Background/Purpose: Rheumatoid arthritis (RA) during pregnancy is a risk factor for several adverse pregnancy and child outcomes. Studies have found higher incidences of neurological and psychiatric diseases, including childhood epilepsy and autism spectrum disorders, in children born to mothers with RA. However, the overall long-term cognitive development of children exposed to maternal RA has scarcely been examined.

In this study, we examine the overall cognitive development of children born to mothers with RA by comparing their results in national standardized school tests, to those of their peers. The Danish national school tests are mandatory, annual tests conducted in all Danish public schools since 2010.

Methods: All singleton children born in Denmark between 1995 and 2008, who were listed in the Danish national school test register were included in this study (n=738,862). Children exposed to maternal RA in utero were identified through linkage of national registers. In subgroup analyses, we classified exposure according to maternal RA serostatus, and also included a maternal preclinical RA group (defined as the mother receiving a diagnosis of RA up to 3 years after birth of the child).

The Danish National School Tests are standardized, adaptive computer-based tests.  Children are tested in reading in grades 2, 4, 6 and 8, and in mathematics in grades 3 and 6. Results from all reading and mathematics tests, from 2010 until 2018, were included. We compared adjusted differences of means by maternal RA exposure separately for each test. We adjusted for potential confounders, i.e. maternal age, maternal educational level, nationality and smoking during pregnancy. We also compiled school test results from all tests, in reading and mathematics separately, and analysed them as repeated measurements for each child, using multilevel regression models. Missing data was handled by multiple imputations.

Results:  In total, 816 (0.1%) children were exposed to maternal RA in utero.

There were no differences in test scores in any of the reading tests between maternal RA exposed and unexposed children in grades 2, 4, 6 and 8.

In mathematics, exposed children scored marginally worse in both grades 3 and 6, compared to their unexposed peers (adjusted mean differences were -0.15 Standard Deviations (SD) (95% CI: -0.24; -0.07) and -0.17 SD (95% CI: -0.26; -0.07), respectively). 

Results did not change when combining the tests for all grade levels in multilevel regressions (adjusted mean differences were: reading: -0.01 SD (95% CI: -0.08; 0.06) and mathematics: -0.13 SD (95% CI: -0.20; -0.05)).

Children exposed to preclinical RA in utero showed the same pattern of test performance as children exposed to diagnosed maternal RA. There was no appreciable differences between children by maternal RA serostatus.

Conclusion: In this long-term national follow-up study of cognitive development in children, maternal RA exposed children performed similar to their peers in national reading tests. We observed a small, but consistent association with poorer performance on mathematics tests among the exposed children. This was comparable to children exposed to preclinical RA, indicating that RA treatment may not be the underlying cause.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rheumatoid-arthritis-in-pregnancy-and-offspring-school-performance-a-danish-nationwide-register-based-study/