Causal effects of breastfeeding on childhood health outcomes: A Mendelian randomization analysis of mental and physical health

母乳喂养对儿童健康结果的因果效应:一项关于心理和生理健康的孟德尔随机化分析

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Abstract

Breastfeeding has been extensively documented to confer numerous health benefits. However, establishing causal relationships, particularly with respect to childhood mental and physical health, has been challenging due to confounding variables inherent in observational studies. This study leverages a Mendelian randomization (MR) approach to rigorously investigate the causal impacts of breastfeeding on various childhood health outcomes. A total of 49 single-nucleotide polymorphisms were chosen as instrumental variables after employing linkage disequilibrium screening to ensure strong associations with breastfeeding and minimal confounding. Genetic associations and outcome data were extracted from publicly available genome-wide association studies. Primary MR analyses were conducted using the inverse-variance weighted (IVW) method, supplemented by MR-Egger, weighted median, weighted mode, and simple mode analyses to assess sensitivity. The MR analysis did not reveal significant causal relationships between breastfeeding and childhood mental health outcomes, which included intelligence (PIVW = .165), absence epilepsy (PIVW = .894), social disorders (PIVW = .781), and emotional disorders (PIVW = .598). Nevertheless, a significant protective effect of breastfeeding on the risk of childhood asthma was observed (PIVW = .033, odds ratio: 0.997, 95% confidence interval: 0.936-0.997). No causal associations were identified for other physical health outcomes, such as height, sunburn, obesity, and allergy. Sensitivity analyses corroborated these findings, indicating no pleiotropic effects. This MR study provides robust evidence supporting a protective effect of breastfeeding against childhood asthma. However, breastfeeding does not appear to significantly influence other mental or physical health outcomes. These findings highlight the critical public health implications of breastfeeding for reducing the incidence of childhood asthma. Further investigations are warranted across diverse populations to generalize these results and elucidate underlying biological mechanisms.

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