Cytokines, Fetal Growth, and RA


From the Journal Of Reproductive Immunology

Major Finding: IL-10 in the first trimester seems to protect against low birth weight, while IL-6 seems to increase the risk. TNF-alpha exerts its influence in the third trimester, when higher levels also seem to protect against lower birth weights.

Data Source: A study of 302 pregnant women with rheumatoid arthritis and 33 controls.

Disclosures: The study was funded by the Dutch Arthritis Association. Dr. Dolhain did not disclose any pertinent financial relationships.

Circulating cytokines appear to influence fetal growth in pregnant women who have rheumatoid arthritis, results of a Dutch study suggest.

High levels of interleukin-10, IL-6, and TNF-alpha might all play a role, each acting independently – and at different stages of pregnancy – to increase the risk of low birth weight among infants born to these mothers, Dr. Radboud Dolhain and colleagues wrote (J. Reprod. Immunol. 2010 [doi: 10.1016/j.jri.2010.08.010]).

Dr. Dolhain of Erasmus University Medical Centre, Rotterdam, the Netherlands, and his coinvestigators examined circulating cytokines in 134 pregnant patients with rheumatoid arthritis during their first trimester, 168 in their third trimester, and 33 healthy controls. Birth weights were analyzed using standard deviation scores.

Disease activity in the women was based on the disease activity score for 28 joints (DAS28); the scale runs from 0–10, with higher numbers indicating greater disease activity.

Since IL-10, IL-6 and TNF-alpha generally decrease during pregnancy, the investigators sought to determine if any increasing gestational levels correlated with birth weight. Among the first trimester patients, 12 had detectable IL-10; all of these women had a higher disease activity score than did those with no IL-10 (mean DAS28 4.4 vs. 3.6).

Birth weights were compared between the two groups, which were matched with regard to disease activity, parity, and prednisone use.

The mean birth weight standard deviation was significantly greater in the IL-10 positive group (0.92) than in the matched negative group (0.15), Dr. Dolhain and his associates reported.

This association with IL-10 was not seen in the third trimester pregnancies.

The investigators then examined the effect of IL-6 by stratifying IL-6 levels and disease activity scores in the first and third trimester.

In the two groups with high disease activity (DAS28 3.8 or higher), birth weight standard deviation was significantly lower in mothers with high IL-6.

In the high IL-6 group, the birth weight standard deviation was −0.19, compared with 0.36 in the low IL-6 group.

Again, the authors found no such association in the third trimester.

“In the first trimester, elevated IL-10 seems to protect against the negative influence of RA disease activity on birth weight, [while] IL-6 seems to amplify this negative influence,” the investigators wrote.

“Both cytokines create a birth weight standard deviation of more than 0.50, which is considered clinically relevant. In the third trimester, there is no influence, suggesting an early critical window.”

TNF-alpha, however, did exert an influence in the third trimester of pregnancy, Dr. Dolhain and his colleagues noted. Stratifying TNF-alpha in the same way, they concluded that the birth weight standard deviation was lower in the group with low TNF-alpha (0.05) than in the group with high TNF-alpha (0.52).

This association was not present in the first trimester.

The finding that increased TNF-alpha is associated with better birth weights may require a rethinking of anti–TNF-alpha therapy for pregnant women, they suggested.

This implies that “TNF blockers, which are more and more prescribed during pregnancy to treat rheumatoid arthritis, should be used with caution,” Dr. Dolhain and his associates said.

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