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

BACKGROUND: The association between normal range thyroid function and offspring birth weight has been postulated, but evidence from observational studies is prone to be confounded. We conducted a two-sample Mendelian randomization (MR) study to explore the causal effects of maternal thyroid stimulating hormone (TSH) and free thyroxine (FT4) on birth weight. METHODS: We utilized public shared summary-level statistics from European-ancestry genome wide association studies. We obtained 40 and 21 single nucleotide polymorphisms as instrumental variables, which were associated with TSH and FT4 levels at genome-wide significance (P < 5 × 10(−8)). Partitioned maternal effects on birth weight were retrieved from datasets contributed by the Early Growth Genetics Consortium. Inverse-variance weighted method was employed in the primary MR analysis and multiple sensitivity analyses were implemented. RESULTS: Genetically determined normal range thyroid function was not causally associated with offspring birth weight. Each one standard deviation (SD) increase in maternal TSH was associated with 0.002 SD higher of birth weight (95% confidence interval [CI], −0.021 to 0.025; P = 0.87). Similarly, change in birth weight was −0.001 SD (95% CI, −0.031 to 0.029; P = 0.94) per one SD higher in maternal FT4. Consistent results were yielded via additional MR methods. Sensitivity analyses demonstrated no presence of horizontal pleiotropy or heterogeneity. CONCLUSION: This MR study did not identify a causality between normal range thyroid function and offspring birth weight in the Europeans.