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Stillbirth, one of the most common adverse pregnancy outcomes, is especially prevalent in low and middle-income countries (LMICs). Understanding the causes of stillbirth is crucial to developing effective interventions. In this commentary, investigators working across several LMICs discuss the most useful investigations to determine causes of stillbirths in LMICs. Useful data were defined as 1) feasible to obtain accurately and 2) informative to determine or help eliminate a cause of death. Recently, new tools for LMIC settings to determine cause of death in stillbirths, including minimally invasive tissue sampling (MITS) – a method using needle biopsies to obtain internal organ tissue from deceased fetuses for histology and pathogen identification in those tissues have become available. While placental histology has been available for some time, the development of the Amsterdam Criteria in 2016 has provided a useful framework to categorize placental lesions. The authors recommend focusing on the clinical history, the placental evaluation, the external examination of the fetus, and, when available, fetal tissue obtained by MITS, especially of the lung (focused on histology and microbiology) and brain/cerebral spinal fluid (CSF) and fetal blood (focused on microbiological analysis). The authors recognize that this approach may not identify some causes of stillbirth, including some genetic abnormalities and internal organ anomalies, but believe it will identify the most common causes of stillbirth, and most of the preventable causes.

Background The causes of some stillbirths are unclear, and additional work must be done to investigate the risk factors for stillbirths. Objective To apply the International Classification of Disease-10 (ICD-10) for antepartum stillbirth at a referral center in eastern China. Methods Antepartum stillbirths were grouped according to the cause of death according to the International Classification of Disease-10 (ICD-10) criteria. The main maternal condition at the time of antepartum stillbirth was assigned to each patient. Results Antepartum stillbirths were mostly classified as fetal deaths of unspecified cause, antepartum hypoxia. Although more than half of the mothers were without an identified condition at the time of the antepartum stillbirth, where there was a maternal condition associated with perinatal death, maternal medical and surgical conditions and maternal complications during pregnancy were most common. Of all the stillbirths, 51.2% occurred between 28 and 37 weeks of gestation, the main causes of stillbirth at different gestational ages also differed. Autopsy and chromosomal microarray analysis (CMA) were recommended in all stillbirths, but only 3.6% received autopsy and 10.5% underwent chromosomal microarray analysis. Conclusions The ICD-10 is helpful in classifying the causes of stillbirths, but more than half of the stillbirths in our study were unexplained; therefore, additional work must be done. And the ICD-10 score may need to be improved, such as by classifying stillbirths according to gestational age. Autopsy and CMA could help determine the cause of stillbirth, but the acceptance of these methods is currently low.

There is a lack of studying vital registration and disease classification systems in low- and middle-income countries. This study aimed to assess health care professionals' (HCPs') level of awareness, knowledge, use, and perceived barriers of the International Classification of Diseases, 10th version (ICD-10) as well as their perceptions of the electronic neonatal death registration system. A mixed method approach including descriptive cross-sectional quantitative and focus groups with HCPs (physicians, nurses, and midwives) was used to collect data from four major selected hospitals in Jordan. A total of 16 focus groups were conducted. Also, a survey, which included three case studies about the ability of nurses and physicians to identify cause of death, was completed using structured face-to-face interviews. Overall, there was congruency between both the quantitative results and the qualitative findings. The majority of nurses and physicians in the four hospitals were not familiar with the ICD-10 coding system and hence reported minimal use of the coding system. Additionally, the majority of HCPs were not aware whether or not their departments used the ICD-10 to record perinatal mortality. These HCPs identified that lack of knowledge, time, staff and support, and an effective and comprehensive electronic system that allows physicians to accurately choose the exact cause of death were their main barriers to the use of the ICD-10 coding system. Our findings emphasize the importance of developing an effective and comprehensive electronic system which allows HCPs to accurately report and register all perinatal deaths. This system needs to account for the direct and indirect causes of death and for contributing factors such as maternal conditions at the time of perinatal death. Training HCPs on how to use the system is vital for the success and accuracy of the data registration process.

Background Every year, an estimated 2.6 million stillbirths occur worldwide, with up to 98% occurring in low- and middle-income countries (LMIC). There is a paucity of primary data on cause of stillbirth from LMIC, and particularly from sub-Saharan Africa to inform effective interventions. This study aimed to identify the cause of stillbirths in low- and middle-income settings and compare methods of assessment. Methods This was a prospective, observational study in 12 hospitals in Kenya, Malawi, Sierra Leone and Zimbabwe. Stillbirths (28 weeks or more) were reviewed to assign the cause of death by healthcare providers, an expert panel and by using computer-based algorithms. Agreement between the three methods was compared using Kappa (κ) analysis. Cause of stillbirth and level of agreement between the methods used to assign cause of death. Results One thousand five hundred sixty-three stillbirths were studied. The stillbirth rate (per 1000 births) was 20.3 in Malawi, 34.7 in Zimbabwe, 38.8 in Kenya and 118.1 in Sierra Leone. Half (50.7%) of all stillbirths occurred during the intrapartum period. Cause of death (range) overall varied by method of assessment and included: asphyxia (18.5–37.4%), placental disorders (8.4–15.1%), maternal hypertensive disorders (5.1–13.6%), infections (4.3–9.0%), cord problems (3.3–6.5%), and ruptured uterus due to obstructed labour (2.6–6.1%). Cause of stillbirth was unknown in 17.9–26.0% of cases. Moderate agreement was observed for cause of stillbirth as assigned by the expert panel and by hospital-based healthcare providers who conducted perinatal death review (κ = 0.69; p  < 0.0005). There was only minimal agreement between expert panel review or healthcare provider review and computer-based algorithms (κ = 0.34; 0.31 respectively p  < 0.0005). Conclusions For the majority of stillbirths, an underlying likely cause of death could be determined despite limited diagnostic capacity. In these settings, more diagnostic information is, however, needed to establish a more specific cause of death for the majority of stillbirths. Existing computer-based algorithms used to assign cause of death require revision.

This chapter contains sections titled: Unexplained stillbirths Fetal growth restriction: the hidden factor Pathological examination and IUGR Assessing stillbirth by the fetal growth potential Prevalence of IUGR amongst stillbirths IUGR in epidemiological research IUGR and clinical strategies for stillbirth prevention Clinical practice points References

This chapter contains sections titled: Components of evaluation for possible causes of stillbirth Summary References

This chapter contains sections titled: Maternal age Race and ethnicity Pregnancy history Social environment Maternal substance use Maternal nutrition Maternal mental illness Maternal health care Summary and conclusions References

This chapter contains sections titled: Cytogenetic causes of stillbirth Cytogenetic abnormalities of the fetus Placental cytogenetics Single‐gene disorders Evaluation of stillborn pregnancies to identify genetic causes Conclusion References

Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15–60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5–24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates—a measure of relative inequality—increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7–87·2), and for men in Singapore, at 81·3 years (78·8–83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.

Background Understanding the magnitude and clinical causes of maternal and perinatal mortality are basic requirements for positive change. Facility-based information offers a contextualized resource for clinical and organizational quality improvement. We describe the magnitude of institutional maternal mortality, causes of death and cause-specific case fatality rates, as well as stillbirth and pre-discharge neonatal death rates. Methods This paper draws on secondary data from 40 low and middle income countries that conducted emergency obstetric and newborn care assessments over the last 10 years. We reviewed 6.5 million deliveries, surveyed in 15,411 facilities. Most of the data were extracted from reports and aggregated with excel. Results Hemorrhage and hypertensive diseases contributed to about one third of institutional maternal deaths and indirect causes contributed another third (given the overrepresentation of sub-Saharan African countries with large proportions of indirect causes). The most lethal obstetric complication, across all regions, was ruptured uterus, followed by sepsis in Latin America and the Caribbean and sub-Saharan Africa. Stillbirth rates exceeded pre-discharge neonatal death rates in nearly all countries, possibly because women and their newborns were discharged soon after birth. Conclusions To a large extent, facility-based findings mirror what population-based systematic reviews have also documented. As coverage of a skilled attendant at birth increases, proportionally more deaths will occur in facilities, making improvements in record-keeping and health management information systems, especially for stillbirths and early neonatal deaths, all the more critical.