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Objective: To explore potential reasons for differences in preterm neonatal mortality in neonatal intensive care units (NICUs) in India and Pakistan. Design: A prospective observational study, the Project to Understand and Research Stillbirth and Preterms in Southeast Asia (PURPOSe) was conducted July 2018 to February 2020. Setting: Three hospitals in Davangere, India, and a large public hospital in Karachi, Pakistan. Population: Of a total of 3,202 preterm infants enrolled, 1,512 were admitted to a study NICU. Methods: We collected data for neonates, including length of stay, diagnoses, and diagnostic tests. Main outcome measures: Neonatal mortality, tests performed, diagnoses ascertained. Results: For infants of equivalent weights and gestational ages, neonatal mortality in Pakistan was twice that in the Indian NICU. The mean newborn length of stay in Pakistan was 2 days compared with 10 days for India. Fewer diagnostics and other investigations were used to determine neonatal condition or guide treatment in the Pakistani NICU. Because of limited information from testing in Pakistan concerning clinical respiratory distress, respiratory distress syndrome appeared to be over‐diagnosed, whereas other conditions including pneumonia, sepsis, necrotising entercolitis and intraventricular haemorrhage were rarely diagnosed. Conclusion: In the Pakistani site, the limited resources available to the NICU appeared related to a shorter length of stay and decreased diagnostic testing, likely explaining the higher mortality. With improved care, reduction in mortality among preterm neonates should be achievable. [ABSTRACT FROM AUTHOR]

The PURPOSe study was a prospective, observational study conducted in India and Pakistan to determine the cause of death for stillbirths and preterm neonatal deaths, using clinical data together with minimally invasive tissue sampling (MITS) and the histologic and polymerase chain reaction (PCR) evaluation of fetal/neonatal tissues and the placenta. After evaluating all available data, an independent panel chose a maternal, a placental and a fetal/neonatal cause of death. Here, we summarise the major results. Among the most important findings were that most stillbirths were caused by fetal asphyxia, often preceded by placental malperfusion, and clinically associated with pre‐eclampsia, placental abruption and a small‐for‐gestational‐age fetus. The preterm neonatal deaths were primarily caused by birth asphyxia, followed by various infections. An important finding was that many of the preterm neonatal deaths were caused by a nosocomial infection acquired after neonatal intensive care (NICU) admission; the most common organisms were Acinetobacter baumannii, followed by Klebsiella pneumoniae, Escherichia coli/Shigella and Haemophilus influenzae. Group B streptococcus was less commonly present in the placentas or internal organs of the neonatal deaths. [ABSTRACT FROM AUTHOR]

Objective: Group B streptococcus (GBS) has been associated with adverse pregnancy outcomes, but few prospective studies have assessed its prevalence in low‐ and middle‐income country settings. We sought to evaluate the prevalence of GBS by polymerase chain reaction (PCR) in internal organ tissues and placentas of deceased neonates and stillbirths. Design: This was a prospective, observational study. Setting: The study was conducted in hospitals in India and Pakistan. Population: Pregnant women with stillbirths or preterm births were recruited at delivery, as was a group of women with term, live births, to serve as a control group. Methods: A rectovaginal culture was collected from the women in Pakistan to assess GBS carriage. Using PCR, we evaluated GBS in various tissues of stillbirths and deceased neonates and their placentas, as well as the placentas of live‐born preterm and term control infants. Main outcome measures: GBS identified by PCR in various tissues and the placentas; rate of stillbirths and 28‐day neonatal deaths. Results: The most obvious finding from this series of analyses from India and Pakistan was that no matter the country, the condition of the subject, the tissue studied or the methodology used, the prevalence of GBS was low, generally ranging between 3% and 6%. Among the risk factors evaluated, only GBS positivity in primigravidae was increased. Conclusions: GBS diagnosed by PCR was identified in <6% of internal organs of stillbirths and neonatal deaths, and their placentas, and control groups in South Asian sites. This is consistent with other reports from South Asia and is lower than the reported GBS rates from the USA, Europe and Africa. [ABSTRACT FROM AUTHOR]

Objective: To evaluate perinatal outcomes in preterm multiple compared with singleton pregnancies in India and Pakistan. Design: Prospective, observational study. Settings: Study hospitals in India and Pakistan. Population: We evaluated 3897 preterm pregnancies. These mothers gave birth to 3615 (92.8%) singleton infants, 267 (6.8%) sets of twins, 14 (0.4%) sets of triplets and one set of quadruplets. Main outcome measures: Neonatal mortality, stillbirth, cause of death. Results: Of the singleton infants, 691 (19.1%) were stillborn and 2924 (80.9%) live born. Of the 534 infants from twin pregnancies, 41 (7.7%) were stillborn and 493 (92.3%) were live born. Of the 267 sets of twins, in 14 cases (5.2%) both were stillborn, in 13 cases (4.8%) one was stillborn and one live born, and in 240 cases (90.0%) both were live born. In both preterm twins and preterm singletons, the three most common causes of death were intrauterine hypoxia, infections acquired prior to birth and infections acquired at or after birth. The preterm twins appeared less likely to have died from intrauterine hypoxia but more likely to have died from infections acquired at or after birth. Respiratory distress syndrome (RDS) was less likely considered by the panel to be the primary cause of death in either the twins (9.6%) or singletons (9.7%). Congenital anomalies were also not often judged to be the cause of death in either the preterm twins 2 (2.4%) or singletons 27 (5.3%). Conclusion: In the PURPOSe study, neonatal mortality rates in preterm twins compared with singletons when evaluated by sex, GA, birthweight and SGA, were generally similar to rates of preterm singleton neonatal mortality in those groups. Thus, the higher rate of mortality in live‐born twin infants is related to the fact that these infants were more likely to be born earlier rather than to any inherent characteristics of the babies themselves. [ABSTRACT FROM AUTHOR]

Objective: To examine internal organ tissues and placentas of stillbirths for various pathogens. Design: Prospective, observational study. Settings: Three study hospitals in India and a large maternity hospital in Pakistan. Population: Stillborn infants delivered in a study hospital. Methods: A prospective observational study. Main outcome measures: Organisms identified by pathogen polymerase chain reaction (PCR) in internal organs and placental tissues of stillbirths. Results: Of 2437 stillbirth internal tissues, 8.3% (95% CI 7.2–9.4) were positive. Organisms were most commonly detected in brain (12.3%), cerebrospinal fluid (CSF) (9.5%) and whole blood (8.4%). Ureaplasma urealyticum/parvum was the organism most frequently detected in at least one internal organ (6.4% of stillbirths and 2% of all tissues). Escherichia coli/Shigella was the next most common (4.1% one or more internal organ tissue sample and 1.3% of tissue samples), followed by Staphylococcus aureus in at least one internal organ tissue (1.9% and 0.9% of all tissues). None of the other organisms was found in more than 1.4% of the tissue samples in stillbirths or more than 0.6% of the internal tissues examined. In the placenta tissue, membrane or cord blood combined, 42.8% (95% CI 40.2–45.3) had at least one organism identified, with U. urealyticum/parvum representing the most commonly identified (27.8%). Conclusions: In about 8% of stillbirths, there was evidence of a pathogen in an internal organ. Ureaplasma urealyticum/parvum was the most common organism found in the placenta and in the internal tissues, especially in the fetal brain. [ABSTRACT FROM AUTHOR]

Background We identified pathogens found in internal organs and placentas of deceased preterm infants cared for in hospitals in India and Pakistan. Methods Prospective, observational study conducted in delivery units and neonatal intensive care units. Tissue samples from deceased neonates obtained by minimally invasive tissue sampling and placentas were examined for 73 different pathogens using multiplex polymerase chain reaction (PCR). Results Tissue for pathogen PCR was obtained from liver, lung, brain, blood, cerebrospinal fluid, and placentas from 377 deceased preterm infants. Between 17.6% and 34.1% of each type of tissue had at least 1 organism identified. Organism detection was highest in blood (34.1%), followed by lung (31.1%), liver (23.3%), cerebrospinal fluid (22.3%), and brain (17.6%). A total of 49.7% of the deceased infants had at least 1 organism. Acinetobacter baumannii was in 28.4% of the neonates compared with 14.6% for Klebsiella pneumoniae , 11.9% for Escherichia coli/Shigella , and 11.1% for Haemophilus influenzae. Group B streptococcus was identified in only 1.3% of the neonatal deaths. A. baumannii was rarely found in the placenta and was found more commonly in the internal organs of neonates who died later in the neonatal period. The most common organism found in placentas was Ureaplasma urealyticum in 34% of the samples, with no other organism found in >4% of samples. Conclusions In organ samples from deceased infants in India and Pakistan, evaluated with multiplex pathogen PCR, A. baumannii was the most commonly identified organism. Group B streptococcus was rarely found. A. baumannii was rarely found in the placentas of these deceased neonates. [ABSTRACT FROM AUTHOR]

Introduction: Maternal infections likely are an important cause of stillbirths, especially in sub-Saharan Africa and south Asia, where the burden is highest. Due to the lack of routine testing for infection, which can be complex and often expensive, the prevalence of infection during pregnancy and the association of many infections with stillbirth are not well-documented, especially in low-resource countries. Methods: Following an extensive literature review of infection and stillbirth initially published in 2010, we conducted a review of literature in the last 10 years to identify infections associated with stillbirth, focused on those in low-resource settings. Results: During the last 10 years, over 40 bacterial, viral and other pathogens have been associated with stillbirth. Newly emerging viral infections such as Denge as well as several well-established, but not yet eliminated infections such as rubella have been associated with stillbirth. Two of the maternal infections most strongly associated with stillbirth, each with about a 2-fold risk, are malaria and syphilis but others have been associated with risk in a range of studies. With a lack of routine antenatal screening, many pathogens are identified as associated with stillbirth only through case reports. Infection remains an important, yet understudied, cause of stillbirth. Conclusion: Research studies to determine definitive associations between various infections and stillbirth are important to better understand the role of infections and strategies to reduce infection-related stillbirth. [ABSTRACT FROM AUTHOR]

Background Review of data from multiple sources is often necessary to determine cause of death for stillbirths and neonatal deaths, especially in low- to middle-income countries (LMICs) where available data may vary. The minimally invasive tissue sampling (MITS) procedure provides granular histologic and microbiologic data that clinical reports and verbal autopsies cannot provide. Expert panel evaluation of data from individual deaths can be resource-intensive but remains essential to accurately infer causes of death. Methods The Project to Understand and Research Preterms and Stillbirths in South Asia (PURPOSe) study uses review panels to evaluate causes of death in 2 LMICs. To make the process manageable, a subset of the study variables was selected with professional input and organized into case reports. Case reports include clinical information, laboratory results, fetal or neonatal organ histology and polymerase chain reaction results from tissue obtained by MITS. Panelists evaluated the complete case report forms and then determined the cause of death based on available data. Results Computerized case reports averaged 2 to 3 pages. Approximately 6 to 8 cases were reviewed and discussed per 1-hour panel meeting. All panelists were provided the same information; missing data were noted. This limited bias between panelists and across meetings. Study teams notably took ownership of data quality. Conclusions Standardized case reports for cause-of-death determination panel evaluation improve the efficiency of the review process, clarify available information, and limit bias across panelists, time, and location. [ABSTRACT FROM AUTHOR]