There is a significantly higher risk of very preterm birth (< 32 weeks’ gestation) in thyroid peroxidase antibody (TPOAb)-positive women compared to TPOAb-negative women, especially when thyroid stimulating hormone (TSH) is above 4.0 mU/L. These are the two main findings of a systematic review and individual participant meta-analysis of the association between thyroid function test abnormalities and thyroid autoimmunity with preterm birth (PTB) in JAMA.
“There is a large heterogeneity amongst all previously published studies about this association,” said principal investigator Tim Korevaar, MD, PhD, a postdoctoral research fellow in thyroid diseases at Erasmus University Medical Center in Rotterdam, Netherlands. “For example, the definition of thyroid dysfunction including subclinical hypothyroidism varies greatly, thus limiting the interpretability in clinic and any efforts to translate all these previous studies into clinical recommendations.”
The review comprised 19 prospective cohort studies found mostly by searching the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials and Google Scholar databases from inception through March 2018.Mean age of the 47,045 pregnant women included for analysis was 29 years, with a mean gestational age at blood sampling of 12.9 weeks.
Of the study population, 3.1% had subclinical hypothyroidism (increased thyrotropin concentration with normal free thyroxine [FT4] concentration) and 2.2% had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration).
In addition, 7.5% of the women were TPO antibody-positive and 5.0% delivered prematurely.
Risk of PTB was statistically significantly higher for women with subclinical hypothyroidism than euthyroid women: 6.1% vs. 5.0%, respectively, with an absolute risk difference of 1.4% (95% confidence interval [CI]: 0% to 3.2%) and an odds ratio (OR) of 1.29 (95% CI: 1.01 to 1.64). Similarly, risk of PTB among women with isolated hypothyroxinemia was 7.1% compared to 5.0% in euthyroid women, with an absolute risk difference of 2.3% (95% CI: 0.6% to 4.5%) and an OR of 1.46 (95% CI: 1.12 to 1.90).
In continuous analyses, each one unit increase in the standard deviation (SD) for higher maternal thyrotropin concentration was associated with a higher risk of PTB, for an absolute risk difference of 0.2% (95% CI: 0% to 0.4%) per one SD and an OR of 1.04 (95% CI: 1.00 to 1.09) per one SD.
Thyroid peroxidase antibody–positive women also had a higher risk of PTB compared to TPO antibody–negative women: 6.6% vs. 4.9%, respectively, with an absolute risk difference of 1.6% (95% CI: 0.7% to 2.8%) and an OR of 1.33 (95% CI: 1.15 to 1.56).
“Our findings validate a reflex TPOAb measurement for women with a TSH above 4 and also imply that it is important to actively plan to assess early gestational thyroid function tests in women known to be TPOAb-positive preconception,” Dr. Korevaar told Contemporary OB/GYN.
“However, we did not expect that isolated hypothyroxinemia and TPOAb positivity would be risk factors for predominantly very preterm birth rather than for preterm birth (< 37 weeks’ gestation),” Dr. Korevaar said. “Previous studies have lacked adequate numbers to distinguish these two different outcomes, mainly because very preterm birth is uncommon, occurring in about 1% of pregnancies.”
Dr. Korevaar said it is important to distinguish the two outcomes because “very preterm birth has a much more detrimental effect on child health than does preterm birth that occurs after 32 weeks.”
Dr. Korevaar and his associates have initiated other studies within the consortium of thyroid and pregnancy, focusing on birth weight or the role of triiodothyronine (T3).
Dr. Korevaar receives lecture fees from Berlin Chemie, Quidel and Goodlife Healthcare.