Pregnancy outcomes in preterm multiple gestations: Results from a prospective study in India and Pakistan (PURPOSe).

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.

Birth asphyxia is under-rated as a cause of preterm neonatal mortality in low- and middle-income countries: A prospective, observational study from PURPOSe.

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.

Factors Associated With Parental Acceptance of Minimally Invasive Tissue Sampling to Identify the Causes of Stillbirth and Neonatal Death.

BACKGROUND: Minimally invasive tissue sampling (MITS) is a noninvasive technique used to determine the cause of deaths. Very little is known about the factors that affect MITS acceptance or refusal. We present findings from a prospective study conducted in Southeast Asia on the reasons for accepting or refusing MITS. METHODS: This substudy was conducted in India and Pakistan to determine the acceptability of MITS in women who had a stillbirth or preterm live birth who later died. A formal questionnaire was used to gather observations during the consent for MITS, such as reasons for acceptance or refusal of MITS, as well as which family members were involved in the decision process. RESULTS: In Pakistan, the MITS acceptability forms were completed for 470 of 477 women (98.5%) with an eligible stillbirth for this substudy, and 334 of 337 (99.1%) with an eligible preterm neonatal death. In India, MITS acceptability forms were completed in 219 of 305 women (71.8%) with an eligible stillbirth and 260 of 264 (98.4%) with an eligible preterm neonatal death. In India, the most common reasons for MITS refusal for both stillbirths and preterm neonatal deaths were cultural concerns, while in Pakistan, the most common reason for MITS refusal was a potential delay in the funeral. The primary reason for accepting MITS was that the parents wanted to understand the cause of death. At both sites, fathers, mothers, and relatives, often in consultation, choose whether or not to accept MITS to determine the cause of death in stillbirths and preterm neonatal deaths. CONCLUSIONS: MITS was more commonly accepted in India than in Pakistan. Cultural concerns in India and funeral delays in Pakistan were common reasons for refusal. Parents from both sites were curious to know the cause of stillbirths and preterm neonatal deaths. The father, mother, and relatives were key decision makers for consenting to or declining MITS.

Perceptions and experiences of men and women towards acceptability and use of contraceptives in underserved areas of Karachi, Pakistan: a midline qualitative assessment of Sukh initiative, Karachi Pakistan.

BACKGROUND: Family planning (FP) is an essential component of Sustainable Development Goals (SDG) and contributes directly to SDG targets 3.7 and 5.6. In Pakistan, contraceptive use has remained stagnant over the past 5 years. This change has been very slow when compared to the FP2020 pledge. The Sukh initiative project was conceived and implemented to alleviate these challenges by providing access to quality contraceptive methods in some underserved areas of Karachi, Pakistan. A qualitative study was conducted to understand the perceptions and experiences of men and women towards acceptability and contraceptive use. METHODS: A qualitative study was conducted at ten Sukh stations located in four towns of Karachi. Focus group discussions (FGDs) were conducted with married women of reproductive age (MWRA) and married men who received FP services through the Sukh initiative. Study participants were purposively sampled for focus group discussions (FGDs). Interview data was manually transcribed and analyzed using thematic analysis. RESULTS: A total of 20 FDGs (Men = 10 FGDs; MWRA = 10 FGDs) were conducted. Three overarching themes were identified: (I) Appropriateness and means to promote contraceptive use; (II) Equity and Accessibility to contraceptives; and (III) Perspective on available FP services. Generally, both men and women were informed about FP methods but women were more cognizant of FP information. The door to door services by community health workers in Sukh initiative areas was largely appreciated both by women and men as it has made the accessibility and availability of the information and services easy. Women suggested that the Sukh initiative should bring some strategies that can help men broaden their perspective towards FP. The study informed that the men feel left out from the FP programs. Therefore, male participants expressed keen interest in initiatives for men in their communities that would cater to their FP needs. CONCLUSIONS: This qualitative study provided a unique opportunity to understand the perceptions of men and women towards the phenomena of contraceptive use. The study identified the need for trained and qualified female and male healthcare providers and well-established health facilities alongside door-to-door services.

A comparison of MITS counseling and informed consent processes in Pakistan, India, Bangladesh, Kenya, and Ethiopia.

Globally, more than 5 million stillbirths and neonatal deaths occur annually. For many, the cause of death (CoD) is unknown. Minimally invasive tissue sampling (MITS) has been increasingly used in postmortem examinations for ascertaining the CoD in stillbirths and neonates. Our study compared the counseling and consent methods used in MITS projects in five countries in Africa and south Asia. Key informant interviews were conducted with researchers to describe the characteristics and backgrounds of counselors, the environment and timing of consent and perceived facilitators and barriers encountered during the consent process. Counselors at all sites had backgrounds in social science, psychology and counseling or clinical expertise in obstetrics/gynecology or pediatrics. All counsellors received training about techniques for building rapport and offering emotional support to families; training duration and methods differed across sites. Counselling environments varied significantly; some sites allocated a separate room, others counselled families at the bedside or nursing stations. All counsellors had a central role in explaining the MITS procedure to families in their local languages. Most sites did not use visual aids during the process, relying solely on verbal descriptions. In most sites, parents were approached within one hour of death. The time needed for decision making by families varied from a few minutes to 24 h. In most sites, extended family took part in the decision making. Because many parents wanted burial as soon as possible, counsellors ensured that MITS would be conducted promptly after receiving consent. Barriers to consent included decreased comprehension of information due to the emotional and psychological impact of grief. Moreover, having more family members engaged in decision-making increased the complexity of counselling and achieving consensus to consent for the procedure. While each site adapted their approach to fit the context, consistencies and similarities across sites were observed.

Perceptions of parents and religious leaders regarding minimal invasive tissue sampling to identify the cause of death in stillbirths and neonates: results from a qualitative study.

BACKGROUND: Recently, the minimal invasive tissue sampling (MITS) procedure has been developed to support determination of the cause of death as an alternate to conventional autopsy, especially in countries where complete diagnostic autopsy is not routine. To assess the feasibility of implementation of the MITS procedure for a study to determine cause of death in premature births and stillbirths in south Asia, we explored the views and perceptions of parents and religious leaders on the acceptability of MITS. METHODS: A qualitative study was conducted at the National Institute of Child Health (NICH) hospital of Karachi, Pakistan. Focus group discussions (FGDs) were conducted with parents of newborns who visited well-baby clinics of the NICH hospital for post-natal check-ups. Key-informant interviews (KIIs) were conducted with religious leaders. Data were analyzed using NVivo 10 software. RESULTS: A total of 13 interviews (FGDs = 8; KIIs = 5) were conducted. Three overarching themes were identified: (I) acceptability of MITS; (II) concerns affecting the implementation of MITS; and (III) religious and cultural perspectives. Participants' acceptance of MITS was based on personal, religious, cultural and social beliefs. Parents widely recognized the need for this procedure in cases where the couple had experienced multiple stillbirths, neonatal deaths and miscarriages. Counseling of parents was considered vital to address emotional concerns of the parents and the family. Religious leaders indicated acceptability of the MITS procedure from a religious perspective and advised that respect for the deceased and consent of the guardians is mandatory when performing MITS. CONCLUSIONS: This qualitative study provided a unique opportunity to understand the views of parents and religious leaders towards the use of MITS. Generally, MITS appears to be an acceptable method for identifying the cause of death in neonates and stillbirths, provided that the deceased is respected and buried as soon as possible without any delays and parents are counseled appropriately. Findings from this research are essential in approaching families for consent for MITS.

Perceptions of parents and healthcare professionals regarding minimal invasive tissue sampling to identify the cause of death in stillbirths and neonates: a qualitative study protocol.

BACKGROUND: Globally, around 2.6 million neonatal deaths occur world-wide every year and the numbers of stillbirths is almost similar. Pakistan is ranked among the highest countries in the world for neonatal mortality. In 2016, for every 1000 babies born in Pakistan, 46 died before the end of the first month of life. Also, Pakistan had the highest rate of stillbirths (43.1/1000 births) in 2015. To meet sustainable development (SDG) targets of reducing neonatal mortality and stillbirths, it is essential to gain understanding about the causes of neonatal death and stillbirths. In Pakistan, full autopsies are conducted only in medico-legal cases and are very rarely performed to identify a definitive cause of death (CoD) and because of cost and insufficient staff are generally not feasible. Recently, minimally invasive tissue sampling (MITS) has been used to determine CoD in neonates and stillbirths as it addresses some of the socio-cultural and religious barriers to autopsy. However, it is not known how families and communities will perceive this procedure; therefore, exploring family and healthcare professionals' perceptions regarding MITS is essential in determining acceptable and feasible approaches for Pakistan. METHODS: The study will employ an exploratory qualitative research design. The study will be conducted at the National Institute of Child Health (NICH) hospital of Karachi. The data collection method will consist of key-informant interviews (KIIs) and focus group discussions (FGDs). FGDs will be conducted with the families and relatives of newborns who are visiting the outpatient department (OPD) and well-baby clinics of NICH hospital. KIIs will be conducted with the NICH - medical director, healthcare providers, professionals involved in proceedings related to death and dying, religious leaders, health sector representatives from the government, public health experts, maternal and child health (MCH) specialists, obstetricians and neonatologists and experts from the bioethics committee. Study data will be analyzed using NVivo 10 software. DISCUSSION: The research will help explore specific cultural, religious and socio-behavioral factors that may increase or decrease the acceptability of MITS for identifying COD in neonates and stillbirths. The findings of the qualitative study will provide a better understanding of parents' and healthcare professionals' attitudes towards the use of MITS on neonatal deaths and stillborns.

The causes of stillbirths in south Asia: results from a prospective study in India and Pakistan (PURPOSe).

BACKGROUND: South Asia contributes more than a third of all global stillbirths, yet the causes remain largely unstudied in this region. New investigations, including novel assessments of placental and fetal tissues, facilitate more precise determination of the underlying causes of stillbirth. We sought to assess underlying and contributing causes of stillbirth from settings in India and Pakistan. METHODS: In this prospective cohort study (PURPOSe), we report the cause of death in stillbirths in hospitals in central India and south Pakistan (Davangere, India [three public and private hospitals] and Karachi, Pakistan [one public maternity and one children's hospital]). Women aged 15 years or older and with a known stillbirth (defined as a pregnancy at 20 or more weeks of gestation with the in-utero death of a fetus) weighing 1000 g or more were included in the study. Maternal clinical factors, placental evaluation, fetal tissue evaluation (from minimally invasive tissue sampling), and PCR for microbial pathogens were used to identify the causes of death. An expert panel reviewed available data for all stillbirths to identify the primary and contributing maternal, placental, and fetal causes of stillbirth. FINDINGS: Between Sept 1, 2018, and Feb 12, 2020, 981 stillborns were included and, of those, 611 were reviewed by the expert panel. The primary maternal causes of stillbirth were hypertensive disease in 221 (36%) of 611 stillbirths, followed by severe anaemia in 66 (11%) stillbirths. The primary placental causes were maternal and fetal vascular malperfusion, in 289 (47%) stillbirths. The primary fetal cause of stillbirth was intrauterine hypoxia, in 437 (72%) stillbirths. We assessed the overlap of main causes and 116 (19%) stillbirths had intrauterine hypoxia, placental malperfusion, and eclampsia or pre-eclampsia indicated as primary causes of death. Infection (including of the placenta, its membranes, and in the fetus) and congenital anomalies also were causative of stillbirth. INTERPRETATION: In south Asia, fetal asphyxia is the major cause of stillbirth. Several placental lesions, especially those associated with maternal and fetal vascular malperfusion and placental abruption, have an important role in asphyxia and fetal death. Maternal hypertension, and especially pre-eclampsia, is often the primary maternal condition associated with this pathway. FUNDING: Bill & Melinda Gates Foundation.

The causes of preterm neonatal deaths in India and Pakistan (PURPOSe): a prospective cohort study.

BACKGROUND: Preterm birth remains the major cause of neonatal death worldwide. South Asia contributes disproportionately to deaths among preterm births worldwide, yet few population-based studies have assessed the underlying causes of deaths. Novel evaluations, including histological and bacteriological assessments of placental and fetal tissues, facilitate more precise determination of the underlying causes of preterm deaths. We sought to assess underlying and contributing causes of preterm neonatal deaths in India and Pakistan. METHODS: The project to understand and research preterm pregnancy outcomes and stillbirths in South Asia (PURPOSe) was a prospective cohort study done in three hospitals in Davangere, India, and two hospitals in Karachi, Pakistan. All pregnant females older than 14 years were screened at the time of presentation for delivery, and those with an expected or known preterm birth, defined as less than 37 weeks of gestation, were enrolled. Liveborn neonates with a weight of 1000 g or more who died by 28 days after birth were included in analyses. Placentas were collected and histologically evaluated. In addition, among all neonatal deaths, with consent, minimally invasive tissue sampling was performed for histological analyses. PCR testing was performed to assess microbial pathogens in the placental, blood, and fetal tissues collected. An independent panel reviewed available data, including clinical description of the case and all clinical maternal, fetal, and placental findings, and results of PCR bacteriological investigation and minimally invasive tissue sampling histology, from all eligible preterm neonates to determine the primary and contributing maternal, placental, and neonatal causes of death. FINDINGS: Between July 1, 2018, and March 26, 2020, of the 3470 preterm neonates enrolled, 804 (23%) died by 28 days after birth, and, of those, 615 were eligible and had their cases reviewed by the panel. Primary maternal causes of neonatal death were hypertensive disease (204 [33%] of 615 cases), followed by maternal complication of pregnancy (76 [12%]) and preterm labour (76 [11%]), whereas the primary placental causes were maternal and fetal vascular malperfusion (172 [28%] of 615) and chorioamnionitis, funisitis, or both (149 [26%]). The primary neonatal cause of death was intrauterine hypoxia (212 [34%] of 615) followed by congenital infections (126 [20%]), neonatal infections (122 [20%]), and respiratory distress syndrome (126 [20%]). INTERPRETATION: In south Asia, intrauterine hypoxia and congenital infections were the major causes of neonatal death among preterm babies. Maternal hypertensive disorders and placental disorders, especially maternal and fetal vascular malperfusion and placental abruption, substantially contributed to these deaths. FUNDING: Bill & Melinda Gates Foundation.

Relationship Between Foot Length and Gestational Age in Pakistan.

Preterm births have a high risk of mortality. Therefore, knowledge of the gestational age (GA) at birth is crucial to guide the appropriate management of a newborn. Common methods for estimating GA such as the last menstrual period, ultrasonography, and post-natal Ballard scoring have some limitations. This study aimed to determine the relationship between foot length and GA to develop and validate an equation for predicting GA of Pakistani newborns. We conducted a prospective study in a large obstetric hospital in Pakistan. Data for this analysis were extracted from the hospital files of eligible women by trained study midwives. Midwives were also trained in performing the Ballard examination and taking foot length using a disposable measuring tape within an hour of the birth. The GA was calculated using an android-based GA calculator. Simple and multiple linear regression were used to construct predicting equations for GA. Both the foot length and GA were available for 1542 cases. The median GA was 34.5 (IQR 4.7) weeks and the median foot length was 7 cm (IQR 1.4). There was a positive linear relationship between foot length and GA (r 2 81.7%, P-value < .001). Stratified analysis showed an r 2 of 81.7% for males and 81.6% for females. The r 2 for stillbirths was 84.1% and, 82.3% for live births. The r 2 for macerated stillbirths was 88.6% and 90.6% for fresh stillbirths. In resource poor settings, the use of foot length can estimate GA in both live births and stillbirths and can easily identify preterm infants.

Factors associated with the discontinuation of modern methods of contraception in the low income areas of Sukh Initiative Karachi: A community-based case control study.

INTRODUCTION: Discontinuation of a contraceptive method soon after its initiation is becoming a public health problem in Low middle income countries and may result in unintended pregnancy and related unwanted consequences. A better understanding of factors behind discontinuation of a modern method would help in designing interventions to continue its use till desired spacing goals are achieved. OBJECTIVE: To determine factors associated with the discontinuation of modern contraceptive methods within six months of its use compared to continued use of modern method for at least six months in low-income areas of Karachi, Pakistan. METHODS: A community-based case-control study was conducted in low-income areas of Karachi. Cases were 137 users who discontinued a modern contraceptive method within 6 months of initiation and were not using any method at the time of interview, while controls were 276 continuous users of modern method for at least last six months from the time of interview. Information was collected by using a structured questionnaire. Applied logistic regression was used to identify the associated factors for discontinuation. RESULTS: The mean ages of discontinued and continued users were 29.3±5.3 years and 29.2±5.4 years respectively. A larger proportion of the discontinued users had no formal education (43.8%) as compared to the continued users (27.9%). The factors associated with discontinuation of a modern method of contraception were belonging to Sindhi ethnicity [OR: 2.54, 95%CI 1.16-5.57], experiencing side effects [OR: 15.12; 95% CI 7.50-30.51], difficulty in accessing contraceptives by themselves [OR: 0.40, 95%CI 0.19-0.83] and difficulty in reaching clinics for management of the side effects [OR: 4.10, 95%CI 2.38-7.05]. Moreover, women having support from the husband for contraceptive use were less likely to discontinue the method [OR: 0.58, 95% CI 0.34-0.98]. CONCLUSIONS: Sindhi ethnicity and side effects of modern methods of contraception were identified as major factors for discontinuation in low-income populations. Similarly, women who had difficulty in travelling to reach clinics for treatment also contributed to discontinuation. Furthermore, women using long acting methods and those supported by their husbands were less likely to discontinue the contraceptive methods. Findings emphasize a need to focus on Sindhi ethnicity and trainings of service providers on management of side effects and provision of high quality of services.

Perceptions of health professionals regarding minimally invasive tissue sampling (MITS) to identify the cause of death in stillbirths and neonates: results from a qualitative study.

BACKGROUND: Pakistan is considered to be one of the riskiest places in the world for childbirth as measured by its high stillbirth and neonatal mortality rates. Complete diagnostic autopsy remains the gold standard to determine the cause of death (CoD); however, it is not routinely implemented due to religious objections, sociocultural beliefs, limited resources and low demand from physicians and families. Recently, minimally invasive tissue sampling (MITS) using needle biopsies of multiple tissues to obtain tissue for histological examination and organism identification with PCR has been developed and promoted to determine CoD in low-resource areas. To ensure successful implementation of MITS, it is important to understand health professionals' attitudes and perceptions related to MITS. METHODS: A qualitative study was conducted at the National Institute of Child Health (NICH), Karachi, Pakistan. Focus group discussions (FGDs) and Key-informant interviews (KIIs) were conducted with health professionals including doctors, nurses, trainees, clinicians, bioethics experts and public health experts to explore their perceptions and views on acceptability of MITS. Data were analyzed using NVivo 10 software. RESULTS: A total of 12 interviews (FGDs = 4; KIIs = 8) were conducted. Four overarching themes were identified: (I) acceptability of MITS; (II) perceived benefits of the MITS procedure; (III) factors facilitating the implementation of MITS; and (IV) health system requirements for implementing the MITS procedure. Generally, MITS was considered as a positive development for the health system. Diagnostic accuracy and identification of less common causes of death were highlighted as two main benefits of the MITS procedure. The study highlighted a number of facilitators for the acceptability of MITS including effective counseling, building trust with parents, fast procedure time, and approaching families within a few hours of death. In addition, lack of skilled staff, poorly equipped healthcare facilities and the potential high cost to conduct MITS were identified as challenges for the implementation of MITS. CONCLUSIONS: This formative research provided a unique opportunity to explore health professionals' views and attitudes towards the MITS procedure. Such insights are crucial to ensure successful implementation and integration of a new technique into the existing health system. The research identified the factors influencing the acceptability of MITS among health professionals in Pakistan. The study also informed factors that could help facilitate the implementation of the MITS procedures in the context of Pakistan and similar settings.