MADRID – Having a child was associated with ACPA-negative but not ACPA-positive rheumatoid arthritis in a case-control study of almost 5,000 women living in Sweden.
The odds ratio (OR) for ACPA (anti–citrullinated protein antibody)–negative rheumatoid arthritis (RA) comparing parous with nulliparous women was 2.1 in women aged 18-44 years. The effect was not seen in older women, with an OR of 0.9 for women aged 45-70 years.
"The risk seems to be more pronounced in the postpartum period [in the] 2 years before the onset of [RA] symptoms," Cecilia Orellana reported at the annual European Congress of Rheumatology. Indeed, the odds of developing ACPA-positive disease within the first year of childbirth (OR = 2.6) was higher than within 2 years (OR = 1.8).
Ms. Orellana, a second-year postgraduate student within the Institute of Environmental Medicine at the Karolinska Institutet in Stockholm, also noted that the risk of ACPA-negative RA appeared higher in women who had their first child at a young age. The OR for ACPA-negative RA in women younger than 23 years was 2.5, followed by 2.1 for those aged 23-26 years, 1.8 for those aged 27-30 years, and 1.5 for those older than 30 years.
The link between parity and RA has been studied before with some findings suggesting no association and others finding a possible protective effect of parity on the risk of RA. This is the only study to date to look at parity in relation to ACPA status (Ann. Rheum. Dis. 2013;72[Suppl. 3]:102).
The case-control study involved 2,035 women with RA and 2,911 age-matched controls enrolled in the ongoing Swedish EIRA (Epidemiological Investigation of RA) study during 1996-2009. Nearly two-thirds (64%) of women with RA were ACPA positive.
ORs were adjusted for smoking status, education, body mass index, age of menarche, and oral contraceptive use, but none of these adjustments altered the risk of developing RA.
The biological mechanisms behind the increased risk for ACPA-negative RA in women who have given birth needs further study, Ms. Orellana concluded.
The findings appear "counterintuitive" to what clinicians might assume, Dr. Christopher Buckley, professor of rheumatology at the University of Birmingham, England, said in an interview.
"I would have predicted that if women had had more children, there might have been more [ACPA-positive] disease, because you are more likely to have immune suppression, but this [study] actually suggests that women are protected from [ACPA-positive] disease," said Dr. Buckley, who was not involved in the study. "This might mean that pregnancy is not a bad thing," he said, adding that if women do get pregnant they are more likely to have ACPA-negative disease, which actually carries a better prognosis.
As for how these data could help clinicians advise women, Dr. Buckley noted that it is of course very likely that there is more than a single factor at play. Other factors would almost certainly be influencing the risk of RA. But these data beg the question as to how many children a woman might need to have to produce an effect. Since parity seems to influence ACPA-negative RA risk in younger women, the findings might be most relevant in the developing world where women tend to have their children at a younger age.
"It’s one of those results that is completely counterintuitive," Dr. Buckley said, "which usually tells you that there is something going on."
Ms. Orellana and Dr. Buckley had no disclosures. The study was supported by grants from the Swedish Medical Research Council, the Swedish Council for Working Life and Social Research, King Gustav V’s 80-year Foundation, the Swedish Rheumatic Foundation, the Stockholm County Council, and the insurance company AFA.