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\begin{document}

\title{Implementing Effective Investigations for Cause of Stillbirth}



\author[1]{Elizabeth McClure}%
\author[2]{Robert L Goldenberg}%
\affil[1]{RTI International}%
\affil[2]{Columbia University Medical Center}%


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  \date{May 08, 2024}


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BJOG-22-0382.R1: Implementing Effective Investigations for Cause of
Stillbirth

Elizabeth M McClure, PhD

Robert L Goldenberg, MD

RTI International, Durham, NC

Columbia University, New York, NY

Stillbirth is one of the most common adverse pregnancy outcomes in low
and middle-income countries (LMICs), with rates in the range of 40 to 50
per thousand births in some regions {[}1{]}. International goals aim for
no country to have a rate of \textgreater{}10 per thousand births by
2035 {[}Hug L, et al. Lancet. 2021;398(10302):772-85{]}. To achieve
this, a better understanding of stillbirth causes often requiring
additional investigations is critical. For several reasons, including
low prioritization, inadequate resources, and hesitancy by families and
providers, investigations on stillbirth causes in LMICs have been
limited to date.

Bedwell et al used a grounded theory approach to explore the views of
women, partners, families, health workers and community leaders in
Malawi, Tanzania, and Zambia regarding investigations to determine the
cause(s) of stillbirth {[}Bedwell et al, BJOG (in press){]}. While most
would like more information regarding the stillbirth, the authors noted
cultural and religious obstacles to performing the investigations,
including preferences for quick burial, reluctance to disfigure the
deceased fetus, concerns about blame, as well as costs.

One test to inform cause of stillbirths is minimally invasive tissue
sampling (MITS), using needle biopsies to obtain internal organ tissue
for histological evaluation and microbial analyses. For a study on
causes of stillbirth in Pakistan and India, we explored the
acceptability of MITS among parents, relatives, religious leaders, and
government officials {[}Feroz A, et al. Reprod Health.2019;16(1):53{]}.
The perceived benefits included knowing the cause of death, and both
personal and societal benefits in preventing subsequent stillbirths.
Concerns regarded rapid burial and reluctance to disfigure the
stillborn. In Pakistan, with some caveats, religious leaders approved,
and, when MITS was undertaken, in both Pakistan and India, approximately
50\% of the parents consented for the MITS procedure.

Because obstacles to testing in general and to MITS specifically relate
to time, cost, and disfigurement, we have considered which examinations
feasible in LMICs provide the most information at minimal cost. Page et
al., in a similar exercise in a US study, noted that the most useful
test was placental histology (65\%) followed by full autopsy (42\%)
{[}Page JM, Obstet Gynecol 2017;129(4):699-706.{]}. No other tests were
useful for \textgreater{}12\% of cases. Similar studies have rarely been
performed in LMICs. The prevalence of the causes relates to the
frequency of tests' usefulness. In high-income countries where birth
asphyxia and infection have been reduced, congenital and genetic
anomalies have assumed a larger proportion of stillbirths, and testing
for those conditions using karyotyping and other genetic tests become
proportionately more important. However, in many LMICs, birth asphyxia
remains the major cause of stillbirth and genetic issues play a smaller
proportional role.

To develop the most effective methodology to determine cause of
stillbirth, the prevalent conditions, and the tests' usefulness to
diagnose those conditions should be considered together. Importantly,
the community and other stakeholder's perceived benefits and obstacles
to various tests as described in the Bedwell, et al must be considered
to ultimately be successful in implementing the necessary
investigations.

For LMICs, given that asphyxia and infection appear to be major causes
of stillbirth, tests to diagnose these conditions will likely be
important to implement, including the obstetric history and histological
placental evaluation for diagnosing asphyxia and infection. Of potential
information gained from MITS, histology of the fetal lung, and
bacteriological assessment of the fetal blood and brain/CSF may be the
most useful. Thus, by considering the prevalence of the causes of
stillbirth, the usefulness of tests to diagnose the prevalent
conditions, and importantly addressing the community's sense of benefit
and obstacles, an effective approach to stillbirth cause of death
investigation can be developed.

Declaration of Interest: The authors declare no conflicts of interest.

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