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To help inform global guidelines on infant feeding, this systematic review synthesizes evidence related to the presence of the Ebola virus (EBOV) in breast milk and its potential risk of viral transmission to the infant when breastfeeding. We relied on a comprehensive search strategy to identify studies including women with suspected, probable, or confirmed EBOV infection, intending to breastfeed or give breast milk to an infant. Our search identified 10,454 records, and after deduplication and screening, we assessed 148 full texts. We included eight studies reporting on 10 breastfeeding mothers and their children (one mother with twins), who provided breast milk samples for assessment. EBOV was detected via RT‐PCR or viral culture in seven out of ten breast milk samples. Four out of the five‐breastfed infants with EBOV‐positive breast milk were found positive for EBOV infection, and all of these EBOV‐positive infants died. Since previous reports have detected EBOV in tears, saliva, sweat, and contaminated surfaces, with the current evidence, it is not possible to conclude with certainty that breast milk was the main route of EBOV transmission., Understanding maternal‐to‐child transmission routes is key to lowering, and ultimately preventing, the exposure of Ebola virus (EBOV) in pediatric populations. We undertook a systematic review of the available scientific literature to determine whether EBOV can be transmitted through breast milk and to describe the outcomes of the infants that ingested EBOV laboratory‐confirmed breast milk.

Background The impact of deworming on parasite load, nutritional status and other health outcomes of non-pregnant adolescent girls and adult women is uncertain. Methods MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform, the Cochrane Database of Systematic Reviews and Food and Technology Abstracts databases were searched until 24 September 2018. Studies were included if they were randomised controlled trials (RCTs), controlled before and after studies or interrupted time studies comparing deworming with no intervention or placebo in non-pregnant adolescent girls and women 10 to 49 years old. Outcomes of interest included parasite load, reinfection, anaemia, severe anaemia, iron deficiency, diarrhoea or all-cause morbidity. Risk of bias was assessed using the Cochrane risk of bias tool. Results We included four RCTs of mass deworming involving 1086 participants, in the analyses. Mass deworming probably reduces the prevalence of roundworm infection (RR 0.29; 95% CI 0.14 to 0.62; 2 trials; 1498 participants, moderate certainty evidence), prevalence of hookworm infection (RR 0.32; 95% CI 0.18 to 0.59; 2 trials; 1498 participants, moderate certainty evidence), prevalence of whipworm infection (RR 0.77; 95% CI 0.65 to 0.91; 2 trials; 1498 participants, moderate certainty evidence) compared to the control group. Deworming may make little or no difference in prevalence of anaemia (RR 0.82; 95% CI 0.60 to 1.11, 3 studies, 683 participants, low certainty evidence) and prevalence of iron-deficiency (RR 0.89; 95% CI 0.64 to 1.23, 1 study, 186 participants, low certainty evidence) compared to control. We are uncertain whether deworming reduces the prevalence of severe anaemia compared to control as the certainty of evidence was very low. None of the included studies assessed screen and treat deworming or reported reinfection, diarrhoea or adverse events. Conclusions Mass deworming probably reduces the prevalence of soil-transmitted helminth infections but may have little or no effect on anaemia and iron-deficiency in adolescent girls and non-pregnant women in comparison to no intervention or placebo. We are uncertain about the effect on severe anaemia. These results are limited by sparse data and the moderate to very low quality of evidence available. Systematic review registration The protocol was registered in PROSPERO (registration number: CRD42016039557). Primary source of funding: Evidence and Programme Guidance unit, Department of Nutrition for Health and Development, World Health Organization (WHO). Electronic supplementary material The online version of this article (10.1186/s13643-018-0859-6) contains supplementary material, which is available to authorized users.

To gain new insights into the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding practices, we systematically searched regional and international databases and screened 1,658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant. Fourteen studies met our inclusion criteria and inform this analysis. These studies reported on 97 mother-children pairs who provided breast milk for ZIKV assessment. Seventeen breast milk samples from different women were found positive for ZIKV via RT-PCR, and ZIKV replication was found in cell cultures from five out of seven breast milk samples from different women. Only three out of six infants who had ZIKV infection were breastfed, no evidence of clinical complications were found to be associated with ZIKV RNA in breast milk. This review updates our previous report by synthesizing the evidence from 12 new articles and we find no evidence of mother-to-child transmission through breast milk intake or breastfeeding. As the certainty of the present evidence is low, additional studies are still warranted to completely understand any potential of transmission of ZIKV through breastfeeding.

IntroductionRapid, robust and continually updated evidence synthesis is required to inform management of COVID-19 in pregnant and postpartum women and to keep pace with the emerging evidence during the pandemic.Methods and analysisWe plan to undertake a living systematic review to assess the prevalence, clinical manifestations, risk factors, rates of maternal and perinatal complications, potential for mother-to-child transmission, accuracy of diagnostic tests and effectiveness of treatment for COVID-19 in pregnant and postpartum women (including after miscarriage or abortion). We will search Medline, Embase, WHO COVID-19 database, preprint servers, the China National Knowledge Infrastructure system and Wanfang databases from 1 December 2019. We will supplement our search with studies mapped by Cochrane Fertility and Gynaecology group, Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), COVID-19 study repositories, reference lists and social media blogs. The search will be updated every week and not be restricted by language. We will include observational cohort (≥10 participants) and randomised studies reporting on prevalence of COVID-19 in pregnant and postpartum women, the rates of clinical manifestations and outcomes, risk factors in pregnant and postpartum women alone or in comparison with non-pregnant women with COVID-19 or pregnant women without COVID-19 and studies on tests and treatments for COVID-19. We will additionally include case reports and series with evidence on mother-to-child transmission of SARS-CoV-2 in utero, intrapartum or postpartum. We will appraise the quality of the included studies using appropriate tools to assess the risk of bias. At least two independent reviewers will undertake study selection, quality assessment and data extraction every 2 weeks. We will synthesise the findings using quantitative random effects meta-analysis and report OR or proportions with 95% CIs and prediction intervals. Case reports and series will be reported as qualitative narrative synthesis. Heterogeneity will be reported as I2 and τ2 statistics.Ethics and disseminationEthical approval is not required as this is a synthesis of primary data. Regular updates of the results will be published on a dedicated website (https://www.birmingham.ac.uk/research/who-collaborating-centre/pregcov/index.aspx) and disseminated through publications, social media and webinars.PROSPERO registration numberCRD42020178076.

The pandemic of coronavirus disease 2019 (COVID‐19) is caused by infection with a novel coronavirus strain, the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). At present, there is limited information on potential transmission of the infection from mother to child, particularly through breast milk and breastfeeding. Here, we provide a living systematic review to capture information that might necessitate changes in the guidance on breast milk and breastfeeding given the uncertainty in this area. Our search retrieved 19,414 total records; 605 were considered for full‐text eligibility and no ongoing trials were identified. Our review includes 340 records, 37 with breast milk samples and 303 without. The 37 articles with analyzed breast milk samples reported on 77 mothers who were breastfeeding their children; among them, 19 of 77 children were confirmed COVID‐19 cases based on RT‐PCR assays, including 14 neonates and five older infants. Nine of the 68 analyzed breast milk samples from mothers with COVID‐19 were positive for SARS‐CoV‐2 RNA; of the exposed infants, four were positive and two were negative for COVID‐19. Currently, there is no evidence of SARS‐CoV‐2 transmission through breast milk. Studies are needed with longer follow‐up periods that collect data on infant feeding practices and on viral presence in breast milk., The objective of this review is to assess available evidence related to the possible transmission of SARS‐ CoV‐2 through breast milk and through breastfeeding (i.e., related bodily fluids, such as blood, sweat, and respiratory droplets) or droplet transmission due to close contact with the infant or young child via skin‐to‐skin exposure or airborne transmission. The review aims to support policymakers in making evidence‐informed global, regional, and national guidelines on infant feeding in the context of the ongoing pandemic.

Children and adolescents with overweight and obesity are a global health concern. This is an integrative overview of six Cochrane systematic reviews, providing an up-to-date synthesis of the evidence examining interventions for the treatment of children and adolescents with overweight or obesity. The data extraction and quality assessments for each review were conducted by one author and checked by a second. The six high quality reviews provide evidence on the effectiveness of behaviour changing interventions conducted in children

BACKGROUND: Adequate nutrients early in life promote cognitive development and are critical for proper growth and functioning. The effect of individual nutrients consumed through food is often not the same as consuming the same nutrients in supplementary form due to 'food synergy', the biological and chemical interrelations that occur between nutrients. Animal‐source foods, such as eggs, meat, fish, and dairy, are energy dense and contain multiple micronutrients and essential fatty acids with high bioavailability. The benefits of animal‐source foods may include higher food synergy relative to fortified foods as well as decreasing dependence on external suppliers of fortified foods. OBJECTIVES: To assess the effectiveness of animal‐source foods compared to any other feeding interventions or no intervention in improving growth and developmental outcomes in children aged 6 to 59 months. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, 18 other databases, and three trials registers up to August 2018. We also contacted authors and known experts in the field for assistance in identifying ongoing or unpublished data, and searched the reference lists of included studies and reviews, and websites of relevant organizations, for other studies that may not have been captured by our electronic searches. SELECTION CRITERIA: We included randomized controlled trials and quasi‐randomized controlled trials of any duration, where children between 5 months and 59 months (6 years) of age were provided with an animal‐source food (e.g. consumption of milk, meat, or eggs), prepared with any cooking method, compared with any intervention or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility using prespecified criteria, extracted data, assessed risk of bias, and graded the quality of the evidence using the GRADE approach. MAIN RESULTS: Study characteristics We included 6 studies that analyzed data from 3036 children aged 5 to 50 months. The studies were conducted in China, the Democratic Republic of Congo, Ecuador, Guatemala, Pakistan, the USA, and Zambia, and lasted between 5 and 12 months. Three studies were funded, in part, by government entities; one study was supported by a nonprofit organization. Two studies did not report a funding source. Three studies compared the effects of feeding an animal‐source food with a fortified (iron or iron and zinc), or unfortified cereal; two used a control group with no intervention; one compared a meat‐based diet to a dairy‐based diet. The types of animal‐source foods tested included yogurt, eggs, cheese, lyophilized (freeze‐dried) beef product, ground and frozen pork, puréed and jarred beef with gravy or pork, and powdered whey protein. We judged four studies to be at unclear risk of bias overall; three studies because they were funded by an industry with a plausible interest in the outcome of the intervention; and one study because there was insufficient information to assess five of the seven bias 'Risk of bias' domains. We judged two of the six studies to be at high risk of bias overall; one study because there was significant baseline imbalance in length‐for‐age z scores (LAZ) between groups and evidence of selective reporting; the other study because there there was both a significant baseline imbalance in LAZ and weight‐for‐age z scores (WAZ) between groups, and a large‐scale social media campaign that may have influenced care received at home in the control group. Key results Animal‐source foods versus cereal‐based foods or no intervention Five studies (2972 children) measured change in linear growth with either height‐for‐age z scores (HAZ) or LAZ. Three studies (592 children) reported a significant increase in HAZ and LAZ in the intervention group compared to the control group. Two studies (2380 children) reported a decline in LAZ in both groups. In one study (1062 children) there was no difference between the groups in the rate of decline; in the other (1318 children) the decrease in LAZ was significantly smaller in the intervention group. Five studies (2972 children) measured weight gain using WAZ. Three studies (592 children) reported a significant increase in WAZ in the intervention group compared to the control group. In two studies (2380 children), WAZ decreased in both groups. In one of these studies (1318 children), the decrease in the intervention group was significantly smaller than in the control group. In the other study (1062 children), there was no difference between the groups. Three studies (1612 children) reported impacts on all‐cause morbidity, but metrics were inconsistent between studies. One study with yogurt (402 children) reported a significant reduction in duration and incidence of diarrhea and upper respiratory infections in the intervention group. One study with eggs (148 children) reported a significant increase in the incidence of diarrhea in the intervention group, but this may have been due to cultural associations with eggs and gastrointestional problems. There were no other significant differences in fever, respiratory infections, or skin conditions between groups. The third study (1062 children) found no differences between intervention and control groups across morbidity measures. No studies reported data on anemia. Meat‐based diet versus dairy‐based diet One study (64 children) measured change in LAZ and WAZ in infants fed either a meat‐based diet or dairy‐based diet. There was a significant increase in LAZ among infants consuming the meat‐based diet and a significant decrease in LAZ among infants consuming a dairy‐based diet. WAZ increased in both groups, with no significant difference between groups. The study did not assess all‐cause morbidity or anemia. Quality of the evidence We rated the quality of the evidence as very low overall due to baseline imbalances between intervention and control groups, high heterogeneity in meta‐analysis, and imprecision due to wide confidence intervals and inconsistent direction of effects. We have little confidence in the results; further research is likely to change the estimate of magnitude and direction of treatment effect. AUTHORS' CONCLUSIONS: Given the limited quality of the evidence, we are uncertain of the effects of the provision of animal‐source food versus cereal products or no intervention on the growth or development of children. More adequately powered trials with deliberately selected animal‐source foods are needed.

Excluded studies. (DOCX 20 kb)

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PRISMA checklist. (DOC 63 kb)

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The Baby-Friendly Hospital Initiative (BFHI) implemented through the "Ten Steps to Successful Breastfeeding" has been widely promoted as an intervention that improves breastfeeding rates. Step 2 requires the training of all healthcare staff in skills that are necessary to implement the policy. This systematic review provides evidence about the effect of training healthcare staff in hospitals and birth centers on breastfeeding outcomes. Randomized controlled trials (RCT), quasi-RCT, and controlled before and after (CBA) studies comparing training of healthcare staff on breastfeeding and supportive feeding practices with no training were included in this review. We searched CENTRAL PubMed, EMBASE, CINAHL, Web of Science, and the British Nursing Index for studies. Studies were screened against predetermined criteria, and risk of bias of included studies was assessed using the Risk of Bias Assessment tool for Non-Randomized Studies for non-RCT studies and the Cochrane Handbook for Systematic Reviews of Interventions for RCT studies. Of the six studies included in this review, three were RCT whereas three were CBA studies. The studies were conducted in 5 countries and involved 390 healthcare staff. Provision of educational interventions aimed at increasing knowledge and practice of BFHI and support was found to improve health worker's knowledge, attitude, and compliance with the BFHI practices. In one study, the rate of exclusive breastfeeding increased at the intervention site but no differences were found for breastfeeding initiation rates. All included studies had methodological limitations, and study designs and methodologies lacked comparability.

Children and adolescents with overweight and obesity are a global health concern. This is an integrative overview of six Cochrane systematic reviews, providing an up-to-date synthesis of the evidence examining interventions for the treatment of children and adolescents with overweight or obesity. The data extraction and quality assessments for each review were conducted by one author and checked by a second. The six high quality reviews provide evidence on the effectiveness of behaviour changing interventions conducted in children6 years (7 trials), 6-11 years (70 trials), adolescents 12-17 years (44 trials) and interventions that target only parents of children aged 5-11 years (20 trials); in addition to interventions examining surgery (1 trial) and drugs (21 trials). Most of the evidence was derived from high-income countries and published in the last two decades. Collectively, the evidence suggests that multi-component behaviour changing interventions may be beneficial in achieving small reductions in body weight status in children of all ages, with low adverse event occurrence were reported. More research is required to understand which specific intervention components are most effective and in whom, and how best to maintain intervention effects. Evidence from surgical and drug interventions was too limited to make inferences about use and safety, and adverse events were a serious consideration.

Background The prevalence of stunting, underweight, and micronutrient deficiencies are persistently high in young children in the Philippines, and among other factors, suboptimal infant and young child feeding behavior may contribute to these forms of malnutrition. Objective To improve the understanding of contributors associated with the nutritional status of children 6 to 23 months of age living in urban areas of the Philippines. Methods A cross-sectional survey was conducted covering five urban centers in the Philippines. Data on infant and young child feeding and nutritional status (including wasting, stunting, underweight, anemia, iron deficiency, and vitamin A deficiency) were collected for 1,784 children. Results Among children from urban and predominantly poor and very poor households, 26% were stunted, 18% were underweight, and 5% were wasted. Forty-two percent were anemic, 28% were iron deficient, and 3% were vitamin A deficient. About half of the children were breastfed within an hour after birth, were breastfed at the time of the survey, and had been continuously breastfed up to 1 year of age. Of the factors investigated, low socio-economic status, use of cheaper cooking fuel, and nonuse of multivitamins were all independently associated with stunting. The prevalence of anemia, iron deficiency, and vitamin A deficiency were independently associated with the same factors and poorer sanitation facilities, lower maternal education, current unemployment, and inflammation. Conclusions These factors merit attention in future programming, and interventions may include promotion of the timely introduction of appropriate fortified complementary foods, the use of affordable multiple micronutrient preparations, and measures to reduce infections.

Hepatitis B virus (HBV) infection remains a significant health burden world-wide, although vaccines help decrease this problem. We previously identified associations of single nucleotide polymorphisms in several candidate genes with vaccine-induced peak antibody level (anti-HBs), which is predictive of long-term vaccine efficacy and protection against infection and persistent carriage; here we report on a haplotype-based analysis. A total of 688 SNPs from 117 genes were examined for a two, three and four sliding window haplotype analysis in a Gambian cohort. Analysis was performed on 197 unrelated individuals, 454 individuals from 174 families, and the combined sample (N = 651). Global and individual haplotype association tests were carried out (adjusted for covariates), employing peak anti-HBs level as outcome. Five genes (CD44, CD58, CDC42, IL19 and IL1R1) had at least one significant haplotype in the unrelated or family analysis as well as the combined analysis. Previous single locus results were confirmed for CD44 (combined global p = 9.1x10(-5) for rs353644-rs353630-rs7937602) and CD58 (combined global p = 0.008 for rs1414275-rs11588376-rs1016140). Haplotypes in CDC42, IL19 and IL1R1 also associated with peak anti-HBs level. We have identified strong haplotype effects on HBV vaccine-induced antibody level in five genes, three of which, CDC42, IL19 and IL1R1, did not show evidence of association in a single SNP analyses and corroborated the majority of these effects in two datasets. The haplotype analysis identified associations with HBV vaccine-induced immunity in several new genes.

Our objective was to identify the determinants of anemia among rural Filipino children aged 12-71 months.A cross-sectional survey was conducted among 2090 preschool children from 8 rural villages in Cebu, an area non-endemic for malaria and schistosomiasis. Hemoglobin (Hb) concentration was determined using a HemoCue hemoglobinometer and zinc protoporphyrin (ZPP) concentration was measured with a hematofluorometer. A 3-day non-consecutive 24-hour food recall interview with the child's primary caregiver was done to estimate the child's dietary intake. Stool analysis for presence of soil-transmitted helminths was performed through a concentration technique. A separate interview on household socio-economic status with the child's primary caregiver was conducted.Mean Hb concentration was 12.0 g/dL (SD 1.3). 16.1% were anemic. Age and sex had a significant interaction in their effect on Hb concentration. Females had higher Hb concentration between 12 to 23 months of age. Hb levels equalize between the 2 genders at around 24 months and increase with similar increments until 71 months of age. All dietary parameters improved Hb concentration with increasing intake. In the multiple regression, however, only the index for bioavailable iron and vitamin C intakes remained independent factors. None of the helminths or combination of helminths had significant effects on Hb concentration. Among the socio-economic variables, maternal educational attainment and water supply were significant independent factors. Mean ZPP concentration was 72.07 (SD 46.45) and 30.8% were iron deficient. As with Hb concentration, age and sex had a significant interaction in their effect on ZPP concentration, with females having lower ZPP levels before 24 months of age. Bioavailable iron (animal iron + 0.3*plant iron) had a significant effect on ZPP concentration at levels of at least 15% of the iron requirement. This was seen even after controlling for multivitamin supplementation.The control of anemia among preschoolers can be achieved through a combination of various nutritional interventions such as micronutrient supplementation, food fortification and nutrition education. Our findings emphasize the importance of a multi-sectoral approach to nutritional problems--the importance of empowering women (through engagement and education) and of maintaining a healthy physical environment (water and sanitation) are often peripheral concerns of nutritionists. Our study highlights the importance of supporting initiatives that address these issues not only for their core benefit, but also for the potential benefit to nutrition.

To determine the effect of a school-based weekly iron supplementation delivery system (WISDS) on the prevalence of anemia among anemic schoolchildren.Two hundred and forty-two Filipino schoolchildren aged 6-12 years with hemoglobin (Hb) concentration12 g/dl and enrolled for school year 2003-2004. UNICEF iron-folate tablets containing 60 mg elemental iron and 0.40 mg folic acid were given weekly through directly observed supplementation by the teachers for 27 weeks. Compliance to iron supplementation was monitored by the teachers and was recorded using a monitoring form and a supplementation calendar. Hb concentration, weight and height were determined at baseline and at post-intervention.At post-intervention, the participants' mean Hb concentration increased by 0.4 g/dl (95% confidence interval =0.3, 0.5 g/dl; P0.0001), anemia prevalence was reduced by 53.7, and 84.3% of the participants had 100% compliance to supplementation.The school-based WISDS reduced anemia prevalence among anemic schoolchildren and resulted in high compliance to and coverage of iron supplementation.

BACKGROUND: Carriage of hepatitis B virus (HBV) is a major risk factor for liver cirrhosis and hepatocellular carcinoma. Infant vaccination has been effective in preventing horizontal transmission during early childhood. It is unknown whether protection is maintained into early adulthood. METHODS: In 1984, early childhood vaccination was introduced in 2 rural Gambian villages. In 2003, serological assessment of 81.5% of 1,350 eligible participants 1-24 years old was done, to determine vaccine efficacy against infection and carriage. RESULTS: Overall vaccine efficacy against infection and carriage was 83.4% (95% confidence interval [CI], 79.8%-86.6%) and 96.5% (85% CI, 93.9%-98.9%), respectively. Vaccine efficacy against infection was similar when restricted to primary responders (85.3%), but a significant effect of peak antibody concentration was found. Both vaccine efficacy and levels of hepatitis B surface antibody (anti-HBs) decreased with age, resulting in a vaccine efficacy against infection and carriage among 20-24-year-old participants of 70.9% (95% CI, 60.4%-80.5%) and 91.1% (95% CI, 75.8%-100%), respectively. Fifteen years after vaccination, fewer than half of the vaccinees had detectable anti-HBs. The prevalence of carriage in the unvaccinated population was similar to the prevalence 20 years earlier. CONCLUSIONS: HBV vaccination early during life can provide long-lasting protection against carriage, despite decreasing antibody levels. The role played by subclinical boosting and the necessity of a booster need to be evaluated.

We have developed a methodology for comparing the seasonal influences on two outcomes, when those influences may act cumulatively or instantaneously. We have used this to compare the seasonal pattern of intrauterine growth retardation (IUGR, as reflected by weight-for-gestational-age) and preterm delivery (as assessed by Dubowitz scoring) among 1718 infants born in rural Gambia. Both outcomes were analysed as binary variables: small-for-gestational-age (SGA

Recent animal studies suggest that preconceptional undernutrition shortens gestation. We retested this idea among rural Gambian women who experience annual fluctuations in energy balance caused by the rains (with lowest weights in September to November) using records from 1918 infants. Pregnancies conceived in September to November were significantly shorter than those from better-fed months (38.6 vs 39.0 weeks; log-rank chi 2 = 17.4, P < .0001).

Background: Low birth weight (LBW) can result from prematurity or intrauterine growth restriction (IUGR) and result in small-for-gestational-age (SGA) infants. Prematurity and IUGR may have different etiologies and consequences. Objective: Our objective was to analyze seasonal patterns of prematurity and SGA in a rural African community and to compare them against variations in nutritional and ecologic variables that may provide insight into likely causative factors. Design: Fourier series were used to compare the seasonality of prematurity (

Background Zika virus (ZIKV) infection is an emerging mosquito-borne disease, which is associated with an increase in central nervous system malformations and newborn microcephaly cases. This review investigated evidence of breastfeeding transmission from ZIKV-infected mothers to their children and the presence of ZIKV infection in breastfeeding-related fluids. Methodology/Principal findings We conducted a systematic review of observational studies, case studies, and surveillance reports involving breastfeeding women with ZIKV infection in several international databases. Data extraction and analysis were conducted following a PROSPERO-registered protocol. From 472 non-duplicate records, two case reports met criteria for inclusion. We reviewed three cases of ZIKV infection among lactating mothers near the time of delivery. Two of the three (2/3) associated newborns had evidence of ZIKV infection. ZIKV was detected in breast milk of all three mothers. Breast milk detection results were positive in all mothers (3/3) by RT-PCR, one was positive by culture (1/3), and none was tested for ZIKV-specific antibodies. Serum samples were ZIKV positive in all mothers (3/3), and sweat was not tested for ZIKV. Conclusions/Significance We describe three cases of ZIKV-infected breastfeeding mothers who were symptomatic within three days of delivery, and two cases with ZIKV-infected newborns. While ZIKV was detected in the breast milk of all three mothers, the data are not sufficient to conclude ZIKV transmission via breastfeeding. More evidence is needed to distinguish breastfeeding transmission from other perinatal transmission routes., Author summary Zika virus (ZIKV) infection was considered a mild fever illness until the recent and ongoing outbreak in South America revealed that the virus can cause microcephaly and other neurological disorders. ZIKV is primarily transmitted by mosquitoes, but can also spread from person to person through sex, blood transfusion, and from mother to child during pregnancy or delivery. It is unknown if ZIKV can spread from mother to child during breastfeeding. We conducted a systematic review of the literature to summarize evidence of ZIKV transmission via breastfeeding and the presence ZIKV in breast milk. Our search resulted in 2 case reports that described 3 mothers and their newborns. ZIKV was confirmed in the blood and breast milk of all 3 mothers and in the blood of 2 newborns. More evidence is needed to confirm if ZIKV is transmitted via breastfeeding.

The following information was missing from the Funding section: "The study was supported by funding from the NIHR Oxford Biomedical Research Centre programme."

The following information was missing from the Funding section: "The study was supported by funding from the NIHR Oxford Biomedical Research Centre programme."

Throughout most of the mammalian genome, genetically regulated developmental programming establishes diverse yet predictable epigenetic states across differentiated cells and tissues. At metastable epialleles (MEs), conversely, epigenotype is established stochastically in the early embryo then maintained in differentiated lineages, resulting in dramatic and systemic interindividual variation in epigenetic regulation. In the mouse, maternal nutrition affects this process, with permanent phenotypic consequences for the offspring. MEs have not previously been identified in humans. Here, using an innovative 2-tissue parallel epigenomic screen, we identified putative MEs in the human genome. In autopsy samples, we showed that DNA methylation at these loci is highly correlated across tissues representing all 3 embryonic germ layer lineages. Monozygotic twin pairs exhibited substantial discordance in DNA methylation at these loci, suggesting that their epigenetic state is established stochastically. We then tested for persistent epigenetic effects of periconceptional nutrition in rural Gambians, who experience dramatic seasonal fluctuations in nutritional status. DNA methylation at MEs was elevated in individuals conceived during the nutritionally challenged rainy season, providing the first evidence of a permanent, systemic effect of periconceptional environment on human epigenotype. At MEs, epigenetic regulation in internal organs and tissues varies among individuals and can be deduced from peripheral blood DNA. MEs should therefore facilitate an improved understanding of the role of interindividual epigenetic variation in human disease., Author Summary There is growing interest in the possibility that interindividual epigenetic variation plays an important role in a broad range of human diseases. The tissue-specificity of epigenetic regulation, however, will in many cases make it difficult to obtain the appropriate tissues in which to perform large-scale studies linking epigenetic dysregulation to disease. We have used an innovative two-tissue DNA methylation screen to identify genomic regions that exhibit interindividual epigenetic variation which occurs systemically—i.e. similarly in all tissues. Such regions—called metastable epialleles—have previously been identified in mice because they cause visible phenotypic variation amongst genetically identical individuals. Indeed, we found that even monozygotic twins show substantial epigenetic discordance at these loci. Further, we show that, as in mice, establishment of DNA methylation at these putative human metastable epialleles is labile to maternal environment around the time of conception. Metastable epialleles should facilitate an improved understanding both of the role of interindividual epigenetic variation in human disease and of the effects of early environment on the establishment of human epigenotype.

To determine the efficacy of pandesal baked from wheat flour fortified with iron, with or without vitamin A (VA), in improving anemic schoolchildren's iron and anthropometric status.Anemic 6- to 12-year-old Filipino children (n = 250) received two 60 g pandesal daily for 8 months. They were randomized into 1 of 4 groups: (1) iron-fortified (with hydrogen-reduced iron at 80 mg/kg, electrolytic iron at 80 mg/kg, or ferrous fumarate at 40 mg/kg), (2) iron and VA-fortified, (3) VA-fortified (at 490 RE/100 g), and (4) nonfortified flour. Hemoglobin (Hb) and zinc protoporphyrin (ZnPP) concentrations and weight and height were determined before and after intervention. Analyses of variance and chi-square and multiple regression analyses were performed.Mean Hb increased by 1.3 g/dL (p0.001) and mean ZnPP decreased by 24.4 micromol/mol (p0.001) after 8 months. Anemia decreased to 26% and iron deficiency decreased from 58% to 12%. After controls were applied for baseline concentration, age, and gender, Hb concentration at post intervention was significantly higher in the Iron + VA group than in the nonfortified group (coefficient = 0.37; p = 0.034). The odds of being iron deficient at post intervention were significantly lower in the Iron group than in the nonfortified group after controls were applied for age, gender, and baseline prevalence (coefficient = 0.12; p = 0.006). None of the 3 fortified groups had significantly different weight-for-age z-score, body mass index-for-age z-score, or height-for-age z-score compared with the nonfortified group after controls were applied for baseline z-scores, age, and gender.Our study shows that in a non-malaria-endemic area, iron fortification of flour significantly reduced the prevalence of iron deficiency among anemic schoolchildren, and double fortification with iron and VA significantly improved Hb status.

To determine the effects of eating carotene-rich green and yellow vegetables on the prevalence of anaemia, iron deficiency and iron-deficiency anaemia in schoolchildren.Schoolchildren (n=104), aged 9-12 years, received standardized meals containing 4.2 mg of provitamin A carotenoids/day (mainly beta-carotene) from yellow and green leafy vegetables and at least 7 g dietary fat/day. The meals were provided three times/day, 5 days/week, for 9 weeks at school. Before and after the dietary intervention, total-body vitamin A pool size was assessed by using the deuterated-retinol-dilution method; serum retinol and beta-carotene concentrations were measured by high-performance liquid chromatography; and whole blood haemoglobin (Hb) and zinc protoporphyrin (ZnPP) concentrations were measured by using a photometer and a hematofluorometer, respectively.After 9 weeks, the mean total-body vitamin A pool size increased twofold (95% confidence interval (CI): -0.11, -0.07 micromol retinol; P0.001), and serum beta-carotene concentration increased fivefold (95% CI: -0.97, -0.79 micromol/l; P0.001). Blood Hb (95% CI: -1.02, -0.52 g per 100 ml; P0.001) and ZnPP increased (95% CI: -11.82, -4.57 microol/mol haem; P0.001). The prevalence of anaemia (Hb11.5 g per 100 ml) decreased from 12.5 to 1.9% (P0.001). There were no significant changes in the prevalence of iron deficiency or iron-deficiency anaemia.Ingestion of carotene-rich yellow and green leafy vegetables improves the total-body vitamin A pool size and Hb concentration, and decreases anaemia rates in Filipino schoolchildren, with no effect on iron deficiency or iron-deficiency anaemia rates.

Dietary diversification through home gardening is a sustainable strategy that can address multiple micronutrient deficiencies. This cross-sectional study aimed to determine the association between home gardening and the dietary diversity of preschool-aged children. Households with children aged 2 to 5 years (n=200) were surveyed from Baras and Angono in the province of Rizal, Philippines in January 2008. Food security was determined based on the US Department of Agriculture Food Security Questionnaire. Dietary diversity score was based on the number of unique food groups consumed during the past 24 hours. The Student t test was performed to compare means between groups (households with gardens vs households without gardens) whereas proportions between groups were compared using Pearson's χ 2 analyses. Multiple linear regression was performed to model the adjusted regression coefficients for the quantitative outcome variables by exposure variable. Around 52.5% of children were from households with a fruit and/or vegetable garden. Children from households with gardens had higher dietary diversity scores whether using the all-inclusive dietary diversity score (6.12 vs 5.62; P =0.040) or applying a 10-g minimum intake for each food group (5.89 vs 5.37; P =0.044) compared with children who lived in homes without a garden. Children from households with gardens were significantly more likely to eat vegetables more frequently (χ 2 =9.06; P =0.029). The presence or absence of a garden was not significantly associated with food security. Having a home garden was positively associated with the child's diet diversity and with frequency of vegetable consumption. Households without gardens may benefit from interventions promoting gardens as a means to improve diet quality.

ObjectiveTo determine the effectiveness of a redesigned Fe supplementation delivery system (ISDS) in improving Hb concentrations and compliance among pregnant women.DesignA controlled before and after study design was used. Interviews and Hb measurements of randomly selected pregnant women in both treatment areas were conducted at baseline and after 6 months. The redesigned ISDS, reached by consensus based on the surveys and focus group discussions, involved the health workers in spot mapping and clustering; Fe tablets’ distribution, monitoring and promotion; and counselling of pregnant women.SettingNegros Occidental and Negros Oriental, Philippines.SubjectsIn total, 1180 pregnant women given Fe/folic acid tablets daily through the redesigned ISDS in the experimental areas and the existing ISDS in the control areas.ResultsThere were significantly more anaemic pregnant women in the experimental than in the control area at baseline (50·7 v. 37·3 %; P = 0·001). However, at endline, the anaemia prevalence rate in the experimental area was comparable to that of the control (35·6 v. 33·1 %; P = 0·530). Also, the mean Hb concentration increased significantly in the experimental area by 0·5 g/dl (P = 0·002). An increase in the actual number of prenatal visits/trimester in the experimental area was observed (from 0·99 to 1·66; P < 0·0001). Pregnant women in the experimental area were four times more likely to take Fe tablets (OR = 3·79; P < 0·001) and sixteen times more likely to being monitored for Fe intake (OR = 16·86; P < 0·001) compared to the control.ConclusionsThe redesigned ISDS was effective in improving the Hb concentration and health-related behaviour of pregnant women.

BACKGROUND: Vaccination against hepatitis B virus infection (HBV) is safe and effective; however, vaccine-induced antibody level wanes over time. Peak vaccine-induced anti-HBs level is directly related to antibody decay, as well as risk of infection and persistent carriage despite vaccination. We investigated the role of host genetic factors in long-term immunity against HBV infection based on peak anti-HBs level and seroconversion to anti-HBc. METHODS: We analyzed 715 SNP across 133 candidate genes in 662 infant vaccinees from The Gambia, assessing peak vaccine-induced anti-HBs level and core antibody (anti-HBc) status, whilst adjusting for covariates. A replication study comprised 43 SNPs in a further 393 individuals. RESULTS: In our initial screen we found variation in IFNG, MAPK8, and IL10RA to affect peak anti-HBs level (GMTratio of < 0.6 or > 1.5 and P < or = 0.001) and lesser associations in other genes. Odds of core-conversion was associated with variation in CD163. A coding change in ITGAL (R719V) with likely functional relevance showed evidence of association with increased peak anti-HBs level in both screens (1st screen: s595_22 GMTratio 1.71, P = 0.013; 2nd screen: s595_22 GMTratio 2.15, P = 0.011). CONCLUSION: This is to our knowledge the largest study to date assessing genetic determinants of HBV vaccine-induced immunity. We report on associations with anti-HBs level, which is directly related to durability of antibody level and predictive of vaccine efficacy long-term. A coding change in ITGAL, which plays a central role in immune cell interaction, was shown to exert beneficial effects on induction of peak antibody level in response to HBV vaccination. Variation in this gene does not appear to have been studied in relation to immune responses to viral or vaccine challenges previously. Our findings suggest that genetic variation in loci other than the HLA region affect immunity induced by HBV vaccination.

Background The salt iodization law of the Philippines required that iodized salt sold at retail not be exposed to direct sunlight, high temperature and relative humidity, and contamination with moisture and dust from the environment. However, because the majority of local consumers buy salt displayed in open heaps, it was suggested that iodized salt should be sold in the same manner for greater accessibility and availability. Objective We aimed to provide evidence on the stability of iodine in local aged and fresh salt iodized at 100 ppm iodine and exposed to various market and storage conditions. Methods Samples of salt in open heaps and repacked salt were exposed for 4 weeks, and salt packed in woven polypropylene bags was stored for 6 months. The iodine content of the salt was determined by the iodometric titration method, and the moisture content was determined by the oven-drying method. Results For all types of exposed salt, iodine levels were above 60 ppm after the end of the study (4 weeks). Within each salt type, losses were greater for open-heap salt than for repacked salt. The greatest drop in moisture content occurred in the first week for most types of salt and exposure combinations. Moisture content was linearly correlated with iodine content. Iodine levels in stored salt remained above 60 ppm even after 6 months. Conclusions Iodized salt is able to retain iodine above the recommended levels despite exposure to an open environment and use of ordinary packaging materials while being sold at retail and kept in storage.

Background/Aim The study aimed at developing a real-time quantitative PCR assay to monitor HBV serum virus load of chronic carriers enrolled in therapeutic trials. Method Quantitative real-time PCR assay was carried out using SYBR-Green signal detection and primers specific to the S gene. Thermal cycling was performed in an ABi 5700 sequence detection system. The assay was calibrated against an international HBV DNA standard and inter- and intra-assay reproducibility determined. Levels of viral load were monitored for 1-year in lamivudine treated carriers. Correlation between HBV DNA levels and HBeAg sero-status was determined in untreated carriers. Results The qPCR assay showed good intra- and inter-assay reproducibility over a wide dynamic range (1.5 × 103 to 1.5 × 108 copies/mL) and correlated well with those from a commercial assay (r = 0.91, (p < 0.001). Viral load levels dropped dramatically but temporarily during and after a short course of lamivudine therapy. HBV DNA was a more reliable indicator of the presence of virus than HBe antigen and was detected in 77.0% (161/209) of HBeAg negative and in all HBeAg positive carriers. Conclusion This method is reliable, accurate, and reproducible. HBV DNA Quantification by qPCR can be used to monitor the efficacy of HBV therapy and useful in understanding the natural history of HBV in an endemic area.

OBJECTIVE: To determine differential improvements in mortality rates according to age, and to discuss differences in neonatal and post-neonatal mortality rates, using longitudinal data from the past 50 years in three rural Gambian villages. METHODS: All villagers whose date of birth was recorded were followed up until death or October 1997. A Lexis expansion was performed to categorize age: early neonatal, late neonatal, infant, 1-4 years, 5-14 years and 15 or more years. Calendar time was divided into three periods -- prior to 1975, 1975-1984 and after 1985, representing different levels of clinical care. Cox regression and likelihood-ratio test were used to model the hazards ratios. RESULTS: There were 3981 subjects included in the analysis with a total of 59 002 person-years follow-up. There was a dramatic decrease in neonatal (44 to 15), infant (162 to 36) and under-five mortality rates (397-66 per 1000) from pre-1975 to the present. The disproportionate decrease in the mortality rates means that neonatal deaths accounted for a greater percentage of post-natal deaths in later years. There was a marked seasonality in mortality rates with significantly more deaths in the 'hungry' season prior to 1975 (odds = 1.87; 95% CI = 1.62-2.17) and from 1975 to 1984 (odds = 1.84; 95% CI = 1.34-2.53). This seasonality of death has diminished in recent years (odds = 1.23; 95% CI = 0.85-1.76). CONCLUSION: Our analysis indicates a dramatic reduction in mortality rates and an attenuation in the seasonality of death. It is likely that the efficient implementation of basic currently available health measures was one of the key elements in achieving such a major reduction in mortality. Language: en

The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 (rs689) allele and birth length [effect size 17.5 (5.2–29.8) mm; P = 0.004; n = 361]. Significant associations were also found between the maternally inherited African-specific SNP 28 (rs5506) allele and post-natal weight gain [effect size 0.19 (0.05–0.32) z score points/year; P = 0.005; n = 728). These results suggest that in the Gambian population studied there are associations between polymorphic variation in the genetically diverse INS gene and foetal and early growth characteristics, which contribute to overall polygenic associations with these traits. Electronic supplementary material The online version of this article (doi:10.1007/s00439-009-0681-2) contains supplementary material, which is available to authorized users.

Background Variation in the fat mass and obesity associated (FTO) gene has been reproducibly associated with body mass index (BMI) and obesity in populations of White European origin. Data from Asians and African-Americans is less conclusive. Methods We assessed the effect of 16 FTO polymorphisms on body mass in a large population of predominantly lean Gambians (Nmax 2208) participating in a long-term surveillance program providing contemporary and early-life anthropometric measurements. Results Sixteen FTO tagSNPs screened here, including several associated with BMI in Europeans, were not associated with birth weight (BWT), early weight gain in 1–2 year olds, BMI in adults (≥ 18 y), or weight-for-height (WFH) z-score across all ages. No association was seen between genotype and WFH z-score or other measures of body mass. The confidence limits indicate that the effect size for WFH z-score never exceeded 0.17 units per allele copy for any SNP (excluding the three SNPs with allele < 15%). with much the lowest allele frequency. The confidence interval of the effect size for rs9939609 did not overlap that reported previously in Europeans. Conclusion To our knowledge this is the first study of FTO gene variation in a well-characterised African population. Our results suggest that FTO gene variation does not influence measures of body mass in Gambians living a traditional lifestyle, or has a smaller effect than that detected in Europeans. These findings are not directly comparable to results from previous studies in African-Americans due to differences in study design and analysis. It is also possible that any effect of FTO genotype on body mass is of limited relevance in a lean population where little excess food is available, compared to similar ethnic populations where food supply is plentiful.