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Children whose mothers have rheumatoid arthritis (RA) are at risk for being born preterm, a Danish study found.

The risk of birth before 37 weeks of gestation was 1.5 times higher for babies whose mothers had been diagnosed with RA before the birth (OR 1.48, 95% CI 1.20-1.84) after adjustment for factors including maternal age, education, smoking, parity, paternal RA, and birth year, according to Ane L. Rom, MPH, of Copenhagen University, and colleagues.

Risk was also increased for children exposed to preclinical RA -- whose mothers were diagnosed later but who may already have developed autoantibodies and inflammation -- with an adjusted odds ratio of 1.32 (95% CI 1.07-1.64), the researchers reported online in .

In contrast, exposure to paternal RA was not associated with preterm birth (OR 1.07, 95% CI 0.75-1.54).

"Clinicians should be aware of the increased risk of preterm birth not only in women diagnosed with RA but also among women with signs of preclinical RA," Rom and colleagues wrote.

While maternal rheumatic diseases overall have been associated with adverse outcomes in pregnancy, less is known specifically about RA and very little is known about the effects of preclinical RA, when clinical manifestations have not yet become apparent.

To address these knowledge gaps, the researchers obtained data from Denmark's Medical Birth Registry for births between 1977 and 2008, and from the Danish National Hospital Registry for diagnoses of RA.

Birth information included weight, length, head and abdominal circumferences, gestational age at the time of birth, and weight of the placenta.

Among almost 2 million singleton births during the study period, 2,101 of the offspring were considered exposed to maternal RA, 11,455 were exposed to preclinical maternal RA, and 1,086 were exposed to paternal RA.

Compared with unexposed children, those whose mothers had RA were lighter, having birth weights that were 87 grams lower (95% CI minus 111.23-minus 62.84) and placental weights that were 14 grams lower (95% CI minus 21.46-minus 5.43). Weight of the placenta was considered "an indicator of a mechanism for growth restriction," the researchers explained.

Other measures of fetal growth such as head and abdominal circumference were similar for exposed and unexposed babies.

When the measures of fetal growth were adjusted for gestational age, the associations were attenuated by 30% to 68%, but were still statistically significant for weight, length, and placental weight, "suggesting that an effect of RA-induced modulation persists:"

• Birth weight, -44.97 g (95% CI minus 65.05-minus 24.89)
• Birth length, -0.174 cm (95% CI minus 0.27-minus 0.08)
• Placental weight, -9.05 g (95% CI minus 16.8-minus 1.3)

Various sensitivity and subanalyses also were performed, such as using only firstborn children and considering the timing of maternal RA diagnosis, with similar results as the main analysis.

"In this nationwide cohort study, children exposed to maternal RA have a slightly lower fetal size at birth compared to unexposed children," the researchers wrote.

They hypothesized that fetal growth may be influenced by "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 pointed out that the lack of association with paternal RA argues against genetics being strongly influential, and the fact that preclinical RA exposure also was associated with preterm birth lessens the likelihood of medication use being the primary cause, because mothers who did not yet have a diagnosis of RA were unlikely to be taking medications for the disease.

Despite the finding of heightened risk of preterm birth, the authors noted that the overall effect on birth size was small, although "low weight at birth may indicate poor fetal growth during pregnancy, which could potentially lead to impaired health later in life."

"For 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. Whether it has long-term health consequences for children of mothers with RA is unknown and needs to be studied," they concluded.

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