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. 2024 Aug 13;58(32):14110-14120.
doi: 10.1021/acs.est.4c01945. Epub 2024 Jul 17.

Prenatal Parental Exposure to Metals and Birth Defects: A Prospective Birth Cohort Study

Hong Lv  1   2   3 , Yangqian Jiang  1   4 , Kan Ye  5 , Jinghan Wang  1   4 , Weiting Wang  1   4 , Jiangbo Du  1   2   3 , Lingmin Hu  1   6 , Wenhui Guo  1   2 , Rui Qin  1   4 , Xin Xu  1   4 , Yuanyan Dou  1   2 , Tianyu Sun  1   2 , Xiaoyu Liu  1   2 , Bo Xu  1   2 , Xiumei Han  1   2 , Kun Zhou  1   2 , Shiyao Tao  1   2 , Qun Lu  1   4 , Tao Jiang  1   7 , Yang Zhao  1   7 , Guangfu Jin  1   2   3 , Hongxia Ma  1   2   3 , Yankai Xia  1   8 , Jiong Li  1   2 , Hongbing Shen  1   2   3 , Xia Chi  9 , Yuan Lin  1   3   4 , Zhibin Hu  1   2   3 , Jiangsu Birth Cohort Jbc Study Group
Affiliations

Prenatal Parental Exposure to Metals and Birth Defects: A Prospective Birth Cohort Study

Hong Lv et al. Environ Sci Technol. .

Abstract

While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent-offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21-91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse's exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.

Keywords: birth cohort; birth defect; maternal exposure; metal; parental exposure; paternal exposure.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Joint effects of paternal and maternal high exposures to individual metals (V, Cr, Ni, Cu, Se) on the risk of birth defects in offspring. Analyses were adjusted for parental age, education, BMI, and tobacco use, maternal folic acid or multivitamin supplements, household income, area of residence, and parity. High: equal or above median level; Low: below median level.
Figure 2
Figure 2
Effects of paternal, maternal, and parental exposure to metal mixtures on the risk of birth defects in offspring by Bayesian kernel machine regression (BKMR). (A) Joint effects (adjusted RR and 95% CI) of paternal (Ti, V, Cr, Mn, Co, Ni, Cu, Se), maternal (V, Cr, Ni, Cu, Se, Sb), and parental (paternal Ti, V, Cr, Mn, Co, Ni, Cu, Se, and maternal V, Cr, Ni, Cu, Se, Sb) exposure to metal mixtures when setting all metals to a particular quantile were compared to when setting all metals to the 50th percentile. (B) Relative importance of individual components of parental exposure to metal mixtures on the prediction of birth defects in offspring is determined using posterior inclusion probability (PIP). Analyses for paternal exposures were adjusted for paternal age, education, and BMI, parental tobacco use, household income, area of residence, and parity. Analyses for maternal exposures were adjusted for maternal age, education, BMI, folic acid or multivitamin supplements, parental tobacco use, household income, area of residence, and parity. Analyses for parental exposures were adjusted for parental age, education, BMI and tobacco use, maternal folic acid or multivitamin supplements, household income, area of residence, and parity. Abbreviations: RR, risk ratio; CI, confidence interval.
Figure 3
Figure 3
Joint effects of parental exposure to a metal mixture on the risk of birth defect subtypes in offspring by Bayesian kernel machine regression (BKMR). The y-axis shows the adjusted RR and 95% CI when setting all metals to the quantile specified on the x-axis compared to setting all metals to the 50th percentile. Analyses were adjusted for parental age, education, BMI, and tobacco use, maternal folic acid or multivitamin supplements, household income, area of residence, and parity. (A) Eye, ear, face, and neck defects. (B) Circulatory system defects. (C) Genital organ defects. (D) Urinary system defects. (E) Musculoskeletal system defects. (F) Others (nervous system defects, respiratory system defects, cleft lip and cleft palate defects, digestive system defects, chromosomal abnormalities, and other birth defects). Abbreviations: RR, risk ratio; CI, confidence interval.
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