Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis

Area of Science:

• Endocrinology
• Reproductive Medicine
• Clinical Epidemiology

Background:

• International guidelines advocate for targeted screening of gestational thyroid dysfunction.
• Current risk factors used for screening demonstrate limited discriminative ability.
• Accurate identification of thyroid dysfunction during pregnancy is crucial for maternal and fetal health.

Purpose of the Study:

• To quantify the risk for thyroid function test abnormalities associated with specific risk factors used in current international guidelines.
• To evaluate the predictive value of commonly used risk factors for gestational thyroid dysfunction.
• To identify more reliable indicators for targeted screening.

Main Methods:

• Prospective cohort studies including data on maternal thyroid function and risk factors (age, BMI, parity, smoking, IVF, twin pregnancy, gestational age, education, antibodies).
• Exclusion of participants with pre-existing thyroid disease or thyroid-interfering medication.
• Analysis of individual participant data using mixed-effects regression models to determine primary outcomes (overt/subclinical hypothyroidism, treatment indication).

Main Results:

• The study included 65,559 participants across 25 cohorts.
• Commonly recommended risk factors (age >30, parity ≥2, BMI ≥40) had low predictive ability (AUC 0.58-0.63).
• Thyroid peroxidase antibody (TPOAb) positivity significantly increased the risk for hypothyroidism (e.g., combined positivity risk 7.0% for overt, 20.0% for subclinical). Twin pregnancies were linked to higher overt hyperthyroidism risk (5.6% vs. 0.7%).

Conclusions:

• Assessed risk factors possess poor predictive ability, questioning their clinical utility for targeted gestational thyroid dysfunction screening.
• Thyroid peroxidase antibody (TPOAb) positivity emerged as a relevant and significant risk factor for hypothyroidism during pregnancy.
• Findings suggest a need to re-evaluate current screening strategies and consider antibody status more prominently.