Many women with rheumatoid arthritis (RA) will have one or more pregnancies while having RA. Little is known about long term pregnancy outcomes for children born by women with RA but studies show more perinatal complications and fetal growth restriction which may activate fetal programming. Fetal programming in this group of children has not been investigated due to lack of large datasets that allow long-term follow up of children born to mothers with RA. Medications used to treat RA may also be harmful to the fetus, since medications are often required to manage disease activity during pre-conception and early stages of pregnancy. Our long-term aim is to investigate health conditions as measured by mortality and hospital discharge diagnoses in children born by mothers who had RA taking into consideration birth weight, gestational age and perinatal complications.
Specific aims : To set up a cohort of children born by women who had been hospitalized for RA and a cohort of children born by mothers without this history. To record congenital malformation, gestational age, birth weight and other reproductive failures in these cohorts. To further characterize exposed pregnancies according to treatment for RA in the pregnancies that occurred after 1995. These cohorts can be followed for up to 30 years at present but follow may be continued if needed. Design and Methods: A National cohort study using national registries in Denmark, with complete information on all Danish citizens (5.5 million and about 65,000 births per year) as well as long-term follow up of their children. Prescription data will be obtained from the National Registry of Medicinal Product Statistics and diagnoses will be obtained from the National Patient Registry of Hospital Discharges. Data on social and occupational factors will be available from the other national registers. All data in all registers are personally identifiable by means of the civil registration number (CPR) that has been given to all citizens from 1968 and forward in time. The CPR allows for linkage between registers and for linkage of biological and adopted children to the parents. Outcomes: Miscarriages, birth defects, adverse pregnancy outcomes, disease pattern in childhood and early adulthood. Exposures: RA, medical treatments for RA during pregnancy, RA in mother, mothers with RA who were medically treated during pregnancy. Statistical analyses: Data will be analyzed using Cox models. Several potential confounders will be taken into consideration such as age, parity, cohabitation, social conditions and place of living. All analyses will be performed using Stata/SAS Statistical software packages. Implications: The findings will add evidence on adverse birth outcomes and long term disease patterns in children born by mothers with RA. Knowledge will be generated about the potential differential impact of different RA treatments on the unintended outcomes. The results will indicate if more active monitoring and early intervention are needed to reduce the potentially increased risk for the unborn child. The study may also provide additional information on the potential fetotoxic effects of drugs used in treating RA.

Public Health Relevance

Our results will add evidence on adverse birth outcomes and disease patterns in childhood and early adulthood among children born by mothers with rheumatoid arthritis (RA). Furthermore, using this disease as a model makes it possible to study long-term programming effects related to the expected impact the disease has on fetal growth. Our results will contribute to the sparse knowledge about the long-term impact of RA treatment during pregnancy, and knowledge will be generated about the potential differential impact of different RA treatments on the unintended outcomes. The findings can be extrapolated to the U.S. population since both diagnostic practice and treatments are similar.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Exploratory/Developmental Grants (R21)
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Neurological, Aging and Musculoskeletal Epidemiology (NAME)
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Witter, James
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University of California Los Angeles
Public Health & Prev Medicine
Schools of Public Health
Los Angeles
United States
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