Epidemiology behind the alarmingly high rate of stillbirths in Bangladesh

Epidemiology behind the alarmingly high rate of stillbirths in Bangladesh
Objectives
To evaluate whether there is an infectious driver of the high rate of stillbirths experienced by women in Bangladesh.
Rationale
Of the 2.6 million stillbirths that occur each year, 98% occur in low- and middle-income countries (LMICs). Determining the causes of and preventing stillbirths has been largely neglected as a global health priority; they were not included in the Millennium Development Goals or the Sustainable Development Goals. Yet stillbirth remains an important indicator of antenatal care access and quality, and knowledge about stillbirth has the potential to improve maternal and newborn outcomes. Additionally, because stillbirths occur disproportionately in disadvantaged groups, stillbirth rates are an indicator of health equity. Despite the lack of attention given to stillbirths, the cost of preventing stillbirths in LMICs offers a 10-25-fold return through the added economic and social value that surviving children would offer to their families and communities.
The Every Newborn Action Plan laid out by the World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF) proposes a target of 12 or fewer stillbirths per 1000 total births by 2030, though global average reduction rates are far below what is necessary to achieve this goal. UNICEF reported that in 2019 the global stillbirth rate was 13.9 stillbirths per 1000 total births. However, other data suggest more variable results, as per a prospective Global Network study published in 2020 that found an overall stillbirth rate of 28.2 per 1000 births (in defined geographic areas across 7 sites in low-resource settings in: Kenya, Zambia, Democratic Republic of Congo, India, Pakistan, and Guatemala). Understanding causes of stillbirths is hindered by a lack of national estimates. Within the limited surveillance systems that exist, no cause is identified in nearly half of all stillbirths, though maternal infections are a substantial contributor. Accordingly, one of the most cost-effective interventions for preventing stillbirths is screening for and treating infectious diseases. Bangladesh is among the 10 countries with the highest number of stillbirths, with an average of 25.4 stillbirths per 1000 births. One study in Bangladesh implicated maternal infections in 21.5% of stillbirths. Another study reported that maternal infections were the third leading cause of stillbirths being responsible for 18% of the known etiologies. However, in both published studies, maternal infection was based on reported symptoms and no confirmation of type of infection was provided. In an ongoing study of causes of childhood mortality in Bangladesh investigators have recovered bacteria from blood samples of stillborn babies in whom no maternal infection was suspected (unpublished data). These findings further support the contention that infectious diseases are a major cause of stillbirths.
The notion that the amniotic environment is sterile in healthy pregnancies has been increasingly challenged since the introduction of molecular-based pathogen detection methods, though the evidence is far from clear. Nonetheless, detection of bacteria and viruses in the amniotic fluid has frequently been associated with pregnancy complications such as preterm labor, premature rupture of membranes, and stillbirths, even in the absence of maternal symptoms. This has been recently exemplified in the outbreak of Zika virus that induced a panoply of fetal consequences, including stillbirth, following even asymptomatic maternal infection. The proposed mechanism for intrauterine infections leading to adverse birth outcomes is that the presence of microorganisms increases inflammation which interferes with the normal labor cascade, which may in turn create an unfavorable prenatal environment.
Our hypothesis is that intrauterine infections are an underrecognized factor contributing to excess stillbirths in Bangladesh. We propose to address the gap in understanding etiologies of stillbirths by performing metagenomic sequencing on placental tissues of stillborn babies. The alternate hypothesis would be that stillbirths are caused by non-infectious etiologies, which we plan to address through interviews and a separate arm that will endeavor to evaluate and characterize potential environmental exposures to heavy metals.
Project Dates
2020-2024
Stage of Work
Explication of causal pathways that generate the problem.
1) What’s been accomplished: participant enrollment.
2) What we’re focusing on now: sample collection.
To Learn More About This Work
Stanford Health Policy: Rosenkranz Prize Winner Leads Effort to Protect Health-Care Workers from COVID-19 in Under-Resourced Countries
People
Primary Contact: Ashley Styczynski
Stanford University
Funding
Stanford Rosenkranz Prize 2020
Stanford Maternal & Child Health Research Institute (MCHRI): 2022 Master's Tuition Program Award