The influence of early life factors on the risk of developing rheumatoid arthritis

Abstract

SummaryRheumatoid arthritis (RA) is a chronic inflammatory disease that develops as a result of the interaction between genetic and environmental risk factors. Although increasing evidence shows the importance of genes in determining the risk of RA, it is clear that environmental factors also have a vital role. Studies to date have tended to concentrate on environmental influences around the time of disease onset. However, a number of pieces of evidence, including the fact that autoantibodies, such as rheumatoid factor (RF), can develop several years before the onset of clinical disease, suggest that environmental factors may influence disease susceptibility during early life. Several recent studies lend weight to this possibility, with an increased risk of RA in the offspring of mothers who smoked during pregnancy and in those with higher birth weight. There has also been a suggestion that the risk of RA is reduced in breast-fed infants. We describe the evidence surrounding the effect of early life factors on the risk of developing RA and possible mechanisms by which they may act.

Low birthweight is associated with an increased risk of LADA and type 2 diabetes: results from a Swedish case–control study

“…There was nothing to suggest that low birthweight is associated with autoimmunity per se; if anything, LADA patients with low birthweight tended to have lower GADA levels. This is in agreement with previous findings for type 1 diabetes [9,10] and other autoimmune diseases, including rheumatoid arthritis [23,24] and multiple sclerosis [25], suggesting an increased risk associated with high, but not low, birthweight.…”

Prenatal alcohol exposure alters the course and severity of adjuvant-induced arthritis in female rats

“…Environmental factors acting during sensitive periods of development are known to exert organizational effects on physiological/neurobiological systems, resulting in changes that can persist throughout life and influence the risk for diseases or disorders in adulthood (Welberg and Seckl, 2001; Owen et al, 2005) including the risk for RA (Del Rey et al, 2010; Colebatch and Edwards, 2011). Fetal programming is generally thought to facilitate the organism's adaptation to the postnatal environment.…”

Childhood socioeconomic factors and perinatal characteristics influence development of rheumatoid arthritis in adulthood

“…Maternal smoke exposure is associated with low birthweight31 but we saw no evidence of confounding by maternal or other household smoking (not shown). Cortisol dysregulation has also been proposed as a mechanism for the effects of birth weight and RA,32 suggesting an interesting link with SES findings, and recent studies show a U-shaped association with high and low birthweight both impacting adult cortisol levels 33 34…”