Mothers with rheumatoid arthritis (RA) and those with preclinical disease are more likely to give birth prematurely and to infants who weigh slightly less than their nonexposed counterparts, according to a large Danish population study published online November 13 in Arthritis & Rheumatology.
Although prior studies have examined the effect of maternal rheumatic disease in pregnancy, none have focused specifically on RA, and few have included indicators of fetal growth measured at birth.
To correct this deficit, Ane Rom, MPH, from Copenhagen University Hospital in Denmark, and colleagues analyzed national registry data for 1,917,723 singletons born between 1977 and 2008, 2101 of whom had been exposed to maternal RA and 11,455 to preclinical aspects of the disease.
Results showed that exposure to maternal RA and preclinical RA increased the risk for preterm birth by factors of 1.48 (95% confidence interval [CI], 1.20 - 1.84) and 1.32 (95% CI, 1.07 - 1.64), respectively. The model was adjusted for maternal age, education, parity, birth year, and paternal RA, which was not found to be a risk factor (OR, 1.32; 95% CI, 1.07 - 1.64).
"Obstetricians should be aware of the increased risk of preterm birth in women with RA and among those with preclinical signs of the disease," Dr Rom emphasized in a journal news release.
The researchers found slight reductions in mean birth weight (RA: −87.04 g [95% CI, −111.23 to −62.84]; preclinical RA: −46.65 g [95% CI, −57.11 to −36.19]) and placental weight (−13.45 g [95% CI, −21.46 to −5.43]; preclinical RA: −4.61 [95% CI, −12.23 to 3.01]).
“[F]or all indicators of fetal growth gestational age seems to explain a great part of the effect of RA. However, differences in birth weight, birth length and weight of placenta remained statistically significant after adjustment for gestational age suggesting that an effect of RA induced modulation persists,” the authors write.
Other indicators of fetal growth were not affected by RA and preclinical RA, including birth length (mean Δ, −0.38 and −0.22 cm), head circumference (mean Δ, −0.13 and −0.12 cm), and abdominal circumference (mean Δ, −0.20 and −0.17 cm).
Commenting on potential mechanisms behind the findings, the authors hypothesize that "maternal RA may affect fetal growth either through fetal programming related to the effect RA may have on the intrauterine environment, through genetic factors, or due to medications taken through pregnancy."
However, they also note that reductions in fetal size may be attributed in part to reduced gestational time and that the lack of effect observed for paternal RA would indicate against genetics as a main factor. Also, the similarity in outcomes for mothers with RA (presumably taking medication during pregnancy) and those with preclinical disease (RA not yet diagnosed) argues against a large negative therapeutic effect.
Moreover, it is possible that certain treatments for RA may be beneficial in terms of fetal outcome.
"Experts on pregnancy in RA such as Dr Eliza Chakravarty and Dr Megan Clowse have speculated that treating women with disease-modifying antirheumatic drugs to control the RA during pregnancy might lower the incidence of low birth weight babies," Brian Kaye, MD, told Medscape Medical News, noting that rheumatologists have traditionally taken women off medication during pregnancy because of concerns regarding potential fetal effects.
"To my knowledge, there is no study looking at pregnancy outcomes in women on disease-modifying antirheumatic drugs vs not on them while pregnant to test this hypothesis," Dr Kaye added.
Dr Kaye is a clinical professor of medicine at the University of California, San Francisco; adjunct professor at Touro University California; and a practicing rheumatologist at Sutter East Bay Medical Foundation in Berkeley and Orinda, California.
Although more research is needed to elucidate the link between maternal RA and long-term outcomes, the researchers emphasize that, "[f]or women with RA, it is reassuring that only a small reduction in fetal growth was found for most of their children, which will have little, if any, impact on perinatal conditions for the child."
This study was funded by grants from the National Institute of Health, The Danish Council for Independent Research, and the Augustinus Foundation. The authors and Dr Kaye have disclosed no relevant financial relationships.
Arthritis Rheum. Published online November 13, 2014. Abstract
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Cite this: RA Increases Risk for Preterm Birth - Medscape - Nov 19, 2014.