The ongoing Zika virus (ZIKV) epidemic in Latin America presented a unique opportunity to develop a neurodevelopmental assessment protocol for children in a lower middle-income country. Although studies of neurodevelopment in young children have taken place in many diverse global settings, we are not aware of any study that has provided a high level of detail about how a measure was selected and then specifically translated and adapted in a lowresource setting. Here, we describe considerations in measurement selection and then the process of translation and adaptation to assess neurodevelopmental outcomes of infants and young children with postnatal exposure to ZIKV in rural Guatemala. We provide a framework to other research teams seeking to develop similar assessment models across the globe.

Background: Children in low-and lower middle income countries (LMICs) often have poorer language skills compared with children from high-income countries. Limited availability of culturally and linguistically appropriate assessment measures in LMICs, especially for young children, can hinder early identification and prevention efforts. Here, we describe receptive language (RL) skills among young children in rural Guatemala and report on the validity of a translated and culturally adapted developmental measure of RL. Methods: Children (n = 157; m = 53.6 months, range = 42-68 months) enrolled in a prospective cohort study of postnatally acquired Zika virus infection were administered the Test de Vocabulario en Imagenes Peabody (TVIP) and the RL scale from a translated and adapted version of the Mullen Scales of Early Learning (MSEL). Performance on the TVIP was compared with the Latin American normative sample. Correlational analysis examined the relationship between performance on the TVIP and the MSEL-RL.Results: Mean scores were significantly below the normative sample mean on the TVIP, t(126) = −11.04, p < .001; d = 1.00. Performance on the TVIP among children who passed the practice items (n = 127) was significantly positively associated with performance on the MSEL-RL (r = .50, p < .001), but not significantly associated with age or gender. Older age (p < .0001) and female gender (p = .018) were associated with passing the TVIP practice items. Conclusions: Delays in RL vocabulary were identified among young children in rural Guatemala on the TVIP. The association between scores on the TVIP and the RL scale of the MSEL provides preliminary support for the construct validity of this translated and adapted version of the MSEL. Edwin J. Austrias and Flor M. Muñoz are co-senior authors.

Microcephaly, an anthropometric marker of reduced brain volume and predictor of developmental disability, is rare in high-income countries. Recent reports show the prevalence of microcephaly to be much higher in lower resource settings. We calculated the prevalence of microcephaly in infants and young children (n = 642; age range = 0.1–35.9 months), examined trends in occipitofrontal circumference (OFC) growth in the year after birth and evaluated the relationship between OFC and performance on the Mullen Scales of Early Learning (MSEL) in rural Guatemala. Multivariable regression analyses adjusted for age were performed: (1) a model comparing concurrent MSEL performance and OFC at all visits per child, (2) concurrent OFC and MSEL performance by age group, and (3) OFC at enrollment and MSEL at final visit by age group. Prevalence of microcephaly ranged from 10.1% to 25.0%. OFC z-score decreased for most infants throughout the first year after birth. A significant positive association between continuous OFC measurement and MSEL score suggested that children with smaller OFC may do worse on ND tests conducted both concurrently and ∼1 year later. Results were variable when analyzed by OFC cutoff scores and stratified by 6-month age groups. OFC should be considered for inclusion in developmental screening assessments at the individual and population level, especially when performance-based testing is not feasible.

In this study, we review the implementation, reliability, and validity of the Pediatric Quality of Life Inventory (PedsQL), a measure of health-related quality of life, in young children in rural Guatemala. Mothers of 842 children ( age range = 1-60 months) completed the PedsQL Generic Core Scales 4.0 serially for 1 year. Low (Pearson’s r = 0.28, P < .0001) to moderate (Pearson’s r = 0.65, P < .0001) consistency in responding over time was shown. The PedsQL did not discriminate reliably between healthy children and those with stunting or wasting. PedsQL scores were not lower during the time of an acute illness. While we found low to moderate evidence for the reliability of the PedsQL in healthy children, it did not discriminate between healthy children and those with stunting, wasting or other acute illness.

Objective: We aimed to evaluate the association between cumulative illness with neurodevelopment and growth outcomes in a birth cohort of Guatemalan infants. Study Design: 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 completed 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, six months, and one year. Results: Out 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 of the mean). In multivariable analysis, greater cumulative weeks 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 weeks of diarrheal/vomiting illness alone (p=0.66). No association was shown between cumulative weeks 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 the inflammatory profile associated with these syndromic illnesses and their impact on neurodevelopment in the first years of life.