The Relationship Between Thyroid Function or Subclinical Hypothyroidism in Early Pregnancy and Risk of Low Birth Weight and Small for Gestational Age of the Offspring: A Multicentre Prospective Cohort Study.

Objective

To examine how maternal thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase antibody (TPOAb) status in early pregnancy relate to low birth weight (LBW) or small for gestational age (SGA) outcomes.

Methods

This prospective cohort analysis utilized data from 125,365 singleton pregnancies in the China Birth Cohort Study (2018-2022), with participants enrolled at 6-13+6weeks gestation from 9 tertiary hospitals. The potential associations among maternal thyroid functional indices, spectrum of thyroid dysfunction, and adverse neonatal outcomes (LBW/SGA) were statistically evaluated employing generalized linear mixed modeling techniques. Besides, to verify the consistency of these findings, we conducted comprehensive subgroup analyses across multiple demographic and clinical strata.

Results

Among the final 86,015 eligible participants, LBW and SGA occurred in 3.18% (n=2,731) and 3.56% (n=3,060), respectively. After adjusting for maternal and neonatal characteristics, analyses revealed significant negative associations between circulating maternal thyroid hormone levels and offspring birth weight measurements (per 1 mIU/L increase in TSH: β = -5.62, 95% CI: -7.29 to -3.95, P < 0.001; per 1 pmol/L increase in FT4: β = -1.43, 95% CI: -2.21 to -0.65, P < 0.001). First-trimester subclinical hypothyroidism (SCH) was associated with increased risks of both LBW (aOR = 1.29, 95% CI: 1.04-1.59; P = 0.021) and SGA (aOR = 1.18, 95% CI:1.01-1.38; P = 0.037). Women in the highest TSH quintile had 20% higher LBW risk (aOR = 1.20, 95% CI: 1.02-1.41; P = 0.028) and 16% higher SGA risk compared to the lowest quintile (aOR = 1.16, 95% CI: 1.03-1.30; P = 0.012). The associations of TSH and FT4 with LBW and SGA were consistent across all subgroups.

Conclusions

Elevated maternal TSH, elevated FT4 (even within high-normal ranges), and SCH in early pregnancy serve as significant risk indicators for LBW and SGA.