In Utero Exposure to Metals and Birth Outcomes in an Artisanal and Small-Scale Gold Mining Birth Cohort in Madre de Dios, Peru

Abstract

Background: Few birth cohorts in South America evaluate the joint effect of minerals and toxic metals on neonatal health. In Madre de Dios, Peru, mercury exposure is prevalent owing to artisanal gold mining, yet its effect on neonatal health is unknown.

Objectives: We aimed to determine whether toxic metals are associated with lower birth weight and shorter gestational age independently of antenatal care and other maternal well-being factors.

Methods: Data are from the COhorte de NAcimiento de MAdre de Dios (CONAMAD) birth cohort, which enrolled pregnant women in Madre de Dios prior to their third trimester and obtained maternal and cord blood samples at birth. We use structural equation models (SEMs) to construct latent variables for the maternal metals environment (ME) and the fetal environment (FE) using concentrations of calcium, iron, selenium, zinc, magnesium, mercury, lead, and arsenic measured in maternal and cord blood, respectively. We then assessed the relationship between the latent variables ME and FE, toxic metals, prenatal visits, hypertension, and their effect on gestational age and birth weight.

Results: Among 198 mothers successfully enrolled and followed at birth, 29% had blood mercury levels that exceeded the U.S. Centers for Disease Control and Prevention threshold of $5.8\mu g/L$ and 2 mothers surpassed the former $5\text{-}\mu g/\text{dL}$ threshold for blood lead. The current threshold value is $3.5\mu g/\text{dL}$. Minerals and toxic metals loaded onto ME and FE latent variables. ME was associated with FE ($\beta =$0.24; 95% CI: 0.05, 0.45). FE was associated with longer gestational age ($\beta =$2.31; 95% CI: $-0.3$, 4.51) and heavier birth weight. Mercury exposure was not directly associated with health outcomes. A 1% increase in maternal blood lead shortened gestational age by 0.05 d ($\beta =$$-0.75$; 95% CI: $-1.51$, $-0.13$), which at the $5\text{-}\mu g/\text{dL}$ threshold resulted in a loss of 3.6 gestational days and $76.5g$ in birth weight for newborns. Prenatal care visits were associated with improved birth outcomes, with a doubling of visits from 6 to 12 associated with 5.5 more gestational days (95% CI: 1.6, 9.4) and $319g$ of birth weight (95% CI: 287.6, 350.7).

Discussion: Maternal lead, even at low exposures, was associated with shorter gestation and lower birth weight. Studies that focus only on harmful exposures or nutrition may mischaracterize the dynamic maternal ME and FE. SEMs provide a framework to evaluate these complex relationships during pregnancy and reduce overcontrolling that can occur with linear regression. https://doi.org/10.1289/EHP10557.

Figure 1.

CONAMAD Study Region, Madre de Dios, Peru. The capital of Madre de Dios, Puerto Maldonado, is labeled with a star and shown in the red inset map in the upper right. Note: CONAMAD, COhorte de NAcimiento de MAdre de Dios.

Figure 2.

Theoretical latent model with evaluated covariates. Note: anemia status (yes/no), measured hemoglobin values below recommended guidelines by gestational week at enrollment and birth; As, arsenic; Ca, calcium; Fe, iron; Hg, mercury; hypertension, the development of gestational hypertension (systolic blood pressure $>140\text{\hspace{0.17em}mmHg}$); Mg, magnesium; parity, number of prior births; Pb, lead; prenatal visits, number of prenatal care visits prior to birth; Se, selenium; SES, socioeconomic status; Zn, zinc.

Figure 3.

Heat map of minerals and toxic metal correlations in maternal (VB) and cord (CB) blood for the CONAMAD birth cohort conducted in Madre de Dios, Peru, from 2017 to 2018. The Pearson correlation value is shown for maternal and fetal minerals/toxic metals, with significant positive and negative correlations represented by red and blue shading, respectively ($p<0.05$). Nonsignificant correlations are white. $p$-Values are provided in Table S6. Note: As, arsenic; Ca, calcium; Cd, cadmium; CONAMAD, COhorte de NAcimiento de MAdre de Dios; Fe, iron; Hg, mercury; Mg, magnesium; Pb, lead; Se, selenium; Zn, zinc.

Figure 4.

Final model diagram of toxic metals, minerals, and covariates on birth outcomes of concern for the CONAMAD birth cohort conducted in Madre de Dios, Peru, from 2017 to 2018. Final model diagram includes hypertension (HPT), age, sex, prenatal visits, and maternal blood Pb levels ($\mathrm{\mu }\mathrm{g}/\text{dL}$), with the maternal metals environment and fetal metals environment as latent variables (ME and FE, respectively). Values shown are unstandardized $\mathrm{\beta }$ values with transparency dependent on $p$-value as provided in Table 4. Boxes are colored by maternal blood (black), cord blood (light gray), traditional covariates (dark gray), ME (black), FE (light gray), and neonatal health outcomes (white). Note: As, arsenic; Ca, calcium; CONAMAD, COhorte de NAcimiento de MAdre de Dios; Fe, iron; Hg, mercury; Mg, magnesium; Pb, lead; Se, selenium; Zn, zinc.

Figure 5.

Effect of maternal Pb levels and hypertension on gestation for the CONAMAD birth cohort conducted in Madre de Dios, Peru, from 2017 to 2018. Days of pregnancy lost from ${\log }_{10}$ Pb maternal blood concentration ($\mathrm{\mu }\mathrm{g}/\text{dL}$) for mothers with an average FE (50th percentile, center, dotted lines) with the 25th and 75th quartiles for FE (shaded region and dashed lines). Horizontal, black dashed line represents no days of pregnancy lost. Hypertensive and nonhypertensive mothers are shown as red circles and blue triangles, respectively. Values used are from Table 4. The circle and square demonstrate where days of pregnancy lost become negative for the 25th and 75th percentiles of the FE, respectively, demonstrating a 34% increase in Pb exposure before the 75th percentile suffers days of lost pregnancy. Vertical red line represents the former $5\text{-}\mathrm{\mu }\mathrm{g}/\text{dL}$ reference level set by the U.S. Centers for Disease Control and Prevention. Note: FE, fetal environment; Pb, lead.