Update on the Transmission of Zika Virus Through Breast Milk and Breastfeeding: A Systematic Review of the Evidence.

We systematically searched regional and international databases and screened 1658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant to examine the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding-related practices. 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 was found to be associated with ZIKV RNA in breast milk. This review updates our previous report by including 12 new articles, in which we found no evidence of ZIKV 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 determine if ZIKV can be transmitted through breastfeeding.

Transmission of SARS-CoV-2 through breast milk and breastfeeding: a living systematic review.

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.

Presence of Ebola virus in breast milk and risk of mother-to-child transmission: synthesis of evidence.

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.

Clinical manifestations, prevalence, risk factors, outcomes, transmission, diagnosis and treatment of COVID-19 in pregnancy and postpartum: a living systematic review protocol.

INTRODUCTION: Rapid, 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 ANALYSIS: We 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 DISSEMINATION: Ethical 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 NUMBER: CRD42020178076.

Correction: Interventions for treating children and adolescents with overweight and obesity: an overview of Cochrane reviews.

This paper was originally published under a standard licence. This has now been amended to a CC BY licence in the PDF and HTML.

Effectiveness of provision of animal-source foods for supporting optimal growth and development in children 6 to 59 months of age.

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 characteristicsWe 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 resultsAnimal-source foods versus cereal-based foods or no interventionFive 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 dietOne 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 evidenceWe 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.

Deworming in non-pregnant adolescent girls and adult women: a systematic review and meta-analysis.

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).

Interventions for treating children and adolescents with overweight and obesity: an overview of Cochrane reviews.

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 <6 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.

Health Facility Staff Training for Improving Breastfeeding Outcome: A Systematic Review for Step 2 of the Baby-Friendly Hospital Initiative.

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.

Predictors of anemia in preschool children: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

Background: A lack of information on the etiology of anemia has hampered the design and monitoring of anemia-control efforts.Objective: We aimed to evaluate predictors of anemia in preschool children (PSC) (age range: 6-59 mo) by country and infection-burden category.Design: Cross-sectional data from 16 surveys (n = 29,293) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed separately and pooled by category of infection burden. We assessed relations between anemia (hemoglobin concentration <110 g/L) and severe anemia (hemoglobin concentration <70 g/L) and individual-level (age, anthropometric measures, micronutrient deficiencies, malaria, and inflammation) and household-level predictors; we also examined the proportion of anemia with concomitant iron deficiency (defined as an inflammation-adjusted ferritin concentration <12 µg/L). Countries were grouped into 4 categories on the basis of risk and burden of infectious disease, and a pooled multivariable logistic regression analysis was conducted for each group.Results: Iron deficiency, malaria, breastfeeding, stunting, underweight, inflammation, low socioeconomic status, and poor sanitation were each associated with anemia in >50% of surveys. Associations between breastfeeding and anemia were attenuated by controlling for child age, which was negatively associated with anemia. The most consistent predictors of severe anemia were malaria, poor sanitation, and underweight. In multivariable pooled models, child age, iron deficiency, and stunting independently predicted anemia and severe anemia. Inflammation was generally associated with anemia in the high- and very high-infection groups but not in the low- and medium-infection groups. In PSC with anemia, 50%, 30%, 55%, and 58% of children had concomitant iron deficiency in low-, medium-, high-, and very high-infection categories, respectively.Conclusions: Although causal inference is limited by cross-sectional survey data, results suggest anemia-control programs should address both iron deficiency and infections. The relative importance of factors that are associated with anemia varies by setting, and thus, country-specific data are needed to guide programs.

Factors associated with inflammation in preschool children and women of reproductive age: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

Background: In many settings, populations experience recurrent exposure to inflammatory agents that catalyze fluctuations in the concentrations of acute-phase proteins and certain micronutrient biomarkers such as C-reactive protein (CRP), α-1-acid glycoprotein (AGP), ferritin, and retinol. Few data are available on the prevalence and predictors of inflammation in diverse settings.Objective: We aimed to assess the relation between inflammation (CRP concentration >5 mg/L or AGP concentration >1 g/L) and covariates, such as demographics, reported illness, and anthropometric status, in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y).Design: Cross-sectional data from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project from 29,765 PSC in 16 surveys and 25,731 WRA in 10 surveys were used to model bivariable and multivariable relations.Results: The inflammation prevalence was 6.0-40.2% in PSC and 7.9-29.5% in WRA (elevated CRP) and 21.2-64.3% in PSC and 7.1-26.7% in WRA (elevated AGP). In PSC, inflammation was consistently positively associated with recent fever and malaria but not with other recent illnesses. In multivariable models that were adjusted for age, sex, urban or rural residence, and socioeconomic status, elevated AGP was positively associated with stunting (height-for-age z score <-2) in 7 of 10 surveys. In WRA, elevated CRP was positively associated with obesity [body mass index (in kg/m2) ≥30] in 7 of 9 surveys. Other covariates showed inconsistent patterns of association with inflammation. In a pooled analysis of surveys that measured malaria, stunting was associated with elevated AGP but not CRP in PSC, and obesity was associated with both elevated CRP and AGP in WRA.Conclusions: Recent morbidity and abnormal anthropometric status are consistently associated with inflammation across a range of environments, whereas more commonly collected demographic covariates were not. Because of the challenge of defining a general demographic population or environmental profile that is more likely to experience inflammation, inflammatory markers should be measured in surveys to account for their effects.

Transmission of Zika virus through breast milk and other breastfeeding-related bodily-fluids: A systematic review.

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.

Effects and safety of periconceptional oral folate supplementation for preventing birth defects.

BACKGROUND: It has been reported that neural tube defects (NTD) can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear. OBJECTIVES: This review aims to examine whether periconceptional folate supplementation reduces the risk of neural tube and other congenital anomalies (including cleft palate) without causing adverse outcomes in mothers or babies. This is an update of a previously published Cochrane review on this topic. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2015). Additionally, we searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (31 August 2015) and contacted relevant organisations to identify ongoing and unpublished studies. SELECTION CRITERIA: We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, checked data entry for accuracy and assessed the risk of bias of the included studies. We assessed the quality of the body of evidence using the GRADE approach. MAIN RESULTS: Five trials involving 7391 women (2033 with a history of a pregnancy affected by a NTD and 5358 with no history of NTDs) were included. Four comparisons were made: 1) supplementation with any folate versus no intervention, placebo or other micronutrients without folate (five trials); 2) supplementation with folic acid alone versus no treatment or placebo (one trial); 3) supplementation with folate plus other micronutrients versus other micronutrients without folate (four trials); and 4) supplementation with folate plus other micronutrients versus the same other micronutrients without folate (two trials). The risk of bias of the trials was variable. Only one trial was considered to be at low risk of bias. The remaining studies lacked clarity regarding the randomisation method or whether the allocation to the intervention was concealed. All the participants were blinded to the intervention, though blinding was unclear for outcome assessors in the five trials.The results of the first comparison involving 6708 births with information on NTDs and other infant outcomes, show a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.17 to 0.58); five studies; 6708 births; high quality evidence). Only one study assessed the incidence of NTDs and showed no evidence of an effect (RR 0.07, 95% CI 0.00 to 1.32; 4862 births) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.34, 95% CI 0.18 to 0.64); four studies; 1846 births). Subgroup analyses suggest that the positive effect of folic acid on NTD incidence and recurrence is not affected by the explored daily folic acid dosage (400 µg (0.4 mg) or higher) or whether folic acid is given alone or with other vitamins and minerals. These results are consistent across all four review comparisons.There is no evidence of any preventive or negative effects on cleft palate (RR 0.73, 95% CI 0.05 to 10.89; three studies; 5612 births; low quality evidence), cleft lip ((RR 0.79, 95% CI 0.14 to 4.36; three studies; 5612 births; low quality evidence), congenital cardiovascular defects (RR 0.57, 95% CI 0.24 to 1.33; three studies; 5612 births; low quality evidence), miscarriages (RR 1.10, 95% CI 0.94 to 1.28; five studies; 7391 pregnancies; moderate quality evidence) or any other birth defects (RR 0.94, 95% CI 0.53 to 1.66; three studies; 5612 births; low quality evidence). There were no included trials assessing the effects of this intervention on neonatal death, maternal blood folate or anaemia at term. AUTHORS' CONCLUSIONS: Folic acid, alone or in combination with vitamins and minerals, prevents NTDs, but does not have a clear effect on other birth defects.

Infant and young child feeding practices in urban Philippines and their associations with stunting, anemia, and deficiencies of iron and vitamin A.

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 socioeconomic 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.

Home gardening is associated with Filipino preschool children's dietary diversity.

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.

Host genetic factors and vaccine-induced immunity to HBV infection: haplotype analysis.

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.

Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles.

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.

Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth.

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.