Victor Akelo

Background: Oral glucose tolerance test (OGTT), the gold standard for diagnosing gestational diabetes mellitus (GDM), faces significant implementation challenges, prompting interest in alternative biomarkers, such as glycated hemoglobin (HbA1c), for early detection. This study aimed to assess the association between early pregnancy HbA1c and subsequent GDM and adverse perinatal outcomes in low- and middle-income countries. Methods: We analyzed data from the Pregnancy Risk, Infant Surveillance, and Measurement Alliance - Maternal and Newborn Health (PRISMA-MNH) cohort, which followed pregnant women enrolled before 20 weeks of gestation across five study sites in Kenya, India, Pakistan, and Zambia. We excluded participants with overt diabetes, severe anemia (Hb 2 ) than women without GDM. The AUC for HbA1c alone in predicting GDM was 0.65 (95% confidence interval 0.63–0.67). A single early HbA1c threshold of 5.4%, based on the largest Youden’s index, showed limited predictive performance (sensitivity 46.7%, specificity 75.8%). A two-threshold approach identified rule-out and rule-in cutoffs of 5.0% (sensitivity 80.3%, specificity 35.6%) and 5.5% (sensitivity 34.5%, specificity 83.1%), respectively. In adjusted models, each 0.1% increase in HbA1c was associated with a 12% higher risk (RR 1.12, 95% CI 1.10–1.15) of GDM, while no significant associations were observed for any secondary outcomes. Conclusion: Early pregnancy HbA1c is independently associated with an increased risk of subsequent GDM. However, it demonstrated limited discriminatory ability as a standalone alternative to OGTT for identifying women who would later develop GDM. The identified rule-out threshold may help identify women at low risk of GDM, although the majority would still require OGTT for definitive diagnosis.

BACKGROUND: Adverse consequences of neonatal hyperbilirubinemia disproportionately affect babies in low- and middle-income countries. Laboratory measurement of total serum bilirubin is limited in low-resource settings, necessitating simpler alternatives. Our study aimed to evaluate the diagnostic accuracy of visual inspection of jaundice via the World Health Organization Integrated Management of Childhood Illnesses algorithm compared to transcutaneous bilirubinometry for the identification of hyperbilirubinemia in community settings. METHODS: Hyperbilirubinemia was assessed by visual inspection for jaundice and transcutaneous bilirubinometry at 0-72 hours, 3-5 days, and 5-14 days postnatal in the PRISMA prospective cohort study in six sites in Asia and Africa. We assessed sensitivity, specificity, and positive and negative percent agreement. RESULTS: We analyzed data from 14,331 infants, including 1,852 preterm infants. 15% had hyperbilirubinemia, as defined by transcutaneous bilirubin values and the NICE nomograms, at 3-5 days postnatal. Visual inspection had a sensitivity of 16%, specificity of 96%, positive percent agreement of 56%, and negative percent agreement of 86% at 3-5 days postnatal age, pooled across all sites and gestational ages, versus transcutaneous bilirubin defined by NICE nomograms. CONCLUSION: The poor sensitivity of visual inspection underscores an urgent need for accurate, affordable screening tools to improve screening for hyperbilirubinemia. Impact Statement: We found poor sensitivity of visual inspection, identifying fewer than one in five neonatal jaundice cases, suggesting much worse diagnostic accuracy in this community-based context across five low- and middle-income countries (LMICs) as compared to the previous studies conducted in health facilities. Among preterm infants, sensitivity was modestly higher than in term infants but remained clinically inadequate, reinforcing that visual inspection alone is insufficient for this high-risk group. Despite standardized training and biannual refresher sessions, our study suggests that training for health care workers alone is unlikely to make visual inspection a reliable case-detection tool. Our findings suggest that the WHO should re-evaluate the IMCI recommendations to include tools with higher diagnostic accuracy to identify neonatal jaundice. Community-level jaundice screening should move beyond visual inspection alone towards validated, low-cost, objective tools; icterometers and smartphone apps with high diagnostic accuracy are promising alternatives.

Background: Anemia affects one in three pregnant women worldwide, with the greatest burden in South Asia and sub-Saharan Africa. During pregnancy, anemia has been linked to an increased risk of adverse maternal and neonatal health outcomes. Despite widespread recognition that anemia can complicate pregnancy, critical gaps persist in our understanding of the specific causes of maternal anemia and the cutoffs used to diagnose anemia in each trimester and in the postpartum period. Methods and analysis: The Redefining Maternal Anemia in Pregnancy and Postpartum (ReMAPP) study is a multisite, prospective, cohort study nested within the Pregnancy Risk, Infant Surveillance, and Measurement Alliance (PRISMA) Maternal and Newborn Health study. Research sites are located in Kenya, Ghana, Zambia, India, and Pakistan. Participants are up to 12,000 pregnant women who provide serial venous blood samples for hemoglobin assessment at five time points: at <20 weeks, 20 weeks, 28 weeks, and 36 weeks gestation and at six weeks postpartum. We will use two analytical approaches to estimate hemoglobin thresholds for defining anemia: (1) clinical decision limits for cutoffs in each trimester and at six weeks postpartum based on associations of hemoglobin levels with adverse maternal, fetal, and neonatal health outcomes and (2) reference limits for gestational-week-specific cutoffs and at six weeks postpartum for mild, moderate, and severe anemia based on tail statistical percentiles of hemoglobin values in a reference (i.e., clinically healthy) subpopulation. We will also conduct biomarker-intensive testing among a sub-sample of participants in each trimester to explore underlying contributing factors of maternal anemia. Ethics and dissemination: The study received local and national ethical approvals from all participating institutions. Findings from multisite analyses will be published among open-access, peer-reviewed journals and disseminated with local, national, and international partners. Registration: ClinicalTrials.gov (ID: PRISMA-MNH 2022; NCT05904145 ) Strengths and limitations: Novel study design to allow multiple analytical approaches (clinical decision limits and reference limits) in the same population to establish hemoglobin thresholds. Use of gold standard methods and external quality assurance programs to ensure harmonized hemoglobin measurement across sites. Inclusion of biomarker-intensive study arm to examine the etiology of anemia among pregnant women. All data is contributed by populations historically underrepresented in research in low- and middle-income countries.

Background Child mortality in Kenya is 41 per 1,000 live births, despite extensive investment in maternal, newborn, and child health interventions. Caregivers’ health-seeking for childhood illness is an important determinant of child survival, and delayed healthcare is associated with high child mortality. We explore determinants of health-seeking decisions for childhood illnesses among caregivers in western Kenya. Methods We conducted a qualitative study of 88 community members between April 2017 and February 2018 using purposive sampling in an informal urban settlement in Kisumu County, and in rural Siaya County. Key informant interviews, semi-structured interviews and focus group discussions were performed. We adopted the Partners for Applied Social Sciences model focusing on factors that influence the decision-making process to seek healthcare for sick infants and children. The discussions were audio-recorded and transcribed. Data management was completed on Nvivo® software. Iterative analysis process was utilized and themes were identified and collated. Results Our findings reveal four thematic areas: Illness interpretation, the role of social relationship on illness recognition and response, medical pluralism and healthcare access. Participants reported some illnesses are caused by supernatural powers and some by biological factors, and that the illness etiology would determine the health-seeking pathway. It was common to seek consensus from respected community members on the diagnosis and therefore presumed cause and necessary treatment for a child’s illness. Medical pluralism was commonly practiced and caregivers would alternate between biomedicine and traditional medicine. Accessibility of healthcare may determine the health seeking pathway. Caregivers unable to afford biomedical care may choose traditional medicine as a cheaper alternative. Conclusion Health seeking behavior was driven by illness interpretation, financial cost associated with healthcare and advice from extended family and community. These findings enrich the perspectives of health education programs to develop health messages that address factors that hinder prompt health care seeking.

Background Child mortality in Kenya is 41 per 1,000 live births, despite extensive investment in maternal, newborn, and child health interventions. Caregivers’ health-seeking for childhood illness is an important determinant of child survival, and delayed healthcare is associated with high child mortality. We explore determinants of health-seeking decisions for childhood illnesses among caregivers in western Kenya. Methods We conducted a qualitative study of 88 community members between April 2017 and February 2018 using purposive sampling in an informal urban settlement in Kisumu County, and in rural Siaya County. Key informant interviews, semi-structured interviews and focus group discussions were performed. We adopted the Partners for Applied Social Sciences model focusing on factors that influence the decision-making process to seek healthcare for sick infants and children. The discussions were audio-recorded and transcribed. Data management was completed on Nvivo® software. Iterative analysis process was utilized and themes were identified and collated. Results Our findings reveal four thematic areas: Illness interpretation, the role of social relationship on illness recognition and response, medical pluralism and healthcare access. Participants reported some illnesses are caused by supernatural powers and some by biological factors, and that the illness etiology would determine the health-seeking pathway. It was common to seek consensus from respected community members on the diagnosis and therefore presumed cause and necessary treatment for a child’s illness. Medical pluralism was commonly practiced and caregivers would alternate between biomedicine and traditional medicine. Accessibility of healthcare may determine the health seeking pathway. Caregivers unable to afford biomedical care may choose traditional medicine as a cheaper alternative. Conclusion Health seeking behavior was driven by illness interpretation, financial cost associated with healthcare and advice from extended family and community. These findings enrich the perspectives of health education programs to develop health messages that address factors that hinder prompt health care seeking.

Background Child mortality in Kenya is 41 per 1,000 live births, despite extensive investment in maternal, newborn, and child health interventions. Caregivers’ health-seeking for childhood illness is an important determinant of child survival, and delayed healthcare is associated with high child mortality. We explore determinants of health-seeking decisions for childhood illnesses among caregivers in western Kenya. Methods We conducted a qualitative study of 88 community members between April 2017 and February 2018 using purposive sampling in an informal urban settlement in Kisumu County, and in rural Siaya County. Key informant interviews, semi-structured interviews and focus group discussions were performed. We adopted the Partners for Applied Social Sciences model focusing on factors that influence the decision-making process to seek healthcare for sick infants and children. The discussions were audio-recorded and transcribed. Data management was completed on Nvivo® software. Iterative analysis process was utilized and themes were identified and collated. Results Our findings reveal four thematic areas: Illness interpretation, the role of social relationship on illness recognition and response, medical pluralism and healthcare access. Participants reported some illnesses are caused by supernatural powers and some by biological factors, and that the illness etiology would determine the health-seeking pathway. It was common to seek consensus from respected community members on the diagnosis and therefore presumed cause and necessary treatment for a child’s illness. Medical pluralism was commonly practiced and caregivers would alternate between biomedicine and traditional medicine. Accessibility of healthcare may determine the health seeking pathway. Caregivers unable to afford biomedical care may choose traditional medicine as a cheaper alternative. Conclusion Health seeking behavior was driven by illness interpretation, financial cost associated with healthcare and advice from extended family and community. These findings enrich the perspectives of health education programs to develop health messages that address factors that hinder prompt health care seeking.

Background The Masimo Total Hemoglobin SpHb® is a continuous and non-invasive handheld device to measure hemoglobin levels. Previous research has found that SpHb is able to accurately detect hemoglobin levels in adult patients with a similar degree of bias and standard deviation to point-of-care invasive method measurements. Generally, limited clinical evidence, lack of validation of Masimo at higher than and lower than hemoglobin threshold values, and scientific consensus supporting the use of Masimo for accurate hemoglobin testing for the diagnosis of anemia during pregnancy calls for further research. Methods and analysis The proposed prospective cohort will be nested within the ongoing Pregnancy Risk and Infant Surveillance and Measurement Alliance (PRISMA) Maternal and Newborn Health (MNH) study. Three study sites (located in Zambia, Kenya, and Pakistan) will participate and collect hemoglobin data at five time points (<20 weeks, 20 weeks, 28 weeks, 36 weeks’ gestation, and six weeks postpartum). We will measure hemoglobin using a venous blood sample via hematology auto-analyzer complete blood count (gold standard) and the non-invasive device. The primary objective is to assess agreement between Masimo total hemoglobin and complete blood count and on a continuous scale using Intraclass Correlation Coefficient and Bland-Altman Analysis. The second objective is to assess agreement between the two measures on a binary scale using Positive Percentage Agreement and Negative Percentage Agreement, Cohen’s Kappa, and McNemar Test. On an ordinal scale, agreement will be measured using Weighted Cohen’s Kappa and Harrel’s Concordance Index. Lastly, we will assess factors that might affect the accuracy of Masimo total hemoglobin using linear mixed models. Conclusions The primary aim of this study is to assess the validity of the non-invasive Masimo device compared to the gold standard method of invasive hemoglobin measurements during pregnancy and postpartum periods for the diagnosis of anemia.

Background: The Masimo Total Hemoglobin SpHb® is a continuous and non-invasive handheld device to measure hemoglobin levels. Previous research has found that SpHb is able to accurately detect hemoglobin levels in adult patients with a similar degree of bias and standard deviation to point-of-care invasive method measurements. Generally, limited clinical evidence, lack of validation of Masimo at higher than and lower than hemoglobin threshold values, and scientific consensus supporting the use of Masimo for accurate hemoglobin testing for the diagnosis of anemia during pregnancy calls for further research. Methods and analysis: The proposed prospective cohort will be nested within the ongoing Pregnancy Risk and Infant Surveillance and Measurement Alliance (PRISMA) Maternal and Newborn Health (MNH) study. Three study sites (located in Zambia, Kenya, and Pakistan) will participate and collect hemoglobin data at five time points (<20 weeks, 20 weeks, 28 weeks, 36 weeks’ gestation, and six weeks postpartum). We will measure hemoglobin using a venous blood sample via hematology auto-analyzer complete blood count (gold standard) and the non-invasive device. The primary objective is to assess agreement between Masimo total hemoglobin and complete blood count and on a continuous scale using Intraclass Correlation Coefficient and Bland-Altman Analysis. The second objective is to assess agreement between the two measures on a binary scale using Positive Percentage Agreement and Negative Percentage Agreement, Cohen’s Kappa, and McNemar Test. On an ordinal scale, agreement will be measured using Weighted Cohen’s Kappa and Harrel’s Concordance Index. Lastly, we will assess factors that might affect the accuracy of Masimo total hemoglobin using linear mixed models. Conclusions: The primary aim of this study is to assess the validity of the non-invasive Masimo device compared to the gold standard method of invasive hemoglobin measurements during pregnancy and postpartum periods for the diagnosis of anemia.

Background: Approximately 80% of the population residing in sub-Saharan Africa relies on Traditional Medicine (TM). However, literature on factors motivating the use of TM for children under the age of five in these settings is limited. Such information can guide policy formulation for integration of TM into mainstream health care services. This study aimed to describe the motivation on use of TM among caregivers of children residing in rural and urban communities in western Kenya. Methods: The socio-behavioral sciences (SBS) arm of the Child Health and Mortality Prevention Surveillance (CHAMPS) program in western Kenya, conducted a cross-sectional qualitative study in Manyatta—an urban informal settlement located in Kisumu town and Karemo—a rural setting in Siaya County. We performed 29 in-depth interviews, 5 focus group discussions and 11 semi-structured interviews with community representatives (n = 53), health workers (n = 17), and community leaders (n = 18). All the participants were purposively sampled. We performed thematic analysis using both inductive and deductive approaches. Data management was completed on Nvivo 11.0 software (QSR International, Melbourne, Australia). Results: Our findings reveal that some caregivers prefer TM to treat some childhood diseases. Use of TM was informed by illness beliefs about etiology of disease. We observed an appreciation from the study participants that malaria can effectively be treated by Conventional Medicine (CM) while TM was preferred to treat measles and diseases believed to be associated with supernatural etiology such as witchcraft, evil spirit or breaching cultural taboos. TM was also used in instances where CM failed to provide a diagnosis or when CM was ‘slow’. TM in such cases was used as a last resort. Conclusion: We observed varied beliefs that motivate caregivers’ choice of TM use among children in western Kenya. It is therefore crucial to consider perceptions and socio-cultural beliefs about illnesses when formulating interventions that are geared towards child health.

Background: The current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death. Methods and findings: We examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child n = 282, 38%); among those with preterm birth complications, 256 (91%) had additional conditions in causal chains, including 184 (65%) with a different preterm birth complication, 128 (45%) with neonatal sepsis, 69 (24%) with lower respiratory infection (LRI), 60 (21%) with meningitis, and 25 (9%) with perinatal asphyxia/hypoxia. Of the 278 infant deaths, 212 (79%) had ≥1 additional cause of death (CoD) beyond the underlying cause. The 2 most common underlying conditions in infants were malnutrition and congenital birth defects; LRI and sepsis were the most common additional conditions in causal chains, each accounting for approximately half of deaths with either underlying condition. Of the 241 child deaths, 178 (75%) had ≥1 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had ≥1 other condition in the causal chain, most commonly sepsis, followed by LRI, malaria, and diarrheal disease. Including all positions in the causal chain for neonatal deaths resulted in 19-fold and 11-fold increases in attributable roles for meningitis and LRI, respectively. For infant deaths, the proportion caused by meningitis and sepsis increased by 16-fold and 11-fold, respectively; for child deaths, sepsis and LRI are increased 12-fold and 10-fold, respectively. While comprehensive CoD determinations were done for a substantial number of deaths, there is potential for bias regarding which deaths in surveillance areas underwent minimally invasive tissue sampling (MITS), potentially reducing representativeness of findings. Conclusions: Including conditions that appear anywhere in the causal chain, rather than considering underlying condition alone, markedly changed the proportion of deaths attributed to various diagnoses, especially LRI, sepsis, and meningitis. While CHAMPS methods cannot determine when 2 conditions cause death independently or may be synergistic, our findings suggest that considering the chain of events leading to death can better guide research and prevention priorities aimed at reducing child deaths.