Neural tube defects as a cause of death among stillbirths, infants, and children younger than 5 years in sub-Saharan Africa and southeast Asia: an analysis of the CHAMPS network.

Neural tube defects are common birth defects resulting in severe morbidity and mortality; they can largely be prevented with periconceptional maternal intake of folic acid. Understanding the occurrence of neural tube defects and their contribution to mortality in settings where their burden is highest could inform prevention and health-care policy. We aimed to estimate the mortality attributed to neural tube defects in seven countries in sub-Saharan Africa and southeast Asia. This analysis used data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network and health and demographic surveillance systems from South Africa, Mozambique, Bangladesh, Kenya, Mali, Ethiopia, and Sierra Leone. All stillbirths and infants and children younger than 5 years who died, who were enrolled in CHAMPS, whose families consented to post-mortem minimally invasive tissue sampling (MITS) between Jan 1, 2017, and Dec 31, 2021, and who were assigned a cause of death by a determination of cause of death panel as of May 24, 2022, were included in this analysis, regardless the cause of death. MITS and advanced diagnostic methods were used to describe the frequency and characteristics of neural tube defects among eligible deaths, identify risk factors, and estimate the mortality fraction and mortality rate (per 10 000 births) by CHAMPS site. Causes of death were determined for 3232 stillbirths, infants, and children younger than 5 years, of whom 69 (2%) died with a neural tube defect. Most deaths with a neural tube defect were stillbirths (51 [74%]); 46 (67%) were neural tube defects incompatible with life (ie, anencephaly, craniorachischisis, or iniencephaly) and 22 (32%) were spina bifida. Deaths with a neural tube defect were more common in Ethiopia (adjusted odds ratio 8·09 [95% CI 2·84-23·02]), among female individuals (4·40 [2·44-7·93]), and among those whose mothers had no antenatal care (2·48 [1·12-5·51]). Ethiopia had the highest adjusted mortality fraction of deaths with neural tube defects (7·5% [6·7-8·4]) and the highest adjusted mortality rate attributed to neural tube defects (104·0 per 10 000 births [92·9-116·4]), 4-23 times greater than in any other site. CHAMPS identified neural tube defects, a largely preventable condition, as a common cause of death among stillbirths and neonatal deaths, especially in Ethiopia. Implementing interventions such as mandatory folic acid fortification could reduce mortality due to neural tube defects. Bill & Melinda Gates Foundation.

Madrid L ，Vyas KJ ，Kancherla V ，Leulseged H ，Suchdev PS ，Bassat Q ，Sow SO ，El Arifeen S ，Madhi SA ，Onyango D ，Ogbuanu I ，Scott JAG ，Blau D ，Mandomando I ，Keita AM ，Gurley ES ，Mahtab S ，Akelo V ，Sannoh S ，Tilahun Y ，Varo R ，Onwuchekwa U ，Rahman A ，Adam Y ，Omore R ，Lako S ，Xerinda E ，Islam KM ，Wise A ，Tippet-Barr BA ，Kaluma E ，Ajanovic S ，Kotloff KL ，Hossain MZ ，Mutevedzi P ，Tapia MD ，Rogena E ，Moses F ，Whitney CG ，Assefa N ，CHAMPS Consortium ... -  《Lancet Global Health》

Initial findings from a novel population-based child mortality surveillance approach: a descriptive study.

Sub-Saharan Africa and south Asia contributed 81% of 5·9 million under-5 deaths and 77% of 2·6 million stillbirths worldwide in 2015. Vital registration and verbal autopsy data are mainstays for the estimation of leading causes of death, but both are non-specific and focus on a single underlying cause. We aimed to provide granular data on the contributory causes of death in stillborn fetuses and in deceased neonates and children younger than 5 years, to inform child mortality prevention efforts. The Child Health and Mortality Prevention Surveillance (CHAMPS) Network was established at sites in seven countries (Baliakandi, Bangladesh; Harar and Kersa, Ethiopia; Siaya and Kisumu, Kenya; Bamako, Mali; Manhiça, Mozambique; Bombali, Sierra Leone; and Soweto, South Africa) to collect standardised, population-based, longitudinal data on under-5 mortality and stillbirths in sub-Saharan Africa and south Asia, to improve the accuracy of determining causes of death. Here, we analysed data obtained in the first 2 years after the implementation of CHAMPS at the first five operational sites, during which surveillance and post-mortem diagnostics, including minimally invasive tissue sampling (MITS), were used. Data were abstracted from all available clinical records of deceased children, and relevant maternal health records were also extracted for stillbirths and neonatal deaths, to incorporate reported pregnancy or delivery complications. Expert panels followed standardised procedures to characterise causal chains leading to death, including underlying, intermediate (comorbid or antecedent causes), and immediate causes of death for stillbirths, neonatal deaths, and child (age 1-59 months) deaths. Between Dec 10, 2016, and Dec 31, 2018, MITS procedures were implemented at five sites in Mozambique, South Africa, Kenya, Mali, and Bangladesh. We screened 2385 death notifications for inclusion eligibility, following which 1295 families were approached for consent; consent was provided for MITS by 963 (74%) of 1295 eligible cases approached. At least one cause of death was identified in 912 (98%) of 933 cases (180 stillbirths, 449 neonatal deaths, and 304 child deaths); two or more conditions were identified in the causal chain for 585 (63%) of 933 cases. The most common underlying causes of stillbirth were perinatal asphyxia or hypoxia (130 [72%] of 180 stillbirths) and congenital infection or sepsis (27 [15%]). The most common underlying causes of neonatal death were preterm birth complications (187 [42%] of 449 neonatal deaths), perinatal asphyxia or hypoxia (98 [22%]), and neonatal sepsis (50 [11%]). The most common underlying causes of child deaths were congenital birth defects (39 [13%] of 304 deaths), lower respiratory infection (37 [12%]), and HIV (35 [12%]). In 503 (54%) of 933 cases, at least one contributory pathogen was identified. Cytomegalovirus, Escherichia coli, group B Streptococcus, and other infections contributed to 30 (17%) of 180 stillbirths. Among neonatal deaths with underlying prematurity, 60% were precipitated by other infectious causes. Of the 275 child deaths with infectious causes, the most common contributory pathogens were Klebsiella pneumoniae (86 [31%]), Streptococcus pneumoniae (54 [20%]), HIV (40 [15%]), and cytomegalovirus (34 [12%]), and multiple infections were common. Lower respiratory tract infection contributed to 174 (57%) of 304 child deaths. Cause of death determination using MITS enabled detailed characterisation of contributing conditions. Global estimates of child mortality aetiologies, which are currently based on a single syndromic cause for each death, will be strengthened by findings from CHAMPS. This approach adds specificity and provides a more complete overview of the chain of events leading to death, highlighting multiple potential interventions to prevent under-5 mortality and stillbirths. Bill & Melinda Gates Foundation.

Taylor AW ，Blau DM ，Bassat Q ，Onyango D ，Kotloff KL ，Arifeen SE ，Mandomando I ，Chawana R ，Baillie VL ，Akelo V ，Tapia MD ，Salzberg NT ，Keita AM ，Morris T ，Nair S ，Assefa N ，Seale AC ，Scott JAG ，Kaiser R ，Jambai A ，Barr BAT ，Gurley ES ，Ordi J ，Zaki SR ，Sow SO ，Islam F ，Rahman A ，Dowell SF ，Koplan JP ，Raghunathan PL ，Madhi SA ，Breiman RF ，CHAMPS Consortium ... -  《Lancet Global Health》

Prioritizing Health Care Strategies to Reduce Childhood Mortality.

Madewell ZJ ，Whitney CG ，Velaphi S ，Mutevedzi P ，Mahtab S ，Madhi SA ，Fritz A ，Swaray-Deen A ，Sesay T ，Ogbuanu IU ，Mannah MT ，Xerinda EG ，Sitoe A ，Mandomando I ，Bassat Q ，Ajanovic S ，Tapia MD ，Sow SO ，Mehta A ，Kotloff KL ，Keita AM ，Tippett Barr BA ，Onyango D ，Oele E ，Igunza KA ，Agaya J ，Akelo V ，Scott JAG ，Madrid L ，Kelil YE ，Dufera T ，Assefa N ，Gurley ES ，El Arifeen S ，Spotts Whitney EA ，Seib K ，Rees CA ，Blau DM ，Child Health and Mortality Prevention Surveillance Network ... -  《JAMA Network Open》

Child deaths caused by Klebsiella pneumoniae in sub-Saharan Africa and south Asia: a secondary analysis of Child Health and Mortality Prevention Surveillance (CHAMPS) data.

Verani JR ，Blau DM ，Gurley ES ，Akelo V ，Assefa N ，Baillie V ，Bassat Q ，Berhane M ，Bunn J ，Cossa ACA ，El Arifeen S ，Gunturu R ，Hale M ，Igunza A ，Keita AM ，Kenneh S ，Kotloff KL ，Kowuor D ，Mabunda R ，Madewell ZJ ，Madhi S ，Madrid L ，Mahtab S ，Miguel J ，Murila FV ，Ogbuanu IU ，Ojulong J ，Onyango D ，Oundo JO ，Scott JAG ，Sow S ，Tapia M ，Traore CB ，Velaphi S ，Whitney CG ，Mandomando I ，Breiman RF ... -  《Lancet Microbe》

Causes of stillbirth and death among children younger than 5 years in eastern Hararghe, Ethiopia: a population-based post-mortem study.

Child mortality is high in Ethiopia, but reliable data on the causes of death are scarce. We aimed to gather data for the contributory causes of stillbirth and child deaths in eastern Ethiopia. In this population-based post-mortem study, we established a death-notification system in health facilities and in the community in Kersa (rural), Haramaya (rural) and Harar (urban) in eastern Ethiopia, at a new site of the Child Health and Mortality Prevention Surveillance (CHAMPS) network. We collected ante-mortem data, did verbal autopsies, and collected post-mortem samples via minimally invasive tissue sampling from stillbirths (weighing at least 1000 g or with an estimated gestational age of at least 28 weeks) and children who died younger than 5 years. Children-or their mothers, in the case of stillbirths and deaths in children younger than 6 months-had to have lived in the catchment area for the past 6 months to be included. Molecular, microbiological, and histopathological analyses were done in collected samples. Cause of death was established by an expert panel on the basis of these data and classified as underlying, comorbid, or immediate separately for stillbirths, neonatal deaths (deaths aged 0-27 days), and child deaths (aged 28 days to <5 years). Between Feb 4, 2019, and Feb 3, 2021, 312 deaths were eligible for inclusion, and the families gave consent in 195 (63%) cases. Cause of death was established in 193 (99%) cases. Among 114 stillbirths, the underlying cause of death was perinatal asphyxia or hypoxia in 60 (53%) and birth defects in 24 (21%). Among 59 neonatal deaths, the most common underlying cause was perinatal asphyxia or hypoxia (17 [29%]) and the most common immediate cause of death was neonatal sepsis, which occurred in 27 (60%). Among 20 deaths in children aged 28 days to 59 months, malnutrition was the leading underlying cause (15 [75%]) and infections were common immediate and comorbid causes. Pathogens were identified in 19 (95%) child deaths, most commonly Klebsiella pneumoniae and Streptococcus pneumoniae. Perinatal asphyxia or hypoxia, infections, and birth defects accounted for most stillbirths and child deaths. Most deaths could have been prevented with feasible interventions, such as improved maternity services, folate supplementation, and improved vaccine uptake. Bill & Melinda Gates Foundation.

Madrid L ，Alemu A ，Seale AC ，Oundo J ，Tesfaye T ，Marami D ，Yigzaw H ，Ibrahim A ，Degefa K ，Dufera T ，Teklemariam Z ，Gure T ，Leulseged H ，Wittmann S ，Abayneh M ，Fentaw S ，Temesgen F ，Yeshi MM ，Dubale M ，Girma Z ，Ackley C ，Damisse B ，Breines M ，Orlien SMS ，Blau DM ，Breiman RF ，Abate E ，Dessie Y ，Assefa N ，Scott JAG ，CHAMPS Ethiopia Study Group ... -  《Lancet Global Health》