High Rates of Placental Inflammation Among Samples Collected by the MOMI Consortium.

BACKGROUND: The Multi-Omics for Mothers and Infants (MOMI) consortium aims to improve birth outcomes. Preterm birth is a major obstetric complication globally causing significant infant and childhood morbidity and mortality. OBJECTIVES: We analyzed placental samples (basal plate, placenta/chorionic villi and/or the chorionic plate) collected by the 5 MOMI sites: The Alliance for Maternal and Newborn Health Improvement (AMANHI) Bangladesh, AMANHI Pakistan, AMANHI Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Bangladesh and GAPPS Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN: The teams provided biopsies from 166 singleton preterm (<37 weeks) and 175 term (≥37 weeks) deliveries. They were formalin-fixed and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphological analyses. Other placental biopsies (n = 35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS: The morphological analyses revealed a surprisingly high rate of inflammation involving the basal plate, placenta/chorionic villi and/or the chorionic plate. The rate in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs. the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes as differentially expressed (DE) between placentas from preterm vs. term births (123 upregulated, 144 downregulated). Mapping the DE genes onto single cell RNA-seq data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathological findings, GO (Gene Ontology) analyses highlighted leukocyte infiltration/activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION: The relationship between placental inflammation and preterm birth is appreciated in developed countries. Here, we show that this link also exists in developing geographies. Also, among the participating sites, we found geographic- and/or population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Predictors of Respiratory Syncytial Virus, Influenza Virus, and Human Metapneumovirus Carriage in Children Under 5 Years With WHO-Defined Fast-Breathing Pneumonia in Pakistan.

BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in children < 5 years. We describe nasopharyngeal carriage of respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus among children with fast-breathing pneumonia in Karachi, Pakistan. METHODS: We performed a cross-sectional analysis of nasopharyngeal swabs from children aged 2-59 months with fast-breathing pneumonia, enrolled in the randomized trial of amoxicillin versus placebo for fast-breathing pneumonia (RETAPP) (NCT02372461) from 2014 to 2016. Swabs were collected using WHO standardized methods, processed at the Aga Khan University, Pakistan. Viral detection was performed using LUMINEX xTAG respiratory viral panel assay and logistic regression identified clinical and sociodemographic predictors. FINDINGS: Of the 1000 children tested, 92.2% (n = 922) were positive for viral carriage. RSV, hMPV, and influenza virus were detected in 59 (6.4%), 56 (6.1%), and 58 (6.3%) children and co-infections in three samples (two RSV-hMPV and one influenza-hMPV). RSV carriage was common in infants (56%), we observed a higher occurrence of fever in children with hMPV and influenza virus (80% and 88%, respectively) and fast breathing in RSV (80%) carriage. RSV carriage was positively associated with a history of fast/difficulty breathing (aOR: 1.96, 95% CI 1.02-3.76) and low oxygen saturation (aOR: 2.52, 95% CI 1.32-4.82), hMPV carriage was positively associated with a complete vaccination status (aOR: 2.22, 95% CI 1.23-4.00) and body temperature ≥ 37.5°C (aOR: 2.34, 95% CI 1.35-4.04) whereas influenza viral carriage was associated with body temperature ≥ 37.5°C (aOR: 4.48, 95% CI 2.53-7.93). CONCLUSION: We observed a high nasopharyngeal viral carriage among children with WHO-defined fast-breathing pneumonia in Pakistan. Fever, difficulty in breathing, hypoxia and vaccination status are important clinical predictors for viral nonsevere community-acquired pneumonia.

Secondary attack rates and determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) household transmission in Pakistan: A case-ascertained prospective, longitudinal study.

BACKGROUND: Households are considered ideal settings for studying the transmission dynamics of an infectious disease. METHODS: A prospective study was conducted, based on the World Health Organization FFX protocol from October 2020 to January,2021. Household contacts of laboratory-confirmed index cases were followed up for their symptomatic history, nasal swabs for RT-PCR,and blood samples for anti-SARS CoV-2 antibodies were collected at enrollment and days 7, 14 and 28. We estimated secondary attack rate (SAR), effective household case cluster size and determinants of secondary infection among susceptible household contacts using multivariable logistic regression. RESULTS: We enrolled 77 index cases and their 543 contacts. Out of these, 252 contacts were susceptible at the time of enrollment. There were 77 household clusters, out of which, transmission took place in 20 (25.9%) giving rise to 34 cases. The acquired secondary attack rate (SAR) was 14.0% (95% CI 9.0-18.0). The effective household case cluster size was 0.46 (95%CI 0.33,0.56). Reported symptoms of nausea and vomiting (aOR, 7.9; 95% CI, 1.4-45.5) and fatigue (aOR, 9.3; 95% CI, 3.8-22.7) were associated with SARS-CoV-2 transmission. CONCLUSIONS: We observed a low SARS-CoV-2 secondary attack rate in the backdrop of high seroprevalence and asymptomatic transmission among households in Karachi, Pakistan.

Global Immunization Crisis Amid the COVID-19 Pandemic: Implications for Pediatric Oncology.

Declining herd immunity and severe manifestation of vaccine preventable infections underscores the need for vaccinations campaigns to urgently vaccinate children who missed their routine immunizations.

Environmental surveillance for COVID-19 using SARS-CoV-2 RNA concentration in wastewater - a study in District East, Karachi, Pakistan.

Background: Wastewater-based surveillance is used to track the temporal patterns of the SARS-CoV-2 virus in communities. Viral RNA particle detection in wastewater samples can indicate an outbreak within a catchment area. We describe the feasibility of using a sewage network to monitor SARS-CoV-2 trend and use of genomic sequencing to describe the viral variant abundance in an urban district in Karachi, Pakistan. This was among the first studies from Pakistan to demonstrate the surveillance for SARS-CoV-2 from a semi-formal sewage system. Methods: Four sites draining into the Lyari River in District East, Karachi, were identified and included in the current study. Raw sewage samples were collected early morning twice weekly from each site between June 10, 2021 and January 17, 2022, using Bag Mediated Filtration System (BMFS). Secondary concentration of filtered samples was achieved by ultracentrifugation and skim milk flocculation. SARS-CoV-2 RNA concentrations in the samples were estimated using PCR (Qiagen ProMega kits for N1 & N2 genes). A distributed-lag negative binomial regression model within a hierarchical Bayesian framework was used to describe the relationship between wastewater RNA concentration and COVID-19 cases from the catchment area. Genomic sequencing was performed using Illumina iSeq100. Findings: Among the 151 raw sewage samples included in the study, 123 samples (81.5%) tested positive for N1 or N2 genes. The average SARS-CoV-2 RNA concentrations in the sewage samples at each lag (1-14 days prior) were associated with the cases reported for the respective days, with a peak association observed on lag day 10 (RR: 1.15; 95% Credible Interval: 1.10-1.21). Genomic sequencing showed that the delta variant dominated till September 2022, while the omicron variant was identified in November 2022. Interpretation: Wastewater-based surveillance, together with genomic sequencing provides valuable information for monitoring the community temporal trend of SARS-CoV-2. Funding: PATH, Bill & Melinda Gates Foundation, and Global Innovation Fund.

Early to mid-pregnancy HbA1c levels and its association with adverse pregnancy outcomes in three low middle-income countries in Asia and Sub-Saharan Africa.

BACKGROUND: Hyperglycemia during pregnancy leads to adverse maternal and fetal outcomes. Thus, strict monitoring of blood glucose levels is warranted. This study aims to determine the association of early to mid-pregnancy HbA1c levels with the development of pregnancy complications in women from three countries in South Asia and Sub-Saharan Africa. METHODS: We performed a secondary analysis of the AMANHI (Alliance for Maternal and Newborn Health Improvement) cohort, which enrolled 10,001 pregnant women between May 2014 and June 2018 across Sylhet-Bangladesh, Karachi-Pakistan, and Pemba Island-Tanzania. HbA1c assays were performed at enrollment (8 to < 20 gestational weeks), and epidemiological data were collected during 2-3 monthly household visits. The women were followed-up till the postpartum period to determine the pregnancy outcomes. Multivariable logistic regression models assessed the association between elevated HbA1c levels and adverse events while controlling for potential confounders. RESULTS: A total of 9,510 pregnant women were included in the analysis. The mean HbA1c level at enrollment was found to be the highest in Bangladesh (5.31 ± 0.37), followed by Tanzania (5.22 ± 0.49) and then Pakistan (5.07 ± 0.58). We report 339 stillbirths and 9,039 live births. Among the live births were 892 preterm births, 892 deliveries via cesarean section, and 532 LGA babies. In the multivariate pooled analysis, maternal HbA1c levels of ≥ 6.5 were associated with increased risks of stillbirths (aRR = 6.3, 95% CI = 3.4,11.6); preterm births (aRR = 3.5, 95% CI = 1.8-6.7); and Large for Gestational Age (aRR = 5.5, 95% CI = 2.9-10.6). CONCLUSION: Maternal HbA1c level is an independent risk factor for predicting adverse pregnancy outcomes such as stillbirth, preterm birth, and LGA among women in South Asia and Sub-Saharan Africa. These groups may benefit from early interventional strategies.

Human Milk Micronutrients and Child Growth and Body Composition in the First 2 years: A Systematic Review.

Human milk (HM) provides a plethora of nutritional and non-nutritional compounds that support infant development. For many compounds, concentrations vary substantially among mothers and across lactation, and their impact on infant growth is poorly understood. We systematically searched MEDLINE, Embase, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born infants. Outcomes included weight-for-length, length-for-age, weight-for-age, body mass index (in kg/m2)-for-age, and growth velocity. From 9992 abstracts screened, 144 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Micronutrients (vitamins and minerals) are reported here, based on 28 articles involving 2526 mother-infant dyads. Studies varied markedly in their designs, sampling times, geographic and socioeconomic settings, reporting practices, and the HM analytes and infant anthropometrics measured. Meta-analysis was not possible because data were sparse for most micronutrients. The most-studied minerals were zinc (15 articles, 1423 dyads) and calcium (7 articles, 714 dyads). HM iodine, manganese, calcium, and zinc concentrations were positively associated with several outcomes (each in ≥2 studies), whereas magnesium (in a single study) was negatively associated with linear growth during early lactation. However, few studies measured HM intake, adjusted for confounders, provided adequate information about complementary and formula feeding, or adequately described HM collection protocols. Only 4 studies (17%) had high overall quality scores. The biological functions of individual HM micronutrients are likely influenced by other HM components; yet, only 1 study analyzed data from multiple micronutrients simultaneously, and few addressed other HM components. Thus, available evidence on this topic is largely inconclusive and fails to address the complex composition of HM. High-quality research employing chronobiology and systems biology approaches is required to understand how HM components work independently and together to influence infant growth and to identify new avenues for future maternal, newborn, or infant nutritional interventions.

Human Milk Macronutrients and Child Growth and Body Composition in the First Two Years: A Systematic Review.

Among exclusively breastfed infants, human milk (HM) provides complete nutrition in the first mo of life and remains an important energy source as long as breastfeeding continues. Consisting of digestible carbohydrates, proteins, and amino acids, as well as fats and fatty acids, macronutrients in human milk have been well studied; however, many aspects related to their relationship to growth in early life are still not well understood. We systematically searched Medline, EMBASE, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born healthy infants. From 9992 abstracts screened, 57 articles reporting observations from 5979 dyads were included and categorized based on their reporting of HM macronutrients and infant growth. There was substantial heterogeneity in anthropometric outcome measurement, milk collection timelines, and HM sampling strategies; thus, meta-analysis was not possible. In general, digestible carbohydrates were positively associated with infant weight outcomes. Protein was positively associated with infant length, but no associations were reported for infant weight. Finally, HM fat was not consistently associated with any infant growth metrics, though various associations were reported in single studies. Fatty acid intakes were generally positively associated with head circumference, except for docosahexaenoic acid. Our synthesis of the literature was limited by differences in milk collection strategies, heterogeneity in anthropometric outcomes and analytical methodologies, and by insufficient reporting of results. Moving forward, HM researchers should accurately record and account for breastfeeding exclusivity, use consistent sampling protocols that account for the temporal variation in HM macronutrients, and use reliable, sensitive, and accurate techniques for HM macronutrient analysis.

Human Milk Bioactive Components and Child Growth and Body Composition in the First 2 Years: A Systematic Review.

Human milk (HM) contains macronutrients, micronutrients, and a multitude of other bioactive factors, which can have a long-term impact on infant growth and development. We systematically searched MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born infants. From 9992 abstracts screened, 141 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Bioactives including hormones, HM oligosaccharides (HMOs), and immunomodulatory components are reported here, based on 75 articles from 69 unique studies reporting observations from 9980 dyads. Research designs, milk collection strategies, sampling times, geographic and socioeconomic settings, reporting practices, and outcomes varied considerably. Meta-analyses were not possible because data collection times and reporting were inconsistent among the studies included. Few measured infant HM intake, adjusted for confounders, precisely captured breastfeeding exclusivity, or adequately described HM collection protocols. Only 5 studies (6%) had high overall quality scores. Hormones were the most extensively examined bioactive with 46 articles (n = 6773 dyads), compared with 13 (n = 2640 dyads) for HMOs and 12 (n = 1422 dyads) for immunomodulatory components. Two studies conducted untargeted metabolomics. Leptin and adiponectin demonstrated inverse associations with infant growth, although several studies found no associations. No consistent associations were found between individual HMOs and infant growth outcomes. Among immunomodulatory components in HM, IL-6 demonstrated inverse relationships with infant growth. Current research on HM bioactives is largely inconclusive and is insufficient to address the complex composition of HM. Future research should ideally capture HM intake, use biologically relevant anthropometrics, and integrate components across categories, embracing a systems biology approach to better understand how HM components work independently and synergistically to influence infant growth.

Cohort profile: the Pregnancy Risk Infant Surveillance and Measurement Alliance (PRISMA) - Pakistan.

PURPOSE: Pakistan has disproportionately high maternal and neonatal morbidity and mortality. There is a lack of detailed, population-representative data to provide evidence for risk factors, morbidities and mortality among pregnant women and their newborns. The Pregnancy Risk, Infant Surveillance and Measurement Alliance (PRISMA) is a multicountry open cohort that aims to collect high-dimensional, standardised data across five South Asian and African countries for estimating risk and developing innovative strategies to optimise pregnancy outcomes for mothers and their newborns. This study presents the baseline maternal and neonatal characteristics of the Pakistan site occurring prior to the launch of a multisite, harmonised protocol. PARTICIPANTS: PRISMA Pakistan study is being conducted at two periurban field sites in Karachi, Pakistan. These sites have primary healthcare clinics where pregnant women and their newborns are followed during the antenatal, intrapartum and postnatal periods up to 1 year after delivery. All encounters are captured electronically through a custom-built Android application. A total of 3731 pregnant women with a mean age of 26.6±5.8 years at the time of pregnancy with neonatal outcomes between January 2021 and August 2022 serve as a baseline for the PRISMA Pakistan study. FINDINGS TO DATE: In this cohort, live births accounted for the majority of pregnancy outcomes (92%, n=3478), followed by miscarriages/abortions (5.5%, n=205) and stillbirths (2.6%, n=98). Twenty-two per cent of women (n=786) delivered at home. One out of every four neonates was low birth weight (<2500 g), and one out of every five was preterm (gestational age <37 weeks). The maternal mortality rate was 172/100 000 pregnancies, the neonatal mortality rate was 52/1000 live births and the stillbirth rate was 27/1000 births. The three most common causes of neonatal deaths obtained through verbal autopsy were perinatal asphyxia (39.6%), preterm births (19.8%) and infections (12.6%). FUTURE PLANS: The PRISMA cohort will provide data-driven insights to prioritise and design interventions to improve maternal and neonatal outcomes in low-resource regions. TRIAL REGISTRATION NUMBER: NCT05904145.

Building up a genomic surveillance platform for SARS-CoV-2 in the middle of a pandemic: a true North-South collaboration.

Next-generation sequencing technology has revolutionised pathogen surveillance over the last two decades. However, the benefits are not equitably distributed, with developing countries lagging far behind in acquiring the required technology and analytical capacity. Recent declines in the cost associated with sequencing-equipment and running consumables have created an opportunity for broader adoption. During the COVID-19 pandemic, rapid diagnostics development and DNA sequencing revolutionised the ability to diagnose and sequence SARS-CoV-2 rapidly. Socioeconomic inequalities substantially impact the ability to sequence SARS-CoV-2 strains and undermine a developing country's pandemic preparedness. Low- and middle-income countries face additional challenges in establishing, maintaining and expanding genomic surveillance. We present our experience of establishing a genomic surveillance system at the Aga Khan University, Karachi, Pakistan. Despite being at a leading health sciences research institute in the country, we encountered significant challenges. These were related to collecting standardised contextual data for SARS-CoV-2 samples, procuring sequencing reagents and consumables, and challenges with library preparation, sequencing and submission of high-quality SARS-CoV-2 genomes. Several technical roadblocks ensued during the implementation of the genomic surveillance framework, which were resolved in collaboration with our partners. High-quality genome sequences were then deposited on open-access platforms per the best practices. Subsequently, these efforts culminated in deploying Pakistan's first SARS-CoV-2 phyllo surveillance map as a Nextstrain build. Our experience offers lessons for the successful development of Genomic Surveillance Infrastructure in resource-limited settings struck by a pandemic.

Knowledge, attitudes, and practices toward seasonal influenza vaccination among healthcare workers and pregnant women in Pakistan: A mixed methods approach.

Vaccine hesitancy is a significant public health issue globally. We aim to document the barriers toward seasonal influenza vaccine uptake among healthcare workers (HCWs) and pregnant women (PW) in Pakistan. We performed a concurrent mixed methods study in four cities (Karachi, Islamabad, Quetta, and Peshawar) across Pakistan from September to December 2021. The quantitative component consisted of independent cross-sectional surveys for PW and HCWs, and the qualitative component comprised of in-depth interviews (IDIs) and focus group discussions (FGDs) among HCWs. Simple linear regression was used to determine the association of sociodemographic variables with knowledge, attitudes, and practices. Overall, 750 PW and 420 HCWs were enrolled. Among the PW, 44% were willing to receive the vaccine if available free of cost. Only 44% of the HCWs were vaccinated; however, 86% intended to get vaccinated and were willing to recommend the vaccine to their patients. HCWs refused vaccine due to side-effects (65%), cost (57%), and allergies (36%). An education level of secondary school and above was predictive of higher attitude and knowledge scores while having received the COVID-19 vaccine was associated with higher practice scores for both PW and HCWs. Several themes emerged from the interviews: 1) HCWs' knowledge of influenza and its prevention, 2) HCWs' perception of motivators and barriers to influenza vaccine uptake and 3) HCWs' attitudes towrd vaccine promotion. We report low influenza vaccine coverage among HCWs and PW in Pakistan. Educational campaigns addressing misconceptions, and improving affordability and accessibility through government interventions, can improve vaccine uptake.

Comparison of Masimo Total Hemoglobin SpHb® continuous non-invasive hemoglobin monitoring device with laboratory complete blood count measurement using venous sample: Protocol for an observational substudy of the Pregnancy Risk and Infant Surveillance and Measurement Alliance Maternal and Newborn Health (PRISMA MNH) study.

Background: The Masimo Total Hemoglobin SpHb® is a continuous and non-invasive handheld device to measure hemoglobin levels. Previous research has found that SpHb is able to accurately detect hemoglobin levels in adult patients with a similar degree of bias and standard deviation to point-of-care invasive method measurements. Generally, limited clinical evidence, lack of validation of Masimo at higher than and lower than hemoglobin threshold values, and scientific consensus supporting the use of Masimo for accurate hemoglobin testing for the diagnosis of anemia during pregnancy calls for further research. Methods and analysis: The proposed prospective cohort will be nested within the ongoing Pregnancy Risk and Infant Surveillance and Measurement Alliance (PRISMA) Maternal and Newborn Health (MNH) study. Three study sites (located in Zambia, Kenya, and Pakistan) will participate and collect hemoglobin data at five time points (<20 weeks, 20 weeks, 28 weeks, 36 weeks' gestation, and six weeks postpartum). We will measure hemoglobin using a venous blood sample via hematology auto-analyzer complete blood count (gold standard) and the non-invasive device. The primary objective is to assess agreement between Masimo total hemoglobin and complete blood count and on a continuous scale using Intraclass Correlation Coefficient and Bland-Altman Analysis. The second objective is to assess agreement between the two measures on a binary scale using Positive Percentage Agreement and Negative Percentage Agreement, Cohen's Kappa, and McNemar Test. On an ordinal scale, agreement will be measured using Weighted Cohen's Kappa and Harrel's Concordance Index. Lastly, we will assess factors that might affect the accuracy of Masimo total hemoglobin using linear mixed models. Conclusions: The primary aim of this study is to assess the validity of the non-invasive Masimo device compared to the gold standard method of invasive hemoglobin measurements during pregnancy and postpartum periods for the diagnosis of anemia.

Structural Changes in the Brain on Magnetic Resonance Imaging in Malnourished Children: A Scoping Review of the Literature.

BACKGROUND: This review was conducted to summarize the current evidence on the structural findings seen in brain magnetic resonance imaging (MRI) in malnourished children and the effect of optimized nutritional supplementation on brain development as studied through MRI. METHODS: A systematic search was carried out in PubMed, Embase, The Cochrane Library, Web of Science (Clarivate Analytics), WHO ICTRP Clinical Trials in Children, and ClinicalTrials.gov using a predefined search criterion for relevant literature from inception to January 2022. The primary outcome of the study was structural changes observed in the brain on MRI. RESULTS: The most common abnormal findings on MRI in malnourished infants were cerebral atrophy and dilated ventricles. Furthermore, a higher proportion of breast milk, calorie, and lipid intake in the diet was significantly associated with increased brain volumes; this also increased the likelihood of normal MRI scores at term. When followed till adolescence, it was observed that these infants had increased neonatal weight gain and a higher intelligence quotient when compared with the group. CONCLUSIONS: In conclusion, most children with moderate/severe malnutrition had abnormal MRI findings, mostly cerebral atrophy with or without ventricular dilatation. Since none of the studies measured the degree of atrophy or ventricular dilatation, it was not possible to assess the effect of the severity of malnutrition on brain atrophy. A universal measurement or scoring system for assessing the degree of brain atrophy is needed to help correlate the severity of malnutrition with the degree of brain atrophy and monitor the effects of nutritional rehabilitation over time.

Newborn weight nomograms in selected low and middle-income countries.

Growth impairment is common in low- and middle-income countries (LMIC) and may begin during early infancy, increasing morbidity and mortality. To ensure healthy infant growth, healthcare providers in high-income countries (HIC) track newborn weight change using tools developed and validated in HIC. To understand the utility of these tools for LMIC, we conducted a secondary analysis to compare weight trajectories in the first 5 days of life among newborns born in our LMIC cohort to an existing HIC newborn weight tool designed to track early weight change. Between April 2019 and March 2020, a convenience sample of 741 singleton healthy breastfeeding newborns who weighed ≥ 2000 g at birth were enrolled at selected health facilities in Guinea-Bissau, Nepal, Pakistan, and Uganda. Using a standardized protocol, newborn weights were obtained within 6 h of birth and at 1, 2, 3, 4, and 5 days, and nomograms depicting newborn weight change were generated. The trajectories of early newborn weight change in our cohort were largely similar to published norms derived from HIC infants, with the exceptions that initial newborn weight loss in Guinea-Bissau was more pronounced than HIC norms and newborn weight gain following weight nadir was more pronounced in Guinea-Bissau, Pakistan, and Uganda than HIC norms. These data demonstrate that HIC newborn weight change tools may have utility in LMIC settings.

Process evaluation of paediatric fellowship training programs at a University Hospital in Pakistan.

BACKGROUND: Fellowship programs offer training in a subspecialty focusing on distinct and advanced clinical/academic skills. This advanced postgraduate training allows physicians, who desire a more specialized practice, to further develop clinical, academic, research, and leadership/administrative skills. The Aga Khan University (AKU) is one of the few institutes offering paediatric sub-specialty training in Pakistan. We aimed to evaluate the current Paediatric fellowship programs at AKU. METHODS: Process evaluation of six paediatric fellowship programs (cardiology, neurology, endocrinology, critical care medicine, neonatology, and infectious disease) was conducted from September 2020 to April 2021 by senior clinicians and medical educationists. Evidence was collected through document review (using existing postgraduate medical education program information form), observation of teaching and learning support, and focused group discussions/interviews with program faculty and fellows were conducted. A review of the evaluation report was done as part of this study. This study received an exemption from the ethical review committee. The quantitative data were analyzed using SPSS (22.0) while the reports of discussion with fellows and friends underwent content analysis. RESULTS: All fellowship programs met the criteria for having a robust competency-based fellowship curriculum as per the institutional and national guidelines. Formative assessment in the form of continuous evaluation was found to be integrated into all the fellowship programs, however, most of the programs were found to lack a summative assessment plan. Fellows in training and program faculty were satisfied with the opportunities for mentorship, teaching, and learning. Thematic analysis of the discussion reports with faculty and fellows revealed three key themes including, program aspects translating into strengthening the training, gaps in the training program in delivering the expectations, and making ways to reach par excellence. CONCLUSIONS: The process evaluation of paediatric fellowship programs provided an opportunity to holistically review the current strengths and quality of the training in individual programs along with the unmet needs of the trainees. This will help the program stakeholders to prioritize, align and allocate the resources to further enhance the quality of training and outcome of individual fellowship programs to ensure wider impacts at a regional, national, and international health system level.

Comparative predictive power of serum vs plasma proteomic signatures in feto-maternal medicine.

BACKGROUND: Blood proteins are frequently measured in serum or plasma, because they provide a wealth of information. Differences in the ex vivo processing of serum and plasma raise concerns that proteomic health and disease signatures derived from serum or plasma differ in content and quality. However, little is known about their respective power to predict feto-maternal health outcomes. Predictive power is a sentinel characteristic to determine the clinical use of biosignatures. OBJECTIVE: This study aimed to compare the power of serum and plasma proteomic signatures to predict a physiological pregnancy outcome. STUDY DESIGN: Paired serum and plasma samples from 73 women were obtained from biorepositories of a multinational prospective cohort study on pregnancy outcomes. Gestational age at the time of sampling was the predicted outcome, because the proteomic signatures have been validated for such a prediction. Multivariate and cross-validated models were independently derived for serum and plasma proteins. RESULTS: A total of 1116 proteins were measured in 88 paired samples from 73 women with a highly multiplexed platform using proximity extension technology (Olink Proteomics Inc, Watertown, MA). The plasma proteomic signature showed a higher predictive power (R=0.64; confidence interval, 0.42-0.79; P=3.5×10-6) than the serum signature (R=0.45; confidence interval, 0.18-0.66; P=2.2×10-3). The serum signature was validated in plasma with a similar predictive power (R=0.58; confidence interval, 0.34-0.75; P=4.8×10-5), whereas the plasma signature was validated in serum with reduced predictive power (R=0.53; confidence interval, 0.27-0.72; P=2.6×10-4). Signature proteins largely overlapped in the serum and plasma, but the strength of association with gestational age was weaker for serum proteins. CONCLUSION: Findings suggest that serum proteomics are less informative than plasma proteomics. They are compatible with the view that the partial ex-vivo degradation and modification of serum proteins during sample processing are an underlying reason. The rationale for collecting and analyzing serum and plasma samples should be carefully considered when deriving proteomic biosignatures to ascertain that specimens of the highest scientific and clinical yield are processed. Findings suggest that plasma is the preferred matrix.

Student experiences of simulation-based learning and its impact on their performance in Objective Structured Clinical Examination in Pediatrics - A mixed method study.

Objective: This study aims to assess the effectiveness of integrating simulation for teaching pediatric clinical examination skills to undergraduate, MBBS Year-IV medical students at The Aga Khan University, Karachi, Pakistan. Methods: In this mixed method study, the Objective Structured Clinical Examination (OSCE) scores of the students who were taught using simulation (batch 2017-2018) were compared with the batch of the academic year 2016 -2017 (taught via traditional methods). In order to explore the experiences of the intervention group, a questionnaire with four open-ended questions was administered at the end of the clerkship. Results: Students who were taught by simulation, scored significantly higher on the clinical skills stations in Objective Structured Clinical Examination, than in the pre-intervention group (p-value <0.01). The students quoted safety of the learning environment, opportunities for deliberate practice, debriefing and facilitation skills maximized quoted that their experience of learning through simulation, however, some challenges were identified for future improvement. Conclusion: The result of the study suggested simulation as a useful instructional strategy for teaching examination skills to students in their early years. The student gained confidence through deliberate practice and feedback without compromising patient safety, which translated into improved performance in the high-stakes OSCE examination at the end of the clerkship.

Co-carriage of Staphylococcus aureus and Streptococcus pneumoniae among children younger than 2 years of age in a rural population in Pakistan.

Objectives: Staphylococcus aureus and Streptococcus pneumoniae are common colonizers of the human nasopharynx. In this study, we describe S. aureus nasopharyngeal carriage and evaluate its association with S. pneumoniae carriage post-10-valent pneumococcal conjugate vaccine (PCV10) introduction in Pakistan. Methods: A serial cross-sectional study was undertaken from 2014 to 2018, children <2 years were randomly selected, and nasopharyngeal swabs were collected using standard WHO guidelines. S. aureus and S. pneumoniae isolates were identified using standard methods and tested for antimicrobial susceptibility by the standard Kirby-Bauer disk-diffusion method as per Clinical & Laboratory Standards Institute (CLSI) recommendations. Regression analysis was used to determine predictors associated with S. aureus carriage. Results: We enrolled 3140 children. S. aureus carriage prevalence was 5.6% (176/3140), and 50.1% (81/176) of the isolates were methicillin-resistant S. aureus (MRSA). S. aureus carriage was higher in the absence of pneumococcus compared to isolates in which pneumococcus was present (7.5% vs 5.0%). S. aureus carriage was negatively associated with pneumococcal carriage, being in 3rd and 4th year of enrollment, and vaccination with two and three PCV10 doses, in addition, fast breathing, ≥2 outpatients visits, and rainy season were positively associated. The following resistance rates were observed: 98.9% for penicillin, 74.4% for fusidic acid, and 23.3% for gentamicin, 10.2% for erythromycin, and 8.5% for cotrimoxazole. All isolates were susceptible to amikacin. Conclusions: Overall S. aureus carriage prevalence was low, PCV10 vaccine was protective against the carriage. The proportion of MRSA carriage and antimicrobial resistance was high in this community warranting continuous monitoring for invasive infections.

Pregnant Women's Experiences with Midwifery-Led Antenatal Care Services in Peri-Urban Communities in Karachi, Pakistan.

Purpose: To understand pregnant women's experience with midwifery-led antenatal care services using the Respectful Maternity Care charter in primary health centers in Karachi, Pakistan. Methods: This cross-sectional study was at Rehri Goth and Ibrahim Hyderi, two peri-urban communities in Karachi, Pakistan, where women receive antenatal care services. All pregnant women in their third trimester who consented during the study period were included. The participants were asked about access to care, antenatal care experience, person-centered approach, and general satisfaction with the facility using a pre-designed questionnaire. These themes were mapped onto the universal Respectful Maternity Care charter. Descriptive statistics were used to summarize the findings in each of these themes. Multivariable logistic regression techniques to determine the relationship between the dependent and independent variables. Results: There were 904 women who agreed to participate in this study during January to December 2021. Majority of the women (94%, n=854) were satisfied with the operating hours and cleanliness. More than 90% of the women reported positive experiences regarding privacy, respectful treatment by midwives, and non-discriminatory care. However, 40% (n=362) of the women reported not receiving adequate information and informed consent before a medical procedure, while 65% (n=587) reported poor counseling for birth preparedness. Maternal age, women's occupation, women's education, and parity were found to be significantly associated with respect provided, satisfaction with counseling and the consent process. Conclusion: This study reported satisfaction of pregnant women with the facility's ambiance, respect, and care; however, poor communication skills regarding consent and antenatal counseling were reported. The findings suggest the need for more efficient strategies, such as regular respectful maternity care and technical training to strengthen midwife-patient interactions and enhance overall satisfaction, thus improving maternal and newborn outcomes.