Effect of Maternal and Newborn Care Service Package on Perinatal and Newborn Mortality: A Cluster Randomized Clinical Trial.

Importance: In resource-constrained settings where the neonatal mortality rate (NMR) is high due to preventable causes and health systems are underused, community-based interventions can increase newborn survival by improving health care practices. Objectives: To develop and evaluate the effectiveness of a community-based maternal and newborn care services package to reduce perinatal and neonatal mortality in rural Pakistan. Design, Setting, and Participants: This cluster randomized clinical trial was conducted between November 1, 2012, and December 31, 2013, in district Rahim Yar Khan in the province of Punjab. A cluster was defined as an administrative union council. Any consenting pregnant resident of the study area, regardless of gestational age, was enrolled. An ongoing pregnancy surveillance system identified 12 529 and 12 333 pregnancies in the intervention and control clusters, respectively; 9410 pregnancies were excluded from analysis due to continuation of pregnancy at the end of the study, loss to follow-up, or miscarriage. Participants were followed up until the 40th postpartum day. Statistical analysis was performed from January to May 2014. Intervention: A maternal and newborn health pack, training for community- and facility-based health care professionals, and community mobilization through counseling and education sessions. Main Outcomes and Measures: The primary outcome was perinatal mortality, defined as stillbirths per 1000 births and neonatal death within 7 days per 1000 live births. The secondary outcome was neonatal mortality, defined as death within 28 days of life per 1000 live births. Systematic random sampling was used to allocate 10 clusters each to intervention and control groups. Analysis was conducted on a modified intention-to-treat basis. Results: For the control group vs the intervention group, the total number of households was 33 188 vs 34 315, the median number of households per cluster was 3092 (IQR, 3018-3467) vs 3469 (IQR, 3019-4075), the total population was 229 155 vs 234 674, the mean (SD) number of residents per household was 6.9 (9.5) vs 6.8 (9.6), the number of males per 100 females (ie, the sex ratio) was 104.2 vs 103.7, and the mean (SD) number of children younger than 5 years per household was 1.0 (4.2) vs 1.0 (4.3). Altogether, 7598 births from conrol clusters and 8017 births from intervention clusters were analyzed. There was no significant difference in perinatal mortality between the intervention and control clusters (rate ratio, 0.86; 95% CI, 0.69-1.08; P = .19). The NMR was lower among the intervention than the control clusters (39.2/1000 live births vs 52.2/1000 live births; rate ratio, 0.75; 95% CI, 0.58-0.95; P = .02). The frequencies of antenatal visits and facility births were similar between the 2 groups. However, clean delivery practices were higher among intervention clusters than control clusters (63.2% [2284 of 3616] vs 13.2% [455 of 3458]; P < .001). Chlorhexidine use was also more common among intervention clusters than control clusters (55.9% [4271 of 7642] vs 0.3% [19 of 7203]; P < .001). Conclusions and Relevance: This pragmatic cluster randomized clinical trial demonstrated a reduction in NMR that occurred in the background of improved household intrapartum and newborn care practices. However, the effect of the intervention on antenatal visits, facility births, and perinatal mortality rates was inconclusive, highlighting areas requiring further research. Nevertheless, the improvement in NMR underscores the effectiveness of community-based programs in low-resource settings. Trial Registration: ClinicalTrials.gov Identifier: NCT01751945.

Effectiveness of unconditional cash transfers combined with lipid-based nutrient supplement and/or behavior change communication to prevent stunting among children in Pakistan: a cluster randomized controlled trial.

BACKGROUND: In Pakistan, the prevalence of stunting among children younger than 5 y has remained above WHO critical thresholds (≥30%) over the past 2 decades. OBJECTIVES: We hypothesized that an unconditional cash transfer (UCT) combined with lipid-based nutrient supplement (LNS) and/or social and behavior change communication (SBCC) will prevent stunting among children 6-23 mo of age. METHODS: This was a 4-arm, community-based cluster randomized controlled trial conducted in the district of Rahim Yar Khan, Pakistan. A total of 1729 children (UCT, n = 434; UCT + SBCC, n = 433; UCT + LNS, n = 430; and UCT + LNS + SBCC, n = 432) were enrolled at 6 mo of age and measured monthly for 18 mo until the age of 24 mo. RESULTS: At 24 mo of age, children who received UCT + LNS [rate ratio (RR): 0.85; 95% CI: 0.74, 0.97; P = 0.015) and UCT + LNS + SBCC (RR: 0.86; 95% CI: 0.77, 0.96; P = 0.007) had a significantly lower risk of being stunted compared with the UCT arm. No significant difference was noted among children who received UCT + SBCC (RR: 1.03; 95% CI: 0.91, 1.16; P = 0.675) in the risk of being stunted compared with the UCT arm. The pooled prevalence of stunting among children aged 6-23 mo was 41.7%, 44.8%, 38.5%, and 39.3% in UCT, UCT + SBCC, UCT + LNS, and UCT + LNS + SBCC, respectively. In pairwise comparisons, a significant impact on stunting among children in UCT + LNS (P = 0.029) and UCT + LNS + SBCC (P = <0.001) was noted compared with the UCT arm. CONCLUSIONS: UCT combined with LNS and UCT + LNS + SBCC were effective in reducing the prevalence of stunting among children aged 6-23 mo in marginalized populations. UCT + SBCC was not effective in reducing the child stunting prevalence. This trial was registered at clinicaltrials.gov as NCT03299218.

Effect of an integrated neonatal care kit on cause-specific neonatal mortality in rural Pakistan.

BACKGROUND: In 2018, Pakistan had the world's highest neonatal mortality rate. Within Pakistan, most neonatal deaths occur in rural areas where access to health facilities is limited, and robust vital registration systems are lacking. To improve newborn survival, there is a need to better understand the causes of neonatal death in high burden settings and engage caregivers in the promotion of newborn health. OBJECTIVE: To describe the causes of neonatal death in a rural area in Pakistan and to estimate the effect of an integrated neonatal care kit (iNCK) on cause-specific neonatal mortality. METHODS: We analyzed data from a community-based, cluster-randomized controlled trial of 5286 neonates in Rahim Yar Khan (RYK), Punjab, Pakistan between April 2014 and August 2015. In intervention clusters, Lady Health Workers (LHW) delivered the iNCK and education on its use to pregnant women while control clusters received the local standard of care. The iNCK included interventions to prevent and identify signs of infection, identify low birthweight (LBW), and identify and manage hypothermia. Verbal autopsies were attempted for all deaths. The primary outcome was cause-specific neonatal mortality. RESULTS: Verbal autopsies were conducted for 84 (57%) of the 147 reported neonatal deaths. The leading causes of death were infection (44%), intrapartum-related complications (26%) and prematurity/LBW (20%). There were no significant differences in neonatal mortality due to prematurity/LBW (RR 0.43; 95% CI 0.15-1.24), infection (RR 1.10; 95% CI 0.58-2.10) or intrapartum-related complications (RR 1.04; 95% CI 0.0.45-2.41) among neonates who died in the intervention arm compared to those who died in the control arm. CONCLUSION: The major causes of neonatal deaths in RYK, Pakistan mirror the global landscape of neonatal deaths. The iNCK did not significantly reduce any cause-specific neonatal mortality.

Specialized Nutritious Food Combined With Cash Transfers and Social and Behavior Change Communication to Prevent Stunting Among Children Aged 6 to 23 Months in Pakistan: Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: In Pakistan, the prevalence of stunting in children younger than 5 years has remained above global critical levels over the past two decades, with the stunting rate being 40.2% in 2018. Children living in rural areas and in the poorest households suffer the most from stunting across the country-43.2% in rural areas and 51.4% in the lowest wealth quintile. As a continuing public health concern, it is essential that stunting prevention is a national priority in order to ensure human capital development, especially among the poorest households. OBJECTIVE: The primary objective of this study is to determine the effect of a medium quantity of a lipid-based nutrient supplement (LNS) combined with unconditional cash transfers and social and behavior change communication (SBCC) on reduction of stunting in children aged 6 to 23 months. METHODS: A 5-arm cluster randomized controlled trial will be conducted in the district of Rahim Yar Khan in Punjab, Pakistan. The intervention packages will be (1) cash only, (2) cash with LNS, (3) cash with SBCC, and (4) cash with SBCC and LNS. The control arm will receive routine standard of care. We will enroll children at 6 months of age and follow up on a monthly basis up to 24 months of age. A total of 2000 children, 400 in each arm, will be enrolled to detect a 20% reduction in the prevalence of stunting among children aged 24 months. Length, weight, food intake, compliance to interventions, morbidities, and other relevant data will be collected at enrollment and on a monthly basis over the period of 18 months. The process evaluation will assess acceptability of the interventions and potential barriers to implementation through focus group discussions and in-depth interviews with the target population and relevant stakeholders. Furthermore, a cost analysis will be conducted to assess the cost-effectiveness of each intervention package. RESULTS: The study protocol was approved by the Ethics Review Committee of Aga Khan University in Pakistan on January 4, 2017. Data collection began in May 2017 and was completed in July 2019. Data analyses are yet to be completed. This study will explore the effectiveness of intervention packages comprised of cash transfers from Benazir Income Support Programme with or without additional LNS and SBCC in preventing childhood stunting. We expect the results to be published in peer-reviewed journals by autumn of 2020. CONCLUSIONS: The findings of this trial will provide robust evidence as to which intervention packages can have significant effects on linear growth of children and design effective intervention packages to prevent stunting in children aged 6 to 23 months. TRIAL REGISTRATION: ClinicalTrials.gov NCT03299218; https://clinicaltrials.gov/ct2/show/NCT03299218. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19001.

Effect of an integrated neonatal care kit on neonatal health outcomes: a cluster randomised controlled trial in rural Pakistan.

INTRODUCTION: In 2016, 2.6 million children died during their first month of life. We assessed the effectiveness of an integrated neonatal care kit (iNCK) on neonatal survival and other health outcomes in rural Pakistan. METHODS: We conducted a community-based, cluster randomised, pragmatic, open-label, controlled intervention trial in Rahim Yar Khan, Punjab, Pakistan. Clusters, 150 villages and their lady health workers (LHWs), were randomly assigned to deliver the iNCK (intervention) or standard of care (control). In intervention clusters, LHWs delivered the iNCK and education on its use to pregnant women. The iNCK contained a clean birth kit, chlorhexidine, sunflower oil, a continuous temperature monitor (ThermoSpot), a heat reflective blanket and reusable heat pack. LHWs were also given a hand-held scale. The iNCK was implemented primarily by caregivers. The primary outcome was all-cause neonatal mortality. Outcomes are reported at the individual level, adjusted for cluster allocation. Enrolment took place between April 2014 and July 2015 and participant follow-up concluded in August 2015. RESULTS: 5451 pregnant women (2663 and 2788 in intervention and control arms, respectively) and their 5286 liveborn newborns (2585 and 2701 in intervention and control arms, respectively) were enrolled. 147 newborn deaths were reported, 65 in the intervention arm (25.4 per 1000 live births) compared with 82 in the control arm (30.6 per 1000 live births). Neonatal mortality was not significantly different between treatment groups (risk ratio 0.83, 95% CI 0.58 - 1.18; p = 0.30). CONCLUSION: Providing co-packaged interventions directly to women did not significantly reduce neonatal mortality. Further research is needed to improve compliance with intended iNCK use.

Evaluation of the uptake and impact of neonatal vitamin A supplementation delivered through the Lady Health Worker programme on neonatal and infant morbidity and mortality in rural Pakistan: an effectiveness trial.

BACKGROUND: Despite evidence for the benefits of vitamin A supplementation (VAS) among children 6 to 59 months of age, the feasibility of introduction and potential benefit of VAS in the neonatal period in public health programmes is uncertain. OBJECTIVE: The primary objective was to evaluate the feasibility and effectiveness of early neonatal VAS (single dose of 50 000 international units within 48-72 hours after birth) delivered through the public sector Lady Health Worker (LHW) programme in rural Pakistan and to document its association with a reduction in mortality at 6 months of age. METHODS: A community-based, cluster randomised, placebo-controlled trial was undertaken in two districts of rural Pakistan. LHWs dispensed vitamin A/placebo in identical capsules to newborn infants within 48-72 hours of birth. Follow-up visits were undertaken at 1 week of age and every 4 weeks thereafter until 6 months of age. RESULTS: Of a total of 15 433 consecutive pregnancies among eligible women of reproductive age, 13 225 pregnancies were registered, 12 218 live births identified and 11 028 newborn infants reached by LHWs. Of these, 5380 (49%) received neonatal VAS and 5648 (51%) placebo. The LHWs successfully delivered the capsules to 79% of newborns within 72 hours of birth with no significant adverse effects. Although the proportion of days observed with symptoms of fever, diarrhoea or rapid breathing were lower with neonatal VAS, these differences were not statistically significant. Mortality rates in the two groups were comparable at 6 months of age. CONCLUSIONS: While our study demonstrated that neonatal VAS was safe and could be feasibly delivered by LHWs in Pakistan as part of their early postnatal visits, the overall lack of benefit on neonatal and 6-month morbidity and mortality in our population suggests the need for further evaluation of this intervention in populations at risk. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00674089.

Improved accessibility of emergency obstetrics and newborn care (EmONC) services for maternal and newborn health: a community based project.

BACKGROUND: Every year an estimated three million neonates die globally and two hundred thousand of these deaths occur in Pakistan. Majority of these neonates die in rural areas of underdeveloped countries from preventable causes (infections, complications related to low birth weight and prematurity). Similarly about three hundred thousand mother died in 2010 and Pakistan is among ten countries where sixty percent burden of these deaths is concentrated. Maternal and neonatal mortality remain to be unacceptably high in Pakistan especially in rural areas where more than half of births occur. METHOD/DESIGN: This community based cluster randomized controlled trial will evaluate the impact of an Emergency Obstetric and Newborn Care (EmONC) package in the intervention arm compared to standard of care in control arm. Perinatal and neonatal mortality are primary outcome measure for this trial. The trial will be implemented in 20 clusters (Union councils) of District Rahimyar Khan, Pakistan. The EmONC package consists of provision of maternal and neonatal health pack (clean delivery kit, emollient, chlorhexidine) for safe motherhood and newborn wellbeing and training of community level and facility based health care providers with emphasis on referral of complicated cases to nearest public health facilities and community mobilization. DISCUSSION: Even though there is substantial evidence in support of effectiveness of various health interventions for improving maternal, neonatal and child health. Reduction in perinatal and neonatal mortality remains a big challenge in resource constrained and diverse countries like Pakistan and achieving MDG 4 and 5 appears to be a distant reality. A comprehensive package of community based low cost interventions along the continuum of care tailored according to the socio cultural environment coupled with existing health force capacity building may result in improving the maternal and neonatal outcomes. The findings of this proposed community based trial will provide sufficient evidence on feasibility, acceptability and effectiveness to the policy makers for replicating and scaling up the interventions within the health system.