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Genetically predicted maternal prepregnancy BMI increased risk of childhood intestinal malformation: evidence from a Mendelian randomization study

Published online by Cambridge University Press:  01 September 2025

Siqi Xie Open the ORCID record for Siqi Xie [Opens in a new window] ,
Xiaojin Zhuang ,
Lan Liu ,
Yifan Fang  and
Bing Zhang Open the ORCID record for Bing Zhang [Opens in a new window]
Siqi Xie
Affiliation:
Fujian Children’s Hospital (Fujian Branch of Shanghai Children’s Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China
Xiaojin Zhuang
Affiliation:
Fujian Children’s Hospital (Fujian Branch of Shanghai Children’s Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China
Lan Liu
Affiliation:
Fujian Children’s Hospital (Fujian Branch of Shanghai Children’s Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China
Yifan Fang
Affiliation:
Fujian Children’s Hospital (Fujian Branch of Shanghai Children’s Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China
Bing Zhang*
Affiliation:
Fujian Children’s Hospital (Fujian Branch of Shanghai Children’s Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China
*
Corresponding author: Bing Zhang; Email: 306365306@qq.com
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Abstract

The study aimed to explore the causal effect of maternal prepregnancy body mass index (BMI) on congenital malformations of intestine (CMI). The genome-wide association data of BMI and CMI were obtained via the Mendelian randomization (MR) base platform. Single nucleotide polymorphisms (SNPs) significantly associated with BMI in females were identified and used as instrumental variables, and the causal relationship between BMI in females and CMI was examined using the bidirectional two-sample MR analyses research method. Three statistical methods including inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression were employed. A total of 36 SNPs significantly associated with BMI in females were identified in the study (P < 5 × 10−8; linkage disequilibrium r2 < 0.001). Consistent association between BMI in females and CMI was observed when evaluated by different methods (IVW: odds ratio (OR) 0.364, 95% confidence interval (CI) 0.144–0.922; weighted median estimator: OR 0.395, 95% CI 0.096–1.619; MR-Egger Method: OR 0.244, 95% CI 0.020–2.974), which suggests that BMI in females is negatively associated with increased risk of CMI. The MR analysis provided the strong evidence to indicate that decreasing BMI in females might be causally associated with the risk of CMI.

Keywords

Congenital malformations of intestinebody mass index in femalesMendelian randomization

Information

Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 16 , 2025 , e34
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Copyright
© The Author(s), 2025. Published by Cambridge University Press in association with The International Society for Developmental Origins of Health and Disease (DOHaD)

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Footnotes

Siqi Xie, Xiaojin Zhuang and Lan Liu are contributed equally to this work.

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