BackgroundThe 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.MethodsA 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.ResultsThe 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).ConclusionProviding 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.

BackgroundChildhood 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).MethodsWe 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.ResultsAfter 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.ConclusionProvision 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.

IntroductionZinc 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.MethodsA 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).ResultsThere 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.ConclusionsZinc 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.

BackgroundInfection 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.MethodsWe 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.ResultsA 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).ConclusionsThe 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.

BackgroundZinc 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 methodsA 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.ResultsThe 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)ConclusionZinc supplementation results in reductions in diarrhea and pneumonia mortality.

BackgroundGiven 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.MethodsA 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.ResultsAfter 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.ConclusionBreastfeeding 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.