Search

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.

Background The preconception period is an ideal time to introduce interventions relating to nutrition and other lifestyle factors to ensure good pregnancy preparedness, and to promote health of mothers and babies. In adolescents, malnutrition and early pregnancy are the common challenges, particularly among those who live in low‐ and middle‐income countries (LMIC) where 99% of all maternal and newborn deaths occur. These girls receive little or no attention until their first pregnancy and often the interventions after pregnancy are too late to revert any detrimental health risks that may have occurred due to malnutrition and early pregnancy. Objectives To synthesise the evidence of the effectiveness of preconception care interventions relating to delayed age at first pregnancy, optimising inter‐pregnancy intervals, periconception folic acid, and periconception iron‐folic acid supplementation on maternal, pregnancy, birth and child outcomes. Search Methods Numerous electronic databases (e.g., CINAHL, ERIC) and databases of selected development agencies or research firms were systematically searched for all available years up to July 2019. In addition, we searched the reference lists of relevant articles and reviews, and asked experts in the area about ongoing and unpublished studies. Selection Criteria Primary studies, including large‐scale programme evaluations that assessed the effectiveness of interventions using randomised controlled trials (RCTs) or quasi‐experimental designs (natural experiments, controlled before‐after studies, regression discontinuity designs, interrupted time series [ITS]), that targeted women of reproductive age (i.e., 10–49 years) during the pre‐ and periconceptional period in LMICs were included. Interventions were compared against no intervention, standard of care or placebo. Data Collection and Analysis Two or more review authors independently reviewed searches, selected studies for inclusion or exclusion, extracted data and assessed risk of bias. We used random‐effects model to conduct meta‐analyses, given the diverse contexts, participants, and interventions, and separate meta‐analyses for the same outcome was performed with different study designs (ITS, RCTs and controlled before after studies). For each comparison, the findings were descriptively summarised in text which included detailing the contextual factors (e.g., setting) to assess their impact on the implementation and effectiveness of each intervention. Main Results We included a total of 43 studies; two of these were included in both delaying pregnancy and optimising interpregnancy intervals resulting in 26 studies for delaying the age at first pregnancy (14 RCTs, 12 quasi‐experimental), four for optimising interpregnancy intervals (one RCT, three quasi‐experimental), five on periconceptional folic acid supplementation (two RCTs, three quasi‐experimental), and 10 on periconceptional iron‐folic acid supplementation (nine RCTs, one quasi‐experimental). Geographically, studies were predominantly conducted across Africa and Asia, with few studies from North and Central America and took place in a combination of settings including community, schools and clinical. The education on sexual health and contraception interventions to delay the age at first pregnancy may make little or no difference on risk of unintended pregnancy (risk ratio [RR], 0.42; 95% confidence internal [CI], 0.07–3.26; two studies, =490; random‐effect; χ 2 p .009; I 2 = 85%; low certainty of evidence using GRADE assessment), however, it significantly improved the use of condom (ever) (RR, 1.54; 95% CI, 1.08–2.20; six studies, n = 1604; random‐effect, heterogeneity: χ 2 p .004; I 2 = 71%). Education on sexual health and and provision of contraceptive along with involvement of male partneron optimising interpregnancy intervals probably makes little or no difference on the risk of unintended pregnancies when compared to education on sexual health only (RR, 0.32; 95% CI, 0.01–7.45; one study, n = 45; moderate certainty of evidence using GRADE assessments). However, education on sexual health and contraception intervention alone or with provision of contraceptive showed a significant improvement in the uptake of contraceptive method. We are uncertain whether periconceptional folic acid supplementation reduces the incidence of neural tube defects (NTDs) (RR, 0.53; 95% CI, 0.41–0.77; two studies, n = 248,056; random‐effect; heterogeneity: χ 2 p .36; I 2 = 0%; very low certainty of evidence using GRADE assessment). We are uncertain whether preconception iron‐folic acid supplementation reduces anaemia (RR, 0.66; 95% CI, 0.53–0.81; six studies; n = 3430, random‐effect; heterogeneity: χ 2 p

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.

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; I2 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; I2 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; I2 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; I2 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; I2 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; I2 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.

Adolescence is a critical stage in the life cycle, and adequate nutrition is necessary for the proper growth and development of individuals and their offspring. Here, we comprehensively review all published systematic reviews (through October 2016) on adolescents (10-19 years) and women of reproductive age, including pregnant women, which targeted interventions related to nutrition. For interventions where there was no existing systematic review on adolescents, we reviewed primary studies/trials. We included interventions on micronutrient supplementation (iron, folic acid, iron-folic acid (IFA), calcium, vitamin D, vitamin A, zinc, iodine, and multiple micronutrients), food/protein energy supplementation, nutrition education for pregnant adolescents, obesity prevention and management, and management of gestational diabetes. We identified a total of 35 systematic reviews, of which only five were conducted on adolescents, and 107 primary studies on adolescents. Our review suggests that iron alone, IFA, zinc, and multiple micronutrient supplementation in adolescents can significantly improve serum hemoglobin concentration. While zinc supplementation in pregnant adolescents showed improvements in preterm birth and low birth weight, we found a paucity of trials on calcium, vitamin D, vitamin A, and iodine supplementation. We found limited evidence on food/protein energy supplementation in adolescents. Interventions to prevent and manage obesity showed a nonsignificant impact on reducing body mass index. This review underscores the importance of adolescent nutrition interventions. It is imperative that countries design nutritional interventions, particularly for adolescents.

The economic and social well-being of any country will one day depend on its current adolescent population. To provide a good foundation for healthy adolescent development, healthy diet, along with physical activity and adequate nutrients, is necessary. Therefore, addressing the nutrition needs of adolescents could be an important step toward breaking the vicious cycle of intergenerational malnutrition, chronic diseases, and poverty. These problems could be addressed with timely recognition and appropriately delivered interventions. Our aim here is to review the existing guidelines on various aspects of nutrition interventions for adolescents and young women. We review all of the major existing guidelines on adolescent nutrition. We were able to find 18 guideline bodies that covered some form of nutritional advice in guidelines that targeted adolescents. Although the guidelines that focus specifically on this age group are limited in scope, we also extrapolated recommendations from guidelines focused on adults, women of reproductive age, and pregnant women, which were based on evidence that included populations of adolescent girls. We were able to extract and synthesize specific directives for nutrition in adolescents, macro- and micronutrient supplementation, exercise, obesity, and nutrition during preconception, pregnancy, and the postconception period.

Adolescence is the period of development that begins at puberty and ends in early adulthood. Most commonly, adolescence is divided into three developmental periods: early adolescence (10-14 years of age), late adolescence (15-19 years of age), and young adulthood (20-24 years of age). Adolescence is marked by physical and sexual maturation, social and economic independence, development of identity, acquisition of skills needed to carry out adult relationships and roles, and the capacity for abstract reasoning. Adolescence is characterized by a rapid pace of growth that is second only to that of infancy. Nutrition and the adolescent transition are closely intertwined, since eating patterns and behaviors are influenced by many factors, including peer influences, parental modeling, food availability, food preferences, cost, convenience, personal and cultural beliefs, mass media, and body image. Here, we describe the physiology, metabolism, and nutritional requirements for adolescents and pregnant adolescents, as well as nutrition-related behavior and current trends in adolescent nutrition. We conclude with thoughts on the implications for nutrition interventions and priority areas that would require further investigation.

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.

Background The preconception period is an ideal time to introduce interventions relating to nutrition and other lifestyle factors to ensure good pregnancy preparedness, and to promote health of mothers and babies. In adolescents, malnutrition and early pregnancy are the common challenges, particularly among those who live in low‐ and middle‐income countries (LMIC) where 99% of all maternal and newborn deaths occur. These girls receive little or no attention until their first pregnancy and often the interventions after pregnancy are too late to revert any detrimental health risks that may have occurred due to malnutrition and early pregnancy. Objectives To synthesise the evidence of the effectiveness of preconception care interventions relating to delayed age at first pregnancy, optimising inter‐pregnancy intervals, periconception folic acid, and periconception iron‐folic acid supplementation on maternal, pregnancy, birth and child outcomes. Search Methods Numerous electronic databases (e.g., CINAHL, ERIC) and databases of selected development agencies or research firms were systematically searched for all available years up to July 2019. In addition, we searched the reference lists of relevant articles and reviews, and asked experts in the area about ongoing and unpublished studies. Selection Criteria Primary studies, including large‐scale programme evaluations that assessed the effectiveness of interventions using randomised controlled trials (RCTs) or quasi‐experimental designs (natural experiments, controlled before‐after studies, regression discontinuity designs, interrupted time series [ITS]), that targeted women of reproductive age (i.e., 10–49 years) during the pre‐ and periconceptional period in LMICs were included. Interventions were compared against no intervention, standard of care or placebo. Data Collection and Analysis Two or more review authors independently reviewed searches, selected studies for inclusion or exclusion, extracted data and assessed risk of bias. We used random‐effects model to conduct meta‐analyses, given the diverse contexts, participants, and interventions, and separate meta‐analyses for the same outcome was performed with different study designs (ITS, RCTs and controlled before after studies). For each comparison, the findings were descriptively summarised in text which included detailing the contextual factors (e.g., setting) to assess their impact on the implementation and effectiveness of each intervention. Main Results We included a total of 43 studies; two of these were included in both delaying pregnancy and optimising interpregnancy intervals resulting in 26 studies for delaying the age at first pregnancy (14 RCTs, 12 quasi‐experimental), four for optimising interpregnancy intervals (one RCT, three quasi‐experimental), five on periconceptional folic acid supplementation (two RCTs, three quasi‐experimental), and 10 on periconceptional iron‐folic acid supplementation (nine RCTs, one quasi‐experimental). Geographically, studies were predominantly conducted across Africa and Asia, with few studies from North and Central America and took place in a combination of settings including community, schools and clinical. The education on sexual health and contraception interventions to delay the age at first pregnancy may make little or no difference on risk of unintended pregnancy (risk ratio [RR], 0.42; 95% confidence internal [CI], 0.07–3.26; two studies, =490; random‐effect; χ 2 p .009; I 2 = 85%; low certainty of evidence using GRADE assessment), however, it significantly improved the use of condom (ever) (RR, 1.54; 95% CI, 1.08–2.20; six studies, n = 1604; random‐effect, heterogeneity: χ 2 p .004; I 2 = 71%). Education on sexual health and and provision of contraceptive along with involvement of male partneron optimising interpregnancy intervals probably makes little or no difference on the risk of unintended pregnancies when compared to education on sexual health only (RR, 0.32; 95% CI, 0.01–7.45; one study, n = 45; moderate certainty of evidence using GRADE assessments). However, education on sexual health and contraception intervention alone or with provision of contraceptive showed a significant improvement in the uptake of contraceptive method. We are uncertain whether periconceptional folic acid supplementation reduces the incidence of neural tube defects (NTDs) (RR, 0.53; 95% CI, 0.41–0.77; two studies, n = 248,056; random‐effect; heterogeneity: χ 2 p .36; I 2 = 0%; very low certainty of evidence using GRADE assessment). We are uncertain whether preconception iron‐folic acid supplementation reduces anaemia (RR, 0.66; 95% CI, 0.53–0.81; six studies; n = 3430, random‐effect; heterogeneity: χ 2 p

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.

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 IFA Maternal 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 MMN Maternal 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.

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.

Background Infections during pregnancy confers increased risk of maternal and perinatal morbidity and mortality. However, the case for advocating Haemophilus influenzae type B (Hib) and viral Influenza vaccinations in pregnancy is still debatable. Objectives To assess the impact of Hib and viral Influenza vaccinations during pregnancy on maternal, neonatal and infant health outcomes compared to placebo/control. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (29 January 2015) and reference lists of retrieved studies. Selection criteria All randomised controlled clinical trials (including cluster-randomised trials) and quasi-randomised trials evaluating Hib or viral influenza vaccination during pregnancy compared with no vaccination or placebo. Data collection and analysis Two review authors independently assessed trials for inclusion, risk of bias and extracted data. Data were checked for accuracy. Main results Two trials were included this review. One (involving 213 women and 213 neonates) evaluated the impact of Hib vaccination during pregnancy and the other study (involving 2116 women and 2049 neonates) evaluated the impact of viral influenza vaccination during pregnancy. Overall, the HiB vaccination trial was judged to be at 'high risk of bias' due to inadequate randomisation while the other trial was judged to be at 'low risk of bias'. Hib vaccination during pregnancy versus placebo One trial involving 213 women and 213 neonates evaluating the impact of Hib vaccination during pregnancy was included under this comparison. The study did not report on any of this review's prespecified primary outcomes (including mortality, respiratory tract infection and sepsis) or secondary outcomes (including adverse events) except preterm delivery. There was no clear difference between the Hib vaccination and placebo control groups in terms of preterm delivery (risk ratio (RR) 1.28, 95% confidence interval (CI) 0.12 to 13.86, one study, 213 participants), fetal distress (RR 1.23, 95% CI 0.67 to 2.26, one study, 213 infants), intubation (RR 1.03, 95% CI 0.55 to 1.95, one study, 213 infants) and neonatal jaundice (RR 1.01, 95% CI 0.52 to 1.97, one study, 213 infants). We could not grade the evidence for quality due to lack of outcome data. Viral influenza vaccination during pregnancy versus placebo One trial involving 2116 women and 2049 infants evaluating the impact of trivalent inactivated influenza vaccine (IIV3) during pregnancy was included under this comparison. There was no clear difference between the viral influenza and placebo control group in terms of most of this review's primary outcomes: maternal death (RR 4.96, 95% CI 0.24 to 103.24, moderate quality evidence), infant death up to 175 days after birth (RR 0.71, 95% CI 0.37 to 1.37, moderate quality evidence), perinatal death (stillbirth and death in the first week of life) (RR 1.32, 95% CI 0.73 to 2.38, moderate quality evidence), influenza-like illness in women (RR 0.96, 95% CI 0.79 to 1.16) or their babies (RR 1.02, 95% CI 0.94 to 1.09), any respiratory illness in women (RR 0.97, 95% CI 0.91 to 1.04, high quality evidence) or their babies (RR 1.01, 95% CI 0.95 to 1.07, high quality evidence). There were also no clear differences between vaccination and placebo control groups in terms of maternal hospitalisation for any infection (RR 2.27, 95% CI 0.94 to 5.49; 2116 women, moderate quality evidence), and neonatal hospitalisation for sepsis (RR 1.60, 95% CI 0.73 to 3.50; 2049 infants, moderate quality evidence). However, viral influenza vaccination during pregnancy was associated with a reduction in reverse-transcriptase–polymerase-chain-reaction (RT-PCR) confirmed influenza among infants (RR 0.51, 95% CI 0.30 to 0.88, one study, 2049 infants) and women (RR 0.50, 95% CI 0.29 to 0.86, one study, 2116 women). In terms of this review's secondary outcomes, there were no clear differences in terms of the impact on pregnancy outcomes (miscarriage, preterm labour and stillbirth), hospitalisation for respiratory infection among women and infants. Similarly, there was no difference between the viral influenza vaccine and placebo control groups in terms of any adverse systemic reactions. Authors' conclusions There is limited evidence (from one small trial at a high risk of bias) on the effectiveness on Hib during pregnancy for improving maternal, neonatal and infant health outcomes. Evidence from one large high quality trial on the effectiveness of viral influenza vaccine during pregnancy suggests reduced RT-PCR confirmed influenza among women and their babies, suggesting the potential of this strategy for scale up but further evidence from varying contexts is required. Further trials for both Hib and viral influenza vaccines with appropriate study designs and suitable comparison groups are required. There are currently two 'ongoing' studies - these will be incorporated into the review in future updates.

Background Worldwide, pneumonia is the leading cause of death amongst children under five years of age, and accounts for approximately two million deaths annually. Pneumonia can be classified according to the World Health Organization (WHO) guidelines. Classification includes assessment of certain clinical signs and symptoms, and the severity of the disease. Treatment is then tailored according to the classification. For non-severe pneumonia, the WHO recommends treatment with oral antibiotics. We used the 2014 WHO definition of non-severe pneumonia for this review: an acute episode of cough, or difficulty in breathing, combined with fast breathing and chest indrawing. The WHO recommends treating non-severe pneumonia with oral antibiotics. Pneumonia is more commonly caused by viruses that do not require antibiotic treatment, but pneumonia caused by bacteria needs management with antibiotics to avoid complications. There is no clear way to quickly distinguish between viral and bacterial pneumonia. It is considered safe to give antibiotics, however, this may lead to the development of antibiotic resistance, and thus, limit their use in future infections. Therefore, it is essential to explore the efficacy of antibiotics for children with WHO-defined non-severe pneumonia and wheeze. Objectives To evaluate the efficacy of antibiotic therapy versus no antibiotic therapy for children aged 2 to 59 months with WHO-defined non-severe pneumonia and wheeze. Search methods We searched CENTRAL, MEDLINE, Embase, four other databases, and two trial registers (December 2020). Selection criteria We included randomised controlled trials (RCTs) evaluating the efficacy of antibiotic therapy versus no antibiotic therapy for children, aged 2 to 59 months, with non-severe pneumonia and wheeze. We defined non-severe pneumonia as 'a cough or difficulty in breathing, with rapid breathing (a respiratory rate of 50 breaths per minute or more for children aged 2 to 12 months, or a respiratory rate of 40 breaths per minute or more for children aged 12 to 59 months), chest indrawing and wheeze'. We excluded trials involving children with severe or very severe pneumonia, and non-RCTs. Data collection and analysis Our primary outcomes were clinical cure and treatment failure; secondary outcomes were relapse, mortality, and treatment harms. We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence. Two review authors independently assessed the search results, extracted data, assessed risk of bias and the certainty of the evidence. We contacted the authors of two included trials and the author of the trial awaiting classification to obtain missing numerical outcome data. Main results We included three trials involving 3256 children aged between 2 to 59 months, who exhibited features of non-severe pneumonia with wheeze. The included trials were multi-centre, double-blind, randomised, placebo-controlled trials carried out in Malawi, Pakistan, and India. The children were treated with a three-day course of amoxicillin or placebo, and were followed up for a total of two weeks. We assessed the included trials at overall low risk of bias for random sequence generation, allocation concealment, blinding, attrition bias, and selective reporting. Only one trial was assessed to be at high risk for blinding of outcome assessors. One trial is awaiting classification Antibiotic therapy may result in a reduction of treatment failure by 20% (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.68 to 0.94; three trials; 3222 participants; low-certainty evidence). Antibiotic therapy probably results in little or no difference to clinical cure (RR 1.02, 95% CI 0.96 to 1.08; one trial; 456 participants; moderate-certainty evidence), and in little or no difference to relapse (RR 1.00, 95% CI 0.74 to 1.34; three trials; 2795 participants; low-certainty evidence), and treatment harms (RR 0.81, 95% CI 0.60 to 1.09; three trials, 3253 participants; low-certainty evidence). Two trials (2112 participants ) reported on mortality; no deaths occurred in either group. One trial reported cases of hospitalisation, diarrhoea (with and without dehydration), rash (without itch), tremors, mild nausea and vomiting. Authors' conclusions We do not currently have enough evidence to support or challenge the continued use of antibiotics for the treatment of non-severe pneumonia. There is a clear need for RCTs to address this question in children aged 2 to 59 months with 2014 WHO-defined non-severe pneumonia and wheeze.