The prevalence of histologic acute chorioamnionitis among HIV infected pregnant women in Uganda and its association with adverse birth outcomes

PLoS ONE, Volume 14, No. 4, Year 2019

Interpretation

Background Preterm birth (PTB) is a leading cause of neonatal mortality and longer-term morbidity. Acute chorioamnionitis (ACA) is a common cause of PTB, however, there are limited data on the prevalence of ACA and its association with PTB in resource limited settings. Methods Data and samples came from a clinical trial evaluating novel strategies for the prevention of malaria in HIV infected pregnant women in Uganda. Women were enrolled between 12-28 weeks of gestation and followed through delivery. For each placenta delivered, three placental tissue types (membrane roll, umbilical cord and chorionic plate/villous parenchyma) were collected. Slides were assessed for diagnosis of maternal and fetal ACA by microscopic evaluation of neutrophilic infiltration using a standardized grading scale. The primary outcomes were PTB (<37 weeks), low birth weight (LBW, <2500 grams), and small-for-gestational age (SGA, birth weight <10th percentile for age). Univariate and multivariate logistic regression were used to estimate associations between 1) maternal characteristics (age, education, wealth, gravidity, gestational age at enrollment, placental malaria, anti-malarial prophylaxis treatment regimen, HIV disease parameters) and ACA, and 2) associations between ACA and adverse birth outcomes. Findings A total of 193 placentas were included in the analysis. The prevalence of maternal and fetal ACA was 44.5% and 28.0%, respectively. HIV infected women between 28-43 years of age had a higher risk of maternal ACA compared to those between 17-21 years of age (50.9% vs. 19.1%; aOR = 4.00 (1.10-14.5), p = 0.04) and the diagnosis of severe maternal ACA was associated with a significantly higher risk of PTB (28.6% vs. 6.0%; aOR = 6.04 (1.87- 19.5), p = 0.003), LBW (33.3% vs. 9.4%; aOR = 4.86 (1.65-14.3); p = 0.004), and SGA (28.6% vs. 10.1%; aOR = 3.70 (1.20-11.4), p = 0.02). No maternal characteristics were significantly associated with fetal ACA and the diagnosis of fetal ACA was not associated with adverse birth outcomes. Conclusions Histological evidence of severe maternal ACA was associated with an increased risk of PTB, LBW, and SGA in HIV infected, pregnant Ugandan women. Clinical data and biological samples for this study came from a double-blinded randomized clinical trial (Registration number {"type":"clinical-trial","attrs":{"text":"NCT02282293","term_id":"NCT02282293"}}NCT02282293) evaluating intermittent preventive therapy for malaria in pregnancy (IPTp) among HIV infected women in Tororo, Uganda [20]. Two hundred HIV infected pregnant women at least 16 years of age were enrolled at 12–28 weeks gestational age, between December 2014 to November 2015, and were randomized to daily trimethoprim-sulfamethoxazole (TMP-SMX) plus monthly dihydroartemisinin-piperaquine (DP) or daily TMP-SMX alone [20]. The study physician estimated gestational age using last menstrual period and fetal measurements obtained by a standardized abdominal ultrasound exam. All women were provided with combination antiretroviral therapy (ART) consisting of Efavirenz (EFV)/tenofovir/lamivudine. Women received routine HIV care per the Uganda Ministry of Health guidelines, and HIV-1 RNA monitoring was additionally performed. Participants were prospectively followed until delivery, at which point the placenta was harvested and prepared (as described below) for microscopic examination and diagnosis of ACA. At enrollment, a long-lasting insecticide treated net was provided to every participant and a detailed history including a household questionnaire and physical assessment/examination was obtained. Study participants were closely monitored throughout pregnancy by monthly assessments and collection of blood samples, and all their health care needs were provided by a dedicated study clinic open seven days a week. Participants were encouraged to deliver at the hospital. However, in the event of a home or other health facility delivery, participants were visited by the study staff at the time of delivery or as soon as possible afterwards. Upon delivery, a comprehensive assessment of birth outcomes was made, including neonatal evaluation for congenital anomalies, measurement of birth weight and gestational age. All placental sampling was done within 30 minutes of delivery. Placental specimens were fixed in 10% Neutral Buffered Formalin for 24 hours, and stored at room temperature in 70% ethanol prior to tissue processing. The following placental tissues were collected: placental membranes (“membrane roll”), umbilical cord (two cross-sectional slices, one proximal and one distal to where the cord inserts into the placental disc), chorionic plate with villous parenchyma, and basal plate with villous parenchyma. The basal plate/villous parenchyma section was used for diagnosis of PM in our separately reported studies [16, 20, 21], while the other three sections (membrane roll, umbilical cord, chorionic plate/villous parenchyma) were used as described below for the diagnosis of ACA in the study reported here. For microscopic diagnosis of ACA, three placental specimens were utilized: membrane roll, umbilical cord, and chorionic plate/villous parenchyma. In the Tororo, Uganda laboratory, specimens were dehydrated through a series of ethanol washes, cleared in xylene and embedded in paraffin wax blocks. A 3 μm thick section from each tissue block was obtained using a rotary microtome and sections mounted onto glass slides via a floatation water bath. Slides were baked in a hot air oven at 60°C for 30 minutes, de-paraffinized in xylene, dehydrated through a series of ethanol washes, stained with Hematoxylin and Eosin (H&E), and mounted with organic mounting media. Diagnosis of ACA was made by standard light microscopic examination (Nikon Eclipse Ci-L microscope with DS-Ri2 color camera) of the three placental biopsy slides (membrane roll, umbilical cord, and chorionic plate/villous parenchyma) (Fig 1). Diagnosis of a maternal acute inflammatory response to infection (“maternal ACA”) was indicated by detection of neutrophils within the chorioamnion layers of the membrane roll and/or the chorionic plate. Diagnosis of a fetal acute inflammatory response to infection (“fetal ACA”) was indicated by detection of neutrophils with or without eosinophils within the vascular smooth muscle of the umbilical cord vessels and/or the chorionic plate vasculature [9]. Diagnosis was rendered in blinded fashion by a placental pathologist (G.R.) and noted on a standardized case record form. (A&B) Normal umbilical cord. *indicates lumen of umbilical vessels. (C) Umbilical vein with heavy neutrophilic infiltrate (arrows point to aggregates of neutrophils) and early degeneration of smooth muscle cells diagnostic of severe fetal ACA. (D) Normal chorionic plate/villous parenchyma. Arrow indicates the chorionic plate, and * indicates lumen of a fetal chorionic plate vessel. (E) Chorionic plate with heavy neutrophilic infiltrate in the walls of a fetal chorionic plate vessel (severe fetal ACA) and neutrophils in the subchorionic fibrin layer (maternal ACA). Arrows point to aggregates of neutrophils. (F&G) Normal membrane roll. (H) Membrane roll with neutrophilic microabscess diagnostic of severe maternal ACA (arrows point to neutrophils). In G and H, {-bracket indicates amnion, [-bracket indicates chorion, and arrow indicates decidua parietalis. Scale bars are 1 mm (panels A, D, F) and 200 μM (panels B, C, E, G, H). Grading of maternal ACA and fetal ACA was assigned using the standardized diagnostic framework of the Perinatal Section of the Society for Pediatric Pathologists [9]. Grade was recorded on the case record form as either: no evidence of ACA, mild (scattered mostly single, isolated neutrophils), moderate (small clusters of neutrophils) and severe (presence of neutrophilic microabscesses). Specifically, severe maternal ACA was defined as the presence of microabscesses measuring greater than or equal to 10 x 20 neutrophils in extent, and present within at least three foci, or with neutrophils present as a contiguous band. Severe fetal ACA was defined as the presence of near confluent intramural neutrophils with attenuation/degeneration of vascular smooth muscle cells. The maternal characteristics examined included: maternal age and gestational age at enrollment, education, household wealth index, and gravity. Maternal characteristics pertaining to malaria included: IPTp regimen (either TMP-SMX plus DP or TMP-SMX alone), and evidence of PM defined by histopathology. Additionally, the following maternal characteristic pertaining to HIV infection were assessed: duration since HIV diagnosed, duration since ART was begun, WHO HIV stage at enrollment, CD4 T-cell count at delivery, and viral load at delivery. None of the women enrolled were WHO HIV stage 4 (defined as AIDS). ACA was categorized as maternal ACA (the presence of maternal acute inflammation, defined above) and fetal ACA (the presence of fetal acute inflammation, defined above). Maternal and fetal ACA were each categorized into a grading scale: none/mild, moderate and severe (defined above). The birth outcomes assessed were PTB (delivery at <37 weeks), LBW (birth weight <2500 grams, and SGA (birth weight <10th percentile for age). Data were coded, double entered into a Microsoft access database and analyzed using Stata 14 (Stata Corp, College Station TX). Participants’ baseline maternal characteristics were expressed as means ± SD for continuous variables, while categorical variables were expressed as proportions. Univariate and multivariate logistic regression were used to 1) measure associations between maternal characteristics and maternal and fetal ACA, and 2) measure associations between maternal and fetal ACA and the risk of adverse birth outcomes. P values < 0.05 were considered statistically significant. Measures of association in both univariate and multivariate models were expressed as odds ratios (OR) or adjusted odds ratios (aOR) and respective 95% confidence intervals (CI). Gravidity was not included in the final multivariate model due to correlation with maternal age. All study participants provided informed written consent. Ethical approval was obtained from the Uganda National Council of Science and Technology (UNCST #HS 1708), Makerere University School of Medicine Research and Ethics Committee, the Makerere University School of Biomedical Sciences Research and Ethics Committee (#SBS-REC 159), and the University of California, San Francisco, Committee on Human Research (CHR #14–13900).

AI Digest

Study Justification:

This study aimed to investigate the prevalence of histologic acute chorioamnionitis (ACA) among HIV-infected pregnant women in Uganda and its association with adverse birth outcomes. The justification for this study is based on the importance of understanding the factors contributing to preterm birth (PTB) and its associated morbidity and mortality, as well as the limited data available on ACA in resource-limited settings.

Highlights:

– The study included 193 placentas from HIV-infected pregnant women in Uganda.
– The prevalence of maternal ACA was found to be 44.5%, while fetal ACA was 28.0%.
– HIV-infected women between 28-43 years of age had a higher risk of maternal ACA compared to those between 17-21 years of age.
– Severe maternal ACA was associated with a significantly higher risk of PTB, low birth weight (LBW), and small-for-gestational age (SGA) infants.
– No maternal characteristics were significantly associated with fetal ACA, and fetal ACA was not associated with adverse birth outcomes.

Recommendations:

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

1. Increased focus on preventing and managing ACA in HIV-infected pregnant women, particularly in older age groups.
2. Implementation of strategies to reduce the risk of PTB, LBW, and SGA infants in HIV-infected pregnant women with severe maternal ACA.
3. Further research to explore additional factors contributing to ACA and adverse birth outcomes in this population.

Key Role Players:

To address the recommendations, the following key role players may be needed:

1. Healthcare providers specializing in obstetrics and gynecology, infectious diseases, and maternal-fetal medicine.
2. Public health officials and policymakers involved in maternal and child health programs.
3. Researchers and scientists specializing in HIV, chorioamnionitis, and birth outcomes.
4. Community health workers and educators to disseminate information and provide support to HIV-infected pregnant women.

Cost Items for Planning Recommendations:

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

1. Research funding for further studies on ACA and adverse birth outcomes in HIV-infected pregnant women.
2. Training and capacity-building programs for healthcare providers to improve knowledge and skills in managing ACA and preventing adverse birth outcomes.
3. Development and implementation of educational materials and campaigns targeting HIV-infected pregnant women to raise awareness about the risks of ACA and the importance of early detection and management.
4. Provision of necessary medical equipment and supplies for diagnosing and treating ACA.
5. Monitoring and evaluation activities to assess the impact of interventions and track progress in reducing adverse birth outcomes in this population.
Please note that the provided information is based on the description and findings of the study mentioned in the given text.

Strength of Evidence

The strength of evidence for this abstract is 8 out of 10.
The evidence in the abstract is strong, as it is based on a clinical trial with a large sample size. The study design includes multivariate logistic regression analysis to estimate associations between variables. However, to improve the evidence, it would be helpful to provide more details on the methodology, such as the specific criteria used for diagnosing ACA and the statistical methods used for analysis.

Abstract

Clinical data and biological samples for this study came from a double-blinded randomized clinical trial (Registration number {"type":"clinical-trial","attrs":{"text":"NCT02282293","term_id":"NCT02282293"}}NCT02282293) evaluating intermittent preventive therapy for malaria in pregnancy (IPTp) among HIV infected women in Tororo, Uganda [20]. Two hundred HIV infected pregnant women at least 16 years of age were enrolled at 12–28 weeks gestational age, between December 2014 to November 2015, and were randomized to daily trimethoprim-sulfamethoxazole (TMP-SMX) plus monthly dihydroartemisinin-piperaquine (DP) or daily TMP-SMX alone [20]. The study physician estimated gestational age using last menstrual period and fetal measurements obtained by a standardized abdominal ultrasound exam. All women were provided with combination antiretroviral therapy (ART) consisting of Efavirenz (EFV)/tenofovir/lamivudine. Women received routine HIV care per the Uganda Ministry of Health guidelines, and HIV-1 RNA monitoring was additionally performed. Participants were prospectively followed until delivery, at which point the placenta was harvested and prepared (as described below) for microscopic examination and diagnosis of ACA. At enrollment, a long-lasting insecticide treated net was provided to every participant and a detailed history including a household questionnaire and physical assessment/examination was obtained. Study participants were closely monitored throughout pregnancy by monthly assessments and collection of blood samples, and all their health care needs were provided by a dedicated study clinic open seven days a week. Participants were encouraged to deliver at the hospital. However, in the event of a home or other health facility delivery, participants were visited by the study staff at the time of delivery or as soon as possible afterwards. Upon delivery, a comprehensive assessment of birth outcomes was made, including neonatal evaluation for congenital anomalies, measurement of birth weight and gestational age. All placental sampling was done within 30 minutes of delivery. Placental specimens were fixed in 10% Neutral Buffered Formalin for 24 hours, and stored at room temperature in 70% ethanol prior to tissue processing. The following placental tissues were collected: placental membranes (“membrane roll”), umbilical cord (two cross-sectional slices, one proximal and one distal to where the cord inserts into the placental disc), chorionic plate with villous parenchyma, and basal plate with villous parenchyma. The basal plate/villous parenchyma section was used for diagnosis of PM in our separately reported studies [16, 20, 21], while the other three sections (membrane roll, umbilical cord, chorionic plate/villous parenchyma) were used as described below for the diagnosis of ACA in the study reported here. For microscopic diagnosis of ACA, three placental specimens were utilized: membrane roll, umbilical cord, and chorionic plate/villous parenchyma. In the Tororo, Uganda laboratory, specimens were dehydrated through a series of ethanol washes, cleared in xylene and embedded in paraffin wax blocks. A 3 μm thick section from each tissue block was obtained using a rotary microtome and sections mounted onto glass slides via a floatation water bath. Slides were baked in a hot air oven at 60°C for 30 minutes, de-paraffinized in xylene, dehydrated through a series of ethanol washes, stained with Hematoxylin and Eosin (H&E), and mounted with organic mounting media. Diagnosis of ACA was made by standard light microscopic examination (Nikon Eclipse Ci-L microscope with DS-Ri2 color camera) of the three placental biopsy slides (membrane roll, umbilical cord, and chorionic plate/villous parenchyma) (Fig 1). Diagnosis of a maternal acute inflammatory response to infection (“maternal ACA”) was indicated by detection of neutrophils within the chorioamnion layers of the membrane roll and/or the chorionic plate. Diagnosis of a fetal acute inflammatory response to infection (“fetal ACA”) was indicated by detection of neutrophils with or without eosinophils within the vascular smooth muscle of the umbilical cord vessels and/or the chorionic plate vasculature [9]. Diagnosis was rendered in blinded fashion by a placental pathologist (G.R.) and noted on a standardized case record form. (A&B) Normal umbilical cord. *indicates lumen of umbilical vessels. (C) Umbilical vein with heavy neutrophilic infiltrate (arrows point to aggregates of neutrophils) and early degeneration of smooth muscle cells diagnostic of severe fetal ACA. (D) Normal chorionic plate/villous parenchyma. Arrow indicates the chorionic plate, and * indicates lumen of a fetal chorionic plate vessel. (E) Chorionic plate with heavy neutrophilic infiltrate in the walls of a fetal chorionic plate vessel (severe fetal ACA) and neutrophils in the subchorionic fibrin layer (maternal ACA). Arrows point to aggregates of neutrophils. (F&G) Normal membrane roll. (H) Membrane roll with neutrophilic microabscess diagnostic of severe maternal ACA (arrows point to neutrophils). In G and H, {-bracket indicates amnion, [-bracket indicates chorion, and arrow indicates decidua parietalis. Scale bars are 1 mm (panels A, D, F) and 200 μM (panels B, C, E, G, H). Grading of maternal ACA and fetal ACA was assigned using the standardized diagnostic framework of the Perinatal Section of the Society for Pediatric Pathologists [9]. Grade was recorded on the case record form as either: no evidence of ACA, mild (scattered mostly single, isolated neutrophils), moderate (small clusters of neutrophils) and severe (presence of neutrophilic microabscesses). Specifically, severe maternal ACA was defined as the presence of microabscesses measuring greater than or equal to 10 x 20 neutrophils in extent, and present within at least three foci, or with neutrophils present as a contiguous band. Severe fetal ACA was defined as the presence of near confluent intramural neutrophils with attenuation/degeneration of vascular smooth muscle cells. The maternal characteristics examined included: maternal age and gestational age at enrollment, education, household wealth index, and gravity. Maternal characteristics pertaining to malaria included: IPTp regimen (either TMP-SMX plus DP or TMP-SMX alone), and evidence of PM defined by histopathology. Additionally, the following maternal characteristic pertaining to HIV infection were assessed: duration since HIV diagnosed, duration since ART was begun, WHO HIV stage at enrollment, CD4 T-cell count at delivery, and viral load at delivery. None of the women enrolled were WHO HIV stage 4 (defined as AIDS). ACA was categorized as maternal ACA (the presence of maternal acute inflammation, defined above) and fetal ACA (the presence of fetal acute inflammation, defined above). Maternal and fetal ACA were each categorized into a grading scale: none/mild, moderate and severe (defined above). The birth outcomes assessed were PTB (delivery at <37 weeks), LBW (birth weight <2500 grams, and SGA (birth weight <10th percentile for age). Data were coded, double entered into a Microsoft access database and analyzed using Stata 14 (Stata Corp, College Station TX). Participants’ baseline maternal characteristics were expressed as means ± SD for continuous variables, while categorical variables were expressed as proportions. Univariate and multivariate logistic regression were used to 1) measure associations between maternal characteristics and maternal and fetal ACA, and 2) measure associations between maternal and fetal ACA and the risk of adverse birth outcomes. P values < 0.05 were considered statistically significant. Measures of association in both univariate and multivariate models were expressed as odds ratios (OR) or adjusted odds ratios (aOR) and respective 95% confidence intervals (CI). Gravidity was not included in the final multivariate model due to correlation with maternal age. All study participants provided informed written consent. Ethical approval was obtained from the Uganda National Council of Science and Technology (UNCST #HS 1708), Makerere University School of Medicine Research and Ethics Committee, the Makerere University School of Biomedical Sciences Research and Ethics Committee (#SBS-REC 159), and the University of California, San Francisco, Committee on Human Research (CHR #14–13900).

Materials

N/A

Innovations

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

1. Telemedicine: Implementing telemedicine services could allow pregnant women in remote or underserved areas to access prenatal care and consultations with healthcare providers through video calls or phone calls. This would help overcome geographical barriers and increase access to maternal health services.

2. Mobile health (mHealth) applications: Developing mobile applications that provide information and resources related to maternal health, such as prenatal care guidelines, nutrition advice, and appointment reminders, can empower pregnant women to take control of their health and access important information easily.

3. Community health workers: Training and deploying community health workers who can provide basic prenatal care, education, and support to pregnant women in their communities. These workers can help bridge the gap between healthcare facilities and pregnant women, especially in rural or low-resource settings.

4. Transportation solutions: Improving transportation infrastructure and implementing transportation services specifically for pregnant women, such as ambulances or dedicated vehicles, can ensure timely access to healthcare facilities during emergencies or for routine check-ups.

5. Health education programs: Implementing comprehensive health education programs that focus on maternal health, including topics such as nutrition, hygiene, and prenatal care. These programs can be conducted in schools, community centers, or through digital platforms to reach a wider audience.

6. Maternal health clinics: Establishing dedicated maternal health clinics or expanding existing healthcare facilities to provide specialized care for pregnant women. These clinics can offer a range of services, including prenatal care, antenatal classes, and postnatal care, all in one location.

7. Public-private partnerships: Collaborating with private healthcare providers and organizations to improve access to maternal health services. This could involve subsidizing costs, providing training and resources, or leveraging existing infrastructure to reach more pregnant women.

It’s important to note that the implementation of these innovations should be context-specific and take into account the local healthcare system, cultural norms, and available resources.

AI Innovations Description

The recommendation to improve access to maternal health based on the study is to implement interventions that focus on preventing and treating acute chorioamnionitis (ACA) in HIV-infected pregnant women in resource-limited settings. This can be achieved through the following strategies:

1. Strengthening antenatal care: Ensure that pregnant women receive regular antenatal check-ups and screenings for infections, including ACA. This will help in early detection and timely management of ACA, reducing the risk of adverse birth outcomes.

2. Education and awareness: Provide comprehensive education to pregnant women about the risks of ACA and the importance of seeking timely medical care. This includes educating them about the signs and symptoms of ACA and the potential consequences for both the mother and the baby.

3. Access to healthcare facilities: Improve access to healthcare facilities equipped with skilled healthcare providers who can diagnose and manage ACA effectively. This may involve increasing the number of healthcare facilities in resource-limited settings and ensuring that they are adequately staffed and equipped.

4. Integration of services: Integrate maternal health services with HIV care and treatment programs. This will ensure that HIV-infected pregnant women receive comprehensive care that addresses both their HIV status and their maternal health needs, including the prevention and management of ACA.

5. Research and innovation: Support further research and innovation in the prevention, diagnosis, and treatment of ACA. This can include the development of new diagnostic tools, treatment guidelines, and interventions specifically tailored for resource-limited settings.

By implementing these recommendations, it is possible to improve access to maternal health and reduce the incidence of adverse birth outcomes associated with ACA in HIV-infected pregnant women.

AI Innovations Methodology

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

1. Strengthening Antenatal Care: Implementing comprehensive antenatal care programs that include regular check-ups, screenings, and education for pregnant women. This can help identify and address potential health issues early on, including acute chorioamnionitis.

2. Improving HIV Care and Management: Enhancing HIV care and management for pregnant women, including access to antiretroviral therapy (ART) and regular monitoring of HIV-1 RNA levels. This can help reduce the risk of adverse birth outcomes associated with HIV infection.

3. Enhancing Malaria Prevention Strategies: Integrating effective malaria prevention strategies, such as intermittent preventive therapy for malaria in pregnancy (IPTp), into routine antenatal care. This can help reduce the risk of malaria-related complications during pregnancy, which may indirectly improve maternal health outcomes.

4. Promoting Hospital Deliveries: Encouraging pregnant women to deliver at hospitals or health facilities where they can receive appropriate medical care and interventions. This can help ensure timely access to skilled birth attendants and emergency obstetric care, reducing the risk of complications during childbirth.

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

1. Data Collection: Gather data on the current state of maternal health access, including indicators such as antenatal care coverage, HIV care and management, malaria prevention strategies, and delivery practices.

2. Define Metrics: Identify specific metrics to measure the impact of the recommendations, such as the percentage increase in antenatal care attendance, the reduction in HIV transmission rates, or the increase in hospital deliveries.

3. Modeling: Use statistical modeling techniques to simulate the potential impact of the recommendations on the defined metrics. This could involve developing mathematical models that take into account various factors, such as population demographics, healthcare infrastructure, and resource availability.

4. Sensitivity Analysis: Conduct sensitivity analysis to assess the robustness of the results and understand the potential variations in outcomes based on different scenarios or assumptions.

5. Evaluation and Validation: Validate the model’s predictions by comparing them with real-world data or conducting pilot studies to assess the feasibility and effectiveness of implementing the recommendations.

6. Policy Recommendations: Based on the simulation results, provide evidence-based policy recommendations to stakeholders, policymakers, and healthcare providers to guide decision-making and resource allocation for improving access to maternal health.

It’s important to note that the methodology described above is a general framework and may need to be adapted based on the specific context and available data.

Author

Dima Health

Statistics:

Citations: 6

Identifiers:

DOI: 10.1371/journal.pone.0215058

Research Areas:

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

Study Countries:

Uganda

Study Design:

Cross Sectional Study, randomised-control-trial

Study Approach:

Quantitative

Participants Gender:

Female