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.