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

Abstract

Background: 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.

Methods: 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.

Findings: 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.

Interpretation: 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.

Funding: Bill & Melinda Gates Foundation.

Figure 1

Flow diagram Flow of participants from ascertainment of stillbirth and deaths in children younger than 5 years to CHAMPS enrolment, MITS consent, cause of death determination, and neural tube defect anywhere in the causal chain, by site. Where 2021 HDSS data were not available, 2020 HDSS data were substituted. CHAMPS=Child Health and Mortality Prevention Surveillance Network. DeCoDe=determination of cause of death. MITS=minimally invasive tissue sampling. HDSS=health and demographic surveillance systems. *Eligible stillbirths and deaths in children younger than 5 years never enrolled in CHAMPS. †Deaths enrolled in CHAMPS not eligible for or refused MITS.

Figure 2

Characteristics of CHAMPS deaths consented for MITS and with fatal neural tube defects anywhere in the mortality causal chain, by site (n=69) Missing data for maternal age: Bangladesh n=1; Ethiopia n=14; Mozambique n=1; South Africa n=5. Missing data for religion: Ethiopia n=3; Mozambique n=3; South Africa n=4. Missing data for number of antenatal care visits: Bangladesh n=1; Ethiopia n=28; Mozambique n=2; Sierra Leone n=1; South Africa n=5. CHAMPS=Child Health and Mortality Prevention Surveillance Network. MITS=minimally invasive tissue sampling.

Figure 3

Crude and adjusted cause-specific mortality fractions and total under-5 mortality due to fatal neural tube defects among all stillbirths and deaths in children younger than 5 years in the target population by site, controlling for age Dashed line denotes expected rate of 5–6 deaths per 10 000 births when an effective national folic acid fortification programme is implemented. CHAMPS=Child Health and Mortality Prevention Surveillance Network. CrL=Bayesian credible interval. HDSS=health and demographic surveillance systems. *Target population consists of all deaths enrolled in CHAMPS, regardless of minimally invasive tissue sampling consent. †Quelimane was included in the estimate where the target population was all CHAMPS deaths but excluded when it was the catchment area because HDSS data were not available. ‡Faridpur was included in the estimate where the target population was all CHAMPS deaths but excluded when it was the catchment area because HDSS data were not available.