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Research article

Urinary Arsenic Metabolism and Birth Outcomes in Tacna, Peru, 2019: A Prospective Cohort Study

Authors
  • Diego Fano-Sizgorich (Universidad Peruana Cayetano Heredia)
  • Matthew Gribble orcid logo (Department of Epidemiology, University of Alabama at Birmingham, Birmingham AL 35294)
  • Cinthya Vásquez-Velásquez orcid logo (Universidad)
  • Claudio Ramírez-Atencio orcid logo (Universidad Nacional Jorge Basadre Grohmann)
  • Julio Aguilar (Universidad Nacional Jorge Basadre Grohmann)
  • Jeffrey K. Wickliffe orcid logo (University of Alabama at Birmingham)
  • Maureen Y. Lichtveld orcid logo (University of Pittsburgh)
  • Dana B. Barr orcid logo (Emory University)
  • Gustavo F. Gonzales orcid logo (Universidad Peruana Cayetano Heredia)

This article is a preprint and is currently undergoing peer review by UCL Open: Environment.

Abstract

Arsenic exposure during pregnancy might affect foetal development. Arsenic metabolism may modulate the potential damage to the foetus. Tacna has the highest arsenic exposure levels in Peru. However, this region has the highest birth weight in Peru. It is not known if arsenic exposure is affecting maternal-perinatal health in Tacna. The study aimed to evaluate the association between urinary arsenic metabolism and birth outcomes, specifically birth weight and gestational age at birth in Tacna, Peru. A prospective cohort study was conducted, involving 158 pregnant women in Tacna, Peru, during January-November 2019. Participants were enrolled in their second trimester and followed-up until birth. Urine samples were collected in the second and third trimester. Urine samples were analyzed for total arsenic concentration and its species. Generalized estimating equations (GEE) analysis was used to evaluate the association of interest. Inter-differences in arsenic toxicokinetics, calculated with principal component analysis (PCA) was included as an interaction term. Analysis was stratified by pregnancy trimester. The median total urinary arsenic (tAs) concentration was 33.34 µg/L. Inorganic arsenic (iAs) and Dimethylarsinic acid (DMA) were higher in the second trimester. Dimethylarsinic acid (DMA) was the predominant component (84.78% of total urinary arsenic). No significant association was found between urinary arsenic exposure and birthweight or gestational age at birth. The association was not affected by arsenic metabolism. Stratified analyses by pregnancy trimester also showed no significant associations. Urinary arsenic was not associated with birthweight, and this null relationship remained unaffected by arsenic toxicokinetic differences reflected in urine.

Keywords: Birth weight, Foetal development, Gestational age, Toxicity, Pregnant women, Latin America

Funding

  • Fogarty International Center (grant D43 TW011502)
  • Fogarty International Center (FIC) (grant 5U01TW010107)
  • Fogarty International Center (FIC) (grant 5U2RTW010114)
  • National Institute of Environmental Health Sciences (NIEHS) (grant P30 ES019776)
Preprint Under Review
License
Creative Commons Attribution 4.0

 Open peer review from Zafar Adeel

Review
The authors explore the association of birth weight to exposure to arsenic, presumably consumed through drinking water. The selected population in Tacna, Peru is exposed to arsenic level of greater than 10 microgram/litre (also ppb) - which is a guideline value described by the World Health Organization (WHO). Based on the study of 158 pregnant women, the authors find no correlation between the arsenic metabolites found in urine samples and the corresponding birthweight.

The authors should consider the following general observations:

1. In the grand scheme, the arsenic exposure through drinking water in Tacna appears to be on the low side - which range from 10 to 25 ppb (based on citation 6, which is the authors' paper published in 2021). In their analysis, the authors compare their findings to those from Bangladesh where the concentrations are often one to two orders of magnitude greater, resulting in marked health impacts including those on pregnancy. The authors should acknowledge this major difference when they undertake such comparisons.

2. The authors do not provide strong evidence for ingestion routes for arsenic. Put differently, they do not present drinking water arsenic concentrations, and there is no attempt at correlating drinking water arsenic concentration to the DMA concentrations, which is a primary arsenic metabolite.

The authors should consider the following revisions:

a. The descriptive paragraph on arsenic in drinking water (lines 10-16) needs to be revised by including a summary of arsenic concentrations found in drinking water, including their speciation (i.e., arsenite vs. arsenate). They should also comment on how these values concentrations compared with those found elsewhere, particularly in Bangladesh/India (partly because they reference Bangladesh in their discussion later in the paper).

b. In the Discussion session, there are several references to arsenic concentration (valued at µg/L) that do not clarify whether they are talking about arsenic concentration in the drinking water or the composite value in urine samples. For example, one can surmise they are referring to arsenic concentration in water on line 131. Whereas the tAs levels listed on line 133 are referring to arsenic in the urine level, one may surmise. This obfuscation, ostensibly not intentional, causes some difficulty for the reader and the chances of miscommunication are great. The authors should revise their presentation of values and clearly distinguish between arsenic concentrations in water and those in urine samples.

c. The statement on line 152, the way it is phrased could be misleading: "Some studies did not find any significant association with adverse birth outcomes, even with exposure levels ≥10 µg/L." 10 µg/L is the lowest end of the adverse value (although no level of arsenic is absolutely safe) identified as a "guideline" by WHO. There should not be an expectation, as implied here, to always observe adverse health impacts any time drinking water concentration goes above 10 µg/L.

d. Some of the explanations provided in the paragraph (line 196-204) seems highly speculative. The authors should consider re-phrasing these statements.

Note:
This review refers to round of peer review and may pertain to an earlier version of the document.