Investigating causal relation between prenatal arsenic exposure and birthweight: Are smaller infants more susceptible?

Abstract

Background Shortening of gestation and intrauterine growth restriction (IUGR) are the two main determinants of birthweight. Low birthweight has been linked with prenatal arsenic exposure, but the causal relation between arsenic and birthweight is not well understood.. Objectives We applied a quantile causal mediation analysis approach to determine the association between prenatal arsenic exposure and birthweight in relation to shortening of gestation and IUGR, and whether the susceptibility of arsenic exposure varies by infant birth sizes. Methods In a longitudinal birth cohort in Bangladesh, we measured arsenic in drinking water (n=1,182) collected at enrollment and maternal toenails (n=1,104) collected ≤1-month postpartum using inductively coupled plasma mass spectrometry. Gestational age was determined using ultrasound at ≤16 weeks’ gestation. Demographic information was collected using a structured questionnaire. Results Of 1,184 singleton livebirths, 16.4% (n=194) were low birthweight (<2500 g), 21.9% (n=259) preterm (<37 weeks’ gestation), and 9.2% (n=109) both low birthweight and preterm. The median concentrations of arsenic in drinking water and maternal toenails were 2.2 µg/L (range: bellow the level of detection [LOD]–1400) and 1.2 µg/g (range: <LOD–46.6), respectively. Prenatal arsenic exposure was negatively associated with birthweight, where the magnitude of the association varied across birthweight percentiles. The effect of arsenic on birthweight mediated via shortening of gestation affected all infants irrespective of birth sizes (β range: 10th percentile= −19.7g [95% CI: −26.7, −103.3] to 90th percentile= −10.9g [95% CI: −18.5, −5.9] per natural log water arsenic increase), whereas the effect via pathways independent of gestational age affected only the smaller infants (β range: 10th percentile= −28.0g [95% CI: −43.8, −9.9] to 20th percentile= −14.9g [95% CI: −30.3, −1.7] per natural log water arsenic increase). Similar pattern was observed for maternal toenail arsenic. Conclusions The susceptibility of prenatal arsenic exposure varied by infant birth sizes, placing smaller infants at greater risk of lower birthweight by shortening of gestation and possibly growth restriction. It is important to mitigate prenatal arsenic exposure to improve perinatal outcomes in Bangladesh.

Prenatal arsenic exposure, child marriage, and pregnancy weight gain: Associations with preterm birth in Bangladesh

“…We used data from a prospective birth cohort established in Bangladesh during 2008–2011. The details of this study, including details of recruitment and enrollment have been previously reported (13). Briefly, women were eligible to participate if they were ≥18 years old with an ultrasound confirmed singleton pregnancy of ≤16 weeks’ gestation; used a tube well as their primary source of drinking water; had been using the same drinking water source for >6 months; and intended to live in her current residence throughout pregnancy.…”

Regulation of birthweight by placenta-derived miRNAs: evidence from an arsenic-exposed birth cohort in Bangladesh

“…In this study, we observed that the effect of miR-1290 on birthweight was stronger when the arsenic concentration was higher in cord blood. In utero arsenic exposure has been associated with increased risk of preterm birth [57] and lower birthweight [27] in this population. Therefore, higher expression of miR-1290 in the placenta could potentially influence birthweight via shortened gestational age and increased arsenic toxicity.…”

“…During 2008-2011, we enrolled 1,613 pregnant women aged ≥ 18 years with an ultrasound-confirmed singleton pregnancy of ≤ 16 weeks of gestation and followed them throughout pregnancy. Details of this study, including recruitment and enrollment criteria were previously reported [25,27]. At the end of follow-up, 1,184 singleton live births were recorded after exclusions due to loss of contact before delivery (n = 99), participation withdrawal (n = 121), miscarriage (n = 132), stillbirth (n = 72), and multiple pregnancies (n = 5).…”

“…Furthermore, the expression of miRNAs is sensitive to environmental exposures, including inorganic arsenic [24], which is an independent risk factor for preterm birth [25] and lower birthweight [26,27]. Therefore, it is possible that the effect of placenta-derived miRNAs on birthweight can be modified by in utero arsenic exposure.…”

Unconventional natural gas development and adverse birth outcomes in Pennsylvania: The potential mediating role of antenatal anxiety and depression

“…Mediation analyses can help uncover mechanisms of action that may explain the association between environmental exposures and perinatal health outcomes (Anthopolos et al, 2014;Ferguson et al, 2016;Rahman et al, 2017). In the present retrospective cohort study, we used stochastic direct and indirect effects (also called randomized interventional effects) (Rudolph et al, 2017;VanderWeele and Tchetgen Tchetgen, 2017) to evaluate maternal mental health during pregnancy as a potential mediator of a previously observed relationship between UNGD and adverse birth outcomes in Pennsylvania (Casey et al, 2016).…”