Objectives: The “fetal origins of adult disease” hypothesis suggests the uterine environment can influence the susceptibility of a fetus to future disease. We examine whether the fetal environment, as reflected by birthweight, could modulate an individual’s future risk of rheumatoid arthritis (RA).
Methods: The relationship between birthweight and the risk of incident RA was studied in 87 077 women followed prospectively in the Nurses’ Health Study cohort. New cases of RA diagnosed between 1976 and 2002 were confirmed in 619 women. The association between birthweight and the future development of RA was studied in age-adjusted and Cox proportional hazard models adjusting for age and potential confounders, including history of maternal diabetes, childhood socioeconomic status, prematurity, maternal and paternal smoking, as well as additionally adjusting for risk factors for RA including smoking, age at menarche, use of oral contraceptives, use of post-menopausal hormones, total lifetime breastfeeding, and body mass index (BMI) at age 18.
Results: In an age-adjusted model, birthweight >4.54 kg vs birthweight 3.2–3.85 kg was associated with a two-fold increased risk of RA (relative risk (RR) = 2.1, 95% CI 1.4 to 3.3). Further adjusting for potential confounders and risk factors did not change this relationship (RR = 2.0, 95% CI 1.3 to 3.0). Findings were similar when we limited cases to those with rheumatoid factor positive RA (RR = 2.1, 95% CI = 1.2 to 3.6).
Conclusions: In this large prospective cohort, birthweight >4.54 kg was associated with a two-fold increased risk of adult onset RA, compared with those of average birthweight. Further study of this observation may provide insight into the pathogenesis of RA.
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Competing interests: None. The study funding sources had no role in study design, collection, analysis, or interpretation of data, writing of the manuscript, or the decision to submit for publication.
Funding: This research was supported by NIH grants, CA87969, R01 AR49880, K24 AR0524-01, K12 HD051959, and K23 AR050607-01. LAM was supported by an American College of Rheumatology Clinician Investigator Fellowship Award. She is also supported by an Arthritis Investigator/Clinical Investigator Award from the National and New York State Arthritis Foundation. KHC is supported by an Arthritis Investigator Award from the American College of Rheumatology and the Arthritis Foundation, a Building Interdisciplinary Research Collaborations in Women’s Health (BIRCWH) Award jointly funded by NIMH, NIAID, NICHD, and OD, and the Katherine Swan Ginsburg Memorial Award. JFS is supported by a Doctoral Dissertation Award from the Arthritis Foundation.
Ethics approval: The Partners HealthCare System Institutional Review Board approved this study.
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