Are thyroid function test abnormalities a risk factor for preterm birth?

  • Korevaar TIM & al.
  • JAMA
  • 20 Aug 2019

  • curated by Sarfaroj Khan
  • UK Clinical Digest
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  • In pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and thyroid peroxidase (TPO) antibody positivity were significantly associated with an increased risk for preterm birth.

Why this matters

  • Findings provide insights toward improving clinical decision-making strategies that should consider the potential harms and benefits of thyroid function screening programs and levothyroxine treatment during pregnancy.

Study design

  • 19 prospective cohort studies involving 47,045 pregnant women met eligibility criteria after a search across electronic databases.
  • Primary outcome: preterm birth (
  • Secondary outcomes: very preterm birth (
  • Funding: Netherlands Organization for Scientific Research.

Key results

  • Of 47,045 pregnant women, 1234 (3.1%) and 904 (2.2%) had subclinical hypothyroidism, isolated hypothyroxinemia, respectively and 3043 (7.5%) were TPO antibody positive.
  • Preterm and very preterm births were reported in 2357 (5.0%) and 349 (0.7%) pregnant women, respectively.
  • Women with subclinical hypothyroidism were at an increased risk for preterm birth vs those with euthyroidism (OR, 1.29; 95% CI, 1.01-1.64; P=.03)
  • Women with isolated hypothyroxinemia vs those with euthyroidism had a higher risk for preterm (OR, 1.46; 95% CI, 1.12-1.90; P=.004) and very preterm (OR, 2.57; 95% CI, 1.55-4.27; P<.001 births.>
  • In continuous analyses, each 1SD higher maternal thyrotropin concentration was associated with a higher risk for preterm birth (OR, 1.04 [95% CI, 1.00-1.09] per 1SD; P=.04).
  • TPO antibody-positive vs -negative women were at a higher risk for preterm (OR, 1.33; 95% CI, 1.15-1.56) and very preterm (OR, 2.45; 95% CI, 1.81-3.32; P<.001 for both births.>


  • Lack of statistical power to investigate the risk for very preterm birth in specific sub-groups.
  • Only 5 of 19 studies had data available on thyroglobulin antibodies.

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