Pregnancy and the Risk of Rheumatoid Arthritis in a Highly Predisposed North American Native Population

Abstract

In this unique population, greater parity significantly reduced the odds of RA; an early age at first birth increased the odds, and the postpartum period was confirmed as high risk for RA onset. The protective effect of repeated exposure to the ameliorating hormonal and immunological changes of pregnancy may counterbalance the effect of early exposure to the postpartum reversal of these changes.

Menopause and Possible Effect on Association Between Age and Anticyclic Citrullinated Peptide Antibodies in Women At Risk of Rheumatoid Arthritis

“…These findings are consistent with studies that have reported that the postmenopausal period, an early age at menopause, the postpartum period, and treatment with antiestrogen agents were associated with RA onset 5,6,7 . All these phenomena have in common an acute decline in estrogen bioavailability.…”

Reproductive history and postmenopausal rheumatoid arthritis among women 60 years or older

“…6 First, RA symptoms may be alleviated through microchimerism, whereby fetal DNA can circulate in maternal blood for decades after birth, resulting in broader self-recognition by the immune system. 7 Estrogen, progesterone, and cortisol levels increase during the course of a pregnancy, favoring cytokine profiles and CD4 + regulatory T-cells that counter cell-mediated autoimmunity, all of which substantially decline in the postpartum period. 6 Second, maternal-fetal disparity in human leukocyte antigen class II antigens may be important for reducing RA symptoms during pregnancy.…”

“…This beneficial effect of microchimerism is expected to wane with time since last pregnancy. 7 Fourth, nulliparous women may be at increased risk for inflammation of multiple joints, potentially because of hormonal imbalances resulting from infertility, a heterogeneous condition affecting 10% of the general population and 25% of women diagnosed with RA. 6 Third, pregnancy can delay the onset of RA symptoms with better prognosis.…”

Individuals at risk of seropositive rheumatoid arthritis: the evolving story

“…Instead, there are consistent data supporting that estrogens have a protective effect in the clinical development of the disease. These include that early menopause is associated with the subsequent development of RA, most of the patients experience partial or complete remission during pregnancy but relapse during the postpartum period, and there is a reduction in the incidence of disease onset during pregnancy but the incidence increases in the postpartum [57,[59][60][61][62][63][64][65][66][67]. Interestingly, estrogens have both pro-and anti-inflammatory effects that may explain their paradox in RA pathogenesis.…”