Prenatal Mancozeb Exposure, Excess Manganese, and Neurodevelopment at 1 Year of Age in the Infants’ Environmental Health (ISA) Study

Abstract

Background:Although growing evidence suggests that early-life excess manganese (Mn) impairs neurodevelopment, data on the neurodevelopmental effects of mancozeb, a fungicide containing Mn, and its main metabolite ethylenethiourea (ETU) are limited.Objective:We examined whether prenatal mancozeb exposure and excess Mn were associated with neurodevelopment in 355 1-y-old infants living near banana plantations with frequent aerial mancozeb spraying in Costa Rica.Methods:We measured urinary ETU, hair Mn, and blood Mn concentrations in samples collected 1–3 times during pregnancy from mothers enrolled in the Infants’ Environmental Health (ISA) study. We then assessed neurodevelopment in their 1-y-old infants using the Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III). We estimated exposure–outcome associations using linear regression models adjusted for maternal education, parity, gestational age at birth, child age, Home Observation for Measurement of the Environment score, and location of neurodevelopmental assessment.Results:Median (P25–P75) urinary ETU, hair Mn, and blood Mn measured during pregnancy were 3.3μg/L (2.4–4.9; specific gravity–corrected), 1.7μg/g (0.9–4.1), and 24.0μg/L (20.3–28.0), respectively. Among girls, higher ETU was associated with lower social-emotional scores [β per 10-fold increase=−7.4 points (95% CI: −15.2, 0.4)], whereas higher hair Mn was associated with lower cognitive scores [−3.0 (−6.1, 0.1)]. Among boys, higher hair Mn was associated with lower social-emotional scores [−4.6 (−8.5, −0.8)]. We observed null associations for blood Mn, language, and motor outcomes.Conclusions:Our findings indicate that maternal exposure to mancozeb and excess Mn during pregnancy may have adverse and sex-specific effects on infant neurodevelopment. https://doi.org/10.1289/EHP1955

Biomarkers of environmental manganese exposure and associations with childhood neurodevelopment: a systematic review and meta-analysis

“…In children under 6 years of age, evidence from cohort studies in Table 1 revealed that higher manganese exposure had a negative effect on neurodevelopment [29][30][31][32][33][34][35][36], mainly cognitive and motor development. These studies enrolled pregnant women and mainly collected biomarker tissues, such as cord blood, maternal blood and hair, as well as placenta at delivery [29,30,32,[34][35][36].…”

Prenatal Manganese Exposure and Long-Term Neuropsychological Development at 4 Years of Age in a Population-Based Birth Cohort

“…Our results show linear associations with all the cognitive and psychomotor scales. Similarly, studies using chronic exposure measures (hair or dentine Mn levels) also indicate a linear association between prenatal Mn and long-term cognitive outcomes [15,49]. Gunier et al [14] described a linear association with cognitive development but a non-linear association with psychomotor development, while other authors proposed an inverted U-shape association between maternal blood Mn and neurodevelopment [1] and some studies have suggested that there may be a threshold value above which there is an association with neurodevelopment [1,31].…”

Association between Female Reproductive Health and Mancozeb: Systematic Review of Experimental Models

“…A sensitive segment of the population, exposed to mancozeb, is represented by pregnant women, who use agricultural products and are at risk from their side effects. In this context, mancozeb crosses the blood-placenta [48,51,52] and the blood-milk barriers [53], compromising the development of offspring, from intrauterine to postnatal life [54].…”