Circulating maternal cytokines influence fetal growth in pregnant women with rheumatoid arthritis

Ann Rheum Dis. 2013 Dec;72(12):1995-2001. doi: 10.1136/annrheumdis-2012-202539. Epub 2012 Dec 21.


Background: High rheumatoid arthritis (RA) disease activity during pregnancy is associated with a lower birth weight. Active RA is characterised by high circulating levels of cytokines, which can mediate placental growth and remodelling.

Objectives: To assess the influence of maternal serum cytokine levels on birth weight in RA pregnancy.

Methods: This study is embedded in the PARA Study, a prospective study on RA and pregnancy. In the present study, 161 pregnant women with RA and 32 healthy pregnant women were studied. The main outcome measures were birth weight SD score (birth weight SDS) in relation to maternal serum levels of interleukin-10 (IL-10), interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα) at three different time points: preconception and during the first and third trimester. Single-nucleotide polymorphisms (SNPs) in the corresponding cytokine genes were also studied.

Results: During the first trimester, IL-10 was detectable in 16% of patients with RA, IL-6 in 71%, and TNFα in all patients with RA. Mean birth weight SDS of children born to mothers with RA was higher when IL-10 level was high compared with low (difference=0.75; p=0.04), and lower when IL-6 was high compared with low (difference=0.50; p<0.01) in the first trimester. No correlation was seen at the other time points studied or with TNFα. Cytokine levels were not related to their corresponding SNPs.

Conclusions: Maternal IL-10 and IL-6 levels are associated with fetal growth in RA. In the first trimester, high IL-10 levels are associated with higher birth weight SDS, and high IL-6 levels are associated with lower birth weight SDS, even after correction for disease activity.

Keywords: Cytokines; DAS28; Rheumatoid Arthritis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / genetics
  • Birth Weight / physiology
  • Cytokines / blood*
  • Cytokines / genetics
  • Female
  • Fetal Development / physiology*
  • Humans
  • Infant, Newborn
  • Interleukin-10 / blood
  • Interleukin-10 / genetics
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Pregnancy Complications / blood*
  • Pregnancy Complications / genetics
  • Prospective Studies
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics


  • Cytokines
  • IL10 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10