BACKGROUND:Many children who experience abusive head trauma (AHT) have long-term, multidisciplinary healthcare needs. However, little is known about longitudinal follow-up or characteristics associated with medical retention. Prior longitudinal studies of outcomes have been hampered by low retention, raising questions about barriers to follow-up after the diagnosis of AHT. In order to facilitate follow-up care, we created a comprehensive, multidisciplinary clinic for children with AHT. OBJECTIVE:Describe patient retention in a multidisciplinary clinic for children with AHT and examine associations between injury characteristics and child placement outcomes with retention metrics. PARTICIPANTS AND SETTING:Data were abstracted from the medical charts of all children diagnosed with AHT from 6/1/2011 to 12/31/2020 at a single center and referred to a dedicated follow-up AHT clinic (Non-Accidental Brain Injury Care Clinic; NABICC). METHOD:We calculated the number of follow-up visits over 24 months. We used multivariable regression to determine the association between demographics, injury characteristics, and child placement outcomes with clinic retention. RESULTS:Over the study period, 407 patients were diagnosed with AHT and 365 (90%) children survived to hospital discharge. Eighty percent attended at least one NABICC follow-up visit, with an average of 4.5 visits over 24 months. In univariate analysis, parenchymal injuries, retinal hemorrhage, increasing PICU days, and removal from the home were statistically correlated with increased number of follow-up visits. In multivariable regression analyses, subdural hemorrhage, parenchymal injuries, PICU days, and out-of-home placement were all significantly associated with increased visits. Younger children had more visits compared to older children (≥ 24 months). CONCLUSION:Retention was high in this longitudinal, multi-disciplinary AHT clinic. Retention is associated with severe injury and out-of-home placement. This model of care has potential to advance clinical care and outcomes research.

This Viewpoint discusses the limits of using the Ages and Stages Questionnaire (ASQ) as a primary outcome measure of child development instead of its initial purpose as a developmental screener.

BACKGROUND:Prenatal Zika virus (ZIKV) infection leads to microcephaly and adverse neurodevelopment. The effects of postnatal ZIKV infection on the developing brain are unknown. We assessed the neurodevelopmental outcomes of children exposed postnatally during the ZIKV epidemic. METHODS:A prospective study enrolled infants 0-3 months of age and their mothers, and children 1.5-3.5 years of age in rural Guatemala from 2017 and were followed for 12 months until 2019. Neurodevelopment was evaluated using the Mullen Scales of Early Learning (MSEL). ZIKV and dengue virus (DENV) infections were identified by polymerase chain reaction (PCR) using active surveillance. Serological analyses, stratified by age group flavivirus serostatus at enrollment, were conducted using a focus reduction neutralization test. RESULTS:Of 1371 enrolled participants, 1187 (86.6%) completed the study. No PCR-confirmed ZIKV infections were identified during the study period. One-third of 1.5-3.5-year-old children were ZIKV-seropositive at enrollment (likely postnatal infection). Twenty participants (5.8%) tested positive for DENV by PCR (11 infants, 5 children and 4 mothers); 15 (75%) were DENV-3 infections and 5 were DENV-2. The incidence of DENV infection in infants was 2.6%. No significant differences in MSEL scores were found between infants born seropositive versus seronegative for ZIKV or DENV. DENV seropositivity at enrollment in 1.5-5-year-old children was associated with lower MSEL scores for fine motor, visual reception and language, and microcephaly at 12 months versus seronegative children (all P < 0.05). CONCLUSIONS:Postnatal ZIKV infection in children from rural Guatemala was not associated with worse neurodevelopmental outcomes. DENV seropositivity was associated with a higher risk of microcephaly in infants and worse neurodevelopmental outcomes in children.

Growing evidence implicates environmental enteric dysfunction (EED) as a driver of poor growth and neurodevelopment (ND) in early childhood. To investigate these findings, a cross-sectional study examining associations between biomarkers reflecting various domains of EED and growth and ND in Guatemalan infants was conducted. A subset of 114 cohort infants was randomly selected from a 2017-2019 population-based cohort study of 499 infants in rural southwest Guatemala. Growth and neurodevelopmental performance were assessed at a household visit at ∼13 months of age using the Mullen Scales of Early Learning (MSEL). Serum samples collected at the visit were analyzed for concentrations of biomarkers, assessing inflammation (α-1 acid glycoprotein), intestinal repair (glucagon-like peptide-2), and intestinal barrier disruption (anti-flagellin immunoglobulin A [anti-FliC IgA]). Multivariable regression analyses, adjusting for relevant confounders, were conducted to define the associations between these EED biomarkers and length-for-age z-scores (LAZ) and neurodevelopmental performance. Analyses both including and excluding infants who exhibited acute infectious disease symptoms at the time of the visit were planned. However, no significant associations were found between these biomarkers and LAZ or MSEL scores in the analysis of all children. Removing infants with acute infectious symptoms revealed an association between anti-FliC IgA and MSEL. Specifically, an increase of 10 ng/L in anti-FliC IgA concentration was associated with a decrease in the MSEL Early Learning Composite (ELC) raw score of 3.2 points, equating to approximately a nine-point decrease in the ELC standard score. Having higher levels of anti-FliC IgA may represent a significant risk to long-term health and development.

Objective: We aim to describe health care, vocational, and educational transitions in young adults with pediatric-onset disabilities and to examine the associations with social determinants of health and depressive symptoms. Design: This cross-sectional study used multinomial and binary logistic regression to examine the associations of sociodemographic factors and depressive symptoms with health care, educational, and vocational transitions. Setting: Participants were recruited from outpatient specialty clinics in a rehabilitation medicine department at a quaternary academic children's hospital. Participants: Transition age adults with acquired brain injury (17), spina bifida (10), and neuromuscular disorders (28) participated in this study. Interventions: Not applicable. Main Outcome Measures: Participants provided information about their current health care utilization and educational/vocational status. Results: Twenty-five percent of participants were unsure of their primary resource for preventative health care; this uncertainty was associated with White race/Hispanic ethnicity (P=.004) and public insurance (P=.02). When asked about their primary health care resource if they are sick or have an immediate health-related question, 18% identified the emergency department; this was significantly related to greater neighborhood disadvantage (P=.009). Considering current educational and vocational status, having a job while also going to school was associated with more self-reported depressive symptoms (P=.009) and younger age (P=.02). Conclusions: Outcomes during the transition to adulthood are related to multiple factors, including race and ethnicity, public insurance, neighborhood disadvantage, and depressive symptoms. Targeted interventions to support health care, vocational, and educational transitions in the context of social determinants of health and mental health status are needed. Archives of Physical Medicine and Rehabilitation 2025;106:674-81 (c) 2024 by the American Congress of Rehabilitation Medicine.

PURPOSE/OBJECTIVE:The transition from childhood to adulthood often involves emotional challenges. These problems may be especially prominent for transition-age adults (TAA) with pediatric-onset disabilities, although there are currently few studies that speak to this. The aim of this study is to characterize depressive symptoms and the association with family functioning in a sample of TAA with pediatric-onset disabilities. RESEARCH METHOD/DESIGN:This sample is comprised of 55 TAA (18-28 years of age, M = 20.88, SD = 2.49) who were followed by pediatric rehabilitation medicine clinics. Participants have childhood acquired brain injury (n = 17), spina bifida (n = 10), or neuromuscular disorders (n = 28). Participants completed the Center for Epidemiological Studies-Depression scale and the Family Assessment Device Short Form. RESULTS:Clinically elevated depressive symptoms were endorsed by 65.4% of the sample. Forty-five percent of those with elevated depressive symptoms were not currently receiving psychotherapy services. Poorer family functioning on the Family Assessment Device Short Form and older age were independently associated with more depressive symptoms, controlling for medical condition, mobility status, and other relevant sociodemographic factors. CONCLUSIONS/IMPLICATIONS:Emotional problems are quite common in TAA with a history of acquired brain injury, spina bifida, and neuromuscular disorders, yet are seemingly inadequately managed. In view of the results of this study, TAA with pediatric-onset disabilities are likely to benefit from interventions that bolster emotional well-being and target risk factors related to their family system. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

OBJECTIVE:We examined the associations of executive functioning and social determinants of health with medical self-management skills in transition-age adults (TAA) with pediatric-onset disabilities. METHOD:This cross-sectional pilot study included 47 young adults between the ages of 18-28 and their informants (e.g., parents, partners, siblings). Participants were followed by pediatric rehabilitation clinics for acquired brain injury (ABI = 16), neuromuscular disorders (NMD = 22), or spina bifida (SB = 9). Informants completed the Behavior Rating Inventory of Executive Functions - Adult Version, from which we reported the General Executive Composite. To assess medical self-management, young adult participants completed the Transition Readiness Assessment Questionnaire (TRAQ). RESULTS:Using generalized linear regression with the TRAQ as the dependent measure, better informant-rated executive functioning skills were associated with more favorable ratings of healthcare self-management with a large effect size (β = -0.62, p < .001). With a small effect size, there was also a main effect of participant race and ethnicity (β = 0.27, p = .049). Marginalized identities, specifically identification as of Indigenous and Black races, were associated with poorer ratings of healthcare self-management skills. CONCLUSIONS:Lower executive functioning skills and some marginalized identities are linked to poorer healthcare self-management in this sample of TAA with pediatric-onset disabilities. These findings highlight the value of neuropsychologists in identifying cognitive challenges and implementing targeted interventions in the context of social determinants of health.

BACKGROUND:Premature birth is a risk factor for abusive head trauma (AHT), but no prior studies have compared preterm and term infants with AHT. OBJECTIVE:To assess differences in demographics, family/contextual factors, and outcomes between preterm and term infants with AHT. PARTICIPANTS AND SETTING:403 patients (70 preterm) treated for AHT between 2012 and 2020 at a tertiary care children's hospital. METHODS:Data were collected via chart review. Demographics, family/contextual variables, and a composite score for each Bayley Scales of Infant Development domain were compared between preterm and term patients with independent samples t-tests, chi-square tests, and binary logistic regression. Gestational age (GA) corrected and uncorrected Bayley scores for preterm patients were compared using a repeated measures ANOVA. RESULTS:Preterm infants had significantly lower height (p < .001, d = 0.50) and weight (p < .001, d = 0.44) percentiles, but no other significant demographic or family/contextual differences were found. Preterm children earned numerically higher Bayley scores than term infants with GA correction and lower scores without correction. Corrected Bayley scores were significantly higher than uncorrected for preterm infants in the Cognitive (p < .001, η2p = 0.083), Expressive Language (p = .005, η2p = 0.052), Fine Motor (p = .001, η2p = 0.045), and Gross Motor (p = .008, η2p = 0.031) domains. CONCLUSIONS:While no significant differences in demographics or family/contextual variables were observed, age corrected Bayley scores were significantly higher than uncorrected scores for preterm infants with AHT.

BACKGROUND:Abusive head trauma (AHT), a leading cause of death from child physical abuse, disproportionately impacts the youngest children. Identifying children at highest risk following AHT has been hampered by the lack of a widely accepted measure of brain injury severity in infants and toddlers. OBJECTIVE:Identify clinical factors associated with mortality from AHT. PARTICIPANTS AND SETTING:403 patients (mean age 10.8 months) treated for AHT between 2012 and 2020 at a tertiary care children's hospital. METHODS:Single-center retrospective chart review. We tested relationships between covariates and mortality with t-tests and chi-square tests; these analyses guided development of a multivariable model using binary logistic regression. RESULTS:Forty-two of 403 children died (10.4 %). In bivariate analyses, mortality was linked to lower Glasgow Coma Scale (GCS; d = 2.07, p < .001), older age (d = -0.55, p = .009), midline shift (Φ = 0.10, p = .04), eye injuries (V = 0.42, p < .001), fractures (Φ = 0.14, p = .004), abdominal/visceral injuries (Φ = 0.14, p = .005), neurosurgical interventions (V = 0.22, p < .001), and intubation (Φ = 0.37, p < .001). Older children were at risk for more severe brain injuries and abdominal/visceral injuries. In the multivariable model, lower GCS (p < .001) and more fractures (p = .02) were associated with mortality. CONCLUSIONS:Our data support the use of GCS in infants and toddlers following AHT. Older children were more likely to die than younger children, with evidence for differing injury patterns by age.

We explored social, demographic, and health risk factors for occipitofrontal circumference (OFC) growth in infants living in a rural, low-resource region of Guatemala. OFC was measured at enrollment (0.1–2.9 months of age) and one year later (11.5–16.1 months of age) for 430 infants participating in a prospective cohort study conducted between 2017 and 2019. Potential predictors were collected at enrollment or were measured during the year of the study. We performed a two-stage risk factor analysis, using univariate regression modeling to identify potential risk factors, followed by multivariable regression modeling to identify independent, significant risk factors for smaller OFC at birth and 1 year in this low resource setting. Mean OFC at enrollment was -0.4 (1.2) and at 1 year was -1.1 (0.9). Probable zika exposure in utero and shorter maternal height were independently, significantly associated with smaller OFC at both enrollment and 1 year. Exposure to cigarette smoking in utero was independently significantly associated with smaller OFC at enrollment. Infant complications at birth, microcephaly at enrollment and stunting at enrollment were also independently significantly associated with smaller OFC at 1 year (all p-values < 0.05). No exposures measured during the study were associated with OFC at 1 year. All the independent predictors of small OFC during the study period were present at enrollment (within the first 3 months of life), including maternal height, and smoking and ZIKV exposure during pregnancy. Exposures after the first three months of life were not predictive of OFC at one year. Continued work to identify specific risk factors and develop targeted prevention programs is warranted. The prevalence of microcephaly and poor occipitofrontal (OFC) growth may be higher in lower- and middle-income countries than in high-income countries, although the reasons for this are not known. Maternal height and previous zika exposure were associated with smaller OFC at both enrollment and 1 year later, while exposure to cigarette smoking in utero was associated with smaller OFC at enrollment. Infant complications at birth, microcephaly and stunting at enrollment were also independently significantly associated with smaller OFC at 1 year. Targeted interventions may reduce the prevalence of microcephaly and poor OFC growth, with related benefits in child neurodevelopment.

Purpose/Objective: Inflicted traumatic brain injury (iTBI), or abusive head injury, is a common cause of mortality and disability among infants and toddlers. Social determinants of health (SDoH) have a critical and multifaceted impact on iTBI, influencing both prevalence and outcomes. The area deprivation index (ADI) is a comprehensive metric of SDoH developed to assist in understanding how community-level socioeconomic factors influence patient outcomes. The current study sought to describe the sociodemographic characteristics, including ADI, of a cohort of 373 infants and young children who sustained an iTBI. Research Method/Design: This study was a retrospective analysis utilizing a cohort of pediatric patients treated for iTBI at a large, tertiary care children's hospital serving seven states in the Rocky Mountain region. Results: Mortality prevalence was higher among older children, and older children were more likely to have a longer stay in the pediatric intensive care unit. Children who were identified as Hispanic/Latino lived in areas with greater socioeconomic disadvantage than children identified as non-Hispanic/Latino. Specifically, participants who were identified as White Hispanic/Latino lived in areas with greater disadvantage than children who were identified as White non-Hispanic/Latino. There were no other significant differences by race. Contrary to hypotheses, ADI was not significantly related to mortality, injury severity, or follow-up visits. Conclusions/Implications: While SDoH are known to influence outcomes in iTBI, it may be necessary to incorporate individual or family-level SDoH variables within this clinical sample and examine the interaction between individual and community-level factors. Impact and Implications Although the importance of considering social determinants of health in the context of inflicted traumatic brain injury has been well established, few studies have incorporated community-level indices when examining the impact of social determinants of health. This study is among the first to examine community-level factors in a large cohort of pediatric patients being treated following inflicted traumatic brain injury, using the area deprivation index, a 17-factor index of economic deprivation, alongside individual sociodemographic factors. Future research and policy decisions must consider the dynamic interactions between both individual and community-level factors in order to identify modifiable mechanisms, ultimately facilitating access to services and mitigating health inequities.

To characterize risk factors, timing, semiology, and severity of post-traumatic epilepsy (PTE) in children with abusive head trauma (AHT).

ABSTRACTBACKGROUNDThere is growing evidence that environmental enteric dysfunction (EED) is a driver of poor growth and neurodevelopment (ND) in early childhood. To further investigate this, we measured the associations between biomarkers reflecting various domains of EED and growth and ND in Guatemalan infants. METHODS. A subset of 114 cohort infants were randomly selected for inclusion from a 2017-2019 population-based cohort study of 499 young infants in rural southwest Guatemala. Growth and neurodevelopmental performance using the Mullen Scales of Early Learning (MSEL) were assessed at a household visit around 12 months of age. Serum samples collected at the visit were analyzed for concentrations of α-1 acid glycoprotein (AGP), glucagon-like peptide-2 (GLP-2), and anti-flagellin IgA (Anti-FliC IgA), Multivariable regression analyses adjusted for relevant confounders were conducted to define associations between these EED biomarkers and length-for-age z-score (LAZ) and neurodevelopmental performance. We planneda priorito conduct analyses with and without excluding infants who had acute infectious disease symptoms (fever, cough, vomiting, diarrhea) at the 12-month visit.RESULTSNo significant association between biomarkers representing different domains of EED and LAZ or MSEL scores at 12-14 months of age was found. However, removing children with acute infectious symptoms uncovered an association between Anti-FliC IgA and MSEL. Specifically, an increase in 10ng/L in Anti-FliC IgA concentration was associated in a decrease in the MSEL Early Learning Composite (ELC) raw score of 3.2 points, which equates to approximately a 9-point decrease in the ELC standard score.CONCLUSIONSIn this study, having increased levels of Anti-FliC IgA was associated with lower ND in the first year of life and may represent an important risk to long-term health and development.AUTHOR SUMMARYThere is growing evidence that a key driver of stunting and poor neurodevelopment in low-resource settings is environmental enteric dysfunction. Environmental enteric dysfunction is a subclinical condition of the small intestine that may include chronic mucosal inflammation and/or increased intestinal permeability; it is common in children experiencing repeated infections with fecal-oral pathogens. In this preliminary study, we examined the link between biomarkers of environmental enteric dysfunction and neurodevelopment in 114 infants. After excluding children with acute infectious symptoms (which could transiently modify biomarker levels), we found a strong link between one marker of EED and poor neurodevelopment, independent of child growth. Further research is warranted to explore the associations between EED and ND to guide future interventions to reduce these risks.

Social-emotional difficulties are common sequelae of traumatic brain injury (TBI). Children who have experienced inflicted TBI (iTBI) may be at increased risk for social-emotional problems due to the risk factors associated with both early neurologic injury and with child maltreatment. We characterized the associations among injury severity, caregiver type (i.e., biological parents, non-kinship, kinship), and child social-emotional functioning in 41 infants and young children who had sustained iTBI and were seen in a large, regional children's hospital. This study was a retrospective analysis, utilizing data collected from the medical record as part of routine clinical care. Social-emotional functioning was assessed with the Bayley Scales of Infant and Toddler Development-Third Edition. Children with more severe injuries were rated as having worse social-emotional functioning. Caregiver type was associated with child social-emotional scores, above and beyond injury and demographic predictors. Biological parents were more likely to report better social-emotional skills than non-kinship caregivers, with the pattern of results suggesting that rater bias plays a role in this difference. In order to ensure that children are accurately identified for supports, these relationships should be considered when interpreting caregiver report of social-emotional skills.

This Viewpoint discusses the concern about the long-term predictive validity of early childhood development (ECD) assessments and how this concern reflects a misunderstanding of the constructs of ECD and intelligence, how they are assessed, and the myriad of other influences on the growth and trajectory of intellectual ability in children.

Abstract Stunting (<−2 SD of length- or height-for-age on WHO growth curves) is the most used predictor of child neurodevelopmental (ND) risk. Occipitofrontal head circumference (OFC) may be an equally feasible, but more direct and robust predictor. We explored association of the two measurements with ND outcome, separately and combined, and examined if cutoffs are more efficacious than continuous measures in predicting ND risk. Infants and young children in rural Guatemala (n = 642; age range = 0.1–35.9 months) were enrolled in a prospective natural history study, and their ND was tested using the Mullen Scales of Early Learning (MSEL) longitudinally. Length- or height-for-age and OFC-for-age were calculated. We performed age-adjusted multivariable regression analyses to explore the association between 1) length or height and ND, 2) OFC and ND, and 3) both length or height and OFC combined, with ND; concurrently, predictively, and longitudinally, as continuous variables and using WHO z-score cutoffs. Continuous length- or height-for-age and OFC z-scores were more strongly associated with MSEL than the traditional -2 SD WHO cutoff. The combination of height-for-age z-score and OFC z-score was consistently, strongly associated with the MSEL Early Learning Composite concurrently (p-values 0.0004–0.11), predictively (p-value 0.001–0.07), with the exception of the 18–24 months age group which had very few records, and in the longitudinal model (p-value <0.0001–0.004). The combination of continuous length- or height-for-age and OFC shows additional utility in estimating ND risk in infants and young children. Measurement of OFC may improve precision of prediction of ND risk in infants and young children.

Objective:Inflicted traumatic brain injury (TBI) is one of the leading causes of childhood injury and death. Studies have consistently demonstrated worse outcomes for children with inflicted TBIs compared to accidental TBIs. Out of home placement, a known developmental risk factor, is a frequent occurrence in inflicted TBI, which may also contribute to worse outcomes for children. Little is known about what injury, child, and family factors predict out-of-home versus in-home placements. We hypothesize that injury severity, child, and family risk factors will be predictive of out-of-home placement after hospital discharge from an inflicted TBI.Participants and Methods:Participants included 175 children with inflicted head injuries ages who received care at a large children’s hospital from 2012 to 2021. 88% of children were alive at discharge and were included in the study. The total sample included 154 children. Ages ranged from 0.2 to 76 months (M = 11.81, SD = 14.50) and 64.9 % were male. Race/Ethnicity distribution was as follows: 66.9% White, 29.9% Latinx or Hispanic, 4.6% Black, 3.3% American Indian or Alaskan, and 22.5% identified another race or ethnicity or identified as multiracial. Measures included injury severity (e.g., days spent in the PICU, post-resuscitation GCS), child (e.g., race/ethnicity, gender), and family factors (e.g., prior history of domestic violence, type of insurance). Individual logistic regressions were run to assess the effect of each injury severity, child, and family factor on placement after hospital discharge.Results:Results indicated that having a caregiver with a history of mental health difficulties and/or a history of substance abuse increased the likelihood of an out-of-home placement for the child after an inflicted TBI. Results also demonstrated that the more caregiver psychosocial concerns reported, the higher the risk of an out-of-home placement for the child after discharge from the hospital. Finally, results indicated that having public insurance significantly increased the risk of an out-of-home placement for the child after discharge from the hospital. Post-hoc analyses were conducted to assess the effect of insurance type on out-of-home placement, while controlling for psychosocial concerns. Results indicated that, even when taking total psychosocial concerns into account, having public insurance significantly increased the risk of an out-of-home placement. Logistic regressions were carried out to assess the effect of injury severity, child, and every other family factor (e.g., prior criminal history) on placement after hospital discharge and the overall models were not significant.Conclusions:One explanation for these findings is that families with public insurance have less of a social safety net and, thus, are unable to meet the needs of a child with an inflicted TBI. However, we cannot rule out the effect of bias in child welfare practices. Similarly, caregivers with histories of mental health difficulties and substance abuse are likely to have a harder time meeting their child’s needs and providing a stable household, increasing the likelihood of an out-of-home placement. Despite expectations, child and injury severity factors did not play a role in placement decisions after an inflicted TBI, indicating that placement decisions rely more heavily on caregivers’ abilities to meet the child’s needs rather than the child’s medical complexity or the severity of the inflicted TBI.

Background: Infectious disease exposures in early life are increasingly recognized as a risk factor for poor subsequent growth and neurodevelopment. We aimed to evaluate the association between cumulative illness with neurodevelopment and growth outcomes in a birth cohort of Guatemalan infants. Methods: From June 2017 to July 2018, infants 0–3 months of age living in a resource-limited region of rural southwest Guatemala were enrolled and underwent weekly at-home surveillance for caregiver-reported cough, fever, and vomiting/diarrhea. They also underwent anthropometric assessments and neurodevelopmental testing with the Mullen Scales of Early Learning (MSEL) at enrollment, 6 months, and 1 year. Results: Of 499 enrolled infants, 430 (86.2%) completed all study procedures and were included in the analysis. At 12–15 months of age, 140 (32.6%) infants had stunting (length-for-age Z [LAZ] score < –2 SD) and 72 (16.7%) had microcephaly (occipital-frontal circumference [OFC] < –2 SD). In multivariable analysis, greater cumulative instances of reported cough illness (beta = –0.08/illness-week, P = 0.06) and febrile illness (beta = –0.36/illness-week, P < 0.001) were marginally or significantly associated with lower MSEL Early Learning Composite (ELC) Score at 12–15 months, respectively; there was no association with any illness (cough, fever, and/or vomiting/diarrhea; P = 0.27) or with cumulative instances of diarrheal/vomiting illness alone ( P = 0.66). No association was shown between cumulative instances of illness and stunting or microcephaly at 12–15 months. Conclusions: These findings highlight the negative cumulative consequences of frequent febrile and respiratory illness on neurodevelopment during infancy. Future studies should explore pathogen-specific illnesses, host response associated with these syndromic illnesses, and their association with neurodevelopment.

Caregiver report is the most feasible way to assess early childhood development but is susceptible to the influences of response style and sociodemographic factors. In a sample of 571 caregiver-infant dyads (47.8% female; 48% White), we compared caregiver reports on the Ages and Stages Questionnaire-Third Edition (ASQ-3) with reports on a novel, web-based assessment, PediaTrac™. Ratings on PediaTrac correlated with ratings on the ASQ-3 at all time points (2, 4, 6, and 9 months). Caregiver age, response style, and sociodemographic factors accounted for significant variance on both measures. Developmental reporting of early childhood skills is influenced by caregiver response style and sociodemographic factors. These influences must be considered in order to ensure the accurate identification of infant developmental status.

Performancebased assessment is considered the gold standard for measuring child neurodevelopment (ND). However, such assessment is often not feasible in lowresource settings (LRSs) because it is timeconsuming, resourceintensive, and available assessment tools are often not validated in the local language or lack regional or local norms. In the absence of direct developmental assessment, estimates of children at increased risk of ND impairment (‘ND risk’) and health policies that aim to improve child ND are usually based on populationbased metrics of child linear growth (i.e., stunting defined as <2 SD below the mean in heightforage or lengthforage, WHO). However, there is growing evidence that while stunting continues to be a robust proxy for child physical health and nutritional status, it is likely not the best proxy for ND risk, as the causal pathways of stunting and ND are complex and incompletely overlap. We propose that occipitofrontal head circumference (OFC) may be a more direct and appropriate proxy, as well as a feasible and costeffective method of identifying children at highest ND risk in LRSs. Research from highincome countries (HICs) suggests that OFC is a robust anthropometric measurement of brain volume, and several studies have demonstrated this relationship on neuroimaging. An extensive body of research from HICs has shown that when an OFC is 2 SD or more below the mean on the WHO growth charts, consistent with a diagnosis of microcephaly, there is an elevated risk of adverse ND outcome. Microcephaly is a relatively rare occurrence in HICs. For example, in the USA and Europe, the reported prevalence of microcephaly ranges from 2.0 to 14.7 per 10 000 live births. 4 5 The Zika epidemic both heightened and highlighted the concern about microcephaly in children in LRSs and led to further research showing that its prevalence may be substantially higher than in HICs. Studies from Guatemala and Brazil conducted prior to the Zika epidemic reported prevalences of microcephaly of 1216 and 350 per 10 000 live births, respectively. 7 Additionally, several studies in LRSs have shown increasing prevalence of microcephaly as children age, similar to what is commonly observed with stunting. In a study conducted in India, 33% of children were reported to meet criteria for microcephaly at birth, increasing to 50% by the end of first year of life. A similar phenomenon of increasing prevalence with age was reported in rural Nepal, where over half of children had an OFC equal to 2 SD or below WHO growth standards by age 4 years. While the specific aetiology of microcephaly is often not known, the higher prevalences reported in LRSs compared with HICs, and known associations, such as lower socioeconomic status and parental OFC, strongly implicate the intergenerational impact and cumulative adverse risks of living in poverty on child growth. Some have disregarded these reports of elevated prevalence of microcephaly in LRSs, arguing that the numbers must be inflated due to an inappropriate application of a global growth standard in groups of people who are genetically smaller in stature. This premise is challenged by the 2006 WHO Multicentre Growth Study, in which very small differences in growth were found among children globally when nutritional and other risks associated with living in poverty were minimised. A pair of studies from Nepal showed that healthy children had OFCs that were within normal range when using the WHO growth standards but that 50% of children living in more rural, impoverished areas met criteria for microcephaly using the same metrics. While it is well known that many risk factors associated with living in poverty, including elevated rates of preterm birth, intrauterine growth restriction and congenital infections, have adverse impacts on the growth and development of the brain, OFC has been historically understudied in LRSs. One reason is the belief in the global health community that OFC is spared under conditions of nutritional stress. However, recent data from LRSs suggest that OFC might be a sensitive marker of the ND risks of living in poverty, may be more directly affected by repeated illness and undernutrition than previously appreciated, and likely incompletely overlaps with stunting, suggesting both shared as well as separate aetiologies. 12 13 In order to understand whether or not clinically significant microcephaly is being overidentified with global growth standards, we must study the direct association between child OFC and ND outcomes in all resource settings. This association has been identified in HICs, and research in LRSs is beginning to reveal similar associations. In the multicountry MALED Study, OFC was associated with ND outcome and noted to be a stronger predictor of ND than stunting status. Several other studies around the world, including our studies in rural Guatemala, have also reported an association between small OFC and poor ND outcome in children. 14 Therefore, the clinical and public health community should consider that global growth standards may be applied to OFC, can serve as an indicator of the risks associated with living in poverty and of ND risk, and that the prevalence of microcephaly may be equivalently high and even more clinically concerning than stunting. More research focusing on the association between child OFC and ND risk in LRSs is needed; child OFC should be routinely collected at all medical visits (with global harmonisation of measurement methods to minimise the potential for errors) in the context of nutritional monitoring and in relevant research studies involving young children. These additional data will help us determine if the measurement of OFC can serve as a more accurate proxy of ND risk than stunting, and whether OFC is feasible to measure accurately. Because research suggests that the <2 SD cutoff to define stunting may be arbitrary and continuous heightforage analysis may better define risk, a similar analysis to determine whether OFC should be assessed as a continuous metric or specific cutoff should be conducted. In addition, tracking OFC trends throughout early Children’s Hospital Colorado, Aurora, Colorado, USA Department of Physical Medicine and Rehabilitation, University of Colorado Denver School of Medicine, Aurora, Colorado, USA Center for Global Health and Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA