Relationships between environmental exposures and birth outcomes
Authors: Jeanette A Stingone
Journal: The Lancet Planetary Health (2017)

WHO estimates that complications related to preterm delivery are the leading causes of neonatal deaths,1Liu L Oza S Hogan D et al.Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis.Lancet. 2015; 385: 430-440Summary Full Text Full Text PDF PubMed Scopus (1981) Google Scholar and 80% of neonatal deaths worldwide are in small babies.2Lawn JE Blencowe H Oza S et al.Every newborn: progress, priorities, and potential beyond survival.Lancet. 2014; 384: 189-205Summary Full Text Full Text PDF PubMed Scopus (1030) Google Scholar There has been considerable research examining how modifiable environmental factors might influence these outcomes, although findings have been mixed.3Ferguson KK O'Neill MS Meeker JD Environmental contaminant exposures and preterm birth: a comprehensive review.J Toxicol Environ Health B Crit Rev. 2013; 16: 69-113Crossref PubMed Scopus (113) Google Scholar With industrialisation increasingly affecting the world's population, understanding the potential for environmental exposures to contribute to these birth outcomes is necessary to inform future environmental and public health policies. In The Lancet Planetary Health, Jie Hu and colleagues4Hu J Xia W Pan X et al.Association of adverse birth outcomes with prenatal exposure to vanadium: a population-based cohort study.Lancet Planet Health. 2017; 1: e230-e241Summary Full Text Full Text PDF Scopus (43) Google Scholar leveraged a population-based, prospective birth cohort in China to investigate the relationship between maternal exposure to metals during pregnancy and birth outcomes such as preterm delivery and low birthweight. Hu and colleagues reported greater odds of both preterm delivery and low birthweight with higher urinary concentrations of vanadium during the third trimester, even after adjusting for biomarkers of other metals associated with adverse birth outcomes. Health effects of vanadium have not been well-documented, particularly in terms of pregnancy and fetal health. However, the focus on vanadium is timely as research suggests that there is widespread contamination of soil by vanadium in parts of China due to mining and industrial activities.5Yang J Teng Y Wu J et al.Current status and associated human health risk of vanadium in soil in China.Chemosphere. 2017; 171: 635-643Crossref PubMed Scopus (106) Google Scholar Additionally, this study raises many points of consideration for future studies aiming to characterise the effects of environmental exposures that result from anthropogenic emissions. Hu and colleagues examined the association between birth outcomes and biological markers of exposure to vanadium while considering the role of other metals as both confounders and effect modifiers. The consideration of how multiple exposures combine or interact to contribute to adverse health outcomes is of growing interest in the field of environmental health.6Taylor KW Joubert BR Braun JM et al.Statistical approaches for assessing health effects of environmental chemical mixtures in epidemiology: lessons from an innovative workshop.Environ Health Perspect. 2016; 124: A227-A229Crossref PubMed Scopus (131) Google Scholar, 7Carlin DJ Rider CV Woychik R Birnbaum LS Unraveling the health effects of environmental mixtures: an NIEHS priority.Environ Health Perspect. 2013; 121: A6-A8Crossref PubMed Scopus (107) Google Scholar Industrial processes, motor vehicle exhausts, and other anthropogenic activities emit multiple pollutants simultaneously. The effects of these mixtures and multiple exposures are not well characterised, because most studies examine pollutants individually.7Carlin DJ Rider CV Woychik R Birnbaum LS Unraveling the health effects of environmental mixtures: an NIEHS priority.Environ Health Perspect. 2013; 121: A6-A8Crossref PubMed Scopus (107) Google Scholar Hu and colleagues evaluated how other metals affected the relationship between vanadium and birth outcomes, identifying an interaction between vanadium and chromium.4Hu J Xia W Pan X et al.Association of adverse birth outcomes with prenatal exposure to vanadium: a population-based cohort study.Lancet Planet Health. 2017; 1: e230-e241Summary Full Text Full Text PDF Scopus (43) Google Scholar They observed that women with high biological measures of both vanadium and chromium had eight-times higher odds of preterm delivery as women with low concentrations for both contaminants, whereas women with high concentrations of vanadium, but lower levels of chromium, had only two-times increased odds of preterm delivery. With many communities being simultaneously exposed to multiple contaminants, documenting the combined effects of environmental exposures is crucial for risk assessment.7Carlin DJ Rider CV Woychik R Birnbaum LS Unraveling the health effects of environmental mixtures: an NIEHS priority.Environ Health Perspect. 2013; 121: A6-A8Crossref PubMed Scopus (107) Google Scholar A growing number of approaches aim to identify health-relevant environmental mixtures within high-dimensional exposure data and estimate the collective effect of multiple exposures on the risk of adverse birth outcomes.6Taylor KW Joubert BR Braun JM et al.Statistical approaches for assessing health effects of environmental chemical mixtures in epidemiology: lessons from an innovative workshop.Environ Health Perspect. 2016; 124: A227-A229Crossref PubMed Scopus (131) Google Scholar Examples from the past 2 years have used machine learning techniques8Lenters V Portengen L Rignell-Hydbom A et al.Prenatal phthalate, perfluoroalkyl acid, and organochlorine exposures and term birth weight in three birth cohorts: multi-pollutant models based on elastic net regression.Environ Health Perspect. 2016; 124: 365-372PubMed Google Scholar and data-driven regression techniques9Govarts E Remy S Bruckers L et al.Combined effects of prenatal exposures to environmental chemicals on birth weight.Int J Environ Res Public Health. 2016; 13: 495Crossref Scopus (76) Google Scholar to simultaneously assess the relationship between birth outcomes and several biological measures of exposure. The use of biological measures of exposure in this context can be regarded as a strength because the concentrations of several pollutants can be assessed simultaneously using a single sample. However, there are known limitations to prospective birth cohort studies that rely on biological markers of exposure that need to be considered. Due to the short time window between exposure assessment and outcome, there is the potential for biomarkers of exposure to be affected by the underlying pathology that contributes to the adverse birth outcome.10Savitz DA Invited commentary: interpreting associations between exposure biomarkers and pregnancy outcome.Am J Epidemiol. 2014; 179: 545-547Crossref PubMed Scopus (18) Google Scholar Hu and colleagues partially guarded against this by excluding urine samples from emergency admissions for delivery. Future studies should also consider taking repeat biospecimens starting in early pregnancy, as suggested by Hu and colleagues. The availability of biological samples from multiple points during pregnancy would allow researchers to assess temporal variability during pregnancy and the potential role of underlying pathologies. Additionally, multiple measurements during pregnancy can aid in the identification of specific windows of vulnerability. Although necessary for designing successful interventions, pollutant source and route of exposure are not always known in studies using biological measures.10Savitz DA Invited commentary: interpreting associations between exposure biomarkers and pregnancy outcome.Am J Epidemiol. 2014; 179: 545-547Crossref PubMed Scopus (18) Google Scholar Hu and colleagues acknowledge that the women in their study potentially had several routes of exposure to vanadium, including diet and ambient air. Additional research that aims to link anthropogenic sources with the biological markers of exposure that account for metabolism is needed for such findings to have an effect on public health policy. Studies that incorporate multiple domains of exposure, as well as intermediate measures of biological response, will allow for the exploration of pathways from external exposure to adverse birth outcomes, which could improve knowledge of causal relationships and identify potential targets for intervention.11Stingone JA Buck Louis GM Nakayama SF et al.Toward greater implementation of the exposome research paradigm within environmental epidemiology.Annu Rev Public Health. 2017; 38: 315-327Crossref PubMed Scopus (59) Google Scholar Understanding the environmental contributors to adverse birth outcomes is crucial for reducing their incidence. Studies that build on the approach taken by Hu and colleagues and consider several pollutants, multiple time-windows, and the relationship between internal and external measures of exposure will advance our knowledge and inform prevention efforts. I declare no competing interests. I am supported by a grant from the US National Institute of Environmental Health Sciences (K99ES027022). This content is solely the responsibility of the author and does not represent the official views of the National Institutes of Health. Association of adverse birth outcomes with prenatal exposure to vanadium: a population-based cohort studyOur findings reveal a relationship between prenatal exposure to higher levels of vanadium and increased risk of adverse birth outcomes, suggesting that vanadium might be a potential toxic metal for human beings. Further studies are needed to replicate the observed associations and investigate the interaction effects of prenatal exposure to different metals on adverse birth outcomes. Full-Text PDF Open Access