Birth outcomes and survival by sex among newborns and children under 2 in the Birhan Cohort: a prospective cohort study in the Amhara Region of Ethiopia.

INTRODUCTION: Despite the progress in reducing child mortality, the rate remains high, particularly in sub-Saharan African countries. Limited data exist on child survival and other birth outcomes by sex. This study compared survival rates and birth outcomes by sex among neonates and children under 2 in Ethiopia. METHODS: Women who gave birth after 28 weeks of gestation and their newborns were included in the analysis. Survival probabilities were estimated for males and females in the neonatal period as well as the 2-year period following birth using Kaplan-Meier curves. HRs and 95% CIs were compared between males and females under 2. Descriptive statistics and χ2 tests were used to determine the sex-disaggregated variation in the birth outcomes of preterm birth, low birth weight (LBW), stillbirth, small for gestational age (SGA) and large for gestational age (LGA). RESULTS: The study included a total of 3904 women and child pairs. The neonatal mortality rate for males (3.4%, 95% CI 2.6% to 4.2%) was higher compared with females (1.7%, 95% CI 1.1% to 2.3%). The hazard of death during the first 28 days of life was approximately two times higher for males compared with females (HR 1.99, 95% CI 1.30 to 3.06) but was not significantly different after this period. While there was a non-significant difference between males and females in the proportion of preterm, LBW and LGA births, we found a significantly higher proportion of stillbirth (2.7% vs 1.3%, p=0.003) and SGA (20.5% vs 15.6%, p<0.001) for males compared with females. CONCLUSIONS: This study identified a significant sex difference in mortality and birth outcomes. We recommend focusing future research on the mechanisms of these sex differences in order to better design intervention programmes to reduce disparities and improve outcomes for neonates.

Estimates and determinants of health facility delivery in the Birhan cohort in Ethiopia.

Health facility delivery is one of the critical indicators to monitor progress towards the provision of skilled delivery care and reduction in perinatal mortality. In Ethiopia, utilization of health facilities for skilled delivery care has been increasing but varies greatly by region and among specific socio-demography groups. We aimed to measure the prevalence and determinants of health facility delivery in the Amhara region in Ethiopia. From December 2018 to November 2020, we conducted a longitudinal study from a cohort of 2801 pregnant women and described the location of delivery and the association with determinants. We interviewed a subset of women who delivered in the community and analyzed responses using the three delays model to understand reasons for not using health facility services. A multivariable poisson regression model with robust error variance was used to estimate the presence and magnitude of association between location of delivery and the determinants. Of the 2,482 pregnant women followed through to birth, 73.6% (n = 1,826) gave birth in health facilities, 24.3% (n = 604) gave birth at home and 2.1% (n = 52) delivered on the way to a health facility. Determinants associated with increased likelihood of delivery at a health facility included formal maternal education, shorter travel times to health facilities, primiparity, higher wealth index and having attended at least one ANC visit. Most common reasons mothers gave for not delivering in a health facility were delays in individual/family decision to seek care. The proportion of deliveries occurring in health facilities is increasing but falls below targets. Interventions that focus on the identified social-demographic determinants and delays are warranted.

Carriage of antimicrobial-resistant Enterobacterales among pregnant women and newborns in Amhara, Ethiopia.

OBJECTIVES: Infections are one of the most common causes of neonatal mortality, and maternal colonization has been associated with neonatal infection. In this study, we sought to quantify carriage prevalence of extended-spectrum-beta-lactamase (ESBL) -producing and carbapenem-resistant Enterobacterales (CRE) among pregnant women and their neonates and to characterize risk factors for carriage in rural Amhara, Ethiopia. METHODS: We conducted a prospective cohort study nested in the Birhan field site. We collected rectal and vaginal samples from 211 pregnant women in their third trimester and/or during labor/delivery and perirectal or stool samples from 159 of their neonates in the first week of life. RESULTS: We found that carriage of ESBL-producing organisms was fairly common (women: 22.3%, 95% CI: 16.8-28.5; neonates: 24.5%, 95% CI: 18.1-32.0), while carriage of CRE (women: 0.9%, 95% CI: 0.1-3.4; neonates: 2.5%, 95% CI: 0.7-6.3) was rare. Neonates whose mothers tested positive for ESBL-producing organisms were nearly twice as likely to also test positive for ESBL-producing organisms (38.7% vs 21.1%, P-value = 0.06). Carriage of ESBL-producing organisms was also associated with Woreda (district) of sample collection and recent antibiotic use. CONCLUSION: Understanding carriage patterns of potential pathogens and antibiotic susceptibility among pregnant women and newborns will inform local, data-driven recommendations to prevent and treat neonatal infections.

Prevalence, Incidence, and Reversal Pattern of Childhood Stunting From Birth to Age 2 Years in Ethiopia.

Importance: Although there has been a reduction in stunting (low-height-for-age and low-length-for-age), a proxy of malnutrition, the prevalence of malnutrition in Ethiopia is still high. Child growth patterns and estimates of stunting are needed to increase awareness and resources to improve the potential for recovery. Objective: To estimate the prevalence, incidence, and reversal of stunting among children aged 0 to 24 months. Design, Setting, and Participants: This population-based cohort study of the Birhan Maternal and Child Health cohort in North Shewa Zone, Amhara, Ethiopia, was conducted between December 2018 and November 2020. Eligible participants included children aged 0 to 24 months who were enrolled during the study period and had their length measured at least once. Data analysis occurred from Month Year to Month Year. Main Outcomes and Measures: The primary outcome of this study was stunting, defined as length-for-age z score (LAZ) at least 2 SDs below the mean. Z scores were also used to determine the prevalence, incidence, and reversal of stunting at each key time point. Growth velocity was determined in centimeters per month between key time points and compared with global World Health Organization (WHO) standards for the same time periods. Heterogeneity was addressed by excluding outliers in sensitivity analyses using modeled growth trajectories for each child. Results: A total of 4354 children were enrolled, out of which 3674 (84.4%; 1786 [48.7%] female) had their length measured at least once and were included in this study. The median population-level length was consistently below WHO growth standards from birth to 2 years of age. The observed prevalence of stunting was highest by 2 years of age at 57.4% (95% CI, 54.8%-9 60.0%). Incidence of stunting increased over time and reached 51.0% (95% CI, 45.3%-56.6%) between ages 12 and 24 months. Reversal was 63.5% (95% CI, 54.8%-71.4%) by age 6 months and 45.2% (95% CI, 36.0%-54.8%) by age 2 years. Growth velocity point estimate differences were slowest compared with WHO standards during the neonatal period (-1.4 cm/month for girls and -1.6 cm/month for boys). There was substantial heterogeneity in anthropometric measurements. Conclusions and Relevance: The evidence from this cohort study highlights a chronically malnourished population with much of the burden associated with growth faltering during the neonatal periods as well as after 6 months of age. To end all forms of malnutrition, growth faltering in populations such as that in young children in Amhara, Ethiopia, needs to be addressed.

Antenatal care coverage in a low-resource setting: Estimations from the Birhan Cohort.

Antenatal care (ANC) coverage estimates commonly rely on self-reported data, which may carry biases. Leveraging prospectively collected longitudinal data from the Birhan field site and its pregnancy and birth cohort, the Birhan Cohort, this study aimed to estimate the coverage of ANC, minimizing assumptions and biases due to self-reported information and describing retention patterns in ANC in rural Amhara, Ethiopia. The study population were women enrolled and followed during pregnancy between December 2018 and April 2020. ANC visits were measured by prospective facility chart abstraction and self-report at enrollment. The primary study outcomes were the total number of ANC visits attended during pregnancy and the coverage of at least one, four, or eight ANC visits. Additionally, we estimated ANC retention patterns. We included 2069 women, of which 150 (7.2%) women enrolled <13 weeks of gestation with complete prospective facility reporting. Among these 150 women, ANC coverage of at least one visit was 97.3%, whereas coverage of four visits or more was 34.0%. Among all women, coverage of one ANC visit was 92.3%, while coverage of four or more visits was 28.8%. No women were found to have attended eight or more ANC visits. On retention in care, 70.3% of participants who had an ANC visit between weeks 28 and <36 of gestation did not return for a subsequent visit. Despite the high proportion of pregnant women who accessed ANC at least once in our study area, the coverage of four visits remains low. Further efforts are needed to enhance access to more ANC visits, retain women in care, and adhere to the most recent Ethiopian National ANC guideline of at least eight ANC visits. It is essential to identify the factors that lead a large proportion of women to discontinue ANC follow-up.

Health care seeking behaviors of pregnant women in rural Amhara, Ethiopia: a qualitative study of perceptions of pregnant women, community members, and health care providers.

Introduction: in Ethiopia, increasing access to basic antenatal and neonatal health services may improve maternal and newborn survival. This study examined perceptions regarding antenatal health seeking behaviors from pregnant women, their families, community members, and health care providers in rural Amhara, Ethiopia. Methods: the study was conducted in four rural districts of the Amhara region of Ethiopia. A total of forty participants who were living and working within the catchment areas of the selected health centres were interviewed from October 3rd through October 14th, 2018. A phenomenological qualitative study design was used to understand participants' perceptions and experiences about pregnant women's health care seeking behaviors. Results: early disclosure of pregnancy status was not common in the study area. However, the data from the present study further provided new information, suggesting that some women did disclose their pregnancy status early but preferentially only to their partners and close relatives. Most women did not seek care unless sick or experienced new discomfort or pain. Some reasons for the low utilization of available antenatal services include long distance to health facilities, lack of transportation, difficult topography, and discomfort with male providers. Conclusion: despite the rapid expansion of health posts and deployment of health extension workers since 2003, there are still critical barriers to accessing facility-based care that limit women's health care seeking practices.

Setting a research agenda to advance maternal, newborn, and child health in Ethiopia: An adapted CHNRI prioritization exercise.

Background: Critical to the improvement of maternal, newborn, and child health (MNCH) in Ethiopia - where 14 000 mothers die from pregnancy-, childbirth-, or postpartum-related complications each year - is high-quality research and its effective translation into policy and practice. While Ethiopia has rapidly expanded the number of institutions that train and conduct MNCH research, the absence of a shared research agenda inhibits a coordinated approach to inform critical MNCH policy needs. The HaSET Maternal and Child Health Research Program (MCHRP) conducted a mixed methods formative assessment and prioritization exercise to guide investments in future MNCH research in Ethiopia. Methods: We adapted the Child Health and Nutrition Research Initiative (CHNRI) method, soliciting 56 priority research questions via key informant interviews. Through an online survey, experts scored these on their ability to generate new, actionable evidence that could inform more effective and equitable MNCH programs in Ethiopia. At a workshop in Addis Ababa, experts scored the questions by answerability and ethics, usefulness, disease burden reduction, and impact on equity. Research priority scores were calculated for both the online survey and workshop scoring and averaged to attain a ranked priority list. We validated and contextualized the results by conducting consensus-building discussions with MNCH experts and two community workshops. In total, approximately 100 participants were involved. Results: Average research priority scores ranged from 58.4 to 83.7 out of 100.0. The top identified research priorities speak to critical needs in the Ethiopian context: to improve population coverage of proven interventions like integrated community case management (ICCM), family integrated newborn care, and kangaroo mother care (KMC); to better understand the determinants of outcomes like home deliveries, immunization drop-out, and antenatal and postpartum care-seeking; and to strengthen health system and workforce capabilities. Conclusions: This exercise expanded on the CHNRI methodology by comparing prioritization across different audiences, formats, and criteria. Agreement between both scoring rounds and consensus-building discussions was strong, demonstrating the reliability of the CHNRI method. By sharing this research priority list broadly among researchers, practitioners, and donors, we aim to improve coordinated MNCH evidence generation and translation into policy in Ethiopia.

Development of Prediction Models for Antenatal Care Attendance in Amhara Region, Ethiopia.

Importance: Antenatal care prevents maternal and neonatal deaths and improves birth outcomes. There is a lack of predictive models to identify pregnant women who are at high risk of failing to attend antenatal care in low-resource settings. Objective: To develop a series of predictive models to identify women who are at high risk of failing to attend antenatal care in a rural setting in Ethiopia. Design, Setting, and Participants: This prognostic study used data from the Birhan Health and Demographic Surveillance System and its associated pregnancy and child cohort. The study was conducted at the Birhan field site, North Shewa zone, Ethiopia, a platform for community- and facility-based research and training, with a focus on maternal and child health. Participants included women enrolled during pregnancy in the pregnancy and child cohort between December 2018 and March 2020, who were followed-up in home and facility visits. Data were analyzed from April to December 2022. Exposures: A wide range of sociodemographic, economic, medical, environmental, and pregnancy-related factors were considered as potential predictors. The selection of potential predictors was guided by literature review and expert knowledge. Main Outcomes and Measures: The outcome of interest was failing to attend at least 1 antenatal care visit during pregnancy. Prediction models were developed using logistic regression with regularization via the least absolute shrinkage and selection operator and ensemble decision trees and assessed using the area under the receiving operator characteristic curve (AUC). Results: The study sample included 2195 participants (mean [SD] age, 26.8 [6.1] years; mean [SD] gestational age at enrolment, 25.5 [8.8] weeks). A total of 582 women (26.5%) failed to attend antenatal care during cohort follow-up. The AUC was 0.61 (95% CI, 0.58-0.64) for the regularized logistic regression model at conception, with higher values for models predicting at weeks 13 (AUC, 0.68; 95% CI, 0.66-0.71) and 24 (AUC, 0.66; 95% CI, 0.64-0.69). AUC values were similar with slightly higher performance for the ensembles of decision trees (conception: AUC, 0.62; 95% CI, 0.59-0.65; 13 weeks: AUC, 0.70; 95% CI, 0.67-0.72; 24 weeks: AUC, 0.67; 95% CI, 0.64-0.69). Conclusions and Relevance: This prognostic study presents a series of prediction models for antenatal care attendance with modest performance. The developed models may be useful to identify women at high risk of missing their antenatal care visits to target interventions to improve attendance rates. This study opens the possibility to develop and validate easy-to-use tools to project health-related behaviors in settings with scarce resources.

Development of risk prediction models for preterm delivery in a rural setting in Ethiopia.

Background: Preterm birth complications are the leading causes of death among children under five years. However, the inability to accurately identify pregnancies at high risk of preterm delivery is a key practical challenge, especially in resource-constrained settings with limited availability of biomarkers assessment. Methods: We evaluated whether risk of preterm delivery can be predicted using available data from a pregnancy and birth cohort in Amhara region, Ethiopia. All participants were enrolled in the cohort between December 2018 and March 2020. The study outcome was preterm delivery, defined as any delivery occurring before week 37 of gestation regardless of vital status of the foetus or neonate. A range of sociodemographic, clinical, environmental, and pregnancy-related factors were considered as potential inputs. We used Cox and accelerated failure time models, alongside decision tree ensembles to predict risk of preterm delivery. We estimated model discrimination using the area-under-the-curve (AUC) and simulated the conditional distributions of cervical length (CL) and foetal fibronectin (FFN) to ascertain whether they could improve model performance. Results: We included 2493 pregnancies; among them, 138 women were censored due to loss-to-follow-up before delivery. Overall, predictive performance of models was poor. The AUC was highest for the tree ensemble classifier (0.60, 95% confidence interval = 0.57-0.63). When models were calibrated so that 90% of women who experienced a preterm delivery were classified as high risk, at least 75% of those classified as high risk did not experience the outcome. The simulation of CL and FFN distributions did not significantly improve models' performance. Conclusions: Prediction of preterm delivery remains a major challenge. In resource-limited settings, predicting high-risk deliveries would not only save lives, but also inform resource allocation. It may not be possible to accurately predict risk of preterm delivery without investing in novel technologies to identify genetic factors, immunological biomarkers, or the expression of specific proteins.

Implementation science to design, test and scale up effective Kangaroo Mother Care in Oromia region, Ethiopia.

AIM: To develop a locally tested and optimised Kangaroo Mother Care (KMC) scale-up model to achieve high population-based effective coverage of KMC in Oromia region. METHOD: We conducted an implementation research study to design and test KMC scale-up models from March 2017 to March 2019 in five hospitals and 39 health centres covering a population of 1.1 million in Oromia region, Ethiopia. We evaluated the models by measuring effective KMC coverage (at least 8 hours of skin-to-skin care plus exclusive breastfeeding) for newborns weighing <2000 g in the 24 hours before discharge from the KMC facility and on the 7th-day post-discharge. RESULTS: After three cycles of iterative model implementation, we developed a KMC scale-up model that resulted in increased population-based effective KMC coverage. We enhanced the existing health system by strengthening the health system, reinforcing the linkages between the health system and communities and improving community engagement. Our final model achieved effective KMC coverage of 54%: 95% CI [49, 60] in the 24 hours before discharge from the facility and 38%: 95% CI [32, 43] on the 7th-day post-discharge. CONCLUSION: Through iterative testing and adaptations, a model to scale up KMC that achieves 54% population-based effective coverage of KMC can be developed.

Impact of the COVID-19 pandemic on utilisation of facility-based essential maternal and child health services from March to August 2020 compared with pre-pandemic March-August 2019: a mixed-methods study in North Shewa Zone, Ethiopia.

INTRODUCTION: Health systems are often weakened by public health emergencies that make it harder to access health services. We aimed to assess maternal, newborn and child health (MNCH) service utilisation during the first 6 months of the COVID-19 pandemic compared with prior to the pandemic. METHODS: We conducted a mixed study design in eight health facilities that are part of the Birhan field site in Amhara, Ethiopia and compared the trend of service utilisation in the first 6 months of COVID-19 with the corresponding time and data points of the preceding year. RESULT: New family planning visits (43.2 to 28.5/month, p=0.014) and sick under 5 child visits (225.0 to 139.8/month, p=0.007) declined over the first 6 months of the pandemic compared with the same period in the preceding year. Antenatal (208.9 to 181.7/month, p=0.433) and postnatal care (26.6 to 19.8/month, p=0.155) visits, facility delivery rates (90.7 to 84.2/month, p=0.776), and family planning visits (313.3 to 273.4/month, p=0.415) declined, although this did not reach statistical significance. Routine immunisation visits (37.0 to 36.8/month, p=0.982) for children were maintained. Interviews with healthcare providers and clients highlighted several barriers to service utilisation during COVID-19, including fear of disease transmission, economic hardship, and transport service disruptions and restrictions. Enablers of service utilisation included communities' decreased fear of COVID-19 and awareness-raising activities. CONCLUSION: We observed a decline in essential MNCH services particularly in sick children and new family planning visits. To improve the resiliency of fragile health systems, resources are needed to continuously monitor service utilisation and clients' evolving concerns during public health emergencies.

Survival status and predictors of mortality among low-birthweight neonates admitted to KMC units of five public hospitals in Ethiopia: Frailty survival regression model.

BACKGROUND: Low birth weight (LBW) and preterm birth are leading causes of under-five and neonatal mortality globally. Data about the timing of death and outcomes for LBW and preterm births are limited in Ethiopia and could be used to strengthen neonatal healthcare. This study describes the incidence of neonatal mortality rates (NMR) stratified by newborn size at birth for gestational age and identifies its predictors at five public hospitals in Ethiopia. METHODS: A prospective follow-up study enrolled 808 LBW neonates from March 2017 to February 2019. Sex-specific birthweight for gestational age percentile was constructed using Intergrowth 21st charts. Mortality patterns by birthweight for-gestational-age-specific survival curves were compared using the log-rank test and Kaplan-Meier survival curves. A random-effects frailty survival model was employed to identify predictors of time to death. RESULTS: Among the 808 newborns, the birthweight distribution was 3.2% <1000 g, 28.3% <1500 g, and 68.1% <2000 g, respectively. Birthweight for gestational age categories were 40.0% both preterm and small for gestational age (SGA), 20.4% term SGA, 35.4% appropriate weight for gestational age, and 4.2% large for gestational age (LGA). The sample included 242 deaths, of which 47.5% were both preterm and SGA. The incidence rate of mortality was 16.17/1000 (95% CI 14.26-18.34) neonatal-days of observation. Neonatal characteristics independently related to increased risk of time-to-death were male sex (adjusted hazards ratio [AHR] 3.21 95% CI 1.33-7.76), born preterm (AHR 8.56 95% CI 1.59-46.14), having been diagnosed with a complication (AHR 4.68 95% CI 1.49-14.76); some maternal characteristics and newborn care practices (like lack of effective KMC, AHR 3.54 95% CI 1.14-11.02) were also significantly associated with time-to-death. CONCLUSIONS: High mortality rates were measured for low birthweight neonates-especially those both preterm and SGA births-even in the context of tertiary care. These findings highlight the need for improved quality of neonatal care, especially for the smallest newborns.

Factors associated with small-for-gestational-age births among preterm babies born <2000 g: a multifacility cross-sectional study in Ethiopia.

OBJECTIVES: This study aimed to determine the prevalence of small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA); compare variations in multiple risk factors, and identify factors associated with SGA births among preterm babies born <2000 g. DESIGN: Cross-sectional study. SETTING: The study was conducted at five public hospitals in Oromia Regional State and Addis Ababa City Administration, Ethiopia. PARTICIPANTS: 531 singleton preterm babies born <2000 g from March 2017 to February 2019. OUTCOME MEASURES: Birth size-for-gestational-age was an outcome variable. Birth size-for-gestational-age centiles were produced using Intergrowth-21st data. Newborn birth size-for-gestational-age below the 10th percentile were classified as SGA; those>10th to 90th percentiles were classified as AGA; those >90th percentiles, as large-for-gestational-age, according to sex. SGA and AGA prevalence were determined. Babies were compared for variations in multiple risk factors. RESULTS: Among 531 babies included, the sex distribution was: 55.44% males and 44.56% females. The prevalences of SGA and AGA were 46.14% and 53.86%, respectively. The percentage of SGA was slightly greater among males (47.62%) than females (44.30%), but not statistically significant The prevalence of SGA was significantly varied between pre-eclamptic mothers (32.42%, 95% CI 22.36% to 43.22%) and non-pre-eclamptic mothers (57.94%, 95% CI 53.21% to 62.54%). Mothers who had a history of stillbirth (adjusted OR (AOR) 2.96 95% CI 1.04 to 8.54), pre-eclamptic mothers (AOR 3.36, 95% CI 1.95 to 5.79) and being born extremely low birth weight (AOR 10.48, 95% CI 2.24 to 49.02) were risk factors significantly associated with SGA in this population. CONCLUSION: Prevalence of SGA was very high in these population in the study area. Maternal pre-eclampsia substantially increases the risk of SGA. Hence, given the negative consequences of SGA, maternal and newborn health frameworks must look for and use evidence on gestational age and birth weight to assess the newborn's risks and direct care.

Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study: protocol of a pragmatic clinical effectiveness study to improve birth outcomes in Ethiopia.

INTRODUCTION: The WHO Nutrition Target aims to reduce the global prevalence of low birth weight by 30% by the year 2025. The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study will test the impact of packages of pregnancy interventions to enhance maternal nutrition and infection management on birth outcomes in rural Ethiopia. METHODS AND ANALYSIS: ENAT is a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. Eligible pregnant women presenting at antenatal care (ANC) visits at <24 weeks gestation are enrolled (n=2400). ANC quality is strengthened across all centres. Health centres are randomised to receive an enhanced nutrition package (ENP) or standard nutrition care, and within each health centre, individual women are randomised to receive an enhanced infection management package (EIMP) or standard infection care. At ENP centres, women receive a regular supply of adequately iodised salt and iron-folate (IFA), enhanced nutrition counselling and those with mid-upper arm circumference of <23 cm receive a micronutrient fortified balanced energy protein supplement (corn soya blend) until delivery. In standard nutrition centres, women receive routine counselling and IFA. EIMP women have additional screening/treatment for urinary and sexual/reproductive tract infections and intensive deworming. Non-EIMP women are managed syndromically per Ministry of Health Guidelines. Participants are followed until 1-month post partum, and a subset until 6 months. The primary study outcomes are newborn weight and length measured at <72 hours of age. Secondary outcomes include preterm birth, low birth weight and stillbirth rates; newborn head circumference; infant weight and length for age z-scores at birth; maternal anaemia; and weight gain during pregnancy. ETHICS AND DISSEMINATION: ENAT is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (001-A1-2019) and Mass General Brigham (2018P002479). Results will be disseminated to local and international stakeholders. REGISTRATION NUMBER: ISRCTN15116516.

Characterisation of Staphylococci species from neonatal blood cultures in low- and middle-income countries.

BACKGROUND: In low- and middle-income countries (LMIC) Staphylococcus aureus is regarded as one of the leading bacterial causes of neonatal sepsis, however there is limited knowledge on the species diversity and antimicrobial resistance caused by Gram-positive bacteria (GPB). METHODS: We characterised GPB isolates from neonatal blood cultures from LMICs in Africa (Ethiopia, Nigeria, Rwanda, and South Africa) and South-Asia (Bangladesh and Pakistan) between 2015-2017. We determined minimum inhibitory concentrations and performed whole genome sequencing (WGS) on Staphylococci isolates recovered and clinical data collected related to the onset of sepsis and the outcome of the neonate up to 60 days of age. RESULTS: From the isolates recovered from blood cultures, Staphylococci species were most frequently identified. Out of 100 S. aureus isolates sequenced, 18 different sequence types (ST) were found which unveiled two small epidemiological clusters caused by methicillin resistant S. aureus (MRSA) in Pakistan (ST8) and South Africa (ST5), both with high mortality (n = 6/17). One-third of S. aureus was MRSA, with methicillin resistance also detected in Staphylococcus epidermidis, Staphylococcus haemolyticus and Mammaliicoccus sciuri. Through additional WGS analysis we report a cluster of M. sciuri in Pakistan identified between July-November 2017. CONCLUSIONS: In total we identified 14 different GPB bacterial species, however Staphylococci was dominant. These findings highlight the need of a prospective genomic epidemiology study to comprehensively assess the true burden of GPB neonatal sepsis focusing specifically on mechanisms of resistance and virulence across species and in relation to neonatal outcome.

Estimates of Stillbirths, Neonatal Mortality, and Medically Vulnerable Live Births in Amhara, Ethiopia.

Importance: Data on birth outcomes and early mortality are scarce, especially in settings with limited resources. Total births, both stillbirths and live births, are often not counted, yet such data are critical to allocate resources and target interventions to improve survival. Objective: To estimate the prevalence of stillbirths, neonatal deaths, and medically vulnerable phenotypes, such as preterm births, small-for-gestational-age (SGA), large-for-gestational-age (LGA), and low-birth-weight (LBW) births, in a setting where these key indicators remain largely unknown. Design, Setting, and Participants: This prospective pregnancy cohort study of women and their newborns was conducted between December 12, 2018, and November 5, 2020. The study was conducted in North Shewa Zone, Amhara, Ethiopia. Data were analyzed from July 2021 to May 2022. Main Outcomes and Measures: Pregnancy status, gestational age, birth weight, and vital status were measured to estimate the prevalence of stillbirths, live births, and medically vulnerable live births (ie, preterm, SGA, LGA, and LBW births). For mortality outcomes, the prevalence of neonatal (overall, early, and late) and perinatal mortality were estimated. Results: Among the 2801 enrolled women, the median (IQR) age at conception was 26.5 (22.2-31.0) years, and the median (IQR) gestational age at enrollment was 24 (17-31) weeks. Of the 2628 women (93.8%) with outcome data, 101 pregnancies (3.8%) resulted in an early loss (<28 gestational weeks). Among the 2527 remaining pregnant women, there were 2518 births between 28 and less than 46 weeks' gestation; 2459 (97.7%; 95% CI, 97.0%-98.2%) were live births and 59 (2.3%; 95% CI, 1.8%-3.0%) were stillbirths. Many newborns (41.7%) were born preterm, SGA, LGA, or LBW. The estimated prevalence was 15.1% (95% CI, 13.7%-16.6%) for preterm births, 23.1% (95% CI, 21.3%-25.1%) for SGA births, 10.6% (95% CI, 9.3%-12.1%) for LGA births, and 9.4% (95% CI, 8.2%-10.8%) for LBW births. Among live births, the overall prevalence of neonatal mortality was 3.1% (95% CI, 2.5%-3.9%); mortality was higher among preterm births (7.2%; 95% CI, 4.9%-10.4%), LBW births (12.2%; 95% CI, 8.2%-17.7%), and SGA births (4.1%; 95% CI, 2.6%-6.5%). The prevalence of early neonatal mortality was almost twice as high as the prevalence of late neonatal mortality. The perinatal mortality prevalence was 4.3% (95% CI, 3.6%-5.2%), with a 1.2:1 ratio of stillbirths to first-week deaths. Conclusions and Relevance: These findings have important implications for newborn health and survival. For policy makers and programmers, accurate data on key indicators of neonatal health provide information for resource allocation and to evaluate progress. For researchers, the findings underlie the importance for further research to develop and deliver interventions that improve health outcomes.

Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study.

BACKGROUND: Neonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs. METHODS: The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Data for sepsis-associated factors in the four domains of health care, maternal, birth and neonatal, and living environment were collected for all mothers and neonates enrolled. Primary outcomes were clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality in neonates during the first 60 days of life. Incidence proportion of livebirths for clinically suspected sepsis and laboratory-confirmed sepsis and incidence rate per 1000 neonate-days for all-cause mortality were calculated. Modified Poisson regression was used to investigate factors associated with neonatal sepsis and parametric survival models for factors associated with all-cause mortality. FINDINGS: Between Nov 12, 2015 and Feb 1, 2018, 29 483 mothers and 30 557 neonates were enrolled. The incidence of clinically suspected sepsis was 166·0 (95% CI 97·69-234·24) per 1000 livebirths, laboratory-confirmed sepsis was 46·9 (19·04-74·79) per 1000 livebirths, and all-cause mortality was 0·83 (0·37-2·00) per 1000 neonate-days. Maternal hypertension, previous maternal hospitalisation within 12 months, average or higher monthly household income, ward size (>11 beds), ward type (neonatal), living in a rural environment, preterm birth, perinatal asphyxia, and multiple births were associated with an increased risk of clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality. The majority (881 [72·5%] of 1215) of laboratory-confirmed sepsis cases occurred within the first 3 days of life. INTERPRETATION: Findings from this study highlight the substantial proportion of neonates who develop neonatal sepsis, and the high mortality rates among neonates with sepsis in LMICs. More efficient and effective identification of neonatal sepsis is needed to target interventions to reduce its incidence and subsequent mortality in LMICs. FUNDING: Bill & Melinda Gates Foundation.

Birhan maternal and child health cohort: a study protocol.

INTRODUCTION: Reliable estimates on maternal and child morbidity and mortality are essential for health programmes and policies. Data are needed in populations, which have the highest burden of disease but also have the least evidence and research, to design and evaluate health interventions to prevent illnesses and deaths that occur worldwide each year. METHODS AND ANALYSIS: The Birhan Maternal and Child Health cohort is an open prospective pregnancy and birth cohort nested within the Birhan Health and Demographic Surveillance System. An estimated 2500 pregnant women are enrolled each year and followed through pregnancy, birth and the postpartum period. Newborns are followed through 2 years of life to assess growth and development. Baseline medical data, signs and symptoms, laboratory test results, anthropometrics and pregnancy and birth outcomes (stillbirth, preterm birth, low birth weight) are collected from both home and health facility visits. We will calculate the period prevalence and incidence of primary morbidity and mortality outcomes. ETHICS AND DISSEMINATION: The cohort has received ethical approval. Findings will be disseminated at scientific conferences, peer-reviewed journals and to relevant stakeholders including the Ministry of Health.