Prenatal metal levels and congenital anomalies of the kidney and urinary tract: The Japan Environment and Children's Study.

Yuka Iwaya, Masafumi Sanefuji, Kei Nishiyama, Yuri Sonoda, Norio Hamada, Reiko Suga, Masayuki Ochiai, Masayuki Shimono, Koichi Kusuhara, Shouichi Ohga

Journal: The Science of the total environment 2023;890():164356

PMID: 37230340

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Abstract

BACKGROUND

Prenatal exposure to metal elements has been reported as a potential risk factor for congenital malformation. However, studies on the relationship with congenital anomalies of the kidney and urinary tract (CAKUT) are very scarce.

METHODS

Participants of a prospective cohort from the Japan Environment and Children's Study, conducted at 15 research centers, were recruited between January 2011 and March 2014. The exposure factors were concentrations of lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se), and manganese (Mn) measured from maternal whole blood in the second or third trimester. The primary outcome was CAKUT diagnosed during the first three years of life, which was classified into isolated cases and complicated cases accompanied by extrarenal congenital defects. To conduct a nested case-control design within the cohort, we selected 351 isolated cases with 1404 matched controls, and 79 complicated cases with 316 matched controls.

RESULTS

A logistic regression model was used to examine the associations between individual metal concentrations and each subtype of CAKUT. A higher level of Se was associated with an increased risk of isolated CAKUT (adjusted odds ratio [95 % confidence interval]: 3.22 [1.33-7.77]). Meanwhile, higher levels of Pb and Mn were associated with a reduced risk of the complicated subtype (0.46 [0.24-0.90] and 0.33 [0.15-0.73], respectively). A Bayesian kernel machine regression model accounting for mixed effects of multiple metals further demonstrated that a higher level of Mn alone was significantly associated with a reduced occurrence of the complicated subtype.

CONCLUSIONS

Using a stringent statistical approach, the present study demonstrated that a higher Mn concentration in the maternal blood was associated with a lower risk of complicated CAKUT in offspring. Further cohort and experimental studies are needed to verify the clinical impact of this finding.

Address: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: [email protected].; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan. Electronic address: [email protected].; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: [email protected].; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Research Center for Environment and Developmental Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: [email protected].; Research Center for Environment and Developmental Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: [email protected].; Regional Center for Japan Environment and Children's Study, University of Occupational and Environmental Health, Kitakyushu, Japan. Electronic address: [email protected].; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Research Center for Environment and Developmental Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: [email protected].; Regional Center for Japan Environment and Children's Study, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pediatrics, University of Occupational and Environmental Health, Kitakyushu, Japan. Electronic address: [email protected].; Regional Center for Japan Environment and Children's Study, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pediatrics, University of Occupational and Environmental Health, Kitakyushu, Japan. Electronic address: [email protected].; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Research Center for Environment and Developmental Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: [email protected].

DOI: 10.1016/j.scitotenv.2023.164356

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MeSH Terms: Japan, Lead, Vesico-Ureteral Reflux, Mercury, Child, Female, Prospective Studies, Selenium, Pregnancy, Urogenital Abnormalities, Kidney, Urinary Tract, Humans, Bayes Theorem