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Abstract
BackgroundThe 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.MethodsWe 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.ResultsGenetically 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.ConclusionThis MR study did not identify a causality between normal range thyroid function and offspring birth weight in the Europeans.
Highlights
Thyroid dysfunction features altered thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations [1] and is involved in pathophysiological conditions of multiple systems [2,3,4,5,6,7]
By the main Mendelian randomization (MR) method (Figure 2B), change in birth weight was −0.001 standard deviation (SD) per one SD higher in maternal FT4
There was no causal relationship between genetically predicted TSH concentrations and offspring birth weight
Summary
Thyroid dysfunction features altered thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations [1] and is involved in pathophysiological conditions of multiple systems [2,3,4,5,6,7]. Recent studies suggested that normal thyrotropin within the upper reference range or subclinical hypothyroidism may exert positive [10, 11], negative [12, 13], or null [14, 15] effects on offspring birth weight. Whether maternal normal range TSH or FT4 levels are associated with newborn birth weight, and whether large or small for gestational age, remains inconclusive. 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
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