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Background: The impact of direct and indirect drivers on linear growth and wasting in young children is of public health interest. While the contributions of poverty, maternal education, empowerment and birth weight to early childhood growth are well recognized, the contribution of environmental factors like heat, precipitation, agriculture outputs and food security in comparable datasets is less well established., Objectives: To investigate the association of length-for-age z-score (LAZ) and weight-for-length z-score (WLZ) with various indicators among children under 2 years of age in Pakistan using representative household level nutrition surveys and ecological datasets., Methods: Using geo-tagged metadata from Pakistan's 2011 and 2018 National Nutrition Surveys (NNS), anthropometric data from 29,887 children (9,231 from 2011 and 20,656 from 2018) were analyzed. Dietary intake and food security data for 140 districts were linked to gridded data on temperature, precipitation and soil moisture, and district measures of agriculture production of edible crops. Multiple linear regressions assessed factors associated with length for age Z score (LAZ) and weight for length z scores (WLZ) in index children., Results: LAZ was positively associated with improved socio-economic conditions (β=0.06), food security (β=0.10), birth size (β=0.26), maternal age (β=0.02), BMI (β=0.02), height (β=0.02) and dietary score (β=0.03). Negative associations with LAZ were found for increased temperature, precipitation, diarrhea, household crowding and parity. Similar patterns were observed with WLZ for higher surface temperatures and precipitation were associated with declines in linear growth, alongside increased diarrhea prevalence and higher maternal parity., Conclusions: Apart from recognized multifactorial drivers of stunting and wasting among children such as poverty, food insecurity and maternal undernutrition, our analysis suggest the potential independent association with climatic factors such as heat and excess precipitation over time. These findings underscore the need for further research and potential integration of climatic mitigation and adaptation with nutrition response strategies., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Zulfiqar Bhutta reports financial support was provided by Gates Ventures. Zulfiqar Bhutta reports financial support was provided by Bill and Melinda Gates Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Background: Numerous studies have investigated the efficacy of probiotics in treating acute and persistent diarrhoea. However, probiotics have not been established as a recommended management option for diarrhoeal illness by the World Health Organization (WHO). Therefore, we conducted a systematic review of randomised controlled trials to assess the efficacy of probiotics for the management of acute and persistent diarrhoea in children., Methods: A systematic search on PubMed, CINAHL, Wiley Cochrane Library, Scopus, Clinicaltrials.gov, and WHO International Clinical Trials Registry Platform (ICTRP) was performed. All studies published in the year 2000 and onwards that assessed the use of probiotics in the management of acute and persistent diarrhoea in children aged 0-10 years were included. The risk of bias was assessed using the Cochrane Risk of Bias II (RoB-2) tool and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. This review was commissioned by WHO for revision of their guidelines for childhood diarrhoea management., Results: The review included 98 studies with a total of 17 236 participants. Studies were categorised based on the WHO definition of diarrhoea or author-specified definition. In studies considering the WHO definition of diarrhoea, the probiotics group was more likely to achieve clinical cure (risk ratio = 1.12 (95% confidence interval (CI) = 1.01, 1.24, studies = 14)) and reduce the duration of diarrhoea (mean difference = -13.27 hours (95% CI = -16.72, -9.83, studies = 33)) than the control group in children with acute diarrhoea. However, the effect size was small, and statistical heterogeneity was very high, leading to low certainty of evidence. In children with persistent diarrhoea, probiotics reduced the duration of diarrhoea by 95 hours (mean difference = -96.45 (95% CI = -110.53, -82.37, studies = 2)), but the certainty of the evidence was very low., Conclusions: The results from this systematic review suggest low certainty of evidence for the effect of probiotics on clinical cure and duration of diarrhoea in children. There was significant diversity in the genus, species, dosages, and duration of treatment in the trial and administration. High levels of heterogeneity reduced the certainty of evidence. Large-scale randomised clinical trials are needed to evaluate specific probiotic strains and doses. In addition, cost-effective analysis studies are needed to be explored in future research., Registration: The protocol for this review was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023449200)., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests. YBN is a staff member of the World Health Organization. The authors alone are responsible for the views expressed in this article, and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: Oral rehydration solution (ORS) is crucial in the management of diarrhoea. Until the early 2000s, the standard formulation of glucose-based ORS with a total osmolarity of 311 mmol/L was being used for this purpose. However, due to concerns about sodium levels and cases of hypernatremia, a low-osmolarity ORS solution (LORS) with an osmolarity of 245mmol/L or less was developed to replace the standard ORS. With this systematic review, we aimed to assess the effectiveness of LORS compared to standard ORS for the treatment of acute and persistent diarrhoea., Methods: We comprehensively searched PubMed, CINAHL, the Cochrane Library, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, and Scopus until 20 July 2023 for studies published after 1990 assessing the efficacy of LORS in acute and persistent diarrhoea in children under 10 years of age. Meta-analysis was conducted using the RevMan software. We performed log approximation for all the values for an outcome when studies reported arithmetic and geometric means per the Cochrane Handbook. We otherwise used the Cochrane Risk of Bias II tool to assess the risk of bias in individual studies, and assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. This review was commissioned by the WHO for revision of guidelines for childhood diarrhoea., Results: For the comparison of LORS to standard ORS in acute diarrhoea, our findings suggest that there was a significant decrease in the duration of diarrhoea (mean difference (MD) = -0.28; 95% confidence interval (CI) = -0.41, -0.15; moderate certainty of evidence), stool output (MD = -0.25; 95% CI = -0.35, -0.16; very low certainty of evidence), and ORS intake (MD = -0.18; 95% CI = -0.28, -0.07; moderate certainty of evidence) in patients receiving LORS. There was a comparable effect on the number of patients cured within five days, treatment failure, and frequency of unscheduled intravenous therapy (risk ratio (RR) = 0.77; 95% CI = 0.72, 9.38; low certainty of evidence). For persistent diarrhoea, there was a significant decrease in duration of diarrhoea (MD = -30.60; 95% CI = -48.95, -12.25), stool output (MD = -14.00; 95% CI = -26.63, -1.37), and ORS intake (MD = -21.40; 95% CI = -41.01, -1.79), while there was a comparable effect on the number of patients cured., Conclusion: Our findings suggest that LORS should continue to be recommended in children under the age of 10 years with acute watery or persistent diarrhoea and upholds the current WHO recommendations., Registration: PROSPERO: CRD42023438762., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose the following activities and/or relationships: YBN is staff member of the World Health Organization., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: The use of antibiotics in the treatment of acute and persistent watery diarrhoea has long been a subject of contention. While the advantages of using antimicrobials are acknowledged, concerns remain regarding potential adverse effects and antibiotic resistance. Therefore, we conducted a systematic review and meta-analysis to assess the efficacy of antibiotics compared to placebos for the treatment of diarrhoea., Methods: We searched PubMed, CINAHL, the Cochrane Library, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, and Scopus from inception until 20 July 2023 for studies published after the year 2000 assessing antibiotics vs placebo in acute and persistent diarrhoea and/or blood in stools in children less than 10 years of age. We conducted a meta-analysis for the included studies, assessed them using the Risk of Bias 2 tool, and evaluated their quality of evidence through the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. This review was commissioned by WHO for revision of their guidelines for childhood diarrhoea management., Results: We included five randomised controlled trials (RCTs) for acute watery diarrhoea and no study for bloody diarrhoea. Our findings suggest that there is a significant increase in clinical cure (risk ratio (RR) = 2.28; 95% confidence interval (CI) = 1.52, 3.41; low certainty evidence) and parasitological cure (RR = 2.86; 95% CI = 1.72 to 4.74; low certainty evidence) among children with acute watery diarrhoea in the antibiotic group when compared to the placebo group. The duration of diarrhoea (in hours) was significantly reduced (mean difference = -24.90; 95% CI = -34.09, -15.71; low certainty evidence) in the intervention group, while the effect on all-cause mortality (RR = 0.71; 95% CI = 0.40, 1.27; moderate certainty evidence) and the need for intravenous fluid infusion (RR = 0.50; 95% CI = 0.05, 5.17; very low certainty evidence) were comparable between the two groups., Conclusions: In children under 10 years of age suffering from acute watery or persistent diarrhoea, antibiotics led to an apparent increase in cure rates. However, considering the low certainty of evidence, low number of studies with small sample sizes, and the fact that most studies were conducted in a single country, further investigation and cautious interpretation are warranted, as is a large multi-country RCT that would allow for firmer conclusions., Registration: PROSPERO: CRD42023447133., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose the following activities and/or relationships: YBN is staff member of the World Health Organization., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: Zinc is a micronutrient that plays a role in immune system strengthening and regulation of intestinal epithelial cells, and can reduce the duration and severity of diarrhoea. We conducted a systematic review of randomised controlled trials (RCTs) to assess the effectiveness of zinc compared to no zinc for the management of acute and persistent diarrhoea in children., Methods: We searched PubMed, the Cochrane Library, Scopus, CINAHL, ClinicalTrials.gov, and World Health Organization (WHO) International Clinical Trials Registry Platform from inception until 31 July 2023 for studies published from year 2000 onwards that assessed the use of zinc in the management of acute and persistent diarrhoea in children aged less than 10 years. We conducted the meta-analysis in Cochrane's RevMan software, determined risk of bias in individual studies using the Risk of Bias 2 (RoB 2) tool, and assessed the quality of evidence through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. This review was commissioned by the WHO for revision of their guidelines for childhood diarrhoea management., Results: We included 38 RCTs in this systematic review. Our findings suggest that, in children with acute diarrhoea, zinc supplementation resulted in a greater proportion of children who recovered from diarrhoea at last follow-up (risk ratio (RR) = 1.07; 95% confidence interval (CI) = 1.03, 1.1; moderate certainty of evidence) and a reduction in the duration of diarrhoea (mean difference (MD) = -13.27 hours; 95% CI = -17.66, -8.89; moderate certainty of evidence) when compared to placebo. A significant number of children in the zinc group compared to placebo experienced vomiting (RR = 1.46; 95% CI = 1.22, 1.76; moderate certainty of evidence), however, there were few vomiting episodes in low-dose zinc group compared to high-dose (RR = 0.80; 95% CI = 0.72, 0.89; moderate certainty of evidence). In children with persistent diarrhoea, zinc supplementation led to a greater proportion of children who recovered from diarrhoea (RR = 1.75; 95% CI = 1.34, 2.30; low certainty of evidence). The low certainty of evidence ratings were mostly due to high heterogeneity among the studies., Conclusions: Zinc should continue to be recommended in children under the age of 10 years with acute or persistent diarrhoea, but moderate certainty of evidence concludes that the dose of zinc should be reduced. However, further multi-country randomised clinical trials are required with a direct comparison to assess the appropriate dosage, duration and adverse effects., Registration: PROSPERO: CRD42023439028., Competing Interests: Disclosure of interests: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose the following activities and/or relationships: YBN is staff member of the World Health Organization., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Objective: We examined associations between fat free mass (FFM) and fat mass (FM) accretion during the first 1000 days of life and neurodevelopment in term-born, low-risk infants from Karachi, Pakistan., Design: Prospective, observational study nested within the larger Multi-Center Body Composition Reference Study. FFM, FM, and fat% were estimated using measured deuterium dilution method. Neurodevelopmental outcomes were assessed at 24 months on the INTER-NDA (INTERGROWTH-21st Project Neurodevelopment Assessment) (n = 132)., Results: Children with gross motor delays had significantly lower FFM at 18 months (8.01 ± 0.97 kg vs. 7.55 ± 0.20 kg). Children with positive and negative behavior problems had significantly higher fat% at 24 months (20.62 ± 4.30% vs. 18.23 ± 5.46%) and 20.89 ± 4.24% vs. 18.54 ± 5.38%). No associations remained significant after adjusting for covariates. Trajectory modeling showed that between 12 and 18 months, negative behavior scores changed by 13.8 points for every standard deviation change in fat accretion., Conclusions: Our findings highlight the importance of balancing neurodevelopment and metabolic risk when designing nutritional interventions for young children., (© 2023. The Author(s).)

Approximately five billion people do not have access to necessary surgical treatment globally and up to 85% of children in LMICs are affected with conditions requiring surgical care by the age of 15 years. It is crucial to identify common surgical conditions in children in Pakistan to inform healthcare professionals and policymakers for effective resource allocation. This representative cross-sectional household survey conducted on children aged 5-10 years assessed existing surgical diseases and healthcare-seeking behaviors in the two largest provinces (Sindh and Punjab) of Pakistan. The data was collected through a validated cross-sectional survey tool [Surgeons OverSeas Assessment of Surgical Need (SOSAS)]. Caregivers were asked about their child's recent and past surgical conditions in six distinct anatomical regions and pictures were taken of identified conditions after appropriate consent for further diagnosis. Health-seeking behaviors including the kind of treatment sought, the nature of care received, and the reasons for not receiving care were noted. 13.5% of children surveyed reported a surgical condition, with a similar distribution across urban (13.2%) and rural (13.7) areas and the most common cause was trauma. The greatest number of surgical conditions were found to be on the head and neck region (57.7%), while the back accounted for the least number of conditions (1.7%). Our results outline a need for organizing all entities (governmental, non-governmental, and private) involved in child health to ensure efficient resource allocation to cater to existing surgical problems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Qazi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To describe presenting diagnoses and rates and causes of death by age category and sex among children with acute illness brought to a district headquarter hospital in Pakistan., Design: Prospective cohort study., Setting: Sanghar district headquarter hospital, Sindh, Pakistan between December 2019 and April 2020 and August 2020 and December 2020., Participants: 3850 children 0-14 years presenting with acute illness to the emergency and outpatient departments and 1286 children admitted to the inpatient department., Outcome Measures: The primary outcome was Global Burden of Disease diagnosis category. Secondary outcomes were 28-day mortality rate, cause of death and healthcare delays, defined as delay in care-seeking, delay in reaching the healthcare facility and delay in appropriate treatment., Results: Communicable diseases were the most common presenting diagnoses among outpatients and among inpatients aged 1 month to 9 years. Non-communicable diseases and nutritional disorders were more common with increasing age. Few children presented with injuries. Newborn period (age <28 days) was associated with increased odds of death (OR 4.34 [95% CI 2.38 to 8.18], p<0.001, reference age 28 days-14 years) and there was no significant difference in odds of death between female vs male children (OR 1.12, 95% CI 0.6 to 2.04, p=0.72). 47 children died in the hospital (3.6%) and three (0.2%) died within 28 days of admission. Most children who died were <28 days old (n=32/50, 64%); leading diagnoses included neonatal sepsis/meningitis (n=13/50, 26%), neonatal encephalopathy (n=7/50, 14%) and lower respiratory tract infections (n=6/50, 12%). Delays in care-seeking (n=15) and in receiving appropriate treatment (n=12) were common., Conclusion: This study adds to sparse literature surrounding the epidemiology of disease and hospital outcomes for children with acute illness seeking healthcare in rural Pakistan and, in particular, among children aged 5-14 years. Further studies should include public and private hospitals within a single region to comprehensively describe patterns of care-seeking and interfacility transfer in district health systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Undernutrition during pregnancy is linked to adverse pregnancy and birth outcomes and has downstream effects on the growth and development of children. The gut microbiome has a profound influence on the nutritional status of the host. This phenomenon is understudied in settings with a high prevalence of undernutrition, and further investigation is warranted to better understand such interactions., Methods and Analysis: This is a prospective, longitudinal observational study to investigate the relationship between prokaryotic and eukaryotic microbes in the gut and their association with maternal body mass index (BMI), gestational weight gain, and birth and infant outcomes among young mothers (17-24 years) in Matiari District, Pakistan. We aim to enrol 400 pregnant women with low and normal BMIs at the time of recruitment (<16 weeks of gestation). To determine the weight gain during pregnancy, maternal weight is measured in the first and third trimesters. Gut microbiome dynamics (bacterial and eukaryotic) will be assessed using 16S and 18S rDNA surveys applied to the maternal stool samples. Birth outcomes include birth weight, small for gestational age, large for gestational age, preterm birth and mortality. Infant growth and nutritional parameters include WHO z-scores for weight, length and head circumference at birth through infancy. To determine the impact of the maternal microbiome, including exposure to pathogens and parasites on the development of the infant microbiome, we will analyse maternal and infant microbiome composition, micronutrients in serum using metallomics (eg, zinc, magnesium and selenium) and macronutrients in the stool. Metatranscriptomics metabolomics and markers of inflammation will be selectively deployed on stool samples to see the variations in dietary intake and maternal nutritional status. We will also use animal models to explore the bacterial and eukaryotic components of the microbiome., Ethics and Dissemination: The study is approved by the National Bioethics Committee (NBC) in Pakistan, the Ethics Review Committee (ERC) at Aga Khan University and the Research Ethics Board (REB) at the Hospital for Sick Children, and findings will be published in peer-reviewed journals., Trial Registration Number: NCT05108675., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Infants are at a higher risk of severe illness with COVID-19 infection compared to older children. While COVID-19 vaccination is not recommended for young infants, they can acquire maternally-derived anti-SARS-CoV-2 antibodies passively through the placenta and breastmilk. We described the persistence of infection-induced maternal antibodies in infant circulation at 9-12 months of age., Methodology: This was a cross-sectional study nested within the INTERCOVID multinational cohort study. For each COVID positive pregnant woman, two unmatched consecutive COVID negative pregnant women were enrolled between April and September 2020. Women with a positive PCR test, radiographic signs consistent with COVID-19, or at least 2 predefined symptoms of COVID-19 were considered as COVID positive. For this nested cross-sectional study, all COVID positive and either one of the COVID negative participants recruited from the Aga Khan University, Pakistan were approached 9-12 months after delivery, and maternal and infant sera were collected for antibody detection., Results: Altogether, 83 mothers provided consent, of whom 32 (38.6 %) were COVID positive and 51 (61.4 %) were COVID negative during pregnancy. Anti-SARS-CoV-2 antibodies were present in 13 (41 %) infants born to COVID positive and 19 (39 %) infants born to COVID negative mothers (p = 0.87). The presence of reactive antibodies in infants at follow-up was associated with maternal antibodies at follow-up (OR:9.50, 95 % CI:2.03-44.42; p = 0.004). COVID infection occurred in 3 (6 %) infants born to COVID negative mothers while no infant born to a COVID positive mother had a history of infection (p = 0.27)., Conclusion: The presence of reactive anti-SARS-CoV-2 antibodies in infants at 9-12 months of age is associated with maternal seropositivity 9-12 months after delivery rather than maternal infection during pregnancy. Further studies are required to validate these findings and assess whether passive immunity in infants is protective against COVID-19 infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Introduction: After trivalent oral poliovirus vaccine (tOPV) cessation, Pakistan has maintained immunity to type 2 poliovirus by administering inactivated polio vaccine (IPV) in routine immunization, alongside monovalent OPV type 2 (mOPV2) and IPV in supplementary immunization activities (SIAs). This study assesses the change in poliovirus type 2 immunity after tOPV withdrawal and due to SIAs with mOPV2 and IPV among children aged 6-11 months., Methods: Three cross-sectional sequential serological surveys were conducted in 12 polio high-risk areas of Pakistan. 25 clusters from each geographical stratum were selected utilizing probability proportional to size., Results: Seroprevalence of type 2 poliovirus was 49%, with significant variation observed among surveyed areas; <30% in Pishin, >80% in Killa Abdullah, Mardan & Swabi, and Rawalpindi. SIAs with IPV improved immunity from 38 to 57% in Karachi and 60 to 88% in Khyber. SIAs with IPV following mOPV2 improved immunity from 62 to 65% in Killa Abdullah, and combined mOPV2 and IPV SIAs in Pishin improved immunity from 28 to 89%. Results also reflected that immunity rates for serotypes 1 and 3 were consistently above 90% during all three phases and across all geographical areas., Conclusion: The study findings highlight the importance of implementing effective vaccination strategies to prevent the re-emergence of poliovirus. Moreover, the results provide crucial information for policymakers working toward achieving global polio eradication., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hussain, Umer, Khan, Sajid, Ahmed, Begum, Iqbal, Alam, Safdar, Baig, Voorman, Partridge and Soofi.)

Background: The current polio epidemiology in Pakistan poses a unique challenge for global eradication as the country is affected by ongoing endemic poliovirus transmission. Across the country, 40 union councils (UCs) which serve as core reservoirs for poliovirus with continuous incidences of polio cases are categorized as super-high-risk union councils (SHRUCs)., Methodology: A cross-sectional survey was conducted in 39 SHRUCs using a two-stage stratified cluster sampling technique. 6,976 children aged 12-23 months were covered. A structured questionnaire was used for data collection. Data were analyzed using STATA version 17., Results: Based on both vaccination records and recall, 48.3% of children were fully-, 35.4 % were partially-, and 16.3% were non-vaccinated in the SHRUC districts. A child is considered fully vaccinated when h/she completed vaccination for BCG, OPV0, OPV 1-3, Penta 1-3, PCV 1-3, IPV, and MCV1. Vaccination cards were seen for over half of the children in the SHRUC districts of Khyber Pakhtunkhwa (KP) and the majority of the SHRUC districts in Sindh, except for the SHRUC district of Malir the districts of Balochistan. Results for polio vacancies show that 60.9% of children from the SHRUC districts were vaccinated with at least three doses of OPV and one dose of IPV, while 20.4% were vaccinated with any OPV doses or IPV and 18.7% of children did not receive any polio vaccines. The dropout rate between vaccine visits was higher than the WHO-recommended cutoff point of 10% for all vaccine doses in the SHRUC districts. The likelihood of being fully vaccinated was higher among the children of educated parents. Full vaccination was found significant among the children of any SHRUC districts compared to district Killa Abdullah., Conclusion: Context-specific strategies with more focus on community engagement and targeted mobilization, along with robust monitoring mechanisms, would help address the underlying challenges of under-immunization in the SHRUCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Maternal and newborn mortality in Pakistan remains as a major public health challenge. Pakistan faces significant infrastructure challenges and inadequate access to quality health care, exacerbated by sociocultural factors. Facility-based audit systems coupled with community engagement are key elements in achieving improved health system performance. We describe an implementation approach adapted from the World Health Organization audit cycle in real-world settings, with a plan to scale-up through mixed methods evaluation plan., Objective: This study aims to implement a locally acceptable and relevant audit system and evaluate its feasibility within the rural health system of Pakistan for scale-up., Methods: The implementation of the audit system comprises six phases: (1) identify facility and community leadership through consultative meetings with government district health offices, (2) establish the audit committee under the supervision of district health officer, (3) initiate audit with ongoing community engagement, (4) train the audit committee members, (5) launch the World Health Organization audit cycle (monthly meetings), and (6) quarterly review and refresher training. Data from all deliveries, live births, maternal deaths, maternal near misses, stillbirths, and neonatal deaths will be identified and recorded from four sources: (1) secondary-level care rural health facilities, (2) lady health workers' registers, (3) community representatives, and (4) project routine survey team. Concurrent quantitative and qualitative data will be drawn from case assessments, process analysis, and recommendations as components of iterative improvement cycles during the project. Outcomes will be the geographic distribution of mortality to measure the reach, proportion of facilities initiated to implement an audit system for measuring the adoption, proportion of audit committees with community representation, and proportion of audit committee members' sharing feedback regularly to measure acceptability and feasibility. In addition, outcomes of effectiveness will be measured based on data recording and reporting trends, identified modifiable factors for mortality and morbidity as underpinned by the Three Delays framework. Qualitative data will be analyzed based on perceived facilitators, barriers, and lessons learned for policy implications. Results will be summarized in frequencies and percentages and triangulated by the project team. Data will be analyzed using Stata (version 16; StataCorp) and NVivo (Lumivero) software., Results: The study will be implemented for 20 months, followed by an additional 4-month period for follow-up. Initial results will be presented to the district health office and the District Health Program Management Team Meeting in the districts., Conclusions: This study will generate evidence about the feasibility and potential scale-up of a facility-based mortality audit system with integrated community engagement in rural Pakistan. Audit committees will complete the feedback loop linking health care providers, community representatives, and district health officials (policy makers). This implementation approach will serve decision makers in improving maternal and perinatal health outcomes., International Registered Report Identifier (irrid): DERR1-10.2196/49578., (©Zahid Memon, Wardah Ahmed, Shah Muhammad, Sajid Soofi, Shanti Chohan, Arjumand Rizvi, Paul Barach, Zulfiqar A Bhutta. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 30.11.2023.)

Context: The timing of introducing complementary feeding (CF) is crucial because premature or delayed CF can be associated with adverse health outcomes in childhood and adulthood., Objective: This systematic review aims to evaluate the impact of the timing of CF introduction on health, nutrition, and developmental outcomes among normal-term infants., Data Sources: Electronic databases and trial registries were searched, along with the reference lists of the included studies and relevant systematic reviews., Data Extraction: Two investigators independently extracted data from the included studies on a standardized data-extraction form., Data Analysis: Data were meta-analyzed separately for randomized controlled trials (RCTs) and observational studies on the basis of early introduction of CF (< 3 months, < 4 months, < 6 months of age) or late introduction of CF (> 6 months, > 8 months of age). Evidence was summarized according to GRADE criteria. In total, 268 documents were included in the review, of which 7 were RCTs (from 24 articles) and 217 were observational studies (from 244 articles). Evidence from RCTs did not suggest an impact of early introduction, while low-certainty evidence from observational studies suggested that early introduction of CF (< 6 months) might increase body mass index (BMI) z score and overweight/obesity. Early introduction at < 3 months might increase BMI and odds of lower respiratory tract infection (LRTI), and early introduction at < 4 months might increase height, LRTI, and systolic and diastolic blood pressure (BP). For late introduction of CF, there was a lack of evidence from RCTs, but low-certainty evidence from observational studies suggests that late introduction of CF (> 6 months) might decrease height, BMI, and systolic and diastolic BP and might increase odds of intestinal helminth infection, while late introduction of CF (> 8 months) might increase height-for-age z score., Conclusion: Insufficient evidence does suggest increased adiposity with early introduction of CF. Hence, the current recommendation of introduction of CF should stand, though more robust studies, especially from low- and middle-income settings, are needed., Systematic Review Registration: PROSPERO registration number CRD42020218517., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Anemia remains a global public health problem, especially in developing countries. It affects primarily children under five (CU5), women of reproductive age (WRA), and pregnant women due to their higher need for iron. The most common form of anemia is iron-deficiency anemia (IDA). IDA is estimated to cause half of all anemia cases and one million deaths per year worldwide. However, there remains a lack of well-documented and biochemically assessed prevalence of IDA based on the representative population-based samples globally and regionally. In this study, we aimed to assess the National Nutrition Survey (NNS) 2018 to identify the prevalence and risk factors of IDA in Pakistani CU5 and WRA., Methods: Secondary analysis was conducted on the NNS 2018, a cross-sectional survey, which collected data on dietary practices, malnutrition, and food insecurity. Anemia was defined as hemoglobin levels < 11.0 g/dL in children and 12.0 g/dL in women. IDA was defined as low hemoglobin and low ferritin (<12 ng/mL) levels, adjusted for inflammation using AGP and CRP biomarkers in CU5 and WRA. Univariate and multivariable logistic regressions were conducted using Stata statistical software (version 16). We also compared the IDA rates of NNS 2018 and 2011., Results: A total of 17,814 CU5 and 22,114 WRA were included in the analysis. Of the CU5, 28.9% had IDA, while 18.4% of WRA reported to experience IDA. Among the CU5, IDA was most prevalent among male children aged 6-23 months living in rural areas and with the presence of diarrhea and fevers in the last 2 weeks. Children whose mothers had no education, were aged 20-34 years, and employed, had a higher prevalence of IDA. Married WRA, who are employed, living in rural areas, and with no education, had a higher prevalence of IDA. In the multivariable logistic regression, children aged 6-23 months (AOR = 1.19, 95% CI [1.08-1.33], p < 0.001) and with the presence of diarrhea in the last 2 weeks (AOR = 1.32, 95% CI [1.13-1.54], p < 0.001) or fever (AOR = 1.16, 95% CI [1.02-1.32], p = 0.02) had higher odds of IDA. At the household level, the odds of IDA among CU5 were higher in the poorest households (AOR = 1.27, 95% CI [1.08-1.50], p = 0.005), with ≥5 CU5 (AOR = 1.99, 95% CI [1.28-3.11], p = 0.002), and with no access to improved sanitation facilities (AOR = 1.17, 95% CI [1.02-1.34], p = 0.026). For WRA, the multivariable logistic regression found that the odds of IDA were higher among women with vitamin A deficiency (Severe: AOR = 1.26, 95% CI [1.05-1.52], p = 0.013; Mild: AOR = 1.36, 95% CI [1.23-1.51], p < 0.001), zinc deficiency (AOR = 1.42, 95% CI [1.28-1.57], p < 0.001), no education (AOR = 1.53, 95% CI [1.30-1.81], p < 0.001), and from severely food insecure households (AOR = 1.20, 95% CI [1.07-1.34], p = 0.001). The odds of IDA were lower among women whose body mass index was overweight (AOR = 0.77, 95% CI [0.69-0.86], p < 0.001) or obese (AOR = 0.71, 95% CI [0.62-0.81], p < 0.001)., Conclusions: The child's age, presence of diarrhea or fever, place of residence, household size, wealth status, and access to sanitation facilities were significantly associated with IDA among CU5 in Pakistan. For WRA, education, body mass index, vitamin A and zinc status, household food security status, wealth status, and access to sanitation facilities were significantly associated with IDA. Large, well-established, government-funded programmes focused on micronutrient supplementation, food fortification, the diversification of food supplies, and the treatment and prevention of infectious and parasitic diseases are needed to prevent IDA and all forms of anemia among children and women in Pakistan., Competing Interests: No personal conflict of interest are declared.

Background: Adopted in 2015, the sustainable development goals (SDGs) have set specific targets (SDG 3.2) for countries to reduce their neonatal mortality rate (NMR) to below 12 deaths per 1000 live births and under 5 mortality rate (U5MR) to below 25 deaths per 1000 live births by 2030. For Pakistan to achieve these targets, there is a need to measure these rates and understand the predictors of child mortality at sub-national level. Launched in 2016, the Umeed-e-Nau (UeN) or New Hope project is based on scaling up proven and effective Maternal and Newborn Child Health (MNCH) interventions in 8 of the highest burden districts of the country, using existing public sector platforms in Pakistan at both the community and facility level. The primary aim of the project is to reduce perinatal mortality in these districts by 20% from baseline., Methods: We report overall neonatal and post neonatal mortality rates for the two years preceding the UeN baseline household survey. Rates were calculated using the synthetic cohort probability method and predictors of neonatal and post neonatal mortality examined using Cox regression. To investigate spatial variations in the mortality rates, we calculated Moran's I at the district level using predicted probabilities of mortality. Finally, we create district level maps of predicted under 5 child mortality using a stochastic partial differentiation approach., Findings: A total of 26,258 children contributed to the analysis of mortality with 838 deaths in the neonatal period and 2236 under-5 deaths during the observation period from March 1, 2015 to March 17, 2017. Overall, we estimated the NMR to be 29.2 per 1000 live births (95% CI: 26.9-31.4) and the U5MR to be 86.1 per 1000 live births (95% CI: 85.5-86.8). We found evidence of within-district geospatial clustering of under 5 mortality (P < 0.0001) and that social factors (poverty, illiteracy, multiparity), poor coverage of community health workers and distance from health facilities were strongly associated with child mortality., Interpretation: Important factors associated with neonatal and post-neonatal mortality in our study population included maternal education, parity, household size and gender. Additionally, antenatal care coverage (at least 4 visits) was specifically associated with neonatal mortality only, whereas, LHW coverage and distance to health facility were strongly associated with post-neonatal mortality. These findings emphasise the need for comprehensive, multisectoral strategies to be implemented for future maternal and child health programs and outreach services in rural areas., Funding: The study was funded by an unrestricted grant from the Bill & Melinda Gates Foundation to the Aga Khan University (Grant OPP 1148892)., Competing Interests: Primary funding from BMGF was received by the Aga Khan University and subcontract for analysis and support was extended to the Centre for Global Child Health in Toronto. None of the authors received individual funding. All the authors declare no relevant conflicts of interest., (© 2023 The Author(s).)

Background: Cervical cancer is a major cause of cancer-related deaths among women worldwide. Paucity of data on cervical cancer burden in countries like Pakistan hamper requisite resource allocation., Objective: To estimate the burden of cervical cancer in Pakistan using available data sources., Methods: We performed a systematic review to identify relevant data on Pakistan between 1995 to 2022. Study data identified through the systematic review that provided enough information to allow age specific incidence rates and age standardized incidence rates (ASIR) calculations for cervical cancer were merged. Population at risk estimates were derived and adjusted for important variables in the care-seeking pathway. The calculated ASIRs were applied to 2020 population estimates to estimate the number of cervical cancer cases in Pakistan., Results: A total of 13 studies reported ASIRs for cervical cancer for Pakistan. Among the studies selected, the Karachi Cancer Registry reported the highest disease burden estimates for all reported time periods: 1995-1997 ASIR = 6.81, 1998-2002 ASIR = 7.47, and 2017-2019 ASIR = 6.02 per 100,000 women. Using data from Karachi, Punjab and Pakistan Atomic Energy Cancer Registries from 2015-2019, we derived an unadjusted ASIR for cervical cancer of 4.16 per 100,000 women (95% UI 3.28, 5.28). Varying model assumptions produced adjusted ASIRs ranging from 5.2 to 8.4 per 100,000 women. We derived an adjusted ASIR of 7.60, (95% UI 5.98, 10.01) and estimated 6166 (95% UI 4833, 8305) new cases of cervical cancer per year., Conclusion: The estimated cervical cancer burden in Pakistan is higher than the WHO target. Estimates are sensitive to health seeking behavior, and appropriate physician diagnostic intervention, factors that are relevant to the case of cervical cancer, a stigmatized disease in a low-lower middle income country setting. These estimates make the case for approaching cervical cancer elimination through a multi-pronged strategy., (© 2023. The Author(s).)

Objective: To explore the perceptions and experiences of healthcare professionals, including female health visitors, female health workers, community midwives, and heads of departments of healthcare facilities, regarding the importance of the Safe Motherhood Initiative (SMI), its pillars, and its foundational principles., Design: Qualitative descriptive exploratory study., Setting: This study was conducted in healthcare centres in 10 districts in Pakistan: six in Gilgit Baltistan, two in Chitral, and two in Sindh., Participants: Healthcare professionals were recruited using a purposive sampling technique. In total, 14 in-depth interviews were conducted., Findings: The following themes emerged through thematic analysis: (1) health and well-being of mothers and newborns; (2) strengthening the SMI pillars; (3) equity of health services; and (4) effective strategies for behaviour modification. Each theme had two categories., Key Conclusions: The health and well-being of mothers and newborns are key indicators; as such, interventions should be made to promote their quality of life. Capacity building and refresher training on antenatal care, childbirth, postnatal care, postabortion care, and family planning can be considered effective to enhance the competencies of healthcare professionals., Implications for Practice: The findings of this study suggest that healthcare professionals should receive training to enhance their competencies and provide safe care., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023. Published by Elsevier Ltd.)

The profile of the intestinal microbiota is known to be altered in malnourished young children in low- and middle-income countries. However, there are limited studies longitudinally evaluating the intestinal microbiota in malnourished young children in resource-limited settings over the first two years of life. In this longitudinal pilot study, we determined the effect of age, residential location, and intervention on the composition, relative abundance, and diversity of the intestinal microbiota in a representative sample of children under 24 months of age with no diarrhea in the preceding 72 h in the urban and rural areas of Sindh, Pakistan nested within a cluster-randomized trial evaluating the effect of zinc and micronutrients on growth and morbidity (ClinicalTrials.gov Identifier: NCT00705445). The major findings were age-related with significant changes in alpha and beta diversity with increasing age. There was a significant increase in the relative abundance of the Firmicutes and Bacteroidetes phyla and a significant decrease in that of the Actinobacteria and Proteobacteria phyla ( p < 0.0001). There were significant increases in the relative abundances of the major genera Bifidobacterium, Escherichia/Shigella and Streptococcus ( p < 0.0001), and no significant change in the relative abundance of Lactobacillus . Using the LEfSE algorithm, differentially abundant taxa were identified between children in the first and second years of age, between those residing in rural and urban areas, and those who received different interventions at different ages from 3 to 24 months. The numbers of malnourished (underweight, wasted, stunted) or well-nourished children at each age, in each intervention arm, and at urban or rural sites were too small to determine if there were significant differences in alpha or beta diversity or differentially abundant taxa among them. Further longitudinal studies with larger numbers of well-nourished and malnourished children are required to fully characterize the intestinal microbiota of children in this region.

Background: Gender discrimination is any unequal treatment of a person based on their sex. Women and girls are most likely to experience the negative impact of gender discrimination. The aim of this study is to assess the factors that influence gender discrimination in Pakistan, and its impact on women's life., Methods: A mixed method approach was used in the study in which a systematic review was done in phase one to explore the themes on gender discrimination, and qualitative interviews were conducted in phase two to explore the perception of people regarding gender discrimination. The qualitative interviews (in-depth interviews and focus group discussions) were conducted from married men and women, adolescent boys and girls, Healthcare Professionals (HCPs), Lady Health Visitors (LHVs) and Community Midwives (CMWs). The qualitative interviews were analyzed both manually and electronically through QSR NVivo 10. The triangulation of data from the systematic review and qualitative interviews were done to explore the gender discrimination related issues in Pakistan., Results: The six major themes have emerged from the systematic review and qualitative interviews. It includes (1) Status of a woman in the society (2) Gender inequality in health (3) Gender inequality in education (4) Gender inequality in employment (5) Gender biased social norms and cultural practices and (6) Micro and macro level recommendations. In addition, a woman is often viewed as a sexual object and dependent being who lacks self identity unless being married. Furthermore, women are restricted to household and child rearing responsibilities and are often neglected and forced to suppress self-expression. Likewise, men are viewed as dominant figures in lives of women who usually makes all family decisions. They are considered as financial providers and source of protection. Moreover, women face gender discrimination in many aspects of life including education and access to health care., Conclusion: Gender discrimination is deeply rooted in the Pakistani society. To prevent gender discrimination, the entire society, especially women should be educated and gendered sensitized to improve the status of women in Pakistan., (© 2022. The Author(s).)

Puerperal sepsis is an important cause of maternal morbidity and mortality in developing countries. Awareness of local terminology for its signs and symptoms may improve communication about this illness, what actions to take when symptoms appear, timely care seeking, and clinical outcomes. This formative research aimed to improve recognition and management of postpartum sepsis in Pakistan by eliciting local terms used for postpartum illnesses and symptoms. We conducted 32 in-depth interviews with recently delivered women, their relatives, traditional birth attendants, and health care providers to explore postpartum experiences. Terms for symptoms and illness are used interchangeably (i.e. bukhar , the Urdu word for fever), many variations exist for the same term, and gradations of severity for each term as not associated with different types of illnesses. The lack of a designated term for postpartum sepsis in Urdu delays care-seeking and proper diagnosis, particularly at the community level. Ideally, a common lexicon for symptoms and postpartum sepsis would be developed but this may not be feasible or appropriate given the nature of the Urdu language and local understandings of postpartum illness. These insights can inform how we approach educational campaigns, the development of clinical algorithms that focus on symptoms, and counselling protocols.

Afghanistan continues to experience challenges affecting polio eradication. Mass polio vaccination campaigns, which aim to protect children under the age of 5, are a key eradication strategy. To date, the polio program in Afghanistan has only employed facility-based seroprevalence surveys, which can be subject to sampling bias. We describe the feasibility in implementing a cross-sectional household poliovirus seroprevalence survey based on geographical information systems (GIS) in three districts. Digital maps with randomly selected predetermined starting points were provided to teams, with a total target of 1,632 households. Teams were instructed to navigate to predetermined starting points and enrol the closest household within 60 m. To assess effectiveness of these methods, we calculated percentages for total households enrolled with valid geocoordinates collected within the designated boundary, and whether the Euclidean distance of households were within 60 m of a predetermined starting point. A normalized difference vegetation index (NDVI) image ratio was conducted to further investigate variability in team performances. The study enrolled a total of 78% of the target sample with 52% of all households within 60 m of a pre-selected point and 79% within the designated cluster boundary. Success varied considerably between the four target areas ranging from 42% enrolment of the target sample in one place to 90% enrolment of the target sample in another. Interviews with the field teams revealed that differences in security status and amount of non-residential land cover were key barriers to higher enrolment rates. Our findings indicate household poliovirus seroprevalence surveys using GIS-based sampling can be effectively implemented in polio endemic countries to capture representative samples. We also proposed ways to achieve higher success rates if these methods are to be used in the future, particularly in areas with concerns of insecurity or spatially dispersed residential units.

Objective: Risk factors predisposing infants to community-acquired bacterial infections during the first 2 months of life are poorly understood in South Asia. Identifying risk factors for infection could lead to improved preventive measures and antibiotic stewardship., Methods: Five sites in Bangladesh, India and Pakistan enrolled mother-child pairs via population-based pregnancy surveillance by community health workers. Medical, sociodemographic and epidemiological risk factor data were collected. Young infants aged 0-59 days with signs of possible serious bacterial infection (pSBI) and age-matched controls provided blood and respiratory specimens that were analysed by blood culture and real-time PCR. These tests were used to build a Bayesian partial latent class model (PLCM) capable of attributing the probable cause of each infant's infection in the ANISA study. The collected risk factors from all mother-child pairs were classified and analysed against the PLCM using bivariate and stepwise logistic multivariable regression modelling to determine risk factors of probable bacterial infection., Results: Among 63 114 infants born, 14 655 were assessed and 6022 had signs of pSBI; of these, 81% (4859) provided blood samples for culture, 71% (4216) provided blood samples for quantitative PCR (qPCR) and 86% (5209) provided respiratory qPCR samples. Risk factors associated with bacterial-attributed infections included: low (relative risk (RR) 1.73, 95% credible interval (CrI) 1.42 to 2.11) and very low birth weight (RR 5.77, 95% CrI 3.73 to 8.94), male sex (RR 1.27, 95% CrI 1.07 to 1.52), breathing problems at birth (RR 2.50, 95% CrI 1.96 to 3.18), premature rupture of membranes (PROMs) (RR 1.27, 95% CrI 1.03 to 1.58) and being in the lowest three socioeconomic status quintiles (first RR 1.52, 95% CrI 1.07 to 2.16; second RR 1.41, 95% CrI 1.00 to 1.97; third RR 1.42, 95% CrI 1.01 to 1.99)., Conclusion: Distinct risk factors: birth weight, male sex, breathing problems at birth and PROM were significantly associated with the development of bacterial sepsis across South Asian community settings, supporting refined clinical discernment and targeted use of antimicrobials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Systematic assessment of childhood asthma is challenging in low- and middle-income country (LMIC) settings due to the lack of standardised and validated methodologies. We describe the contextual challenges and adaptation strategies in the implementation of a community-based asthma assessment in four resource-constrained settings in Bangladesh, India, and Pakistan., Method: We followed a group of children of age 6-8 years for 12 months to record their respiratory health outcomes. The study participants were enrolled at four study sites of the 'Aetiology of Neonatal Infection in South Asia (ANISA)' study. We standardised the research methods for the sites, trained field staff for uniform data collection and provided a 'Child Card' to the caregiver to record the illness history of the participants. We visited the children on three different occasions to collect data on respiratory-related illnesses. The lung function of the children was assessed in the outreach clinics using portable spirometers before and after 6-minute exercise, and capillary blood was examined under light microscopes to determine eosinophil levels., Results: We enrolled 1512 children, 95.5% (1476/1512) of them completed the follow-up, and 81.5% (1232/1512) participants attended the lung function assessment tests. Pre- and post-exercise spirometry was performed successfully in 88.6% (1091/1232) and 85.7% (1056/1232) of children who attempted these tests. Limited access to health care services, shortage of skilled human resources, and cultural diversity were the main challenges in adopting uniform procedures across all sites. Designing the study implementation plan based on the local contexts and providing extensive training of the healthcare workers helped us to overcome these challenges., Conclusion: This study can be seen as a large-scale feasibility assessment of applying spirometry and exercise challenge tests in community settings of LMICs and provides confidence to build capacity to evaluate children's respiratory outcomes in future translational research studies., Competing Interests: Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Introduction: The oral polio vaccine (OPV) has substantial results in eliminating wild poliovirus and the vaccine of choice in polio eradication. However, the mucosal immunity induced by the OPV is still uncertain. Literature has shown that bovine lactoferrin (BLF) is a safe and useful protein found in cow's milk with extraordinary antimicrobial, antiviral, antiinflammatory and immune-modulatory functions that help children's gut to fight against micro-organisms like poliovirus. However, limited data exist regarding the effect of BLF on polio vaccine immune response. The primary objective is to evaluate the effect of BLF in enhancing mucosal and humoral immunity in children following the administration of oral and inactivated polio vaccines., Methods and Analysis: This is a two-arm double-blinded randomised controlled trial comparing 462 neonates (231 in both groups) receiving either BLF or placebo with breast milk. The intervention is administered from day 1 till 6 weeks of age to a full-term healthy singleton newborn born at the Aga Khan University Hospitals, Karachi, Pakistan. The primary outcome is the seroconversion, 1 month after the receipt of two doses of OPV (at 10 weeks). For descriptive statistical analysis, Stata will be used, the frequency with percentages will be reported to describe baseline characteristics of the participants. A χ 2 test will be used to compare categorical variables and a simple t test to compare continuous variables. The proportion of seroconversion and shedding will be compared using χ 2 test or Fisher's exact test., Ethics and Dissemination: The Ethics approval has been granted by the Ethics Review Committee (ERC) of Aga Khan University for the proposed trial (ID: 2019-1955-5013). Furthermore, the National Bioethics Committee (NBC) of Pakistan has also approved the study for human subject research (ID: 4-87/NBC-443/19/669). Study findings will be disseminated through presentations at scientific conferences and educational practice workshops and will be published in an international peer-reviewed scientific journal., Trial Registration Number: NCT04432935; ClinicalTrials.gov., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the cost-effectiveness of distribution of the integrated neonatal care kit (iNCK) by community health workers from the healthcare payer perspective in Rahimyar Khan, Pakistan., Setting: Rahimyar Khan, Pakistan., Participants: N/A., Intervention: Cost-utility analysis using a Markov model based on cluster randomised controlled trial (cRCT: NCT02130856) data and a literature review. We compared distribution of the iNCK to pregnant mothers to local standard of care and followed infants over a lifetime horizon., Primary and Secondary Outcome Measures: The primary outcome was incremental net monetary benefit (INMB, at a cost-effectiveness threshold of US$15.50), discounted at 3%. Secondary outcomes were life years, disability-adjusted life years (DALYs) and costs., Results: At a cost-effectiveness threshold of US$15.50, distribution of the iNCK resulted in lower expected DALYs (28.7 vs 29.6 years) at lower expected cost (US$52.50 vs 55.20), translating to an INMB of US$10.22 per iNCK distributed. These results were sensitive to the baseline risk of infection, cost of the iNCK and the estimated effect of the iNCK on the relative risk of infection. At relative risks of infection below 0.79 and iNCK costs below US$25.90, the iNCK remained cost-effective compared with current local standard of care., Conclusion: The distribution of the iNCK dominated the current local standard of care (ie, the iNCK is less costly and more effective than current care standards). Most of the cost-effectiveness of the iNCK was attributable to a reduction in neonatal infection., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)