Implementation of a clinical breast exam and referral program in a rural district of Pakistan.

BACKGROUND: The role of clinical breast examination (CBE) for early detection of breast cancer is extremely important in lower-middle-income countries (LMICs) where access to breast imaging is limited. Our study aimed to describe the outcomes of a community outreach breast education, home CBE and referral program for early recognition of breast abnormalities and improvement of breast cancer awareness in a rural district of Pakistan. METHODS: Eight health care workers (HCW) and a gynecologist were educated on basic breast cancer knowledge and trained to create breast cancer awareness and conduct CBE in the community. They were then deployed in the Dadu district of Pakistan where they carried out home visits to perform CBE in the community. Breast cancer awareness was assessed in the community using a standardized questionnaire and standard educational intervention was performed. Clinically detectable breast lesions were identified during home CBE and women were referred to the study gynecologist to confirm the presence of clinical abnormalities. Those confirmed to have clinical abnormalities were referred for imaging. Follow-up home visits were carried out to assess reasons for non-compliance in patients who did not follow-through with the gynecologist appointment or prescribed imaging and re-enforce the need for follow-up. RESULTS: Basic breast cancer knowledge of HCWs and study gynecologist improved post-intervention. HCWs conducted home CBE in 8757 women. Of these, 149 were warranted a CBE by a physician (to avoid missing an abnormality), while 20 were found to have a definitive lump by HCWs, all were referred to the study gynecologist (CBE checkpoint). Only 50% (10/20) of those with a suspected lump complied with the referral to the gynecologist, where 90% concordance was found between their CBEs. Follow-up home visits were conducted in 119/169 non-compliant patients. Major reasons for non-compliance were a lack of understanding of the risks and financial constraints. A significant improvement was observed in the community's breast cancer knowledge at the follow-up visits using the standardized post-test. CONCLUSIONS: Basic and focused education of HCWs can increase their knowledge and dispel myths. Hand-on structured training can enable HCWs to perform CBE. Community awareness is essential for patient compliance and for early-detection, diagnosis, and treatment.

Exploring the path to polio eradication: insights from consecutive seroprevalence surveys among Pakistani children.

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.

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.

Association of maternal, obstetric, fetal, and neonatal mortality outcomes with Lady Health Worker coverage from a cross-sectional survey of >10,000 households in Gilgit-Baltistan, Pakistan.

Pakistan has among the highest rates of maternal, perinatal, and neonatal mortality globally. Many of these deaths are potentially preventable with low-cost, scalable interventions delivered through community-based health worker programs to the most remote communities. We conducted a cross-sectional survey of 10,264 households during the baseline phase of a cluster randomized controlled trial (cRCT) in Gilgit-Baltistan, Pakistan from June-August 2021. The survey was conducted through a stratified, two-stage sampling design with the objective of estimating the neonatal mortality rate (NMR) within the study catchment area, and informing implementation of the cRCT. Study outcomes were self-reported and included neonatal death, stillbirth, health facility delivery, maternal death, postpartum hemorrhage (PPH), and Lady Health Worker (LHW) coverage. Summary statistics (proportions and rates) were weighted according to the sampling design, and mixed-effects Poisson regression was conducted to explore the relationship between LHW coverage and maternal/newborn outcomes. We identified 7,600 women who gave birth in the past five years, among whom 13% reported experiencing PPH. The maternal mortality ratio was 225 maternal deaths per 100,000 live births (95% confidence interval [CI] 137-369). Among 12,376 total births, the stillbirth rate was 41.4 per 1,000 births (95% CI 36.8-46.7) and the perinatal mortality rate was 53.0 per 1,000 births (95% CI 47.6-59.0). Among 11,863 live births, NMR was 16.2 per 1,000 live births (95% CI 13.6-19.3) and 65% were delivered at a health facility. LHW home visits were associated with declines in PPH (risk ratio [RR] 0.89 per each additional visit, 95% CI 0.83-0.96) and late neonatal mortality (RR 0.80, 95% CI 0.67-0.97). Intracluster correlation coefficients were also estimated to inform the planning of future trials. The high rates of maternal, perinatal, and neonatal death in Gilgit-Baltistan continue to fall behind targets of the 2030 Sustainable Development Goals.

A Holistic Strategy of Mother and Child Health Care to Improve the Coverage of Routine and Polio Immunization in Pakistan: Results from a Demonstration Project.

BACKGROUND: The eradication of poliovirus and improving routine immunization (RI) coverage rates present significant challenges in Pakistan. There is a need for interventions that focus on strengthening community engagement to improve routine immunization coverage. Our primary objective is to assess the impact of an integrated strategy designed to enhance community engagement and maternal and child health immunization campaigns on immunization coverage in Pakistan's high-risk union councils of polio-endemic districts. METHOD: We implemented an integrated approach for routine immunization and maternal and child health in the polio-endemic district of Pakistan. This approach involved setting up health camps and actively engaging and mobilizing the local community. An independent team conducted surveys at three key points: baseline, midline, and endline, to evaluate immunization coverage among children under the age of five. The primary outcome measures for the study were coverage of OPV, IPV, and changes in the proportion of unvaccinated and fully vaccinated children. To select clusters and eligible households in each cluster, we utilized a 30 × 15 cluster sampling technique. Multivariable associations between socio-demographic factors and changes in the proportion of fully vaccinated children at the UC level were assessed using hierarchical linear regression models. RESULTS: A total of 256,946 children under the age of five (122,950 at baseline and 133,996 at endline) were enrolled in the study. By the endline, full immunization coverage had increased to 60% or more in all three study areas compared to the baseline. Additionally, there was a significant increase in the coverage of both OPV and IPV across all three provinces at the endline. The full immunization rates were assessed on three levels of the framework: the distal, intermediate (access and environment), and proximal level (camp attendance and effectiveness). At the distal level, on multivariate analysis, family size was found to be a significant predictor of change in immunity within the families (ß = 0.68; p ≤ 0.0001). At the intermediate level, the likelihood of full immunization decreased with the decrease in knowledge about vaccination (ß = -0.38; p = 0.002), knowledge about polio vaccine (ß = -0.25; p = 0.011), and knowledge about IPV (ß = -0.06; p = 0.546). Perceived obstacles to vaccination were fear of adverse events (ß = -0.4; p ≤ 0.0001) and lack of education (ß = 0.23; p = 0.031), which were found to be significant in bivariate and multivariate analyses. At the proximal level, community mobilization (ß = 0.26; p = 0.008) and attendance at health camp (ß = 0.21; p ≤ 0.0001) were found to enhance full immunization coverage. On the other hand, the most prominent reason for not attending health camp included no need to attend the health camp as the child was not ill (ß = -0.13; p = 0.008). CONCLUSIONS: This study found that community mobilization and attendance at health camps significantly enhanced full immunization coverage. The findings highlight the importance of community engagement and targeted interventions in improving immunization coverage and addressing barriers to healthcare seeking.

Determinants of immunization in polio super high-risk union councils of Pakistan.

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.

Exploring the long-term seroprevalence of SARS-CoV-2 antibodies in infants born to women with clinical or laboratory-confirmed COVID-19.

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.

An integrated newborn care kit (iNCK) to save newborn lives and improve health outcomes in Gilgit Baltistan (GB), Pakistan: study protocol for a cluster randomized controlled trial.

BACKGROUND: Ongoing high neonatal mortality rates (NMRs) represent a global challenge. In 2021, of the 5 million deaths reported worldwide for children under five years of age, 47% were newborns. Pakistan has one of the five highest national NMRs in the world, with an estimated 39 neonatal deaths per 1,000 live births. Reducing newborn deaths requires sustainable, evidence-based, and cost-effective interventions that can be integrated within existing community healthcare infrastructure across regions with high NMR. METHODS: This pragmatic, community-based, parallel-arm, open-label, cluster randomized controlled trial aims to estimate the effect of Lady Health Workers (LHWs) providing an integrated newborn care kit (iNCK) with educational instructions to pregnant women in their third trimester, compared to the local standard of care in Gilgit-Baltistan, Pakistan, on neonatal mortality and other newborn and maternal health outcomes. The iNCK contains a clean birth kit, 4% chlorhexidine topical gel, sunflower oil emollient, a ThermoSpot™ temperature monitoring sticker, a fleece blanket, a click-to-heat reusable warmer, three 200 µg misoprostol tablets, and a pictorial instruction guide and diary. LHWs are also provided with a handheld scale to weigh the newborn. The primary study outcome is neonatal mortality, defined as a newborn death in the first 28 days of life. DISCUSSION: This study will generate policy-relevant knowledge on the effectiveness of integrating evidence-based maternal and newborn interventions and delivering them directly to pregnant women via existing community health infrastructure, for reducing neonatal mortality and morbidity, in a remote, mountainous area with a high NMR. TRIAL REGISTRATION: NCT04798833, March 15, 2021.

Facility-Based Audit System With Integrated Community Engagement to Improve Maternal and Perinatal Health Outcomes in Rural Pakistan: Protocol for a Mixed Methods Implementation Study.

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.

Does IPV Boost Intestinal Immunity among Children under Five Years of Age? An Experience from Pakistan.

The oral poliovirus vaccine (OPV) has been the mainstay of polio eradication, especially in low-income countries, and its use has eliminated wild poliovirus type 2. However, the inactivated poliovirus vaccine (IPV) is safer than OPV, as IPV protects against paralytic poliomyelitis without producing adverse reactions. The present study compared mucosal and humoral responses to poliovirus vaccines administered to previously OPV-immunized children to assess the immunity gap in children in areas of high poliovirus transmission. A cluster-randomized trial was implemented in three high-risk districts of Pakistan-Karachi, Kashmore, and Bajaur-from June 2013 to May 2014. This trial was community-oriented and included three arms, focusing on healthy children below five years of age. The study involved the randomization of 387 clusters, of which 360 were included in the final analysis. The control arm (A) received the routine polio program bivalent poliovirus vaccine (bOPV). The second arm (B) received additional interventions, including health camps providing routine vaccinations and preventive maternal and child health services. In addition to the interventions in arm B, the third arm (C) was also provided with IPV. Blood and stool samples were gathered from children to evaluate humoral and intestinal immunity. The highest levels of poliovirus type 1 serum antibodies were observed in Group C (IPV + OPV). The titers for poliovirus type 2 (P2) and poliovirus type 3 (P3) were noticeably higher in those who had received a routine OPV dose than in those who had not across all study groups and visits. Providing an IPV booster after at least two OPV doses could potentially fill immunity gaps in regions where OPV does not show high efficacy. However, IPV only marginally enhances humoral immunity and fails to offer intestinal immunity, which is critical to stop the infection and spread of live poliovirus in populations that have not been exposed before.

Predictors and disparities in neonatal and under 5 mortality in rural Pakistan: cross sectional analysis.

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).

Prevalence and Risk Factors for Iron Deficiency Anemia among Children under Five and Women of Reproductive Age in Pakistan: Findings from the National Nutrition Survey 2018.

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.

Determinants of Stunting among Children under Five in Pakistan.

INTRODUCTION: Child stunting remains a public health concern. It is characterized as poor cognitive and physical development in children due to inadequate nutrition during the first 1000 days of life. Across south Asia, Pakistan has the second-highest prevalence of stunting. This study assessed the most recent nationally representative data, the National Nutrition Survey (NNS) 2018, to identify the stunting prevalence and determinants among Pakistani children under five. METHODS: The NNS 2018, a cross-sectional household-level survey, was used to conduct a secondary analysis. Data on malnutrition, dietary practices, and food insecurity were used to identify the prevalence of stunting among children under five years in terms of demographic, socioeconomic, and geographic characteristics. The prevalence of stunting was calculated using the World Health Organization (WHO) height for age z-score references. Univariate and multivariable logistic regressions were conducted to identify the factors associated with child stunting. RESULTS: The analysis showed that out of 52,602 children under five, 40.0% were found to be stunted. Male children living in rural areas were more susceptible to stunting. Furthermore, stunting was more prevalent among children whose mothers had no education, were between 20 and 34, and were employed. In the multivariable logistic regression, male children (AOR = 1.08, 95% CI [1.04-1.14], p < 0.001) from rural areas (AOR = 1.07, 95% CI [1.01-1.14], p = 0.014), with the presence of diarrhea in the last two weeks (AOR = 1.15, 95% CI [1.06-1.25], p < 0.001) and mothers who had no education (AOR = 1.57, 95% CI [1.42-1.73], p < 0.001) or lower levels of education (primary: AOR = 1.35, 95% CI [1.21-1.51], p < 0.001; middle: AOR = 1.29, 95% CI [1.15-1.45], p < 0.001), had higher odds of stunting. Younger children aged < 6 months (AOR = 0.53, 95% CI [0.48-0.58], p < 0.001) and 6-23 months (AOR = 0.89, 95% CI [0.84-0.94], p < 0.001), with mothers aged 35-49 years (AOR = 0.78, 95% CI [0.66-0.92], p = 0.003), had lower odds of stunting. At the household level, the odds of child stunting were higher in lower-income households (AOR = 1.64, 95% CI [1.46-1.83], p < 0.001) with ≥ 7 members (AOR = 1.09, 95% CI [1.04-1.15], p < 0.001), with no access to improved sanitation facilities (AOR = 1.14, 95% CI [1.06-1.22], p < 0.001) and experiencing severe food insecurity (AOR = 1.07, 95% CI [1.01-1.14], p = 0.02). CONCLUSION: Child stunting in Pakistan is strongly associated with various factors, including gender, age, diarrhea, residence, maternal age and education, household size, food and wealth status, and access to sanitation. To address this, interventions must be introduced to make locally available food and nutritious supplements more affordable, improve access to safe water and sanitation, and promote female education for long-term reductions in stunting rates.

Exploring Knowledge and Perceptions of Polio Disease and Its Immunization in Polio High-Risk Areas of Pakistan.

Pakistan is one of the few countries where poliovirus transmission still persists, despite intensive efforts to eradicate the disease. Adequate vaccination coverage is essential to achieve polio eradication, but misconceptions about polio vaccines have hindered vaccination efforts. To address this issue, we conducted a mixed-methods study to explore knowledge and perceptions regarding polio disease and immunization in high-risk areas of Pakistan. We collected quantitative data from 3780, 1258, and 2100 households in Karachi, Bajaur, and Pishin, respectively, and supplemented this with qualitative data from focus group discussions and in-depth interviews. Our findings reveal a high level of awareness about polio and its immunization; however, misperceptions about the polio vaccine persist, leading to refusal for both polio vaccines and routine immunizations. Our study provides up-to-date data on knowledge and perceptions of polio and its immunization and identifies critical gaps. These findings can inform the development of future strategies and innovative approaches to improve the success of the polio program in Pakistan.

Differential associations between body composition indices and neurodevelopment during early life in term-born infants: findings from the Pakistan cohort: Multi-Center Body Composition Reference Study.

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.

National cervical cancer burden estimation through systematic review and analysis of publicly available data in Pakistan.

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.

Factors Associated with Vaccine Refusal (Polio and Routine Immunization) in High-Risk Areas of Pakistan: A Matched Case-Control Study.

BACKGROUND: Pakistan has subpar childhood immunization rates and immunization activities have faced several challenges over the past years. We evaluated the social-behavioral and cultural barriers and risk factors for refusal of polio, Routine Immunization (RI), or both in high-risk areas of poliovirus circulation. METHODS: A matched case-control study was conducted from April to July 2017 in eight super high-risk Union Councils of five towns in Karachi, Pakistan. A total of 3 groups, each with 250 cases, including refusals for the Oral Polio Vaccine (OPV) in campaigns (national immunization days and supplementary immunization activities), RI, and both, were matched with 500 controls and identified using surveillance records. Sociodemographic characteristics, household information, and immunization history were assessed. Study outcomes included social-behavioral and cultural barriers and reasons for vaccine refusal. Data were analyzed in STATA using conditional logistic regression. RESULTS: RI refusal was associated with illiteracy and fear of the vaccine's adverse effects, while OPV refusals were linked to the mother's decision authority and the assumption that the OPV caused infertility. Conversely, higher socioeconomic status (SES) and knowledge of and willingness to vaccinate with Inactivated Polio Vaccine (IPV) were inversely associated with RI; and lower SES, walking to the vaccination point, knowledge of IPV, and an understanding of contracting polio were inversely associated with OPV refusals, with the latter two also inversely associated with complete vaccine refusal. CONCLUSION: Education, knowledge and understanding of vaccines, and socioeconomic determinants influenced OPV and RI refusals among children. Effective interventions are needed to address knowledge gaps and misconceptions among parents.

Drivers of malnutrition among late adolescent and young women in rural Pakistan: a cross-sectional assessment of the MaPPS trial.

OBJECTIVE: This study aimed to characterise the burden of malnutrition and assess how underlying determinants at the structural and intermediary levels contributed to malnutrition among late adolescent and young women in rural Pakistan. DESIGN: Cross-sectional enrolment data assessment. SETTING AND PARTICIPANTS: This study was conducted using data from adolescent and young women (n=25 447) enrolled in the Matiari emPowerment and Preconception Supplementation Trial, collected from June 2017 to July 2018 in Matiari District, Pakistan. The WHO-based cut-offs were applied to anthropometric measures to estimate body mass index (BMI) categories (underweight, overweight, obese) and stunting. Hierarchical models were generated to evaluate the association between the determinants with BMI categories and stunting among late adolescent girls and young women, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcomes of interest were BMI categories and stunting. Explanatory variables included measures of socioeconomic status, education, occupation, health, well-being, food security, empowerment and food practices. RESULTS: Regardless of age group, the prevalence of underweight was high (36.9%; 95% CI 36.3% to 37.5%). More late adolescent girls were underweight, while more young women were overweight/obese (p<0.001). Stunting affected 9.2% (95% CI 8.9% to 9.6%) of participants, of which 35.7% were additionally underweight and 7.3% overweight/obese. Compared with those in the normal weight category, those underweight were more likely to be impoverished and less empowered. Those overweight/obese were more likely to be from a higher wealth quintile and food secure. Increased education level and food security were associated with reductions stunting risk. CONCLUSIONS: This study informs the data gap and need for comprehensive research on adolescent nutritional status. Findings suggest factors related to poverty played an important, underlying role in undernutrition among participants. Commitment to improving the nutritional status of all adolescent and young women in Pakistan will be critical given the observed burden of malnutrition. TRIAL REGISTRATION NUMBER: NCT03287882.

Optimal timing of introduction of complementary feeding: a systematic review and meta-analysis.

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.

Infections and nutrient deficiencies during infancy predict impaired growth at 5 years: Findings from the MAL-ED study in Pakistan.

Background: Socio-economic, nutritional, and infectious factors have been associated with impaired infant growth, but how the presence of these factors during infancy affects growth around 5 years is not well understood. Methods: This secondary analysis of the MAL-ED cohort included 277 children from Pakistan for whom socio-demographic, breastfeeding, complementary foods, illness, nutritional biomarkers, stool pathogens and environmental enteropathy indicators between 0 and 11 months were recorded. We used linear regression models to analyze associations of these indicators with height-for-age (HAZ), weight-for-age (WAZ) and weight-for-height (WLZ) at 54-66 months (~5 years), and Poisson regression with robust standard errors to estimate risk ratios for stunting and underweight ~5 years, controlling for gender, first available weight, and income. Results: Among the 237 infants followed longitudinally and evaluated at about 5 years of age, exclusive breastfeeding was short (median = 14 days). Complementary feeding started before 6 months with rice, bread, noodles, or sugary foods. Roots, dairy products, fruits/vegetables, and animal-source foods were provided later than recommended (9-12 months). Anemia (70.9%), deficiencies in iron (22.0%), zinc (80.0%), vitamin A (53.4%) and iodine (13.3%) were common. Most infants (>90%) presented with diarrhea and respiratory infections in their first year. At ~5 years, low WAZ (mean-1.91 ± 0.06) and LAZ (-2.11 ± 0.06) resulted in high prevalence of stunting (55.5%) and underweight (44.4%) but a relatively low rate of wasting (5.5%). While 3.4% had concurrent stunting and wasting ~5 years, 37.8% of children had coexisting stunting and underweight. A higher income and receiving formula or dairy products during infancy were associated with a higher LAZ ~5 years, but infant's history of hospitalizations and more respiratory infections were associated with lower LAZ and higher risk of stunting ~5 years. Infants' intake of commercial baby foods and higher serum-transferrin receptors were associated with higher WAZ and lower risk of underweight ~5 years. Presence of Campylobacter and fecal neopterin >6.8 nmol/L in the first year were associated with increased risk of underweight ~5 years. Conclusion: Growth indicators ~5 years were associated with poverty, inappropriate complementary feeding, and infections during the first year of life, which supports the early start of public health interventions for preventing growth delay ~5 years.