Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine performance under ‘real world’ conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential.
The case-control methodology is frequently used to evaluate vaccine effectiveness post-licensure. The results of such studies provide important insight into the level of protection afforded by vaccines in a ‘real world’ context, and are commonly used to guide vaccine policy decisions. However, the potential for bias and confounding are important limitations to this method, and the results of a poorly conducted or incorrectly interpreted case-control study can mislead policies. In 2012, a group of experts met to review recent experience with case-control studies evaluating vaccine effectiveness; we summarize the recommendations of that group regarding best practices for data collection, analysis, and presentation of the results of case-control vaccine effectiveness studies. Vaccination status is the primary exposure of interest, but can be challenging to assess accurately and with minimal bias. Investigators should understand factors associated with vaccination as well as the availability of documented vaccination status in the study context; case-control studies may not be a valid method for evaluating vaccine effectiveness in settings where many children lack a documented immunization history. To avoid bias, it is essential to use the same methods and effort gathering vaccination data from cases and controls. Variables that may confound the association between illness and vaccination are also important to capture as completely as possible, and where relevant, adjust for in the analysis according to the analytic plan. In presenting results from case-control vaccine effectiveness studies, investigators should describe enrollment among eligible cases and controls as well as the proportion with no documented vaccine history. Emphasis should be placed on confidence intervals, rather than point estimates, of vaccine effectiveness. Case-control studies are a useful approach for evaluating vaccine effectiveness; however careful attention must be paid to the collection, analysis and presentation of the data in order to best inform evidence-based vaccine policies.
Background Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials.
Methods An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials.
Results A randomised trial can usefully be classified as ‘health equity relevant’ if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as ‘health equity relevant’ may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies.
Conclusion The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity.
randomized controlled trials
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Objective To examine gender differences in infant survival on the first day of life, in the first week of life, and in the neonatal and post-neonatal periods by socio-demographic and economic variables.
Design Secondary data analysis was performed on data from a cluster randomised trial on the effect of implementation of the Integrated Management of Neonatal and Childhood Illness programme, India.
Settings The study setting was Palwal and Faridabad, districts of Haryana, a state in North India.
Measures Multiple logistic regression models taking the cluster design into account were used to estimate gender differences in mortality in different periods of infancy.
Results A total of 60 480 infants were included in these analyses. Of 4060 infant deaths, 2054 were female (7.2% of all females born) and 2006 were male (6.3% of all males born). The death rate was significantly higher in females in the post-neonatal period but not during the neonatal period. The odds of death at 29–180 days and at 181–365 days were 1.4 (95% CI 1.3 to 1.6) and 1.7 (95% CI: 1.4 to 2.0) higher in females compared with males, respectively. This increase was seen across all socio-demographic and economic strata.
Conclusion Gender differences during the post-neonatal period are a major threat to the survival and health of female infants in India. Programmes need to identify measures that can specifically reduce female mortality.
BACKGROUND: Yearly, nearly all the estimated worldwide 2.7 million neonatal deaths occur in low- and middle-income countries. Infections, including those affecting the umbilical cord (omphalitis), are a significant factor in approximately a third of these deaths. In fact, the odds of all-cause mortality are 46% higher among neonates with omphalitis than in those without. Five large randomized controlled trials in Asia and Sub-Saharan Africa (SSA) have examined the effect of multiple cord stump applications with 4% chlorhexidine (CHX) for at least 7 days on the risk of omphalitis and neonatal death. These studies, all community-based, show that multiple CHX applications reduced the risk of omphalitis. Of these trials, only one study from South Asia (the Bangladeshi study) and none from Africa examined the effect of a single application of CHX as soon as possible after birth. In this Bangladeshi trial, CHX led to a reduction in the risk of mild-moderate omphalitis and neonatal death. It is important, in an African setting, to explore the effect of a single application among health-facility births. A single application is programmatically much simpler to implement than daily applications for 7 days. Therefore, our study compares umbilical cord cleansing with a single application of 4% CHX at birth with dry cord care among Ugandan babies born in health facilities, on the risk of omphalitis and severe neonatal illness.
METHODS: The CHX study is a facility-based, individually randomized controlled trial that will be conducted among 4760 newborns in Uganda. The primary outcomes are severe illness and omphalitis during the neonatal period. Analysis will be by intention-to-treat.
DISCUSSION: This study will provide novel evidence, from a Sub-Saharan African setting, of the effect of umbilical cord cleansing with a single application of 4% CHX at birth and identify modifiable risk factors for omphalitis.
TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02606565. Registered on 12 November 2015.
KEYWORDS: Chlorhexidine; Neonatal; Newborn; Omphalitis; Severe illness; Trial
BACKGROUND: Around 70% neonatal deaths occur in low birth weight (LBW) babies. Globally, 15% of babies are born with LBW. Kangaroo Mother Care (KMC) appears to be an effective way to reduce mortality and morbidity among LBW babies. KMC comprises of early and continuous skin-to-skin contact between mother and baby as well as exclusive breastfeeding. Evidence derived from hospital-based studies shows that KMC results in a 40% relative reduction in mortality, a 58% relative reduction in the risk of nosocomial infections or sepsis, shorter hospital stay, and a lower risk of lower respiratory tract infections in babies with birth weight <2000 g. There has been considerable interest in KMC initiated outside health facilities for LBW babies born at home or discharged early. Currently, there is insufficient evidence to support initiation of KMC in the community (cKMC). Formative research in our study setting, where 24% of babies are born with LBW, demonstrated that KMC is feasible and acceptable when initiated at home for LBW babies. The aim of this trial is to determine the impact of cKMC on the survival of these babies.
METHODS/DESIGN: This randomized controlled trial is being undertaken in the Palwal and Faridabad districts in the State of Haryana, India. Neonates weighing 1500-2250 g identified within 3 days of birth and their mothers are being enrolled. Other inclusion criteria are that the family is likely to be available in the study area over the next 6 months, that KMC was not initiated in the delivery facility, and that the infant does not have an illness requiring hospitalization. Eligible neonates are randomized into intervention and control groups. The intervention is delivered through home visits during the first month of life by study workers with a background and education similar to that of workers in the government health system. An independent study team collects mortality and morbidity data as well as anthropometric measurements during periodic home visits. The primary outcomes of the study are postenrollment neonatal mortality and mortality between enrollment and 6 months of age. The secondary outcomes are breastfeeding practices; prevalence of illnesses and care-seeking practices for the same; hospitalizations; weight and length gain; and, in a subsample, neurodevelopment.
DISCUSSION: This efficacy trial will answer the question whether the benefits of KMC observed in hospital settings can also be observed when KMC is started in the community. The formative research used for intervention development suggests that the necessary high level of KMC adoption can be reached in the community, addressing a problem that seriously constrained conclusions in the only other trial in which researchers examined the benefits of cKMC.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02653534. Registered on 26 December 2015 (retrospectively registered).
KEYWORDS: Community-initiated Kangaroo Mother Care; Low birth weight babies; Mortality
BACKGROUND: In Burkina Faso, it is not uncommon for mothers to drink alcohol, even during pregnancy. We aimed to study the association between maternal alcohol consumption during pregnancy and the child's cognitive performance using the Kaufman Assessment Battery for Children, 2nd edition (KABC-II) and the Children's Category Test Level 1 (CCT-1) in rural Burkina Faso.
METHODS:We conducted a follow-up study of a community cluster-randomised Exclusive breastfeeding trial, and re-enrolled the children in rural Burkina Faso. A total of 518 children (268 boys and 250 girls) aged 6-8 years were assessed using the KABC-II and the CCT-1. We examined the effect size difference using Cohen's d and conducted a linear regression analysis to examine the association.
RESULTS: Self-reported alcohol consumption during pregnancy was 18.5% (96/518). Children whose mothers reported alcohol consumption during pregnancy performed significantly poorly for memory and spatial abilities tests from small effect size difference for 'Atlantis' (0.27) and 'Triangle' (0.29) to moderate effect size difference for 'Number recall' (0.72) compared to children whose mothers did not consume alcohol during pregnancy; the exposed children scored significantly higher errors with a small effect size (0.37) at problem solving (CCT-1) test compared to unexposed children. At unstandardized and standardized multivariable analysis, children whose mothers reported alcohol consumption during pregnancy performed significantly poorer for memory-'Atlantis' (p = 0.03) and 'Number recall' (p = 0.0001), and spatial ability tests-'Triangle' (p = 0.03); they scored significantly higher errors at problem solving CCT-1 test (p = 0.002); all the results were adjusted for age, sex, schooling, stunting, father's education, mother's employment and the promotion of exclusive breastfeeding. No statistical association was found for visual abilities-'Conceptual Thinking', 'Face recognition', 'Story completion', and reasoning tests-'Rover', 'Block counting', and 'Pattern Reasoning'.
CONCLUSION: Maternal alcohol consumption during pregnancy is associated with poorer cognitive performance for memory, spatial ability, and problem solving tests in the offspring in rural Burkina Faso. Futures studies needs to assess in more detail the maternal alcohol consumption patterns in Burkina Faso and possible preventive strategies.
KEYWORDS: Africa; Burkina Faso; CCT-1; Child development; Children; Cognitive test; KABC-II; Maternal alcohol consumption; Pregnancy
BACKGROUND: There is no consensus on optimal Vitamin D status. The objective of this study was to estimate the extent to which vitamin D status predicts illness duration and treatment failure in children with severe pneumonia by using different cut-offs for vitamin D concentration.
METHODS: We measured the plasma-concentration of 25(OH)D in 568 children hospitalized with WHO-defined severe pneumonia. The associations between vitamin D status, using the most frequently used cut-offs of vitamin D insufficiency (25(OH)D <50 and <75 nmol/l) and risk of treatment failure and time until recovery were analysed in multiple logistic regression and Cox proportional hazards models, respectively.
RESULTS: Of the 568 children, 322 (56.7%) had plasma-25(OH)D ≥75 nmol/l, 179 (31.5%) 50-74.9 nmol/l and 67 (%) <50 nmol/l. Plasma-25(OH)D <50 nmol/l was associated with increased risk of treatment failure and longer time until recovery.
CONCLUSION: Our findings indicate that low vitamin D status (25(OH)D <50 nmol/l) is an independent risk factor for treatment failure and delayed recovery of severe lower respiratory infections in children.
TRIAL REGISTRATION: NCT00252304.Pediatric Research accepted article preview online, 05 July 2017. doi:10.1038/pr.2017.71.
BACKGROUND: An estimated 2.7 of the 5.9 million deaths in children under 5 years of age occur in the neonatal period. Severe infections contribute to almost a quarter of these deaths. Mortality due to severe infections in developing country settings is substantial despite antibiotic therapy. Effective interventions that can be added to standard therapy for severe infections are required to reduce case fatality.METHODS/DESIGN:This is a double-blind randomized placebo-controlled parallel group superiority trial to investigate the effect of zinc administered orally as an adjunct to standard therapy to infants aged 3 days up to 2 months (59 days) hospitalized with clinical severe infection, that will be undertaken in seven hospitals in Delhi, India and Kathmandu, Nepal. In a 1:1 ratio, we will randomly assign young infants to receive 10 mg of elemental zinc or placebo orally in addition to the standard therapy for a total of 14 days. The primary outcomes hospital case fatality, which is death due to any cause and at any time after enrolment while hospitalized for the illness episode, and extended case fatality, which encompasses the period until 12 weeks after enrolment.
DISCUSSION: A previous study showed a beneficial effect of zinc in reducing the risk of treatment failure, as well as a non-significant effect on case fatality. This study was not powered to detect an effect on case fatality, which this current study is. If the results are consistent with this earlier trial, we would have provided strong evidence for recommending zinc as an adjunct to standard therapy for clinical severe infection in young infants.
TRIAL REGISTRATION: Universal Trial Number: U1111-1187-6479, Clinical Trials Registry - India: CTRI/2017/02/007966 : Registered on February 27, 2017.
KEYWORDS: India; Infants; Neonate; Nepal; Sepsis; Severe infection; Zinc
OBJECTIVE:To estimate the effect of distal and proximal early life-course factors on early childhood caries (ECC) in 5-year-old Ugandan children, particularly focusing on the causal effect of exclusive breast feeding (EBF) on ECC using directed acyclic graphs (DAGs) for confounder selection.
METHODS:This study had a nested prospective cohort design, focusing on 5 years of follow-ups of caregiver-children pairs from the PROMISE-EBF trial (ClinicalTrials.gov no: NCT00397150) conducted in 2011 in Eastern Uganda. Data were from recruitment interviews, 24-week, 2-year and 5-year follow-ups of a cohort of 417 mother-children pairs. Trained research assistants performed interviews with caregivers in the local language and ECC was recorded under field conditions using the World Health Organization's (WHO) decayed missing or filled teeth (dmft) index. Early life-course factors in terms of socio-demographic characteristics, EBF and other feeding habits were assessed at the various follow-ups. The outcome (ECC; dmft>0) was assessed at the 5-year follow-up. Causal diagrams as DAGs were constructed to guide the selection of confounding and collider variables to be included in or excluded from the final multivariable analysis. Negative binomial regression analyses were performed based on two comparative DAGs representing different causal models.
RESULTS:Model 1 based on DAG 1, showed EBF to be a protective factor against ECC, with an IRR and 95% CI of 0.62 (0.43-0.91). According to Model 2 based on DAG 2, EBF and having both parents living together had protective effects: the corresponding IRRs and 95% CI were 0.60 (0.41-0.88) and 0.48 (0.25-0.90), respectively.
CONCLUSIONS:Both plausible models indicated that being exclusively breastfed for 24 weeks had a protective causal effect against ECC. Further research, examining the unmeasured variables included in the DAGs is necessary to strengthen the present finding and allow stronger causal claims.
To estimate the effect of distal and proximal early life-course factors on early childhood caries (ECC) in 5-year-old Ugandan children, particularly focusing on the causal effect of exclusive breast feeding (EBF) on ECC using directed acyclic graphs (DAGs) for confounder selection.
This study had a nested prospective cohort design, focusing on 5 years of follow-ups of caregiver-children pairs from the PROMISE-EBF trial (ClinicalTrials.gov no: NCT00397150) conducted in 2011 in Eastern Uganda. Data were from recruitment interviews, 24-week, 2-year and 5-year follow-ups of a cohort of 417 mother-children pairs. Trained research assistants performed interviews with caregivers in the local language and ECC was recorded under field conditions using the World Health Organization's (WHO) decayed missing or filled teeth (dmft) index. Early life-course factors in terms of socio-demographic characteristics, EBF and other feeding habits were assessed at the various follow-ups. The outcome (ECC; dmft>0) was assessed at the 5-year follow-up. Causal diagrams as DAGs were constructed to guide the selection of confounding and collider variables to be included in or excluded from the final multivariable analysis. Negative binomial regression analyses were performed based on two comparative DAGs representing different causal models.
Model 1 based on DAG 1, showed EBF to be a protective factor against ECC, with an IRR and 95% CI of 0.62 (0.43-0.91). According to Model 2 based on DAG 2, EBF and having both parents living together had protective effects: the corresponding IRRs and 95% CI were 0.60 (0.41-0.88) and 0.48 (0.25-0.90), respectively.
Both plausible models indicated that being exclusively breastfed for 24 weeks had a protective causal effect against ECC. Further research, examining the unmeasured variables included in the DAGs is necessary to strengthen the present finding and allow stronger causal claims.
In 2012, Tororo District had the highest malaria burden in Uganda with community Plasmodium prevalence of 48%. To control malaria in the district, the Ministry of Health introduced universal distribution of long lasting insecticide-treated nets (LLINs) in 2013 and added indoor residual spraying (IRS) in 2014. This study assessed malaria incidence, test positivity rates and outpatient (OPD) attendance due to malaria before and after vector control interventions.
This study was based on analysis of Health Management Information System (HMIS) secondary malaria surveillance data of 2,727,850 patient records in OPD registers of 61 health facilities from 2012 to 2015. The analysis estimated monthly malaria incidence for the entire population and also separately for <5- and ≥5-year-olds before and after introduction of vector control interventions; determined laboratory test positivity rates and annual percentage of malaria cases in OPD. Chi square for trends was used to analyse annual change in malaria incidence and logistic regression for monthly reduction.
Following universal LLINs coverage, the annual mean monthly malaria incidence fell from 95 cases in 2013 to 76 cases per 1000 in 2014 with no significant monthly reduction (OR = 0.99, 95% CI 0.96-1.01, P = 0.37). Among children <5 years, the malaria incidence reduced from 130 to 100 cases per 1000 (OR = 0.98, 95% CI 0.97-1.00, P = 0.08) when LLINs were used alone in 2014, but declined to 45 per 1000 in 2015 when IRS was combined with LLINs (OR = 0.94, 95% CI 0.91-0.996, P < 0.0001). Among individuals aged ≥5 years, mean monthly malaria incidence reduced from 59 to 52 cases per 1000 (OR = 0.99, 95% CI 0.97-1.02, P = 0.8) when LLINs were used alone in 2014, but reduced significantly to 25 per 1000 in 2015 (OR = 0.91, 95% CI 0.88-0.94, P < 0.0001). Malaria test positivity rate reduced from 57% in 2013 to 30% (Chi = 15, P < 0.0001) in 2015. Slide positivity rate reduced from 45% in 2013 to 21% in 2015 (P = 0.004) while RDT positivity declined from 69 to 40%.
A rapid reduction in malaria incidence was observed in Tororo District following the introduction of IRS in addition to LLINs. There was no significant reduction in malaria incidence following universal distribution of LLINs to communities before introduction of IRS.
Control; Incidence; Malaria; Reduction; Vector
Accurate and consistent classification of causes and associated conditions for perinatal deaths is essential to inform strategies to reduce the five million which occur globally each year. With the majority of deaths occurring in low- and middle-income countries (LMICs), their needs must be prioritised. The aim of this paper is to review the classification of perinatal death, the contemporary classification systems including the World Health Organization's International Classification of Diseases - Perinatal Mortality (ICD-PM), and next steps. During the period from 2009 to 2014, a total of 81 new or modified classification systems were identified with the majority developed in high-income countries (HICs). Structure, definitions and rules and therefore data on causes vary widely and implementation is suboptimal. Whereas system testing is limited, none appears ideal. Several systems result in a high proportion of unexplained stillbirths, prompting HICs to use more detailed systems that require data unavailable in low-income countries. Some systems appear to perform well across these different settings. ICD-PM addresses some shortcomings of ICD-10 for perinatal deaths, but important limitations remain, especially for stillbirths. A global approach to classification is needed and seems feasible. The new ICD-PM system is an important step forward and improvements will be enhanced by wide-scale use and evaluation. Implementation requires national-level support and dedicated resources. Future research should focus on implementation strategies and evaluation methods, defining placental pathologies, and ways to engage parents in the process.
Bacillus Calmette-Guérin (BCG) vaccination may have nonspecific effects, i.e., effects on childhood morbidity and mortality that go beyond its effect on the risk of childhood tuberculosis (TB). Though the available scientific literature is mostly from observational studies, and is fraught with controversy, BCG vaccination at birth may protect infants in high-mortality populations against serious infections other than TB. Yet, other studies indicate that giving BCG later in infancy may modify immune responses to non-TB antigens and potentially enhance immunity, potentially also against tuberculosis (TB). It is unclear whether BCG vaccination very early in life offers adequate protection against TB and other infections among HIV-1-exposed children because even those who remain uninfected with HIV-1 show signs of impaired immunocompetence early in infancy. This study will compare BCG vaccination at birth with BCG vaccination at 14 weeks of age in HIV-1-exposed infants.
This is an individually randomized controlled trial in 2200 HIV-1-exposed infants. The intervention is BCG vaccination within 24 h of birth while the comparator is BCG given at 14 weeks of age. The study co-primary outcomes are severe illness in the first 14 weeks of life, and production of tumor necrosis factor, interleukin (IL)-1β, IL-6 and interferon-γ in response to mycobacterial and nonmycobacterial antigens. The study is being conducted in three health centers in Uganda.
A well-timed BCG vaccination could have important nonspecific effects in HIV-1-exposed infants. This trial could inform the development of appropriate timing of BCG vaccination for HIV-1-exposed infants.
ClinicalTrials.gov, identifier: NCT02606526. Registered on 12 November 2015.
BCG Vaccination Infants HIV-1-exposed Nonspecific effects Trial
Parental knowledge on child development is important for maximal developmental potential. This study was conducted to assess mothers’ knowledge on child development in Nepal. The Caregivers Knowledge of Child Development Inventory (CKCDI) was used to interview mothers. Total of 1272 mothers were interviewed. Out of the total CKCDI score of 40, mean score (SD) obtained by mothers was 20 (4.8). Mothers’ knowledge on the developmental milestone composite was better than stimulation composite with scores of 11.14 (3.09) and 8.9 (3.17), respectively (p < .005). Few mothers (38%) identified the correct ages of developmental milestones. Although most of the mothers knew about teaching their children to count or name colors, few knew when to start to read with children. With low level of knowledge on child development among Nepalese mothers, early childhood development programmes should be considered integrated with other health care programmes targeting young children and families.
Using data for World Bank
Development Indicators (2015) database from 1995 to 2013, this paper explores the impact of public health expenditure on national health outcomes in Tanzania while GDP per capita and improved sanitation facilities as explanatory variables were controlled for. Two national health outcomes indicators namely, infant and under-five mortality were used as dependent variables.
With separate modeling approach, Frequentist and Bayesian based on time series and Markov Chain Monte Carlo (MCMC) respectively,
empirical evidence shows that income, represented by real GDP per capita lower infant and under-five mortality in Tanzania. Under both
methodological approach regardless of the sample size, we failed to support evidence that, public health expenditure and improved
sanitation facilities had an impact on child health outcomes. Our results imply that, public health spending in Tanzania is poorly targeted to bring good child health outcomes. The paper draws attention to policy makers in Tanzania to focus either within public health spending composition or beyond to other close determinants of infant and under-five mortality.
Background: Poor vitamin B-12 (cobalamin) status is widespread in South Asia. Insufficient vitamin B-12 status has been linked to poor neurodevelopment in young children.
Objective: We measured the associations between vitamin B-12 status in infancy (2–12 mo) and the development and cognitive functioning in Nepalese children 5 y later.
Design: Vitamin B-12 status was assessed in infancy with the use of plasma cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). At 5 y of age, we measured development with the use of the Ages and Stages Questionnaire, 3rd edition (ASQ-3), and cognitive functioning by using the Developmental Neuropsychological Assessment, 2nd edition (NEPSY II), in 320 children. In regression models, we estimated the associations between vitamin B-12 status, including a combined indicator of vitamin B-12 status (3cB12) and scores on the ASQ-3 and NEPSY II subtests.
Results: All markers of vitamin B-12 status with the exception of plasma cobalamin were significantly associated with the total ASQ-3 scores in the multiple regression models. A 1-unit increase in the 3cB12 score was associated with an increase in the total ASQ-3 score of 4.88 (95% CI: 2.09, 7.68; P = 0.001). Increases in both plasma tHcy and MMA (indicating poorer status) were associated with a decrease in scores on the NEPSY II affect recognition and geometric puzzle subtests. Each unit increment in 3cB12 scores was associated with increases of 0.82 (95% CI: 0.49, 1.14; P < 0.0005), 0.59 (95% CI: 0.10, 1.09; P = 0.020), and 0.24 (95% CI: 0.02, 0.47; P = 0.035) in the affect recognition, geometric puzzle, and block construction scores, respectively.
Conclusions: Vitamin B-12 status in infancy is associated with development and performance on social perception tasks and visuospatial abilities at 5 y of age. The long-term effects of poor vitamin B-12 status in infancy need further investigation in randomized controlled trials.
Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this paper, we examined the extent to which vitamin-D deficiency (<10 ng/ml) predicts ALRI, clinical pneumonia and diarrhea among 6 to 30 months old children.
We used data from a randomized controlled trial (RCT) of daily folic acid and/or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Generalized estimating equations (GEE) were used to examine the associations between vitamin-D deficiency and episodes of ALRI, clinical pneumonia and diarrhea.
Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status and season), that the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not associated with episodes of diarrhea or clinical pneumonia.
Vitamin-D deficiency is common in young children in New Delhi and is associated with a higher risk of ALRI. The role of vitamin D in Indian children needs to be elucidated in further studies.
BACKGROUND:Child health interventions were drastically scaled up in the period leading up to 2015 as countries aimed at meeting the 2015 target of the Millennium Development Goals (MDGs). MDGs were defined in terms of achieving improvements in average health. Significant improvements in average child health are documented, but evidence also points to rising inequality. It is important to investigate factors that drive the increasing disparities in order to inform the post-2015 development agenda of reducing inequality, as captured in the Sustainable Development Goals (SDGs). We investigated changes in socioeconomic inequality in stunting and fever in Zambia in 2007 and 2014. Unlike the huge literature that seeks to quantify the contribution of different determinants on the observed inequality at any given time, we quantify determinants of changes in inequality.METHODS:Data from the 2007 and 2014 waves of the Zambia Demographic and Health Survey (DHS) were utilized. Our sample consisted of children aged 0-5 years (n = 5,616 in 2007 and n = 12,714 in 2014). We employed multilevel models to assess the determinants of stunting and fever, which are two important child health indicators. The concentration index (CI) was used to measure the magnitude of inequality. Changes in inequality of stunting and fever were investigated using Oaxaca-type decomposition of the CI. In this approach, the change in the CI for stunting/fever is decomposed into changes in CI for each determinant and changes in the effect-measured as an elasticity-of each determinant on stunting/fever.
RESULTS:While average rates of stunting reduced in 2014 socioeconomic inequality in stunting increased significantly. Inequality in fever incidence also increased significantly, but average rates of fever did not reduce. The increase in the inequality (CI) of determinants accounted for the largest part (42.5%) of the increase in inequality of stunting, while the increase in the effect of determinants explained 35% of the increase. The determinants with the greatest total contribution (change in CI plus change in effect) to the increase in inequality of stunting were mother's height and weight, wealth, birth order, facility delivery, duration of breastfeeding, and maternal education. For fever, almost all (86%) the increase in inequality was accounted for by the increase in the effect of determinants of fever, while the distribution of determinants mattered less. The determinants with the greatest total contribution to the increase in inequality of fever were wealth, maternal education, birth order and breastfeeding duration. In the multilevel model, we found that the likelihood of a child being stunted or experiencing fever depends on the community in which they live.
CONCLUSIONS: To curb the increase in inequality of stunting and fever, policy may focus on improving levels of, and reducing inequality in, access to facility deliveries, maternal nutrition (which may be related to maternal weight and height), complementary feeding (for breastfed children), wealth, maternal education, and child care (related to birth order effects). Improving overall levels of these determinants contribute to the persistence of inequality if these determinants are unequally concentrated on the well off to begin with.
Poor vitamin D status has been associated with increased risk and severity of respiratory tract infections. Whether or not inflammation and infection affects 25-hydroxy vitamin D (25(OH)D) concentration is controversial and is important in the interpretation of observational studies using plasma-25(OH)D as a biomarker for status. Our objectives were to measure whether 25(OH)D concentration was altered by an episode of acute lower respiratory tract infection and whether markers of inflammation predicted the 25(OH)D concentration. Children aged 2-35 months with severe (n = 43) and non-severe (n = 387) community-acquired, WHO-defined pneumonia were included. 25(OH)D concentration and inflammatory markers (cytokines, chemokines, and growth factors) were measured in plasma during the acute phase and 14, 45, and 90 days later. Predictors for 25(OH)D concentrations were identified in multiple linear regression models. Mean 25(OH)D concentration during the acute phase and after recovery (14, 45, and 90 days) was 84.4 nmol/L ± 33.6, and 80.6 ± 35.4, respectively. None of the inflammatory markers predicted 25(OH)D concentration in the multiple regression models. Age was the most important predictor for 25(OH)D concentration, and there were no differences in 25(OH)D concentrations during illness and after 14, 45, and 90 days when adjusting for age. Infection and inflammation did not alter the 25(OH)D concentration in young children with acute lower respiratory tract infections.
KEYWORDS: Nepal; acute lower respiratory tract infection; children; inflammation; vitamin D