Pre-and post-natal macronutrient supplementation for HIV-positive women in Tanzania: Effects on infant birth weight and HIV transmission

PLoS ONE, Volume 13, No. 10, Year 2018

Interpretation

Objective To determine if a protein-calorie supplement (PCS) plus a micronutrient supplement (MNS) improves outcomes for HIV-infected lactating women and their infants. Design Randomized, controlled trial. Setting Dar es Salaam, Tanzania Subjects, participants Pregnant HIV-infected women enrolled in PMTCT programs who intended to breastfeed for 6 months. Intervention Randomization 1:1 to administration of a PCS plus MNS versus MNS alone among 96 eligible women beginning in the third trimester and continuing for 6 months of breast-feeding. Main outcome measure(s) Primary: infant weight at 3 months. Secondary: maternal BMI at 6 months. Results PCS resulted in significant increases in daily energy intake compared to MNS at all time points (range of differences: +388-719 Kcal); and increases in daily protein intake (range of differences: +22-33 gm). Infant birth weight (excluding twins) was higher in the PCS than MNS groups: 3.30 kg vs 3.04 kg (p = 0.04). Infant weight at 3 months did not differ between PCS and MNS groups: 5.63 kg vs 5.99 kg (p = 0.07). Maternal BMI at 6 months did not differ between PCS and MNS groups: 24.3 vs 23.8 kg/m2 (p = 0.68). HIV transmission occurred in 0 infants in the PCS group vs 4 in the MNS group (p = 0.03). Conclusions In comparison to MNS the PCS + MNS intervention was well tolerated, increased maternal energy and protein intake, and increased infant birth weight, but not weight at 3 months or maternal BMI at 6 months. Reduced infant HIV transmission in the PCS + MNS group was observed. Trial registration Clinical Trials.Gov NCT01461863. Copyright: The study was designed as a randomized controlled trial to determine if a protein calorie macronutrient supplement (PCS) plus micronutrient supplement (MNS) improved health outcomes in HIV-infected lactating women and their infants compared to MNS alone. HIV-infected women ≥18 years old in their last trimester of pregnancy were screened from April 2011 to July 2012 at 5 antenatal clinics (3 district hospitals, 2 local clinics) in Dar es Salaam, Tanzania during their last trimester. Eligibility required that the woman be free of acute illness, have a BMI ≥18.5 kg/m2 and intend to exclusively breastfeed her infant for at least 3 months. All women were required to be enrolled in anti-retroviral therapy (ART) programs for Prevention of Mother to Child Transmission of HIV infection (PMCT). After informed consent, subjects in the third trimester were interviewed to obtain socio-demographic information including age, residence, financial and employment status of both the patient and her partner, highest level of education, income spent specifically on food, and number and ages of persons living in the same household. Phlebotomy was performed for CD4 count and albumin and all subjects had anthropometric evaluations, twenty-four hour dietary recall and food insecurity evaluations. Weight (kg) and, height (recumbent length in infants) were determined following standard protocols and using calibrated instruments. Skin fold thicknesses (mm) at five different areas including the triceps, subscapular, suprailiac, abdomen, and thigh as well as circumferences (cm) around the mid-upper arm, waist, hip, and thigh were determined by one of 3 three trained observers using calibrated Lange skinfold calipers and a Gulick II, non-stretch, pliable tape measure [14]. Trained research nutritionists or study nurses evaluated dietary intake using a multiple pass 24-hour dietary recall to list all beverages and foods consumed in the previous day [15]. Multiple passes by the interviewer probed for food preparation and missed food items; standardized food models were used to determine portion size. Energy and protein intakes were then calculated using the Tanzania Food Composition tables [16]. Nutritional education and counseling based on distinct World Health Organization (WHO) and Tanzanian Ministry of Health National Guidelines for HIV-positive women, was provided [17]. All subjects were administered the Household Food Insecurity Access Scale (HFIAS), which was adapted from the Food and Nutritional Technical Assistance II Project (FANTA-2) to determine availability and accessibility of food in each woman’s household [18]. An adapted questionnaire contained a total of nine yes or no questions followed by a “frequency-of-occurrence” question. Some questions inquired about the subject’s perception of food vulnerability while other questions addressed the subject’s behavioral responses due to food insecurity. Based on the answers given by the client, a score was assigned to each woman ranging from 0 (no insecurity) to 27 (maximum insecurity). Phlebotomy was performed to confirm HIV infection and determine the CD4 count. Subjects were required to have two positive rapid HIV tests: Determine HIV-1/2 Ag/Ab (Alere, Chiba, Japan) and Uni Gold HIV-1/2 (Trinity Biotech, Bray, Ireland). Women who tested positive and were unaware of their current HIV status were provided ELISA results, CD4 results, appropriate counseling, referred to a Ministry of Health Care and Treatment Center (CTC) if not already under care and then entered in the study. Subjects with a discordant ELISA result (one positive, one negative) were not eligible and referred to a CTC for further testing. In the pilot study the daily dietary intakes of HIV-infected lactating subjects were compared to recommendations of the World Health Organization (WHO) to achieve a mean energy target of 2854 Kcal (which includes an additional 10% increase in energy for HIV infection) and protein target of 86 gm (based on 12% of calories) [13]. Subjects were found to have a median daily dietary energy deficit 2 weeks after delivery of 517 Kcal and a mean daily dietary protein deficit of 29 gm; mean deficits at 6 weeks were 686 Kcal and 36 gm [19–23]. Subjects in the pilot study then participated in focus groups to test the palatability and acceptability several potential protein-calorie supplements (PCS). The supplement that was chosen for the present study was a porridge (Dar-uji) manufactured from locally available ingredients including flour (maize, soybeans, sorghum and millet), full cream dried milk, and sugar (Jamahedo Health Foods, Arusha, Tanzania). The PCS was provided in daily packets containing 1062 Kcal and 42 gm protein, amounts that would cover the 75th percentile of deficits observed in the pilot study. Thirty packets of PCS were given to participants every four weeks. Each 250 mg packet was to be mixed with boiling water and consumed over the course of one day. The micronutrient supplement (MNS) was the standard combination of vitamins and minerals provide to patients with HIV infection by the Ministry of Health of Tanzania (Tishcon Corporation, Salsbury, MD). MNS consisted of 1.4mg thiamine, 1.4 mg riboflavin, 18 mg niacin, 1.9 mg vitamin B-6, 2.6 mg vitamin B-12, 70 ug vitamin C, 10 mg vitamin E and 0.4 mg folic acid [24]. All mothers also received 60 mg ferrous sulfate orally (PO) once daily and 1 mg folic acid PO once daily during pregnancy A randomization list was generated by the a study statistician and provided to the study team. Consecutive eligible subjects were randomized 1:1 in block sizes of 4 and 6 to receive the intervention (PCS plus MNS) or control (MNS alone). Subjects were provided with a four week supply. In addition subjects in the PCS intervention group were also given a supply of PCS packets so that 280 Kcal/day was provided for every child less than age 7 years living in the household with the subject. All mothers were seen monthly after enrollment in the third trimester at the study clinic, then at home 2–4 weeks after birth, and again at the study clinic monthly for 6 months after infant birth and again at 9 and 15 months after infant birth. At each visit thru 6 months subjects were provided with the supplements, had anthropometric evaluation, and a 24-hour dietary recall. ART use and clinical history were recorded. Laboratory tests including CD4 count were obtained and breast milk samples collected 2–4 weeks after delivery and again 3 months after delivery. Breast milk analysis will be the subject of a separate report. All infants were examined at the initial home visit and then seen monthly for 6 months, again at 9 months and at 15 months for a medical history and measurement of weight and length. ART use and clinical history were recorded. At 15 months phlebotomy was performed per protocol to perform a single rapid HIV test, Uni Gold HIV-1/2 (Trinity Biotech, Bray, Ireland). Results of HIV testing that had been performed outside the study at government clinics were recorded, typically on infants who had been ill or died. or on infants who had been found to be HIV positive per protocol at 15 months. This testing included results of dried blood spot (DBS) HIV PCR testing at Tanzania Ministry of Health (MOH) HIV clinics where such testing is recommended at 2–3 months for all infants born to HIV-positive mothers. Hospital records were requested on infants who died as inpatients during the study. The study was approved by the Institutional Review Board at Geisel School of Medicine and the Research Ethics Committee of the Muhimbili University of Health and Allied Sciences (MUHAS). The primary endpoint for the trial was infant weight at 3 months. A sample size of 96 subjects, 48 subjects in each group, was calculated based on type 1 and 2 error rates of 5% and 20% respectively, a minimally clinically effect size of 0.5 kg, assuming that the standard deviation of weight at 2 months among HIV infected infants born on the African continent is approximately 0.7 kg (IQR = 4.0 to 4.9 kg. [25]. The primary endpoint, infant weight at 3 months, was compared between the two study arms using a two-sample t-test. The secondary endpoint was maternal BMI 6 months after delivery. Maternal BMI (as well as weight and mid upper arm circumference) at 6 months post-delivery was compared between the two study arms using a linear model that controlled for maternal BMI at baseline. Laboratory parameters including maternal CD4 were compared in the same manner. Dietary intakes were compared between the two arms at specific time points using t-tests. Infant mortality was compared between the two study arms using Fisher’s exact test. The incidence of infant HIV infection as determined by DBS at 2 months or HIV ELISA at 15 months was compared between the study arms using Fisher’s exact test and also a log rank test that censored follow-up at 18 months or death. The main analyses included all mothers and infants. As a sensitivity analysis we repeated analyses excluding mothers of twins, and twins.

AI Digest

Study Justification:

The study aimed to investigate the effects of a protein-calorie supplement (PCS) plus a micronutrient supplement (MNS) on HIV-infected lactating women and their infants in Tanzania. The justification for the study was to determine if this supplementation would improve outcomes for these women and their infants, specifically in terms of infant birth weight and HIV transmission.

Highlights:

– The study was a randomized controlled trial conducted in Dar es Salaam, Tanzania.
– Pregnant HIV-infected women enrolled in Prevention of Mother to Child Transmission of HIV infection (PMTCT) programs were included in the study.
– The intervention involved randomizing women to receive either a PCS plus MNS or MNS alone during the third trimester of pregnancy and continuing for 6 months of breastfeeding.
– The primary outcome measure was infant weight at 3 months, and secondary outcomes included maternal BMI at 6 months.
– The results showed that the PCS group had significant increases in daily energy and protein intake compared to the MNS group.
– Infant birth weight was higher in the PCS group compared to the MNS group.
– There was no significant difference in infant weight at 3 months or maternal BMI at 6 months between the two groups.
– HIV transmission occurred in 0 infants in the PCS group compared to 4 infants in the MNS group.

Recommendations:

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

1. Implement the use of a protein-calorie supplement (PCS) plus a micronutrient supplement (MNS) for HIV-infected lactating women in Tanzania.
2. Promote the use of PCS and MNS during pregnancy and breastfeeding to improve infant birth weight and reduce HIV transmission.
3. Provide nutritional education and counseling based on World Health Organization (WHO) and Tanzanian Ministry of Health guidelines for HIV-positive women.

Key Role Players:

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

1. Healthcare providers: Including doctors, nurses, and nutritionists who can provide guidance and support to HIV-infected lactating women.
2. Government agencies: Such as the Tanzanian Ministry of Health, responsible for implementing policies and programs related to HIV prevention and maternal health.
3. Non-governmental organizations (NGOs): Organizations working in the field of HIV/AIDS and maternal health, who can provide resources and support for implementing the recommendations.

Cost Items for Planning Recommendations:

While the actual cost may vary, the following cost items should be considered in planning the recommendations:

1. Procurement of protein-calorie supplements (PCS) and micronutrient supplements (MNS).
2. Training and capacity building for healthcare providers on the use of PCS and MNS.
3. Nutritional education and counseling materials.
4. Monitoring and evaluation of the program’s effectiveness.
5. Collaboration and coordination efforts between government agencies and NGOs.
Please note that the provided information is a summary of the study and its findings. For more detailed information, please refer to the publication in PLoS ONE, Volume 13, No. 10, Year 2018.

Strength of Evidence

The strength of evidence for this abstract is 7 out of 10.
The evidence in the abstract is moderately strong. The study design is a randomized controlled trial, which is a robust method. The sample size of 96 subjects is adequate. The study measured various outcomes including infant birth weight, infant weight at 3 months, maternal BMI at 6 months, and HIV transmission. The results showed significant increases in daily energy and protein intake with the protein-calorie supplement (PCS) plus micronutrient supplement (MNS) compared to MNS alone. Infant birth weight was higher in the PCS group, and there was a reduced incidence of infant HIV transmission in the PCS group. However, infant weight at 3 months and maternal BMI at 6 months did not differ significantly between the groups. To improve the evidence, the study could consider increasing the sample size for more statistical power and conducting longer-term follow-up to assess additional outcomes. Additionally, the abstract could provide more details on the methodology and statistical analysis used.

Abstract

The study was designed as a randomized controlled trial to determine if a protein calorie macronutrient supplement (PCS) plus micronutrient supplement (MNS) improved health outcomes in HIV-infected lactating women and their infants compared to MNS alone. HIV-infected women ≥18 years old in their last trimester of pregnancy were screened from April 2011 to July 2012 at 5 antenatal clinics (3 district hospitals, 2 local clinics) in Dar es Salaam, Tanzania during their last trimester. Eligibility required that the woman be free of acute illness, have a BMI ≥18.5 kg/m2 and intend to exclusively breastfeed her infant for at least 3 months. All women were required to be enrolled in anti-retroviral therapy (ART) programs for Prevention of Mother to Child Transmission of HIV infection (PMCT). After informed consent, subjects in the third trimester were interviewed to obtain socio-demographic information including age, residence, financial and employment status of both the patient and her partner, highest level of education, income spent specifically on food, and number and ages of persons living in the same household. Phlebotomy was performed for CD4 count and albumin and all subjects had anthropometric evaluations, twenty-four hour dietary recall and food insecurity evaluations. Weight (kg) and, height (recumbent length in infants) were determined following standard protocols and using calibrated instruments. Skin fold thicknesses (mm) at five different areas including the triceps, subscapular, suprailiac, abdomen, and thigh as well as circumferences (cm) around the mid-upper arm, waist, hip, and thigh were determined by one of 3 three trained observers using calibrated Lange skinfold calipers and a Gulick II, non-stretch, pliable tape measure [14]. Trained research nutritionists or study nurses evaluated dietary intake using a multiple pass 24-hour dietary recall to list all beverages and foods consumed in the previous day [15]. Multiple passes by the interviewer probed for food preparation and missed food items; standardized food models were used to determine portion size. Energy and protein intakes were then calculated using the Tanzania Food Composition tables [16]. Nutritional education and counseling based on distinct World Health Organization (WHO) and Tanzanian Ministry of Health National Guidelines for HIV-positive women, was provided [17]. All subjects were administered the Household Food Insecurity Access Scale (HFIAS), which was adapted from the Food and Nutritional Technical Assistance II Project (FANTA-2) to determine availability and accessibility of food in each woman’s household [18]. An adapted questionnaire contained a total of nine yes or no questions followed by a “frequency-of-occurrence” question. Some questions inquired about the subject’s perception of food vulnerability while other questions addressed the subject’s behavioral responses due to food insecurity. Based on the answers given by the client, a score was assigned to each woman ranging from 0 (no insecurity) to 27 (maximum insecurity). Phlebotomy was performed to confirm HIV infection and determine the CD4 count. Subjects were required to have two positive rapid HIV tests: Determine HIV-1/2 Ag/Ab (Alere, Chiba, Japan) and Uni Gold HIV-1/2 (Trinity Biotech, Bray, Ireland). Women who tested positive and were unaware of their current HIV status were provided ELISA results, CD4 results, appropriate counseling, referred to a Ministry of Health Care and Treatment Center (CTC) if not already under care and then entered in the study. Subjects with a discordant ELISA result (one positive, one negative) were not eligible and referred to a CTC for further testing. In the pilot study the daily dietary intakes of HIV-infected lactating subjects were compared to recommendations of the World Health Organization (WHO) to achieve a mean energy target of 2854 Kcal (which includes an additional 10% increase in energy for HIV infection) and protein target of 86 gm (based on 12% of calories) [13]. Subjects were found to have a median daily dietary energy deficit 2 weeks after delivery of 517 Kcal and a mean daily dietary protein deficit of 29 gm; mean deficits at 6 weeks were 686 Kcal and 36 gm [19–23]. Subjects in the pilot study then participated in focus groups to test the palatability and acceptability several potential protein-calorie supplements (PCS). The supplement that was chosen for the present study was a porridge (Dar-uji) manufactured from locally available ingredients including flour (maize, soybeans, sorghum and millet), full cream dried milk, and sugar (Jamahedo Health Foods, Arusha, Tanzania). The PCS was provided in daily packets containing 1062 Kcal and 42 gm protein, amounts that would cover the 75th percentile of deficits observed in the pilot study. Thirty packets of PCS were given to participants every four weeks. Each 250 mg packet was to be mixed with boiling water and consumed over the course of one day. The micronutrient supplement (MNS) was the standard combination of vitamins and minerals provide to patients with HIV infection by the Ministry of Health of Tanzania (Tishcon Corporation, Salsbury, MD). MNS consisted of 1.4mg thiamine, 1.4 mg riboflavin, 18 mg niacin, 1.9 mg vitamin B-6, 2.6 mg vitamin B-12, 70 ug vitamin C, 10 mg vitamin E and 0.4 mg folic acid [24]. All mothers also received 60 mg ferrous sulfate orally (PO) once daily and 1 mg folic acid PO once daily during pregnancy A randomization list was generated by the a study statistician and provided to the study team. Consecutive eligible subjects were randomized 1:1 in block sizes of 4 and 6 to receive the intervention (PCS plus MNS) or control (MNS alone). Subjects were provided with a four week supply. In addition subjects in the PCS intervention group were also given a supply of PCS packets so that 280 Kcal/day was provided for every child less than age 7 years living in the household with the subject. All mothers were seen monthly after enrollment in the third trimester at the study clinic, then at home 2–4 weeks after birth, and again at the study clinic monthly for 6 months after infant birth and again at 9 and 15 months after infant birth. At each visit thru 6 months subjects were provided with the supplements, had anthropometric evaluation, and a 24-hour dietary recall. ART use and clinical history were recorded. Laboratory tests including CD4 count were obtained and breast milk samples collected 2–4 weeks after delivery and again 3 months after delivery. Breast milk analysis will be the subject of a separate report. All infants were examined at the initial home visit and then seen monthly for 6 months, again at 9 months and at 15 months for a medical history and measurement of weight and length. ART use and clinical history were recorded. At 15 months phlebotomy was performed per protocol to perform a single rapid HIV test, Uni Gold HIV-1/2 (Trinity Biotech, Bray, Ireland). Results of HIV testing that had been performed outside the study at government clinics were recorded, typically on infants who had been ill or died. or on infants who had been found to be HIV positive per protocol at 15 months. This testing included results of dried blood spot (DBS) HIV PCR testing at Tanzania Ministry of Health (MOH) HIV clinics where such testing is recommended at 2–3 months for all infants born to HIV-positive mothers. Hospital records were requested on infants who died as inpatients during the study. The study was approved by the Institutional Review Board at Geisel School of Medicine and the Research Ethics Committee of the Muhimbili University of Health and Allied Sciences (MUHAS). The primary endpoint for the trial was infant weight at 3 months. A sample size of 96 subjects, 48 subjects in each group, was calculated based on type 1 and 2 error rates of 5% and 20% respectively, a minimally clinically effect size of 0.5 kg, assuming that the standard deviation of weight at 2 months among HIV infected infants born on the African continent is approximately 0.7 kg (IQR = 4.0 to 4.9 kg. [25]. The primary endpoint, infant weight at 3 months, was compared between the two study arms using a two-sample t-test. The secondary endpoint was maternal BMI 6 months after delivery. Maternal BMI (as well as weight and mid upper arm circumference) at 6 months post-delivery was compared between the two study arms using a linear model that controlled for maternal BMI at baseline. Laboratory parameters including maternal CD4 were compared in the same manner. Dietary intakes were compared between the two arms at specific time points using t-tests. Infant mortality was compared between the two study arms using Fisher’s exact test. The incidence of infant HIV infection as determined by DBS at 2 months or HIV ELISA at 15 months was compared between the study arms using Fisher’s exact test and also a log rank test that censored follow-up at 18 months or death. The main analyses included all mothers and infants. As a sensitivity analysis we repeated analyses excluding mothers of twins, and twins.

Materials

Innovations

The innovation in this study is the use of a protein-calorie supplement (PCS) plus a micronutrient supplement (MNS) to improve outcomes for HIV-infected lactating women and their infants. The study aimed to determine if this supplementation improved infant birth weight and reduced HIV transmission. The results showed that the PCS + MNS intervention increased maternal energy and protein intake, increased infant birth weight, and reduced infant HIV transmission compared to the MNS alone group.

AI Innovations Description

The recommendation from the study is to provide a protein-calorie supplement (PCS) along with a micronutrient supplement (MNS) to HIV-positive lactating women in Tanzania. This intervention aims to improve outcomes for both the mothers and their infants. The study found that the PCS + MNS intervention resulted in increased daily energy and protein intake for the mothers, as well as higher infant birth weights compared to the group receiving only MNS. Additionally, the incidence of HIV transmission from mother to infant was lower in the PCS + MNS group. This recommendation suggests that providing macronutrient supplementation to HIV-positive women during pregnancy and breastfeeding can improve maternal and infant health outcomes, including birth weight and HIV transmission rates.

AI Innovations Methodology

Based on the provided study, the innovation recommendation to improve access to maternal health could be the implementation of pre- and post-natal macronutrient supplementation for HIV-positive women in Tanzania. This intervention involves providing a protein-calorie supplement (PCS) along with a micronutrient supplement (MNS) to HIV-infected lactating women during their last trimester of pregnancy and continuing for 6 months of breastfeeding.

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

1. Study Design: Conduct a randomized controlled trial similar to the original study design. Randomly assign eligible pregnant HIV-positive women to two groups: one receiving the PCS plus MNS intervention and the other receiving MNS alone.

2. Sample Selection: Identify and recruit pregnant HIV-positive women from antenatal clinics in Dar es Salaam, Tanzania, who meet the eligibility criteria for the study.

3. Data Collection: Collect socio-demographic information, including age, residence, financial and employment status, education level, income spent on food, and household composition. Perform phlebotomy for CD4 count and albumin, and conduct anthropometric evaluations, dietary recall, and food insecurity evaluations.

4. Intervention: Provide the PCS plus MNS intervention to the intervention group, while the control group receives MNS alone. Ensure adherence to the intervention by providing regular supplies of the PCS and MNS.

5. Outcome Measures: Measure primary outcomes such as infant weight at 3 months and secondary outcomes such as maternal BMI at 6 months. Collect data on other relevant variables, including HIV transmission rates and nutritional intake.

6. Data Analysis: Analyze the collected data using appropriate statistical methods. Compare the outcomes between the intervention and control groups using t-tests, linear models, Fisher’s exact test, and log-rank tests, as described in the original study.

7. Interpretation of Results: Evaluate the impact of the PCS plus MNS intervention on improving access to maternal health by assessing the differences in outcomes between the intervention and control groups. Consider the statistical significance and clinical relevance of the findings.

8. Recommendations: Based on the results, make recommendations for the implementation of pre- and post-natal macronutrient supplementation for HIV-positive women in Tanzania to improve access to maternal health. Consider factors such as feasibility, scalability, and potential benefits and risks.

9. Further Research: Identify any limitations or gaps in the study and suggest areas for further research to enhance the understanding of the intervention’s impact on improving access to maternal health.

By following this methodology, researchers can simulate the impact of the recommended innovation and gather evidence to support its implementation for improving access to maternal health in Tanzania.

Author

Dima Health

Statistics:

Citations: 2

Identifiers:

DOI: 10.1371/journal.pone.0201038

Research Areas:

Community Interventions, Disparities, Environmental, Food Security, Health System and Policy, Infectious Diseases, Maternal Access, Maternal and Child Health, Quality of Care, Sexual and Reproductive Health, Social Determinants

Study Countries:

Tanzania

Study Design:

Cohort Study, randomised-control-trial

Study Approach:

Quantitative

Participants Gender:

Female