Predictors of vaccination card retention in children 12-59 months old in Karachi, Pakistan

Objective: To determine the factors associated with retaining the vaccination card among care takers of 12-59 months old children in Karachi, Pakistan.Methods: This was an analytical cross-sectional study in Karachi. Households were randomly selected throughout a multistage cluster sampling technique. Data was collected for 504 children of 12- 59 months of age. Questionnaire was administered to caretakers to gather information regarding the children\u27s vaccination status, socio-demographic characteristics and reviewing their vaccination cards. Statistical analysis was done by SPSS 19 using logistic regression.Results: Among 462 vaccinated children, caretakers of 33% provided vaccination cards. Odds of card retention decrease if the caretaker has a large household i.e., \u3e5 people sharing one room (AOR 0.277, 95% CI: 0.096, 0.797) and if the child is of four to five years of age (AOR 0.544, 95% CI: 0.305, 0.970). Gender of the child, and the caretaker\u27s education and access to electronic media were not significant predictors of vaccination card retention in our study.Conclusion: Our study showed that vaccination card retention for children 12-59 months of age was low (33%) in Karachi. There is a need to educate caretakers of young children regarding the importance of keeping vaccination card and to disseminate this information through healthcare providers. Improving vaccination card retention is one of the key measures which will help towards accurately estimating coverage and to inform health policy decisions

Comparing neonatal respiratory morbidity in neonates delivered at term by elective Caesarean section with and without dexamethasone: retrospective cohort study

Objective: To assess the effect of dexamethasone on neonatal respiratory morbidity in babies delivered by early term elective lower segment Caesarean section. Method: The retrospective cohort study was conducted at a secondary level hospital in Karachi. It reviewed the medical record of pregnant women and their babies who were delivered by elective lower segment Caesarean section between January 1 and June 30, 2013, at 37-38+6 weeks of pregnancy. The women were divided into exposed group (Group A) who received prophylactic dexamethasone, and non-exposed group (Group B) who did not receive dexamethasone Neonatal respiratory morbidity was compared between the two groups. Data was analysed using SPSS 19.Results: The 196 subjects in the study were equally divided in two groups. In Group A, only 1(1%) baby developed transient tachypnoea compared to 10(10%) babies in Group B (p=0.005). Besides, 11(11%) babies were admitted to nursery in Group B compared to 1(1%) in Group A (p=0.005). No baby was referred to any tertiary care hospital for intensive care.Conclusion: Beneficial effects of prophylactic dexamethasone in neonatal respiratory morbidity were found, but further prospective studies with large sample size are required

Long term effectiveness of cognitive behavior therapy for treatment of postpartum depression: A systematic review and meta-analysis

Background: The existing trials on the long term effectiveness of cognitive behavior therapy (CBT) for the treatment of postpartum depression have conflicting results. Therefore, we performed a systematic review to summarize the current evidence.Methodology: Literature search was performed using electronic databases Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsychINFO were explored from January 2000 to March 2013.All peer-reviewed English-published randomized controlled trials were eligible if they assessed the long term (at least at 24 weeks post partum) effectiveness of CBT versus standard postpartum care for prevention of postpartum depression. Data from eligible studies were abstracted by using structured data extraction form and pooled for calculation of relative risk ratio.Results: Five randomized controlled trials fulfilled eligibility criteria. In the included studies, the total number of women was 1087 with age ranged from 17 years to 42 years. Assessment carried on the ‘Cochrane Risk of Bias Tool’ showed the trials included in this review had low risk of bias. Two trials had sample size less than 50. Two out of five trials reported beneficial effect of CBT whereas three trials found no difference. Meta-analysis [random effect model] revealed 30% reduction in the prevalence of depression in the intervention group as compared with the control group [RR: 0.70 (95% C.I: 0.55 to 0.90)]. However, these results showed effectiveness of intervention because of one large trial and excluding this trial, there was no significant difference.Conclusion: In this systematic review, we found a beneficial effect of CBT in the prevention of postpartum depression at 24 weeks of postpartum period. However, the evidence is limited by a small number of trials with results being dominated by a single large trial. Robust research with larger sample size is needed to determine the long-term effectiveness of CBT for treatment of postpartum depression

Mucosal genomics implicate lymphocyte activation and lipid metabolism in refractory environmental enteric dysfunction

Background & aims: Environmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED.Methods: The Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan. Biomarkers were measured at 9 months and tested for association with growth at 24 months. The duodenal methylome and transcriptome was determined in 52 undernourished SEEM participants and 42 North American controls and celiac disease patients.Results: After accounting for growth at study entry, circulating IGF-1 and ferritin predicted linear growth, whereas leptin correlated with future weight gain. The EED transcriptome exhibited suppression of antioxidant, detoxification, and lipid metabolism genes, and induction of anti-microbial response, interferon, and lymphocyte activation genes. Relative to celiac disease, suppression of antioxidant and detoxification genes and induction of anti-microbial response genes were EED-specific. At the epigenetic level, EED showed hyper-methylation of epithelial metabolism and barrier function genes, and hypo-methylation of immune response and cell proliferation genes. Duodenal co-expression modules showed association between lymphocyte proliferation and epithelial metabolic genes and histologic severity, fecal energy loss, and wasting (weight-for-length/height Z\u3c-2.0). Leptin was associated with expression of epithelial carbohydrate metabolism and stem cell renewal genes. Immune response genes were attenuated by giardia colonization.Conclusions: Children with reduced circulating IGF-1 are more likely to experience stunting. Leptin and a gene signature for lymphocyte activation and dysregulated lipid metabolism are implicated in wasting, suggesting new approaches for EED refractory to nutritional intervention

Environmental enteropathy in undernourished Pakistani children: Clinical and histomorphometric analyses

Despite nutrition interventions, stunting thought to be secondary to underlying environmental enteropathy (EE) remains pervasive among infants residing in resource-poor countries and remains poorly characterized. From a birth cohort of 380 children, 65 malnourished infants received 12 weeks of nutritional supplementation with ready-to-use therapeutic food (RUTF). Eleven children with insufficient response to RUTF underwent upper endoscopy with duodenal biopsies, which were compared with U.S., age-matched specimens for healthy, celiac disease, non-celiac villous atrophy, non-celiac intraepithelial lymphocytosis, and graft-versus-host disease patients. Of the 11 children biopsied, EE was found in 10 (91%) with one subject with celiac disease. Morphometry demonstrated decreased villus-to-crypt (V:C) ratios in EE relative to healthy and non-celiac lymphocytosis patients. Environmental enteropathy villus volumes were significantly decreased relative to healthy controls. In EE, average CD3+ cells per 100 epithelial cells and per 1,000 µm2 of lamina propria and the number of lamina propria CD20+ B-cell aggregates were increased relative to all other groups. Our results indicate that V:C ratios are reduced in EE but are less severe than in celiac disease. Environmental enteropathy intraepithelial and lamina propria T lymphocytosis is of greater magnitude than that in celiac disease. The increases in lamina propria B and T lymphocytes suggest that non-cytolytic lymphocytic activation may be a more prominent feature of EE relative to celiac disease. These results provide new insights into shared yet distinct histological and immunological features of EE and celiac disease in children

A novel histological index for evaluation of environmental enteric dysfunction identifies geographic-specific features of enteropathy among children with suboptimal growth

Background: A major limitation to understanding the etiopathogenesis of environmental enteric dysfunction (EED) is the lack of a comprehensive, reproducible histologic framework for characterizing the small bowel lesions. We hypothesized that the development of such a system will identify unique histology features for EED, and that some features might correlate with clinical severity.Methods: Duodenal endoscopic biopsies from two cohorts where EED is prevalent (Pakistan, Zambia) and North American children with and without gluten sensitive enteropathy (GSE) were processed for routine hematoxylin & eosin (H&E) staining, and scanned to produce whole slide images (WSIs) which we shared among study pathologists via a secure web browser-based platform. A semi-quantitative scoring index composed of 11 parameters encompassing tissue injury and response patterns commonly observed in routine clinical practice was constructed by three gastrointestinal pathologists, with input from EED experts. The pathologists then read the WSIs using the EED histology index, and inter-observer reliability was assessed. The histology index was further used to identify within- and between-child variations as well as features common across and unique to each cohort, and those that correlated with host phenotype.Results: Eight of the 11 histologic scoring parameters showed useful degrees of variation. The overall concordance across all parameters was 96% weighted agreement, kappa 0.70, and Gwet\u27s AC 0.93. Zambian and Pakistani tissues shared some histologic features with GSE, but most features were distinct, particularly abundance of intraepithelial lymphocytes in the Pakistani cohort, and marked villous destruction and loss of secretory cell lineages in the Zambian cohort.Conclusions: We propose the first EED histology index for interpreting duodenal biopsies. This index should be useful in future clinical and translational studies of this widespread, poorly understood, and highly consequential disorder, which might be caused by multiple contributing processes, in different regions of the world

Machine learning model demonstrates stunting at birth and systemic inflammatory biomarkers as predictors of subsequent infant growth - A four-year prospective study

Background: Stunting affects up to one-third of the children in low-to-middle income countries (LMICs) and has been correlated with decline in cognitive capacity and vaccine immunogenicity. Early identification of infants at risk is critical for early intervention and prevention of morbidity. The aim of this study was to investigate patterns of growth in infants up through 48 months of age to assess whether the growth of infants with stunting eventually improved as well as the potential predictors of growth.Methods: Height-for-age z-scores (HAZ) of children from Matiari (rural site, Pakistan) at birth, 18 months, and 48 months were obtained. Results of serum-based biomarkers collected at 6 and 9 months were recorded. A descriptive analysis of the population was followed by assessment of growth predictors via traditional machine learning random forest models.Results: Of the 107 children who were followed up till 48 months of age, 51% were stunted (HAZ \u3c - 2) at birth which increased to 54% by 48 months of age. Stunting status for the majority of children at 48 months was found to be the same as at 18 months. Most children with large gains started off stunted or severely stunted, while all of those with notably large losses were not stunted at birth. Random forest models identified HAZ at birth as the most important feature in predicting HAZ at 18 months. Of the biomarkers, AGP (Alpha- 1-acid Glycoprotein), CRP (C-Reactive Protein), and IL1 (interleukin-1) were identified as strong subsequent growth predictors across both the classification and regressor models.Conclusion: We demonstrated that children most children with stunting at birth remained stunted at 48 months of age. Value was added for predicting growth outcomes with the use of traditional machine learning random forest models. HAZ at birth was found to be a strong predictor of subsequent growth in infants up through 48 months of age. Biomarkers of systemic inflammation, AGP, CRP, IL1, were also strong predictors of growth outcomes. These findings provide support for continued focus on interventions prenatally, at birth, and early infancy in children at risk for stunting who live in resource-constrained regions of the world

Promising biomarkers of environmental enteric dysfunction: a prospective cohort study in Pakistani children.

Environmental Enteric Dysfunction (EED), a syndrome characterized by chronic gut inflammation, contributes towards stunting and poor response to enteric vaccines in children in developing countries. In this study, we evaluated major putative biomarkers of EED using growth faltering as its clinical proxy. Newborns (n = 380) were enrolled and followed till 18 months with monthly anthropometry. Biomarkersassociated with gut and systemic inflammation were assessed at 6 and 9 months. Linear mixed effects model was used to determine the associations of these biomarkers with growth faltering between birth and 18 months. Fecal myeloperoxidase (neutrophil activation marker) at 6 months [β = -0.207, p = 0.005], and serum GLP 2 (enterocyte proliferation marker) at 6 and 9 months [6M: β = -0.271, p = 0.035; 9M: β = -0.267, p = 0.045] were associated with decreasing LAZ score. Ferritin at 6 and 9 months was associated with decreasing LAZ score [6M: β = -0.882, p \u3c 0.0001; 9M: β = -0.714, p \u3c 0.0001] and so was CRP [β = -0.451, p = 0.039] and AGP [β = -0.443, p = 0.012] at 9 months. Both gut specific and systemic biomarkers correlated negatively with IGF-1, but only weakly correlated, if at all with each other. We therefore conclude that EED may be contributing directly towards growth faltering, and this pathway is not entirely through the pathway of systemic inflammation

Study of environmental enteropathy and malnutrition (SEEM) in Pakistan: protocols for biopsy based biomarker discovery and validation

Background: Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children \u3c 5 years are attributable to under-nutrition, making the study of EE an area of critical priority. Methods: Community based intervention study, divided into two sub-studies, 1) Longitudinal analyses and 2) Biopsy studies for identification of EE features via omics analyses. Birth cohorts in Matiari, Pakistan established: moderately or severely malnourished (weight for height Z score (WHZ) \u3c − 2) children, and well-nourished (WHZ \u3e 0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal analyses). Participants will receive appropriate educational and nutritional interventions; non-responders will undergo further evaluation to determine eligibility for further workup, including upper gastrointestinal endoscopy. Histopathological changes in duodenal biopsies will be compared with duodenal biopsies obtained from USA controls who have celiac disease, Crohn’s disease, or who were found to have normal histopathology. RNA-Seq will be employed to characterize mucosal gene expression across groups. Duodenal biopsies, luminal aspirates from the duodenum, and fecal samples will be analyzed to define microbial community composition (omic analyses). The relationship between histopathology, mucosal gene expression, and community configuration will be assessed using a variety of bioinformatic tools to gain better understanding of disease pathogenesis and to identify mechanism-based biomarkers. Ethical review committees at all collaborating institutions have approved this study. All results will be made available to the scientific community. Discussion: Operational and ethical constraints for safely obtaining intestinal biopsies from children in resource-poor settings have led to a paucity of human tissue-based investigations to understand and reverse EE in vulnerable populations. Furthermore, EE biomarkers have rarely been correlated with gold standard histopathological confirmation. The Study of Environmental Enteropathy and Malnutrition (SEEM) is designed to better understand the pathophysiology, predictors, biomarkers, and potential management strategies of EE to inform strategies to eradicate this debilitating pathology and accelerate progress towards the 2030 Sustainable Development Goals. Trial registration: Retrospectively registered; clinicaltrials.gov ID NCT03588013

Bile acid profiling reveals distinct signatures in undernourished children with environmental enteric dysfunction

Background: Intestinal inflammation and malabsorption in environmental enteric dysfunction (EED) are associated with early childhood growth faltering in impoverished settings worldwide.Objectives: The goal of this study was to identify candidate biomarkers associated with inflammation, EED histology, and as predictors of later growth outcomes by focusing on the liver-gut axis by investigating the bile acid metabolome.Methods: Undernourished rural Pakistani infants (n = 365) with weight-for-height Z score (WHZ) \u3c -2 were followed up to the age of 24 mo and monitored for growth, infections, and EED. Well-nourished local children (n = 51) were controls, based on consistent WHZ \u3e 0 and height-for-age Z score (HAZ) \u3e -1 on 2 consecutive visits at 3 and 6 mo. Serum bile acid (sBA) profiles were measured by tandem MS at the ages of 3-6 and 9 mo and before nutritional intervention. Biopsies and duodenal aspirates were obtained following upper gastrointestinal endoscopy from a subset of children (n = 63) that responded poorly to nutritional intervention. BA composition in paired plasma and duodenal aspirates was compared based on the severity of EED histopathological scores and correlated to clinical and growth outcomes.Results: Remarkably, \u3e70% of undernourished Pakistani infants displayed elevated sBA concentrations consistent with subclinical cholestasis. Serum glycocholic acid (GCA) correlated with linear growth faltering (HAZ, r = -0.252 and -0.295 at the age of 3-6 and 9 mo, respectively, P Conclusions: Dysregulated bile acid metabolism is associated with growth faltering and EED severity in undernourished children. Restoration of intestinal BA homeostasis may offer a novel therapeutic target for undernutrition in children with EED. This trial was registered at clinicaltrials.gov as NCT03588013