Selenium Status, Its Interaction with Selected Essential and Toxic Elements, and a Possible Sex-Dependent Response In Utero, in a South African Birth Cohort.

Selenium (Se) is an essential trace element and its deficiency in utero may affect fetus development and birth outcomes. The current study aimed to assess serum Se status at delivery and examine the possible association between Se levels and birth outcomes. The interaction of Se with selected essential and toxic elements as well as possible sex-dependent responses in utero were also evaluated. The negative association between Se levels and head circumference of neonates was evident in the total cohort (ß = -0.164; p < 0.001) as well as in the pre-term and full-term cohorts. Significant positive correlations were found between maternal serum Se concentrations and zinc (Zn) and copper (Cu) in the total and regional cohorts. In the total cohort, the toxic elements lead (Pb) and arsenic (As) showed a negative correlation with Se levels, while mercury (Hg), aluminum (Al) and cadmium (Cd) showed a positive correlation. The study found a sex-dependent response in utero for Zn, Cu, Pb, Hg, and Al. The findings of the current study may inform reproductive health policy on Se status in South Africa and highlight the need for sensitive methods to measure Se intake during pregnancy and its complex interactions with other micronutrients and environmental pollutants.

In Utero Exposure to Aluminium and Other Neurotoxic Elements in Urban Coastal South African Women at Delivery: An Emerging Concern.

Aluminium (Al) is a non-essential neurotoxicant and there is limited information regarding exposure to Al in utero. This study sought to evaluate the in utero exposure to Al in urban South African women, its effects on birth outcomes and possible synergistic effects between Al, essential and neurotoxic elements such as lead (Pb), mercury (Hg) and arsenic (As), as well as a a potential sex-dependent response to these elements in neonates. This study has found elevated levels of Al in urban women at delivery. The Spearman's rank correlation coefficients (p-value) of the association between maternal serum Al and birth outcomes (gestational age and parity), and between maternal serum Al and Cu, Zn and Se, were statistically significant. However, in the general and the stratified models, no association was found between any of the birth outcomes and maternal serum Al. The association between maternal serum Al and neurotoxic elements at delivery showed a significant positive correlation for Pb only (rho = 0.361; p < 0.001) which was found to be sex-dependent in neonates (males, rho = 0.285; p < 0.004 and females, rho = 0.444, p < 0.001). Our preliminary findings indicate that in utero exposure to Al is an emerging concern requiring further research and directives from public health authorities.

Prenatal Exposure to Aluminum and Status of Selected Essential Trace Elements in Rural South African Women at Delivery.

This study sought to evaluate the in utero exposure to aluminum and status of selected trace elements in South African women at delivery since aluminum is known to be toxic in all developmental stages even at low concentrations. Serum aluminum was negatively correlated with aluminum in urine, both uncorrected and corrected for creatinine, which suggests the retention of aluminum in body stores. Serum copper and zinc levels were found to be high in this study population. Serum copper levels were negatively correlated with aluminum in serum (ß = -0.095; p = 0.05). There was a marginal negative correlation between aluminum levels in serum and manganese levels in whole blood (ß = -0.087; p = 0.08). Copper levels in maternal serum were negatively correlated with birth weight and the length of neonates. There were a number of positive correlations between maternal characteristics and birth outcomes. Mothers who consumed root vegetables frequently appeared to be protected from aluminum retention and increased body burden since their serum aluminum levels were found to be significantly lower. The findings of the current study can be used as a baseline for further research on aluminum exposure and its associated interactions and outcomes in vulnerable populations.

Reduction of in utero lead exposures in South African populations: Positive impact of unleaded petrol.

BACKGROUND: Prenatal exposure to lead (Pb) has been shown to have negative and irreversible health impacts on foetal and early childhood development, affecting morbidity and mortality in adulthood. This study aimed to assess in utero Pb exposure, examine birth outcomes, and identify confounding factors in the large cohort of South African population, following the legislated removal of Pb from petrol. METHODS: Lead was measured in the maternal blood, urine and cord blood using Inductive Coupled Plasma Mass spectrometry (ICP-MS). The statistical analyses included Spearman's correlation, Wilcoxon rank sum (Mann Whitney), Kruskal-Wallis rank tests and multivariate linear regression. RESULTS: Overall, the geometric mean (GM) of Pb in maternal blood (PbB) was 1.32 µg/dL (n = 640; 95% CI, 1.24-1.40). In the subset cohort, the GM of paired maternal PbB and cord blood (PbC) was 1.73 µg/dL (n = 350; 95% CI, 1.60-1.86) and 1.26 µg/dL (n = 317; 95% CI, 1.18-1.35), respectively with a positive correlation between the log PbB and the log PbC (rho = 0.65, p = <0.001). Birth outcomes showed geographical differences in the gestational age (p<0.001), birth length (p = 0.028) and head circumference (p<0.001), Apgar score at 5 min (p<0.001) and parity (p<0.002). In female neonates, a positive association was found between PbC and head circumference (rho = 0.243; p<0.016). The maternal PbB levels were positively correlated with race, educational status, water sources, cooking fuels and use of pesticides at home. CONCLUSIONS: This study has demonstrated not only the positive impact that the introduction of unleaded petrol and lead-free paint has had on in utero exposure to Pb in South Africa, but has also contributed new data on the topic, in a region where such data and scientific investigations in this field are lacking. Future research should evaluate if similar effects can be detected in young children and the adult population.

Evaluation of in utero exposure to arsenic in South Africa.

Early life exposure to inorganic arsenic (iAs) has been shown to interfere with foetal and early childhood development, and is associated with morbidity and mortality in adulthood. The purpose of this study was to evaluate exposure to As in utero, to determine the association between maternal and cord blood of As and birth outcomes in South African populations. Total arsenic was measured in maternal blood of a total cohort (n=650) and in paired cord blood and urine of a subset cohort (n=317). Overall, the geometric mean (GM) of As in maternal blood was 0.62µg/L (n=650; 95% CI, 0.58-0.66). In the subset cohort, the GM of maternal blood As was 0.96µg/L (n=350; 95% CI, 0.91-1.02); in paired cord blood, the GM was 0.78µg/L (n=317; 95% CI, 0.74-0.83); and in urine (creatinine-corrected), the GM was 14.26µg/g creatinine (n=317; 95% CI, 12.64-16.09). A linear correlation was found between log maternal blood As and log cord blood As (rho=0.80, p<0.001). Birth outcomes showed geographical differences. in gestational age (p<0.001), birth length (p=0.019), head circumference (p<0.001), Apgar score at 5min (p<0.001) and parity (p<0.002). In a multivariate analysis, no association between maternal blood (AsB) levels and birth outcomes were found. However, the lower the gestational age, the higher the levels of maternal AsB (ß=-0.054; 95% CI-0.087 to -0.020) and mothers who had had at least one child were less likely to have higher AsB if compared to those who had never had any child (ß=-0.177; 95CI-0.322 to 0.031). In both univariate and multivariate analyses, being single, and drinking water from communal outdoor taps, boreholes and rivers was associated with higher As levels. The findings suggest that more research is needed to evaluate the impact of low level As exposure on postnatal development.

Relationship between Pesticide Metabolites, Cytokine Patterns, and Asthma-Related Outcomes in Rural Women Workers.

The objective of this study was to investigate the relationship between exposure to organophosphate (OP) and pyrethroid (PYR) pesticides with serum cytokine patterns and asthma-related outcomes among rural women workers. A cross-sectional study was conducted among rural women (n = 211), including those working and living on farms and nearby town dwellers. Pesticide exposure was assessed using urinary metabolite concentrations of OP and PYR pesticides. Health outcome assessment was ascertained through the European Community Respiratory Health Survey (ECRHS) questionnaire, fractional exhaled nitric oxide (FeNO), and serum cytokines associated with asthma. The prevalence of doctor-diagnosed asthma was 11%, adult-onset asthma 9%, and current asthma 6%. In this population, the proportion of T helper type 2 (Th2) cytokines (interleukin (IL)-4, IL-5, and IL-13) detectable in subjects was between 18% and 40%, while the proportion of non-Th2 cytokines (IL-6, IL-8, IL-10, IL-17, and interferon gamma) was between 35% and 71%. Most Th2 and non-Th2 cytokines were positively associated with either OP or PYR metabolites. Non-Th2 cytokines showed much stronger associations with OP metabolites (Dimethyl phosphate OR = 4.23; 95% CI: 1.54-11.65) than Th2 cytokines (Dimethyl phosphate OR = 1.69; 95% CI: 0.83-3.46). This study suggests that exposure to most OP and some PYR pesticides may be associated with asthma-related cytokines, with non-Th2 cytokines demonstrating consistently stronger relationships.

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

BACKGROUND: The 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. METHODS: Cadmium 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. RESULTS: The 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 (ß = - 0.13, p = 0.047). Mothers who reported eating vine vegetables daily had lower levels of CdB (ß = - 0.55, p = 0.025). Maternal smoking was associated with an elevation in natural log-transformed CdB levels in both male and female cohorts. DISCUSSION: Significant 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.

Differences in prenatal exposure to mercury in South African communities residing along the Indian Ocean.

Mercury is a persistent environmental pollutant that has the potential to adversely affect human health, particularly, foetal neurodevelopment. The purpose of the study was to investigate prenatal mercury (Hg) exposure in the population in three sites along the South Africa coast. Study subjects included women (n=350) who were admitted for delivery at the local hospitals. Maternal and cord blood samples were collected to measure total mercury and each participant was required to answer a questionnaire. The 90th percentile of mercury levels in maternal and cord blood of the total population was 1.15 µg/l and 1.67 µg/l, respectively. Site 1 (Manguzi) participants had the highest maternal geometric mean (GM) values of 0.93 µg/l, which was significantly different from Site 2 (Port Shepstone) (0.49 µg/l) and Site 3 (Empangeni) (0.56 µg/l) (ANOVA test, p<0.001). Umbilical cord blood GM Hg level for Site 1 (1.45 µg/l) was more than double the GM Hg level in Site 2 (0.70 µg/l) and Site 3 (0.73 µg/l). Univariate analysis indicated that the following maternal characteristics were positive predictors for elevated umbilical cord Hg levels: maternal blood Hg levels, living with a partner, residing in Site 1, living in informal housing, using wood and gas for cooking, borehole water as a drinking source, and a member of the household being involved in fishing. Maternal dietary predictors of elevated Hg levels in umbilical cord blood included consuming fresh fish, tinned fish, fruit or dairy products, daily. This study provides baseline data and reveals that 2% of the study population were above the EPA's reference value (5.8 µg/l) suggesting low level exposure to mercury in pregnant women and the developing foetus in South Africa. Further research is required to explore the sources of elevated Hg levels in Site 1.

Regional variation in pesticide concentrations in plasma of delivering women residing in rural Indian Ocean coastal regions of South Africa.

Exposure to pesticides places pregnant women and the developing foetus at the highest risk. The objective of this study is to obtain an exposure assessment by investigating levels of pesticides in blood plasma of delivering women. We report on the concentrations of α, ß, γ HCH, endosulfan, HCB and the pyrethroids: cis-permethrin, cyfluthrin, cypermethrin and deltamethrin found in the maternal blood plasma of delivering women (n = 241) in three coastal sites of KwaZulu Natal. γ-HCH and endosulfan 1 and 2 were the most dominant pesticides in all three sites. Significantly, higher levels of γ-HCH and endosulfan were found in site 3 (vicinity of Empangeni) compared to the other two sites (p < 0.05). The GM levels for γ-HCH, endosulfan 1 and 2 were 956, 141 and 21 ng g(-1) lipids in site 3, respectively. The pyrethroid pesticides, HCB, α-HCH and ß-HCH were detected in less than 31% of the samples in all sites. γ-HCH correlated positively and strongly to both endosulfan 1 and 2 (r > 0.47), indicating a common source of exposure. The high levels of γ-HCH and endosulfan in maternal plasma samples in site 3 indicate the current and on-going exposure, which is of great concern for reproductive health and prenatal exposure.

Prenatal exposure to DDT in malaria endemic region following indoor residual spraying and in non-malaria coastal regions of South Africa.

Exemption was granted by the Stockholm Convention in 2004 for use of DDT by indoor residual spraying (IRS) as a malaria vector control. South Africa endorsed the use of DDT in its Malaria Control Programmes in malaria endemic regions and IRS remains a primary method of controlling malaria transmitting mosquitoes in this country. This study examines the impact of IRS on the levels of DDT and its metabolites in maternal blood of delivering women as a measure of prenatal exposure. We report on the concentrations of DDT and its metabolites (p,p'- DDE, p,p'-DDT, o,p'-DDE, o,p'-DDD, p,p'-DDD, and o,p'-DDT) in maternal plasma of 255 delivering women residing in three sites along Indian Ocean, namely in malaria endemic where IRS takes place, low risk and non-malaria sites. Concentrations of measured compounds were found to be significantly higher in the malaria endemic site (p=0.0001): the geometric mean concentration (95% confidence intervals; n=91) for o,p'-DDE was 9 ng/g lipids (7-10); for p,p'-DDE, 3840 ng/g lipids (3008-4902); for o,p'-DDD, 8 ng/g lipids (6-9); for p,p'-DDD, 26 ng/g lipids (20-32); for o,p'-DDT, 168 ng/g lipids (127-221) and for p,p'-DDT, 2194 ng/g lipids (1706-2823). These compounds were also detected in women residing in other sites but in lower concentrations. The maternal characteristics, age, IRS, number of children and breastfeeding were significantly associated for both p,p'-DDE and p,p'-DDT levels in the malaria area where exposure through IRS is predominant. There was no association between maternal characteristics and DDT levels in the low risk and non-malaria area. Results presented are of particular value to the policy decision makers and regulatory toxicology organizations as they characterise the extent of controlled exposure to DDT used exclusively for IRS purposes. Furthermore, findings of this study will form a base for further investigation of foetal exposure to pollutants.

Urinary dialkyl phosphate levels before and after first season chlorpyrifos spraying amongst farm workers in the Western Cape, South Africa.

The study investigated urinary levels of dialkyl phosphates resulting from pesticide exposure amongst 40 farm workers. Workers were tested (urinary dialkyl phosphate levels, anthropometry, short exposure questionnaire) before and after the first day of seasonal chlorpyrifos spraying. Median baseline urinary dialkyl phosphates was high amongst both non-applicators (1587.5 µg/g creatinine, n = 8) and applicators (365.6 µg/g creatinine, n = 9). There was not much evidence of an increase in post-spray dialkyl phosphates levels from pre-spray levels amongst both applicators and non-applicators. Hours mixing, spraying, driving a tractor and hours worked by non-applicators were not significantly associated with an increase in post-spray dialkyl phosphate levels, adjusting for age, height, weight, gender, use of empty pesticide containers and self-reported kidney problems. Past applicator status was weakly positively associated with pre-spray dialkyl phosphate levels adjusting for age, height, weight, and gender, self-reported kidney problems, smoking and alcohol (ß= 1019.5, p = 0.307, R² = 0.28). The high dialkyl phosphate levels call for an epidemiological investigation into the health effects of organophosphorous pesticides.

Increased oxidants and reduced antioxidants in irradiated parenteral nutrition solutions may contribute to the inflammatory response.

BACKGROUND/OBJECTIVES: To measure reactive oxidant production and the decline in antioxidant potential in commercially available, irradiated parenteral nutrition (PN) solutions and the effect that these have on oxidant production in patients in the intensive care unit. SUBJECTS AND METHODS: Vitamin E and malondialdehyde in irradiated and nonirradiated commercially available, PN solutions were measured. The PBN (alpha-phenyl-n-test-butylnitrone (PBN) spin trap was used to measure free radicals and TEMPOL (2,2,6,6-tetramethyl-4-hydroxy-piperidine-oxyl) was used to assess antioxidant capacity. The irradiated PN was administered (as per unit protocol) to 10 patients with gut failure and plasma and urinary isoprostanes and interleukin-6 (IL-6) were measured 1 hour preadministration, at the time of, and 1 and 2 hours postadministration of PN. RESULTS: Irradiation reduced vitamin E significantly (P < .0025). Malondialdehyde products were present in both samples, but more so in irradiated samples (P < .0001), as were free radicals measured by PBN spin trapping. Irradiated samples had a higher scavenging capacity of TEMPOL free radical due to depletion of antioxidants in irradiated samples. Urinary isoprostanes increased at time 2 by 6.3 units relative to time 0 and by 5.23 units relative to time 1(Friedman ANOVA: P < .01413). CONCLUSIONS: Lipid hydroperoxides are formed in PN solutions and increase further following irradiation. This is associated with a significant reduction in vitamin E and antioxidant potential. The increase in urinary isoprostanes indicates a potentially proinflammatory effect of irradiated PN.

Occupational exposure to ethylene oxide during pregnancy and association with adverse reproductive outcomes.

OBJECTIVE: To investigate the association between exposure to ethylene oxide during pregnancy and adverse reproductive outcomes. METHODS: Singleton pregnancies were analysed that: (1) had occurred in women working at the time of the study (2004) in hospital sterilising units using ethylene oxide in Gauteng province, South Africa; (2) was the last recognised pregnancy of these women after the 1 January 1992; and (3) this last recorded pregnancy had occurred while the mother was employed. An adverse reproductive outcome was defined as the occurrence of a spontaneous abortion, still birth or pregnancy loss (combined abortion + still birth). Information on the evolution and outcome of the pregnancy was gathered from the mother using a questionnaire. Information on exposure to ethylene oxide during pregnancy was obtained from three sources, namely walk-through surveys, questionnaire-collected data and measurements of the levels of ethylene oxide in sterilising units at the time of the study (personal and static sampling). RESULTS: The study enrolled 69% of the hospitals in Gauteng using ethylene oxide to sterilise medical equipment. The participation rate for women employed in these sterilising units was 97%, and the study population consisted of 98 singleton pregnancies. Measurements of ethylene oxide showed that operators of sterilisers were still potentially over-exposed. There was a significantly increased risk of spontaneous abortion (POR = 20.8, 95% CI = 2.1-199) and pregnancy loss (POR = 8.6, 95% CI = 1.8-43.7) for pregnancies highly exposed to ethylene oxide compared to low exposed pregnancies. No associations were found between exposure to ethylene oxide and stillbirth. CONCLUSIONS: An increased risk of spontaneous abortion and pregnancy loss was found to be associated with exposure to ethylene oxide during pregnancy.

Lipid peroxidation and trace elements in systemic sclerosis.

Oxidative stress appears to be important in the causation and perpetuation of tissue injury and fibrosis in systemic sclerosis or scleroderma (SSc). We conducted a case-control study to assess lipid peroxidation levels as determined by measuring fasting plasma malondialdehyde (MDA) and serum levels of the trace elements selenium, iron, zinc and copper in SSc. Plasma MDA levels were almost tenfold higher in patients than in controls (p=0.00007), and an inverse relationship between MDA levels and disease duration (r=-0.52, p=0.044) was observed. Selenium levels were lower in patients than in controls (p=0.012). Within the patient cohort, copper correlated inversely with the total skin score (r=-0.52, p=0.03). Our findings provide further evidence that lipid peroxidation is increased and antioxidant capacity is reduced in SSc. The gradual decline in MDA levels with time suggests that antioxidant therapy, if to be useful in SSc, is most likely to be effective early in the course of the disease.