatoid Arthritis Exposure In Utero Increases Chronic Disease Risk in Children

Children born to mothers with rheumatoid arthritis (RA) are at increased risk for certain chronic disorders compared with children born to mothers without RA, according to the results of a Danish national cohort study published in Arthritis Care and Research.

Of the 15 disease types selected for comparison, offspring exposed to maternal RA in utero had considerably higher morbidity in 5 categories compared with children who were not exposed in utero. The most substantial upticks in childhood or adolescent risk were for diagnosis of RA, followed by thyroid disease and epilepsy.

As one of the more common chronic diseases of pregnancy, the potential impact of maternal RA on offspring often causes concern among expectant mothers. However, there has been uncertainty among experts about whether in utero exposure to maternal RA affects the level of risk for certain chronic conditions.

The researchers examined records for all Danish children born from 1989 to 2013, dividing this population into cohorts of children who were exposed (n=2106) or unexposed (n=1,378,539) to maternal RA. They computed crude and adjusted hazard ratios (aHRs) using Cox regression models, while considering a variety of possible confounders.

Of the 5 diagnostic categories with heightened aHRs in the exposed cohort, 3 were statistically significant: RA (aHR, 2.89; 95% CI, 2.06-4.05), thyroid disease (aHR, 2.19; 95% CI 1.14-4.21), and epilepsy (aHR, 1.61; 95% CI 1.16-2.25). The aHRs for both chronic lung disease (aHR, 1.16; 95% CI 0.87-1.55) and anxiety/personality disorders (aHR, 1.15; 95% CI 0.80-1.67) also increased substantially compared with the unexposed cohort, although they were not statistically significant.

The study’s confirmation of the association between chronic diseases of childhood and maternal RA was identified as a major strength. Other observed strengths were the large sample size, the use of register-based data, complete patient follow-up, accounting for confounders, and the focus on a diverse array of chronic illnesses. In addition, outcomes were assessed while investigators were blinded to exposure status, which eliminated the chance of selection or information bias.

The authors also acknowledged that child outcomes could potentially be misclassified and that medication use was not included in the analysis. Socioeconomic information was also unavailable, and general practitioners did not verify patients’ clinical outcomes. In addition, biologic mechanisms of these associations could not be deduced, leaving investigators unable to parse genetic factors from intrauterine environmental influences.

Children exposed to RA in utero may be more likely to be diagnosed during childhood or adolescence with several different chronic conditions. These children have a 61% greater chance for epilepsy and a 2-fold increased risk of developing RA compared with children who were not exposed to RA in utero. These findings represent important challenges for pediatricians, rheumatologists, and general practitioners, who should remain cognizant of the elevated risk for chronic diseases — especially RA, epilepsy, and thyroid disturbances — within this population.

Reference

Jølving LR, Nielsen J, Kesmodel US, Nielsen RG, Beck-Nielsen SS, Nørgård BM. Children born by women with rheumatoid arthritis have increased susceptibility for selected chronic diseases – a nationwide cohort study [published online December 11, 2017]. Arthritis Care Res (Hoboken). doi:10.1002/acr.23461