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.

Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis.

BACKGROUND: Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). OBJECTIVES: This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. METHODS: Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. RESULTS: The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 µg/mL and standard deviation of 0.43 µg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 µg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. CONCLUSIONS: Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.

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.

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.

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.

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.

Pulse oximetry: why oxygen saturation is still not a part of standard pediatric guidelines in low-and-middle-income countries (LMICs).

BACKGROUND: With the high frequency of acute respiratory infections in children worldwide, particularly so in low-resource countries, the development of effective diagnostic support is crucial. While pulse oximetry has been found to be an acceptable method of hypoxemia detection, improving clinical decision making and efficient referral, many healthcare set ups in low- and middle-income countries have not been able to implement pulse oximetry into their practice. MAIN BODY: A review of past pulse oximetry implementation attempts in low- and middle-income countries proposes the barriers and potential solutions for complete integration in the healthcare systems. The addition of pulse oximetry into WHO health guidelines would prove to improve detection of respiratory distress and ensuing therapeutic measures. Incorporation is limited by the cost and unavailability of pulse oximeters, and subsequent oxygen accessibility. This restriction is compounded by the lack of trained personnel, and healthcare provider misconceptions. These hurdles can be combated by focus on low-cost devices, and cooperation at national levels for development in healthcare infrastructure, resource transport, and oxygen delivery systems. CONCLUSION: The implementation of pulse oximetry shows promise to improve child morbidity and mortality from pneumonia in low- and middle-income countries. Steady measures taken to improve access to pulse oximeters and oxygen supplies, along with enhanced medical provider training are encouraging steps to thorough pulse oximetry integration.

Metabolomics of a neonatal cohort from the Alliance for Maternal and Newborn Health Improvement biorepository: Effect of preanalytical variables on reference intervals.

BACKGROUND: The study was conducted to determine reference interval (RI) and evaluate the effect of preanalytical variables on Dried blood spot (DBS)-amino acids, acylcarnitines and succinylacetone of neonates. METHODOLOGY: DBS samples were collected within 48-72 hours of life. Samples were analyzed for biochemical markers on tandem mass spectrometer at the University of Iowa. Comparison of RI across various categorical variables were performed. RESULTS: A total of 610 reference samples were selected based on exclusion criteria; 53.2% being females. Mean gestational age (GA) of mothers at the time of delivery was 38.7±1.6 weeks; 24.5% neonates were of low birth weight and 14.3% were preterm. Out of the total 610 neonates, 23.1% were small for GA. Reference intervals were generated for eleven amino acids, thirty-two acylcarnitines and succinylacetone concentrations. Markers were evaluated with respect to the influence of gender, GA, weight and time of sampling and statistically significant minimal differences were observed for some biomarkers. CONCLUSION: RI for amino acids, succinylacetone and acylcarnitine on DBS has been established for healthy neonates, which could be of use in the clinical practice. Clinically significant effect of GA, weight, gender and time of sampling on these markers were not identified.

The creation of the Global Scales for Early Development (GSED) for children aged 0-3 years: combining subject matter expert judgements with big data.

INTRODUCTION: With the ratification of the Sustainable Development Goals, there is an increased emphasis on early childhood development (ECD) and well-being. The WHO led Global Scales for Early Development (GSED) project aims to provide population and programmatic level measures of ECD for 0-3 years that are valid, reliable and have psychometrically stable performance across geographical, cultural and language contexts. This paper reports on the creation of two measures: (1) the GSED Short Form (GSED-SF)-a caregiver reported measure for population-evaluation-self-administered with no training required and (2) the GSED Long Form (GSED-LF)-a directly administered/observed measure for programmatic evaluation-administered by a trained professional. METHODS: We selected 807 psychometrically best-performing items using a Rasch measurement model from an ECD measurement databank which comprised 66 075 children assessed on 2211 items from 18 ECD measures in 32 countries. From 766 of these items, in-depth subject matter expert judgements were gathered to inform final item selection. Specifically collected were data on (1) conceptual matches between pairs of items originating from different measures, (2) developmental domain(s) measured by each item and (3) perceptions of feasibility of administration of each item in diverse contexts. Prototypes were finalised through a combination of psychometric performance evaluation and expert consensus to optimally identify items. RESULTS: We created the GSED-SF (139 items) and GSED-LF (157 items) for tablet-based and paper-based assessments, with an optimal set of items that fit the Rasch model, met subject matter expert criteria, avoided conceptual overlap, covered multiple domains of child development and were feasible to implement across diverse settings. CONCLUSIONS: State-of-the-art quantitative and qualitative procedures were used to select of theoretically relevant and globally feasible items representing child development for children aged 0-3 years. GSED-SF and GSED-LF will be piloted and validated in children across diverse cultural, demographic, social and language contexts for global use.

Risk factors for community-acquired bacterial infection among young infants in South Asia: a longitudinal cohort study with nested case-control analysis.

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.

Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study.

BACKGROUND: Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context. METHODS: Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster (GPSC) and a clonal complex (CC) were assigned to each genome. Phylogenetic, evolutionary, and spatiotemporal analysis were conducted using the same 24F collection and supplemented with a global collection of genomes belonging to the lineage of interest from the GPS project database (n=25 590). FINDINGS: Serotype 24F was identified in numerous countries mainly due to the clonal spread of three lineages: GPSC10 (CC230), GPSC16 (CC156), and GPSC206 (CC7701). GPSC10 was the only multidrug-resistant lineage. GPSC10 drove the increase in 24F in France and had high invasive disease potential. The international dataset of GPSC10 (n=888) revealed that this lineage expressed 16 other serotypes, with only six included in 13-valent PCV (PCV13). All serotype 24F isolates were clustered in a single clade within the GPSC10 phylogeny and long-range transmissions were detected from Europe to other continents. Spatiotemporal analysis showed GPSC10-24F took 3-5 years to spread across France and a rapid change of serotype composition from PCV13 serotype 19A to 24F during the introduction of PCV13 was observed in neighbouring country Spain. INTERPRETATION: Our work reveals that GPSC10 alone is a challenge for serotype-based vaccine strategy. More systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal diseases. FUNDING: Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention.

Newborn weight change and predictors of underweight in the neonatal period in Guinea-Bissau, Nepal, Pakistan and Uganda.

In low- and middle-income countries (LMIC), growth impairment is common; however, the trajectory of growth over the course of the first month has not been well characterised. To describe newborn growth trajectory and predictors of growth impairment, we assessed growth frequently over the first 30 days among infants born ≥2000 g in Guinea-Bissau, Nepal, Pakistan and Uganda. In this cohort of 741 infants, the mean birth weight was 3036 ± 424 g. For 721 (98%) infants, weight loss occurred for a median of 2 days (interquartile range, 1-4) following birth until weight nadir was reached 5.9 ± 4.3% below birth weight. At 30 days of age, the mean weight was 3934 ± 592 g. The prevalence of being underweight at 30 days ranged from 5% in Uganda to 31% in Pakistan. Of those underweight at 30 days of age, 56 (59%) had not been low birth weight (LBW), and 48 (50%) had reached weight nadir subsequent to 4 days of age. Male sex (relative risk [RR] 2.73 [1.58, 3.57]), LBW (RR 6.41 [4.67, 8.81]), maternal primiparity (1.74 [1.20, 2.51]) and reaching weight nadir subsequent to 4 days of age (RR 5.03 [3.46, 7.31]) were highly predictive of being underweight at 30 days of age. In this LMIC cohort, country of birth, male sex, LBW and maternal primiparity increased the risk of impaired growth, as did the modifiable factor of delayed initiation of growth. Interventions tailored to infants with modifiable risk factors could reduce the burden of growth impairment in LMIC.

Community-based asthma assessment in young children: adaptations for a multicentre longitudinal study in South Asia.

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.

Effect of a community based social marketing strategy on the uptake of clean delivery kits in peri-urban communities of Karachi, Pakistan.

BACKGROUND: Pakistan has one of the highest neonatal and maternal mortality rates in the world. Use of clean delivery kits (CDK) at time of delivery improves maternal and newborn outcome. We test effectiveness of a social marketing strategy to increase uptake of CDKs in a low socioeconomic peri-urban community in Pakistan. METHODS: This was a sequential mixed method study. The quantitative component consisted of two arms. In the prospective intervention arm trained community health workers (CHWs) visited pregnant women twice to prepare them for birth and encourage use of CDKs. Availability of these kits was ensured at accessible stores in these communities. The retrospective control arm consisted of women delivering in same area during the past 3 months identified from pregnancy register. Information was collected on sociodemographic, pregnancy characteristics and use of CDKs at time of delivery in both arms. We compared proportion of women using CDKs during home deliveries in the intervention and control arm. We performed logistic regression analysis to identify factors associated with use of CDKs in intervention arm. We carried out separate focused group discussions (FGDs) with women who used CDKs, with women who did not use CDKs and birth attendants. RESULTS: Total of 568 pregnant women were enrolled in prospective intervention arm and 603 in retrospective control arm. The proportion of women using CDKs during home deliveries in retrospective control arm was 9.4% compared to 23.8% in prospective control arm (p = < 0.001). In final multivariable model, increasing age of pregnant woman and husband having some education was positively associated with CDK use (aOR 1.1;95% CI 1.1-1.2 and aOR 2.2;95% CI 1.3-3.6 respectively). During FGDs, many women were of the thought that kits should be free or included in the amount charged by birth attendants. Assembly of components of kit into one package was appreciated by birth attendants. CONCLUSION: Social marketing strategy targeting pregnant women and their family members resulted in an increase in the uptake of CDKs in our study. Birth attendants were generally satisfied with the assembly of the kit. Many women cited unawareness and cost to be a major impediment in use of CDKs.

Machine learning prediction of gestational age from metabolic screening markers resistant to ambient temperature transportation: Facilitating use of this technology in low resource settings of South Asia and East Africa.

Background: Knowledge of gestational age is critical for guiding preterm neonatal care. In the last decade, metabolic gestational dating approaches emerged in response to a global health need; because in most of the developing world, accurate antenatal gestational age estimates are not feasible. These methods initially developed in North America have now been externally validated in two studies in developing countries, however, require shipment of samples at sub-zero temperature. Methods: A subset of 330 pairs of heel prick dried blood spot samples were shipped on dry ice and in ambient temperature from field sites in Tanzania, Bangladesh and Pakistan to laboratory in Iowa (USA). We evaluated impact on recovery of analytes of shipment temperature, developed and evaluated models for predicting gestational age using a limited set of metabolic screening analytes after excluding 17 analytes that were impacted by shipment conditions of a total of 44 analytes. Results: With the machine learning model using all the analytes, samples shipped in dry ice yielded a Root Mean Square Error (RMSE) of 1.19 weeks compared to 1.58 weeks for samples shipped in ambient temperature. Out of the 44 screening analytes, recovery of 17 analytes was significantly different between the two shipment methods and these were excluded from further machine learning model development. The final model, restricted to stable analytes provided a RMSE of 1.24 (95% confidence interval (CI) = 1.10-1.37) weeks for samples shipped on dry ice and RMSE of 1.28 (95% CI = 1.15-1.39) for samples shipped at ambient temperature. Analysis for discriminating preterm births (gestational age <37 weeks), yielded an area under curve (AUC) of 0.76 (95% CI = 0.71-0.81) for samples shipped on dry ice and AUC of 0.73 (95% CI = 0.67-0.78) for samples shipped in ambient temperature. Conclusions: In this study, we demonstrate that machine learning algorithms developed using a sub-set of newborn screening analytes which are not sensitive to shipment at ambient temperature, can accurately provide estimates of gestational age comparable to those from published regression models from North America using all analytes. If validated in larger samples especially with more newborns <34 weeks, this technology could substantially facilitate implementation in LMICs.

Burden and risk factors for antenatal depression and its effect on preterm birth in South Asia: A population-based cohort study.

INTRODUCTION: Women experience high rates of depression, particularly during pregnancy and the postpartum periods. Using population-based data from Bangladesh and Pakistan, we estimated the burden of antenatal depression, its risk factors, and its effect on preterm birth. METHODS: The study uses the following data: maternal depression measured between 24 and 28 weeks of gestation using the 9-question Patient Health Questionnaire (PHQ-9); data on pregnancy including an ultrasound before 19 weeks of gestation; data on pregnancy outcomes; and data on woman's age, education, parity, weight, height, history of previous illness, prior miscarriage, stillbirth, husband's education, and household socioeconomic data collected during early pregnancy. Using PHQ-9 cutoff score of ≥12, women were categorized into none to mild depression or moderate to moderately severe depression. Using ultrasound data, preterm birth was defined as babies born <37 weeks of gestation. To identify risk ratios (RR) for antenatal depression, unadjusted and adjusted RR and 95% confidence intervals (CI) were calculated using log- binomial model. Log-binomial models were also used for determining the effect of antenatal depression on preterm birth adjusting for potential confounders. Data were analyzed using Stata version 16 (StataCorp LP). RESULTS: About 6% of the women reported moderate to moderately severe depressive symptoms during the antenatal period. A parity of ≥2 and the highest household wealth status were associated with an increased risk of depression. The overall incidence of preterm birth was 13.4%. Maternal antenatal depression was significantly associated with the risk of preterm birth (ARR, 95% CI: 1.34, 1.02-1.74). CONCLUSION: The increased risk of preterm birth in women with antenatal depression in conjunction with other significant risk factors suggests that depression likely occurs within a constellation of other risk factors. Thus, to effectively address the burden of preterm birth, programs require developing and providing integrated care addressing multiple risk factors.

Nutritional support and prophylaxis of azithromycin for pregnant women to improve birth outcomes in peri-urban slums of Karachi, Pakistan-a protocol of multi-arm assessor-blinded randomized controlled trial (Mumta PW trial).

BACKGROUND: Maternal undernutrition is critical in the etiology of poor perinatal outcomes and accounts for 20% of small-for-gestational-age (SGA) births. High levels of food insecurity, antenatal undernourishment, and childhood undernutrition necessitate the supplementation of fortified balanced energy protein (BEP) during pregnancy in low-income settings especially with scarce literature available in this subject. Hence, this paper extensively covers the protocol of such a trial conducted in an urban slum of Karachi, Pakistan. METHODS: The trial is community-based, open-labelled, four-arm, and randomized controlled that will include parallel group assignments with a 1:1:1:1 allocation ratio in low-income squatter settlements in urban Karachi, Pakistan. All pregnant women (PW), if identified between > 8 and < 19 weeks of gestation based on ultrasound, will be offered routine antenatal care (ANC) counseling and voluntary participation in the trial after written informed consent. A total number of 1836 PW will be enrolled with informed consent and randomly allocated to one of the four arms receiving: (1) ANC counseling only (control group), (2) ANC counseling plus BEP supplement (intervention arm 1), (3) ANC counseling plus BEP supplement plus 2 doses azithromycin (intervention arm 2), or (4) ANC counseling plus BEP supplement plus daily single dose of nicotinamide and choline (intervention arm 3). TRIAL REGISTRATION: ClinicalTrials.gov NCT04012177 . Registered on July 9, 2019.