Exploring preconception health in adolescents and young adults: Identifying risk factors and interventions to prevent adverse maternal, perinatal, and child health outcomes-A scoping review.

BACKGROUND: Preconception health provides an opportunity to examine a woman's health status and address modifiable risk factors that can impact both a woman's and her child's health once pregnant. In this review, we aimed to investigate the preconception risk factors and interventions of early pregnancy and its impact on adverse maternal, perinatal and child health outcomes. METHODS: We conducted a scoping review following the PRISMA-ScR guidelines to include relevant literature identified from electronic databases. We included reviews that studied preconception risk factors and interventions among adolescents and young adults, and their impact on maternal, perinatal, and child health outcomes. All identified studies were screened for eligibility, followed by data extraction, and descriptive and thematic analysis. FINDINGS: We identified a total of 10 reviews. The findings suggest an increase in odds of maternal anaemia and maternal deaths among young mothers (up to 17 years) and low birth weight (LBW), preterm birth, stillbirths, and neonatal and perinatal mortality among babies born to mothers up to 17 years compared to those aged 19-25 years in high-income countries. It also suggested an increase in the odds of congenital anomalies among children born to mothers aged 20-24 years. Furthermore, cancer treatment during childhood or young adulthood was associated with an increased risk of preterm birth, LBW, and stillbirths. Interventions such as youth-friendly family planning services showed a significant decrease in abortion rates. Micronutrient supplementation contributed to reducing anaemia among adolescent mothers; however, human papillomavirus (HPV) and herpes simplex virus (HSV) vaccination had little to no impact on stillbirths, ectopic pregnancies, and congenital anomalies. However, one review reported an increased risk of miscarriages among young adults associated with these vaccinations. CONCLUSION: The scoping review identified a scarcity of evidence on preconception risk factors and interventions among adolescents and young adults. This underscores the crucial need for additional research on the subject.

Dietary Strategies for Complementary Feeding between 6 and 24 Months of Age: The Evidence.

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.

Training health workers in clinical breast examination for early detection of breast cancer in low- and middle-income countries.

BACKGROUND: Most women living in low- and middle-income countries (LMICs) present with advanced-stage breast cancer. Limitations of poor serviceable health systems, restricted access to treatment facilities, and lack of breast cancer screening programmes all likely contribute to the late presentation of women with breast cancer living in these countries. Women are diagnosed with advanced disease and frequently do not complete their care due to a number of factors, including financial reasons as health expenditure is largely out of pocket resulting in financial toxicity; health system failures, such as missing services or health worker lack of awareness on common signs and symptoms of cancer; and sociocultural barriers, such as stigma and use of alternative therapies. Clinical breast examination (CBE) is an inexpensive early detection technique for breast cancer in women with palpable breast masses. Training health workers from LMICs to conduct CBE has the potential to improve the quality of the technique and the ability of health workers to detect breast cancers early. OBJECTIVES: To assess whether training in CBE affects the ability of health workers in LMICs to detect early breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Specialised Registry, CENTRAL, MEDLINE, Embase, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal, and ClinicalTrials.gov up to 17 July 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) (including individual and cluster-RCTs), quasi-experimental studies and controlled before-and-after studies if they fulfilled the eligibility criteria. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies for inclusion, and extracted data, assessed risk of bias, and assessed the certainty of the evidence using the GRADE approach. We performed statistical analysis using Review Manager software and presented the main findings of the review in a summary of findings table. MAIN RESULTS: We included four RCTs that screened a total population of 947,190 women for breast cancer, out of which 593 breast cancers were diagnosed. All included studies were cluster-RCTs; two were conducted in India, one in the Philippines, and one in Rwanda. Health workers trained to perform CBE in the included studies were primary health workers, nurses, midwives, and community health workers. Three of the four included studies reported on the primary outcome (breast cancer stage at the time of presentation). Amongst secondary outcomes, included studies reported CBE coverage, follow-up, accuracy of health worker-performed CBE, and breast cancer mortality. None of the included studies reported knowledge attitude practice (KAP) outcomes and cost-effectiveness. Three studies reported diagnosis of breast cancer at early stage (at stage 0+I+II), suggesting that training health workers in CBE may increase the number of women detected with breast cancer at an early stage compared to the non-training group (45% detected versus 31% detected; risk ratio (RR) 1.44, 95% confidence interval (CI) 1.01 to 2.06; three studies; 593 participants; I2 = 0%; low-certainty evidence). Three studies reported diagnosis at late stage (III+IV) suggesting that training health workers in CBE may slightly reduce the number of women detected with breast cancer at late stage compared to the non-training group (13% detected versus 42%, RR 0.58, 95% CI 0.36 to 0.94; three studies; 593 participants; I2 = 52%; low-certainty evidence). Regarding secondary outcomes, two studies reported breast cancer mortality, implying that the evidence is uncertain for the impact on breast cancer mortality (RR 0.88, 95% CI 0.24 to 3.26; two studies; 355 participants; I2 = 68%; very low-certainty evidence). Due to the study heterogeneity, we could not conduct meta-analysis for accuracy of health worker-performed CBE, CBE coverage, and completion of follow-up, and therefore reported narratively using the 'Synthesis without meta-analysis' (SWiM) guideline. Sensitivity of health worker-performed CBE was reported to be 53.2% and 51.7%; while specificity was reported to be 100% and 94.3% respectively in two included studies (very low-certainty evidence). One trial reported CBE coverage with a mean adherence of 67.07% for the first four screening rounds (low-certainty evidence). One trial reported follow-up suggesting that compliance rates for diagnostic confirmation following a positive CBE were 68.29%, 71.20%, 78.84% and 79.98% during the respective first four rounds of screening in the intervention group compared to 90.88%, 82.96%, 79.56% and 80.39% during the respective four rounds of screening in the control group. AUTHORS' CONCLUSIONS: Our review findings suggest some benefit of training health workers from LMICs in CBE on early detection of breast cancer. However, the evidence regarding mortality, accuracy of health worker-performed CBE, and completion of follow up is uncertain and requires further evaluation.

Effectiveness of Dietary Management for Moderate Wasting among Children > 6 Months of Age-A Systematic Review and Meta-Analysis Exploring Different Types, Quantities, and Durations.

Currently, no World Health Organization guidelines exist for the management of approximately 31.8 million moderately wasted children globally. The objective of this review was to synthesise evidence on the optimal type, quantity, and duration of dietary treatment for moderate wasting. Ten electronic databases were searched until the 23rd of August 2021. Experimental studies comparing interventions for the dietary management of moderate wasting were included. Meta-analyses were conducted and results were presented as risk ratios or mean differences with 95% confidence intervals. Seventeen studies comparing specially formulated foods were included involving 23,005 participants. Findings suggest little or no difference in recovery between Fortified Blended Foods (FBFs) with improved micronutrient and/or milk content (enhanced FBFs) and lipid-based nutrient supplements (LNS), whereas children treated with non-enhanced FBFs (locally produced FBFs or standard corn-soy blend) may have lower recovery rates than those treated with LNS. There was no difference in recovery when ready-to-use therapeutic and ready-to-use supplementary food were compared. Other outcomes mostly aligned with results for recovery. In conclusion, LNSs improve recovery compared to non-enhanced FBFs, but are comparable to enhanced FBFs. Programmatic choice of supplement should consider factors such as cost, cost-effectiveness, and acceptability. Further research is required to determine optimal dosing and duration of supplementation.

Interventions for High-Burden Infectious Diseases in Children and Adolescents: A Meta-analysis.

BACKGROUND: Approximately 2.2 million deaths were reported among school-age children and young people in 2019, and infectious diseases remain the leading causes of morbidity and mortality, especially in low and middle-income countries. We aim to synthesize evidence on interventions for high-burden infectious diseases among children and adolescents aged 5 to 19 years. METHODS: We conducted a comprehensive literature search until December 31, 2020. Two review authors independently screened studies for relevance, extracted data, and assessed risk of bias. RESULTS: We included a total of 31 studies, including 81 596 participants. Sixteen studies focused on diarrhea; 6 on tuberculosis; 2 on human immunodeficiency virus; 2 on measles; 1 study each on acute respiratory infections, malaria, and urinary tract infections; and 2 studies targeted multiple diseases. We did not find any study on other high burden infectious diseases among this age group. We could not perform meta-analysis for most outcomes because of variances in interventions and outcomes. Findings suggests that for diarrhea, water treatment, water filtration, and zinc supplementation have some protective effect. For tuberculosis, peer counseling, contingency contract, and training of health care workers led to improvements in tuberculosis detection and treatment completion. Continuation of cotrimoxazole therapy reduced the risk of tuberculosis and hospitalizations among human immunodeficiency virus-infected children and reduced measles complications and pneumonia cases among measles-infected children. Zinc supplementation led to a faster recovery in urinary tract infections with a positive effect in reducing symptoms. CONCLUSIONS: There is scarcity of data on the effectiveness of interventions for high-burden infectious diseases among school-aged children and adolescents.

Interventions for Neglected Tropical Diseases Among Children and Adolescents: A Meta-analysis.

BACKGROUND: Neglected tropical diseases (NTDs) are a group of communicable diseases affecting the poorest populations around the world. OBJECTIVE: To assess the effectiveness of interventions, including mass drug administration (MDA), water, sanitation, and hygiene (WASH), vector control, health education, and micronutrients supplementation, for NTDs among children and adolescents. METHODS: We conducted a literature search on the Cochrane Controlled Trials Register, Medline, and other databases until December 2020. We included randomized controlled trials and quasi-experimental studies conducted among children and adolescents. Two authors independently screened studies for relevance. Two authors independently extracted data, assessed the risk of bias, performed metaanalysis, and rated the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: We included 155 studies (231 articles) involving 262 299 participants. For soil-transmitted helminthiasis, MDA may reduce the prevalence of Ascaris, Trichuris, and hookworm by 58%, 36%, and 57%, respectively. We are uncertain of the effect of health education, WASH, and iron supplementation on soil-transmitted helminthiasis prevalence. For Schistosomiasis, health education probably reduces the intensity and prevalence of S. mansoni, whereas micronutrient supplementation may reduce anemia prevalence and the infection intensity of S. hematobium compared with no supplementation. We are uncertain of the effect of MDA and vector control on Schistosomiasis outcomes. For trachoma, health education probably reduces the prevalence of active Trachoma, whereas we are uncertain of the effect of MDA, WASH, and vector control on Trachoma outcomes. There is limited data on the effectiveness of interventions for NTDs targeting children and adolescents. CONCLUSION: Future studies are needed to evaluate the relative effectiveness and cost-effectiveness of various interventions specifically targeting children and adolescents.

Vitamin C supplementation for prevention and treatment of pneumonia.

BACKGROUND: According to the Global Burden of Disease Study 2015, lower respiratory tract infection is the leading cause of infectious disease death, and the fifth most common cause of death overall. Vitamin C has a role in modulating resistance to infectious agents, therefore vitamin C supplementation may be important in preventing and treating pneumonia. OBJECTIVES: To assess the impact of vitamin C supplementation to prevent and treat pneumonia in children and adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed, CINAHL, LILACS, Web of Science, and two trials registers to 4 March 2020. We also checked references to identify additional studies. We did not apply any publication status or language filters. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (studies using allocation methods that are not random, e.g. date of birth, medical record number) assessing the role of vitamin C supplementation in the prevention and treatment of pneumonia in children and adults compared to control or placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included five studies in the review and identified two ongoing studies. The five included studies involved a total of 2655 participants; two studies were RCTs and three were quasi-RCTs. The included studies were conducted in one high-income country (USA) and three lower-middle-income countries (Bangladesh and Pakistan). Three studies were conducted in hospital inpatient settings, one in school, and one in a military training centre. Three studies included children under five years of age, one study included school-aged children, and one study included adult participants. Two studies assessed the effect of vitamin C supplementation for pneumonia prevention; and three studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment. For pneumonia prevention, the included studies provided supplementation in doses of 1 g daily for 14 weeks, 2 g daily for 8 weeks, and 2 g daily for 14 weeks. For pneumonia treatment, the included studies provided vitamin C supplementation in doses of 125 mg daily and 200 mg daily until the symptoms resolved or discharge, as an adjunct to the pneumonia treatment. Overall, the included studies were judged to be at either high or unclear risk of bias for random sequence generation, allocation concealment, and blinding; and the evidence certainty was very low. Two studies assessed the effect of vitamin C supplementation for pneumonia prevention; we judged the certainty of the evidence as very low. We are uncertain about the effect of vitamin C supplementation on pneumonia incidence and adverse events (urticaria). None of the included studies reported other primary outcomes (pneumonia prevalence and mortality) or any of the secondary outcomes. Three studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment; we judged the certainty of the evidence as very low. We are uncertain of the effect of vitamin C supplementation on duration of illness and hospitalisation. None of the included studies reported other primary or secondary outcomes. AUTHORS' CONCLUSIONS: Due to the small number of included studies and very low certainty of the existing evidence, we are uncertain of the effect of vitamin C supplementation for the prevention and treatment of pneumonia. Further good-quality studies are required to assess the role of vitamin C supplementation in the prevention and treatment of pneumonia.

Effective interventions to address maternal and child malnutrition: an update of the evidence.

Malnutrition-consisting of undernutrition, overweight and obesity, and micronutrient deficiencies-continues to afflict millions of women and children, particularly in low-income and middle-income countries (LMICs). Since the 2013 Lancet Series on maternal and child nutrition, evidence on the ten recommended interventions has increased, along with evidence of newer interventions. Evidence on the effectiveness of antenatal multiple micronutrient supplementation in reducing the risk of stillbirths, low birthweight, and babies born small-for-gestational age has strengthened. Evidence continues to support the provision of supplementary food in food-insecure settings and community-based approaches with the use of locally produced supplementary and therapeutic food to manage children with acute malnutrition. Some emerging interventions, such as preventive small-quantity lipid-based nutrient supplements for children aged 6-23 months, have shown positive effects on child growth. For the prevention and management of childhood obesity, integrated interventions (eg, diet, exercise, and behavioural therapy) are most effective, although there is little evidence from LMICs. Lastly, indirect nutrition strategies, such as malaria prevention, preconception care, water, sanitation, and hygiene promotion, delivered inside and outside the health-care sector also provide important nutritional benefits. Looking forward, greater effort is required to improve intervention coverage, especially for the most vulnerable, and there is a crucial need to address the growing double burden of malnutrition (undernutrition, and overweight and obesity) in LMICs.

Vitamin C supplementation for prevention and treatment of pneumonia.

BACKGROUND: According to the Global Burden of Disease Study 2015, lower respiratory tract infection is the leading cause of infectious disease death, and the fifth most common cause of death overall. Vitamin C has a role in modulating resistance to infectious agents, therefore vitamin C supplementation may be important in preventing and treating pneumonia. OBJECTIVES: To assess the impact of vitamin C supplementation to prevent and treat pneumonia in children and adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PubMed, CINAHL, LILACS, Web of Science, and two trials registers to 4 March 2020. We also checked references to identify additional studies. We did not apply any publication status or language filters. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs (studies using allocation methods that are not random, e.g. date of birth, medical record number) assessing the role of vitamin C supplementation in the prevention and treatment of pneumonia in children and adults compared to control or placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included seven studies in the review and identified two ongoing studies. The seven included studies involved a total of 2774 participants; five studies were RCTs and two were quasi-RCTs. The included studies were conducted in high-income countries (UK, USA and Chile) and lower-middle-income countries (Bangladesh and Pakistan). Four studies were conducted in hospital inpatient settings, two in schools, and one in a military training centre. Three studies included children under five years of age, two school-aged children, one adult participants, and one older participants aged 60 to 90 years. Two studies assessed the effect of vitamin C supplementation for pneumonia prevention; four studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment; and one study assessed the role of vitamin C for both prevention and treatment of pneumonia. For pneumonia prevention, the included studies provided supplementation in doses of 500 mg daily for 14 weeks, 2 g daily for 8 weeks, and 2 g daily for 12 weeks. For pneumonia treatment, the included studies provided vitamin C supplementation in doses of 125 mg daily (until discharge), 200 mg for 4 weeks, and 200 mg until discharge, as an adjunct to the pneumonia treatment. We assessed the included studies as at overall either high or unclear risk of bias for random sequence generation, allocation concealment, and blinding. We judged the quality of the evidence as very low. Three studies assessed the effect of vitamin C supplementation for pneumonia prevention; we judged the quality of the evidence as very low. We are uncertain about the effect of vitamin C supplementation on pneumonia incidence (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.06 to 3.61; 2 studies, 736 participants; I² = 75%; very low-quality evidence) and adverse events (urticaria) (RR 3.11, 95% CI 0.13 to 76.03; 1 study, 674 participants; very low-quality evidence). No included studies reported our other primary outcomes (pneumonia prevalence and mortality) or any of our secondary outcomes. Five studies assessed the effect of vitamin C supplementation as an adjunct to pneumonia treatment; we judged the quality of the evidence as very low. One study reported a decrease in the duration of illness in the vitamin C supplementation group (3.4 days ± 2.54) compared to the control group (4.5 days ± 2.35), and one study reported a decrease in number of days required for improvement in oxygen saturation (1.03 days ± 0.16 versus 1.14 days ± 1.0) and respiratory rate (3.61 days ± 1.50 versus 4.04 days ± 1.62) in the vitamin C supplementation group compared to the control group. We are uncertain of the effect of vitamin C supplementation on mortality due to pneumonia (RR 0.21, 95% CI 0.03 to 1.66; 1 study, 57 participants; very low-quality evidence). One study reported that the mean duration of hospital stay was 6.75 days amongst children in the vitamin C supplementation group and 7.75 days in the control group; another study reported a lower mean duration of hospital stay in the vitamin C supplementation group compared to the control group (109.55 hours ± 27.89 versus 130.64 hours ± 41.76). AUTHORS' CONCLUSIONS: Due to the small number of included studies and very low quality of the existing evidence, we are uncertain of the effect of vitamin C supplementation for the prevention and treatment of pneumonia. Further good-quality studies are required to assess the role of vitamin C supplementation in the prevention and treatment of pneumonia.

Impact of Dietary Interventions during Pregnancy on Maternal, Neonatal, and Child Outcomes in Low- and Middle-Income Countries.

Optimal nutrition plays a crucial role in pregnancy. Maternal malnutrition is a risk factor for maternal, fetal, and neonatal complications and is more prevalent in low and middle-income countries (LMICs). This review aims to study the effectiveness of antenatal macronutrient nutritional interventions on maternal, neonatal, and child outcomes. We searched the CENTRAL, PubMed, Embase, and other databases for randomized controlled trials and quasi-experimental designs on healthy pregnant women in LMICs. We also searched grey literature and reports from Google Scholar, Web of Science, and websites of different organizations. Title/abstract screening, full-text screening, and data extraction filtered 15 studies for inclusion. Balanced energy protein (BEP) supplementation (n = 8) studies showed a reduced incidence of perinatal mortality, stillbirths, low birth weight (LBW) infants, small for gestational age (SGA) babies and increased birth weight. Food distribution programs (FDPs) (n =5) witnessed reduced rates of SGA, stunting, wasting, and increased birth weight and birth length. Studies on intervention for obesity prevention (n = 2) showed reductions in birth weight. Other findings were statistically insignificant. Subgroup analyses were conducted to study the effectiveness of supplementation between regions, location, the timing of supplementation and nutritional status; however, there were a limited number of studies in each subgroup. Data from our review supports the antenatal supplementation of BEP and FDP for the prevention of adverse maternal, neonatal, and child outcomes that can be utilized for future policymaking. However, more research is required before recommending obesity prevention programs.

Effectiveness of Interventions for Managing Acute Malnutrition in Children under Five Years of Age in Low-Income and Middle-Income Countries: A Systematic Review and Meta-Analysis.

Childhood malnutrition is a major public health concern, as it is associated with significant short- and long-term morbidity and mortality. The objective of this review was to comprehensively review the evidence for the management of severe acute malnutrition (SAM) and moderate acute malnutrition (MAM) according to the current World Health Organization (WHO) protocol using facility- and community-based approaches, as well as the effectiveness of ready-to-use therapeutic food (RUTF), ready-to-use supplementary food (RUSF), prophylactic antibiotic use, and vitamin A supplementation. We searched relevant electronic databases until 11 February 2019, and performed a meta-analysis. This review summarizes findings from a total of 42 studies (48 papers), including 35,017 children. Limited data show some benefit of integrated community-based screening, identification, and management of SAM and MAM on improving recovery rate. Facility-based screening and management of uncomplicated SAM has no effect on recovery and mortality, while the effect of therapeutic milk F100 for SAM is comparable to RUTF for weight gain and mortality. Local food and whey RUSF are comparable to standard RUSF for recovery rate and weight gain in MAM, while standard RUSF has additional benefits to CSB. Prophylactic antibiotic administration in uncomplicated SAM improves recovery rate and probably improves weight gain and reduces mortality. Limited data suggest that high-dose vitamin A supplementation is comparable with low-dose vitamin A supplementation for weight gain and mortality among children with SAM.

Effects of preventive nutrition interventions among adolescents on health and nutritional status in low- and middle-income countries: A systematic review.

Background: Malnutrition is one of the most common causes of morbidity and mortality among children and adolescents and is now considered to be one of the largest risk factors responsible for the global burden of diseases along with poor diet. Objectives: The objective of this review was to assess the impact of preventive nutrition interventions (including nutrition education and counselling; micronutrient supplementation/fortification and macronutrient supplementation) to improve the health and nutritional status of adolescents aged 10-19 years in low- and middle-income countries (LMICs). The secondary objective of the review was to assess various contextual factors based on the World Health Organisation (WHO) health system building blocks framework that might potentially impact the effectiveness of these interventions for this age group. Search Methods: The search was conducted on Cochrane Controlled Trials Register (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, the WHO nutrition databases, CAB Global Health, Social Science Citation Index, Scopus, WHO Global Health Index, ADOLEC and EPPI until February 5, 2019. We searched Google Scholar along with key nutrition agencies database such as Nutrition International, the Global Alliance for Improved Nutrition, the World Food Programme and HarvestPlus to search for nonindexed, grey literature to locate relevant programme evaluations and any additional trials. All searches were performed without any restrictions on publication date, language or publication status. Selection Criteria: We included randomised controlled trials, quasiexperimental studies, controlled before-after studies and interrupted time series evaluating the effectiveness of preventive nutrition interventions among adolescents between 10 and 19 years of age from LMICs. Data Collection and Analysis: Two review authors independently assessed trials for inclusion, assessed risk of bias and extracted data from included studies. Meta-analysis was conducted separately for each outcome and intervention. For dichotomous data, we reported risk ratios (RR) with 95% confidence intervals (CI). For continuous data, we reported the mean difference (MD) or standard mean difference (SMD) with 95% CI. Main Results: This review summarises findings from a total of 10 studies from 15 papers including 10,802 participants. All the studies included in this review assessed the impact of micronutrient supplementation/fortification on health and nutritional status among adolescents in LMIC. We did not find any study assessing the impact of nutrition education and counselling or on macronutrient supplementation among adolescents. Micronutrient supplementation/fortification interventions included calcium/vitamin D supplementation/fortification, iron supplementation with or without folic acid, zinc supplementation and multiple micronutrient (MMN) fortification. The majority of the studies (eight out of 10 studies) included adolescent girls aged between 10 and 19 years of age. We did not find any large scale preventive nutrition intervention programmes targeting adolescents in LMICs. We are uncertain of the effect of iron supplementation with or without folic acid on anaemia (daily supplementation; RR: 1.04, 95% CI 0.88, 1.24; one study; 1,160 participants; low quality evidence. Weekly supplementation; RR: 1.07, 95% CI: 0.91, 1.26; one study; 1,247 participants; low quality evidence). We are uncertain of the effect of various micronutrient supplementation/fortification on body mass index (calcium/vitamin D supplementation; (MD: -0.01 kg/m2; 95% CI: -1.20, 1.17; two studies; 730 participants; I 2 94%; very low quality evidence, iron supplementation with or without folic acid; MD: 0.29 kg/m2; 95% CI: -0.25, 0.83; two studies; 652 participants; I 2 69%; very low quality evidence, zinc supplementation; MD: 0.35 kg/m2; 95% CI: -0.15, 0.85; one study; 382 participants; very low quality evidence) and MMN fortification; MD: 0.23 kg/m2, 95% CI: -0.11, 0.57; two studies; 943 participants; I 2 22%; very low quality evidence). None of the included studies reported any other primary outcomes including morbidity or adverse effects. Iron supplementation with or without folic acid may improve haemoglobin concentrations (MD: 0.42 g/dL, 95% CI: 0.13, 0.71; four studies; 1,020 participants; I 2 89%; low quality evidence). Calcium/vitamin D supplementation may improve serum 25(OH) D levels (standardised mean difference [SMD]: 2.85, 95% CI: 0.89, 4.82; two studies; 395 participants; I 2 99%; low quality evidence). We are uncertain of the effect of calcium only supplementation (MD: 0.02 g/cm2, 95% CI: -0.00, 0.04; one study; 233 participants; low quality outcome) and calcium + vitamin D supplementation (MD: 0.02 g/cm2, 95% CI: -0.00, 0.04; one study; 235 participants; low quality evidence) on total bone mineral density (BMD). We are uncertain of the effect of MMN fortification on haemoglobin concentrations (MD: -0.10 g/dL, 95% CI: -0.88, 0.68; two studies; 1102 participants; I 2 100%; very low quality evidence); calcium supplementation on total body bone mineral content (BMC); (MD: 30.20 g, 95% CI: -40.56, 100.96; one study; 233 participants; low quality evidence), calcium + vitamin D supplementation on total body BMC (MD: 21.60 g, 95% CI: -45.32, 88.52; one study; 235 participants; low quality evidence) and zinc supplementation on serum zinc levels (SMD: 6.94, 95% CI: -4.84, 18.71; two studies; 494 participants; very low quality evidence). One study reported the impact of iron supplementation with or without folic acid on cognition of adolescent girls suggesting improved cognition in most of the tests with daily or twice weekly supplementation compared to once weekly or no supplementation. None of the other secondary outcomes were reported including any other development outcomes and all-cause mortality. These findings warrant caution while interpreting due to very few studies and high heterogeneity. Authors' Conclusions: There is limited evidence of micronutrient supplementation/fortification among adolescents on health and nutritional status in LMICs, with lack of evidence on nutrition education and counselling and macronutrient supplementation. The findings are generaliseable for adolescent girls since all studies (except one) targeted female adolescents.

Effectiveness of interventions to manage acute malnutrition in children under 5 years of age in low- and middle-income countries: A systematic review.

Background: Childhood malnutrition is a major public health concern as it is associated with significant short- and long-term morbidity and mortality. Objectives: To comprehensively review the evidence for the management of severe acute malnutrition (SAM) and moderate acute malnutrition (MAM) according to the current World Health Organization protocol using facility- and community-based approaches as well as the effectiveness of ready-to-use therapeutic food (RUTF), ready-to-use supplementary food (RUSF), prophylactic antibiotic use and vitamin A supplementation. Search methods: We searched relevant electronic databases till 11 February 2019. No date or language restrictions were applied. Selection criteria: We included randomised controlled trials (RCTs) and quasi-experimental studies including controlled before-after (CBA) studies and interrupted time series (ITS) studies. Data collection and analysis: Two review authors independently screened studies for relevance, extracted data, assessed risk of bias and rated the quality of the evidence using the GRADE approach. We carried out statistical analysis using Review Manager software and set out the main findings of the review in "Summary of findings" tables. Main results: This review summarises findings from a total of 42 studies (48 papers) including 35,017 children. Thirty-three of the included studies were RCTs; six studies were quasi-experimental and three studies were cost studies. Majority of the studies were judged to be at high risk of bias for blinding of the participants, personnel and outcome assessment. Majority of the outcomes were rated as either moderate or low quality. Outcomes were downgraded mainly due to study limitations, high heterogeneity, imprecision and small sample size. Community-based strategies to screen and manage SAM/MAM versus no community-based strategies (two studies): Integrated community-based management probably improves recovery rate by 4% [risk ratio (RR): 1.04; 95% confidence interval (CI): 1.00 to 1.09; one study; 1,957 participants; moderate-quality outcome], and reduces weight gain by 0.8 g·kg-1·day-1 [mean difference (MD): -0.80 g·kg-1·day-1; 95% CI: -0.82 to -0.78; one study; 1,957 participants; moderate-quality outcome] compared with no community-based strategies, while mortality was similar between the two groups (RR: 0.93; 95% CI: 0.60 to 1.45; one study; 1,957 participants; moderate-quality outcome). Facility-based strategies to screen and manage uncomplicated SAM versus other standard of care (four studies): There was no evidence of effect on recovery (RR: 1.00; 95% CI: 0.80, 1.25; one study; 60 participants; very-low-quality evidence) and mortality (RR: 1.21; 95% CI: 0.75 to 1.94; two studies; 473 participants; low-quality outcome). Facility-based management with RUTF versus F100 ("catch-up" formula to rebuild wasted tissues containing 100 kcal and 2.9 g protein per 100 ml) for SAM (three studies): There was no evidence of effect on weight gain (MD: 2 g·kg-1·day-1; 95% CI: -0.23 to 4.23; three studies; 266 participants; very-low-quality outcome) and mortality (RR: 1.20; 95% CI: 0.34 to 4.22; two studies; 168 participants; low-quality outcome). Community-based management of SAM with standard RUTF compared with other foods (14 studies): There was no evidence of effect on recovery rate when standard RUTF was compared to non-milk/peanut butter-based RUTF (RR: 1.03; 95% CI: 0.99 to 1.08; five studies; 5743 participants; I2 50%; moderate quality outcome), energy-dense, home-prepared food (RR: 1.14; 95% CI 0.95 to 1.36; four studies; 959 participants; I2 75%; low quality outcome), or high oleic RUTF (RR: 1.06; 95% CI: 0.85 to 1.31; one study; 141 participants; moderate quality outcome). Standard RUTF may improve weight gain by 0.5 g·kg-1·day-1 (MD: 0.5 g·kg-1·day-1; 95% CI: 0.02 to 0.99; three studies; 3,069 participants; low-quality outcome) when compared with non-milk/peanut butter-based RUTF and by 5.5 g·kg-1·day-1 when compared with F100 (MD: 5.50 g·kg-1·day-1; 95% CI: 2.92 to 8.08; one study; 70 participants; low-quality outcome). There was no evidence of effect on mortality when standard RUTF was compared with other foods (RR: 0.99; 95% CI: 0.69 to 1.41; nine studies; 7,667 participants; low-quality outcome). RUSF for MAM compared with other foods (14 studies): There was no evidence of effect on recovery rate when standard RUSF was compared with local/home made food (RR: 0.92; 95% CI: 0.64 to 1.33; three studies; 435 participants; low-quality outcome) and whey RUSF (RR: 0.96; 95% CI: 0.92 to 1.00; one study; 2230 participants; high-quality outcome); while standard RUSF may improve recovery by 7% when compared with corn-soy blend (CSB) (RR: 1.07; 95% CI: 1.02 to 1.13; six studies; 5,744 participants; low-quality outcome). There was no evidence of effect on weight gain when standard RUSF was compared with local home made food (MD: -0.75 g·kg-1·day-1; 95% CI: -2.03 to 0.43; one study; 73 participants; low-quality outcome) and whey RUSF (MD: -0.16 g·kg-1·day-1; 95% CI: -0.33 to 0.01; one study; 2,230 participants; high-quality outcome); while standard RUSF may improve weight gain by 0.49 g·kg-1·day-1 when compared with CSB (MD: 0.49 g·kg-1·day-1; 95% CI: 0.10 to 0.87; five studies; 4,354 participants; low-quality outcome). There was no evidence of effect on mortality when standard RUSF was compared with other foods (RR: 0.98; 95% CI: 0.57 to 1.68; eight studies; 8,310 participants; moderate-quality outcome). Prophylactic antibiotic versus no antibiotic (three studies): Prophylactic antibiotic therapy for uncomplicated SAM improves recovery rate by 6% (RR: 1.06; 95% CI: 1.03 to 1.08; two studies; 5,166 participants; high-quality outcome), probably improves weight gain by 0.67 g·kg-1·day-1 (MD: 0.67 g·kg-1·day-1; 95% CI: 0.28, 1.06; two studies; 5,052 participants; moderate-quality outcome) and probably reduces mortality by 26% (RR: 0.74; 95% CI: 0.55, 0.98; three studies; 6944 participants; moderate quality outcome) compared to no antibiotics group. High-dose vitamin A versus low-dose vitamin A (two studies): There was no evidence of effect on weight gain (MD: 0.05 g·kg-1·day-1; 95% CI: -0.08 to 0.18; one study; 207 participants; moderate-quality outcome) and mortality (RR: 7.07; 95% CI: 0.37 to 135.13; one study; 207 participants; moderate-quality outcome). Authors' conclusions: Limited data show some benefit of integrated community-based screening, identification and management of SAM and MAM on improving recovery. Facility-based screening and management of uncomplicated SAM has no benefit on recovery and mortality, while the effect of F100 for SAM is similar to RUTF for weight gain and mortality. Local food and whey RUSF have similar effects as standard RUSF on recovery rate and weight gain in MAM, while standard RUSF has additional benefits to CSB. Prophylactic antibiotic administration in uncomplicated SAM improves recovery rate, weight gain and reduces mortality, while limited data suggest that high-dose vitamin A supplementation is comparable with low-dose vitamin A supplementation for weight gain and mortality among children with SAM.

Food fortification with multiple micronutrients: impact on health outcomes in general population.

BACKGROUND: Vitamins and minerals are essential for growth and maintenance of a healthy body, and have a role in the functioning of almost every organ. Multiple interventions have been designed to improve micronutrient deficiency, and food fortification is one of them. OBJECTIVES: To assess the impact of food fortification with multiple micronutrients on health outcomes in the general population, including men, women and children. SEARCH METHODS: We searched electronic databases up to 29 August 2018, including the Cochrane Central Register of Controlled Trial (CENTRAL), the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register and Cochrane Public Health Specialised Register; MEDLINE; Embase, and 20 other databases, including clinical trial registries. There were no date or language restrictions. We checked reference lists of included studies and relevant systematic reviews for additional papers to be considered for inclusion. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-RCTs, quasi-randomised trials, controlled before-after (CBA) studies and interrupted time series (ITS) studies that assessed the impact of food fortification with multiple micronutrients (MMNs). Primary outcomes included anaemia, micronutrient deficiencies, anthropometric measures, morbidity, all-cause mortality and cause-specific mortality. Secondary outcomes included potential adverse outcomes, serum concentration of specific micronutrients, serum haemoglobin levels and neurodevelopmental and cognitive outcomes. We included food fortification studies from both high-income and low- and middle-income countries (LMICs). DATA COLLECTION AND ANALYSIS: Two review authors independently screened, extracted and quality-appraised the data from eligible studies. We carried out statistical analysis using Review Manager 5 software. We used random-effects meta-analysis for combining data, as the characteristics of study participants and interventions differed significantly. We set out the main findings of the review in 'Summary of findings' tables, using the GRADE approach. MAIN RESULTS: We identified 127 studies as relevant through title/abstract screening, and included 43 studies (48 papers) with 19,585 participants (17,878 children) in the review. All the included studies except three compared MMN fortification with placebo/no intervention. Two studies compared MMN fortification versus iodised salt and one study compared MMN fortification versus calcium fortification alone. Thirty-six studies targeted children; 20 studies were conducted in LMICs. Food vehicles used included staple foods, such as rice and flour; dairy products, including milk and yogurt; non-dairy beverages; biscuits; spreads; and salt. Fourteen of the studies were fully commercially funded, 13 had partial-commercial funding, 14 had non-commercial funding and two studies did not specify the source of funding. We rated all the evidence as of low to very low quality due to study limitations, imprecision, high heterogeneity and small sample size. When compared with placebo/no intervention, MMN fortification may reduce anaemia by 32% (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.56 to 0.84; 11 studies, 3746 participants; low-quality evidence), iron deficiency anaemia by 72% (RR 0.28, 95% CI 0.19 to 0.39; 6 studies, 2189 participants; low-quality evidence), iron deficiency by 56% (RR 0.44, 95% CI 0.32 to 0.60; 11 studies, 3289 participants; low-quality evidence); vitamin A deficiency by 58% (RR 0.42, 95% CI 0.28 to 0.62; 6 studies, 1482 participants; low-quality evidence), vitamin B2 deficiency by 64% (RR 0.36, 95% CI 0.19 to 0.68; 1 study, 296 participants; low-quality evidence), vitamin B6 deficiency by 91% (RR 0.09, 95% CI 0.02 to 0.38; 2 studies, 301 participants; low-quality evidence), vitamin B12 deficiency by 58% (RR 0.42, 95% CI 0.25 to 0.71; 3 studies, 728 participants; low-quality evidence), weight-for-age z-scores (WAZ) (mean difference (MD) 0.1, 95% CI 0.02 to 0.17; 8 studies, 2889 participants; low-quality evidence) and weight-for-height/length z-score (WHZ/WLZ) (MD 0.1, 95% CI 0.02 to 0.18; 6 studies, 1758 participants; low-quality evidence). We are uncertain about the effect of MMN fortification on zinc deficiency (RR 0.84, 95% CI 0.65 to 1.08; 5 studies, 1490 participants; low-quality evidence) and height/length-for-age z-score (HAZ/LAZ) (MD 0.09, 95% CI 0.01 to 0.18; 8 studies, 2889 participants; low-quality evidence). Most of the studies in this comparison were conducted in children. Subgroup analyses of funding sources (commercial versus non-commercial) and duration of intervention did not demonstrate any difference in effects, although this was a relatively small number of studies and the possible association between commercial funding and increased effect estimates has been demonstrated in the wider health literature. We could not conduct subgroup analysis by food vehicle and funding; since there were too few studies in each subgroup to draw any meaningful conclusions. When we compared MMNs versus iodised salt, we are uncertain about the effect of MMN fortification on anaemia (R 0.86, 95% CI 0.37 to 2.01; 1 study, 88 participants; very low-quality evidence), iron deficiency anaemia (RR 0.40, 95% CI 0.09 to 1.83; 2 studies, 245 participants; very low-quality evidence), iron deficiency (RR 0.98, 95% CI 0.82 to 1.17; 1 study, 88 participants; very low-quality evidence) and vitamin A deficiency (RR 0.19, 95% CI 0.07 to 0.55; 2 studies, 363 participants; very low-quality evidence). Both of the studies were conducted in children. Only one study conducted in children compared MMN fortification versus calcium fortification. None of the primary outcomes were reported in the study. None of the included studies reported on morbidity, adverse events, all-cause or cause-specific mortality. AUTHORS' CONCLUSIONS: The evidence from this review suggests that MMN fortification when compared to placebo/no intervention may reduce anaemia, iron deficiency anaemia and micronutrient deficiencies (iron, vitamin A, vitamin B2 and vitamin B6). We are uncertain of the effect of MMN fortification on anthropometric measures (HAZ/LAZ, WAZ and WHZ/WLZ). There are no data to suggest possible adverse effects of MMN fortification, and we could not draw reliable conclusions from various subgroup analyses due to a limited number of studies in each subgroup. We remain cautious about the level of commercial funding in this field, and the possibility that this may be associated with higher effect estimates, although subgroup analysis in this review did not demonstrate any impact of commercial funding. These findings are subject to study limitations, imprecision, high heterogeneity and small sample sizes, and we rated most of the evidence low to very low quality. and hence no concrete conclusions could be drawn from the findings of this review.

Effects of Preventive Nutrition Interventions among Adolescents on Health and Nutritional Status in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

The objective of this review was to assess the impact of preventive nutrition interventions on health and nutritional status of adolescents aged 10-19 years in low- and middle-income countries (LMICs). We searched the databases until 5 February 2019 without any restrictions on publication, date, language, or publication status. A total of 10 studies (15 papers) including 10,802 participants assessing the impact of micronutrient supplementation/fortification were included in this review. We did not find any study assessing the impact of nutrition education and counseling or macronutrient supplementation among adolescents. Among primary outcomes, we are uncertain of the effect of iron supplementation with or without folic acid on anemia (daily supplementation; relative risk (RR): 1.04, 95% confidence interval (CI) 0.42, 2.57; one study; 1160 participants; low-quality evidence; weekly supplementation; RR: 1.07, 95% CI: 0.46, 2.52; one study; 1247 participants; low-quality evidence). We are also uncertain of the effect of various micronutrient supplementation/fortification on body mass index (BMI) (calcium/vitamin D supplementation; (MD: -0.01 kg/m2; 95% CI: -1.20, 1.17; two studies; 730 participants; I2 94%; very-low-quality evidence, iron supplementation with or without folic acid; MD: 0.47 kg/m2; 95% CI: -0.17, 1.11; two studies; 652 participants; I2 37%; very-low-quality evidence, zinc supplementation; MD: 0.35 kg/m2; 95% CI: -0.15, 0.85; one study; 382 participants; very-low-quality evidence) and multiple micronutrient (MMN) fortification; MD: 0.23 kg/m2, 95% CI: -0.11, 0.57; two studies; 943 participants; I2 22%; very-low-quality evidence). None of the included studies reported any other primary outcomes including morbidity or adverse effects. Among secondary outcomes, iron supplementation with or without folic acid may improve hemoglobin concentrations, and calcium/vitamin D supplementation may improve serum 25(OH)D levels, while calcium only supplementation and calcium and vitamin D supplementation may marginally improve total body bone mineral density (BMD). We are uncertain of the effect of MMN fortification on hemoglobin concentrations, calcium supplementation on total body bone mineral content (BMC), calcium + vitamin D supplementation on total body BMC, and zinc supplementation on zinc levels. There is limited evidence of micronutrient supplementation/fortification among adolescents, especially adolescent boys, on health and nutritional status in LMICs. These findings should be interpreted with caution due to the low quality and limited number of studies.

Preventive lipid-based nutrient supplements given with complementary foods to infants and young children 6 to 23 months of age for health, nutrition, and developmental outcomes.

BACKGROUND: One nutritional intervention advocated to prevent malnutrition among children is lipid-based nutrient supplements (LNS). LNS provide a range of vitamins and minerals, but unlike most other micronutrient supplements, LNS also provide energy, protein and essential fatty acids. Alternative recipes and formulations to LNS include fortified blended foods (FBF), which are foods fortified with vitamins and minerals, and micronutrient powders (MNP), which are a combination of vitamins and minerals, OBJECTIVES: To assess the effects and safety of preventive LNS given with complementary foods on health, nutrition and developmental outcomes of non-hospitalised infants and children six to 23 months of age, and whether or not they are more effective than other foods (including FBF or MNP).This review did not assess the effects of LNS as supplementary foods or therapeutic foods in the management of moderate and severe acute malnutrition. SEARCH METHODS: In October 2018, we searched CENTRAL, MEDLINE, Embase, 21 other databases and two trials registers for relevant studies. We also checked the reference lists of included studies and relevant reviews and contacted the authors of studies and other experts in the area for any ongoing and unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs that evaluated the impact of LNS plus complementary foods given at point-of-use (for any dose, frequency, duration) to non-hospitalised infants and young children aged six to 23 months in stable or emergency settings and compared to no intervention, other supplementary foods (i.e. FBF), nutrition counselling or multiple micronutrient supplements or powders for point-of-use fortification of complementary foods. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies for relevance and, for those studies included in the review, extracted data, assessed risk of bias and rated the quality of the evidence using the GRADE approach. We carried out statistical analysis using Review Manager software. We used a random-effects meta-analysis for combining data as the interventions differed significantly. We set out the main findings of the review in 'Summary of findings' tables,. MAIN RESULTS: Our search identified a total of 8124 records, from which we included 17 studies (54 papers) with 23,200 children in the review. The included studies reported on one or more of the pre-specified primary outcomes, and five studies included multiple comparison groups.Overall, the majority of trials were at low risk of bias for random sequence generation, allocation concealment, blinding of outcome assessment, incomplete outcome data, selective reporting and other sources of bias, but at high risk of bias for blinding of participants and personnel due to the nature of the intervention. Using the GRADE approach, we judged the quality of the evidence for most outcomes as low or moderate.LNS+complementary feeding compared with no intervention Thirteen studies compared LNS plus complementary feeding with no intervention. LNS plus complementary feeding reduced the prevalence of moderate stunting by 7% (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.88 to 0.98; nine studies, 13,372 participants; moderate-quality evidence), severe stunting by 15% (RR 0.85, 95% CI 0.74 to 0.98; five studies, 6151 participants; moderate-quality evidence), moderate wasting by 18% (RR 0.82, 95% CI 0.74 to 0.91; eight studies; 13,172 participants; moderate-quality evidence), moderate underweight by 15% (RR 0.85, 95% CI 0.80 to 0.91; eight studies, 13,073 participants; moderate-quality evidence), and anaemia by 21% (RR 0.79, 95% CI 0.69 to 0.90; five studies, 2332 participants; low-quality evidence). There was no impact of LNS plus complementary feeding on severe wasting (RR 1.27, 95% CI 0.66 to 2.46; three studies, 2329 participants) and severe underweight (RR 0.78, 95%CI 0.54 to 1.13; two studies, 1729 participants). Adverse effects did not differ between the groups (RR 0.86, 95% CI 0.74 to 1.01; three studies, 3382 participants).LNS+complementary feeding compared with FBF Five studies compared LNS plus complementary feeding with other FBF, including corn soy blend and UNIMIX. We pooled four of the five studies in meta-analyses and found that, when compared to other FBF, LNS plus complementary feeding significantly reduced the prevalence of moderate stunting (RR 0.89, 95% CI 0.82 to 0.97; three studies, 2828 participants; moderate-quality evidence), moderate wasting (RR 0.79, 95% CI 0.65 to 0.97; two studies, 2290 participants; moderate-quality evidence), and moderate underweight (RR 0.81, 95% CI 0.73 to 0.91; two studies, 2280 participants; moderate-quality evidence). We found no difference between LNS plus complementary feeding and FBF for severe stunting (RR 0.41, 95% CI 0.12 to 1.42; two studies, 729 participants; low-quality evidence), severe wasting (RR 0.64, 95% CI 0.19 to 2.81; two studies, 735 participants; moderate-quality evidence), and severe underweight (RR 1.23, 95% CI 0.67 to 2.25; one study, 173 participants; low-quality evidence).LNS+complementary feeding compared with MNP Four studies compared LNS plus complementary feeding with MNP. We pooled data from three of the four studies in meta-analyses and found that compared to MNP, LNS plus complementary feeding significantly reduced the prevalence of moderate underweight (RR 0.88, 95% CI 0.78 to 0.99; two studies, 2004 participants; moderate-quality evidence) and anaemia (RR 0.38, 95% CI 0.21 to 0.68; two studies, 557 participants; low-quality evidence). There was no difference between LNS plus complementary feeding and MNP for moderate stunting (RR 0.92, 95% CI 0.82 to 1.02; three studies, 2365 participants) and moderate wasting (RR 0.97, 95% CI 0.77 to 1.23; two studies, 2004 participants). AUTHORS' CONCLUSIONS: The findings of this review suggest that LNS plus complementary feeding compared to no intervention is effective at improving growth outcomes and anaemia without adverse effects among children aged six to 23 months in low- and middle-income countries (LMIC) in Asia and Africa, and more effective if provided over a longer duration of time (over 12 months). Limited evidence also suggests that LNS plus complementary feeding is more effective than FBF and MNP at improving growth outcomes.

Integrating nutrition into health systems: What the evidence advocates.

There is considerable evidence of positive health and nutrition outcomes resulting from integrating nutrition-specific interventions into health systems; however, current knowledge on establishing and sustaining effective integration of nutrition into health systems is limited. The objective of this review is to map the existing types of integration platforms and review the evidence on integrated health and nutrition programmes' impacts on specific nutrition outcomes. A literature search was conducted, and integrated nutrition programmes were examined through the lens of the six World Health Organization (WHO) building blocks, including the demand side. Forty-five studies were included in this review, outlining the integration of nutrition-specific interventions with various programmes, including integrated community case management and Integrated Management of Childhood Illness, Child Health Days, immunization, early child development, and cash transfers. Limited quantitative data were suggestive of some positive impact on nutrition and non-nutrition outcomes with no adverse effects on primary programme delivery. Through the lens of the six WHO building blocks, service delivery and health workforce were found to be well-integrated, but governance, information systems, finance and supplies and technology were less well-integrated. Integrating nutrition-specific interventions into health systems may ensure efficient service delivery while having an impact on nutrition outcomes. There is no single successful model of integration; it varies according to the context and demands of the particular setting in which integration occurs. There is a need for more well-planned programmes considering all the health systems building blocks to ensure compliance and sustainability.

Lipid-based nutrient supplements for maternal, birth, and infant developmental outcomes.

BACKGROUND: Ready-to-use lipid-based nutrient supplements (LNS) are a highly nutrient-dense supplement, which could be a good source of macro- and micronutrients for pregnant women who need to supplement their nutrient intake. OBJECTIVES: To assess the effects of LNS for maternal, birth and infant outcomes in pregnant women. Secondary objectives were to explore the most appropriate composition, frequency and duration of LNS administration. SEARCH METHODS: In May 2018, we searched CENTRAL, MEDLINE, Embase, 22 other databases and two trials registers for any published and ongoing studies. We also checked the reference lists of included studies and relevant reviews, and we contacted the authors of included studies and other experts in the field to identify any studies we may have missed, including any unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that compared LNS given in pregnancy to no intervention, placebo, iron folic acid (IFA), multiple micronutrients (MMN) or nutritional counselling. DATA COLLECTION AND ANALYSIS: We used standard Cochrane procedures. MAIN RESULTS: We included four studies in 8018 pregnant women. All four studies took place in stable community settings in low- and middle-income countries: Bangladesh, Burkina Faso, Ghana and Malawi. None were in emergency settings. The oldest trial was published in 2009. Of the four included studies, one compared LNS to IFA, one compared LNS to MMN, and two compared LNS to both IFA and MMN.We considered the included studies to be of medium to high quality, and we rated the quality of the evidence as moderate using the GRADE approach.LNS versus IFAMaternal outcomes: there was no difference between the LNS and IFA groups as regards maternal gestational weight gain per week (standard mean difference (SMD) 0.46, 95% confidence interval (CI) -0.44 to 1.36; 2 studies, 3539 participants). One study (536 participants) showed a two-fold increase in the prevalence of maternal anaemia in the LNS group compared to the IFA group, but no difference between the groups as regards adverse effects. There was no difference between the two groups for maternal mortality (risk ratio (RR) 0.53, 95% CI 0.12 to 2.41; 3 studies, 5628 participants).Birth and infant outcomes: there was no difference between the LNS and IFA groups for low birth weight (LBW) (RR 0.87, 95% CI 0.72 to 1.05; 3 studies, 4826 participants), though newborns in the LNS group had a slightly higher mean birth weight (mean difference (MD) 53.28 g, 95% CI 28.22 to 78.33; 3 studies, 5077 participants) and birth length (cm) (MD 0.24 cm, 95% CI 0.11 to 0.36; 3 studies, 4986 participants). There was a reduction in the proportion of infants who were small for gestational age (SGA) (RR 0.94, 95% CI 0.89 to 0.99; 3 studies, 4823 participants) and had newborn stunting (RR 0.82, 95% CI 0.71 to 0.94; 2 studies, 4166 participants) in the LNS group, but no difference between the LNS and IFA groups for preterm delivery (RR 0.94, 95% CI 0.80 to 1.11; 4 studies, 4924 participants), stillbirth (RR 1.14; 95% CI 0.52 to 2.48; 3 studies, 5575 participants) or neonatal death (RR 0.96, 95% CI 0.14 to 6.51). The current evidence for child developmental outcomes is not sufficient to draw any firm conclusions.LNS versus MMNMaternal outcomes: one study (662 participants) showed no difference between the LNS and MMN groups as regards gestational weight gain per week or adverse effects. Another study (557 participants) showed an increased risk of maternal anaemia in the LNS group compared to the MMN group.Birth and infant outcomes: there was no difference between the LNS and MMN groups for LBW (RR 0.92, 95% CI 0.74 to 1.14; 3 studies, 2404 participants), birth weight (MD 23.67 g, 95% CI -10.53 to 57.86; 3 studies, 2573 participants), birth length (MD 0.20 cm, 95% CI -0.02 to 0.42; 3 studies, 2567 participants), SGA (RR 0.95, 95% CI 0.84 to 1.07; 3 studies, 2393 participants), preterm delivery (RR 1.15, 95% CI 0.93 to 1.42; 3 studies, 2630 participants), head circumference z score (MD 0.10, 95% CI -0.01 to 0.21; 2 studies, 1549 participants) or neonatal death (RR 0.88, 95% CI 0.36 to 2.15; 1 study, 1175 participants). AUTHORS' CONCLUSIONS: Findings from this review suggest that LNS supplementation has a slight, positive effect on weight at birth, length at birth, SGA and newborn stunting compared to IFA. LNS and MMN were comparable for all maternal, birth and infant outcomes. Both IFA and MMN were better at reducing maternal anaemia when compared to LNS. We did not find any trials for LNS given to pregnant women in emergency settings.Readers should interpret the beneficial findings of the review with caution since the evidence comes from a small number of trials, with one-large scale study (conducted in community settings in Bangladesh) driving most of the impact. In addition, effect sizes are too small to propose any concrete recommendation for practice.

Neonatal interventions for preventing cerebral palsy: an overview of Cochrane Systematic Reviews.

BACKGROUND: Cerebral palsy is an umbrella term that encompasses disorders of movement and posture attributed to non-progressive disturbances occurring in the developing foetal or infant brain. As there are diverse risk factors and aetiologies, no one strategy will prevent cerebral palsy. Therefore, there is a need to systematically consider all potentially relevant interventions for prevention. OBJECTIVES: PrimaryTo summarise the evidence from Cochrane Systematic Reviews regarding effects of neonatal interventions for preventing cerebral palsy (reducing cerebral palsy risk).SecondaryTo summarise the evidence from Cochrane Systematic Reviews regarding effects of neonatal interventions that may increase cerebral palsy risk. METHODS: We searched the Cochrane Database of Systematic Reviews (27 November 2016) for reviews of neonatal interventions reporting on cerebral palsy. Two review authors assessed reviews for inclusion, extracted data, and assessed review quality (using AMSTAR and ROBIS) and quality of the evidence (using the GRADE approach). Reviews were organised by topic; findings were summarised in text and were tabulated. Interventions were categorised as effective (high-quality evidence of effectiveness); possibly effective (moderate-quality evidence of effectiveness); ineffective (high-quality evidence of harm); probably ineffective (moderate-quality evidence of harm or lack of effectiveness); and no conclusions possible (low- to very low-quality evidence). MAIN RESULTS: Forty-three Cochrane Reviews were included. A further 102 reviews pre-specified the outcome cerebral palsy, but none of the included randomised controlled trials (RCTs) reported this outcome. Included reviews were generally of high quality and had low risk of bias, as determined by AMSTAR and ROBIS. These reviews involved 454 RCTs; data for cerebral palsy were available from 96 (21%) RCTs involving 15,885 children. Review authors considered interventions for neonates with perinatal asphyxia or with evidence of neonatal encephalopathy (3); interventions for neonates born preterm and/or at low or very low birthweight (33); and interventions for other specific groups of 'at risk' neonates (7). Quality of evidence (GRADE) ranged from very low to high.Interventions for neonates with perinatal asphyxia or with evidence of neonatal encephalopathyEffective interventions: high-quality evidence of effectivenessResearchers found a reduction in cerebral palsy following therapeutic hypothermia versus standard care for newborns with hypoxic ischaemic encephalopathy (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.54 to 0.82; seven trials; 881 children).No conclusions possible: very low-quality evidenceOne review observed no clear differences in cerebral palsy following therapeutic hypothermia versus standard care.Interventions for neonates born preterm and/or at low or very low birthweightPossibly effective interventions: moderate-quality evidence of effectivenessResearchers found a reduction in cerebral palsy with prophylactic methylxanthines (caffeine) versus placebo for endotracheal extubation in preterm infants (RR 0.54, 95% CI 0.32 to 0.92; one trial; 644 children).Probably ineffective interventions: moderate-quality evidence of harmResearchers reported an increase in cerebral palsy (RR 1.45, 95% CI 1.06 to 1.98; 12 trials; 1452 children) and cerebral palsy in assessed survivors (RR 1.50, 95% CI 1.13 to 2.00; 12 trials; 959 children) following early (at less than eight days of age) postnatal corticosteroids versus placebo or no treatment for preventing chronic lung disease in preterm infants.Probably ineffective interventions: moderate-quality evidence of lack of effectivenessTrial results showed no clear differences in cerebral palsy following ethamsylate versus placebo for prevention of morbidity and mortality in preterm or very low birthweight infants (RR 1.13, 95% CI 0.64 to 2.00; three trials, 532 children); volume expansion versus no treatment (RR 0.76, 95% CI 0.48 to 1.20; one trial; 604 children); gelatin versus fresh frozen plasma (RR 0.94, 95% CI 0.52 to 1.69; one trial, 399 children) for prevention of morbidity and mortality in very preterm infants; prophylactic indomethacin versus placebo for preventing mortality and morbidity in preterm infants (RR 1.04, 95% CI 0.77 to 1.40; four trials; 1372 children); synthetic surfactant versus placebo for respiratory distress syndrome in preterm infants (RR 0.76, 95% CI 0.55 to 1.05; five trials; 1557 children); or prophylactic phototherapy versus standard care (starting phototherapy when serum bilirubin reached a pre-specified level) for preventing jaundice in preterm or low birthweight infants (RR 0.96, 95% CI 0.50 to 1.85; two trials; 756 children).No conclusions possible: low- to very low-quality evidenceNo clear differences in cerebral palsy were observed with interventions assessed in 21 reviews.Interventions for other specific groups of 'at risk' neonatesNo conclusions possible: low- to very low-quality evidenceReview authors observed no clear differences in cerebral palsy with interventions assessed in five reviews. AUTHORS' CONCLUSIONS: This overview summarises evidence from Cochrane Systematic Reviews regarding effects of neonatal interventions on cerebral palsy, and can be used by researchers, funding bodies, policy makers, clinicians, and consumers to aid decision-making and evidence translation. To formally assess other benefits and/or harms of included interventions, including impact on risk factors for cerebral palsy, review of the included Reviews is recommended.Therapeutic hypothermia versus standard care for newborns with hypoxic ischaemic encephalopathy can prevent cerebral palsy, and prophylactic methylxanthines (caffeine) versus placebo for endotracheal extubation in preterm infants may reduce cerebral palsy risk. Early (at less than eight days of age) postnatal corticosteroids versus placebo or no treatment for preventing chronic lung disease in preterm infants may increase cerebral palsy risk.Cerebral palsy is rarely identified at birth, has diverse risk factors and aetiologies, and is diagnosed in approximately one in 500 children. To date, only a small proportion of Cochrane Systematic Reviews assessing neonatal interventions have been able to report on this outcome. There is an urgent need for long-term follow-up of RCTs of such interventions addressing risk factors for cerebral palsy (through strategies such as data linkage with registries) and for consideration of the use of relatively new interim assessments (including the General Movements Assessment). Such RCTs must be rigorous in their design and must aim for consistency in cerebral palsy outcome measurement and reporting to facilitate pooling of data and thus to maximise research efforts focused on prevention.