Thyroid antibodies add to risk for pregnancy complications in women with connective tissue disease

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  • Thyroid antibodies can add to the risk for miscarriage, fetal growth restriction, preeclampsia, and preterm delivery in women with connective tissue disease (CTD) and should be routinely considered in pregnant women with CTD. 

Study design

  • To investigate the coexistence of autoimmune thyroid and connective tissue diseases during the first trimester, 150 women with CTD and 150 without were evaluated for obstetric outcomes. 

Key findings

  • In the case group of 150 women, 61 (1.6% of 3852 women screened) had insufficient critera for a diagnosis of CTD, 61 (1.6%) were diagnosed with undefined CTD (UCTD), and 28 (0.7%) were diagnosed with major CTD, including 6 with rheumatoid arthritis, 5 with systemic lupus erythematosus, 8 with Sjögren syndrome, 5 with antiphospholipid syndrome, 2 with systemic sclerosis, 1 with mixed CTD, and 1 with monoarticular arthritis.
  • Overall prevalence of thyroid peroxidase (TPO-a) or thyroglobulin (TG-a) autoantibody detection was 8% (12 of 150) among controls, 62.3% (38 of 61) among UCTD, and 60.7% (17 of 28) in women with major CTD (P<.001 compared with controls for both UCTD and major CTD).
  • After adjustment for confounders, overall CTD (both major and undefined) and TPO-a plus TG-a positivity was associated with increased risk for moderate-severe complications of pregnancy, including miscarriage, fetal growth restriction, preeclampsia, and delivery before 34 weeks.
  • Odds ratios were adjusted for maternal age, nuilliparity, smoking in first trimester, diagnostic category of rheumatic disease, and detection of TPO-ab or TG-ab as explanatory variables.
  • The OR for overall CTD and complications of pregnancy was 3.54 (95% CI, 1.61-7.78).
  • The OR for TPO-a plus TG-a positivity was 2.78 (95% CI, 1.29-5.98).


  • The diagnosis of a definite CTD is uncertain among the 61 women who tested positive for rheumatic antibodies but had insufficient clinical criteria for diagnosis of a rheumatic disorder.

Why this matters

  • Thyroid disorders are associated with such adverse obstetric outcomes as spontaneous abortion, fetal death, fetal growth restriction, preeclampsia, gestational diabetes, and preterm delivery.
  • General population studies have suggested an association between thyroid and connective tissue diseases.
  • Although thyroid or rheumatic autoimmune disorders have been associated with pregnancy complications, there have been no data on the effect of the association between the disorders on pregnancy outcomes.