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Background/Objectives: Sickle cell disease (SCD) impacts about 100,000 people in the US. SCD increases the risk of cholelithiasis and microvascular ischemia, which could increase the risk of acute pancreatitis (AP). Abdominal pain is a common presenting symptom of AP and sickle cell vaso-occlusive crisis. The purpose of our systematic review is to estimate the prevalence and determine the severity of AP in individuals with SCD compared to the general population. Methods: Multiple electronic databases were searched. We included studies that included children and adults (population) and addressed the association of SCD (exposure) with AP (outcome) compared to the same population without SCD (control). Two authors screened titles and abstracts independently, and data were abstracted in duplication from included studies. We registered this protocol in PROSPERO-CRD42023422397. Results: Out of 296 studies screened from multiple electronic databases, we identified 33 studies. These studies included 17 case reports, one case series, and 15 retrospective cohort studies, and 18 studies included children. Eight of the AP case reports were in patients with HbSS genotype, two with sickle beta thalassemia, and one with HbSoArab, and in six case reports, a genotype was not specified. Complications were reported in 11 cases—respiratory complication (in at least four cases), splenic complications (three cases), pancreatic pseudocyst (two cases) and death from AP (one case). Of the four AP cases in the case series, three had HbSS genotype, and two cases had complications and severe pancreatitis. AP prevalence in SCD was estimated to be 2% and 7% in two retrospective studies, but they lacked a comparison group. In retrospective studies that evaluated the etiology of AP in children, biliary disease caused mostly by SCD was present in approximately 12% and 34%, respectively. Conclusions: Data on the prevalence of AP in individuals with SCD are limited. Prospectively designed studies aiming to proactively evaluate AP in individuals with SCD who present with abdominal pain are needed to improve timely diagnosis of AP in SCD and outcomes. [ABSTRACT FROM AUTHOR]

In pregnancies complicated by sickle cell disease (SCD), the maternal-fetal dyad is at high risk for mortality and morbidity. In healthy pregnancies, maternal nutritional status is a critical factor for the healthy growth and development of the fetus. However, there are no reviews of the current research on the nutritional status of pregnant women with SCD and pregnancy outcomes. First, we aim to assess the burden of malnutrition in pregnant women with SCD. Next, we aim to systematically evaluate if pregnant women with SCD who have poor nutritional status are at increased risk for adverse birth outcomes compared to pregnant women with sickle cell disease and normal nutritional status. We will systematically search multiple electronic databases. Our exposure is pregnant women with SCD and poor nutritional status. The primary outcomes of interest include low birth weight (categorical) and birth weight z-scores (continuous). We will also evaluate maternal and perinatal outcomes as secondary outcomes. We will evaluate the risk of bias and overall certainty of evidence with Risk of Bias in Non-randomized Studies—of Interventions (ROBINS-I), and the overall evidence will be assessed using Grading of Recommendation Assessment, Development, and Evaluation (GRADE) criteria. We will pool findings with a meta-analysis if sufficient homogeneity exists among studies. Findings will be published in a peer-reviewed journal and disseminated to SCD advocacy groups. PROSPERO registration number: CRD42023429412. [ABSTRACT FROM AUTHOR]

Suboptimal complementary feeding practices remain highly prevent. This review aims to comprehensively synthesize new emerging evidence on a set of topics related to the selection and consumption of complementary foods. We synthesized evidence related to five key topics focused on nutritional interventions that target the complementary feeding period, based on four systematic reviews that include updated evidence to February 2022. While there have been many studies examining interventions during the complementary feeding period, there is an overall lack of relevant information through which to draw conclusions on the ideal feeding schedule by food type. Similarly, few studies have examined the effects of animal milk versus infant formula for non-breastfed infants (6–11 months), though those that did found a greater risk of anemia among infants who were provided cow's milk. This review highlights a number of interventions that are successful at improving micronutrient status and anthropometry during the complementary feeding period, including fortified blended foods, locally and commercially produced supplementary foods, and small-quantity lipid-based nutrient supplements. Complementary feeding education for caregivers can also be used to improve nutrition outcomes among infants in both food secure and insecure populations. [ABSTRACT FROM AUTHOR]

This study was a systematic review and meta-analysis that assessed the risk of aspiration pneumonia in children with laryngeal penetration or tracheal aspiration via a video-fluoroscopic study (VFSS) and compared the results to those for children with neither condition. Systematic searches were conducted using databases, including PubMed, Cochrane Library, and Web of Science. Meta-analysis was used to obtain summary odds ratios (OR) and 95% confidence intervals (CI). The overall quality of evidence was assessed using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. In total, 13 studies were conducted with 3159 participants. Combined results from six studies showed that laryngeal penetration on VFSS may be associated with aspiration pneumonia compared to no laryngeal penetration; however, the summary estimate was imprecise and included the possibility of no association (OR 1.44, 95% CI 0.94, 2.19, evidence certainty: low). Data from seven studies showed that tracheal aspiration might be associated with aspiration pneumonia compared to no tracheal aspiration (OR 2.72, 95% CI 1.86, 3.98, evidence certainty: moderate). The association between aspiration pneumonia and laryngeal penetration through VFSS seems to be weaker than that for tracheal aspiration. Prospective cohort studies with clear definitions of laryngeal penetration and that measure clinical and patient reported outcomes are needed to further define the association between laryngeal penetration and aspiration pneumonia. [ABSTRACT FROM AUTHOR]

The article describes the case of a 3-week-old Amish female infant who presented to the hospital with tachypnea and worsening abdominal distention for 2 days. Topics covered include the medical history of the patient, the findings of the physical and laboratory examinations which led to the diagnosis of portal vein thrombosis (PVT) in the setting of neonatal sepsis due to group A streptococcal sepsis, and patient outcome following vitamin K and intravenous ampicillin treatments.

The optimal dose of iron in ready-to-use therapeutic foods (RUTF) used to treat uncomplicated severe acute malnutrition (SAM) in community settings is not well established. The objective of this systematic review was to assess if an increased iron dose in RUTF, compared with the standard iron dose in the World Health Organization (WHO)-recommended peanut-based RUTF, improved outcomes in children aged six months or older. We searched multiple electronic databases and only included randomized controlled trials. We pooled the data in a meta-analysis to obtain relative risk (RR) and reported it with a 95% confidence interval (CI). Three studies, one each from Zambia, the Democratic Republic of Congo, and Malawi, were included. In all studies, the RUTF used in the intervention group was milk-free soya–maize–sorghum-based RUTF. The pooled results showed that, compared to the control group, a high iron content in RUTF may lead to increase in hemoglobin concentration (mean difference 0.33 g/dL, 95% CI: 0.02, 0.64, two studies, certainty of evidence: low) and a decrease in any anemia (RR 0.66, 95% CI: 0.48, 0.91, two studies, certainty of evidence: low), but also decrease recovery rates (RR 0.91, 95% CI: 0.84, 0.99, three studies, certainty of evidence: low) and increase mortality (RR 1.30, 95% CI: 0.87, 1.95, three studies, certainty of evidence: moderate). However, the CIs were imprecise for the latter outcome. Future studies with large sample sizes are needed to confirm the beneficial versus harmful effects of high iron content in RUTF in treating uncomplicated SAM in children aged 6-59 months in community settings. [ABSTRACT FROM AUTHOR]

Abstract Background An important determinant of pregnancy outcome is the timely onset of labor and birth. Prolonged gestation complicates 5% to 10% of all pregnancies and confers increased risk to both the fetus and mother. The purpose of this review was to study the possible impact of induction of labour (IOL) for post-term pregnancies compared to expectant management on stillbirths. Methods A systematic review of the published studies including randomized controlled trials, quasi- randomized trials and observational studies was conducted. Search engines used were PubMed, the Cochrane Library, the WHO regional databases and hand search of bibliographies. A standardized data abstraction sheet was used. Recommendations have been made for input to the Lives Saved Tool (LiST) model by following standardized guidelines developed by the Child Health Epidemiology Reference Group (CHERG). Results A total of 25 studies were included in this review. Meta-analysis of 14 randomized controlled trials (RCTs) suggests that a policy of elective IOL for pregnancies at or beyond 41 weeks is associated with significantly fewer perinatal deaths (RR=0.31; 95% CI: 0.11-0.88) compared to expectant management, but no significant difference in the incidence of stillbirth (RR= 0.29; 95% CI: 0.06-1.38) was noted. The included trials evaluating this intervention were small, with few events in the intervention and control group. There was significant decrease in incidence of neonatal morbidity from meconium aspiration (RR = 0.43, 95% CI 0.23-0.79) and macrosomia (RR = 0.72; 95% CI: 0.54 – 0.98). Using CHERG rules, we recommended 69% reduction as a point estimate for the risk of stillbirth with IOL for prolonged gestation (> 41 weeks). Conclusions Induction of labour appears to be an effective way of reducing perinatal morbidity and mortality associated with post-term pregnancies. It should be offered to women with post-term pregnancies after discussing the benefits and risks of induction of labor.

Abstract Background The nutritional status of the mother prior to and during pregnancy plays a vital role in fetal growth and development, and maternal undernourishment may lead to adverse perinatal outcomes including intrauterine growth restriction (IUGR). Several macronutrient interventions had been proposed for adequate protein and energy supplementation during pregnancy. The objective of this paper was to review the effect of balanced protein energy supplementation during pregnancy on birth outcomes. This paper is a part of a series of reviews undertaken for getting estimates of effectiveness of an intervention for input to Lives Saved Tool (LiST) model. Methods A literature search was conducted on PubMed, Cochrane Library and WHO regional data bases to identify randomized trials (RCTs) and quasi RCTs that evaluated the impact of balanced protein energy supplementation in pregnancy. Balanced protein energy supplementation was defined as nutritional supplementation during pregnancy in which proteins provided less than 25% of the total energy content. Those studies were excluded in which the main intervention was dietary advice to pregnant women for increase in protein energy intake, high protein supplementation (i.e. supplementation in which protein provides at least 25% of total energy content), isocaloric protein supplementation (where protein replaces an equal quantity of non-protein energy content), or low energy diet to pregnant women who are either overweight or who exhibit high weight gain earlier in gestation. The primary outcomes were incidence of small for gestational age (SGA) birth, mean birth weight and neonatal mortality. Quality of evidence was evaluated according to the Child Health Epidemiology Reference group (CHERG) adaptation of Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Results The final number of studies included in our review was eleven comprising of both RCTs and quasi-RCTs. Our meta-analysis indicates that providing pregnant females with balanced protein energy supplementation resulted in a significant reduction of 31 % in the risk of giving birth to small for gestational age infants (Relative risk (RR) =0.69, 95% Confidence interval (CI) 0.56 to 0.85). This estimate had been recommended for LiST as a proxy for reduction in IUGR. Pooled results for mean birth weight showed that balanced protein supplemented group gained more weight compared to control [Mean difference 59.89 g, 95 % CI 33.09-86.68]. This effect was more pronounced in malnourished women compared to adequately nourished women. There was no statistically significant effect of balanced protein energy supplementation on neonatal mortality (RR= 0.63, 95% CI 0.37 to 1.06). Conclusion Providing pregnant females with balanced protein energy supplementation leads to reduction in risk of small for gestational age infants, especially among undernourished pregnant women. Given these findings, we can recommend balanced protein energy supplementation as an intervention among undernourished women for inclusion in the LiST model with a point estimate of 31% [95% CI 15% to 44%] reduction in IUGR.

Abstract Background Pre-eclampsia and Eclampsia are relatively common complications of pregnancy, leading to considerable maternal and fetal mortality and morbidity. We sought to review the effect of aspirin, calcium supplementation, antihypertensive agents and magnesium sulphate on risk stillbirths. Methods A systematic literature search was conducted to identify studies evaluating the above interventions. We used a standardized abstraction and grading format and performed meta-analyses where data were available from more than one studies. The estimated effect on stillbirths was determined by applying the standard Child Health Epidemiology Reference Group (CHERG) rules for multiple outcomes. For interventions with insufficient evidence for overall effect, a Delphi process was undertaken to estimate effectiveness. Results We identified 82 relevant studies. For aspirin, maganesium sulphate and use of antihypertensive we found an insignificant decrease in stillbirth and perinatal mortality. For calcium supplementation, there was a borderline significant reduction in stillbirths (RR 0.81, 95 % CI 0.63-1.03). We undertook a Delphi consultation among experts to assess the potential impact of a package of interventions for the management of pre-eclampsia and eclampsia (antihypertensive, magnesium sulphate and C-section if needed). The Delphi process suggested 20% reduction each in both antepartum and intrapartum stillbirths with the use of this package. Conclusions Despite promising benefits of calcium supplementation and aspirin use cases on maternal morbidity and eclampsia in high risk cases, further work is needed to ascertain their benefits in relation to stillbirths. The Delphi process undertaken for assessing potential impact of a package of interventions indicated that this could be associated with 20% reduction in stillbirths, for input into LiST.

Abstract Introduction Vitamin A is important for the integrity and regeneration of respiratory and gastrointestinal epithelia and is involved in regulating human immune function. It has been shown previously that vitamin A has a preventive effect on all-cause and disease specific mortality in children under five. The purpose of this paper was to get a point estimate of efficacy of vitamin A supplementation in reducing cause specific mortality by using Child Health Epidemiology Reference Group (CHERG) guidelines. Methods A literature search was done on PubMed, Cochrane Library and WHO regional data bases using various free and Mesh terms for vitamin A and mortality. Data were abstracted into standardized forms and quality of studies was assessed according to standardized guidelines. Pooled estimates were generated for preventive effect of vitamin A supplementation on all-cause and disease specific mortality of diarrhea, measles, pneumonia, meningitis and sepsis. We did a subgroup analysis for vitamin A supplementation in neonates, infants 1-6 months and children aged 6-59 months. In this paper we have focused on estimation of efficacy of vitamin A supplementation in children 6-59 months of age. Results for neonatal vitamin A supplementation have been presented, however no recommendations are made as more evidence on it would be available soon. Results There were 21 studies evaluating preventive effect of vitamin A supplementation in community settings which reported all-cause mortality. Twelve of these also reported cause specific mortality for diarrhea and pneumonia and six reported measles specific mortality. Combined results from six studies showed that neonatal vitamin A supplementation reduced all-cause mortality by 12 % [Relative risk (RR) 0.88; 95 % confidence interval (CI) 0.79-0.98]. There was no effect of vitamin A supplementation in reducing all-cause mortality in infants 1-6 months of age [RR 1.05; 95 % CI 0.88-1.26]. Pooled results for preventive vitamin A supplementation showed that it reduced all-cause mortality by 25% [RR 0.75; 95 % CI 0.64-0.88] in children 6-59 months of age. Vitamin A supplementation also reduced diarrhea specific mortality by 30% [RR 0.70; 95 % CI 0.58-0.86] in children 6-59 months. This effect has been recommended for inclusion in the Lives Saved Tool. Vitamin A supplementation had no effect on measles [RR 0.71, 95% CI: 0.43-1.16], meningitis [RR 0.73, 95% CI: 0.22-2.48] and pneumonia [RR 0.94, 95% CI: 0.67-1.30] specific mortality. Conclusion Preventive vitamin A supplementation reduces all-cause and diarrhea specific mortality in children 6-59 months of age in community settings in developing countries.

Abstract Background Given the recognized benefits of breastfeeding for the health of the mother and infants, the World Health Organization (WHO) recommends exclusive breastfeeding (EBF) for the first six months of life. However, the prevalence of EBF is low globally in many of the developing and developed countries around the world. There is much interest in the effectiveness of breastfeeding promotion interventions on breastfeeding rates in early infancy. Methods A systematic literature was conducted to identify all studies that evaluated the impact of breastfeeding promotional strategies on any breastfeeding and EBF rates at 4-6 weeks and at 6 months. Data were abstracted into a standard excel sheet by two authors. Meta-analyses were performed with different sub-group analyses. The overall evidence were graded according to the Child Health Epidemiology Reference Group (CHERG) rules using the adapted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria and recommendations made from developing country studies for inclusion into the Live Saved Tool (LiST) model. Results After reviewing 968 abstracts, 268 studies were selected for potential inclusion, of which 53 randomized and quasi-randomized controlled trials were selected for full abstraction. Thirty two studies gave the outcome of EBF at 4-6 weeks postpartum. There was a statistically significant 43% increase in this outcome, with 89% and 20% significant increases in developing and developed countries respectively. Fifteen studies reported EBF outcomes at 6 months. There was an overall 137% increase, with a significant 6 times increase in EBF in developing countries, compared to 1.3 folds increase in developed country studies. Further sub-group analyses proved that prenatal counseling had a significant impact on breastfeeding outcomes at 4-6 weeks, while both prenatal and postnatal counseling were important for EBF at 6 months. Conclusion Breastfeeding promotion interventions increased exclusive and any breastfeeding rates at 4-6 weeks and at 6 months. A relatively greater impact of these interventions was seen in developing countries with 1.89 and 6 folds increase in EBF rates at 4-6 weeks and at 6 months respectively.

Abstract Background Childhood undernutrition is prevalent in low and middle income countries. It is an important indirect cause of child mortality in these countries. According to an estimate, stunting (height for age Z score < -2) and wasting (weight for height Z score < -2) along with intrauterine growth restriction are responsible for about 2.1 million deaths worldwide in children < 5 years of age. This comprises 21 % of all deaths in this age group worldwide. The incidence of stunting is the highest in the first two years of life especially after six months of life when exclusive breastfeeding alone cannot fulfill the energy needs of a rapidly growing child. Complementary feeding for an infant refers to timely introduction of safe and nutritional foods in addition to breast-feeding (BF) i.e. clean and nutritionally rich additional foods introduced at about six months of infant age. Complementary feeding strategies encompass a wide variety of interventions designed to improve not only the quality and quantity of these foods but also improve the feeding behaviors. In this review, we evaluated the effectiveness of two most commonly applied strategies of complementary feeding i.e. timely provision of appropriate complementary foods (± nutritional counseling) and education to mothers about practices of complementary feeding on growth. Recommendations have been made for input to the Lives Saved Tool (LiST) model by following standardized guidelines developed by Child Health Epidemiology Reference Group (CHERG). Methods We conducted a systematic review of published randomized and quasi-randomized trials on PubMed, Cochrane Library and WHO regional databases. The included studies were abstracted and graded according to study design, limitations, intervention details and outcome effects. The primary outcomes were change in weight and height during the study period among children 6-24 months of age. We hypothesized that provision of complementary food and education of mother about complementary food would significantly improve the nutritional status of the children in the intervention group compared to control. Meta-analyses were generated for change in weight and height by two methods. In the first instance, we pooled the results to get weighted mean difference (WMD) which helps to pool studies with different units of measurement and that of different duration. A second meta-analysis was conducted to get a pooled estimate in terms of actual increase in weight (kg) and length (cm) in relation to the intervention, for input into the LiST model. Results After screening 3795 titles, we selected 17 studies for inclusion in the review. The included studies evaluated the impact of provision of complementary foods (±nutritional counseling) and of nutritional counseling alone. Both these interventions were found to result in a significant increase in weight [WMD 0.34 SD, 95% CI 0.11 – 0.56 and 0.30 SD, 95 % CI 0.05-0.54 respectively) and linear growth [WMD 0.26 SD, 95 % CI 0.08-0.43 and 0.21 SD, 95 % CI 0.01-0.41 respectively]. Pooled results for actual increase in weight in kilograms and length in centimeters showed that provision of appropriate complementary foods (±nutritional counseling) resulted in an extra gain of 0.25kg (±0.18) in weight and 0.54 cm (±0.38) in height in children aged 6-24 months. The overall quality grades for these estimates were that of ‘moderate’ level. These estimates have been recommended for inclusion in the Lives Saved Tool (LiST) model. Education of mother about complementary feeding led to an extra weight gain of 0.30 kg (±0.26) and a gain of 0.49 cm (±0.50) in height in the intervention group compared to control. These estimates had been recommended for inclusion in the LiST model with an overall quality grade assessment of ‘moderate’ level. Conclusion Provision of appropriate complementary food, with or without nutritional education, and maternal nutritional counseling alone lead to significant increase in weight and height in children 6-24 months of age. These interventions can significantly reduce the risk of stunting in developing countries and are recommended for inclusion in the LiST tool.

Abstract Background Hypertension in pregnancy stand alone or with proteinuria is one of the leading causes of maternal mortality and morbidity in the world. Epidemiological and clinical studies have shown that an inverse relationship exists between calcium intake and development of hypertension in pregnancy though the effect varies based on baseline calcium intake and pre-existing risk factors. The purpose of this review was to evaluate preventive effect of calcium supplementation during pregnancy on gestational hypertensive disorders and related maternal and neonatal mortality in developing countries. Methods A literature search was carried out on PubMed, Cochrane Library and WHO regional databases. Data were extracted into a standardized excel sheet. Identified studies were graded based on strengths and limitations of studies. All the included studies were from developing countries. Meta-analyses were generated where data were available from more than one study for an outcome. Primary outcomes were maternal mortality, eclampsia, pre-eclampsia, and severe preeclampsia. Neonatal outcomes like neonatal mortality, preterm birth, small for gestational age and low birth weight were also evaluated. We followed standardized guidelines of Child Health Epidemiology Reference Group (CHERG) to generate estimates of effectiveness of calcium supplementation during pregnancy in reducing maternal and neonatal mortality in developing countries, for inclusion in the Lives Saved Tool (LiST). Results Data from 10 randomized controlled trials were included in this review. Pooled analysis showed that calcium supplementation during pregnancy was associated with a significant reduction of 45% in risk of gestational hypertension [Relative risk (RR) 0.55; 95 % confidence interval (CI) 0.36-0.85] and 59% in the risk of pre-eclampsia [RR 0.41; 95 % CI 0.24-0.69] in developing countries. Calcium supplementation during pregnancy was also associated with a significant reduction in neonatal mortality [RR 0.70; 95 % CI 0.56-0.88] and risk of pre-term birth [RR 0.88, 95 % CI 0.78-0.99]. Recommendations for LiST for reduction in maternal mortality were based on risk reduction in gestational hypertensive related severe morbidity/mortality [RR 0.80; 95% CI 0.70-0.91] and that for neonatal mortality were based on risk reduction in all-cause neonatal mortality [RR 0.70; 95% CI 0.56-0.88]. Conclusion Calcium supplementation during pregnancy is associated with a reduction in risk of gestational hypertension, pre-eclampsia neonatal mortality and pre-term birth in developing countries.

Abstract Background Pregnancy is a state of increased requirement of macro- and micronutrients, and malnourishment or inadequate dietary intake before and during pregnancy, can lead to adverse perinatal outcomes including stillbirths. Many nutritional interventions have been proposed during pregnancy according to the nutritional status of the mother and baseline risk factors for different gestational disorders. In this paper, we have reviewed three nutritional interventions including peri-conceptional folic acid supplementation, balanced protein energy supplementation and multiple micronutrients supplementation during pregnancy. This paper is a part of a series to estimate the effect of interventions on stillbirths for input to Live Saved Tool (LiST) model. Methods We systematically reviewed all published literature to identify studies evaluating effectiveness of peri-conceptional folic acid supplementation in reducing neural tube defects (NTD), related stillbirths and balanced protein energy and multiple micronutrients supplementation during pregnancy in reducing all-cause stillbirths. The primary outcome was stillbirths. Meta-analyses were generated where data were available from more than one study. Recommendations were made for the Lives Saved Tool (LiST) model based on rules developed by the Child Health Epidemiology Reference Group (CHERG). Results There were 18 studies that addressed peri-conceptional folic acid supplementation for prevention of neural tube defects (NTDs). Out of these, 7 studies addressed folic acid supplementation while 11 studies evaluated effect of folic acid fortification. Pooled results from 11 fortification studies showed that it reduces primary incidence of NTDs by 41 % [Relative risk (RR) 0.59; 95 % confidence interval (CI) 0.52-0.68]. This estimate has been recommended for inclusion in the LiST as proxy for reduction in stillbirths. Pooled results from three studies considered to be of low quality and suggest that balanced protein energy supplementation during pregnancy could lead to a reduction of 45% in stillbirths [RR 0.55, 95 % CI 0.31-0.97]. While promising, the intervention needs more effectiveness studies before inclusion in any programs. Pooled results from 13 studies evaluating role of multiple micronutrients supplementation during pregnancy showed no significant effect in reducing stillbirths [RR = 0.98; 95% CI: 0.88 – 1.10] or perinatal mortality [RR = 1.07; 95% CI: 0.92 – 1.25; random model]. No recommendations have been made for this intervention for inclusion in the LiST model. Conclusions Peri-conceptional folic acid supplementation reduces stillbirths due to NTDs by approximately 41%, a point estimate recommended for inclusion in LiST.

Abstract Introduction Zinc plays an important role in cellular growth, cellular differentiation and metabolism. The results of previous meta-analyses evaluating effect of zinc supplementation on linear growth are inconsistent. We have updated and evaluated the available evidence according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria and tried to explain the difference in results of the previous reviews. Methods A literature search was done on PubMed, Cochrane Library, IZiNCG database and WHO regional data bases using different terms for zinc and linear growth (height). Data were abstracted in a standardized form. Data were analyzed in two ways i.e. weighted mean difference (effect size) and pooled mean difference for absolute increment in length in centimeters. Random effect models were used for these pooled estimates. We have given our recommendations for effectiveness of zinc supplementation in the form of absolute increment in length (cm) in zinc supplemented group compared to control for input to Live Saves Tool (LiST). Results There were thirty six studies assessing the effect of zinc supplementation on linear growth in children < 5 years from developing countries. In eleven of these studies, zinc was given in combination with other micronutrients (iron, vitamin A, etc). The final effect size after pooling all the data sets (zinc ± iron etc) showed a significant positive effect of zinc supplementation on linear growth [Effect size: 0.13 (95% CI 0.04, 0.21), random model] in the developing countries. A subgroup analysis by excluding those data sets where zinc was supplemented in combination with iron showed a more pronounced effect of zinc supplementation on linear growth [Weighed mean difference 0.19 (95 % CI 0.08, 0.30), random model]. A subgroup analysis from studies that reported actual increase in length (cm) showed that a dose of 10 mg zinc/day for duration of 24 weeks led to a net a gain of 0.37 (±0.25) cm in zinc supplemented group compared to placebo. This estimate is recommended for inclusion in Lives Saved Tool (LiST) model. Conclusions Zinc supplementation has a significant positive effect on linear growth, especially when administered alone, and should be included in national strategies to reduce stunting in children < 5 years of age in developing countries.

Abstract Background There is a strong association between stillbirth and fetal growth restriction. Early detection and management of IUGR can lead to reduce related morbidity and mortality. In this paper we have reviewed effectiveness of fetal movement monitoring and Doppler velocimetry for the detection and surveillance of high risk pregnancies and the effect of this on prevention of stillbirths. We have also reviewed effect of maternal body mass index (BMI) screening, symphysial-fundal height measurement and targeted ultrasound in detection and triage of IUGR in the community. Methods We systematically reviewed all published literature to identify studies related to our interventions. We searched PubMed, Cochrane Library, and all World Health Organization Regional Databases and included publications in any language. Quality of available evidence was assessed using GRADE criteria. Recommendations were made for the Lives Saved Tool (LiST) based on rules developed by the Child Health Epidemiology Group. Given the paucity of evidence related to the effect of detection and management of IUGR on stillbirths, we undertook Delphi based evaluation from experts in the field. Results There was insufficient evidence to recommend against or in favor of routine use of fetal movement monitoring for fetal well being. (1) Detection and triage of IUGR with the help of (1a) maternal BMI screening, (1b) symphysial-fundal height measurement and (1c) targeted ultrasound can be an effective method of reducing IUGR related perinatal morbidity and mortality. Pooled results from sixteen studies shows that Doppler velocimetry of umbilical and fetal arteries in ‘high risk’ pregnancies, coupled with the appropriate intervention, can reduce perinatal mortality by 29 % [RR 0.71, 95 % CI 0.52-0.98]. Pooled results for impact on stillbirth showed a reduction of 35 % [RR 0.65, 95 % CI 0.41-1.04]; however, the results did not reach the conventional limits of statistical significance. This intervention could be potentially recommended for high income settings or middle income countries with improving rates and standards of facility based care. Based on the Delphi, a combination of screening with maternal BMI, Symphysis fundal height and targeted ultrasound followed by the appropriate management could potentially reduce antepartum and intrapartum stillbirth by 20% respectively. This estimate is presently being recommended for inclusion in the LiST. Conclusion There is insufficient evidence to recommend in favor or against fetal movement counting for routine use for testing fetal well being. Doppler velocimetry of umbilical and fetal arteries and appropriate intervention is associated with 29 % (95 % CI 2% to 48 %) reduction in perinatal mortality. Expert opinion suggests that detection and management of IUGR with the help of maternal BMI, symphysial-fundal height measurement and targeted ultrasound could be effective in reducing IUGR related stillbirths by 20%.

Abstract Background Infection is a well acknowledged cause of stillbirths and may account for about half of all perinatal deaths today, especially in developing countries. This review presents the impact of interventions targeting various important infections during pregnancy on stillbirth or perinatal mortality. Methods We undertook a systematic review including all relevant literature on interventions dealing with infections during pregnancy for assessment of effects on stillbirths or perinatal mortality. The quality of the evidence was assessed using the adapted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach by Child Health Epidemiology Reference Group (CHERG). For the outcome of interest, namely stillbirth, we applied the rules developed by CHERG to recommend a final estimate for reduction in stillbirth for input to the Lives Saved Tool (LiST) model. Results A total of 25 studies were included in the review. A random-effects meta-analysis of observational studies of detection and treatment of syphilis during pregnancy showed a significant 80% reduction in stillbirths [Relative risk (RR) = 0.20; 95% confidence interval (CI): 0.12 - 0.34) that is recommended for inclusion in the LiST model. Our meta-analysis showed the malaria prevention interventions i.e. intermittent preventive treatment (IPTp) and insecticide-treated mosquito nets (ITNs) can reduce stillbirths by 22%, however results were not statistically significant (RR = 0.78; 95% CI: 0.59 – 1.03). For human immunodeficiency virus infection, a pooled analysis of 6 radomized controlled trials (RCTs) failed to show a statistically significant reduction in stillbirth with the use of antiretroviral in pregnancy compared to placebo (RR = 0.93; 95% CI: 0.45 – 1.92). Similarly, pooled analysis combining four studies for the treatment of bacterial vaginosis (3 for oral and 1 for vaginal antibiotic) failed to yield a significant impact on perinatal mortality (OR = 0.88; 95% CI: 0.50 – 1.55). Conclusions The clearest evidence of impact in stillbirth reduction was found for adequate prevention and treatment of syphilis infection and possibly malaria. At present, large gaps exist in the growing list of stillbirth risk factors, especially those that are infection related. Potential causes of stillbirths including HIV and TORCH infections need to be investigated further to help establish the role of prevention/treatment and its subsequent impact on stillbirth reduction.

Abstract Background Of the global burden of 2.6 million stillbirths, around 1.2 million occur during labour i.e. are intrapartum deaths. In low-/middle-income countries, a significant proportion of women give birth at home, usually in the absence of a skilled birth attendant. This review discusses the impact of skilled birth attendance (SBA) and the provision of Emergency Obstetric Care (EOC) on stillbirths and perinatal mortality. Methods A systematic literature search was performed on PubMed/MEDLINE, Cochrane Database and the WHO regional libraries. Data of all eligible studies were extracted into a standardized Excel sheet containing variables such as participants’ characteristics, sample size, location, setting, blinding, allocation concealment, intervention and control details and limitations. We undertook a meta-analysis of the impact of SBA on stillbirths. Given the paucity of data from randomized trials or robust quasi-experimental designs, we undertook an expert Delphi consultation to determine impact estimates of provision of Basic and Comprehensive EOC on reducing stillbirths if there would be universal coverage (99%). Results The literature search yielded 871 hits. A total of 21 studies were selected for data abstraction. Our meta-analysis on community-based skilled birth attendance based on two before-after studies showed a 23% significant reduction in stillbirths (RR = 0.77; 95% CI: 0.69 – 0.85). The overall quality grade of available evidence for this intervention on stillbirths was ‘moderate’. The Delphi process supported the estimated reduction in stillbirths by skilled attendance and experts further suggested that the provision of Basic EOC had the potential to avert intrapartum stillbirths by 45% and with provision of Comprehensive EOC this could be reduced by 75%. These estimates are conservative, consistent with historical trends in maternal and perinatal mortality from both developed and developing countries, and are recommended for inclusion in the Lives Saved Tool (LiST) model. Conclusions Both Skilled Birth Attendance and Emergency/or Essential Obstetric Care have the potential to reduce the number of stillbirths seen globally. Further evidence is needed to be able to calculate an effect size.

Abstract Background Zinc deficiency is commonly prevalent in children in developing countries and plays a role in decreased immunity and increased risk of infection. Preventive zinc supplementation in healthy children can reduce mortality due to common causes like diarrhea, pneumonia and malaria. The main objective was to determine all-cause mortality and cause-specific mortality and morbidity in children under five in developing countries for preventive zinc supplementation. Data sources/ review methods A literature search was carried out on PubMed, the Cochrane Library and the WHO regional databases to identify RCTs on zinc supplementation for greater than 3 months in children less than 5 years of age in developing countries and its effect on mortality was analyzed. Results The effect of preventive zinc supplementation on mortality was given in eight trials, while cause specific mortality data was given in five of these eight trials. Zinc supplementation alone was associated with a statistically insignificant 9% (RR = 0.91; 95% CI: 0.82, 1.01) reduction in all cause mortality in the intervention group as compared to controls using a random effect model. The impact on diarrhea-specific mortality of zinc alone was a non-significant 18% reduction (RR = 0.82; 95% CI: 0.64, 1.05) and 15% for pneumonia-specific mortality (RR = 0.85; 95% CI: 0.65, 1.11). The incidence of diarrhea showed a 13% reduction with preventive zinc supplementation (RR = 0.87; 95% CI: 0.81, 0.94) and a 19% reduction in pneumonia morbidity (RR = 0.81; 95% CI: 0.73, 0.90). Keeping in mind the direction of effect of zinc supplementation in reducing diarrhea and pneumonia related morbidity and mortality; we considered all the outcomes for selection of effectiveness estimate for inclusion in the LiST model. After application of the CHERG rules with consideration to quality of evidence and rule # 6, we used the most conservative estimates as a surrogate for mortality. We, therefore, conclude that zinc supplementation in children is associated with a reduction in diarrhea mortality of 13% and pneumonia mortality of 15% for inclusion in the LiST tool. Preventive zinc supplementation had no effect on malaria specific mortality (RR = 0.90; 95% CI: 0.77, 1.06) or incidence of malaria (RR=0.92; 95 % CI 0.82-1.04) Conclusion Zinc supplementation results in reductions in diarrhea and pneumonia mortality.

Background: Almost two billion people who are deficient in vitamins and minerals are women and children in low‐ and middle‐income countries (LMIC). These deficiencies are worsened during pregnancy due to increased energy and nutritional demands, causing adverse outcomes in mother and child. To reduce micronutrient deficiencies, several strategies have been implemented, including diet diversification, large‐scale and targeted fortification, staple crop bio‐fortification and micronutrient supplementation. Objectives: To evaluate and summarize the available evidence on the effects of micronutrient supplementation during pregnancy in LMIC on maternal, fetal, child health and child development outcomes. This review will assess the impact of single micronutrient supplementation (calcium, vitamin A, iron, vitamin D, iodine, zinc, vitamin B12), iron‐folic acid (IFA) supplementation, multiple micronutrient (MMN) supplementation, and lipid‐based nutrient supplementation (LNS) during pregnancy. Search Methods: We searched papers published from 1995 to 31 October 2019 (related programmes and good quality studies pre‐1995 were limited) in CAB Abstracts, CINAHL, Cochrane Central Register of Controlled Trials, Embase, International Initiative for Impact Evaluations, LILACS, Medline, POPLINE, Web of Science, WHOLIS, ProQuest Dissertations & Theses Global, R4D, WHO International Clinical Trials Registry Platform. Non‐indexed grey literature searches were conducted using Google, Google Scholar, and web pages of key international nutrition agencies. Selection Criteria: We included randomized controlled trials (individual and cluster‐randomized) and quasi‐experimental studies that evaluated micronutrient supplementation in healthy, pregnant women of any age and parity living in a LMIC. LMIC were defined by the World Bank Group at the time of the search for this review. While the aim was to include healthy pregnant women, it is likely that these populations had one or more micronutrient deficiencies at baseline; women were not excluded on this basis. Data Collection and Analysis: Two authors independently assessed studies for inclusion and risk of bias, and conducted data extraction. Data were matched to check for accuracy. Quality of evidence was assessed using the GRADE approach. Main Results: A total of 314 papers across 72 studies (451,723 women) were eligible for inclusion, of which 64 studies (439,649 women) contributed to meta‐analyses. Seven studies assessed iron‐folic acid (IFA) supplementation versus folic acid; 34 studies assessed MMN vs. IFA; 4 studies assessed LNS vs. MMN; 13 evaluated iron; 13 assessed zinc; 9 evaluated vitamin A; 11 assessed vitamin D; and 6 assessed calcium. Several studies were eligible for inclusion in multiple types of supplementation. IFA compared to folic acid showed a large and significant (48%) reduction in the risk of maternal anaemia (average risk ratio (RR) 0.52, 95% CI 0.41 to 0.66; studies = 5; participants = 15,540; moderate‐quality evidence). As well, IFA supplementation demonstrated a smaller but significant, 12% reduction in risk of low birthweight (LBW) babies (average RR 0.88, 95% CI 0.78 to 0.99; studies = 4; participants = 17,257; high‐quality evidence). MMN supplementation was defined as any supplement that contained at least 3 micronutrients. Post‐hoc analyses were conducted, where possible, comparing the differences in effect of MMN with 4+ components and MMN with 3 or 4 components. When compared to iron with or without FA, MMN supplementation reduced the risk of LBW by 15% (average RR 0.85, 95% CI 0.77 to 0.93; studies = 28; participants = 79,972); this effect was greater in MMN with >4 micronutrients (average RR 0.79, 95% CI 0.71 to 0.88; studies = 19; participants = 68,138 versus average RR 1.01, 95% CI 0.92 to 1.11; studies = 9; participants = 11,834). There was a small and significant reduction in the risk of stillbirths (average RR 0.91; 95% CI 0.86 to 0.98; studies = 22; participants = 96,772) and a small and significant effect on the risk of small‐for‐gestational age (SGA) (average RR 0.93; 95% CI 0.88 to 0.98; studies = 19; participants = 52,965). For stillbirths and SGA, the effects were greater among those provided MMN with 4+ micronutrients. Children whose mothers had been supplemented with MMN, compared to IFA, demonstrated a 16% reduced risk of diarrhea (average RR 0.84; 95% CI 0.76 to 0.92; studies = 4; participants = 3,142). LNS supplementation, compared to MMN, made no difference to any outcome; however, the evidence is limited. Iron supplementation, when compared to no iron or placebo, showed a large and significant effect on maternal anaemia, a reduction of 47% (average RR 0.53, 95% CI 0.43 to 0.65; studies = 6; participants = 15,737; moderate‐quality evidence) and a small and significant effect on LBW (average RR 0.88, 95% CI 0.78 to 0.99; studies = 4; participants = 17,257; high‐quality evidence). Zinc and vitamin A supplementation, each both compared to placebo, had no impact on any outcome examined with the exception of potentially improving serum/plasma zinc (mean difference (MD) 0.43 umol/L; 95% CI −0.04 to 0.89; studies = 5; participants = 1,202) and serum/plasma retinol (MD 0.13 umol/L; 95% CI −0.03 to 0.30; studies = 6; participants = 1,654), respectively. When compared to placebo, vitamin D supplementation may have reduced the risk of preterm births (average RR 0.64; 95% CI 0.40 to 1.04; studies = 7; participants = 1,262), though the upper CI just crosses the line of no effect. Similarly, calcium supplementation versus placebo may have improved rates of pre‐eclampsia/eclampsia (average RR 0.45; 95% CI 0.19 to 1.06; studies = 4; participants = 9,616), though the upper CI just crosses 1. Authors' Conclusions: The findings suggest that MMN and vitamin supplementation improve maternal and child health outcomes, including maternal anaemia, LBW, preterm birth, SGA, stillbirths, micronutrient deficiencies, and morbidities, including pre‐eclampsia/eclampsia and diarrhea among children. MMN supplementation demonstrated a beneficial impact on the most number of outcomes. In addition, MMN with >4 micronutrients appeared to be more impactful than MMN with only 3 or 4 micronutrients included in the tablet. Very few studies conducted longitudinal analysis on longer‐term health outcomes for the child, such as anthropometric measures and developmental outcomes; this may be an important area for future research. This review may provide some basis to guide continual discourse around replacing IFA supplementation with MMN along with the use of single micronutrient supplementation programs for specific outcomes. [ABSTRACT FROM AUTHOR]

Background: The last two decades have seen a significant decrease in mortality for children <5 years of age in low and middle-income countries (LMICs); however, neonatal (age, 0-28 days) mortality has not decreased at the same rate. We assessed three neonatal nutritional interventions that have the potential of reducing morbidity and mortality during infancy in LMICs. Objectives: To determine the efficacy and effectiveness of synthetic vitamin A, dextrose oral gel, and probiotic supplementation during the neonatal period. Search Methods: We conducted electronic searches for relevant studies on the following databases: PubMed, CINAHL, LILACS, SCOPUS, and CENTRAL, Cochrane Central Register for Controlled Trials, up to November 27, 2019. Selection Criteria: We aimed to include randomized and quasi-experimental studies. The target population was neonates in LMICs. The interventions included synthetic vitamin A supplementation, oral dextrose gel supplementation, and probiotic supplementation during the neonatal period. We included studies from the community and hospital settings irrespective of the gestational age or birth weight of the neonate. Data Collection and Analysis: Two authors screened the titles and extracted the data from selected studies. The risk of bias (ROB) in the included studies was assessed according to the Cochrane Handbook of Systematic Reviews. The primary outcome was all-cause mortality. The secondary outcomes were neonatal sepsis, necrotizing enterocolitis (NEC), prevention and treatment of neonatal hypoglycaemia, adverse events, and neurodevelopmental outcomes. Data were meta-analyzed by random effect models to obtain relative risk (RR) and 95% confidence interval (CI) for dichotomous outcomes and mean difference with 95% CI for continuous outcomes. The overall rating of evidence was determined by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Main Results: Sixteen randomized studies (total participants 169,366) assessed the effect of vitamin A supplementation during the neonatal period. All studies were conducted in low- and middle-income (LMIC) countries. Thirteen studies were conducted in the community setting and three studies were conducted in the hospital setting, specifically in neonatal intensive care units. Studies were conducted in 10 different countries including India (four studies), Guinea-Bissau (three studies), Bangladesh (two studies), and one study each in China, Ghana, Indonesia, Nepal, Pakistan, Tanzania, and Zimbabwe. The overall ROB was low in most of the included studies for neonatal vitamin A supplementation. The pooled results from the community based randomized studies showed that there was no significant difference in all-cause mortality in the vitamin A (intervention) group compared to controls at 1 month (RR, 0.99; 95% CI, 0.90-1.08; six studies with 126,548 participants, statistical heterogeneity I2 0%, funnel plot symmetrical, grade rating high), 6 months (RR, 0.98; 95% CI, 0.89-1.07; 12 studies with 154,940 participants, statistical heterogeneity I2 43%, funnel plot symmetrical, GRADE quality high) and 12 months of age (RR, 1.04; 95% CI, 0.94-1.14; eight studies with 118,376 participants, statistical heterogeneity I2 46%, funnel plot symmetrical, GRADE quality high). Neonatal vitamin A supplementation increased the incidence of bulging fontanelle by 53% compared to control (RR, 1.53; 95% CI, 1.12-2.09; six studies with 100,256 participants, statistical heterogeneity I² 65%, funnel plot symmetrical, GRADE quality high). We did not identify any experimental study that addressed the use of dextrose gel for the prevention and/or treatment of neonatal hypoglycaemia in LMIC. Thirtythree studies assessed the effect of probiotic supplementation during the neonatal period (total participants 11,595; probiotics: 5854 and controls: 5741). All of the included studies were conducted in LMIC and were randomized. Most of the studies were done in the hospital setting and included participants who were preterm (born < 37 weeks gestation) and/or low birth weight (<2500 g birth weight). Studies were conducted in 13 different countries with 10 studies conducted in India, six studies in Turkey, three studies each in China and Iran, two each in Mexico and South Africa, and one each in Bangladesh, Brazil, Colombia, Indonesia, Nepal, Pakistan, and Thailand. Three studies were at high ROB due to lack of appropriate randomization sequence or allocation concealment. Combined data from 25 studies showed that probiotic supplementation reduced all-cause mortality by 20% compared to controls (RR, 0.80; 95% CI, 0.66-0.96; total number of participants 10,998, number needed to treat 100, statistical heterogeneity I² 0%, funnel plot symmetrical, GRADE quality high). Twenty-nine studies reported the effect of probiotics on the incidence of NEC, and the combined results showed a relative reduction of 54% in the intervention group compared to controls (RR, 0.46; 95% CI, 0.35-0.59; total number of participants 5574, number needed to treat 17, statistical heterogeneity I² 24%, funnel plot symmetrical, GRADE quality high). Twenty-one studies assessed the effect of probiotic supplementation during the neonatal period on neonatal sepsis, and the combined results showed a relative reduction of 22% in the intervention group compared to controls (RR, 0.78; 95% CI, 0.70-0.86; total number of participants 9105, number needed to treat 14, statistical heterogeneity I² 23%, funnel plot symmetrical, GRADE quality high). Authors' Conclusions: Vitamin A supplementation during the neonatal period does not reduce all-cause neonatal or infant mortality in LMICs in the community setting. However, neonatal vitamin A supplementation increases the risk of Bulging Fontanelle. No experimental or quasi-experimental studies were available from LMICs to assess the effect of dextrose gel supplementation for the prevention or treatment of neonatal hypoglycaemia. Probiotic supplementation during the neonatal period seems to reduce all-cause mortality, NEC, and sepsis in babies born with low birth weight and/or preterm in the hospital setting. There was clinical heterogeneity in the use of probiotics, and we could not recommend any single strain of probiotics for wider use based on these results. There was a lack of studies on probiotic supplementation in the community setting. More research is needed to assess the effect of probiotics administered to neonates in-home/community setting in LMICs. [ABSTRACT FROM AUTHOR]

Background: Acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children aged less than 5 years in low- and middle-income countries where limited access to potable water, poor sanitation, deficient hygiene, and food product contamination are prevalent. Research on the changing etiology of AGE and associated risk factors in Latin America, including Colombia, is essential to understand the epidemiology of these infections. The primary objectives of this study were to describe etiology of moderate to severe AGE in children less than 5 years of age from Bucaramanga, Colombia, a middle-income country in Latin American, and to identify the presence of emerging E. coli pathotypes. Methodology/Principal findings: This was a prospective, matched for age, case-control study to assess the etiology of moderate to severe AGE in children less than 5 years of age in Bucaramanga, Colombia, South America. We tested for 24 pathogens using locally available diagnostic testing, including stool culture, polymerase chain reaction, microscopy and enzyme-linked immunoassay. Adjusted attributable fractions were calculated to assess the association between AGE and each pathogen in this study population. The study included 861 participants, 431 cases and 430 controls. Enteric pathogens were detected in 71% of cases and in 54% of controls (p = <0.001). Co-infection was identified in 28% of cases and in 14% of controls (p = <0.001). The adjusted attributable fraction showed that Norovirus GII explained 14% (95% CI: 10–18%) of AGE, followed by rotavirus 9.3% (6.4–12%), adenovirus 3% (1–4%), astrovirus 2.9% (0.6–5%), enterotoxigenic Escherichia coli (ETEC) 2.4% (0.4–4%), Cryptosporidium sp. 2% (0.5–4%), Campylobacter sp. 2% (0.2–4%), and Salmonella sp.1.9% (0.3 to 3.5%). Except for Cryptosporidium, all parasite infections were not associated with AGE. Three emergent diarrheagenic E. coli pathotypes were identified in cases (0.7%), including an enteroaggregative/enterotoxigenic E.coli (EAEC/ETEC), an enteroaggregative/enteropathogenic E.coli (EAEC/EPEC), and an emergent enteroinvasive E. coli with a rare O96:H19. No deaths were reported among cases or controls. Conclusions/Significance: Norovirus and rotavirus explained the major proportion of moderate to severe AGE in this study. Higher proportion of infection in cases, in the form of single infections or co-infections, showed association with AGE. Three novel E. coli pathotypes were identified among cases in this geographic region. Author summary: Acute gastroenteritis (AGE) is a leading cause of mortality in children under 5 years of age in low- and middle-income countries (LMIC). The highest burden of AGE disease is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene, making this condition a neglected disease. Limited information on etiology, associated malnutrition, and mortality among underserved communities makes difficult the development of strategies for AGE prevention and treatment. This case-control study among children less than 5 years of age in Bucaramanga, Colombia, revealed that viral followed by bacterial organisms explained the larger proportion of AGE, being norovirus the most common organism. The higher rate of infections and co-infections among cases compared to controls was associated with AGE. This study also reports the identification of three new E. coli pathotypes among cases designated as biofilm-forming enteroinvasive E. coli (BF-EIEC), enteroaggregative/enteropathogenic E. coli, and enteroaggregative/enterotoxigenic E. coli (EAEC/ETEC). [ABSTRACT FROM AUTHOR]

Introduction. Acute diarrheal disease (ADD) is a common cause of morbidity and mortality in children under 5 years of age. Understanding of the etiology of ADD is lacking in most low and middle income countries because reference laboratories detect limited number of pathogens. The objective of this study was to determine the feasibility to conduct a comprehensive case-control study to survey diarrheal pathogens among children with and without moderate-to-severe ADD. Materials and Methods. Microbiology and molecular-based techniques were used to detect viral, bacterial, and parasitic enteropathogens. The study was conducted in Bucaramanga, Colombia, after Institutional Review Board approval was obtained. Results. Ninety children less than 5 years of age were recruited after a written informed consent was obtained from parents or guardians. Forty-five subjects served as cases with ADD and 45 as controls. Thirty-six subjects out of 90 (40.0%) were positive for at least one enteropathogen, that is, 20 (44.4%) cases and 16 (35.5%) controls. Conclusions. The three most common enteric pathogens were enteroaggregative E. coli (10.0%), Norovirus (6.7%), and Salmonella spp. (5.6%). The E. coli pathogens were 18.8% of all infections making them the most frequent pathogens. Half of ADD cases were negative for any pathogens. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is an immune-mediated disease characterized by permanent gastrointestinal tract sensitivity to gluten in genetically predisposed individuals. It has varied clinical manifestations, ranging from gastrointestinal to extraintestinal, including neurological, skin, reproductive and psychiatric symptoms, which makes its diagnosis difficult and challenging. Known neurological manifestations of CD include epilepsy with or without occipital calcification, attention deficit hyperactivity disorder and ataxia, headache, neuropathies and behavior disorders. We present the case of a 14-year-old female with headaches and blurred vision for 1 year; she was noted to have papilledema on ophthalmic examination with increased cerebrospinal fluid opening pressure on lumber puncture and was diagnosed as a case of pseudotumor cerebri (PTC). Meanwhile her workup for chronic constipation revealed elevated tissue transglutaminase IgA and antiendomysial IgA antibodies. Upper gastrointestinal endoscopy with duodenal biopsy confirmed the diagnosis of CD. The patient was started on a gluten-free diet, leading to resolution of not only gastrointestinal symptoms but also to almost complete resolution of symptoms of PTC. This report describes the correlation of CD and PTC as its neurological manifestation. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Zinc deficiency is widespread, and preventive supplementation may have benefits in young children. Effects for children over 5 years of age, and effects when coadministered with other micronutrients are uncertain. These are obstacles to scale-up. This review seeks to determine if preventive supplementation reduces mortality and morbidity for children aged 6 months to 12 years. Design: Systematic review conducted with the Cochrane Developmental, Psychosocial and Learning Problems Group. Two reviewers independently assessed studies. Meta-analyses were performed for mortality, illness and side effects. Data sources: We searched multiple databases, including CENTRAL and MEDLINE in January 2013. Authors were contacted for missing information. Eligibility criteria for selecting studies: Randomised trials of preventive zinc supplementation. Hospitalised children and children with chronic diseases were excluded. Results: 80 randomised trials with 205 401 participants were included. There was a small but non-significant effect on all-cause mortality (risk ratio (RR) 0.95 (95% CI 0.86 to 1.05)). Supplementation may reduce incidence of all-cause diarrhoea (RR 0.87 (0.85 to 0.89)), but there was evidence of reporting bias. There was no evidence of an effect of incidence or prevalence of respiratory infections or malaria. There was moderate quality evidence of a very small effect on linear growth (standardised mean difference 0.09 (0.06 to 0.13)) and an increase in vomiting (RR 1.29 (1.14 to 1.46)). There was no evidence of an effect on iron status. Comparing zinc with and without iron cosupplementation and direct comparisons of zinc plus iron versus zinc administered alone favoured cointervention for some outcomes and zinc alone for other outcomes. Effects may be larger for children over 1 year of age, but most differences were not significant. Conclusions: Benefits of preventive zinc supplementation may outweigh any potentially adverse effects in areas where risk of zinc deficiency is high. Further research should determine optimal intervention characteristics and delivery strategies. [ABSTRACT FROM AUTHOR]