BACKGROUND AND PURPOSE:

• Korevaar et al. (JAMA, 2019) investigated whether maternal thyroid function test levels associated with non-overt, milder thyroid abnormalities and thyroid autoimmunity are risk factors for preterm birth

METHODS:

• Systematic review and meta-analysis
  • Study conducted by the Consortium on Thyroid and Pregnancy—Study Group on Preterm Birth (collaboration of prospective birth cohorts)
  • Individual data was collected so that definitions for thyroid test levels could be standardized
• Data sources
  • Published data: Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases
  • Unpublished data: Open invitations sent to relevant journals, international conferences, social media, and personal contacts
• Inclusion criteria
  • Published and unpublished prospective cohort studies
  • Studies with data on relevant thyroid function tests
    • Thyrotropin (TSH) | Free thyroxine (FT4) | thyroid peroxidase (TPO) antibody
  • Exclusion: Studies only including overt thyroid disease or treatment was administered based on abnormal thyroid function tests
• Definitions:
  • Subclinical hypothyroidism: Increased thyrotropin concentration with normal FT4 concentration
  • Isolated hypothyroxinemia: Decreased FT4 concentration with normal thyrotropin concentration
• Data synthesis and analysis
  • Studies screened by 2 independent reviewers
  • Individual participant data were analyzed using mixed-effects models
  • Adjustments made for: Maternal age | BMI | Ethnicity | Smoking | Parity | Gestational age at blood sampling | Fetal sex
• Primary outcome: Preterm birth (<37 weeks)
• Secondary outcome: Very preterm birth (<32 weeks)

RESULTS:

• 19 cohorts were included | 47,045 pregnant women | 5.0% preterm birth   
  • Subclinical hypothyroidism: 3.1%
  • Isolated hypothyroxinemia: 2.2%
  • TPO antibody positive: 7.5%
• Risk of preterm birth was higher for subclinical hypothyroidism (6.1%) vs euthyroid (5.0%)
  • Odds ratio (OR) 1.29 (95% CI, 1.01 to 1.64)
• Risk of preterm birth was higher for isolated hypothyroxinemia (7.1%) vs euthyroid (5.0%)
  • OR 1.46 (95% CI, 1.12 to 1.90)
  • Risk also increased for very preterm birth (OR 2.57; 95% CI, 1.55 to 4.27)
• Each 1-SD higher maternal TSH concentration was associated with a higher risk of preterm birth
  • Absolute risk difference 0.2% (95% CI, 0% to 0.4%) per 1 SD
  • OR 1.04 (95% CI, 1.00 to 1.09) per 1 SD
• TPO antibody–positive had a higher risk of preterm birth vs TPO antibody–negative
  • Absolute risk difference 1.6% (95% CI, 0.7% to 2.8%)
  • OR 1.33 (95% CI, 1.15 to 1.56)
  • Risk was also increased for very preterm birth (OR 2.45; 95% CI, 1.81 to 3.32)

CONCLUSION:

• Subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were associated with a higher risk of preterm birth
• Authors suggest that while these results do not support universal thyroid screening in pregnancy

The results support the concept of a reflex TPO antibody measurement in women with a thyrotropin concentration higher than 4.0 mIU/L, and gestational thyrotropin monitoring for TPO antibody–positive women prior to conception.

• An accompanying editorial (see ‘Learn More – Primary Sources’) points out that routine screening for TSH, free thyroxine and TPO antibody is not recommended by ACOG or the American Thyroid Association based on previous RCTs and further states

Several recent large, well-done clinical trials that assessed the effect of routine pregnancy screening for and thyroid hormone treatment of subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity have failed to show benefit. It seems plausible that these thyroid testing abnormalities may reflect other nonthyroidal processes rather than thyroid dysfunction.

Learn More – Primary Sources:

Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis

Editorial: Thyroid Function Test Abnormalities During Pregnancy

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