BJOG-22-0382.R1: Implementing Effective Investigations for Cause of StillbirthElizabeth M McClure, PhDRobert L Goldenberg, MDRTI International, Durham, NCColumbia University, New York, NYStillbirth 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 >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 >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.

Preterm neonatal survival: what is the role of prognostic models?Elizabeth M McClure, PhD1Robert L Goldenberg, MD21Social, Statistical and Environmental Sciences, RTI International, Durham, NC2Columbia University, New York, NYEven before the 1960’s and the introduction of the specialty of neonatology, and continuing to the present, numerous efforts have been made to understand the relationship between newborn birthweight and the risk of mortality. (1) With the development of neonatal intensive care units (NICUs), attention to survival rates and neurologic outcomes among those at the lowest birthweights and gestational ages (GA) has grown. (2) Defining the lower limits of GA or birthweight associated with the neonatal outcomes is important for clinicians, families, and others to inform appropriate decision-making and clinical care.To predict newborn survival, numerous models have been developed to estimate risk at specific birthweights and/or GAs. To date, more than 35 have been published, almost exclusively from high-income countries with advanced NICU care. In a study published recently, van Beek et al sought to validate one of these predictive models from the United Kingdom (UK), deemed to be among the highest quality, with the objective of assessing its value for clinical use. (3)Van Beek et al used an independent Dutch population to validate survival among very preterm infants using the UK model’s parameters. Because they found relatively good performance, the authors’ concluded that the model could inform daily clinical practice. However, the generalizability of their results, especially to other populations differing by ethnicity or socioeconomic status, is questionable. The parameters for the model quality focused on birthweight, GA, and gender, but many other metrics (including the racial diversity, quality of care, etc.) were limited. In particular, the interventions available and utilized for obstetric and neonatal care were not specified, which would be important for their goal of clinical use of the model. Importantly, the quality of obstetric care is not considered. (4) Both the availability and quality of specific obstetric and neonatal interventions in any given setting may be among the most important factors impacting survival.Especially important for clinical considerations, long-term outcomes, including severe disabilities, were not addressed. Concerns about neurodevelopmental outcomes in infants at the lower limits of birthweight and GA are as or more important to parents and caregivers than survival. (5) It is thus unclear how this – or virtually any other model - can be useful for “daily clinical practice”.A better strategy to inform clinical care is for individual health-care facilities to maintain neonatal survival and neurological outcome statistics. These types of data within a specific context may be more helpful to physicians, including obstetricians and neonatologists, who often, together with parents and caregivers, make decisions related to interventions prior to delivery or during NICU care. Newborn outcomes, especially at the extreme lower limits of birthweight and GA, remains an area of intense interest. While models may provide some supportive information, it is difficult to imagine that these will ever replace clinical decisions informed by actual outcome data from the specific facility.Conflicts of interest: The authors declare no conflicts of interest.References:1. Goldenberg RL, Nelson KG, Dyer RL, Wayne JB. The variability of viability: the effect of physicians’ perceptions of viability on the survival of very low birth weight infants. Am J Obstet Gynecol 1982; 143:678-84.2. Bottoms SF, Paul RH, Mercer BM, MacPherson CA, Caritis SN, Moawad AW. Obstetric determinants of neonatal survival: antenatal predictors of neonatal survival and morbidity in extremely low birth weight infants. Am J Obstet Gynecol. 1999 80(3 Pt 1):665-9.3. Van Beek P.E, Groenendaal F, Onland W, Koole S, Dijk PH, Dijkmanet KP et al. Prognostic model for predicting survival in very preterm infants: an external validation study. BJOG (in press)4. Goepfert AR, Goldenberg RL, Hauth JC, Bottoms SF, Iams JD, Mercer BM Obstetrical determinants of neonatal neurological morbidity in < or = 1000-gram infants. Am J Perinatol. 1999;16(1):33-42.5. Iams JD, Mercer BM. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. What we have learned about antenatal prediction of neonatal morbidity and mortality. Semin Perinatol 2003:247-52.