Agricultural waste management strategies for environmental sustainability.

Globally, abundant agricultural wastes (AWs) are being generated each day to fulfil the increasing demands of the fast-growing population. The limited and/or improper management of the same has created an urgent need to devise strategies for their timely utilization and valorisation, for agricultural sustainability and human-food and health security. The AWs are generated from different sources including crop residue, agro-industries, livestock, and aquaculture. The main component of the crop residue and agro-industrial waste is cellulose, (the most abundant biopolymer), followed by lignin and hemicellulose (lignocellulosic biomass). The AWs and their processing are a global issue since its vast majority is currently burned or buried in soil, causing pollution of air, water and global warming. Traditionally, some crop residues have been used in combustion, animal fodder, roof thatching, composting, soil mulching, matchsticks and paper production. But, lignocellulosic biomass can also serve as a sustainable source of biofuel (biodiesel, bioethanol, biogas, biohydrogen) and bioenergy in order to mitigate the fossil fuel shortage and climate change issues. Thus, valorisation of lignocellulosic residues has the potential to influence the bioeconomy by producing value-added products including biofertilizers, bio-bricks, bio-coal, bio-plastics, paper, biofuels, industrial enzymes, organic acids etc. This review encompasses circular bioeconomy based various AW management strategies, which involve 'reduction', 'reusing' and 'recycling' of AWs to boost sustainable agriculture and minimise environmental pollution.

High proportion of overt diabetes mellitus in pregnancy and missed opportunity for early detection of diabetes at a tertiary care centre in Pakistan.

OBJECTIVES: To determine the frequency of diabetes in pregnancy (DIP), namely pre-gestational, gestational (GDM) and overt diabetes mellitus (DM) in women registered for delivery. METHODS: A retrospective chart review of antenatal women registered between January 01 to August 31, 2017 was performed. Gestational age, diagnosis of DIP, glucose levels at diagnosis and other relevant data was extracted. The effect of various fasting blood glucose (FBG) thresholds for diagnosis of DIP was assessed. RESULTS: DIP was diagnosed in 21.8% women (pre-gestational: 2%, GDM: 81.2%, overt: DM: 16.8%). In early registrants, 30.2% were detected through screening. However, 55.3% of women registered late. Women with pre-gestational DM were older, had more miscarriages, and greater personal and family history of diabetes versus GDM and overt DM. Raising the diagnostic threshold of FBG from 92 mg/dl to 95 mg/dl missed three women (0.1%) and to 105 mg/dl, missed six women (0.2%). CONCLUSION: We observed a high proportion of overt DM. In early registrants, almost one third of DIP was diagnosed in the first half of pregnancy, an opportunity missed in late registrants. Altering diagnostic thresholds of DIP affected only a small proportion of women.

Characteristics and Survival Outcomes of Children With Hodgkin Lymphoma Treated Primarily With Chemotherapy.

BACKGROUND: Hodgkin disease is a malignant tumor of the lymphatic system that comprises ∼6% of childhood cancers. In developing countries, efforts are made to ensure adherence to standard protocol/regimens, study patients' outcomes, and compare with that in developed world. MATERIALS AND METHODS: We conducted a retrospective medical records' review of 212 children younger than 20 years presenting to The Indus Hospital in Pakistan with previously untreated Hodgkin lymphoma between August 2000 and December 2012. We collected demographic and other epidemiologic variables such as age, sex, stage, subtype of disease, and survival outcomes. RESULTS: The mean±SD age of patients at time of diagnosis was 9.0±3.8 years with a male to female ratio of ∼4.7:1. In total, 44 (20.8%) patients were 5 years of age or above at presentation. Overall, 131 (61.8%) patients presented with B-symptoms and mixed cellularity was the most frequently diagnosed subtype in 65.1% of cases. In total, 170 (80.2%) achieved full remission after completion of chemotherapy. Patients were treated with alternating cycles of ABVD (Adriamycin, Bleomycin, Vincristine, and Dacarbazine) and COPDAC (Cyclophosphamide, Vincristine, Prednisolone, and Dacarbazine). The majority (n=114, 59.1%) received 6 cycles of chemotherapy, 44 (22.8%) received ≤4 cycles followed by 24 (12.4%) receiving 8 cycles. Radiotherapy was administered only to those patients with significant residual disease at the end of chemotherapy (n=20, 10%). The 5-year overall survival and event-free survival in our cohort was 89.6% and 82.1%, respectively. CONCLUSION: Our findings suggest that treatment with 4 to 8 alternating cycles of ABVD/COPDAC has an excellent outcome in childhood Hodgkin disease.

Evaluation of Baseline Cardiac Function by Echocardiography and its Association With Nutritional Status in Pediatric Cancer Patients at The Indus Hospital in Karachi, Pakistan.

INTRODUCTION: Evidence on conducting baseline echocardiogram before starting chemotherapy in pediatric cancer patients is limited from developing countries where malnutrition and infections are common and which may result in cardiac dysfunction. MATERIALS AND METHODS: A prospective, observational study was conducted from October 2016 to May 2017 at The Indus Hospital, Karachi, Pakistan, among children 1 to 16 years of age suffering from cancer. Echocardiography was performed before starting chemotherapy. Associations between body mass index and cardiac abnormalities were studied. RESULTS: A total of 384 children met the inclusion criteria. The median (interquartile range) age was 8.0 (5.0 to 12.0) years and 62.0% (n=238) were male individuals. Twenty-two of 384 (5.7%) children had systolic dysfunction. Four of 22 had moderate-systolic and one of 22 had mild systolic dysfunction, for whom the therapy was altered, and they were treated without anthracyclines. Four of these 5 patients died, and only 1 of 5 survived through high-risk protocol. Seventeen of 22 children had low-normal systolic dysfunction. We found no evidence of an association between body mass index for age and abnormal left ventricular ejection fraction and abnormal fractional shortening (P-trend=0.587; 0.487, respectively). No associations were found of weight-for-age and height-for-age with these outcomes. CONCLUSIONS: In developing countries, echocardiograms should be expeditiously performed and technology made more accessible to rule out cardiac dysfunction and avoid delay in chemotherapy. Malnutrition was not associated with cardiac dysfunction.

Circulating Biomarkers of Dairy Fat and Risk of Incident Diabetes Mellitus Among Men and Women in the United States in Two Large Prospective Cohorts.

BACKGROUND: In prospective studies, the relationship of self-reported consumption of dairy foods with risk of diabetes mellitus is inconsistent. Few studies have assessed dairy fat, using circulating biomarkers, and incident diabetes mellitus. We tested the hypothesis that circulating fatty acid biomarkers of dairy fat, 15:0, 17:0, and t-16:1n-7, are associated with lower incident diabetes mellitus. METHODS AND RESULTS: Among 3333 adults aged 30 to 75 years and free of prevalent diabetes mellitus at baseline, total plasma and erythrocyte fatty acids were measured in blood collected in 1989 to 1990 (Nurses' Health Study) and 1993 to 1994 (Health Professionals Follow-Up Study). Incident diabetes mellitus through 2010 was confirmed by a validated supplementary questionnaire based on symptoms, diagnostic tests, and medications. Risk was assessed by using Cox proportional hazards, with cohort findings combined by meta-analysis. During mean±standard deviation follow-up of 15.2±5.6 years, 277 new cases of diabetes mellitus were diagnosed. In pooled multivariate analyses adjusting for demographics, metabolic risk factors, lifestyle, diet, and other circulating fatty acids, individuals with higher plasma 15:0 had a 44% lower risk of diabetes mellitus (quartiles 4 versus 1, hazard ratio, 0.56; 95% confidence interval, 0.37-0.86; P-trend=0.01); higher plasma 17:0, 43% lower risk (hazard ratio, 0.57; 95% confidence interval, 0.39-0.83; P-trend=0.01); and higher t-16:1n-7, 52% lower risk (hazard ratio, 0.48; 95% confidence interval, 0.33-0.70; P-trend <0.001). Findings were similar for erythrocyte 15:0, 17:0, and t-16:1n-7, although with broader confidence intervals that only achieved statistical significance for 17:0. CONCLUSIONS: In 2 prospective cohorts, higher plasma dairy fatty acid concentrations were associated with lower incident diabetes mellitus. Results were similar for erythrocyte 17:0. Our findings highlight the need to better understand the potential health effects of dairy fat, and the dietary and metabolic determinants of these fatty acids.

Omega-3 Fatty Acids and Incident Ischemic Stroke and Its Atherothrombotic and Cardioembolic Subtypes in 3 US Cohorts.

BACKGROUND AND PURPOSE: The associations of individual long-chain n-3 polyunsaturated fatty acids with incident ischemic stroke and its main subtypes are not well established. We aimed to investigate prospectively the relationship of circulating eicosapentaenoic acid, docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with risk of total ischemic, atherothrombotic, and cardioembolic stroke. METHODS: We measured circulating phospholipid fatty acids at baseline in 3 separate US cohorts: CHS (Cardiovascular Health Study), NHS (Nurses' Health Study), and HPFS (Health Professionals Follow-Up Study). Ischemic strokes were prospectively adjudicated and classified into atherothrombotic (large- and small-vessel infarctions) or cardioembolic by imaging studies and medical records. Risk according to fatty acid levels was assessed using Cox proportional hazards (CHS) or conditional logistic regression (NHS, HPFS) according to study design. Cohort findings were pooled using fixed-effects meta-analysis. RESULTS: A total of 953 incident ischemic strokes were identified (408 atherothrombotic, 256 cardioembolic, and 289 undetermined subtypes) during median follow-up of 11.2 years (CHS) and 8.3 years (pooled, NHS and HPFS). After multivariable adjustment, lower risk of total ischemic stroke was seen with higher DPA (highest versus lowest quartiles; pooled hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.58-0.92) and DHA (HR, 0.80; 95% CI, 0.64-1.00) but not eicosapentaenoic acid (HR, 0.94; 95% CI, 0.77-1.19). DHA was associated with lower risk of atherothrombotic stroke (HR, 0.53; 95% CI, 0.34-0.83) and DPA with lower risk of cardioembolic stroke (HR, 0.58; 95% CI, 0.37-0.92). Findings in each individual cohort were consistent with pooled results. CONCLUSIONS: In 3 large US cohorts, higher circulating levels of DHA were inversely associated with incident atherothrombotic stroke and DPA with cardioembolic stroke. These novel findings suggest differential pathways of benefit for DHA, DPA, and eicosapentaenoic acid.

Impact of Dietary and Metabolic Risk Factors on Cardiovascular and Diabetes Mortality in South Asia: Analysis From the 2010 Global Burden of Disease Study.

OBJECTIVES: To quantify cardiovascular disease and diabetes deaths attributable to dietary and metabolic risks by country, age, sex, and time in South Asian countries. METHODS: We used the 2010 Global Burden of Disease national surveys to characterize risk factor levels by age and sex. We derived etiological effects of risk factors-disease endpoints, by age, from meta-analyses. We defined optimal levels. We combined these inputs with cause-specific mortality rates to compute population-attributable fractions as a percentage of total cardiometabolic deaths. RESULTS: Suboptimal diet was the leading cause of cardiometabolic mortality in 4 of 5 countries, with population-attributable fractions from 40.7% (95% uncertainty interval = 37.4, 44.1) in Bangladesh to 56.9% (95% uncertainty interval = 52.4, 61.5) in Pakistan. High systolic blood pressure was the second leading cause, except in Bangladesh, where it superseded suboptimal diet. This was followed in all nations by high fasting plasma glucose, low fruit intake, and low whole grain intake. Other prominent burdens were more variable, such as low intake of vegetables, low omega-3 fats, and high sodium intake in India, Nepal, and Pakistan. CONCLUSIONS: Important similarities and differences are evident in cardiometabolic mortality burdens of modifiable dietary and metabolic risks across these countries, informing health policy and program priorities.

Vitamin D supplementation for preventing infections in children under five years of age.

BACKGROUND: Vitamin D is a micronutrient important for bone growth and immune function. Deficiency can lead to rickets and has been linked to various infections, including respiratory infections. The evidence on the effects of supplementation on infections in children has not been assessed systematically. OBJECTIVES: To evaluate the role of vitamin D supplementation in preventing pneumonia, tuberculosis (TB), diarrhoea, and malaria in children under five years of age. This includes high-, middle-, and low-income countries. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library, MEDLINE, EMBASE, LILACS, the WHO International Clinical Trials Registry Platform (ICTRP; http://www.who.int/ictrp/en/) , ClinicalTrials.gov and the ISRCTN registry (http://www.isrctn.com/) up to 16 June 2016. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated preventive supplementation of vitamin D (versus placebo or no intervention) in children under five years of age. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts, extracted the data, and assessed the risk of bias of included trials. MAIN RESULTS: Four trials met the inclusion criteria, with a total of 3198 children under five years of age, and were conducted in Afghanistan, Spain, and the USA. Prevalence of vitamin D deficiency varied widely in these populations (range: 73.1% in Afghanistan, 10 to 12% in USA, and 6.2% in Spain). The included trials evaluated mortality (two trials), pneumonia incidence (two trials), diarrhoea incidence (two trials), hospitalization (two trials), and mean serum vitamin D concentrations (four trials).We do not know whether vitamin D supplementation impacts on all-cause mortality because this outcome was underpowered due to few events (risk ratio (RR) 1.43, 95% confidence interval (CI) 0.54 to 3.74; one trial, 3046 participants, low quality evidence).For pneumonia, episodes of 'radiologically confirmed' first or only episode of pneumonia were little different in the supplemented and unsupplemented group (Rate Ratio: 1.06, 95% confidence interval (CI) 0.89 to 1.26; two trials, 3134 participants, moderate quality evidence), and similarly for children with confirmed or unconfirmed pneumonia (RR 0.95, 95% CI 0.87 to 1.04; one trial, 3046 participants). In these two trials there were no obvious differences between supplemented and unsupplemented children regarding episodes of diarrhoea.In the single large trial from Afghanistan, the trial authors reported that vitamin D supplementation was associated with an increase in repeat episodes of pneumonia confirmed by chest radiograph (RR 1.69, 95% CI 1.28 to 2.21; one trial, 3046 participants), but not reflected in the outcome of confirmed or unconfirmed pneumonia (RR 1.06, 95% CI 1.00 to 1.13; one trial, 3046 participants).For hospital admission measured in one small trial, there was no difference detected (RR 0.86, 95% CI 0.20 to 3.62; one trial, 88 participants; very low quality evidence).The mean serum vitamin D concentrations were higher in supplemented compared to unsupplemented children at the end of supplementation (MD 7.72 ng/mL, 95% CI 0.50 to 14.93; four trials, 266 participants, low quality evidence). These results were driven primarily by two smaller trials with large magnitudes of effect. In the other two bigger trials, serum vitamin D concentrations were elevated in the intervention group for most of the trial duration but not at the end of supplementation. This may be due to time elapsed at measurement from the last dose, incomplete compliance, or increased need of vitamin D with infant age.We did not find any trial that reported on the incidence of TB, malaria or febrile illness, duration of pneumonia, duration of diarrhoea, severity of infection, and cause-specific mortality (due to TB, diarrhoea, or malaria). AUTHORS' CONCLUSIONS: Evidence from one large trial did not demonstrate benefit of vitamin D supplementation on the incidence of pneumonia or diarrhoea in children under five years. To our knowledge, trials that evaluated supplementation for preventing other infections, including TB and malaria, have not been performed.

Impact of complications on long-term survival after resection of intrahepatic cholangiocarcinoma.

BACKGROUND: The impact of postoperative complications on the long-term outcomes of patients undergoing surgery for cancer is unclear. The objective of the current study was to define the incidence of complications among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC) and identify the association between morbidity and long-term outcomes. METHODS: A total of 583 patients undergoing surgery with curative intent for ICC between 1990 and 2013 at 1 of 12 participating institutions were identified. The association between the occurrence and severity of postoperative complications on long-term survival was analyzed. RESULTS: The median age of the patients was 59.9 years and the majority of patients were male (52.3%). A total of 91 patients (15.6%) and 153 patients (26.2%) developed a major and minor postoperative complication, respectively; 18 patients (3.5%) died within 90 days of surgery. Median, 1-year, 3-year, and 5-year recurrence-free survival were 10.0 months, 43.3%, 16.7%, and 11.1%, respectively. Postoperative complications (hazard ratio [HR], 1.37, 95% confidence interval [95% CI], 1.08-1.73 [P = .01]) and severity of complications (major vs none: HR, 1.55; 95% CI, 1.14-2.11 [P = .01]; minor vs none: HR, 1.30; 95% CI, 0.99-1.70 [P = .06]) independently predicted shorter recurrence-free survival. Median, 1-year, 3-year, and 5-year overall survival was 27.8 months, 76.8%, 39.0%, and 23.4%, respectively. Postoperative complications (HR, 1.64; 95% CI, 1.30-2.08 [P<.001]) and severity of complications (major vs none: HR, 1.79; 95% CI, 1.31-2.44 [P<.001]; minor vs none: HR, 1.50; 95% CI, 1.15-1.95 [P<.01]) independently predicted shorter overall survival. CONCLUSIONS: Postoperative complications were found to be independent predictors of worse long-term outcomes. The prevention and management of postoperative complications is crucial to increase both short-term and long-term survival.

The Impact of Surgical Margin Status on Long-Term Outcome After Resection for Intrahepatic Cholangiocarcinoma.

BACKGROUND: The influence of margin status on long-term outcome of patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) remains controversial. We sought to study the impact of surgical tumor margin status on recurrence-free survival (RFS) and overall survival (OS) of patients undergoing resection for ICC. METHODS: From a multi-institutional database, 583 patients who underwent hepatic resection for ICC were identified. Demographics data, operative details, pathologic margin status, and long-term outcomes were collected and analyzed. RESULTS: Margin status was positive (R1) in 95 (17.8 %) patients; among patients who underwent an R0 resection (80.9 %), margin width was negative by 1-4 mm in 166 (31.0 %) patients, 5-9 mm in 100 (18.7 %) patients, and ≥1 cm in 174 (32.5 %) patients. Overall, 379 (65.0 %) patients had a recurrence: 61.5 % intrahepatic, 13.5 % extrahepatic, and 25.0 % both intra- and extrahepatic. Median and 5-year RFS and OS was 10.0 months and 9.2 %, and 26.4 months and 23.0 %, respectively. Patients who had an R1 resection had a higher risk of recurrence (hazard ratio [HR] 1.61, 95 % CI 1.15-2.27; p = 0.01) and shorter OS (HR 1.54, 95 % CI 1.12-2.11). Among patients with an R0 resection, margin width was also associated with RFS (1-4 mm: HR 1.32, 95 % CI 0.98-1.78 vs. 5-9 mm: HR 1.21, 95 % CI 0.89-1.66) and OS (1-4 mm: HR 1.95, 95 % CI 0.45-2.63 vs. 5-9 mm: HR 1.21, 95 % CI 0.88-1.68) (referent ≥1 cm; both p ≤ 0.002). Margin status and width remain independently associated with RFS and OS on multivariable analyses. CONCLUSIONS: For patients undergoing resection of ICC, R1 margin status was associated with an inferior long-term outcome. Moreover, there was an incremental worsening RFS and OS as margin width decreased.

Stillbirths: what difference can we make and at what cost?

Worldwide, 2·65 million (uncertainty range 2·08 million to 3·79 million) stillbirths occur yearly, of which 98% occur in countries of low and middle income. Despite the fact that more than 45% of the global burden of stillbirths occur intrapartum, the perception is that little is known about effective interventions, especially those that can be implemented in low-resource settings. We undertook a systematic review of randomised trials and observational studies of interventions which could reduce the burden of stillbirths, particularly in low-income and middle-income countries. We identified several interventions with sufficient evidence to recommend implementation in health systems, including periconceptional folic acid supplementation or fortification, prevention of malaria, and improved detection and management of syphilis during pregnancy in endemic areas. Basic and comprehensive emergency obstetric care were identified as key effective interventions to reduce intrapartum stillbirths. Broad-scale implementation of intervention packages across 68 countries listed as priorities in the Countdown to 2015 report could avert up to 45% of stillbirths according to a model generated from the Lives Saved Tool. The overall costs for these interventions are within the general estimates of cost-effective interventions for maternal care, especially in view of the effects on outcomes across maternal, fetal, and neonatal health.

The association of maternal race and ethnicity and the risk of postpartum hemorrhage.

BACKGROUND: There are profound racial and ethnic disparities in obstetric outcomes in the United States, but little is known about disparities in risk of postpartum hemorrhage (PPH). We explored the association of race and ethnicity on the risk of PPH due to uterine atony with sequential adjustment for possible mediating factors. METHODS: This analysis was based on the Nationwide Inpatient Sample, from between 2005 and 2008. The frequencies of atonic PPH and atonic PPH resulting in transfusion or hysterectomy were estimated. We developed multivariable logistic regression models to estimate the odds of these outcomes in maternal racial/ethnic groups by sequentially adding potential mediators. RESULTS: Hispanic ethnicity and Asian/Pacific Islander race were associated with a statistically significant increased odds of atonic PPH in comparison with Caucasians, despite adjustment for potential mediators (adjusted odds ratio [OR] for Hispanics: 1.21, 99% confidence interval [1.18, 1.25]; for Asians/Pacific Islanders: 1.31 [1.25, 1.38], with Caucasians as reference). Similar results were observed for these racial/ethnic groups for atonic PPH resulting in transfusion or hysterectomy. CONCLUSION: Hispanic ethnicity and Asian/Pacific Islander race are significant risk factors for atonic PPH independent of measured potential mediators; biological differences may play a role.

Effect of routine iron supplementation with or without folic acid on anemia during pregnancy.

INTRODUCTION: Iron deficiency is the most prevalent nutrient deficiency in the world, particularly during pregnancy. According to the literature, anemia, particularly severe anemia, is associated with increased risk of maternal mortality. It also puts mothers at risk of multiple perinatal complications. Numerous studies in the past have evaluated the impact of supplementation with iron and iron-folate but data regarding the efficacy and quality of evidence of these interventions are lacking. This article aims to address the impact of iron with and without folate supplementation on maternal anemia and provides outcome specific quality according to the Child Health Epidemiology Reference Group (CHERG) guidelines. METHODS: We conducted a systematic review of published randomized and quasi-randomized trials on PubMed and the Cochrane Library as per the CHERG guidelines. The studies selected employed daily supplementation of iron with or without folate compared with no intervention/placebo, and also compared intermittent supplementation with the daily regimen. The studies were abstracted and graded according to study design, limitations, intervention specifics and outcome effects. CHERG rules were then applied to evaluate the impact of these interventions on iron deficiency anemia during pregnancy. Recommendations were made for the Lives Saved Tool (LiST). RESULTS: After screening 3550 titles, 31 studies were selected for assessment using CHERG criteria. Daily iron supplementation resulted in 73% reduction in the incidence of anemia at term (RR = 0.27; 95% CI: 0.17 - 0.42; random effects model) and 67% reduction in iron deficiency anemia at term (RR = 0.33; 95% CI: 0.16 - 0.69; random model) compared to no intervention/placebo. For this intervention, both these outcomes were graded as 'moderate' quality evidence. Daily supplementation with iron-folate was associated with 73% reduction in anemia at term (RR = 0.27; 95% CI: 0.12 - 0.56; random model) with a quality grade of 'moderate'. The effect of the same intervention on iron deficiency anemia was non-significant (RR = 0.43; 95% CI: 0.17 - 1.09; random model) and was graded as 'low' quality evidence. There was no difference in rates of anemia at term with intermittent iron-folate vs. daily iron-folate supplementation (RR = 1.61; 95% CI: 0.82 -3.14; random model). CONCLUSION: Applying the CHERG rules, we recommend a 73% reduction in anemia at term with daily iron (alone) supplementation or iron/folate (combined) vs. no intervention or placebo; for inclusion in the LiST model. Given the paucity of studies of intermittent iron or iron-folate supplementation, especially in developing countries, we recommend further evaluation of this intervention in comparison with daily supplementation regimen.

Effect of breastfeeding promotion interventions on breastfeeding rates, with special focus on developing countries.

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.

Impact of maternal education about complementary feeding and provision of complementary foods on child growth in developing countries.

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 0.25 kg (± 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.

The effect of folic acid, protein energy and multiple micronutrient supplements in pregnancy on stillbirths.

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.

Screening and triage of intrauterine growth restriction (IUGR) in general population and high risk pregnancies: a systematic review with a focus on reduction of IUGR related stillbirths.

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%.

Effect of multiple micronutrient supplementation during pregnancy on maternal and birth outcomes.

OBJECTIVES/BACKGROUND: Given the widespread prevalence of micronutrient deficiencies in developing countries, supplementation with multiple micronutrients rather than iron-folate alone, could be of potential benefit to the mother and the fetus. These benefits could relate to prevention of maternal complications and reduction in other adverse pregnancy outcomes such as small-for-gestational age (SGA) births, low birth weight, stillbirths, perinatal and neonatal mortality. This review evaluates the evidence of the impact of multiple micronutrient supplements during pregnancy, in comparison with standard iron-folate supplements, on specific maternal and pregnancy outcomes of relevance to the Lives Saved Tool (LiST). DATA SOURCES/REVIEW METHODS: A systematic review of randomized controlled trials was conducted. Search engines used were PubMed, the Cochrane Library, the WHO regional databases and hand search of bibliographies. A standardized data abstraction and Child Health Epidemiology Reference (CHERG) adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) technique were used for data abstraction and overall quality of evidence. Meta-analyses were performed to calculate summary estimates of utility to the LiST model for the specified outcome of incidence of SGA births. We also evaluated the potential impact of multiple micronutrients on neonatal mortality according to the proportion of deliveries occurring in facilities (using a threshold of 60% to indicate functionality of health systems for skilled births). RESULTS: We included 17 studies for detailed data abstraction. There was no significant benefit of multiple micronutrients as compared to iron folate on maternal anemia in third trimester [Relative risk (RR) = 1.03; 95% confidence interval (CI): 0.87 - 1.22 (random model)]. Our analysis, however, showed a significant reduction in SGA by 9% [RR = 0.91; 95% CI: 0.86 - 0.96 (fixed model)]. In the fixed model, the SGA outcome remained significant only in women with mean body mass index (BMI) ≥ 22 kg/m2. There was an increased risk of neonatal mortality in studies with majority of births at home [RR = 1.47, 95% CI: 1.13-1.92]; such an effect was not evident where ≥ 60% of births occurred in facility settings [RR = 0.94, 95% CI: 0.81-1.09]. Overall there was no increase in the risk of neonatal mortality [RR = 1.05, 95% CI: 0.92 - 1.19 (fixed model)]. CONCLUSION: This review provides evidence of a significant benefit of MMN supplementation during pregnancy on reducing SGA births as compared to iron-folate, with no significant increase in the risk of neonatal mortality in populations where skilled birth care is available and majority of births take place in facilities. Given comparability of impacts on maternal anemia, the decision to replace iron-folate with multiple micronutrients during pregnancy may be taken in the context of available services in health systems and birth outcomes monitored.