Prenatal Exposure to Cadmium, Placental Permeability and Birth Outcomes in Coastal Populations of South Africa

Abstract

BackgroundThe impact of prenatal exposure to cadmium (Cd) on birth outcomes is an area of concern. This study aimed to assess an impact of prenatal Cd exposure on birth outcomes in distinct coastal populations of South Africa.MethodsCadmium was measured in maternal blood (CdB) (n = 641), cord blood and in maternal urine (n = 317). This investigation assessed the associations between CdB (non-transformed) and birth outcomes across the 25th, 50th, and 75th percentile for birth weight, birth length and head circumference, to test for a linear trend. Associations between natural log-transformed maternal CdB, size at birth and other factors were further evaluated using linear mixed-effects modelling with random intercepts.ResultsThe average gestational age in the total sample was 38 weeks; 47% of neonates were female, average birth weight was 3065 g and 11% were of low birth weight (< 2500 g). The geometric mean (GM) of the maternal CdB level was 0.25 μg/L (n = 641; 95% CI, 0.23–0.27). The cord blood Cd level was 0.27 μg/L (n = 317; 95% CI, 0.26–0.29) and urine (creatinine-corrected) Cd level was 0.27 μg/L (n = 318; 95% CI, 0.24–0.29). The CdB cord:maternal ratio in the sub-cohort was 1, suggesting that the placenta offers no protective mechanism to the foetus. An inverse association was found between CdB and the lower birth weight percentile in female neonates only (β = - 0.13, p = 0.047). Mothers who reported eating vine vegetables daily had lower levels of CdB (β = - 0.55, p = 0.025). Maternal smoking was associated with an elevation in natural log-transformed CdB levels in both male and female cohorts.DiscussionSignificant inverse associations between prenatal Cd exposure and birth anthropometry were found in female neonates but not in male neonates, suggesting potential sex differences in the toxico-kinetics and toxico-dynamics of Cd.

Moderate Prenatal Cadmium Exposure and Adverse Birth Outcomes: a Role for Sex‐Specific Differences?

“…This was first proposed by Kippler et al 20, 21. in a cohort in Bangladesh and has subsequently been replicated in cohorts from South Africa and the USA 8, 19. Kippler et al 20.…”

“…This was first proposed by Kippler et al 20,21 in a cohort in Bangladesh and has subsequently been replicated in cohorts from South Africa and the USA. 8,19 Kippler et al 20 suggested several mechanisms for this differential effect: (1) the relative sensitivity of female fetuses compared with male fetuses to a Cd-induced increase in glucocorticoid concentrations reflecting a decrease in 11b-HSD2 activity, with a consequent increase in cortisol level; (2) differential Cd interference with the IGF axis, as there is some evidence that levels of IGF subtypes are sex-specific; (3) the male skeleton may be more resistant to Cd-induced bone damage through differential effects on bone mineralization, bone density, and bone mineral content; (4) there may be effects on in utero sex-specific programming that contribute to the vulnerability of the fetus to environmental stressors. As suggested by Rollin et al 8 these effects may be related to hypomethylation of growth-related genes in girls relative to hypermethylation in boys in response to Cd exposure.…”

“…Its effects on birth outcomes, however, particularly at moderate exposures, are not well understood and in this regard Cd has received far less research attention than its near neighbours in the periodic table, lead and mercury, The placenta is thought to be at least a partial barrier to Cd transfer to the fetus,5, 6 but determination of ratios of Cd in cord blood : maternal blood have left this in doubt (ratios ranging from 0.247 to 1.08,8 with others finding intermediate values9, 10). Studies with moderate maternal blood cadmium levels (B‐Cd; below a suggested reference value of 1 μg/L11) and adjustment for smoking have generally found no associations with birthweight, birth length, head circumference or preterm delivery,8, 12, 13 but other studies have found negative associations particularly with birthweight14, 15, 16 (Table S1). Even where exposure levels are higher and effects could potentially be more evident, again some studies have found no associations with birth outcomes,10, 17 while others have found adverse associations 18.…”

“…Even where exposure levels are higher and effects could potentially be more evident, again some studies have found no associations with birth outcomes,10, 17 while others have found adverse associations 18. It has recently been suggested that adverse events associated with maternal Cd exposure are sex‐specific, with effects on birthweight and birth length being more severe in or confined to girls8, 19, 20, 21 and that this might mask effects in mixed‐sex studies.…”

Placental barrier permeability to Cadmium and Plumbum during cow pregnancy and at the foaling time of mares

“…Проникання лікарських засобів від матері до плода залежить від структури плаценти, Cd в популяціях тварин -від його дородової експозиції (Röllin et al, 2015), у людей -від статевих і вікових відмінностей (Walker et al, 2017). Оцінка проникності Cd взаємозв'язана з статусом гемоглобіну (Bonglaisin et al, 2017) і наявності наночасток, які впливають на проникність плацентарного бар'єра (Muoth еt al., 2015), що узгоджується з отриманими результатами при моделюванні запальних реакцій у відповідь на бактеріальну інфекцію (Sanders еt al., 2015;Qin et al, 2018).…”