The aim of this study was to examine associations of maternal thyroid function with birthweight. The study excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496.
The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birth weight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth.
Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birth weight (–10 to −2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (p interaction=0·10). They identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother–child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT 4]) and 929 (2·2%) had isolated hypothyroxinemia (decreased FT 4 with normal TSH). Isolated hypothyroxinemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference −2·91, −4·49 to −0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birth weight (mean difference 45 g, 18 to 73; p=0·0012). These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy.
To conclude the results showed, Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birth weight (mean difference −38 g, −61 to −15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second.