Trajectory of maternal depression and parasomnias.

Maternal depressive symptoms are associated with poorer sleep quality in their children. Although parasomnias can occur at any age, this group of sleep disorders is more common in children. The aim of this study was to assess whether maternal depression trajectories predict parasomnias at the age of 11 years. Data were from a Birth Cohort of 4231 individuals followed in the city of Pelotas, Brazil. Maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS) at 12, 24, and 48 months, and 6 and 11 years postpartum. Maternal depression trajectories were calculated using a group-based modelling approach. Information on any parasomnias (confused arousals, sleepwalking, night terrors, and nightmares) was provided by the mother. Five trajectories of maternal depressive symptoms were identified: chronic-low (34.9%), chronic-moderate (41.4%), increasing (10.3%), decreasing (8.9%), and chronic-high (4.4%). The prevalence of any parasomnia at the age of 11 years was 16.8% (95% confidence interval [CI] 15.6%-18.1%). Confusional arousal was the most prevalent type of parasomnia (14.5%) and varied from 8.7% to 14.7%, 22.9%, 20.3%, and 27.5% among children of mothers at chronic-low, moderate-low, increasing, decreasing, and chronic-high trajectories, respectively (p < 0.001). Compared to children from mothers in the chronic-low trajectory, the adjusted prevalence ratio for any parasomnia was 1.58 (95% CI 1.29-1.94), 2.34 (95% CI 1.83-2.98), 2.15 (95% CI 1.65-2.81), and 3.07 (95% CI 2.31-4.07) among those from mothers in the moderate-low, increasing, decreasing, and chronic-high trajectory groups, respectively (p < 0.001). In conclusion, parasomnias were more prevalent among children of mothers with chronic symptoms of depression.

Associations between human milk oligosaccharides and infant growth in a Bangladeshi mother-infant cohort.

BACKGROUND: We aimed to estimate associations between human milk oligosaccharides (HMOs) and infant growth (length-for-age (LAZ) and weight-for-length (WLZ) z-scores) at 12 months postnatal age. METHODS: In this secondary analysis of data from a maternal vitamin D trial in Dhaka, Bangladesh (N = 192), absolute concentrations of HMOs were measured in 13 ± 1 week(s) postpartum milk samples, infant anthropometric measurements were obtained soon after birth and at 12 months postpartum, and infant feeding was classified during 6 months postpartum. Associations between individual HMOs or HMO groups and LAZ or WLZ were estimated by multivariable linear regression adjusting for infant feeding pattern, maternal secretor status, and other potential confounders. RESULTS: The concentrations of 6'sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated HMOs were inversely associated with LAZ at 12 months of age, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months. These associations were robust in analyses restricted to infants who were primarily exclusively/predominantly fed human milk during the first 3 (or 6) months. CONCLUSIONS: Since HMOs are both positively and negatively associated with postnatal growth, there is a need for randomized trials to estimate the causal benefits and risks of exogenously administered HMOs on infant growth and other health outcomes. IMPACT: 6'sialyllactose, lacto-N-neotetraose, and the non-fucosylated non-sialylated human milk oligosaccharides (HMOs) were inversely associated with length-for-age z-scores (LAZ) at 12 months, whereas the fucosylated non-sialylated HMO concentration was positively associated with LAZ at 12 months among Bangladeshi infants. Associations between individual and grouped HMOs with infant length growth at 12 months were as strong or stronger in analyses restricted to infants who were exclusively or predominantly fed human milk up to 3 (or 6) months. Randomized trials are needed to characterize the effects of specific HMOs on infant growth, particularly in countries where postnatal linear growth faltering is common.

An integrated newborn care kit (iNCK) to save newborn lives and improve health outcomes in Gilgit Baltistan (GB), Pakistan: study protocol for a cluster randomized controlled trial.

BACKGROUND: Ongoing high neonatal mortality rates (NMRs) represent a global challenge. In 2021, of the 5 million deaths reported worldwide for children under five years of age, 47% were newborns. Pakistan has one of the five highest national NMRs in the world, with an estimated 39 neonatal deaths per 1,000 live births. Reducing newborn deaths requires sustainable, evidence-based, and cost-effective interventions that can be integrated within existing community healthcare infrastructure across regions with high NMR. METHODS: This pragmatic, community-based, parallel-arm, open-label, cluster randomized controlled trial aims to estimate the effect of Lady Health Workers (LHWs) providing an integrated newborn care kit (iNCK) with educational instructions to pregnant women in their third trimester, compared to the local standard of care in Gilgit-Baltistan, Pakistan, on neonatal mortality and other newborn and maternal health outcomes. The iNCK contains a clean birth kit, 4% chlorhexidine topical gel, sunflower oil emollient, a ThermoSpot™ temperature monitoring sticker, a fleece blanket, a click-to-heat reusable warmer, three 200 µg misoprostol tablets, and a pictorial instruction guide and diary. LHWs are also provided with a handheld scale to weigh the newborn. The primary study outcome is neonatal mortality, defined as a newborn death in the first 28 days of life. DISCUSSION: This study will generate policy-relevant knowledge on the effectiveness of integrating evidence-based maternal and newborn interventions and delivering them directly to pregnant women via existing community health infrastructure, for reducing neonatal mortality and morbidity, in a remote, mountainous area with a high NMR. TRIAL REGISTRATION: NCT04798833, March 15, 2021.

Influence of maternal excess weight before pregnancy on breast-feeding and weaning: pooled analyses of four population-based cohorts born between 1982 and 2015.

To investigate the associations of maternal excess weight before pregnancy with (1) weaning at 3 months of age, (2) duration of exclusive breast-feeding at 6 months of age, (3) duration of any breast-feeding at 12 months of age and (4) to compare the magnitude of these associations over four decades. Data were from participants in the Pelotas (Brazil) Birth Cohorts born in 1982 (n 5334), 1993 (n 1442), 2004 (n 4092) and 2015 (n 4102). Maternal pre-pregnancy weight was collected after the delivery and breast-feeding status was assessed when children were 3 and 12 months old. Only in the most recent cohort (2015), women with excess weight (BMI ≥ 25 kg/m2) before pregnancy had higher risk of discontinuing exclusive breast-feeding within the first 6 months postpartum than women with normal weight (hazard ratio = 1·22 (95 % CI 1·15, 1·30)). Duration of any type of breast-feeding until 12 months of age was not affected by pre-pregnancy weight. Excess weight before pregnancy is associated with exclusive breast-feeding only in the most recent birth cohort coinciding with increases in excess weight and breast-feeding over time.

A Bayesian adaptive design for clinical trials of rare efficacy outcomes with multiple definitions.

INTRODUCTION: Bayesian adaptive designs for clinical trials have gained popularity in the recent years due to the flexibility and efficiency that they offer. We consider the scenario where the outcome of interest comprises events with relatively low risk of occurrence and different case definitions resulting in varying control group risk assumptions. This is a scenario that occurs frequently for infectious diseases in global health research. METHODS: We propose a Bayesian adaptive design that incorporates different case definitions of the outcome of interest that vary in stringency. A set of stopping rules are proposed where superiority and futility may be concluded with respect to different outcome definitions and therefore maintain a realistic probability of stopping in trials with low event rates. Through a simulation study, a variety of stopping rules and design configurations are compared. RESULTS: The simulation results are provided in an interactive web application that allows the user to explore and compare the design operating characteristics for a variety of assumptions and design parameters with respect to different outcome definitions. The results for select simulation scenarios are provided in the article. DISCUSSION: Bayesian adaptive designs offer the potential for maximizing the information learned from the data collected through clinical trials. The proposed design enables monitoring and utilizing multiple composite outcomes based on rare events to optimize the trial design operating characteristics.

Direct financial assistance for improved maternal and child health data: a pilot study supporting the health management information system in Malawi.

BACKGROUND: The health management information system (HMIS) is an integral component of a strong health care system. Despite its importance for decision-making, the quality of HMIS data remains of concern in low- and middle-income countries. To address challenges with the quality of maternal and child health (MCH) data gathered within Malawi's HMIS, we conducted a pilot study evaluating different support modalities to district-level HMIS offices. We hypothesized that providing regular, direct financial assistance to HMIS offices would enable staff to establish strategies and priorities based on local context, resulting in more accurate, timely, and complete MCH data. METHODS: The pilot intervention was implemented in Mwanza district, while Chikwawa, Neno, and Ntchisi districts served as control sites given support received from other institutions. The intervention consisted of providing direct financial assistance to Mwanza's HMIS office following the submission of detailed budgets and lists of planned activities. In the control districts, we performed interviews with the HMIS officers to track the HMIS-related activities. We evaluated the intervention by comparing data quality between the post- and pre-intervention periods in the intervention and control districts. Additionally, we conducted interviews with Mwanza's HMIS office staff to determine the acceptability and appropriateness of the intervention. RESULTS: Following the 10-month intervention period, we observed improvements in MCH data quality in Mwanza. The availability and completeness of MCH data collected in the registers increased by 22 and 18 percentage points, respectively. The consistency of MCH data between summary reports and electronic HMIS also improved. In contrast, 2/3 control districts noted minimal changes or reductions in data quality after 10 months. The qualitative interviews confirmed that, despite some challenges, the intervention was well received by the participating HMIS office. HMIS staff preferred our strategy to other conventional strategies that fail to give them the independence to make decisions. CONCLUSIONS: This pilot intervention demonstrated an alternative approach to support HMIS offices in their daily efforts to improve data quality. Given the Ministry of Health's (MoH) interest in strengthening its HMIS, our intervention provides a strategy that the MoH and local and international partners could consider to rapidly improve HMIS data with minimal oversight.

Growth delay: an alternative measure of population health based on child height distributions.

BACKGROUND: Indicators of child height, such as mean height-for-age Z-scores (HAZ), height-for-age difference (HAD) and stunting prevalence, do not account for differences in population-average bone developmental stage. AIM: Propose a measure of child height that conveys the dependency of linear growth on stage rather than chronological age. SUBJECTS AND METHODS: Using Demographic and Health Surveys (2000-2018; 64 countries), we generated: (1) predicted HAZ at specific ages (HAZ regressed on age); (2) height-age (age at which mean height matches the WHO Growth Standards median); (3) Growth delay (GD), the difference between chronological age and height-age; (4) HAD; and (5) stunting prevalence. Metrics were compared based on secular trends within countries and age-related trajectories within surveys. RESULTS: In the most recent surveys (N = 64), GDs ranged from 1.9 to 19.1 months at 60 months chronological age. Cross-sectionally, HAZ, HAD and GD were perfectly correlated, and showed similar secular trends. However, age-related trajectories differed across metrics. Accumulating GD with age demonstrated growth faltering as slower than expected growth for children of the same height-age. Resumption of growth at the median for height-age was rarely observed. CONCLUSION: GD is a population-level measure of child health that reflects the role of delayed skeletal development in linear growth faltering.

Effect of Correcting the Postnatal Age of Preterm-Born Children on Measures of Associations Between Infant Length-for-Age z Scores and Mid-Childhood Outcomes.

Child growth standards are commonly used to derive age- and sex-standardized anthropometric indices but are often inappropriately applied to preterm-born children (<37 weeks of gestational age (GA)) in epidemiology studies. Using the 2004 Pelotas Birth Cohort, we examined the impact of correcting for GA in the application of child growth standards on the magnitude and direction of associations in 2 a priori-selected exposure-outcome scenarios: infant length-for-age z score (LAZ) and mid-childhood body mass index (scenario A), and infant LAZ and mid-childhood intelligence quotient (scenario B). GA was a confounder that had a strong (scenario A) or weak (scenario B) association with the outcome. Compared with uncorrected postnatal age, using GA-corrected postnatal age attenuated the magnitude of associations, particularly in early infancy, and changed inferences for associations at birth. Although differences in the magnitude of associations were small when GA was weakly associated with the outcome, model fit was meaningfully improved using corrected postnatal age. When estimating population-averaged associations with early childhood growth in studies where preterm- and term-born children are included, incorporating heterogeneity in GA at birth in the age scale used to standardize anthropometric indices postnatally provides a useful strategy to reduce standardization errors.

Adolescents' experiences with group antenatal care: Insights from a mixed-methods study in Senegal.

OBJECTIVES: Group antenatal care (G-ANC) is an innovative model in which antenatal care is delivered to a group of 8-12 women of similar gestational age. Evidence from high-income countries suggests G-ANC is particularly effective for women from marginalised populations, including adolescents. The objective of this study was to examine the experiences of Senegalese adolescents engaged in group antenatal care. METHODS: This convergent parallel mixed-methods study is derived from a larger effectiveness-implementation hybrid pilot study conducted in Kaolack district, Senegal. Quantitative data for adolescent participants were collected through baseline and postnatal surveys and descriptively analysed. One-on-one interviews and focus-group discussions were conducted with adolescent participants, and qualitative data were analysed using qualitative descriptive analysis. RESULTS: Forty-five adolescents aged 15-19 participated in G-ANC, with a median age of 18 years. The majority (93.3%) were married, and 64.4% were nulliparous. Findings indicated similar levels of G-ANC participation for adolescent and adult women. The majority (93.1%) of participants who had previously attended individual ANC indicated they would prefer G-ANC to individual care for a future pregnancy. Qualitative findings indicated key facets of consideration relevant to G-ANC for adolescents include social connectedness, the influence of social norms and the opportunity for engagement in healthcare. CONCLUSIONS: This study suggests that G-ANC has the potential to be an adolescent-responsive and culturally appropriate method of delivering antenatal care in Senegal.

Maternal perinatal depression and infant sleep problems at 1 year of age: Subjective and actigraphy data from a population-based birth cohort study.

This study used data from 2,222 mothers and infants participating in a population-based birth cohort to verify whether maternal depression in the perinatal period was associated with poor infant sleep. Mothers who scored ≥13 points on the Edinburgh Postnatal Depression Scale at 16-24 weeks of gestation and/or 3 months after delivery were considered perinatally depressed. The main outcome variable was poor infant sleep at 12 months of age, defined as >3 night wakings, nocturnal wakefulness >1 hr or total sleep duration <9 hr. Infant sleep data were obtained with the Brief Infant Sleep Questionnaire (BISQ) and 24-hr actigraphy monitoring. Prevalence of perinatal depression in the sample was 22.3% (95% confidence interval [CI], 20.5-24.0). After Poisson regression, infants of depressed mothers showed an adjusted relative risk (RR) of 1.44 (95% CI, 1.00-2.08; p = .04) for >3 night wakings with questionnaire-derived data. When actigraphy data were analysed, no association was found between perinatal depression and poor infant sleep (adjusted RR, 1.20; 95% CI, 0.82-1.74; p = .35). In conclusion, although mothers in the depressed group were more likely to report more night wakings, objective data from actigraphy did not replicate this finding. Dysfunctional cognition, maternal behavioural factors and sleep impairment associated with perinatal depression may affect the mother's impression of her infant's sleep.

Relationship of Patent Ductus Arteriosus Echocardiographic Markers With Descending Aorta Diastolic Flow.

OBJECTIVES: To characterize the relationship of echocardiographic markers of left heart overload and flow in peripheral major end-organ vessels (eg, celiac artery) with the presence of reversed holodiastolic flow in the descending aorta, considered a surrogate marker of an increased transductal shunt volume, in preterm patients with a patent ductus arteriosus (PDA). METHODS: This work was a retrospective study of data from echocardiography performed to investigate the hemodynamic significance of a PDA in preterm patients. We studied differences in echocardiographic markers of the PDA shunt volume according to patterns of flow in the postductal descending aorta (no PDA, PDA with antegrade diastolic flow, and PDA with reversed diastolic flow). The strength of the association between each echocardiographic marker and the presence of aortic holodiastolic flow reversal was investigated. RESULTS: We studied 137 patients with a median (interquartile range) birth weight of 850 (694-1030) g and a median gestational age of 25 (24-27) weeks. Among patients with a PDA (113), those with diastolic flow reversal in the descending aorta (44) presented had increased echocardiographic markers representative of the shunt volume (increased left ventricular output, left atrial-to-aortic ratio, pulmonary vein D wave, and shorter isovolumic relaxation time) compared to those with aortic antegrade diastolic flow. A positive, albeit weak, correlation between diastolic flow reversal and shunt volume echocardiographic markers was found. Abnormal diastolic flow in the celiac artery had the strongest correlation (R2  = 0.24). CONCLUSIONS: In preterm patients with a PDA, echocardiographic markers of the shunt volume were more abnormal in patients with reversed diastolic flow in the descending aorta. These data support the assumption that variance in these markers are related to the shunt volume, which needs consideration when adjudicating hemodynamic significance.

Associations of acetaminophen use during pregnancy and the first year of life with neurodevelopment in early childhood.

BACKGROUND: Over-the-counter analgesic use during pregnancy, particularly acetaminophen, may be associated with negative developmental outcomes in children. OBJECTIVE: Estimate associations of prenatal and early-life exposure to acetaminophen in early childhood with cognitive, motor, and language skills in two birth cohorts. METHODS: The American Project Viva cohort (1217 mother-child pairs enrolled 1999-2002) assessed cognition at approximately 3 years using the Peabody Picture Vocabulary Test and the Wide Range Achievement of Visual Motor Abilities (WRAVMA). The Brazilian 2015 Pelotas Birth Cohort (3818 mother-child pairs) assessed cognition at 2 years using the INTERGROWTH-21st Neurodevelopment Assessment. We used linear regression to estimate associations of acetaminophen use during pregnancy (Project Viva and Pelotas) and infancy (Project Viva) with children's cognitive scores adjusted for maternal age, pre-pregnancy body mass index, education, parity, race/ethnicity, smoking and alcohol use during pregnancy, depression during pregnancy, antibiotic and ibuprofen use during pregnancy, household income, and child's sex. RESULTS: In Project Viva, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was associated with lower WRAVMA drawing scores (ß -1.51, 95% CI -2.92, -0.10). However, in Pelotas, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was not associated with INTER-NDA motor scores (ß 0.02; 95% CI -0.05, 0.09) and was associated with higher INTER-NDA total scores (ß 0.08, 95% CI 0.01, 0.16). Other comparisons did not show evidence for any associations. CONCLUSIONS: Inconsistencies and lack of specificity of the findings did not clarify the research question considering that we still have a large variability and uncertainty to define the risk or safety in the use of acetaminophen related to cognition in early childhood. More studies using better exposure assessment and better confounding variables are needed to clarify these associations.

Agreement of antenatal care indicators from self-reported questionnaire and the antenatal care card of women in the 2015 Pelotas birth cohort, Rio Grande do Sul, Brazil.

BACKGROUND: Studies of healthcare service use during the pregnancy-postpartum cycle often rely on self-reported data. The reliability of self-reported information is often questioned as administrative data or medical records, such as antenatal care cards, are usually preferred. In this study, we measured the agreement of antenatal care indicators from self-reported information and antenatal care cards of pregnant women in the 2015 Pelotas Birth Cohort, Brazil. METHODS: In a sample of 3923 mothers, indicator agreement strengths were estimated from Kappa and prevalence-and-bias-adjusted Kappa (PABAK) coefficients. Maternal characteristics associated with indicator agreements were assessed with heterogeneity chi-squared tests. RESULTS: The self-reported questionnaire and the antenatal care card showed a moderate to high agreement in 10 of 21 (48%) antenatal care indicators that assessed care service use, clinical examination and diseases during pregnancy. Counseling indicators performed poorly. Self-reported information presented a higher frequency data and a higher sensitivity but slightly lower specificity when compared to the antenatal card. Factors associated with higher agreement between both data sources included lower maternal age, higher level of education, primiparous status, and being a recipient of health care in the public sector. CONCLUSIONS: Self-reported questionnaire and antenatal care cards provided substantially different information on indicator performance. Reliance on only one source of data to assess antenatal care quality may be questionable for some indicators. From a public health perspective, it is recommended that antenatal care programs use multiple data sources to estimate quality and effectiveness of health promotion and disease prevention in pregnant women and their offspring.

Use and Misuse of Stunting as a Measure of Child Health.

The term "stunting" has become pervasive in international nutrition and child health research, program, and policy circles. Although originally intended as a population-level statistical indicator of children's social and economic deprivation, the conventional anthropometric definition of stunting (height-for-age z scores <-2 SD) is now widely used to define chronic malnutrition. Epidemiologists often portray it as a disease, making inferences about the causes of growth faltering based on comparisons between stunted (i.e., undernourished) and nonstunted children. Stunting is commonly used to monitor public health and nutrition program effectiveness alongside calls for the "elimination of stunting." However, there is no biological basis for the -2 SD cutoff to define stunting, making it a poor individual-level classifier of malnutrition or disease. In fact, in many low- and middle-income countries, children above and below the threshold are similarly affected by growth-limiting exposures. We argue that the common use of stunting as an indicator of child linear growth has contributed to unsubstantiated assumptions about the biological mechanisms underlying linear growth impairment in low- and middle-income countries and has led to a systematic underestimation of the burden of linear growth deficits among children in low-resource settings. Moreover, because nutrition-specific short-term public health interventions may result in relatively minor changes in child height, the use of stunting prevalence to monitor health or nutrition program effectiveness may be inappropriate. A more nuanced approach to the application and interpretation of stunting as an indicator in child growth research and public health programming is warranted.

Effect of correcting for gestational age at birth on population prevalence of early childhood undernutrition.

BACKGROUND: Postmenstrual and/or gestational age-corrected age (CA) is required to apply child growth standards to children born preterm (< 37 weeks gestational age). Yet, CA is rarely used in epidemiologic studies in low- and middle-income countries (LMICs), which may bias population estimates of childhood undernutrition. To evaluate the effect of accounting for GA in the application of growth standards, we used GA-specific standards at birth (INTERGROWTH-21st newborn size standards) in conjunction with CA for preterm-born children in the application of World Health Organization Child Growth Standards postnatally (referred to as 'CA' strategy) versus postnatal age for all children, to estimate mean length-for-age (LAZ) and weight-for-age (WAZ) z scores at 0, 3, 12, 24, and 48-months of age in the 2004 Pelotas (Brazil) Birth Cohort. RESULTS: At birth (n = 4066), mean LAZ was higher and the prevalence of stunting (LAZ < -2) was lower using CA versus postnatal age (mean ± SD): - 0.36 ± 1.19 versus - 0.67 ± 1.32; and 8.3 versus 11.6%, respectively. Odds ratio (OR) and population attributable risk (PAR) of stunting due to preterm birth were attenuated and changed inferences using CA versus postnatal age at birth [OR, 95% confidence interval (CI): 1.32 (95% CI 0.95, 1.82) vs 14.7 (95% CI 11.7, 18.4); PAR 3.1 vs 42.9%]; differences in inferences persisted at 3-months. At 12, 24, and 48-months, preterm birth was associated with stunting, but ORs/PARs remained attenuated using CA compared to postnatal age. Findings were similar for weight-for-age z scores. CONCLUSIONS: Population-based epidemiologic studies in LMICs in which GA is unused or unavailable may overestimate the prevalence of early childhood undernutrition and inflate the fraction of undernutrition attributable to preterm birth.

Conditional random slope: A new approach for estimating individual child growth velocity in epidemiological research.

OBJECTIVES: Conditioning child growth measures on baseline accounts for regression to the mean (RTM). Here, we present the "conditional random slope" (CRS) model, based on a linear-mixed effects model that incorporates a baseline-time interaction term that can accommodate multiple data points for a child while also directly accounting for RTM. METHODS: In two birth cohorts, we applied five approaches to estimate child growth velocities from 0 to 12 months to assess the effect of increasing data density (number of measures per child) on the magnitude of RTM of unconditional estimates, and the correlation and concordance between the CRS and four alternative metrics. Further, we demonstrated the differential effect of the choice of velocity metric on the magnitude of the association between infant growth and stunting at 2 years. RESULTS: RTM was minimally attenuated by increasing data density for unconditional growth modeling approaches. CRS and classical conditional models gave nearly identical estimates with two measures per child. Compared to the CRS estimates, unconditional metrics had moderate correlation (r = 0.65-0.91), but poor agreement in the classification of infants with relatively slow growth (kappa = 0.38-0.78). Estimates of the velocity-stunting association were the same for CRS and classical conditional models but differed substantially between conditional versus unconditional metrics. CONCLUSION: The CRS can leverage the flexibility of linear mixed models while addressing RTM in longitudinal analyses.

Infant sleep hygiene counseling (sleep trial): protocol of a randomized controlled trial.

BACKGROUND: Sleep problems in childhood have been found to be associated with memory and learning impairments, irritability, difficulties in mood modulation, attention and behavioral problems, hyperactivity and impulsivity. Short sleep duration has been found to be associated with overweight and obesity in childhood. This paper describes the protocol of a behavioral intervention planned to promote healthier sleep in infants. METHODS: The study is a 1:1 parallel group single-blinded randomized controlled trial enrolling a total of 552 infants at 3 months of age. The main eligibility criterion is maternal report of the infant's sleep lasting on average less than 15 h per 24 h (daytime and nighttime sleep). Following block randomization, trained fieldworkers conduct home visits of the intervention group mothers and provide standardized advice on general practices that promote infant's self-regulated sleep. A booklet with the intervention content to aid the mother in implementing the intervention was developed and is given to the mothers in the intervention arm. In the two days following the home visit the intervention mothers receive daily telephone calls for intervention reinforcement and at day 3 the fieldworkers conduct a reinforcement visit to support mothers' compliance with the intervention. The main outcome assessed is the between group difference in average nighttime self-regulated sleep duration (the maximum amount of time the child stays asleep or awake without awakening the parents), at ages 6, 12 and 24 months, evaluated by means of actigraphy, activity diary records and questionnaires. The secondary outcomes are conditional linear growth between age 3-12 and 12-24 months and neurocognitive development at ages 12 and 24 months. DISCUSSION: The negative impact of inadequate and insufficient sleep on children's physical and mental health are unquestionable, as well as its impact on cognitive function, academic performance and behavior, all of these being factors to which children in low- and middle-income countries are at higher risk. Behavioral interventions targeting mothers and young children that can be delivered inexpensively and not requiring specialized training can help prevent future issues by reducing the risk to which these children are exposed. TRIAL REGISTRATION: ClinicalTrial.gov NCT02788630 registered on 14 June 2016 (retrospectively registered).

Effect of provision of an integrated neonatal survival kit and early cognitive stimulation package by community health workers on developmental outcomes of infants in Kwale County, Kenya: study protocol for a cluster randomized trial.

BACKGROUND: Each year, more than 200 million children under the age of 5 years, almost all in low- and middle-income countries (LMICs), fail to achieve their developmental potential. Risk factors for compromised development often coexist and include inadequate cognitive stimulation, poverty, nutritional deficiencies, infection and complications of being born low birthweight and/or premature. Moreover, many of these risk factors are closely associated with newborn morbidity and mortality. As compromised development has significant implications on human capital, inexpensive and scalable interventions are urgently needed to promote neurodevelopment and reduce risk factors for impaired development. METHOD/DESIGN: This cluster randomized trial aims at evaluating the impact of volunteer community health workers delivering either an integrated neonatal survival kit, an early stimulation package, or a combination of both interventions, to pregnant women during their third trimester of pregnancy, compared to the current standard of care in Kwale County, Kenya. The neonatal survival kit comprises a clean delivery kit (sterile blade, cord clamp, clean plastic sheet, surgical gloves and hand soap), sunflower oil emollient, chlorhexidine, ThermoSpot(TM), Mylar infant sleeve, and a reusable instant heater. Community health workers are also equipped with a portable hand-held electric scale. The early cognitive stimulation package focuses on enhancing caregiver practices by teaching caregivers three key messages that comprise combining a gentle touch with making eye contact and talking to children, responsive feeding and caregiving, and singing. The primary outcome measure is child development at 12 months of age assessed with the Protocol for Child Monitoring (Infant and Toddler version). The main secondary outcome is newborn mortality. DISCUSSION: This study will provide evidence on effectiveness of delivering an innovative neonatal survival kit and/or early stimulation package to pregnant women in Kwale County, Kenya. Study findings will help inform policy on the most appropriate interventions for promoting healthy brain development and reduction of newborn morbidity and mortality in Kenya and other similar settings. TRIAL REGISTRATION: ClinicalTrial.gov NCT02208960 (August 1, 2014).

WHO Child Growth Standards Are Often Incorrectly Applied to Children Born Preterm in Epidemiologic Research.

In epidemiologic research, there is no standard approach for accounting for gestational age (GA) at birth when interpreting postnatal anthropometric data in analyses of cohorts that include children born preterm (CBP). A scoping review was conducted to describe analytical approaches to account for GA at birth when applying the WHO Growth Standards (WHO-GS) to anthropometric data in epidemiologic studies. We searched PubMed, Scopus, MEDLINE, Embase, and Web of Science for studies that applied WHO-GS, included CBP in the study population, had access to data within 1 mo of age, and were published between 2006 and 2015 in English. Of the 80 included studies that used the WHO-GS, 80% (64 of 80) included all children regardless of GA, whereas 20% (16 of 80) restricted analyses that used WHO-GS to term-born children. Among the 64 studies that included all children, 53 (83%) used chronological age and 11 (17%) used corrected age for CBP. Of the 53 studies that used chronological age, 12 (23%) excluded data that were likely contributed by CBP (e.g., very low birth weight or extremely low outlying z scores) and 19 (36%) adjusted for or stratified by GA at birth in regression analyses. In summary, researchers commonly apply WHO-GS to CBP, usually based on chronological age. Methodologic challenges of analyzing data from CBP in the application of WHO-GS were rarely explicitly addressed. Further efforts are required to establish acceptable approaches to account for heterogeneity in GA at birth in the analysis of post-term anthropometric data in epidemiologic research.

The community-based delivery of an innovative neonatal kit to save newborn lives in rural Pakistan: design of a cluster randomized trial.

BACKGROUND: Worldwide, an estimated 2.9 million neonatal deaths occurred in 2012, accounting for 44% of all under-five deaths. In Pakistan, more than 200,000 newborns die annually and neonatal mortality rates are higher than in any other South Asian country and haven't changed over the last three decades. The high number of neonatal deaths highlights the urgent need for effective and sustainable interventions that target newborn mortality in Pakistan. METHOD/DESIGN: This cluster randomized trial aims at evaluating the impact of delivering an integrated neonatal kit to pregnant women during the third trimester of pregnancy and providing education on how to use the contents (intervention arm) compared to the current standard of care (control arm) in the district of Rahimyar Khan, Punjab province, Pakistan. The kit, which will be distributed through the national Lady Health Worker program, comprises a clean delivery kit (sterile blade, cord clamp, clean plastic sheet, surgical gloves and hand soap), sunflower oil emollient, chlorhexidine, ThermoSpot™, Mylar infant sleeve, and a reusable instant heat pack. Lady health workers will be provided with a standard portable hand-held electric weighing scale. The primary outcome measure is neonatal mortality (death in the first 28 days of life). DISCUSSION: While many cost-effective, evidence-based interventions to save newborn lives exist, they are not always accessible nor have they been integrated into a portable kit designed for home-based implementation entirely by caregivers. The implementation of cost-effective, portable, and easy-to-use interventions has tremendous potential for sustainably reducing neonatal mortality and long-term improvements in population health. The bundling of interventions and commodities together also has much potential for cost-effective delivery and maximizing gains from points of contact. This study will provide empirical evidence on the feasibility and effectiveness of the delivery of an innovative neonatal kit to pregnant women in Pakistan. Together, these findings will help inform policy on the most appropriate interventions to improve newborn survival. TRIAL REGISTRATION: ClinicalTrial.gov NCT02130856. Registered May 1, 2014.