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1.  Protocol for the economic evaluation of the diarrhea alleviation through zinc and oral rehydration salt therapy at scale through private and public providers in rural Gujarat and Uttar Pradesh, India 
Background
Child diarrhea persists as a leading public health problem in India despite evidence supporting zinc and low osmolarity oral rehydration salts as effective treatments. Across 2 years in 2010–2013, the Diarrhea Alleviation using Zinc and Oral Rehydration Salts Therapy (DAZT) program was implemented to operationalize delivery of these interventions at scale through private and public sector providers in rural Gujarat and Uttar Pradesh, India.
Methods/Design
This study evaluates the cost-effectiveness of DAZT program activities relative to status quo conditions existing before the study, comparing a Monte Carlo simulation method with net-benefit regression, discussing the strengths and weaknesses of each approach. A control group was not included in the ‘before and after’ study design as zinc has proven effectiveness for diarrhea treatment. Costs will be calculated using a societal perspective including program implementation and household out-of-pocket payments for care seeking, as well as estimates of wages lost. Outcomes will be measured in terms of episodes averted in net-benefit regression and in terms of the years of life lost component of disability-adjusted life years in the method based on Monte Carlo simulation. The Lives Saved Tool will be used to model anticipated changes in mortality over time and deaths averted based on incremental changes in coverage of oral rehydration salts and zinc. Data will derive from cross-sectional surveys at the start, midpoint, and endpoint of the program. In addition, Lives Saved Tool (LiST) projections will be used to define the reference case value for the ceiling ratio in terms of natural units.
Discussion
This study will be useful both in its application to an economic evaluation of a public health program in its implementation phase but also in its comparison of two methodological approaches to cost-effectiveness analysis. Both policy recommendations and methodological lessons learned will be discussed, recognizing the limitations in drawing strong policy conclusions due to the uncontrolled study design. It is expected that this protocol will be useful to researchers planning what method to use for the evaluation of similar before and after studies.
doi:10.1186/s13012-014-0164-2
PMCID: PMC4335371  PMID: 25407053
Diarrhea; Zinc; Cost-effectiveness; Implementation science; India; Private sector; Community health
2.  Diarrhea in Early Childhood: Short-term Association With Weight and Long-term Association With Length 
American Journal of Epidemiology  2013;178(7):1129-1138.
The short-term association between diarrhea and weight is well-accepted, but the long-term association between diarrhea and growth is less clear. Using data from 7 cohort studies (Peru, 1985–1987; Peru, 1989–1991; Peru, 1995–1998; Brazil, 1989–1998; Guinea-Bissau, 1987–1990; Guinea-Bissau, 1996–1997; and Bangladesh, 1993–1996), we evaluated the lagged relationship between diarrhea and growth in the first 2 years of life. Our analysis included 1,007 children with 597,638 child-days of diarrhea surveillance and 15,629 anthropometric measurements. We calculated the associations between varying diarrhea burdens during lagged 30-day periods and length at 24 months of age. The cumulative association between the average diarrhea burden and length at age 24 months was −0.38 cm (95% confidence interval: −0.59, −0.17). Diarrhea during the 30 days prior to anthropometric measurement was consistently associated with lower weight at most ages, but there was little indication of a short-term association with length. Diarrhea was associated with a small but measurable decrease in linear growth over the long term. These findings support a focus on prevention of diarrhea as part of an overall public health strategy for improving child health and nutrition; however, more research is needed to explore catch-up growth and potential confounders.
doi:10.1093/aje/kwt094
PMCID: PMC3783094  PMID: 23966558
child health; diarrhea; malnutrition; stunting; wasting
3.  Risk of childhood undernutrition related to small-for-gestational age and preterm birth in low- and middle-income countries 
Background Low- and middle-income countries continue to experience a large burden of stunting; 148 million children were estimated to be stunted, around 30–40% of all children in 2011. In many of these countries, foetal growth restriction (FGR) is common, as is subsequent growth faltering in the first 2 years. Although there is agreement that stunting involves both prenatal and postnatal growth failure, the extent to which FGR contributes to stunting and other indicators of nutritional status is uncertain.
Methods Using extant longitudinal birth cohorts (n = 19) with data on birthweight, gestational age and child anthropometry (12–60 months), we estimated study-specific and pooled risk estimates of stunting, wasting and underweight by small-for-gestational age (SGA) and preterm birth.
Results We grouped children according to four combinations of SGA and gestational age: adequate size-for-gestational age (AGA) and preterm; SGA and term; SGA and preterm; and AGA and term (the reference group). Relative to AGA and term, the OR (95% confidence interval) for stunting associated with AGA and preterm, SGA and term, and SGA and preterm was 1.93 (1.71, 2.18), 2.43 (2.22, 2.66) and 4.51 (3.42, 5.93), respectively. A similar magnitude of risk was also observed for wasting and underweight. Low birthweight was associated with 2.5–3.5-fold higher odds of wasting, stunting and underweight. The population attributable risk for overall SGA for outcomes of childhood stunting and wasting was 20% and 30%, respectively.
Conclusions This analysis estimates that childhood undernutrition may have its origins in the foetal period, suggesting a need to intervene early, ideally during pregnancy, with interventions known to reduce FGR and preterm birth.
doi:10.1093/ije/dyt109
PMCID: PMC3816349  PMID: 23920141
Foetal growth restriction; preterm birth; stunting; wasting; childhood
4.  Integrated Community Case Management of Childhood Illness in Ethiopia: Implementation Strength and Quality of Care 
Ethiopia has scaled up integrated community case management of childhood illness (iCCM) in most regions. We assessed the strength of iCCM implementation and the quality of care provided by health extension workers (HEWs). Data collectors observed HEWs' consultations with sick children and carried out gold standard re-examinations. Nearly all HEWs received training and supervision, and essential commodities were available. HEWs provided correct case management for 64% of children. The proportions of children correctly managed for pneumonia, diarrhea, and malnutrition were 72%, 79%, and 59%, respectively. Only 34% of children with severe illness were correctly managed. Health posts saw an average of 16 sick children in the previous 1 month. These results show that iCCM can be implemented at scale and that community-based HEWs can correctly manage multiple illnesses. However, to increase the chances of impact on child mortality, management of severe illness and use of iCCM services must be improved.
doi:10.4269/ajtmh.13-0751
PMCID: PMC4125273  PMID: 24799369
5.  An instrument for the assessment of diarrhoeal severity based on a longitudinal community-based study 
BMJ Open  2014;4(6):e004816.
Objective
Diarrhoea is a significant contributer to morbidity and is among the leading causes of death of children living in poverty. As such, the incidence, duration and severity of diarrhoeal episodes in the household are often key variables of interest in a variety of community-based studies. However, there currently exists no means of defining diarrhoeal severity that are (A) specifically designed and adapted for community-based studies, (B) associated with poorer child outcomes and (C) agreed on by the majority of researchers. Clinical severity scores do exist and are used in healthcare settings, but these tend to focus on relatively moderate-to-severe dehydrating and dysenteric disease, require trained observation of the child and, given the variability of access and utilisation of healthcare, fail to sufficiently describe the spectrum of disease in the community setting.
Design
Longitudinal cohort study.
Setting
Santa Clara de Nanay, a rural community in the Northern Peruvian Amazon.
Participants
442 infants and children 0–72 months of age.
Main outcome measures
Change in weight over 1-month intervals and change in length/height over 9-month intervals.
Results
Diarrhoeal episodes with symptoms of fever, anorexia, vomiting, greater number of liquid stools per day and greater number of total stools per day were associated with poorer weight gain compared with episodes without these symptoms. An instrument to measure the severity was constructed based on the duration of these symptoms over the course of a diarrhoeal episode.
Conclusions
In order to address limitations of existing diarrhoeal severity scores in the context of community-based studies, we propose an instrument comprised of diarrhoea-associated symptoms easily measured by community health workers and based on the association of these symptoms with poorer child growth. This instrument can be used to test the impact of interventions on the burden of diarrhoeal disease.
doi:10.1136/bmjopen-2014-004816
PMCID: PMC4054634  PMID: 24907244
6.  Compliance with Home-based Fortification Strategies for Delivery of Iron and Zinc: Its Effect on Haematological and Growth Markers among 6-24 months Old Children in North India 
ABSTRACT
Compliance is a key component in successful implementation of the delivery of micronutrients among children. The present study evaluates the compliance with two home-based food fortification strategies (fortified complementary food or sprinkle) for providing iron and zinc among children aged 6-24 months. A total of 292 children were randomly allocated to receive either rice-based fortified complementary food and nutrition education (Cf=101), sprinkle and nutrition education (Mp=97), or nutrition education alone as control (Ed=94). All the enrolled children were breastfed at the beginning of the study and were advised to continue breastfeeding. Biweekly information on compliance and anthropometry was collected. Complete haemogram estimation was conducted at baseline and end of the study. Compliance with the fortified complementary food was higher compared to sprinkle (Cf=81%, Mp=64% child-days). Consumption of the fortified complementary food for 6 months resulted in a significant increase in mean haemoglobin in the intervention group compared to control group (Cf 1.29±1.6 g/dL; Ed 0.23±1.3 g/dL; p<0.001). Our results showed that fortified complementary food had higher compliance than sprinkle and is a suitable delivery mechanism for iron and zinc in preschool children.
PMCID: PMC4216958  PMID: 25076659
Compliance; Fortified complementary food; Growth; Iron status; Sprinkle; Zinc
7.  Delivery, immediate newborn and cord care practices in Pemba Tanzania: a qualitative study of community, hospital staff and community level care providers for knowledge, attitudes, belief systems and practices 
Background
Deaths during the neonatal period account for almost two-thirds of all deaths in the first year of life and 40 percent of deaths before the age of five. Most of these deaths could be prevented through proven cost-effective interventions. Although there are some recent data from sub-Saharan Africa, but there is paucity of qualitative data from Zanzibar and cord care practices data from most of East Africa. We undertook a qualitative study in Pemba Island as a pilot to explore the attitudes, beliefs and practices of the community and health workers related to delivery, newborn and cord care with the potential to inform the main chlorhexidine (CHX) trial.
Methods
80 in-depth interviews (IDI) and 11 focus group discussions (FGD) involving mothers, grandmothers, fathers, traditional birth attendants and other health service providers from the community were undertaken. All IDIs and FGDs were audio taped, transcribed and analyzed using ATLAS ti 6.2.
Results
Poor transportation, cost of delivery at hospitals, overcrowding and ill treatment by hospital staff are some of the obstacles for achieving higher institutional delivery. TBAs and health professionals understand the need of using sterilized equipments to reduce risk of infection to both mothers and their babies during delivery. Despite this knowledge, use of gloves during delivery and hand washing before delivery were seldom reported. Early initiation of breastfeeding and feeding colostrum was almost universal. Hospital personnel and trained TBAs understood the importance of keeping babies warm after birth and delayed baby’s first bath. The importance of cord care was well recognized in the community. Nearly all TBAs counseled the mothers to protect the cord from dust, flies and mosquitoes or any other kind of infections by covering it with cloth. There was consensus among respondents that CHX liquid cord cleansing could be successfully implemented in the community with appropriate education and awareness.
Conclusion
The willingness of community in accepting a CHX cord care practice was very high; the only requirement was that a MCH worker needs to do and demonstrate the use to the mother.
Trial registration
ClinicalTrials.gov: NCT01528852
doi:10.1186/1471-2393-14-173
PMCID: PMC4049503  PMID: 24885689
Newborn health; Cord care; Community; Delivery; Breastfeeding; Traditional practices
8.  Lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis 
Respiratory Research  2014;15(1):50.
Background
Guidelines do not currently recommend the use of lung ultrasound (LUS) as an alternative to chest X-ray (CXR) or chest computerized tomography (CT) scan for the diagnosis of pneumonia. We conducted a meta-analysis to summarize existing evidence of the diagnostic accuracy of LUS for pneumonia in adults.
Methods
We conducted a systematic search of published studies comparing the diagnostic accuracy of LUS against a referent CXR or chest CT scan and/or clinical criteria for pneumonia in adults aged ≥18 years. Eligible studies were required to have a CXR and/or chest CT scan at the time of evaluation. We manually extracted descriptive and quantitative information from eligible studies, and calculated pooled sensitivity and specificity using the Mantel-Haenszel method and pooled positive and negative likelihood ratios (LR) using the DerSimonian-Laird method. We assessed for heterogeneity using the Q and I2 statistics.
Results
Our initial search strategy yielded 2726 articles, of which 45 (1.7%) were manually selected for review and 10 (0.4%) were eligible for analyses. These 10 studies provided a combined sample size of 1172 participants. Six studies enrolled adult patients who were either hospitalized or admitted to Emergency Departments with suspicion of pneumonia and 4 studies enrolled critically-ill adult patients. LUS was performed by highly-skilled sonographers in seven studies, by trained physicians in two, and one did not mention level of training. All studies were conducted in high-income settings. LUS took a maximum of 13 minutes to conduct. Nine studies used a 3.5-5 MHz micro-convex transducer and one used a 5–9 MHz convex probe. Pooled sensitivity and specificity for the diagnosis of pneumonia using LUS were 94% (95% CI, 92%-96%) and 96% (94%-97%), respectively; pooled positive and negative LRs were 16.8 (7.7-37.0) and 0.07 (0.05-0.10), respectively; and, the area-under-the-ROC curve was 0.99 (0.98-0.99).
Conclusions
Our meta-analysis supports that LUS, when conducted by highly-skilled sonographers, performs well for the diagnosis of pneumonia. General practitioners and Emergency Medicine physicians should be encouraged to learn LUS since it appears to be an established diagnostic tool in the hands of experienced physicians.
doi:10.1186/1465-9921-15-50
PMCID: PMC4005846  PMID: 24758612
Lung ultrasound; Pneumonia; Meta-analysis
9.  The effect of intrapartum antibiotics on early-onset neonatal sepsis in Dhaka, Bangladesh: a propensity score matched analysis 
BMC Pediatrics  2014;14:104.
Background
We estimate the effect of antibiotics given in the intrapartum period on early-onset neonatal sepsis in Dhaka, Bangladesh using propensity score techniques.
Methods
We followed 600 mother-newborn pairs as part of a cohort study at a maternity center in Dhaka. Some pregnant women received one dose of intravenous antibiotics during labor based on clinician discretion. Newborns were followed over the first seven days of life for early-onset neonatal sepsis defined by a modified version of the World Health Organization Young Infants Integrated Management of Childhood Illnesses criteria.
Using propensity scores we matched women who received antibiotics with similar women who did not. A final logistic regression model predicting sepsis was run in the matched sample controlling for additional potential confounders.
Results
Of the 600 mother-newborn pairs, 48 mothers (8.0%) received antibiotics during the intrapartum period. Seventy-seven newborns (12.8%) were classified with early-onset neonatal sepsis. Antibiotics appeared to be protective (odds ratio 0.381, 95% confidence interval 0.115–1.258), however this was not statistically significant. The results were similar after adjusting for prematurity, wealth status, and maternal colonization status (odds ratio 0.361, 95% confidence interval 0.106–1.225).
Conclusions
Antibiotics administered during the intrapartum period may reduce the risk of early-onset neonatal sepsis in high neonatal mortality settings like Dhaka.
doi:10.1186/1471-2431-14-104
PMCID: PMC4021342  PMID: 24742087
Intrapartum antibiotics; Early-onset neonatal sepsis; Propensity scores; Bangladesh
10.  Estimating Diarrheal Illness and Deaths Attributable to Shigellae and Enterotoxigenic Escherichia coli among Older Children, Adolescents, and Adults in South Asia and Africa 
Introduction
While Shigellae and strains of enterotoxigenic Escherichia coli (ETEC) are important causes of diarrhea-associated morbidity and mortality among infants and young children (<5 years of age), their health impact in older age groups is unclear. We sought to quantify the overall burden of shigellosis and ETEC diarrhea among older children, adolescents, and adults in Africa and South Asia, the two regions with the highest levels of diarrhea-related morbidity and mortality worldwide.
Methods
We employed two distinct methodological approaches to estimate the burden of diarrhea due to Shigellae and ETEC among persons ≥5 years of age in the WHO regions of South Asia (SEAR) and Africa (AFR). Under method 1, we conducted a systematic review to identify the median proportion of total deaths due to diarrhea and then applied this figure to the number of all-cause deaths that occurred in 2010 among this age group. To estimate the total number of diarrhea deaths attributable to Shigellae and ETEC, we subsequently applied previously published estimates of the median percentage of diarrhea hospitalizations due to Shigellae and ETEC to the estimated number of diarrhea deaths. For method 2, we applied previously published incidence rates to 2010 population figures and estimated the total number of episodes due to Shigellae and ETEC using published estimates of the average proportion of pathogen-positive outpatients from studies of >4 pathogens. We then estimated the number of pathogen-specific deaths by determining the number of hospitalized patients and applying the case-fatality rate.
Results
By method 1, there were 19,451 deaths due to Shigellae and 42,973 due to ETEC in AFR, and 20,691 due to Shigellae and 45,713 due to ETEC in SEAR in 2010. By method 2, there were 15.0 million ETEC episodes and 30.4 million episodes due to Shigellae in AFR, and 28.7 million episodes due to ETEC and 58.1 million episodes due to Shigellae in SEAR in 2010. We were unable to identify published case-fatality rates for ETEC and thus could only estimate Shigellae-related deaths using method 2, by which there were 5,308 and 10,158 Shigellae-related deaths in AFR and SEAR in 2010, respectively.
Discussion
Methods 1 and 2 underscore the importance of Shigellae and ETEC as major causes of morbidity and mortality among older children, adolescents, and adults in AFR and SEAR. Understanding the epidemiology of these pathogens is imperative for the development and use of future vaccines and other preventative interventions.
Author Summary
We aimed to estimate the burden of diarrhea due to Shigellae and ETEC among persons ≥5 years of age in Africa and South Asia using two methodological approaches. Method 1 employed diarrhea proportionate mortality and published estimates of pathogen-specific hospitalization. Method 2 utilized published incidence rates and case-fatality rates. Method 1 resulted in 19,451 deaths due to Shigellae and 42,973 deaths due to ETEC in AFR, and 20,691 deaths due to Shigellae and 45,713 deaths due to ETEC in SEAR in 2010. Method 2 resulted in 15.0 million episodes due to ETEC and 30.4 million episodes due to Shigellae in AFR, and 28.7 million episodes due to ETEC and 58.1 million episodes due to Shigellae in SEAR in 2010. These figures highlight the importance of Shigellae and ETEC as major causes of morbidity and mortality among older children, adolescents and adults in Africa and South Asia.
doi:10.1371/journal.pntd.0002705
PMCID: PMC3923718  PMID: 24551265
11.  Effect of Iron/Folic Acid Supplementation on the Outcome of Malaria Episodes Treated with Sulfadoxine-Pyrimethamine 
Malaria Research and Treatment  2014;2014:625905.
Folic acid supplementation may potentially alter the efficacy of sulfadoxine-pyrimethamine (SP) treatment in children with malaria. However, there is lack of evidence from randomized controlled trials and effects of folic acid supplementation on clinical efficacy of SP therapy remain moderately understood among children. In a double masked, placebo-controlled trial among preschool children in Pemba Island (Tanzania), iron and folic acid supplementation (Fe/FA) showed an increased risk of hospitalizations and death. In the present paper, we evaluated if folic acid supplementation reduced the efficacy of malaria treatment and thereby contributed to observed adverse effects. During the study, 1648 children had confirmed malarial episodes and received either sulphadoxine-pyrimethamine (SP) treatment and iron folic acid or SP treatment and placebo. These children were evaluated for recovery and incidence of hospitalization during the next 15, 30, and 140 days. Two groups did not differ in malarial episode or hospitalization rate on subsequent 15, 30, and 140 days. Altered efficacy of SP by folic acid was not observed and did not contribute to adverse events in the previous trial. This trial is registered with Controlled-trials.com ISRCTN59549825.
doi:10.1155/2014/625905
PMCID: PMC3915546  PMID: 24575311
12.  Efficiency of red cell distribution width in identification of children aged 1-3 years with iron deficiency anemia against traditional hematological markers 
BMC Pediatrics  2014;14:8.
Background
Current strategy to identify iron deficiency anemia relies on markers involving high costs. Reports have suggested red cell distribution width (RDW) as a potential screening test for identifying iron deficiency anemia (IDA) but studies in pediatric populations are lacking. Our study elucidates the discriminative ability of RDW for detecting IDA among young children.
Methods
2091 blood reports of children aged 1–3 years from an urban low socio-economic population of Delhi were analyzed to evaluate the sensitivity of RDW in discriminating IDA using receiver’s operating characteristic curve. Hemoglobin and RDW were estimated using coulter, zinc protoporphyrin with AVIV fluorometer and serum ferritin by enzyme linked immunosorbent assay.
Results
A total of 1026 samples were classified as iron deficient anemia using gold standard. As a marker of overall efficiency, area under the curve for RDW was 0.83 (95% CI, 0.81- 0.84; p < 0.001). Sensitivity of RDW at cut-off of 18% to detect iron deficiency anemia was 76.5% and specificity 73.1% yielding a positive predictive value of 73% and negative predictive value of 76%. At a cut-off of RDW 16.4%, the sensitivity was 94% and at a cut-off of 21%, the specificity was 95%. Combination of hemoglobin ≤10 g/dL and RDW >15%, yielded a sensitivity of 99% and specificity of 90%. These data suggest that simple coulter analysis estimating hemoglobin and RDW can be used for identification of children in need for iron therapy.
Conclusions
In India and similar settings, RDW >15% with hemoglobin ≤10.0 g/dL identifies iron deficient anemic children without need for iron status markers which could help reduce cost of management especially in poor settings.
Trial registration
Clinicaltrials.gov NCT00255385.
doi:10.1186/1471-2431-14-8
PMCID: PMC3897999  PMID: 24428927
Iron deficiency anemia; Red cell distribution width; RDW; Receiver’s operating characteristic curve; ROC; Screening; Sensitivity; Specificity; Children
13.  Multiple Norovirus Infections in a Birth Cohort in a Peruvian Periurban Community 
Serial norovirus infections with multiple genotypes were found among a Peruvian birth cohort early in infancy. Protection against the subsequent infection was genotype specific, suggesting that norovirus vaccines may need to target multiple genotypes.
Background. Human noroviruses are among the most common enteropathogens globally, and are a leading cause of infant diarrhea in developing countries. However, data measuring the impact of norovirus at the community level are sparse.
Methods. We followed a birth cohort of children to estimate norovirus infection and diarrhea incidence in a Peruvian community. Stool samples from diarrheal episodes and randomly selected nondiarrheal samples were tested by polymerase chain reaction for norovirus genogroup and genotype. Excretion duration and rotavirus coinfection were evaluated in a subset of episodes.
Results. Two hundred twenty and 189 children were followed to 1 and 2 years of age, respectively. By 1 year, 80% (95% confidence interval [CI], 75%–85%) experienced at least 1 norovirus infection and by 2 years, 71% (95% CI, 65%–77%) had at least 1 episode of norovirus-associated diarrhea. Genogroup II (GII) infections were 3 times more frequent than genogroup 1 (GI) infections. Eighteen genotypes were found; GII genotype 4 accounted for 41%. Median excretion duration was 34.5 days for GII vs 8.5 days for GI infection (P = .0006). Repeat infections by the same genogroup were common, but repeat infections by the same genotype were rare. Mean length-for-age z score at 12 months was lower among children with prior norovirus infection compared to uninfected children (coefficient: −0.33 [95% CI, −.65 to −.01]; P = .04); the effect persisted at 24 months.
Conclusions. Norovirus infection occurs early in life and children experience serial infections with multiple genotypes, suggesting genotype-specific immunity. An effective vaccine would have a substantial impact on morbidity, but may need to target multiple genotypes.
doi:10.1093/cid/cit763
PMCID: PMC3905757  PMID: 24300042
norovirus; infant diarrhea; gastroenteritis; birth cohort; natural infection
14.  Risk of childhood undernutrition related to small-for-gestational age and preterm birth in low- and middle-income countries 
International journal of epidemiology  2013;42(5):10.1093/ije/dyt109.
Background
Low- and middle-income countries continue to experience a large burden of stunting; 148 million children were estimated to be stunted, around 30–40% of all children in 2011. In many of these countries, foetal growth restriction (FGR) is common, as is subsequent growth faltering in the first 2 years. Although there is agreement that stunting involves both prenatal and postnatal growth failure, the extent to which FGR contributes to stunting and other indicators of nutritional status is uncertain.
Methods
Using extant longitudinal birth cohorts (n = 19) with data on birth-weight, gestational age and child anthropometry (12–60 months), we estimated study-specific and pooled risk estimates of stunting, wasting and underweight by small-for-gestational age (SGA) and preterm birth.
Results
We grouped children according to four combinations of SGA and gestational age: adequate size-for-gestational age (AGA) and preterm; SGA and term; SGA and preterm; and AGA and term (the reference group). Relative to AGA and term, the OR (95% confidence interval) for stunting associated with AGA and preterm, SGA and term, and SGA and preterm was 1.93 (1.71, 2.18), 2.43 (2.22, 2.66) and 4.51 (3.42, 5.93), respectively. A similar magnitude of risk was also observed for wasting and underweight. Low birthweight was associated with 2.5–3.5-fold higher odds of wasting, stunting and underweight. The population attributable risk for overall SGA for outcomes of childhood stunting and wasting was 20% and 30%, respectively.
Conclusions
This analysis estimates that childhood undernutrition may have its origins in the foetal period, suggesting a need to intervene early, ideally during pregnancy, with interventions known to reduce FGR and preterm birth.
doi:10.1093/ije/dyt109
PMCID: PMC3816349  PMID: 23920141
Foetal growth restriction; preterm birth; stunting; wasting; childhood
15.  Oral Zinc Supplementation for the Treatment of Acute Diarrhea in Children: A Systematic Review and Meta-Analysis 
Nutrients  2013;5(11):4715-4740.
Evidence supporting the impact of therapeutic zinc supplementation on the duration and severity of diarrhea among children under five is largely derived from studies conducted in South Asia. China experiences a substantial portion of the global burden of diarrhea, but the impact of zinc treatment among children under five has not been well documented by previously published systematic reviews on the topic. We therefore conducted a systematic literature review, which included an exhaustive search of the Chinese literature, in an effort to update previously published estimates of the effect of therapeutic zinc. We conducted systematic literature searches in various databases, including the China National Knowledge Infrastructure (CNKI), and abstracted relevant data from studies meeting our inclusion and exclusion criteria. We used STATA 12.0 to pool select outcomes and to generate estimates of percentage difference and relative risk comparing outcomes between zinc and control groups. We identified 89 Chinese and 15 non-Chinese studies for the review, including studies in 10 countries from all WHO geographic regions, and analyzed a total of 18,822 diarrhea cases (9469 zinc and 9353 control). None of the included Chinese studies had previously been included in published pooled effect estimates. Chinese and non-Chinese studies reported the effect of therapeutic zinc supplementation on decreased episode duration, stool output, stool frequency, hospitalization duration and proportion of episodes lasting beyond three and seven days. Pooling Chinese and non-Chinese studies yielded an overall 26% (95% CI: 20%−32%) reduction in the estimated relative risk of diarrhea lasting beyond three days among zinc-treated children. Studies conducted in and outside China report reductions in morbidity as a result of oral therapeutic zinc supplementation for acute diarrhea among children under five years of age. The WHO recommendation for zinc treatment of diarrhea episodes should be supported in all low- and middle-income countries.
doi:10.3390/nu5114715
PMCID: PMC3847757  PMID: 24284615
zinc; children; global health; China
16.  Millennium Development Goals 4 and 5: progress and challenges 
BMC Medicine  2013;11:225.
The Millennium Development Goals have galvanized efforts to improve child survival (MDG-4) and maternal health (MDG-5). There has been important progress on both MDGs at global level, although it now appears that few countries will reach them by the target date of 2015. There are known and efficacious interventions to address most of the major causes of these deaths, but important gaps remain. The biggest challenge is to ensure that all women and children have access to life-saving interventions. Current levels of intervention coverage are too low, representing missed opportunities. Providing services at the community level is an important emerging priority, but preventing maternal and neonatal deaths also requires access to health facilities. Readers of the Medicine for Global Health collectiona in BMC Medicine are urged to make maternal and child health one of their key concerns, even if they work on other topics.
doi:10.1186/1741-7015-11-225
PMCID: PMC3852291  PMID: 24228742
Child survival; Child mortality; Maternal survival; Maternal health; Maternal mortality; Neonatal mortality; Nutrition; Millennium Development Goals
17.  Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis 
Lancet  2013;382(9890):417-425.
Summary
Background
Babies with low birthweight (<2500 g) are at increased risk of early mortality. However, low birthweight includes babies born preterm and with fetal growth restriction, and not all these infants have a birthweight less than 2500 g. We estimated the neonatal and infant mortality associated with these two characteristics in low-income and middle-income countries.
Methods
For this pooled analysis, we searched all available studies and identified 20 cohorts (providing data for 2 015 019 livebirths) from Asia, Africa, and Latin America that recorded data for birthweight, gestational age, and vital statistics through 28 days of life. Study dates ranged from 1982 through to 2010. We calculated relative risks (RR) and risk differences (RD) for mortality associated with preterm birth (<32 weeks, 32 weeks to <34 weeks, 34 weeks to <37 weeks), small-for-gestational-age (SGA; babies with birthweight in the lowest third percentile and between the third and tenth percentile of a US reference population), and preterm and SGA combinations.
Findings
Pooled overall RRs for preterm were 6·82 (95% CI 3·56–13·07) for neonatal mortality and 2·50 (1·48–4·22) for post-neonatal mortality. Pooled RRs for babies who were SGA (with birthweight in the lowest tenth percentile of the reference population) were 1·83 (95% CI 1·34–2·50) for neonatal mortality and 1·90 (1·32–2·73) for post-neonatal mortality. The neonatal mortality risk of babies who were both preterm and SGA was higher than that of babies with either characteristic alone (15·42; 9·11–26·12).
Interpretation
Many babies in low-income and middle-income countries are SGA. Preterm birth affects a smaller number of neonates than does SGA, but is associated with a higher mortality risk. The mortality risks associated with both characteristics extend beyond the neonatal period. Differentiation of the burden and risk of babies born preterm and SGA rather than with low birthweight could guide prevention and management strategies to speed progress towards Millennium Development Goal 4—the reduction of child mortality.
Funding
Bill & Melinda Gates Foundation.
doi:10.1016/S0140-6736(13)60993-9
PMCID: PMC3796350  PMID: 23746775
18.  Systematic review of probiotics for the treatment of community-acquired acute diarrhea in children 
BMC Public Health  2013;13(Suppl 3):S16.
Background
Oral rehydration salts (ORS), zinc, and continued feeding are the recommended treatments for community-acquired acute diarrhea among young children. However, probiotics are becoming increasingly popular treatments for diarrhea in some countries. We sought to estimate the effect of probiotics on diarrhea morbidity and mortality in children < 5 years of age.
Methods
We conducted a systematic review of randomized controlled trials to estimate the effect of probiotic microorganisms for the treatment of community-acquired acute diarrhea in children. Data were abstracted into a standardized table and study quality was assessed using the Child Health Epidemiology Reference Group (CHERG) adaption of the GRADE technique. We measured the relative effect of probiotic treatment in addition to recommended rehydration on hospitalizations, duration and severity. We then calculated the average percent difference for all continuous outcomes and performed a meta-analysis for discrete outcomes.
Results
We identified 8 studies for inclusion in the final database. No studies reported diarrhea mortality and overall the evidence was low to moderate quality. Probiotics reduced diarrhea duration by 14.0% (95% CI: 3.8-24.2%) and stool frequency on the second day of treatment by 13.1% (95% CI: 0.8 – 25.3%). There was no effect on the risk of diarrhea hospitalizations.
Conclusion
Probiotics may be efficacious in reducing diarrhea duration and stool frequency during a diarrhea episode. However, only few studies have been conducted in low-income countries and none used zinc (the current recommendation) thus additional research is needed to understand the effect of probiotics as adjunct therapy for diarrhea among children in developing countries.
doi:10.1186/1471-2458-13-S3-S16
PMCID: PMC3847198  PMID: 24564646
19.  The effect of umbilical cord cleansing with chlorhexidine on omphalitis and neonatal mortality in community settings in developing countries: a meta-analysis 
BMC Public Health  2013;13(Suppl 3):S15.
Background
There is an increased risk of serious neonatal infection arising through exposure of the umbilical cord to invasive pathogen in home and facility births where hygienic practices are difficult to achieve. The World Health Organization currently recommends ‘dry cord care’ because of insufficient data in favor of or against topical application of an antiseptic. The primary objective of this meta-analysis is to evaluate the effects of application of chlorhexidine (CHX) to the umbilical cord to children born in low income countries on cord infection (omphalitis) and neonatal mortality. Standardized guidelines of Child Health Epidemiology Reference Group (CHERG) were followed to generate estimates of effectiveness of topical chlorhexidine application to umbilical cord for prevention of sepsis specific mortality, for inclusion in the Lives Saved Tool (LiST).
Methods
Systematic review and meta-analysis. Data sources included Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, CINHAL and WHO international clinical trials registry. Only randomized trials were included. Studies of children in hospital settings were excluded. The comparison group received no application to the umbilical cord (dry cord care), no intervention, or a non-CHX intervention. Primary outcomes were omphalitis and all-cause neonatal mortality.
Results
There were three cluster-randomised community trials (total participants 54,624) conducted in Nepal, Bangladesh and Pakistan that assessed impact of CHX application to the newborn umbilical cord for prevention of cord infection and mortality. Application of any CHX to the umbilical cord of the newborn led to a 23% reduction in all-cause neonatal mortality in the intervention group compared to control [RR 0.77, 95 % CI 0.63, 0.94; random effects model, I2=50 %]. The reduction in omphalitis ranged from 27 % to 56 % compared to control group depending on severity of infection. Based on CHERG rules, effect size for all-cause mortality was used for inclusion to LiST model as a proxy for sepsis specific mortality.
Conclusions
Application of CHX to newborn umbilical cord can significantly reduce incidence of umbilical cord infection and all-cause mortality among home births in community settings. This inexpensive and simple intervention can save a significant number of newborn lives in developing countries.
doi:10.1186/1471-2458-13-S3-S15
PMCID: PMC3847355  PMID: 24564621
20.  Breastfeeding for reducing the risk of pneumonia morbidity and mortality in children under two: a systematic literature review and meta-analysis 
BMC Public Health  2013;13(Suppl 3):S18.
Background
Suboptimal breastfeeding practices among infants and young children <24 months of age are associated with elevated risk of pneumonia morbidity and mortality. We conducted a systematic review and meta-analysis to quantify the protective effects of breastfeeding exposure against pneumonia incidence, prevalence, hospitalizations and mortality.
Methods
We conducted a systematic literature review of studies assessing the risk of selected pneumonia morbidity and mortality outcomes by varying levels of breastfeeding exposure among infants and young children <24 months of age. We used random effects meta-analyses to generate pooled effect estimates by outcome, age and exposure level.
Results
Suboptimal breastfeeding elevated the risk of pneumonia morbidity and mortality outcomes across age groups. In particular, pneumonia mortality was higher among not breastfed compared to exclusively breastfed infants 0-5 months of age (RR: 14.97; 95% CI: 0.67-332.74) and among not breastfed compared to breastfed infants and young children 6-23 months of age (RR: 1.92; 95% CI: 0.79-4.68).
Conclusions
Our results highlight the importance of breastfeeding during the first 23 months of life as a key intervention for reducing pneumonia morbidity and mortality.
doi:10.1186/1471-2458-13-S3-S18
PMCID: PMC3847465  PMID: 24564728
21.  The associations of parity and maternal age with small-for-gestational-age, preterm, and neonatal and infant mortality: a meta-analysis 
BMC Public Health  2013;13(Suppl 3):S2.
Background
Previous studies have reported on adverse neonatal outcomes associated with parity and maternal age. Many of these studies have relied on cross-sectional data, from which drawing causal inference is complex. We explore the associations between parity/maternal age and adverse neonatal outcomes using data from cohort studies conducted in low- and middle-income countries (LMIC).
Methods
Data from 14 cohort studies were included. Parity (nulliparous, parity 1-2, parity ≥3) and maternal age (<18 years, 18-<35 years, ≥35 years) categories were matched with each other to create exposure categories, with those who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small-for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds ratios (aOR) were calculated per study and meta-analyzed.
Results
Nulliparous, age <18 year women, compared with women who were parity 1-2 and age 18-<35 years had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR: 1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR: 1.49). Increased odds were also noted for SGA and neonatal mortality for nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity ≥3/age 18-<35 years, and preterm and neonatal mortality for parity ≥3/≥35 years.
Conclusions
Nulliparous women <18 years of age have the highest odds of adverse neonatal outcomes. Family planning has traditionally been the least successful in addressing young age as a risk factor; a renewed focus must be placed on finding effective interventions that delay age at first birth. Higher odds of adverse outcomes are also seen among parity ≥3 / age ≥35 mothers, suggesting that reproductive health interventions need to address the entirety of a woman’s reproductive period.
Funding
Funding was provided by the Bill & Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group.
doi:10.1186/1471-2458-13-S3-S2
PMCID: PMC3847520  PMID: 24564800
22.  The associations of birth intervals with small-for-gestational-age, preterm, and neonatal and infant mortality: a meta-analysis 
BMC Public Health  2013;13(Suppl 3):S3.
Background
Short and long birth intervals have previously been linked to adverse neonatal outcomes. However, much of the existing literature uses cross-sectional studies, from which deriving causal inference is complex. We examine the association between short/long birth intervals and adverse neonatal outcomes by calculating and meta-analyzing associations using original data from cohort studies conducted in low-and middle-income countries (LMIC).
Methods
We identified five cohort studies. Adjusted odds ratios (aOR) were calculated for each study, with birth interval as the exposure and small-for-gestational-age (SGA) and/or preterm birth, and neonatal and infant mortality as outcomes. The associations were controlled for potential confounders and meta-analyzed.
Results
Birth interval of shorter than 18 months had statistically significant increased odds of SGA (pooled aOR: 1.51, 95% CI: 1.31-1.75), preterm (pooled aOR: 1.58, 95% CI: 1.19-2.10) and infant mortality (pooled aOR: 1.83, 95% CI: 1.19-2.81) after controlling for potential confounding factors (reference 36-<60 months). It was also significantly associated with term-SGA, preterm-appropriate-for-gestational-age, and preterm-SGA. Birth interval over 60 months had increased risk of SGA (pooled aOR: 1.22, 95% CI: 1.07-1.39) and term-SGA (pooled aOR: 1.14, 95% CI: 1.03-1.27), but was not associated with other outcomes.
Conclusions
Birth intervals shorter than 18 months are significantly associated with SGA, preterm birth and death in the first year of life. Lack of access to family planning interventions thus contributes to the burden of adverse birth outcomes and infant mortality in LMICs. Programs and policies must assess ways to provide equitable access to reproductive health interventions to mothers before or soon after delivering a child, but also address underlying socioeconomic factors that may modify and worsen the effect of short intervals.
doi:10.1186/1471-2458-13-S3-S3
PMCID: PMC3847557  PMID: 24564484
23.  Global Causes of Diarrheal Disease Mortality in Children <5 Years of Age: A Systematic Review 
PLoS ONE  2013;8(9):e72788.
Estimation of pathogen-specific causes of child diarrhea deaths is needed to guide vaccine development and other prevention strategies. We did a systematic review of articles published between 1990 and 2011 reporting at least one of 13 pathogens in children <5 years of age hospitalized with diarrhea. We included 2011 rotavirus data from the Rotavirus Surveillance Network coordinated by WHO. We excluded studies conducted during diarrhea outbreaks that did not discriminate between inpatient and outpatient cases, reporting nosocomial infections, those conducted in special populations, not done with adequate methods, and rotavirus studies in countries where the rotavirus vaccine was used. Age-adjusted median proportions for each pathogen were calculated and applied to 712 000 deaths due to diarrhea in children under 5 years for 2011, assuming that those observed among children hospitalized for diarrhea represent those causing child diarrhea deaths. 163 articles and WHO studies done in 31 countries were selected representing 286 inpatient studies. Studies seeking only one pathogen found higher proportions for some pathogens than studies seeking multiple pathogens (e.g. 39% rotavirus in 180 single-pathogen studies vs. 20% in 24 studies with 5–13 pathogens, p<0·0001). The percentage of episodes for which no pathogen could be identified was estimated to be 34%; the total of all age-adjusted percentages for pathogens and no-pathogen cases was 138%. Adjusting all proportions, including unknowns, to add to 100%, we estimated that rotavirus caused 197 000 [Uncertainty range (UR) 110 000–295 000], enteropathogenic E. coli 79 000 (UR 31 000–146 000), calicivirus 71 000 (UR 39 000–113 000), and enterotoxigenic E. coli 42 000 (UR 20 000–76 000) deaths. Rotavirus, calicivirus, enteropathogenic and enterotoxigenic E. coli cause more than half of all diarrheal deaths in children <5 years in the world.
doi:10.1371/journal.pone.0072788
PMCID: PMC3762858  PMID: 24023773
24.  Enteric Pathogens and Reactive Arthritis: A Systematic Review of Campylobacter, Salmonella and Shigella-associated Reactive Arthritis 
Reactive arthritis (ReA) is a spondyloarthropathic disorder characterized by inflammation of the joints and tissues occurring after gastrointestinal or genitourinary infections. Diagnostic criteria for ReA do not exist and, therefore, it is subject to clinical opinion resulting in cases with a wide range of symptoms and definitions. Using standardized diagnostic criteria, we conducted a systematic literature review to establish the global incidence of ReA for each of the three most commonly-associated enteric pathogens : Campylobacter, Salmonella, and Shigella. The weighted mean incidence of reactive arthritis was 9, 12, and 12 cases per 1,000 cases of Campylobacter, Salmonella and Shigella infections respectively. To our knowledge, this is the first systematic review of worldwide data that use well-defined criteria to characterize diarrhoea-associated ReA. This information will aid in determining the burden of disease and act as a planning tool for public-health programmes.
PMCID: PMC3805878  PMID: 24288942
Campylobacter; Enteric infections; Incidence; Reactive arthritis; Salmonella; Shigella
25.  Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis 
PLoS Medicine  2013;10(8):e1001502.
Grace Chan and coauthors conducted a systematic review and meta-analysis of studies evaluating the risk of neonatal infection or colonization during the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period.
Please see later in the article for the Editors' Summary
Background
Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections) in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period.
Methods and Findings
We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4%) were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9–11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1–28.5) times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM) had a 2.3 (95% CI 1.0–5.4) times higher odds of infection than newborns of mothers without risk factors.
Conclusions
Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high neonatal mortality, are needed to determine whether targeting treatment of maternal infections or colonization, and/or prophylactic antibiotic treatment of newborns of high risk mothers, may prevent a significant proportion of early-onset neonatal sepsis.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Millennium Development Goal 4 (MDG4)—one of eight goals agreed by world leaders in 2000 to eradicate extreme poverty globally—aims to reduce under-five mortality (deaths) to one-third of its 1990 level (12 million deaths). Progress towards reducing child mortality has accelerated recently, but MDG4 is unlikely to be met, partly because of slow progress towards reducing neonatal mortality—deaths during the first 28 days of life. Neonatal deaths now account for a greater proportion of global child deaths than in 1990. Nearly half of the children who die before their fifth birthday die during the neonatal period, with babies born in low-middle-income countries in sub-Saharan Africa and southern Asia being at the highest risk of neonatal death. Bacterial infections such as infections of the bloodstream (bacteremia/sepsis), lungs (pneumonia), and the brain's protective covering (meningitis) are responsible for a quarter of neonatal deaths. Newborns can acquire infections during birth by picking up bacteria (in particular Group B streptococcus or GBS) that are present in their mother's reproductive tract and that may or may not cause disease in the mother. Bacteria colonizing the maternal perineum (the area between the anus and the vagina) can move up the vaginal canal into the amniotic sac (the fluid-filled bag in which the baby develops). Maternal bacteremia is another source of bacterial transmission from mother to fetus. Other risk factors for neonatal infection include pre-labor rupture of the membranes (PROM) of the amniotic sac, preterm PROM, and prolonged rupture of membranes.
Why Was This Study Done?
In high-income settings, prophylactic (preventative) antibiotic treatment during labor (based on microbiological screening or risk factors such as PROM) and early diagnosis and treatment of sepsis in newborn babies has greatly reduced deaths from early-onset neonatal bacterial infection. Yet, relatively little is known about the risk factors and transmission pathways for this condition globally. In this global systematic review and meta-analysis, the researchers estimate the risk of neonatal bacterial infections (excluding sexually transmitted diseases) among newborns of mothers with bacterial infection or colonization around the time of birth. A systematic review uses predefined criteria to identify all the research on a given topic; meta-analysis is a statistical method for combining the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 83 studies (only seven of which were undertaken in settings with high neonatal mortality) that included data on laboratory-confirmed maternal infection, maternal infection indicated by clinical signs and symptoms, maternal colonization (positive bacterial cultures from the reproductive tract without any signs or symptoms of infection), or risk factors for infection such as PROM and data on neonatal infection (laboratory-confirmed or clinically indicated) or colonization. Because different studies used different definitions for infection and colonization, the researchers pooled the data from subsets of the studies using random effects meta-analysis, which allows for heterogeneity (inconsistencies) between studies. Newborns of mothers with laboratory-confirmed infection had a 6.6-fold higher risk of laboratory-confirmed infection than newborns born to mothers without laboratory-confirmed infection. Newborns of mothers with bacterial colonization had a 9.4-fold higher risk of laboratory-confirmed infection than newborns of non-colonized mothers. Finally, compared to newborns of mothers without risk factors for infection, newborns of mothers with PROM or other risk factors had a 2.3-fold higher risk of infection.
What Do These Findings Mean?
These findings indicate that an increased risk of early-onset neonatal infection is associated with maternal infection and maternal colonization and provide some quantification of the excess risk. Because all the studies were facility-based and mostly from urban settings in high-income countries, these findings provide no information about the risk of neonatal infection among home births, rural births or births at community facilities in low-income countries, which limits their generalizability. Other aspects of the studies included in this systematic review and meta-analysis are also likely to limit the accuracy of the findings. Nevertheless, these findings suggest that better diagnosis and treatment of maternal infections and colonization in low- to middle-income countries where neonatal mortality is high might substantially reduce the incidence of neonatal infections and that the development of a simple algorithm that combines clinical signs and risk factors to diagnose maternal infections might be useful in regions where laboratory facilities are unavailable. Moreover, they highlight the need for more studies of maternal and neonatal infection and colonization in resource-poor settings with high neonatal mortality.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001502.
The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4 and its Childinfo website provides detailed statistics about neonatal survival and health; its Committing to Child Survival: a Promise Renewed webpage includes links to its 2012 progress report and to a video about how new health centers are helping India battle high neonatal death rates
The World Health Organization has information about Millennium Development Goal 4 and about newborn health (some information in several languages)
Countdown to 2015 provides additional information on maternal, newborn, and child survival, including its 2012 report Building a Future for Women and Children
Kidshealth, a resource provided by the not-for-profit Nemours Foundation, has information on neonatal infections for parents (in English and Spanish)
The MedlinePlus Encyclopedia has a page on neonatal sepsis (in English and Spanish)
A personal story about fatal neonatal bacterial meningitis is available on the website of Meningitis UK, a not-for profit organization; the site also includes a survivor story
doi:10.1371/journal.pmed.1001502
PMCID: PMC3747995  PMID: 23976885

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