Is birthweight associated with risk of rheumatoid arthritis? Data from a large cohort study.
OBJECTIVE
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.
Mandl
L A
LA
Division of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York City, New York 10021, USA. MandlL@hss.edu
Costenbader
K H
KH
Simard
J F
JF
Karlson
E W
EW
D000367:Age Factors; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000209:etiology*; D001724:Birth Weight; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008875:Middle Aged; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk