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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: To describe our experience of screening with visual inspection with acetic acid (VIA) and colposcopy to identify women with high‐grade precancerous cervical lesions who were candidates for cryotherapy. Women were screened to determine eligibility for a clinical trial testing the safety and efficacy of a new, simple and inexpensive cryotherapy device (CryoPop®) targeted for use in low and middle‐income countries (LMICs). Design: Prospective cohort study. Setting: Primary and urban health centres in Belagavi, Hubballi and Vijayapur, India. Population: Women in the age‐group 30–49 years, premenopausal, with no prior hysterectomy and no known HIV infection were eligible for screening. Methods: Visual inspection with acetic acid was performed on eligible women following informed consent. VIA‐positive women were referred for colposcopy and biopsy. Biopsies were read by two pathologists independently, with a third pathologist acting as tie‐breaker if needed. Main outcome measures: The primary outcome measures were the number/proportion of women screening positive by VIA and the number/proportion of those women screening VIA‐positive found to have high‐grade cervical lesions on biopsy (cervical intraepithelial neoplasia 2/3 [CIN 2/3]). Demographic variables were compared between women who screened VIA‐positive and those who screened VIA‐negative; a separate comparison of demographic and limited reproductive variables was performed between women who had CIN 2/3 on biopsy and those without CIN 2/3 on biopsy. Chi‐square or Fisher's exact tests for categorical data and t‐tests or analysis of variance for numeric data were used with all tests two‐sided and performed at an alpha 0.05 level of statistical significance. Results: A total of 9130 women were screened with VIA between 4 July 2020 and 31 March 2021. The mean age of all women screened was 37 years (standard deviation = 5.6 years) with 6073 of the women (66.5%) in the 30–39 year range. Only 1% of women reported prior cervical cancer screening. A total of 501 women (5.5%) were VIA‐positive; of these, 401 women underwent colposcopy. Of those who had colposcopy, 17 (4.2%) had high‐grade lesions on biopsy, an additional 164 (40.9%) had low‐grade cervical lesions on biopsy or endocervical curettage and one woman (0.2%) was found to have invasive cancer. VIA‐positive women were younger and had higher levels of education and income; however, women who were VIA‐positive and found to have CIN 2/3 were older, were more likely to be housewives and had higher household income than those without CIN 2/3. Conclusion: Despite the COVID‐19 pandemic, over 9100 women were screened with VIA for precancerous lesions. However, only 17 (4.2%) were found to have biopsy‐proven high‐grade cervical lesions, underscoring the subjective performance of VIA as a screening method. Given that this is significantly lower than rates reported in the literature, it is possible that the prevalence of high‐grade lesions in this population was impacted by screening a younger and more rural population. This study demonstrates that screening is feasible in an organised fashion and can be scaled up rapidly. However, while inexpensive and allowing for same‐day treatment, VIA may be too subjective and have insufficient accuracy clearly to identify lesions requiring treatment, particularly in low‐prevalence and low‐risk populations, calling into question its overall cost‐effectiveness. [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 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]

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]

Objective: To inform digital health design by evaluating diagnostic test properties of antenatal blood pressure (BP) outputs and levels to identify women at risk of adverse outcomes. Design: Planned secondary analysis of cluster randomised trials. Setting: India, Pakistan, Mozambique. Population: Women with in‐community BP measurements and known pregnancy outcomes. Methods: Blood pressure was defined by its outputs (systolic and/or diastolic, systolic only, diastolic only or mean arterial pressure [calculated]) and level: normotension‐1 (<135/85 mmHg), normotension‐2 (135–139/85–89 mmHg), non‐severe hypertension (140–149/90–99 mmHg; 150–154/100–104 mmHg; 155–159/105–109 mmHg) and severe hypertension (≥160/110 mmHg). Dose–response (adjusted risk ratio [aRR]) and diagnostic test properties (negative [−LR] and positive [+LR] likelihood ratios) were estimated. Main Outcome Measures: Maternal/perinatal composites of mortality/morbidity. Results: Among 21 069 pregnancies, different BP outputs had similar aRR, −LR, and +LR for adverse outcomes. No BP level (even normotension‐1) was associated with low risk (all −LR ≥0.20). Across outcomes, risks rose progressively with higher BP levels above normotension‐1. For each of maternal central nervous system events and stillbirth, BP ≥155/105 mmHg showed at least good diagnostic test performance (+LR ≥5.0) and BP ≥135/85 mmHg at least fair performance, similar to BP ≥140/90 mmHg (+LR 2.0–4.99). Conclusions: In the community, normal BP values do not provide reassurance about subsequent adverse outcomes. Given the similar performance of BP cut‐offs of 135/85 and 140/90 mmHg for hypertension, and 155/105 and 160/110 mmHg for severe hypertension, digital decision support for women in the community should consider using these lower thresholds. [ABSTRACT FROM AUTHOR]

Objective: To assess respiratory distress syndrome (RDS) compared with birth asphyxia as the cause of death in preterm newborns, assigned by the neonatal intensive care unit (NICU) physician at the time of death and assigned by a panel with complete obstetric history, placental evaluation, tissue histology and microbiology. Design: Prospective, observational study. Settings Study NICUs in India and Pakistan. Population Preterm infants delivered in study facility. Methods: A total of 410 preterm infants who died in the NICU with cause of death ascertained by the NICU physicians and independently by expert panels. We compared the percentage of cases assigned RDS versus birth asphyxia as cause of death by the physician and the panel. Main outcome measures: RDS and birth asphyxia. Results: Of 410 preterm neonatal deaths, the discharging NICU physicians found RDS as a cause of death among 83.2% of the cases, compared with the panel finding RDS in only 51.0%. In the same neonatal deaths, the NICU physicians found birth asphyxia as a cause of death in 14.9% of the deaths, whereas the panels found birth asphyxia in 57.6% of the deaths. The difference was greater in Pakistan were the physicians attributed 89.7% of the deaths to RDS and less than 1% to birth asphyxia whereas the panel attributed 35.6% of the deaths to RDS and 62.7% to birth asphyxia. Conclusions: NICU physicians who reported cause of death in deceased preterm infants less often attributed the death to birth asphyxia, and instead more often chose RDS, whereas expert panels with more extensive data attributed a greater proportion of deaths to birth asphyxia than did the physicians. Linked article: This article is commented on by Evelyn Verheijen, pp. 2001 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471-0528.17245 [ABSTRACT FROM AUTHOR]

Objective: Stillbirths occur 10–20 times more frequently in low‐income settings compared with high‐income settings. We created a methodology to define the proportion of stillbirths that are potentially preventable in low‐income settings and applied it to stillbirths in sites in India and Pakistan. Design: Prospective observational study. Setting: Three maternity hospitals in Davangere, India and a large public hospital in Karachi, Pakistan. Population: All cases of stillbirth at ≥20 weeks of gestation occurring from July 2018 to February 2020 were screened for participation; 872 stillbirths were included in this analysis. Methods: We prospectively defined the conditions and gestational ages that defined the stillbirth cases considered potentially preventable. Informed consent was sought from the parent(s) once the stillbirth was identified, either before or soon after delivery. All information available, including obstetric and medical history, clinical course, fetal heart sounds on admission, the presence of maceration as well as examination of the stillbirth after delivery, histology, and polymerase chain reaction for infectious pathogens of the placenta and various fetal tissues, was used to assess whether a stillbirth was potentially preventable. Main outcome measures: Whether a stillbirth was determined to be potentially preventable and the criteria for assignment to those categories. Results: Of 984 enrolled, 872 stillbirths at ≥20 weeks of gestation met the inclusion criteria and were included; of these, 55.5% were deemed to be potentially preventable. Of the 649 stillbirths at ≥28 weeks of gestation and ≥1000 g birthweight, 73.5% were considered potentially preventable. The most common conditions associated with a potentially preventable stillbirth at ≥28 weeks of gestation and ≥1000 g birthweight were small for gestational age (SGA) (52.8%), maternal hypertension (50.2%), antepartum haemorrhage (31.4%) and death that occurred after hospital admission (15.7%). Conclusions: Most stillbirths in these sites were deemed preventable and were often associated with maternal hypertension, antepartum haemorrhage, SGA and intrapartum demise. Most stillbirths are preventable by better care for women with hypertension, growth restriction and antepartum haemorrhage. Most stillbirths are preventable by better care for women with hypertension, growth restriction and antepartum haemorrhage. [ABSTRACT FROM AUTHOR]

We had a number of goals for our study.2,3 The first was to develop and describe a methodology to evaluate stillbirth preventability in hospital settings in low- and middle-income countries (LMICs). We thank Drs Sharma and Aggarwal for their positive comments about our PURPOSe study.1 We are pleased to acknowledge their efforts and those of others to determine which stillbirths might be preventable. [Extracted from the article]