Effects of a work schedule with abated quick returns on insomnia, sleepiness and work-related fatigue: Results from a large-scale cluster randomized controlled trial.

STUDY OBJECTIVES: To investigate the effect of a work schedule with abated quick returns (i.e., >11 hours between two shifts) on insomnia, daytime sleepiness, and work-related fatigue compared to a shift schedule maintaining the usual number of quick returns. METHODS: A two-armed cluster randomized controlled trial including 66 units was conducted at a university hospital in Norway. Units with healthcare workers on rotating shift schedules were randomly assigned to a shift schedule with abated quick returns (intervention) or to continue with a schedule including quick returns as usual (control) for six months. Questionnaires assessed symptoms of insomnia (Bergen Insomnia Scale), daytime sleepiness (Epworth Sleepiness Scale), and work-related fatigue (Revised Swedish Occupational Fatigue Inventory) at baseline and towards the end of the intervention. Data was analyzed using multilevel linear mixed-effects models, and Cohen's d was used to calculate the effect size between groups. RESULTS: Overall, 1314 healthcare workers (85.2% female) completed the baseline questionnaire (response rate 49.1%), and 552 completed the follow-up questionnaire. The intervention reduced quick returns from an average of 13.2 (SD=8.7) to 6.7 (SD=6.0), while the control group's average remained relatively unchanged from 13.2 (SD=8.7) to 12.0 (SD=9.3). Results showed a small improvement in symptoms of insomnia (BIS; d=-0.13, p=0.022) and daytime sleepiness (ESS; d=-0.14, p=0.013) in favor of the intervention. No effects were observed on work-related fatigue. CONCLUSIONS: Reducing the number of quick returns resulted in improvements in insomnia and daytime sleepiness. The findings highlight the importance of sufficient rest time in the work schedule of healthcare workers.

Early-Life Enteric Pathogen Exposure, Socioeconomic Status, and School-Age Cognitive Outcomes.

Early-life experiences of enteric infections and diarrheal illness are common in low-resource settings and are hypothesized to affect child development. However, longer-term associations of enteric infections with school-age cognitive outcomes are difficult to estimate due to lack of long-term studies. The objective of this study was to examine the relationship between enteropathogen exposure in the first 2 years of life with school-age cognitive skills in a cohort of children followed from birth until 6 to 8 years in low-resource settings in Brazil, Tanzania, and South Africa. The study included participants from three sites from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health Study who were enrolled just after birth and followed for enteric infections, diarrheal illness, and cognitive development until 2 years of age. When the children were school-age, further data were collected on reasoning skills and semantic/phonemic fluency. We estimated associations between the burden of specific enteric pathogens and etiology-specific diarrhea from 0 to 2 years with cognitive test scores at 6 to 8 years using linear regression and adjusting for confounding variables. In this study, children who carried more enteric pathogens in the first 2 years of life showed overall decreases in school-age cognitive abilities, particularly children who carried protozoa, although this was not statistically significant in this sample. Socioeconomic factors such as maternal education and income were more closely associated with school-age cognitive abilities. Early-life enteric pathogens may have a small, lasting influence on school-age cognitive outcomes, although other socioeconomic factors likely contribute more significantly.

Impact of Shigella infections and inflammation early in life on child growth and school-aged cognitive outcomes: Findings from three birth cohorts over eight years.

BACKGROUND: Shigella infections cause inflammation, which has been hypothesized to mediate the associations between Shigella and child development outcomes among children in low-resource settings. We aimed to assess whether early life inflammation and Shigella infections affect school-aged growth and cognitive outcomes from 6-8 years of age. METHODOLOGY/PRINCIPAL FINDINGS: We conducted follow-up assessments of anthropometry, reasoning skills, and verbal fluency in 451 children at 6-8 years of age in the Brazil, Tanzania, and South Africa sites of MAL-ED, a longitudinal birth cohort study. We estimated the associations between Shigella burden and inflammation with linear growth at 2, 5, and 6-8 years of age, and with the cognitive test scores using linear regression and adjusting for potential confounding variables. We also assessed whether inflammation mediated the associations between Shigella and school-aged outcomes using a regression-based approach to mediation analysis. A high prevalence of Shigella was associated with a 0.32 (95% CI: 0.08, 0.56) z-score lower height-for-age z-score (HAZ) at 6-8 years compared to a low prevalence of Shigella. Intestinal inflammation had a smaller association with HAZ at 6-8 years. Shigella burden had small and consistently negative associations with cognitive outcomes in Brazil and Tanzania, but not South Africa, and the estimates were not statistically significant. Systemic inflammation was strongly associated with lower verbal fluency scores in Brazil (semantic fluency z-score difference: -0.57, 95% CI: -1.05, -0.10; phonemic fluency z-score difference: -0.48, 95% CI: -0.93, -0.03). There was no evidence that intestinal inflammation mediated the association between Shigella and HAZ or cognitive outcomes. CONCLUSIONS/SIGNIFICANCE: While Shigella infections were consistently associated with long-term deficits in linear growth, the estimates of the negative associations between Shigella and cognitive outcomes were imprecise and only observed in the Brazil and Tanzania sites. Systemic inflammation was strongly associated with lower semantic and phonemic fluency scores in Brazil only, highlighting the site-specificity of effects.

The Epidemiology of Sapovirus in the Etiology, Risk Factors, and Interactions of Enteric Infection and Malnutrition and the Consequences for Child Health and Development Study: Evidence of Protection Following Natural Infection.

BACKGROUND: Sapovirus is one of the principal agents of acute viral enteritis in children. Because it has not been routinely included in diagnostic evaluations, the epidemiology and natural history remain poorly described. METHODS: A birth cohort of 1715 children from 8 countries contributed surveillance samples (n = 35 620) and diarrheal specimens (n = 6868) from 0 to 24 months of age. Sapovirus was detected by quantitative polymerase chain reaction concurrently to other enteropathogens using multiarray cards. Logistic regression was used to identify risk factors, and longitudinal models were employed to estimate incidence rates and evaluate evidence of protective immunity. RESULTS: Sapovirus was detected in 24.7% (n = 1665) of diarrheal stools and 12.8% (n = 4429) of monthly surveillance samples. More than 90% of children were infected and 60% experienced sapovirus diarrhea in the first 2 years of life. Breastfeeding and higher socioeconomic status were associated with reduced incidence of infection and illness. Specimens with sapovirus detected had an increased odds of coinfection with rotavirus (odds ratio [OR], 1.6 [95% confidence interval {CI}, 1.3-2.0]), astrovirus (OR, 1.5 [95% CI, 1.3-1.7]), adenovirus (OR, 1.3 [95% CI, 1.1-1.5]), and Shigella (OR, 1.4 [95% CI, 1.3-1.6]). Prior infection with sapovirus conferred a risk reduction of 22% for subsequent infection (hazard ratio [HR], 0.78 [95% CI, .74-.85]) and 24% for subsequent diarrhea (95% CI, 11.0%-35.0%; HR, 0.76). CONCLUSIONS: Sapovirus is a common cause of early childhood diarrhea. Further research on coinfections is warranted. Evidence of acquired immunity was observed even in the absence of genotype-specific analysis for this pathogen of known genetic diversity.

Health-promoting work schedules: protocol for a large-scale cluster randomised controlled trial on the effects of a work schedule without quick returns on sickness absence among healthcare workers.

INTRODUCTION: In shift work, quick returns refer to transitions between two shifts with less than 11 hours available rest time. Twenty-three per cent of employees in European countries reported having quick returns. Quick returns are related to short sleep duration, fatigue, sleepiness, work-related accidents and sickness absence. The present study is the first randomised controlled trial (RCT) to investigate the effect of a work schedule without quick returns for 6 months, compared with a work schedule that maintains quick returns during the same time frame. METHODS AND ANALYSIS: A parallel-group cluster RCT in a target sample of more than 4000 healthcare workers at Haukeland University Hospital in Norway will be conducted. More than 70 hospital units will be assessed for eligibility and randomised to a work schedule without quick returns for 6 months or continue with a schedule that maintains quick returns. The primary outcome is objective records of sickness absence; secondary outcomes are questionnaire data (n≈4000 invited) on sleep and functioning, physical and psychological health, work-related accidents and turnover intention. For a subsample, sleep diaries and objective sleep registrations with radar technology (n≈ 50) will be collected. ETHICS AND DISSEMINATION: The study protocol was approved by the Regional Committee for Medical and Health Research Ethics in Western Norway (2020/200386). Findings from the trial will be disseminated in peer-reviewed journals and presented at national and international conferences. Exploratory analyses of potential mediators and moderators will be reported. User-friendly outputs will be disseminated to relevant stakeholders, unions and other relevant societal groups. TRIAL REGISTRATION NUMBER: NCT04693182.

Cognitive Outcomes at 18 Months: Findings from the Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT) Trial.

Micronutrient deficiencies and enteric infections negatively impact child growth and development. We enrolled children shortly after birth in a randomized, placebo-controlled, 2 × 2 factorial interventional trial in Haydom, Tanzania, to assess nicotinamide and/or antimicrobials (azithromycin and nitazoxanide) effect on length at 18 months of age. Cognitive score at 18 months using the Malawi Developmental Assessment Tool (MDAT), which includes gross motor, fine motor, language, and social assessments, was a secondary outcome. Here, we present the MDAT results of 1,032 children. There was no effect of nicotinamide (change in development-for-age Z score [DAZ] -0.08; 95% CI: -0.16, 0) or antimicrobials (change in DAZ 0.04; 95% CI: -0.06, 0.13) on overall MDAT score. The interventions had no effect on cognitive outcomes in subgroups defined by gender, socioeconomic status, birthweight, and birth season or on MDAT subscores. Further analyses are needed to identify targetable risk factors for impaired cognitive development in these settings.

Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.

BACKGROUND: Stunting among children in low-resource settings is associated with enteric pathogen carriage and micronutrient deficiencies. Our goal was to test whether administration of scheduled antimicrobials and daily nicotinamide improved linear growth in a region with a high prevalence of stunting and enteric pathogen carriage. METHODS AND FINDINGS: We performed a randomized, 2 × 2 factorial, double-blind, placebo-controlled trial in the area around Haydom, Tanzania. Mother-child dyads were enrolled by age 14 days and followed with monthly home visits and every 3-month anthropometry assessments through 18 months. Those randomized to the antimicrobial arm received 2 medications (versus corresponding placebos): azithromycin (single dose of 20 mg/kg) at months 6, 9, 12, and 15 and nitazoxanide (3-day course of 100 mg twice daily) at months 12 and 15. Those randomized to nicotinamide arm received daily nicotinamide to the mother (250 mg pills months 0 to 6) and to the child (100 mg sachets months 6 to 18). Primary outcome was length-for-age z-score (LAZ) at 18 months in the modified intention-to-treat group. Between September 5, 2017 and August 31, 2018, 1,188 children were randomized, of whom 1,084 (n = 277 placebo/placebo, 273 antimicrobial/placebo, 274 placebo/nicotinamide, and 260 antimicrobial/nicotinamide) were included in the modified intention-to-treat analysis. The study was suspended for a 3-month period by the Tanzanian National Institute for Medical Research (NIMR) because of concerns related to the timing of laboratory testing and the total number of serious adverse events (SAEs); this resulted in some participants receiving their final study assessment late. There was a high prevalence of stunting overall (533/1,084, 49.2%). Mean 18-month LAZ did not differ between groups for either intervention (mean LAZ with 95% confidence interval [CI]: antimicrobial: -2.05 CI -2.13, -1.96, placebo: -2.05 CI -2.14, -1.97; mean difference: 0.01 CI -0.13, 0.11, p = 0.91; nicotinamide: -2.06 CI -2.13, -1.95, placebo: -2.04 CI -2.14, -1.98, mean difference 0.03 CI -0.15, 0.09, p = 0.66). There was no difference in LAZ for either intervention after adjusting for possible confounders (baseline LAZ, age in days at 18-month measurement, ward, hospital birth, birth month, years of maternal education, socioeconomic status (SES) quartile category, sex, whether the mother was a member of the Datoga tribe, and mother's height). Adverse events (AEs) and SAEs were overall similar between treatment groups for both the nicotinamide and antimicrobial interventions. Key limitations include the absence of laboratory measures of pathogen carriage and nicotinamide metabolism to provide context for the negative findings. CONCLUSIONS: In this study, we observed that neither scheduled administration of azithromycin and nitazoxanide nor daily provision of nicotinamide was associated with improved growth in this resource-poor setting with a high force of enteric infections. Further research remains critical to identify interventions toward improved early childhood growth in challenging conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03268902.

Influences on catch-up growth using relative versus absolute metrics: evidence from the MAL-ED cohort study.

BACKGROUND: Poor growth in early childhood has been considered irreversible after 2-3 years of age and has been associated with morbidity and mortality over the short-term and with poor economic and cognitive outcomes over the long-term. The MAL-ED cohort study was performed in eight low-income settings with the goal of evaluating relationships between the child's environment and experience (dietary, illness, and pathogen exposure, among others) and their growth and development. The goal of this analysis is to determine whether there are differences in the factors associated with growth from 24 to 60 months using two different metrics. METHODS: Across six MAL-ED sites, 942 children had anthropometry data at 24 and 60 months, as well as information about socioeconomic status, maternal height, gut permeability (lactulose-mannitol z-score (LMZ)), dietary intake from 9 to 24 months, and micronutrient status. Anthropometric changes were in height- or weight-for-age z-score (HAZ, WAZ), their absolute difference from the growth standard median (HAD (cm), WAD (kg)), as well as recovery from stunting/underweight. Outcomes were modeled using multivariate regression. RESULTS: At 24 months, almost half of the cohort was stunted (45%) and 21% were underweight. Among those who were stunted at 24 months (n = 426), 185 (43%) were no longer stunted at 60 months. Most children increased their HAZ from 24 to 60 months (81%), whereas fewer (33%) had positive changes in their HAD. Linear regression models indicate that girls improved less than boys from 24 to 60 months (HAZ: -0.21 (95% CI -0.27, -0.15); HAD: -0.75 (-1.07, -0.43)). Greater intestinal permeability (higher LMZ) at 0-24 months was associated with lower relative and absolute changes from 24 to 60 months (HAZ: -0.10 (-0.16, -0.04); HAD: -0.47 (-0.73, -0.21)). Maternal height (per 10 cm) was positively associated with changes (HAZ: 0.09 (0.03, 0.15); HAD: 0.45 (0.15, 0.75)). Similar relationships were identified for changes in WAZ and WAD. CONCLUSIONS: The study children demonstrated improved growth from 24 to 60 months of age, but only a subset had positive changes in HAD and WAD. The same environmental factors were associated with growth from 24 to 60 months regardless of metric used (change in HAZ or HAD, or WAZ and WAD).

Early Life Experiences and Trajectories of Cognitive Development.

BACKGROUND: Multiple factors constrain the trajectories of child cognitive development, but the drivers that differentiate the trajectories are unknown. We examine how multiple early life experiences differentiate patterns of cognitive development over the first 5 years of life in low-and middle-income settings. METHODS: Cognitive development of 835 children from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite observational cohort study was assessed at 6, 15, 24 (Bayley Scales of Infant and Toddler Development), and 60 months (Wechsler Preschool and Primary Scale of Intelligence). Markers of socioeconomic status, infection, illness, dietary intake and status, anthropometry, and maternal factors were also assessed. Trajectories of development were determined by latent class-mixed models, and factors associated with class membership were examined by discriminant analysis. RESULTS: Five trajectory groups of cognitive development are described. The variables that best discriminated between trajectories included presence of stimulating and learning resources in the home, emotional or verbal responsivity of caregiver and the safety of the home environment (especially at 24 and 60 months), proportion of days (0-24 months) for which the child had diarrhea, acute lower respiratory infection, fever or vomiting, maternal reasoning ability, mean nutrient densities of zinc and phytate, and total energy from complementary foods (9-24 months). CONCLUSIONS: A supporting and nurturing environment was the variable most strongly differentiating the most and least preferable trajectories of cognitive development. In addition, a higher quality diet promoted cognitive development while prolonged illness was indicative of less favorable patterns of development.

Baseline Characteristics of Study Participants in the Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT) Trial.

Recurrent enteric infections and micronutrient deficiencies, including deficiencies in the tryptophan-kynurenine-niacin pathway, have been associated with environmental enteric dysfunction, potentially contributing to poor child growth and development. We are conducting a randomized, placebo-controlled, 2 × 2 factorial interventional trial in a rural population in Haydom, Tanzania, to determine the effect of 1) antimicrobials (azithromycin and nitazoxanide) and/or 2) nicotinamide, a niacin vitamer, on attained length at 18 months. Mother/infant dyads were enrolled within 14 days of the infant's birth from September 2017 to September 2018, with the follow-up to be completed in February 2020. Here, we describe the baseline characteristics of the study cohort, risk factors for low enrollment weight, and neonatal adverse events (AEs). Risk factors for a low enrollment weight included being a firstborn child (-0.54 difference in weight-for-age z-score [WAZ] versus other children, 95% CI: -0.71, -0.37), lower socioeconomic status (-0.28, 95% CI: -0.43, -0.12 difference in WAZ), and birth during the preharvest season (November to March) (-0.22, 95% CI: -0.33, -0.11 difference in WAZ). The most common neonatal serious AEs were respiratory tract infections and neonatal sepsis (2.2 and 1.4 events per 100 child-months, respectively). The study cohort represents a high-risk population for whom interventions to improve child growth and development are urgently needed. Further analyses are needed to understand the persistent impacts of seasonal malnutrition and the interactions between seasonality, socioeconomic status, and the study interventions.

Psychosocial and environmental determinants of child cognitive development in rural south africa and tanzania: findings from the mal-ed cohort.

BACKGROUND: Approximately 66% of children under the age of 5 in Sub-Saharan African countries do not reach their full cognitive potential, the highest percentage in the world. Because the majority of studies investigating child cognitive development have been conducted in high-income countries (HICs), there is limited knowledge regarding the determinants of child development in low- and middle-income countries (LMICs). METHODS: This analysis includes 401 mother-child dyads from the South Africa and Tanzania sites of the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal birth cohort study. We investigated the effect of psychosocial and environmental determinants on child cognitive development measured by the Wechsler Preschool Primary Scales of Intelligence (WPPSI) at 5 years of age using multivariable linear regression. RESULTS: Socioeconomic status was most strongly associated with child cognitive development (WPSSI Score Difference (SD):14.27, 95% CI:1.96, 26.59). Modest associations between the organization of the home environment and its opportunities for cognitive stimulation and child cognitive development were also found (SD: 3.08, 95% CI: 0.65, 5.52 and SD: 3.18, 95% CI: 0.59, 5.76, respectively). CONCLUSION: This study shows a stronger association with child cognitive development at 5 years of age for socioeconomic status compared to more proximal measures of psychosocial and environmental determinants. A better understanding of the role of these factors is needed to inform interventions aiming to alleviate the burden of compromised cognitive development for children in LMICs.

Frequent refresher training on newborn resuscitation and potential impact on perinatal outcome over time in a rural Tanzanian hospital: an observational study.

OBJECTIVES: Globally, perinatal mortality remains high, especially in sub-Saharan countries, mainly because of inadequate obstetric and newborn care. Helping Babies Breathe (HBB) resuscitation training as part of a continuous quality improvement (CQI) programme may improve outcomes. The aim of this study was to describe observed changes in perinatal survival during a 6-year period, while adjusting for relevant perinatal risk factors. SETTING: Delivery rooms and operating theatre in a rural referral hospital in northern-central Tanzania providing comprehensive obstetric and basic newborn care 24 hours a day. The hospital serves approximately 2 million people comprising low social-economic status. PARTICIPANTS: All newborns (n=31 122) born in the hospital from February 2010 through January 2017; 4893 were born in the 1-year baseline period (February 2010 through January 2011), 26 229 in the following CQI period. INTERVENTIONS: The HBB CQI project, including frequent HBB training, was implemented from February 2011. This is a quality assessment analysis of prospectively collected observational data including patient, process and outcome measures of every delivery. Logistic regression modelling was used to construct risk-adjusted variable life adjusted display (VLAD) and cumulative sum (CUSUM) plots to monitor changes in perinatal survival (primary outcome). RESULTS: During the 6-year CQI period, the unadjusted number of extra lives saved according to the VLAD plot was 150 despite more women admitted with pregnancy and labour complications and more caesarean deliveries. After adjusting for these risk factors, the risk-adjusted VLAD plot indicated that an estimated 250 extra lives were saved. The risk-adjusted CUSUM plot confirmed a persistent and steady increase in perinatal survival. CONCLUSIONS: The risk-adjusted statistical process control methods indicate significant improvement in perinatal survival after initiation of the HBB CQI project with continuous focus on newborn resuscitation training during the period, despite a concomitant increase in high-risk deliveries. Risk-adjusted VLAD and CUSUM are useful methods to quantify, illustrate and demonstrate persistent changes in outcome over time.

Early Life Child Micronutrient Status, Maternal Reasoning, and a Nurturing Household Environment have Persistent Influences on Child Cognitive Development at Age 5 years: Results from MAL-ED.

BACKGROUND: Child cognitive development is influenced by early-life insults and protective factors. To what extent these factors have a long-term legacy on child development and hence fulfillment of cognitive potential is unknown. OBJECTIVE: The aim of this study was to examine the relation between early-life factors (birth to 2 y) and cognitive development at 5 y. METHODS: Observational follow-up visits were made of children at 5 y, previously enrolled in the community-based MAL-ED longitudinal cohort. The burden of enteropathogens, prevalence of illness, complementary diet intake, micronutrient status, and household and maternal factors from birth to 2 y were extensively measured and their relation with the Wechsler Preschool Primary Scales of Intelligence at 5 y was examined through use of linear regression. RESULTS: Cognitive T-scores from 813 of 1198 (68%) children were examined and 5 variables had significant associations in multivariable models: mean child plasma transferrin receptor concentration (ß: -1.81, 95% CI: -2.75, -0.86), number of years of maternal education (ß: 0.27, 95% CI: 0.08, 0.45), maternal cognitive reasoning score (ß: 0.09, 95% CI: 0.03, 0.15), household assets score (ß: 0.64, 95% CI: 0.24, 1.04), and HOME child cleanliness factor (ß: 0.60, 95% CI: 0.05, 1.15). In multivariable models, the mean rate of enteropathogen detections, burden of illness, and complementary food intakes between birth and 2 y were not significantly related to 5-y cognition. CONCLUSIONS: A nurturing home context in terms of a healthy/clean environment and household wealth, provision of adequate micronutrients, maternal education, and cognitive reasoning have a strong and persistent influence on child cognitive development. Efforts addressing aspects of poverty around micronutrient status, nurturing caregiving, and enabling home environments are likely to have lasting positive impacts on child cognitive development.

Effects of Child and Maternal Histo-Blood Group Antigen Status on Symptomatic and Asymptomatic Enteric Infections in Early Childhood.

BACKGROUND: Histo-blood group antigens (HBGAs) such as fucosyltransferase (FUT)2 and 3 may act as innate host factors that differentially influence susceptibility of individuals and their offspring to pediatric enteric infections. METHODS: In 3 community-based birth cohorts, FUT2 and FUT3 statuses were ascertained for mother-child dyads. Quantitative polymerase chain reaction panels tested 3663 diarrheal and 18 148 asymptomatic stool samples for 29 enteropathogens. Cumulative diarrhea and infection incidence were compared by child (n = 520) and mothers' (n = 519) HBGA status and hazard ratios (HRs) derived for all-cause diarrhea and specific enteropathogens. RESULTS: Children of secretor (FUT2 positive) mothers had a 38% increased adjusted risk of all-cause diarrhea (HR = 1.38; 95% confidence interval (CI), 1.15-1.66) and significantly reduced time to first diarrheal episode. Child FUT2 and FUT3 positivity reduced the risk for all-cause diarrhea by 29% (HR = 0.81; 95% CI, 0.71-0.93) and 27% (HR = 0.83; 95% CI, 0.74-0.92), respectively. Strong associations between HBGAs and pathogen-specific infection and diarrhea were observed, particularly for noroviruses, rotaviruses, enterotoxigenic Escherichia coli, and Campylobacter jejuni/coli. CONCLUSIONS: Histo-blood group antigens affect incidence of all-cause diarrhea and enteric infections at magnitudes comparable to many common disease control interventions. Studies measuring impacts of interventions on childhood enteric disease should account for both child and mothers' HBGA status.

Seasonal Food Insecurity in Haydom, Tanzania, Is Associated with Low Birthweight and Acute Malnutrition: Results from the MAL-ED Study.

In rural agricultural communities in Africa, particularly those with a single annual harvest, the preharvest period has been associated with increased food insecurity. We estimated the association between seasonal food insecurity and childhood malnutrition in Haydom, Tanzania. Children enrolled in a birth cohort study were followed twice weekly to document food intake and monthly for anthropometry until the age of 2 years. Household food insecurity was reported by caregivers every 6 months. We modeled the seasonality of food insecurity and food consumption, and estimated the impact of birth season on enrollment weight and subsequent malnutrition. Finally, we described the seasonality of admissions for acute malnutrition at a local referral hospital (Haydom Lutheran Hospital) from 2010 to 2015. Food insecurity was highly seasonal, with a peak from December to February. Children born during these 3 months had an average 0.35 z-score (95% CI: 0.12, 0.58) lower enrollment weight than children born in other months. In addition, weight-for-length z-scores measured in these months were on average 0.15 z-scores lower (95% CI: 0.10, 0.20) than that in other months, adjusting for enrollment weight and seasonal infectious diseases, and this disparity was sustained up to the age of 2 years. Correspondingly, the number of admissions with acute malnutrition at the local hospital was highest at this time, with twice as many cases in December-February compared with June-August. We identified acute and chronic malnutrition associated with seasonal food insecurity and intake. Targeting of prenatal care and child-feeding interventions during high food insecurity months may help reduce child malnutrition.

Long working hours are inversely related to sick leave in the following 3 months: a 4-year registry study.

PURPOSE: The aim of this study was to investigate the effects of long working hours (≥ 12 h shifts) on sick leave using objective records of shift work exposure and of sick leave. METHODS: A total of 1538 nurses (mean age 42.5, SD 12.0; response rate 42%) participated. Payroll and archival sick leave data over a 4-year period were retrieved from employers' records and aggregated over every third calendar month. A multilevel negative binomial model was used to investigate the effects of exposure to long working hours, on subsequent sick leave rates the following 3 months. Covariates included prior sick leave, number of shifts worked, night and evening shifts, personality, and demographic characteristics. RESULTS: Exposure to long working hours was associated with fewer sick leave days in the subsequent 3 months [adjusted model, incidence rate ratio (IRR) = 0.946, 95% CI 0.919-0.973, p < 0.001]. The interaction long working hours by a number of work days showed that sick leave days the subsequent 3 months was higher by long shifts when number of shifts was high compared to when number of shifts was low [adjusted model, IRR 1.002, 95% CI 1.000-1.004, p < 0.05]. DISCUSSION: Long working hours was associated with fewer sick leave days. The restorative effects of extra days off with long working hours are discussed as possible explanations to this relationship.

Assessing development across cultures: Invariance of the Bayley-III Scales Across Seven International MAL-ED sites.

The Bayley's Scales of Infant and Toddler Development-Third Edition (Bayley-III) were used to measure the development of 24-month-old children (N = 1,452) in the Interactions of Malnutrition and Enteric Infections: Consequences for Child Health and Development (MAL-ED) study (an international, multisite study on many aspects of child development). This study examined the factor structure and measurement equivalence/invariance of Bayley-III scores across 7 international research sites located in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, and South Africa. Exploratory and confirmatory factor analyses were used to identify the factor structure of Bayley-III scores. Subsequently, reliability analyses and item response theory analyses were applied, and invariance was examined using multiple-indicator, multiple-cause modeling. The findings supported the validity, but not invariance, of Bayley-III language scores at all seven sites and of the cognitive and motor scores at six sites. These findings provide support for the use of scores for research purposes, but mean comparison between sites is not recommended. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT): a protocol for a randomised factorial, double-blind, placebo-controlled trial of azithromycin, nitazoxanide and nicotinamide.

INTRODUCTION: In many developing areas in the world, a high burden of enteric pathogens in early childhood are associated with growth deficits. The tryptophan-kynurenine-niacin pathway has been linked to enteric inflammatory responses to intestinal infections. However, it is not known in these settings whether scheduled antimicrobial intervention to reduce subclinical enteric pathogen carriage or repletion of the tryptophan-kynurenine-niacin pathway improves linear growth and development. METHODS AND ANALYSIS: We are conducting a randomised, placebo-controlled, factorial intervention trial in the rural setting of Haydom, Tanzania. We are recruiting 1188 children within the first 14 days of life, who will be randomised in a 2×2 factorial design to administration of antimicrobials (azithromycin and nitazoxanide, randomised together) and nicotinamide. The nicotinamide is administered as a daily oral dose, which for breast-feeding children aged 0-6 months is given to the mother and for children aged 6-18 months is given to the child directly. Azithromycin is given to the child as a single oral dose at months 6, 9, 12 and 15; nitazoxanide is given as a 3-day course at months 12 and 15. Mother/child pairs are followed via monthly in-home visits. The primary outcome is the child's length-for-age Z-score at 18 months. Secondary outcomes for the child include additional anthropometry measures; stool pathogen burden and bacterial microbiome; systemic and enteric inflammation; blood metabolomics, growth factors, inflammation and nutrition; hydrogen breath assessment to estimate small-intestinal bacterial overgrowth and assessment of cognitive development. Secondary outcomes for the mother include breastmilk content of nicotinamide, other vitamins and amino acids; blood measures of tryptophan-kynurenine-niacin pathway and stool pathogens. ETHICS AND DISSEMINATION: This trial has been approved by the Tanzanian National Institute for Medical Research, the Tanzanian FDA and the University of Virginia IRB. Findings will be presented at national and international conferences and published in peer-review journals. PROTOCOL VERSION: 5.0, 4 December 2017. PROTOCOL SPONSOR: Haydom Lutheran Hospital, Haydom, Manyara, Tanzania. TRIAL REGISTRATION NUMBER: NCT03268902; Pre-results.

Evaluating meteorological data from weather stations, and from satellites and global models for a multi-site epidemiological study.

BACKGROUND: Longitudinal and time series analyses are needed to characterize the associations between hydrometeorological parameters and health outcomes. Earth Observation (EO) climate data products derived from satellites and global model-based reanalysis have the potential to be used as surrogates in situations and locations where weather-station based observations are inadequate or incomplete. However, these products often lack direct evaluation at specific sites of epidemiological interest. METHODS: Standard evaluation metrics of correlation, agreement, bias and error were applied to a set of ten hydrometeorological variables extracted from two quasi-global, commonly used climate data products - the Global Land Data Assimilation System (GLDAS) and Climate Hazards Group InfraRed Precipitation with Stations (CHIRPS) - to evaluate their performance relative to weather-station derived estimates at the specific geographic locations of the eight sites in a multi-site cohort study. These metrics were calculated for both daily estimates and 7-day averages and for a rotavirus-peak-season subset. Then the variables from the two sources were each used as predictors in longitudinal regression models to test their association with rotavirus infection in the cohort after adjusting for covariates. RESULTS: The availability and completeness of station-based validation data varied depending on the variable and study site. The performance of the two gridded climate models varied considerably within the same location and for the same variable across locations, according to different evaluation criteria and for the peak-season compared to the full dataset in ways that showed no obvious pattern. They also differed in the statistical significance of their association with the rotavirus outcome. For some variables, the station-based records showed a strong association while the EO-derived estimates showed none, while for others, the opposite was true. CONCLUSION: Researchers wishing to utilize publicly available climate data - whether EO-derived or station based - are advised to recognize their specific limitations both in the analysis and the interpretation of the results. Epidemiologists engaged in prospective research into environmentally driven diseases should install their own weather monitoring stations at their study sites whenever possible, in order to circumvent the constraints of choosing between distant or incomplete station data or unverified EO estimates.

Exposure to aflatoxin and fumonisin in children at risk for growth impairment in rural Tanzania.

Growth impairment is a major public health issue for children in Tanzania. The question remains as to whether dietary mycotoxins play a role in compromising children's growth. We examined children's exposures to dietary aflatoxin and fumonisin and potential impacts on growth in 114 children under 36 months of age in Haydom, Tanzania. Plasma samples collected from the children at 24 months of age (N = 60) were analyzed for aflatoxin B1-lysine (AFB1-lys) adducts, and urine samples collected between 24 and 36 months of age (N = 94) were analyzed for urinary fumonisin B1 (UFB1). Anthropometric, socioeconomic, and nutritional parameters were measured and growth parameter z-scores were calculated for each child. Seventy-two percent of the children had detectable levels of AFB1-lys, with a mean level of 5.1 (95% CI: 3.5, 6.6) pg/mg albumin; and 80% had detectable levels of UFB1, with a mean of 1.3 (95% CI: 0.8, 1.8) ng/ml. This cohort had a 75% stunting rate [height-for-age z-scores (HAZ) < -2] for children at 36 months. No associations were found between aflatoxin exposures and growth impairment as measured by stunting, underweight [weight-for-age z-scores (WAZ) < -2], or wasting [weight-for-height z-scores (WHZ) < -2]. However, fumonisin exposure was negatively associated with underweight (with non-detectable samples included, p = 0.0285; non-detectable samples excluded, p = 0.005) in this cohort of children. Relatively low aflatoxin exposure at 24 months was not linked with growth impairment, while fumonisin exposure at 24-36 months based on the UFB1 biomarkers may contribute to the high growth impairment rate among children of Haydom, Tanzania; which may be associated with their breast feeding and weaning practices.