Prenatal exposure to cadmium, placental permeability and birth outcomes in coastal populations of South Africa

PLoS ONE, Volume 10, No. 11, Year 2015

Interpretation

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 (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. 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. A total of five sites were included in the study: three sites were situated along the Indian Ocean coast of the KwaZulu Natal (KZN) Province, and two sites were situated along the Atlantic Ocean coast of the Western Cape Province of South Africa (Fig 1). Figure is identical but sites locations were added, and is therefore for representative purposes only. https://www.cia.gov/library/publications/resources/cia-maps-publications/South%20Africa.html. All three sites along the Indian Ocean coast can be defined as rural with varying degrees of agricultural activities. However, their geographical location may predispose them to environmental pollution emanating from mining and industrial activities (site 1); aluminium smelting, mining, coal terminals and ports (site 2); and small industrial activities (site 3). Along the Atlantic Ocean coast, one study site is the urban city of Cape Town, which is surrounded by commercial, industrial and port activities (site 4); and the second site is considered to be rural (site 5), where commercial agriculture and fishing activities dominate. Potential study candidates were recruited by a health worker on duty, from women who were admitted for delivery at the local maternity sections of public hospitals. A trained research assistant briefly explained the objectives of the study and distributed a detailed information sheet about the project. All women who agreed to participate signed an informed consent form and agreed to donate blood before delivery. Participants agreed to answer a socio-demographic questionnaire which also included the topics of diet, lifestyle, and health status. Participants also consented to access and use of hospital birth outcome data for research purposes. The socio-demographic questionnaire was not specifically designed for Cd exposure, but for exposure to environmental pollutants in general. The dietary part of the questionnaire recorded the intake frequency of various basic foods during pregnancy. After delivery, records from hospital files were extracted, including maternal and neonate characteristics such as weight, length and head circumference, gestational age, as well as any birth complications, if any. In total, 650 delivering women participated in the study, of which 641 women, who delivered singleton infants of gestation of more than 20 weeks, were included. Due to financial constraints, the collection of additional samples (pre-partum urine samples and post-partum cord blood samples) was limited to women residing in Sites 1, 2 and 3 (n = 317). From each woman, a volume of 10 ml of venous blood was collected before delivery into BD Vacutainer tube (10 ml capacity and containing EDTA). Participants from the sub-cohort (n = 317) also donated 30 ml of urine before delivery, and 10 ml of umbilical cord blood post-partum. The analyses for Cd content in whole blood and urine were performed using an Inductively Coupled Plasma-Mass Spectrometer (ICP-MS) instrument (Agilent 7500ce ICP-MS with an Octopole Reaction System). Contamination-free vessels and procedures were used throughout, and validation of results was accomplished by including certified standards, as well as certified references quality controls, in the analyses. Briefly, the whole blood samples (0.5ml volumes) were digested with 1 ml nitric acid (Fluka, Trace Select Ultra for trace analysis) at 90°C for 2 hours. After cooling, the internal standard was added and samples were diluted with water to a final volume of 7 ml. Cd was measured in ‘no gas’ acquisition mode with 115In and 197Au as internal standards. Aliquots of each sample were analysed in triplicate. The detection limits (three times the standard deviation of all blank samples) for Cd was 0.03μg/L. For quality assurance, two certified reference controls, viz. Seronorm ™Trace Elements (Sero LTD., Billingstad, Norway) in whole blood (Levels 1 and 2), were analysed with every analytical run, at intervals between every 10 samples. Urine samples (1 ml volumes) were digested with 0.1 ml of 65% ultrapure nitric acid ((Fluka, Trace Select Ultra for trace analysis). An internal standard solution containing 72Ge, 115In and 197Au was added (50 μl) to all samples, reagent blanks, reference controls and calibration standards and made up to 5 ml (5 times sample dilution). Urinary Cd (CdU) levels were measured in ‘no gas’ acquisition mode and percentage recovery, when using certified standards (Seronorm Urine Blank and Lyphchek Level 1&2), was 108.8% and 111.5% for level 1 and 2, respectively. The sample analyses were conducted by the Johannesburg National Institute for Occupational Health (NIOH) laboratory, which participates in the Wadsworth Center—New York State Department of Health Proficiency testing scheme for whole blood and urine. The results obtained are consistently accepted with no indication of bias. Covariate information was obtained during the questionnaire-based interview and from medical records. Maternal weight and height were recorded at the hospital on admission. From the medical records, the following newborn characteristics were retrieved: birth weight (grams), birth length (cm), head circumference (cm) and gestational age (weeks). Preterm labour was defined as mothers giving birth at less than 37 weeks gestational age. Education was categorised as no education, completed primary school, completed secondary school and any level of tertiary education reached. Maternal tobacco smoking was defined as ever or never. Exposure to environmental tobacco smoke (ETS) was defined as exposure to tobacco smoke from smoking by others in the household. A binary classification was used for exposure to indoor smoke from the burning of fossil fuel (wood and coal) for the purpose of heating or cooking, separating women into those exposed to fossil fuel and those not exposed (for example, electricity). Dietary questions relating to vine, root and leafy vegetable intake were assessed and classified as daily, at least once a week and seldom. The statistical analyses were performed using STATA (StataCorp, 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP). The distribution of Cd levels in maternal blood and urine and in cord blood, were skewed and were log transformed. Bivariate analyses between Cd exposure, sizes at birth and covariates were evaluated by Spearman’s correlation coefficient. The non-parametric Wilcoxon rank-sum (Mann-Whitney) and Kruskal-Wallis rank tests were used where appropriate, to make categorical comparisons of the maternal CdB distribution (n = 641) and demographic, dietary, and environmental characteristics. The 25th percentile (lowest quintile), 50th percentile (median quintile), and 75th percentile (highest quintile) were assessed for birth outcomes (birth weight, birth length and head circumference). Furthermore, associations between CdB (non-transformed) and size at birth across the quintiles were assessed using a non-parametric test (nptrend in Stata) to test for linear trend. Linear mixed-effect models with random intercepts were used to identify significant predictors (p < 0.1) of natural logarithm—transformed blood Cd levels and to estimate the amount of variability in measured levels explained by the model. Potential explanatory variables were identified from questionnaire data that were associated with blood Cd levels with a p < 0.2 during univariate analyses: vegetable intake, smoking history, burning of fossil fuel, environmental tobacco smoke exposure, gestational age, parity, size at birth (birth weight, birth length and head circumference), and gender of the newborn. Model fit was compared using log likelihood and Akaike Information Criterion (AIC) statistics. Ethics approval for the study was obtained from the Human Research Ethics Committee of the University of Witwatersrand in Johannesburg (Protocol no. {"type":"entrez-nucleotide","attrs":{"text":"M10742","term_id":"147973"}}M10742), and from the relevant provincial Departments of Health. The sites along the Indian Ocean coast (sites 1 to 3) fall under the Provincial Department of Health of KwaZulu Natal, which issued ethical consent for each site and requested the CEOs of the respective hospitals to allow this research to take place. Each CEO confirmed that he/she allowed the research work to proceed. The sites along the Atlantic Ocean coast (sites 4 and 5) fall under the Western Cape Provincial Department of Health; identical procedures were followed in terms of obtaining consent for the study. Confidentiality was maintained by assigning identification numbers to all study participants. During the informed consent process, it was emphasised that participation was voluntary and could be withdrawn at any time.

AI Digest

Study Justification:

This study aimed to assess the impact of prenatal exposure to cadmium (Cd) on birth outcomes in distinct coastal populations of South Africa. The justification for this study is that prenatal exposure to Cd is a cause for concern and understanding its effects on birth outcomes is important for public health and policy-making.

Study Highlights:

– The study included five sites along the Indian Ocean and Atlantic Ocean coasts of South Africa.
– Cd levels were measured in maternal blood, cord blood, and maternal urine.
– Associations between Cd levels and birth outcomes were assessed.
– Significant inverse associations were found between prenatal Cd exposure and birth anthropometry in female neonates.
– Maternal smoking and vegetable intake were associated with Cd levels.

Study Recommendations:

Based on the findings of the study, the following recommendations can be made:

1. Public health interventions should focus on reducing prenatal exposure to Cd, especially in coastal populations.
2. Pregnant women should be educated about the potential risks of Cd exposure and encouraged to adopt healthy lifestyle behaviors, such as avoiding smoking and consuming a balanced diet.
3. Further research is needed to explore the potential sex differences in the toxico-kinetics and toxico-dynamics of Cd.

Key Role Players:

To address the recommendations, the following key role players are needed:

1. Public health officials and policymakers: They can develop and implement policies and interventions to reduce Cd exposure in coastal populations.
2. Healthcare professionals: They can educate pregnant women about the risks of Cd exposure and provide guidance on healthy lifestyle behaviors.
3. Researchers: They can conduct further studies to better understand the mechanisms and long-term effects of Cd exposure.

Cost Items for Planning Recommendations:

While the actual cost of implementing the recommendations will vary, the following cost items should be considered in planning:

1. Public health campaigns and educational materials: This includes the development and dissemination of information about Cd exposure and its risks.
2. Training and capacity building: This includes training healthcare professionals to effectively communicate and educate pregnant women about Cd exposure.
3. Research funding: Further studies on Cd exposure and its effects may require funding for data collection, analysis, and publication.
4. Monitoring and evaluation: Regular monitoring and evaluation of interventions and policies are necessary to assess their effectiveness and make necessary adjustments.
Please note that the cost items provided are for planning purposes and may not reflect the actual costs associated with implementing the recommendations.

Strength of Evidence

The strength of evidence for this abstract is 7 out of 10.
The evidence in the abstract is moderately strong, but there are some areas for improvement. The study design appears to be robust, with a large sample size and the use of statistical analysis. The associations between prenatal cadmium exposure and birth outcomes are clearly presented. However, there are some limitations to consider. The abstract does not provide information on the representativeness of the study population or the generalizability of the findings. Additionally, the abstract does not mention any potential confounding factors that may have influenced the results. To improve the strength of the evidence, it would be helpful to include information on the recruitment process and the criteria for inclusion in the study. Additionally, providing more details on the statistical methods used and addressing potential confounding factors would enhance the credibility of the findings.

Abstract

A total of five sites were included in the study: three sites were situated along the Indian Ocean coast of the KwaZulu Natal (KZN) Province, and two sites were situated along the Atlantic Ocean coast of the Western Cape Province of South Africa (Fig 1). Figure is identical but sites locations were added, and is therefore for representative purposes only. https://www.cia.gov/library/publications/resources/cia-maps-publications/South%20Africa.html. All three sites along the Indian Ocean coast can be defined as rural with varying degrees of agricultural activities. However, their geographical location may predispose them to environmental pollution emanating from mining and industrial activities (site 1); aluminium smelting, mining, coal terminals and ports (site 2); and small industrial activities (site 3). Along the Atlantic Ocean coast, one study site is the urban city of Cape Town, which is surrounded by commercial, industrial and port activities (site 4); and the second site is considered to be rural (site 5), where commercial agriculture and fishing activities dominate. Potential study candidates were recruited by a health worker on duty, from women who were admitted for delivery at the local maternity sections of public hospitals. A trained research assistant briefly explained the objectives of the study and distributed a detailed information sheet about the project. All women who agreed to participate signed an informed consent form and agreed to donate blood before delivery. Participants agreed to answer a socio-demographic questionnaire which also included the topics of diet, lifestyle, and health status. Participants also consented to access and use of hospital birth outcome data for research purposes. The socio-demographic questionnaire was not specifically designed for Cd exposure, but for exposure to environmental pollutants in general. The dietary part of the questionnaire recorded the intake frequency of various basic foods during pregnancy. After delivery, records from hospital files were extracted, including maternal and neonate characteristics such as weight, length and head circumference, gestational age, as well as any birth complications, if any. In total, 650 delivering women participated in the study, of which 641 women, who delivered singleton infants of gestation of more than 20 weeks, were included. Due to financial constraints, the collection of additional samples (pre-partum urine samples and post-partum cord blood samples) was limited to women residing in Sites 1, 2 and 3 (n = 317). From each woman, a volume of 10 ml of venous blood was collected before delivery into BD Vacutainer tube (10 ml capacity and containing EDTA). Participants from the sub-cohort (n = 317) also donated 30 ml of urine before delivery, and 10 ml of umbilical cord blood post-partum. The analyses for Cd content in whole blood and urine were performed using an Inductively Coupled Plasma-Mass Spectrometer (ICP-MS) instrument (Agilent 7500ce ICP-MS with an Octopole Reaction System). Contamination-free vessels and procedures were used throughout, and validation of results was accomplished by including certified standards, as well as certified references quality controls, in the analyses. Briefly, the whole blood samples (0.5ml volumes) were digested with 1 ml nitric acid (Fluka, Trace Select Ultra for trace analysis) at 90°C for 2 hours. After cooling, the internal standard was added and samples were diluted with water to a final volume of 7 ml. Cd was measured in ‘no gas’ acquisition mode with 115In and 197Au as internal standards. Aliquots of each sample were analysed in triplicate. The detection limits (three times the standard deviation of all blank samples) for Cd was 0.03μg/L. For quality assurance, two certified reference controls, viz. Seronorm ™Trace Elements (Sero LTD., Billingstad, Norway) in whole blood (Levels 1 and 2), were analysed with every analytical run, at intervals between every 10 samples. Urine samples (1 ml volumes) were digested with 0.1 ml of 65% ultrapure nitric acid ((Fluka, Trace Select Ultra for trace analysis). An internal standard solution containing 72Ge, 115In and 197Au was added (50 μl) to all samples, reagent blanks, reference controls and calibration standards and made up to 5 ml (5 times sample dilution). Urinary Cd (CdU) levels were measured in ‘no gas’ acquisition mode and percentage recovery, when using certified standards (Seronorm Urine Blank and Lyphchek Level 1&2), was 108.8% and 111.5% for level 1 and 2, respectively. The sample analyses were conducted by the Johannesburg National Institute for Occupational Health (NIOH) laboratory, which participates in the Wadsworth Center—New York State Department of Health Proficiency testing scheme for whole blood and urine. The results obtained are consistently accepted with no indication of bias. Covariate information was obtained during the questionnaire-based interview and from medical records. Maternal weight and height were recorded at the hospital on admission. From the medical records, the following newborn characteristics were retrieved: birth weight (grams), birth length (cm), head circumference (cm) and gestational age (weeks). Preterm labour was defined as mothers giving birth at less than 37 weeks gestational age. Education was categorised as no education, completed primary school, completed secondary school and any level of tertiary education reached. Maternal tobacco smoking was defined as ever or never. Exposure to environmental tobacco smoke (ETS) was defined as exposure to tobacco smoke from smoking by others in the household. A binary classification was used for exposure to indoor smoke from the burning of fossil fuel (wood and coal) for the purpose of heating or cooking, separating women into those exposed to fossil fuel and those not exposed (for example, electricity). Dietary questions relating to vine, root and leafy vegetable intake were assessed and classified as daily, at least once a week and seldom. The statistical analyses were performed using STATA (StataCorp, 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP). The distribution of Cd levels in maternal blood and urine and in cord blood, were skewed and were log transformed. Bivariate analyses between Cd exposure, sizes at birth and covariates were evaluated by Spearman’s correlation coefficient. The non-parametric Wilcoxon rank-sum (Mann-Whitney) and Kruskal-Wallis rank tests were used where appropriate, to make categorical comparisons of the maternal CdB distribution (n = 641) and demographic, dietary, and environmental characteristics. The 25th percentile (lowest quintile), 50th percentile (median quintile), and 75th percentile (highest quintile) were assessed for birth outcomes (birth weight, birth length and head circumference). Furthermore, associations between CdB (non-transformed) and size at birth across the quintiles were assessed using a non-parametric test (nptrend in Stata) to test for linear trend. Linear mixed-effect models with random intercepts were used to identify significant predictors (p < 0.1) of natural logarithm—transformed blood Cd levels and to estimate the amount of variability in measured levels explained by the model. Potential explanatory variables were identified from questionnaire data that were associated with blood Cd levels with a p < 0.2 during univariate analyses: vegetable intake, smoking history, burning of fossil fuel, environmental tobacco smoke exposure, gestational age, parity, size at birth (birth weight, birth length and head circumference), and gender of the newborn. Model fit was compared using log likelihood and Akaike Information Criterion (AIC) statistics. Ethics approval for the study was obtained from the Human Research Ethics Committee of the University of Witwatersrand in Johannesburg (Protocol no. {"type":"entrez-nucleotide","attrs":{"text":"M10742","term_id":"147973"}}M10742), and from the relevant provincial Departments of Health. The sites along the Indian Ocean coast (sites 1 to 3) fall under the Provincial Department of Health of KwaZulu Natal, which issued ethical consent for each site and requested the CEOs of the respective hospitals to allow this research to take place. Each CEO confirmed that he/she allowed the research work to proceed. The sites along the Atlantic Ocean coast (sites 4 and 5) fall under the Western Cape Provincial Department of Health; identical procedures were followed in terms of obtaining consent for the study. Confidentiality was maintained by assigning identification numbers to all study participants. During the informed consent process, it was emphasised that participation was voluntary and could be withdrawn at any time.

Materials

https://efashare.b-cdn.net/materials/77cb61b659c9b843d67b83e2f74f362e74b247459777409055115dcfbc4889cb/pone.0142455.s001.docx

Innovations

Based on the provided information, here are some potential innovations that could improve access to maternal health:

1. Mobile health clinics: Implementing mobile health clinics that can travel to rural areas and coastal populations, providing prenatal care and screenings for pregnant women. This would help reach women who may have limited access to healthcare facilities.

2. Telemedicine services: Introducing telemedicine services that allow pregnant women to consult with healthcare professionals remotely. This would be particularly beneficial for women in remote areas who may have difficulty traveling to healthcare facilities.

3. Community health workers: Training and deploying community health workers to coastal populations to provide education, support, and basic healthcare services to pregnant women. These workers can help identify and address potential health risks, including exposure to environmental pollutants.

4. Health education campaigns: Conducting targeted health education campaigns to raise awareness about the risks of prenatal exposure to cadmium and other environmental pollutants. These campaigns can provide information on how to minimize exposure and promote healthy lifestyle choices during pregnancy.

5. Collaboration with local industries: Collaborating with local industries, such as mining and manufacturing, to implement measures that reduce environmental pollution and minimize the risk of prenatal exposure to harmful substances like cadmium. This could include implementing stricter regulations, promoting sustainable practices, and conducting regular monitoring of environmental pollutants.

It’s important to note that these recommendations are based on the information provided and may need to be further evaluated and tailored to the specific context and needs of the coastal populations in South Africa.

AI Innovations Description

Based on the provided information, the recommendation to improve access to maternal health would be to implement targeted interventions to reduce prenatal exposure to cadmium (Cd) in coastal populations of South Africa. These interventions could include:

1. Public awareness campaigns: Raise awareness among pregnant women and the general population about the potential risks of Cd exposure during pregnancy. Provide information on the sources of Cd and ways to minimize exposure, such as avoiding certain foods or adopting healthier dietary habits.

2. Environmental regulations and monitoring: Strengthen regulations and monitoring of industrial activities, mining, and agricultural practices that may contribute to Cd pollution. Implement measures to reduce Cd emissions and contamination in the environment, particularly in coastal areas where the study was conducted.

3. Prenatal screening and monitoring: Integrate Cd screening into routine prenatal care to identify women at higher risk of exposure. Regular monitoring of Cd levels in maternal blood and urine can help identify individuals who may require additional support or interventions.

4. Nutritional support and counseling: Provide pregnant women with guidance on healthy eating habits and balanced diets to minimize Cd exposure through contaminated food sources. Emphasize the importance of consuming a variety of fruits, vegetables, and other nutrient-rich foods while avoiding those known to be high in Cd.

5. Smoking cessation programs: Offer smoking cessation programs and support for pregnant women who smoke or are exposed to environmental tobacco smoke. Smoking has been associated with elevated Cd levels, and quitting smoking can help reduce Cd exposure for both the mother and the developing fetus.

6. Collaboration and research: Foster collaboration between healthcare providers, researchers, and policymakers to further investigate the impact of Cd exposure on birth outcomes and develop evidence-based strategies to mitigate its effects. Continued research can help refine interventions and improve maternal health outcomes.

It is important to note that these recommendations are based on the specific findings of the study mentioned and may need to be adapted to the local context and resources available in South Africa.

AI Innovations Methodology

To improve access to maternal health, here are some potential recommendations:

1. Increase availability of prenatal care: Ensure that pregnant women have access to regular check-ups, screenings, and necessary medical interventions throughout their pregnancy.

2. Improve transportation options: Provide reliable and affordable transportation options for pregnant women to reach healthcare facilities, especially in rural areas where access may be limited.

3. Enhance community-based healthcare services: Implement community-based programs that bring healthcare services closer to pregnant women, such as mobile clinics or home visits by healthcare providers.

4. Strengthen health education and awareness: Promote health education programs that focus on prenatal care, nutrition, and healthy lifestyle choices during pregnancy to empower women with knowledge and enable them to make informed decisions.

5. Address socio-economic barriers: Address socio-economic factors that hinder access to maternal health, such as poverty, lack of education, and cultural barriers, by providing financial support, educational opportunities, and culturally sensitive healthcare services.

To simulate the impact of these recommendations on improving access to maternal health, a methodology could include the following steps:

1. Define the baseline: Gather data on the current state of maternal health access, including factors such as the number of pregnant women receiving prenatal care, transportation options, availability of healthcare facilities, and socio-economic indicators.

2. Identify key indicators: Determine the key indicators that will be used to measure the impact of the recommendations, such as the number of pregnant women accessing prenatal care, the reduction in maternal mortality rates, or improvements in birth outcomes.

3. Develop a simulation model: Create a simulation model that incorporates the baseline data and the potential impact of the recommendations. This model should consider factors such as population demographics, geographic distribution, and resource allocation.

4. Input potential changes: Input the potential changes resulting from the recommendations into the simulation model. This could include increasing the number of healthcare facilities, improving transportation options, or implementing community-based programs.

5. Run simulations: Run simulations using the model to assess the impact of the recommendations on the identified key indicators. This will provide estimates of the potential improvements in access to maternal health.

6. Analyze results: Analyze the results of the simulations to determine the effectiveness of the recommendations in improving access to maternal health. This analysis should consider both the quantitative impact on key indicators and any qualitative feedback or insights from stakeholders.

7. Refine and iterate: Based on the analysis, refine the recommendations and simulation model as needed. Iterate the process to further optimize the impact of the recommendations on improving access to maternal health.

By following this methodology, stakeholders can gain insights into the potential impact of various recommendations and make informed decisions on how to improve access to maternal health.

Authors & Co-Authors

Statistics:

Citations: 41

Authors: 4

Identifiers:

DOI: 10.1371/journal.pone.0142455

Research Areas:

Environmental, Health System and Policy, Maternal Access, Maternal and Child Health, Quality of Care, Sexual and Reproductive Health, Social Determinants, Substance Abuse

Study Countries:

South Africa

Study Design:

Cohort Study

Study Approach:

Quantitative

Participants Gender:

Male & Female