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Does Maternal Normal Range Thyroid Function Play a Role in Offspring Birth Weight? Evidence From a Mendelian

Xinghao Zhang1, Pengfei Wu2, Yuyao Chen3

  • 1Department of Ultrasound, Third Xiangya Hospital, Central South University, Changsha, China.

Frontiers in Endocrinology
|December 7, 2020
PubMed
Summary

Maternal thyroid function within the normal range does not causally impact offspring birth weight. This Mendelian randomization study found no significant association between thyroid stimulating hormone (TSH) or free thyroxine (FT4) levels and birth weight in European populations.

Keywords:
Mendelian randomizationbirth weightcausalitygenetic epidemiologythyroid function

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Area of Science:

  • Endocrinology
  • Reproductive Health
  • Genetics

Background:

  • Observational studies suggest a link between normal maternal thyroid function and offspring birth weight, but are limited by confounding factors.
  • Maternal thyroid hormones, including thyroid stimulating hormone (TSH) and free thyroxine (FT4), play a crucial role in fetal development.
  • Understanding the causal relationship is essential for prenatal care and optimizing birth outcomes.

Purpose of the Study:

  • To investigate the potential causal effects of maternal normal-range thyroid stimulating hormone (TSH) and free thyroxine (FT4) on offspring birth weight.
  • To overcome confounding biases inherent in observational studies by employing a Mendelian randomization approach.
  • To provide robust evidence on the thyroid function-birth weight relationship in European populations.

Main Methods:

  • A two-sample Mendelian randomization (MR) study design was utilized.
  • Summary-level statistics from genome-wide association studies (GWAS) in European ancestry individuals were used.
  • Instrumental variables for TSH (40 SNPs) and FT4 (21 SNPs) were identified at genome-wide significance; birth weight data were obtained from the Early Growth Genetics Consortium.

Main Results:

  • Genetically determined normal maternal thyroid function was not found to be causally associated with offspring birth weight.
  • A one standard deviation increase in maternal TSH showed a non-significant association with a 0.002 SD increase in birth weight (95% CI: -0.021 to 0.025).
  • A one standard deviation increase in maternal FT4 showed a non-significant association with a -0.001 SD change in birth weight (95% CI: -0.031 to 0.029).

Conclusions:

  • This Mendelian randomization study found no evidence of a causal relationship between normal maternal thyroid function (TSH and FT4) and offspring birth weight in the studied European population.
  • Sensitivity analyses confirmed the robustness of the findings, indicating no significant horizontal pleiotropy or heterogeneity.
  • The results suggest that variations in thyroid function within the normal range may not be a direct causal determinant of birth weight.