Sequential Mediation by Maternal Weight Gain and Late Blood Metal Concentration in the Association Between Heavy Metal Exposure in Early Pregnancy and Fetal Growth

Sep 30, 2026

Background: Assess the mediation effect of gestational weight gain (GWG) and late-pregnancy blood heavy metal levels linking early-pregnancy metal exposure to fetal growth. Methods: Data from a Korean Children’s Environmental Health Study cohort of 4,712 full-term births were analyzed. Blood levels of lead (Pb), mercury (Hg), and cadmium (Cd) during pregnancy and newborn birthweights were retrieved. Single-exposure models and path analyses tested direct and indirect effects. Results: Late Pb and Cd predicted lower birthweight; early Pb showed mediation through late Pb. Early Hg effects via GWG and late Hg cancelled out. Conclusion: GWG and late heavy metal levels function as mediators, not confounders.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

Introduction

J Korean Med Sci. 2026 Jan 5;41(1):e16 [https://doi.org/10.3346/jkms.2026.41.e16](https://doi.org/10.3346/jkms.2026.41.e16)[ ](https://doi.org/10.3346/jkms.2026.41.e16)eISSN 1598-6357·pISSN 1011-8934 Original Article Public Health & Preventive Medicine Received: Sep 18, 2024 Accepted: May 8, 2025 Published online: Dec 2, 2025 Address for Correspondence: Young Yoo, MD, PhD Department of Pediatrics, Korea University College of Medicine, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Korea. [Email: yoolina@korea.ac.kr](Email: yoolina@korea.ac.kr) © 2026 The Korean Academy of Medical Sciences. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://](https://)[ ](https://)[creativecommons.org/licenses/by-nc/4.0/](creativecommons.org/licenses/by-nc/4.0/)) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ORCID iDs Seung-Ah Choe [https://orcid.org/0000-0001-6270-5020](https://orcid.org/0000-0001-6270-5020)[ ](https://orcid.org/0000-0001-6270-5020)Jue Seong Lee [https://orcid.org/0000-0003-1803-4682](https://orcid.org/0000-0003-1803-4682)[ ](https://orcid.org/0000-0003-1803-4682)Changmin Kang [https://orcid.org/0000-0001-5670-3635](https://orcid.org/0000-0001-5670-3635)[ ](https://orcid.org/0000-0001-5670-3635)Jungheum Jo [https://orcid.org/0000-0002-1925-9499](https://orcid.org/0000-0002-1925-9499)[ ](https://orcid.org/0000-0002-1925-9499)Wonsuck Yoon [https://orcid.org/0000-0002-7665-7629](https://orcid.org/0000-0002-7665-7629)[ ](https://orcid.org/0000-0002-7665-7629)Dae Jin Song [https://orcid.org/0000-0003-0647-3186](https://orcid.org/0000-0003-0647-3186) Sequential Mediation by Maternal Weight Gain and Late Blood Metal Concentration in the Association Between Heavy Metal Exposure in Early Pregnancy and Fetal Growth Seung-Ah Choe ,1 Jue Seong Lee ,2,3 Changmin Kang ,2,3 Jungheum Jo ,4 Wonsuck Yoon ,3 Dae Jin Song ,2,3 Young Yoo ,2,3 and Ko-CHENS Study Group 1Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea 2Department of Pediatrics, Korea University College of Medicine, Seoul, Korea 3Allergy Immunology Center, Korea University, Seoul, Korea 4Environmental Health Research Division, National Institute of Environmental Research, Incheon, Korea ABSTRACT Background: To assess the mediation effect of gestational weight gain (GWG) and blood heavy metal levels in the late pregnancy affecting the association between early pregnancy metal exposure and fetal growth. Methods: We analyzed data from Korean Children’s Environmental Health Study cohort comprising 4,712 full-term births. Blood levels of lead (Pb), mercury (Hg), and cadmium (Cd) during pregnancy, and newborn birthweights were retrieved. We applied single-exposure model to assess the association between heavy metal levels and newborn anthropometric measures and conducted path analyses to examine the direct and indirect effects of heavy metal levels in early pregnancy on newborn measures. Results: Exposure to Pb (β = −15.470, P = 0.036) and Cd (β = −24.150, P = 0.004) during late pregnancy were associated with lower birthweight. Early exposure to Pb was not directly associated with lower birthweight, however, mediation of late exposure to Pb (β = −7.417, P = 0.049) resulted in lower birthweight (β = −14.787, P = 0.036). Early exposure to Hg was associated with higher birthweight, however, indirect paths via GWG (β = 3.626, P = 0.048) and late Hg levels (β = −12.929, P = 0.111) countered each other, resulting in the nullification of the total effect (β = −8.519, P = 0.301) . Conclusion: The effect of Pb exposure in early pregnancy on birthweight was mediated by GWG and Pb exposures during late pregnancy. When assessing the impact of heavy metal exposure on birthweight, it is important to note that GWG and late heavy metal levels act as mediators

FAQs

What was the study’s main goal?

To evaluate whether gestational weight gain (GWG) and late-pregnancy blood heavy metal levels mediate the relationship between early-pregnancy heavy metal exposure and fetal growth measured by birthweight.

How were heavy metals and outcomes assessed?

Blood levels of lead (Pb), mercury (Hg), and cadmium (Cd) during pregnancy were collected, and newborn birthweights were used as anthropometric outcomes in a cohort of 4,712 full-term births.

Which metals showed mediation or direct associations with birthweight?

Late exposure to Pb and Cd was associated with lower birthweight. Early Pb was not directly associated, but its effect was mediated through late Pb. Early Hg showed opposing indirect paths via GWG and late Hg, resulting in a null total effect.

Sep 30, 2026

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