The Impact of Disease-Modifying Antirheumatic Drugs and Biologic Agents on Pregnancy Outcomes and Health of Affected Children---A Nationwide Population Study

It is well-establised that exposure to drugs, along with maternal and fetal factors, are key determinants for fetal development. However, the cause-and-effect relationships between drug exposure and pregnancy outcomes/child health are often subtle and difficult to establish. Most current evidence for adverse drug effects on developing fetus focuses on teratogenicity. However, it is also possible for drugs and chemicals to exert their effects on the fetus and result in subtle changes, such as functional, behavioral changes and future risk for diseases that are much more difficult to identify. Patients with rheumatic diseases are often female predominant with onset during child-bearing ages. The common rheumatic diseases include systemic lupus erythematosus, rheumatoid arthritis, Sjogren’s syndrome, systemic sclerosis, poly/dermatomyositis and spondyloarthritis. Any medication during pregnancy and nursing should be avoided in general. However, for many women with rheumatic diseases, the consequences of not being on medicine and risks of disease flare generally invalidate the practice of total avoidance of antirheumatic drugs. In addition, exposure to antirheumatic drugs is frequently inevitable, especially during first trimester, since little or no symptom can indicate conception. Therefore, a comprehensive survey on the possible adverse effects of antirheumatic drugs on fetus is desirable. Some of the anti-rheumatic drugs are “very old”, such as glucocorticoid, NSAIDs, hydroxychloroquine and sulfasalazine, and limited consensus have been available on the use of these drugs during pregnancy and lactation. Many novel antirheumatic drugs, such as anticytokine agents and B cell depletion agents are available nowadays but only rare evidence on the safety of these drugs during pregnancy is available. The purposes of this study are to assess the risk of inadvertent exposure of antirheumatic drugs during pregnancy on the mother and the children. For the mother, we compare the successful pregnancy, preterm labour and complication among exposed mothers with rheumatic diseases, unexposed mothers with rheumatic diseases and mothers without any rheumatic diseases. For the fetal outcome, we assess the conditions at birth for congenital abnormality, prematurity and intrauterine growth retardation and follow-up these children up to 10 years of age to see whether subtle defects undetectable or unrecognized in the neonate but expressed years after birth exist, such as retardation in growth or neurodevelopment, major infections as a proxy for immune function and major childhood diseases. To achieve the above objectives, we plan to develop an algorism to detect mothers and children using the National Health Insurance Research Database (NHIRD), to obtain all outcomes of mother and children identified, to link the NHIRD to national birth registry to obtain health condition at birth and national death registry to obtain causes of death and to compare the adverse outcomes of mothers and children exposed to antirheumatic drugs to those without to assess the risk of respective drugs.

Project ID:PC10401-0610
External Project ID:MOST103-2314-B182-043-MY2