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While microcephaly is a significant adverse outcome of prenatal exposure to the Zika virus (ZIKV), subtle malformations of cortical development (MCD) have been observed in Zika-exposed children (ZEC), including delays in language, cognition, and motor domains, and visual acuity deficits. Interventions within the first 1,000 days of life can significantly improve developmental outcomes. This study examined a 12-week Responsive Caregiving Intervention on neurodevelopmental outcomes in 24-30-month-old ZEC. A randomized controlled trial was implemented in Grenada, West Indies using an existing ZIKV cohort surveillance study. When children in that study turned 24 months, baseline child neurodevelopmental measures and caregiver interviews were administered. Caregivers who agreed to participate in the 12-week Responsive Caregiving Intervention, implemented when children were 24-30 months of age, were randomly assigned to the Intervention or Waitlist Control group. Children in both groups were re-assessed on the neurodevelopmental measures post-intervention. 233 children from the ZIKV surveillance study met inclusion criteria, of which n = 80 declined participation, n = 42 did not complete the Intervention, and n = 72 missed follow-up assessments given strict timelines in the study design. The final sample for analysis was N = 13 children in the Intervention group and N = 26 children in the Control group. A GEE model analysis showed significantly higher language (p = 0.021) and positive behaviour (p = 0.005) scores for children in the Intervention group compared to the Control group. The Intervention had a medium effect on child language (d = 0.66) and a large effect on positive behaviour (d = 0.83). A 12-week Responsive Caregiving Intervention Programme significantly improves language and positive behaviour scores in 30-month-old normocephalic children who were exposed to ZIKV in utero. The programme provides an option for mothers of ZIKV-exposed children who are seeking an evidence-based neurodevelopmental intervention regardless of known impact of the virus on cortical formation. The study was registered with clinicaltrials.gov (NCT04697147).

Children born to mothers infected by Zika virus (ZIKV) during pregnancy are at increased risk of adverse neurodevelopmental outcomes including microcephaly, epilepsy, and neurocognitive deficits, collectively known as Congenital Zika Virus Syndrome. To study the impact of ZIKV on infant brain development, we collected resting-state electroencephalography (EEG) recordings from 28 normocephalic ZIKV-exposed children and 16 socio-demographically similar but unexposed children at 23–27 months of age. We assessed group differences in frequency band power and brain synchrony, as well as the relationship between these metrics and age. A significant difference ( p  < 0.05, Bonferroni corrected) in Inter-Site Phase Coherence was observed: median Pearson correlation coefficients were 0.15 in unexposed children and 0.07 in ZIKV-exposed children. Results showed that functional brain networks in the unexposed group were developing rapidly, in part by strengthening distal high-frequency and weakening proximal lower frequency connectivity, presumably reflecting normal synaptic growth, myelination and pruning. These maturation patterns were attenuated in the ZIKV-exposed group, suggesting that ZIKV exposure may contribute to neurodevelopmental vulnerabilities that can be detected and quantified by resting-state EEG.

Maternal infection with Zika virus (ZIKV) is associated with a distinct pattern of birth defects, known as congenital Zika syndrome (CZS). In ZIKV-exposed children without CZS, it is often unclear whether they were protected from in utero infection and neurotropism. Early neurodevelopmental assessment is essential for detecting neurodevelopmental delays (NDDs) and prioritizing at-risk children for early intervention. We compared neurodevelopmental outcomes between ZIKV-exposed and unexposed children at 1, 3 and 4 years to assess exposure-associated NDD risk. A total of 384 mother–child dyads were enrolled during a period of active ZIKV transmission (2016–2017) in Grenada, West Indies. Exposure status was based on laboratory assessment of prenatal and postnatal maternal serum. Neurodevelopment was assessed using the Oxford Neurodevelopment Assessment, the NEPSY® Second Edition and Cardiff Vision Tests, at 12 (n = 66), 36 (n = 58) and 48 (n = 59) months, respectively. There were no differences in NDD rates or vision scores between ZIKV-exposed and unexposed children. Rates of microcephaly at birth (0.88% vs. 0.83%, p = 0.81), and childhood stunting and wasting did not differ between groups. Our results show that Grenadian ZIKV-exposed children, the majority of whom were without microcephaly, had similar neurodevelopmental outcomes to unexposed controls up to at least an age of 4 years.

The 2005-06 chikungunya virus (CHIKV) outbreak in La Réunion suggested that mothers could transmit CHIKV to their neonates while viremic during the intrapartum period, and more than half of the infected neonates showed impaired neurodevelopment at two years of age. However, data sparsity precluded an overview of the developmental impact of vertical infection within the whole prenatal period. The current study assessed two-year old children born to mothers who were infected during the 2014 CHIKV outbreak in Grenada to determine the neurodevelopmental impact of perinatal CHIKV infection throughout gestation. Mother and child infection status were confirmed by serologic testing (IgG and IgM) for CHIKV. Cognitive, fine motor, gross motor, language and behavioral outcomes were assessed at two years of age on the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA). No differences in neurodevelopmental outcomes were observed between two-year-old children born to mothers infected with CHIKV during gestation (n = 149) and those born to mothers not infected with CHIKV (n = 161). No differences were found in INTER-NDA scores between children infected with CHIKV (n = 47) and children not infected with CHIKV (n = 592). Likewise, there were no differences between children infected with CHIKV post-partum (n = 19) versus children not infected with CHIKV (n = 592). Our findings suggest that children exposed and/or infected with CHIKV outside of the intrapartum period experience no significant neurodevelopmental delay at two years of age, as measured by the INTER-NDA, compared to their unexposed and/or uninfected peers. These results complement those of previous studies which showed a neurodevelopmental risk only for children infected during the intrapartum period, while the mother was highly viremic. These results might be reassuring for women of childbearing age and public health officials in CHIKV-endemic regions.

Background Adaptation of standardized early child development (ECD) assessments to low- and middle-income countries can be challenging because of culture-specific factors relating to language, content, context, and tool administration, and because the reliance of these tests on specialist healthcare professionals limits their scalability in low resource settings. Methods We report the cross-cultural adaptation of an international, standardized ECD instrument, the INTERGROWTH-21st Project Neurodevelopment Assessment (INTER-NDA), measuring cognitive, language, motor and behavioural outcomes in 2-year-olds, from a UK-based English-speaking population to the English-speaking Caribbean. Children aged 22-30 months were recruited from a pre-existing randomized controlled neurodevelopment intervention study in Grenada, West Indies. Results Eight of 37 INTER-NDA items (22%) were culturally and linguistically adapted for implementation in the Caribbean context. Protocol adherence across seven newly-trained non-specialist child development assessors was 89.9%; six of the seven assessors scored ≥80%. Agreement between the expert assessor and the non-specialist child development assessors was substantial (κ = 0.89 to 1.00 (95% CI [0.58, 1.00]). The inter-rater and test-retest reliability for non-specialist child development assessors was between κ = 0.99 -1.00 (95% CI [0.98, 0.99]) and κ = 0.76 - 1.00 (95% CI [0.33, 1.00]) across all INTER-NDA domains. Conclusions The current study provides evidence to support the use of the adapted INTER-NDA by trained, non-specialist assessors to measure ECD prevalence in the English-speaking Caribbean. It also provides a methodological template for the adaptation of child developmental measures to cultural and linguistic contexts that conform to the cultural standards of the countries in which they are utilized to aid in the measurement of neurodevelopmental impairments (NDIs) in a variety of global clinical settings.

Children with Congenital Zika Syndrome and microcephaly are at high risk for epilepsy; however, the risk is unclear in normocephalic children with prenatal Zika virus (ZIKV) exposure [Exposed Children (EC)]. In this prospective cohort study, we performed epilepsy screening in normocephalic EC alongside a parallel group of normocephalic unexposed children [Unexposed Children (UC)]. We compared the incidence rate of epilepsy among EC and UC at one year of life to global incidence rates. Pregnant women were recruited from public health centers during the ZIKV outbreak in Grenada, West Indies and assessed for prior ZIKV infection using a plasmonic-gold platform that measures IgG antibodies in serum. Normocephalic children born to mothers with positive ZIKV results during pregnancy were classified as EC and those born to mothers with negative ZIKV results during and after pregnancy were classified as UC. Epilepsy screening procedures included a pediatric epilepsy screening questionnaire and video electroencephalography (vEEG). vEEG was collected using a multi-channel microEEG® system for a minimum of 20 minutes along with video recording of participant behavior time-locked to the EEG. vEEGs were interpreted independently by two pediatric epileptologists, who were blinded to ZIKV status, via telemedicine platform. Positive screening cases were referred to a local pediatrician for an epilepsy diagnostic evaluation. Epilepsy screens were positive in 2/71 EC (IR: 0.028; 95% CI: 0.003–0.098) and 0/71 UC. In both epilepsy-positive cases, questionnaire responses and interictal vEEGs were consistent with focal, rather than generalized, seizures. Both children met criteria for a clinical diagnosis of epilepsy and good seizure control was achieved with carbamazepine. Our results indicate that epilepsy rates are modestly elevated in EC. Given our small sample size, results should be considered preliminary. They support the use of epilepsy screening procedures in larger epidemiological studies of children with congenital ZIKV exposure, even in the absence of microcephaly, and provide guidance for conducting epilepsy surveillance in resource limited settings.

Many young children in low- and middle-income countries (LMICs) are at risk of developmental delays. Early child development (ECD) interventions have been shown to improve outcomes, but few interventions have targeted culturally normative violence such as corporal punishment (CP). We partnered with an existing community-based ECD organization in the LMIC of Grenada to implement a parallel controlled-trial single-blind responsive caregiving intervention that educates parents about the developing brain and teaches alternatives to corporal punishment while building parental self-regulation skills and strengthening social-emotional connections between parent and child. Parents and primary caregivers with children under age two were eligible. Allocation to the intervention and waitlist control arms was unblinded and determined by recruitment into the program. Neurodevelopment was assessed by blinded testers when each child turned age two. Primary comparison consisted of neurodevelopmental scores between the intervention and waitlist control groups (Clinicaltrials.gov registration # NCT04697134). Secondary comparison consisted of changes in maternal mental health, home environment, and attitudes towards CP. Children in the intervention group (n = 153) had significantly higher scores than children in the control group ( = 151) on measures of cognition ( = .022), fine motor ( < .0001), gross motor ( = .015), and language development ( = .013). No difference in secondary outcomes, including CP, was detected.

Objective:Neuropsychological assessment of preschool children is essential for early detection of delays and referral for intervention prior to school entry. This is especially relevant in low-and middle-income countries (LMICs), which are disproportionately impacted by micronutrient deficiencies and teratogenic exposures. There are limited options for assessment of preschool learning and memory, developed and validated in resource-limited regions. The Grenada Learning and Memory Scale (GLAMS) was created for use in the Caribbean using an indigenous “ground-up” approach, with feedback from regional stakeholders at various stages of development. The GLAMS contains two subtests - a verbal list-learning task, which imagines a trip to the shop to buy culturally familiar items, and a face-name associative learning task using locally-drawn faces of Caribbean children. There are two versions: a 4-item version for 3-year-olds and a 6-item version for 4 and 5-year-olds. Here we present descriptive data and psychometric features for the GLAMS from an initial preschool sample.Participants and Methods:Participants were recruited from a social-emotional intervention study (SGU IRB#14099) in Grenada between 2019-2021. Children were between 36 and 72 months of age, primarily English-speaking, and had no known history of neurodevelopmental disorders. Trained Early Childhood Assessors administered the GLAMS and NEPSY-II in public preschools and homes across Grenada. Exploratory descriptive statistics characterized participant sociodemographics and test score distributions. Spearman correlations, MannWhitney U, and Kruskal-Wallis tests examined the impact of sociodemographics on test scores. Internal reliability was assessed with coefficient alpha. NEPSY-II subtests were used to assess convergent validity, with the prediction that the highest correlations would be observed for NEPSY-II Sentence Repetition. Test engagement (as reflected by “zero-learning”, “some learning”, and “positive learning curves”) was assessed across each age bracket (in 6-month increments). We assessed and summarized barriers to engagement qualitatively.Results:The sample consisted of 304 children (152 males,152 females). Participants were predominantly Afro-Caribbean and Indo-Caribbean. Parent education and household income (Mdn=$370-740 USD per month) were consistent with the general population. GLAMS internal consistency was reliable (a=0.713). There were age effects on list-learning (rs=0.51; p<0.001), list recall (rs=0.51; p<0.001), face-name learning (rs=0.30;p<0.001), and face-name recall (rs=0.25; p<0.001). There were gender effects on list-learning (p=0.02) and list recall (p=0.01) but not face-name learning or recall. All GLAMS subtests were correlated with NEPSY Sentence Repetition (rs=0.22-0.34; p<0.001). There was sufficient sampling of males and females across all 6 age brackets. As age increased, a higher proportion of children showed a positive learning curve (and fewer “zero-scores”) on verbal learning (X2 =30.88, p<0.001) and face-name learning (X2=22.19, p=0.014), demonstrating increased task engagement as children mature. There were various qualitative observations of why children showed “zero-scores”, ranging from environmental distractions to anxiety and inattention.Conclusions:As far as we know, the GLAMS is the first preschool measure of learning and memory developed indigenously from within the Caribbean. It shows reliable internal consistency, expected age and gender effects and convergent validity. These initial results are encouraging and support continued efforts to establish test-retest and inter-rater reliability. Plans include validation in clinical samples, scale-up to other Caribbean countries, and eventual adaptation across global LMICs.

ObjectiveZika virus (ZIKV) targets neural stem cells in the developing brain. However, the majority of ZIKV-exposed children are born without apparent neurological manifestations. It remains unclear if these children were protected from ZIKV neurotropism or if they harbour subtle pathology that is disruptive to brain development. We assess this by comparing neurodevelopmental outcomes in normocephalic ZIKV-exposed children relative to a parallel control group of unexposed controls.DesignCohort study.SettingPublic health centres in Grenada, West Indies.Patients384 mother–child pairs were enrolled during a period of active ZIKV transmission (April 2016–March 2017) and prospectively followed up to 30 months. Child exposure status was based on laboratory assessment of prenatal and postnatal maternal serum.Main outcome measuresThe INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) package and Cardiff Vision Tests, administered and scored by research staff masked to child’s exposure status.ResultsA total of 131 normocephalic ZIKV exposed (n=68) and unexposed (n=63) children were assessed between 22 and 30 months of age. Approximately half of these children completed vision testing. There were no group differences in sociodemographics. Deficits in visual acuity (31%) and contrast sensitivity (23%) were apparent in the ZIKV-exposed infants in the absence of cognitive, motor, language or behavioural delays.ConclusionsOverall neurodevelopment is likely to be unaffected in ZIKV-exposed children with normal head circumference at birth and normal head growth in the first 2 years of life. However, the visual system may be selectively vulnerable, which indicates the need for vision testing by 3 years of age.