Selenium status, its interaction with selected essential and toxic elements, and a possible sex-dependent response in utero, in a South African birth cohort

International Journal of Environmental Research and Public Health, Volume 18, No. 16, Year 2021

Interpretation

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 (β = −0.164; p < 0.001) as well as in the pre-term and full-term cohorts. Sig-nificant 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 pol-lutants. In total, five study sites were chosen along coastal regions of South Africa (three study sites at the Indian Ocean coast of the KwaZulu-Natal (KZN) province, and two sites at the Atlantic Ocean coast of the Western Cape province) (Figure 1). All sites were rural, except for the urban study site of the city of Cape Town, in the Western Cape province. In the statistical analyses, we report the results for total cohort, Indian Ocean region, and Atlantic Ocean region, which differ by environmental pollution and socioeconomic status. Women admitted for delivery at the maternity sections of public hospitals in the study regions were informed of the study objectives by the medical personnel on duty and a research assistant and invited to participate in the investigation. They were also given a detailed information pamphlet about the study. In total, 650 women agreed to take part in the study, signed informed consent forms, and agreed to donate a blood sample before delivery. Furthermore, all study participants agreed to answer a socio-demographic questionnaire by interview, which included questions on the frequency of intake of various basic foods before and during pregnancy, lifestyle, and self-reported health status. All study participants agreed to allow researchers access to the hospital birth outcome data and understood that participation was voluntary and confidential and that they had the option of withdrawing from the study at any time. Study sites: Sites 1, 2, 3—Indian Ocean; sites 4 and 5—Atlantic Ocean. Figure is identical but site locations have been added, and is therefore for representative purposes only. https://www.cia.gov/library/publications/resources/cia-maps-publications/South%20Africa.html. (accessed on 6 March 2017). A sterile Venoject system and Becton, Dickinson & Company (BD, Franklin Lakes, NJ, USA) collection tubes were used for all blood collections. Each study participant donated 10 mL of venous blood into a non-additive tube to obtain serum fractions for the analyses of Se, copper (Cu), zinc (Zn), and aluminum (Al). The serum tubes were centrifuged and the serum was transferred to acid-washed polypropylene tubes using acid-washed plastic pipettes. For the analyses of toxic elements such as Hg, lead (Pb), manganese (Mn), Cd, and As in maternal whole blood, 10 mL of venous blood was collected into tubes containing ethylene diamine tetra acetic acid (EDTA). Samples of serum (post-centrifugation) and whole blood samples were stored at −20 °C and couriered in a frozen state to the National Institute for Occupational Health (NIOH) laboratory, Johannesburg, South Africa. All precautions to eliminate and prevent contamination at collection and during the preparation of samples were applied throughout. All samples were analyzed using an Agilent Inductively Coupled Plasma Mass Spectrometer (ICP-MS) 7900 with an Octopole Reaction System. The serum samples were analyzed at Lancet Laboratories, Johannesburg, and whole blood samples were analyzed at the NIOH laboratory, Johannesburg, South Africa. Both laboratories participate in a proficiency testing scheme for biological samples. For the measurement of Al, Cu, Zn, and Se in serum, samples were diluted 20-fold with a diluent [ammonia 2.5 mL; butanol 6 mL, 0.1% triton-X 50 µL, and EDTA (50 µg) in 500 mL deionized water]. Ammonia, butanol, and EDTA were purchased from Merck Chemicals (PTY) Ltd., South Africa: Triton-X, calibration standards and internal standards were purchased from Industrial Analytical, South Africa. The following internal standards were also added to the diluent, indium (In, 25 µL), germanium (Ge, 25 µL), scandium (Sc, 25 µL), rhodium (Rh, 250 µL), and iridium (Ir, 250 µL). The ICP-MS instrument was calibrated with calibration standards prepared in a diluent using a multi-element custom standard (SPECTRASCAN–SS028226). The concentrations of the standards for Se, Cu, and Zn ranged from 0.1 to 100 µg/L, and for Al, the range was 0.1 to 50 µg/L. The internal standards used were Sc, Ge, Ge, and Ir for Al, Cu, Zn, and Se, respectively. The instrument was run in general purpose mode using helium gas. Two certified reference controls, Seronorm™ Trace Elements Serum (Sero Ltd., Billingstad, Norway) were analyzed with every analytical run in intervals of 10 samples for quality assurance of all element measurements. The percentage recovery for Cu, Zn, and Se was 88–104%, and 91–114% for Al. The coefficient of variation was 8.76%, 4.56%, 4.87%, and 6.88% for Al, Cu, Zn, and Se, respectively. The limits of quantitation (LoQ) for Al, Cu, Zn, and Se were 0.15, 0.06, 0.31, and 0.17 µg/L, respectively. The collection and analyses of samples for the selected elements manganese (Mn), Hg, Pb, Cd, and As in maternal whole blood have been described previously [40,41,42,43,44]. In short, analyses for the whole blood samples were performed on an ICP-MS, following digestion in nitric acid. Two blood certified reference controls, Seronorm ™ Trace Elements (Sero Ltd., Billingstad, Norway), were used. The percentage recovery of the Seronorm controls for the metals measured in blood ranged from 83–108%. The detection limits for Mn, Hg, Pb, Cd, and As were 0.07, 0.08, 0.04, 0.03, and 0.13 µg/L, respectively. Information on covariates was obtained from interviewer-administered questionnaires and hospital medical birth records of the neonates. Demographic and socio-economic status questions such as age, race/ethnicity, marital status, educational status, employment status, housing type, and source of water supply as well as self-evaluated health status were included in the questionnaire. Questions on nutrition of the mothers before and during pregnancy were also asked; these included the consumption of meat and fish, dairy products, and fruits. Additionally, the types of fuel used for the purpose of either cooking or heating were included in the questionnaire, as were smoking habits. Birth weight (g), birth length (cm), head circumference (cm), gestational age (weeks), Apgar score at 1 and 5 min, and placenta weight (g) were obtained from the medical records of the neonates. Data analyses were carried out using STATA version 12 [39]. The Chi-square test was used to determine if the socio-demographic and economic variables were significantly different between the two coastal regions. Bivariate analyses were carried out between Se exposure and covariates using Spearman’s correlation. All the continuous variables including maternal serum Se were found to be not normally distributed and had a skewed distribution, therefore, their median and geometric mean values were calculated rather that their arithmetic means. The Wilcoxon rank-sum test was used to compare the medians of continuous variables between the two geographical populations. For the categorical variables, missing values were treated as a separate category. Multi-variable adjusted quantile regression analysis was used to explore the risk factors associated with high Se levels in maternal serum using a backward deletion approach, starting with a full model of factors significantly associated with maternal serum Se in the univariate analysis. Statistical significance was set at p < 0.05 for all models. The study protocol was approved by 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 by the Departments of Health of the different provinces. Personal data confidentiality and sample collection were carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki). Confidentiality was maintained by assigning identification numbers to all study participants.

AI Digest

Study Justification:

– Selenium (Se) is an essential trace element that plays a crucial role in fetal development and birth outcomes.
– The study aimed to assess the selenium status in pregnant women at delivery and investigate its association with birth outcomes.
– The study also examined the interaction between selenium and other essential and toxic elements.
– Additionally, the study explored the possibility of a sex-dependent response to selenium levels in utero.

Study Highlights:

– The study found a negative association between selenium levels and head circumference of neonates in the total cohort.
– Positive correlations were observed between maternal serum selenium concentrations and zinc (Zn) and copper (Cu).
– Toxic elements such as lead (Pb), arsenic (As), mercury (Hg), aluminum (Al), and cadmium (Cd) showed correlations with selenium levels.
– A sex-dependent response in utero was observed for zinc, copper, lead, mercury, and aluminum.
– The findings suggest the need for sensitive methods to measure selenium intake during pregnancy and its interactions with other micronutrients and environmental pollutants.

Recommendations for Lay Reader and Policy Maker:

– Reproductive health policy should consider the selenium status in South Africa.
– Sensitive methods should be developed to measure selenium intake during pregnancy.
– The complex interactions between selenium and other micronutrients and environmental pollutants should be further investigated.
– Health education programs should emphasize the importance of adequate selenium intake during pregnancy.
– Further research is needed to understand the sex-dependent response to selenium levels in utero.

Key Role Players:

– Researchers and scientists specializing in nutrition, reproductive health, and environmental health.
– Medical personnel and healthcare providers involved in prenatal care and delivery.
– Policy makers and government officials responsible for public health and nutrition policies.
– Non-governmental organizations (NGOs) working in the field of maternal and child health.

Cost Items for Planning Recommendations:

– Research funding for conducting further studies on selenium status and its interactions.
– Development and implementation of sensitive methods for measuring selenium intake.
– Training and capacity building for healthcare providers on the importance of selenium during pregnancy.
– Public health campaigns and educational materials on selenium and its role in fetal development.
– Monitoring and surveillance systems to track selenium levels and birth outcomes.
– Collaboration and coordination among various stakeholders involved in reproductive health and nutrition programs.

Strength of Evidence

The strength of evidence for this abstract is 7 out of 10.
The evidence in the abstract is rated 7 because it provides specific findings and correlations between selenium levels and birth outcomes, as well as interactions with other elements. However, the abstract does not mention the sample size or the methodology used to collect and analyze the data. To improve the evidence, the abstract should include information about the study design, sample size, and statistical methods used. Additionally, providing more details about the demographic characteristics of the study participants would enhance the strength of the evidence.

Abstract

In total, five study sites were chosen along coastal regions of South Africa (three study sites at the Indian Ocean coast of the KwaZulu-Natal (KZN) province, and two sites at the Atlantic Ocean coast of the Western Cape province) (Figure 1). All sites were rural, except for the urban study site of the city of Cape Town, in the Western Cape province. In the statistical analyses, we report the results for total cohort, Indian Ocean region, and Atlantic Ocean region, which differ by environmental pollution and socioeconomic status. Women admitted for delivery at the maternity sections of public hospitals in the study regions were informed of the study objectives by the medical personnel on duty and a research assistant and invited to participate in the investigation. They were also given a detailed information pamphlet about the study. In total, 650 women agreed to take part in the study, signed informed consent forms, and agreed to donate a blood sample before delivery. Furthermore, all study participants agreed to answer a socio-demographic questionnaire by interview, which included questions on the frequency of intake of various basic foods before and during pregnancy, lifestyle, and self-reported health status. All study participants agreed to allow researchers access to the hospital birth outcome data and understood that participation was voluntary and confidential and that they had the option of withdrawing from the study at any time. Study sites: Sites 1, 2, 3—Indian Ocean; sites 4 and 5—Atlantic Ocean. Figure is identical but site locations have been added, and is therefore for representative purposes only. https://www.cia.gov/library/publications/resources/cia-maps-publications/South%20Africa.html. (accessed on 6 March 2017). A sterile Venoject system and Becton, Dickinson & Company (BD, Franklin Lakes, NJ, USA) collection tubes were used for all blood collections. Each study participant donated 10 mL of venous blood into a non-additive tube to obtain serum fractions for the analyses of Se, copper (Cu), zinc (Zn), and aluminum (Al). The serum tubes were centrifuged and the serum was transferred to acid-washed polypropylene tubes using acid-washed plastic pipettes. For the analyses of toxic elements such as Hg, lead (Pb), manganese (Mn), Cd, and As in maternal whole blood, 10 mL of venous blood was collected into tubes containing ethylene diamine tetra acetic acid (EDTA). Samples of serum (post-centrifugation) and whole blood samples were stored at −20 °C and couriered in a frozen state to the National Institute for Occupational Health (NIOH) laboratory, Johannesburg, South Africa. All precautions to eliminate and prevent contamination at collection and during the preparation of samples were applied throughout. All samples were analyzed using an Agilent Inductively Coupled Plasma Mass Spectrometer (ICP-MS) 7900 with an Octopole Reaction System. The serum samples were analyzed at Lancet Laboratories, Johannesburg, and whole blood samples were analyzed at the NIOH laboratory, Johannesburg, South Africa. Both laboratories participate in a proficiency testing scheme for biological samples. For the measurement of Al, Cu, Zn, and Se in serum, samples were diluted 20-fold with a diluent [ammonia 2.5 mL; butanol 6 mL, 0.1% triton-X 50 µL, and EDTA (50 µg) in 500 mL deionized water]. Ammonia, butanol, and EDTA were purchased from Merck Chemicals (PTY) Ltd., South Africa: Triton-X, calibration standards and internal standards were purchased from Industrial Analytical, South Africa. The following internal standards were also added to the diluent, indium (In, 25 µL), germanium (Ge, 25 µL), scandium (Sc, 25 µL), rhodium (Rh, 250 µL), and iridium (Ir, 250 µL). The ICP-MS instrument was calibrated with calibration standards prepared in a diluent using a multi-element custom standard (SPECTRASCAN–SS028226). The concentrations of the standards for Se, Cu, and Zn ranged from 0.1 to 100 µg/L, and for Al, the range was 0.1 to 50 µg/L. The internal standards used were Sc, Ge, Ge, and Ir for Al, Cu, Zn, and Se, respectively. The instrument was run in general purpose mode using helium gas. Two certified reference controls, Seronorm™ Trace Elements Serum (Sero Ltd., Billingstad, Norway) were analyzed with every analytical run in intervals of 10 samples for quality assurance of all element measurements. The percentage recovery for Cu, Zn, and Se was 88–104%, and 91–114% for Al. The coefficient of variation was 8.76%, 4.56%, 4.87%, and 6.88% for Al, Cu, Zn, and Se, respectively. The limits of quantitation (LoQ) for Al, Cu, Zn, and Se were 0.15, 0.06, 0.31, and 0.17 µg/L, respectively. The collection and analyses of samples for the selected elements manganese (Mn), Hg, Pb, Cd, and As in maternal whole blood have been described previously [40,41,42,43,44]. In short, analyses for the whole blood samples were performed on an ICP-MS, following digestion in nitric acid. Two blood certified reference controls, Seronorm ™ Trace Elements (Sero Ltd., Billingstad, Norway), were used. The percentage recovery of the Seronorm controls for the metals measured in blood ranged from 83–108%. The detection limits for Mn, Hg, Pb, Cd, and As were 0.07, 0.08, 0.04, 0.03, and 0.13 µg/L, respectively. Information on covariates was obtained from interviewer-administered questionnaires and hospital medical birth records of the neonates. Demographic and socio-economic status questions such as age, race/ethnicity, marital status, educational status, employment status, housing type, and source of water supply as well as self-evaluated health status were included in the questionnaire. Questions on nutrition of the mothers before and during pregnancy were also asked; these included the consumption of meat and fish, dairy products, and fruits. Additionally, the types of fuel used for the purpose of either cooking or heating were included in the questionnaire, as were smoking habits. Birth weight (g), birth length (cm), head circumference (cm), gestational age (weeks), Apgar score at 1 and 5 min, and placenta weight (g) were obtained from the medical records of the neonates. Data analyses were carried out using STATA version 12 [39]. The Chi-square test was used to determine if the socio-demographic and economic variables were significantly different between the two coastal regions. Bivariate analyses were carried out between Se exposure and covariates using Spearman’s correlation. All the continuous variables including maternal serum Se were found to be not normally distributed and had a skewed distribution, therefore, their median and geometric mean values were calculated rather that their arithmetic means. The Wilcoxon rank-sum test was used to compare the medians of continuous variables between the two geographical populations. For the categorical variables, missing values were treated as a separate category. Multi-variable adjusted quantile regression analysis was used to explore the risk factors associated with high Se levels in maternal serum using a backward deletion approach, starting with a full model of factors significantly associated with maternal serum Se in the univariate analysis. Statistical significance was set at p < 0.05 for all models. The study protocol was approved by 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 by the Departments of Health of the different provinces. Personal data confidentiality and sample collection were carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki). Confidentiality was maintained by assigning identification numbers to all study participants.

Materials

N/A

Innovations

Based on the provided information, it is not clear what specific innovations are being discussed or how they relate to improving access to maternal health. It appears that the study is focused on assessing selenium levels and their association with birth outcomes, as well as examining the interaction of selenium with other essential and toxic elements. The study also mentions the need for sensitive methods to measure selenium intake during pregnancy and its complex interactions with other micronutrients and environmental pollutants.

To improve access to maternal health, some potential innovations could include:

1. Mobile health (mHealth) applications: Developing mobile apps that provide pregnant women with access to information, resources, and support for maternal health. These apps could include features such as appointment reminders, educational materials, nutrition tracking, and communication with healthcare providers.

2. Telemedicine services: Implementing telemedicine services that allow pregnant women in remote or underserved areas to have virtual consultations with healthcare providers. This can help overcome geographical barriers and improve access to prenatal care.

3. Community health workers: Training and deploying community health workers to provide maternal health education, support, and basic healthcare services in underserved communities. These workers can help bridge the gap between healthcare facilities and pregnant women who may face barriers to accessing care.

4. Maternal health clinics: Establishing dedicated maternal health clinics in areas with high maternal mortality rates or limited access to healthcare facilities. These clinics can provide comprehensive prenatal care, including screenings, vaccinations, and counseling services.

5. Public-private partnerships: Collaborating with private sector organizations to improve access to maternal health services. This can involve leveraging existing infrastructure, resources, and expertise to expand healthcare coverage and reach underserved populations.

It is important to note that these recommendations are general and may not directly address the specific findings or objectives of the mentioned study. Further research and analysis would be needed to determine the most appropriate innovations for improving access to maternal health based on the study’s specific findings and context.

AI Innovations Description

Based on the provided description, the recommendation to improve access to maternal health would be to develop a comprehensive maternal health program that focuses on addressing selenium deficiency in utero. This program should include the following components:

1. Education and Awareness: Provide information to pregnant women and their families about the importance of selenium for fetal development and birth outcomes. This can be done through pamphlets, workshops, and community outreach programs.

2. Screening and Testing: Implement a screening program to identify pregnant women who may be at risk of selenium deficiency. This can be done through routine blood tests during prenatal care visits.

3. Nutritional Support: Offer nutritional counseling and support to pregnant women to ensure they are consuming an adequate amount of selenium-rich foods. This can include incorporating selenium-rich foods into their diet or providing them with selenium supplements if necessary.

4. Collaboration with Healthcare Providers: Work closely with healthcare providers, including doctors, nurses, and midwives, to ensure that they are aware of the importance of selenium in maternal health and are able to provide appropriate guidance and support to pregnant women.

5. Monitoring and Evaluation: Establish a system to monitor the effectiveness of the program and evaluate its impact on maternal and fetal health outcomes. This can include tracking selenium levels in pregnant women, monitoring birth outcomes, and conducting regular assessments of the program’s implementation.

By implementing these recommendations, it is expected that access to maternal health will be improved by addressing selenium deficiency in utero and promoting better birth outcomes for pregnant women.

AI Innovations Methodology

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

1. Mobile Health (mHealth) Applications: Develop mobile applications that provide pregnant women with access to important information and resources related to maternal health. These apps could include features such as prenatal care reminders, educational content, appointment scheduling, and access to healthcare providers through telemedicine.

2. Community Health Workers: Train and deploy community health workers to provide maternal health services in rural and underserved areas. These workers can provide prenatal care, education, and support to pregnant women, as well as facilitate referrals to healthcare facilities when needed.

3. Telemedicine: Implement telemedicine services to connect pregnant women in remote areas with healthcare providers. This would allow for virtual consultations, remote monitoring of vital signs, and timely access to medical advice and guidance.

4. Transportation Solutions: Develop innovative transportation solutions to overcome geographical barriers and improve access to healthcare facilities for pregnant women. This could include mobile clinics, ambulances, or partnerships with ride-sharing services to ensure timely and safe transportation.

To simulate the impact of these recommendations on improving access to maternal health, a methodology could be developed as follows:

1. Define the indicators: Identify key indicators that measure access to maternal health, such as the number of prenatal visits, percentage of women receiving skilled birth attendance, or maternal mortality rates.

2. Collect baseline data: Gather data on the current state of access to maternal health services in the target population. This could involve surveys, interviews, or analysis of existing health records.

3. Develop a simulation model: Create a simulation model that incorporates the proposed innovations and their potential impact on the identified indicators. This model should consider factors such as population size, geographical distribution, healthcare infrastructure, and resource availability.

4. Input data and run simulations: Input the collected baseline data into the simulation model and run multiple simulations to assess the potential impact of the innovations on the selected indicators. This could involve varying parameters such as the coverage and effectiveness of the innovations.

5. Analyze results: Analyze the simulation results to determine the potential improvements in access to maternal health that could be achieved through the recommended innovations. This could include quantifying changes in the selected indicators and identifying any potential challenges or limitations.

6. Refine and validate the model: Continuously refine and validate the simulation model based on feedback from experts, stakeholders, and real-world data. This iterative process will help improve the accuracy and reliability of the simulations.

7. Use the findings for decision-making: Utilize the findings from the simulations to inform decision-making and prioritize the implementation of the recommended innovations. This could involve resource allocation, policy changes, or targeted interventions to improve access to maternal health services.

Authors & Co-Authors

Statistics:

Authors: 4

Identifiers:

DOI: 10.3390/ijerph18168344

ISSN: 16617827

Research Areas:

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

Study Countries:

South Africa

Study Design:

Cohort Study

Study Approach:

Quantitative

Participants Gender:

Female