Mullen Scales Of Early Learning Scores Research Articles

Cognitive control in infancy: Attentional predictors using a tablet-based measure.

Cognitive control is a predictor of later-life outcomes and may underpin higher order executive processes. The present study examines the development of early cognitive control during the first 24-month. We evaluated a tablet-based assessment of cognitive control among infants aged 18- and 24-month. We also examined concurrent and longitudinal associations between attentional disengagement, general cognitive skills and cognitive control. Participants (N=60, 30 female) completed the tablet-task at 18- and 24-month of age. Attentional disengagement and general cognitive development were assessed at 5-, 8-, 12-, 18- and 24-month using an eye-tracking measure and the Mullen Scales of Early Learning (MSEL), respectively. The cognitive control task demonstrated good internal consistency, sensitivity to age-related change in performance and stable individual differences. No associations were found between infant cognitive control and MSEL scores longitudinally or concurrently. The eye-tracking task revealed that slower attentional disengagement at 8-month, but faster disengagement at 18-month, predicted higher cognitive control scores at 24-month. This task may represent a useful tool for measuring emergent cognitive control. The multifaceted relationship between attention and infant cognitive control suggests that the rapid development of the attentional system in infancy results in distinct attentional skills, at different ages, being relevant for cognitive control development.

Identifying critical windows of prenatal phenol, paraben, and pesticide exposure and child neurodevelopment: Findings from a prospective cohort study

BackgroundThis study aimed to investigate how exposure to a mixture of endocrine disrupting chemicals (EDCs) during two points in pregnancy affects early childhood neurodevelopment. MethodsWe analyzed publicly-available data from a high-risk cohort of mothers and their children (2007–2014) that measured six EDCs including methyl-, ethyl- and propyl parabens (MEPB, ETPB, PRPB), Bisphenol-A (BPA), 3,5,6-trichloro-2-pyridinol (TCPy), 3-phenoxybenzoic acid (3-PBA) in prenatal urine samples during the second and third trimesters. Neurodevelopmental scores were assessed using Mullen Scales of Early Learning (MSEL) at age 3. We used mean field variational Bayes for lagged kernel machine regression (MFVB-LKMR) to investigate the association between trimester-specific co-exposure to the six EDCs and MSEL scores at age 3, stratified by sex. ResultsThe analysis included 130 children. For females, the relationship between BPA and 3PBA with MSEL score varied between the two trimesters. In the second trimester, effect estimates for BPA were null but inversely correlated with MSEL score in the third trimester. 3PBA had a negative relationship with MSEL in the second trimester and positive correlation in the third trimester. For males, effect estimates for all EDCs were in opposing directions across trimesters. MFVB-LKMR analysis identified significant two-way interaction between EDCs for MSEL scores in both trimesters. For example, in females, the MSEL scores associated with increased exposure to TCPy were 1.75 units (95%credible interval −0.04, −3.47) lower in the 2nd trimester and 4.61 (95%CI −3.39, −5.84) lower in the third trimester when PRPB was fixed at the 75th percentile compared to when PRPB was fixed at the 25th percentile. ConclusionOur study provides evidence that timing of EDC exposure within the prenatal period may impact neurodevelopmental outcomes in children. More of these varying effects were identified among females. Future research is needed to explore EDC mixtures and the timing of exposure during pregnancy to enhance our understanding of how these chemicals impact child health.

A trial of nurturing care among children who are HIV-exposed and uninfected in eSwatini.

Children who are HIV-exposed and uninfected (CHEU) are a growing population at potential risk of poor neurocognitive development. We tested a nurturing care intervention on children's neurocognitive development and maternal depressive symptoms (primary) with mediation through caregiving activities (secondary). This study was conducted among six intervention and nine comparison antenatal-care/prevention of vertical transmission (ANC/PVT) HIV clinics in eSwatini. We enrolled pregnant women and measured infant development at 9 and 18 months. mothers2mothers (m2m) designed and implemented the clinic-home-community-based intervention. We measured infants' neurodevelopment, maternal depressive symptoms and caregiving activities with the Mullen Scales of Early Learning (MSEL), Edinburgh Postnatal Depression Scale, HOME Inventory and Family Care Indicators. We fitted linear mixed effects regression models with clinic random effects to compare intervention versus comparison arms, and generalised structural equation models to evaluate mediation, adjusting for confounders. Mother-infant pairs (n = 429) participated between January 2016 through May 2018. Socio-demographic characteristics were balanced between arms except for higher rates of peri-urban versus rural residence and single versus married mothers in the comparison group. The 18 month retention was 82% (180/220) intervention, 79% (166/209) comparison arm, with 25 infant deaths. Intervention MSEL scores were significantly, and modestly, higher in receptive language (55.7 [95% CI 54.6, 56.9] vs. 53.7 [95% CI 52.6, 54.8]), expressive language (42.5 [95% CI 41.6, 39.8] vs. 40.8 [95% CI 39.8, 41.7]) and composite MSEL (85.4 [95% CI 83.7, 84.5] vs. 82.7 [95% CI 81.0, 84.5]), with no difference in maternal depressive symptoms or in observations of mother-child interactions. Intervention book-sharing scores were higher (0.63 vs. 0.41) and mediated the effect on MSEL scores (indirect effect, p-values ≤ 0.024). The direct effects on visual reception and expressive language scores were significantly higher in the intervention compared to the comparison arm (coefficients 1.93 [95% CI 0.26, 3.60] and 1.66 [95% CI 0.51, 2.79, respectively]). Nurturing care interventions can be integrated into ANC/PVT clinic-home-community programmes. The intervention, mediated through interactive caregiving activities, increased language development scores among CHEU. Partnering with a local team, m2m, to design and implement a culturally relevant intervention illustrates the ability to impact parent-child play and learning activities that are associated with children's neurodevelopment.

Early childhood tracking application: Correspondence between crowd-based developmental percentiles and clinical tools.

Barriers to child developmental screening lead to delayed diagnosis and intervention. babyTRACKS, a mobile application for tracking developmental milestones, presents parents their child's percentiles computed relative to crowd-based data. This study evaluated correspondence between crowd-based percentiles and traditional development measures. Research analyzed babyTRACKS diaries of 1951 children. Parents recorded attainment age for milestones across Gross Motor, Fine Motor, Language, Cognitive, and Social domains. Fifty-seven parents completed the Ages and Stages Questionnaire (ASQ-3), and 13 families participated in the Mullen Scales of Early Learning (MSEL) expert assessment. Crowd-based percentiles were compared with: Centers for Disease Control (CDC) norms for comparable milestones, ASQ-3 and MSEL scores. babyTRACKS percentiles correlated with the percentage of unmet CDC milestones, and with higher ASQ-3 and MSEL scores across several domains. Children who did not meet CDC age thresholds had lower babyTRACKS percentiles by about 20 points and those at ASQ-3 risk had lower babyTRACKS Fine Motor and Language scores. Repeated measures tests showed significantly higher MSEL versus babyTRACKS percentiles in the Language domain. Although ages and milestones in diary varied, the app percentiles corresponded with traditional measures, particularly in fine motor and language domains. Future research is needed for determining referral thresholds while minimizing false alarms.

Placental morphology in association with autism-related traits in the EARLI study

BackgroundIn prior work we observed differences in morphology features in placentas from an autism-enriched cohort as compared to those from a general population sample. Here we sought to examine whether these differences associate with ASD-related outcomes in the child.MethodsParticipants (n = 101) were drawn from the Early Autism Risk Longitudinal Investigation (EARLI), a cohort following younger siblings of children with autism spectrum disorder (ASD). ASD-related outcomes, including the Social Responsiveness Scale (SRS), Mullen Scales of Early Learning (MSEL) Early Learning Composite, and ASD diagnosis, were assessed at age 3. Crude and adjusted linear regression was used to examine associations between placental morphological features (parametrized continuously and in quartiles) and SRS and MSEL scores; comparisons by ASD case status were explored as secondary analyses due to the small number of cases (n = 20).ResultsIn adjusted analyses, we observed a modest positive association between umbilical cord eccentricity, defined as the ratio of the maximum:minimum radius from the cord insertion point, and SRS scores (Beta = 1.68, 95%CI = 0.45, 2.9). Positive associations were also suggested between placental maximum thickness and cord centrality and SRS scores, though these were estimated with little precision. Associations between other placental morphological features and outcomes were not observed.ConclusionsOur analyses suggested a potential association between umbilical cord features and ASD-related traits, of interest as non-central cord insertion may reflect reduced placenta efficiency. Future studies with larger sample sizes are needed to further examine these and other placental features in association with ASD-related outcomes.

Pre- and Postnatal Fine Particulate Matter Exposure and Childhood Cognitive and Adaptive Function.

Increasing evidence exists for an association between early life fine particulate matter (PM2.5) exposure and several neurodevelopmental outcomes, including autism spectrum disorder (ASD); however, the association between PM2.5 and adaptive and cognitive function remains poorly understood. Participants included 658 children with ASD, 771 with a non-ASD developmental disorder, and 849 population controls from the Study to Explore Early Development. Adaptive functioning was assessed in ASD cases using the Vineland Adaptive Behavior Scales (VABS); cognitive functioning was assessed in all groups using the Mullen Scales of Early Learning (MSEL). A satellite-based model was used to assign PM2.5 exposure averages during pregnancy, each trimester, and the first year of life. Linear regression was used to estimate beta coefficients and 95% confidence intervals, adjusting for maternal age, education, prenatal tobacco use, race-ethnicity, study site, and season of birth. PM2.5 exposure was associated with poorer VABS scores for several domains, including daily living skills and socialization. Associations were present between prenatal PM2.5 and lower MSEL scores for all groups combined; results were most prominent for population controls in stratified analyses. These data suggest that early life PM2.5 exposure is associated with specific aspects of cognitive and adaptive functioning in children with and without ASD.

Dietary Advice Improves Non-Anemic Iron Deficiency

Source: Parkin PC, Borkhoff CM, Macarthur C, et al. Randomized trial of oral iron and diet advice versus diet advice alone in young children with non-anemic iron deficiency [published online ahead of print February 3, 2021]. J Pediatr. 2021. doi:10.1016/j.jpeds.2021.01.073Investigators from multiple Canadian institutions conducted a randomized trial to compare the effect of oral iron supplementation versus diet advice alone on neurodevelopmental outcomes in children. Parents of children with health supervision visits at 1 of 8 primary care practices in Toronto, Canada, during the study period were eligible. Children were included if they were 12-40 months of age and met criteria for non-anemic iron deficiency (NAID), defined as a hemoglobin ≥110 g/L and serum ferritin <14 μg/L. Children were excluded if they had a developmental condition, were born at a gestational age of <35 weeks or birth-weight of <2,500 grams, had acute illness, had previous anemia or iron deficiency, were receiving iron, or had a c-reactive protein ≥10 mg/L. Child demographics were collected at baseline.Participants were randomized to receive either liquid ferrous sulfate (6 mg elemental iron/kg/day) or liquid placebo in 2 divided doses daily by mouth for 4 months. All parents received diet advice on improving iron status via a written guide. Parents and researchers were blinded to treatment arm. Participants received a developmental assessment of gross motor and cognitive at baseline as well as 4 and 12 months after baseline using the Mullen Scales of Early Learning (MSEL).The primary outcome was MSEL scores 4 and 12 months after baseline. Secondary outcomes included serum ferritin values at 4 and 12 months. The investigators used an intention-to-treat analysis to assess the effect of intervention arm on outcomes, adjusting for baseline score, baseline ferritin, and unbalanced demographic characteristics across treatment arms.There were 60 participants randomized. Participants had a mean age of 24.2 months. Serum ferritin and mean MSEL scores were similar across treatment groups at baseline. The mean between-group difference in MSEL scores at 4 months was 1.1 points (95% CI, -4.2, 6.5) and at 12 months was 4.1 points (95% CI, -1.9, 10.1). The mean between-group difference in serum ferritin at 4 months was 16.9 μg/L (95% CI, 6.5, 27.2) and at 12 months was 3.9 μg/L (95% CI, -7.3, 15.1).The investigators conclude that there is no important between-group difference in neurodevelopmental outcomes in young children NAID treated with ferrous sulfate plus diet advice versus diet advice alone, though serum ferritin values are higher among those who received ferrous sulfate 4 months later.Dr Hogan has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.NAID is found in an estimated 11% of US children ages 6 months to 5 years.1 Approximately 25% to 42% of NAID eventually contributes to anemia in this age group.1 Duration, severity, and age onset of NAID may impact neurocognitive skills, breath-holding spells, restless leg syndrome, attention-deficit, pagophagia (ice craving), and athletic performance.2The definitive diagnostic study for NAID is absent iron staining on bone marrow biopsy, an invasive study.3 Although serum ferritin is specific and usually aligned with total body iron stores, normal thresholds vary with age and assay types. Serum ferritin levels rise during and for days to weeks after acute or chronic infection, injury, exercise, and inflammatory conditions.1-3 Consensus among health organizations as to definitions of NAID based on serum ferritin and other biomarkers vary.1-3Strengths of the current study include randomization and longitudinal data. Limitations include a small, homogeneous, well-educated cohort with self-reported medication compliance, adverse effects, and dietary intake. Even though iron supplementation was prescribed for 4 months, both groups had similarly improved ferritin levels after 12 months and equivalent hemoglobin levels throughout. CRP levels were not obtained at 4 and 12 months’ time points to determine the accuracy of the ferritin levels.1-3 Red blood cell indices, transferrin saturation, reticulocyte hemoglobin content, soluble transferrin receptor, and hepcidin—which are available serum biomarkers to help differentiate low iron stores from NAID—were not assessed.1Non-anemic iron deficiency due to inadequate iron intake in children ages 6 months to 5 years seems resolvable with written nutrition education within 12 months. More research is needed to determine whether low serum ferritin levels are associated with neurodevelopmental outcomes. (See AAP Grand Rounds. 2021;45[3]:27.)4The AAP recommends universal screening for anemia with measurement of hemoglobin concentration at approximately 12 months of age.3 Although the association of iron deficiency anemia in infancy and later cognitive deficits is supported by a number of prior studies, the same cannot be said of NAID.3 Unfortunately, the results of the current study are also inconclusive. Perhaps if low-dose ferrous sulfates (3 mg/kg elemental iron/day) had been used, compliance would have improved, potentially leading to differences in neurodevelopmental outcomes. (See AAP Grand Rounds. 2017;38[4]39.)5

Subdural Hemorrhage in Asymptomatic Neonates: Neurodevelopmental Outcomes and MRI Findings at 2 Years.

Background Subdural hemorrhage (SDH) is thought to have a benign course in asymptomatic neonates. However, effects on neurodevelopmental outcomes have not been established. Purpose To evaluate neurodevelopmental outcomes, gray matter volumes, and MRI findings in asymptomatic neonates with SDH compared with control neonates. Materials and Methods This retrospective analysis was conducted between 2003 and 2016 and was based on data from the University of North Carolina Early Brain Development Study. Neurodevelopmental outcomes were evaluated at 2 years of age by using the Mullen Scales of Early Learning (MSEL). All infants were imaged with 3.0-T MRI machines and were evaluated for SDH at baseline (neonates) and at ages 1 and 2 years. Volumetric MRI for brain segmentation was performed at ages 1 and 2 years. A secondary analysis was performed in neonates matched 1:1 with control neonates. Differences in categorical variables were measured by using the Fisher exact test, and the t test was used for continuous variables. Results A total of 311 neonates (mean gestational age ± standard deviation, 39.3 weeks ± 1.5), including 57 with SDH (mean gestational age, 39.5 weeks ± 1.2), were evaluated. The subgroup included 55 neonates with SDH (mean gestational age, 39.6 weeks ± 1.2) and 55 matched control neonates (mean gestational age, 39.7 weeks ± 1.2). Fifty-five of 57 neonates with SDH (97%; 95% CI: 92, 100) were delivered vaginally compared with 157 of 254 control neonates (62%, 95% CI: 56, 68; P < .001). Otherwise, there were no differences in perinatal, maternal, or obstetric parameters. There were no differences in composite MSEL scores (115 ± 15 and 109 ± 16 at 2 years, respectively; P = .05) or gray matter volumes between the neonatal SDH group and control neonates (730 cm3 ± 85 and 742 cm3 ± 76 at 2 years, respectively; P = .70). There was no evidence of rebleeding at follow-up MRI. Conclusion Neurodevelopmental scores and gray matter volumes at age 2 years did not differ between asymptomatic neonates with subdural hemorrhage and control neonates. © RSNA, 2020 Online supplemental material is available for this article.

Prenatal exposure to per- and polyfluoroalkyl substances and cognitive development in infancy and early childhood

Background/Aim: Pregnant women are exposed to per- and polyfluoroalkyl substances (PFAS), suspected neurodevelopmental toxicants. A growing number of epidemiological studies have investigated associations between prenatal PFAS exposure and child’s neurodevelopment, but the results varied by assessment time points and tools. We investigated associations between prenatal exposure to PFAS and child’s cognitive development at multiple assessment time points.Methods: We included 215 mother-child pairs from the MARBLES (Markers of Autism Risk in Babies - Learning Early Signs) longitudinal cohort study. Child’s cognitive functions were assessed using Mullen Scales of Early Learning (MSEL) at 6, 12, 24, and 36 months of age. Nine PFAS were quantified in maternal serum samples collected during pregnancy. We used multiple linear regression to estimate the change in MSEL scores in association with prenatal maternal PFAS concentrations at each assessment time point.Results: Higher prenatal maternal serum perfluorooctanoate (PFOA) was associated with lower MSEL Composite scores only at 24 months (β = -5.62, 95% CI: -10.6, -0.70). When compared to the lowest quartile, the third quartile of perfluorohexane sulfonate (PFHxS) was associated with increased Visual Reception scores at 6, 24, and 36 months. When stratified by child’s sex, females showed stronger associations of PFOA (β = -7.84, 95% CI: -15.1, -0.61) and PFHxS (β = -7.91, 95% CI: -15.2, -0.62) with decreased MSEL Composite scores at 36 months, compared to males.Conclusions: Our results suggest that prenatal PFOA may adversely affect child’s cognitive development at 24 months of age. Further studies using the same assessment tool with larger sample sizes are needed to confirm our findings.Keywords: cognitive development, Mullen Scales of Early Learning, PFAS, prenatal exposureDisclaimer: The findings and conclusions in this abstract are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

Child development, growth and microbiota: follow-up of a randomized education trial in Uganda.

BackgroundUndernutrition impairs child development outcomes and growth. In this follow-up study of an open cluster-randomized intervention trial we examined the effects of an education package delivered to mothers in rural Uganda on their children’s development, growth and gut microbiota at 36 months of age.MethodsThe parental trial included 511 mother-child pairs recruited when the children were 6-8 months. In that trial, a nutrition, stimulation and hygiene education was delivered to mothers in the intervention group while the control group received routine health care. A follow-up sample of 155 pairs (intervention n = 77, control n = 78) were re-enrolled when the children were 24 months. Developmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development (BSID-III) composite scores for cognitive (primary endpoint), language and motor development. Development outcomes were also evaluated using the Ages and Stages Questionnaire (ASQ) and the Mullen Scales of Early Learning (MSEL). Other outcomes included growth and gut microbiota composition.ResultsThe demographic characteristics were not different (P > 0.05) between the intervention and control groups and similar to those of the parental study. The intervention group had higher BSID-III scores than controls, with mean difference 10.13 (95% confidence interval (CI): 3.31-17.05, P = 0.002); 7.59 (1.62-13.66, P = 0.01); 9.00 (2.92-15.40, P = 0.005), for cognitive, language and motor composite scores, respectively. An improvement in the intervention compared to the control group was obtained for both the ASQ and the MSEL scores. The mean difference in height-for-age z-score was higher in the intervention compared to the control group: 0.50 (0.25-0.75, P = 0.0001). Gut microbiota composition did not differ significantly between the two study groups.ConclusionsThe maternal education intervention had positive effects on child development and growth at three years, but did not alter gut microbiota composition. This intervention may be applicable in other low-resource settings.Trial registrationClinicalTrials.gov registration number NCT02098031.

ERP markers are associated with neurodevelopmental outcomes in 1–5 month old infants in rural Africa and the UK

IntroductionInfants and children in low- and middle-income countries are frequently exposed to a range of poverty-related risk factors, increasing their likelihood of poor neurodevelopmental outcomes. There is a need for culturally objective markers, which can be used to study infants from birth, thereby enabling early identification and ultimately intervention during a critical time of neurodevelopment. MethodIn this paper, we investigate developmental changes in auditory event related potentials (ERP) associated with habituation and novelty detection in infants between 1 and 5 months living in the United Kingdom and The Gambia, West Africa. Previous research reports that whereas newborns’ ERP responses are increased when presented with stimuli of higher intensity, this sensory driven response decreases over the first few months of life, giving rise to a cognitively driven, novelty-based response. Anthropometric measures were obtained concurrently with the ERP measures at 1 and 5 months of age. Neurodevelopmental outcome was measured using the Mullen Scales of Early Learning (MSEL) at 5 months of age. ResultsThe described developmental change was observed in the UK cohort, who exhibited an intensity-based response at 1 month and a novelty-based response at 5 months of age. This change was accompanied by greater habituation to stimulus intensity at 5 compared to 1 month. In the Gambian cohort we did not see a change from an intensity-to a novelty-based response, and no change in habituation to stimulus intensity across the two age points. The degree of change from an intensity towards a novelty-based response was further found to be associated with MSEL scores at 5 months of infant age, whereas infants’ growth between 1 and 5 months was not. DiscussionOur study highlights the utility of ERP-based markers to study young infants in rural Africa. By implementing a well-established paradigm in a previously understudied population we have demonstrated its use as a culturally objective tool to better understand early learning in diverse settings world-wide. Results offer insight into the neurodevelopmental processes underpinning early neurocognitive development, which may in the future contribute to early identification of infants at heightened risk of adverse neurodevelopmental outcome.

2801. Post-Natal Zika Virus Infection and Impact on Neurodevelopment Among a Cohort of Children in Rural Guatemala

BackgroundThe impact of early post-natal Zika virus (ZIKV) infection on neurodevelopment (ND) is unknown. A prospective study of post-natal ZIKV infection in rural Guatemala (ZIKV study) enrolled a cohort of children ages 1–5 years, including children previously enrolled in a dengue virus (DENV) study during the 2015–2016 ZIKV epidemic. We evaluated ND outcomes by age and ZIKV infection status.MethodsSubjects enrolled in the ZIKV study June 2017–April 2018 underwent ND testing using the Mullen Scales of Early Learning (MSEL) at baseline and 12 months later. ZIKV/DENV-1/2 FRNT50 was performed on enrollment and on banked serum samples from the 2015 to 2016 subset. ZIKV serostatus and MSEL scores were correlated using multiple linear mixed models, adjusted for age and gender when appropriate, to evaluate their association. Geolocation was used to explore clustering of ZIKV serostatus and MSEL score.ResultsWe enrolled 183 children (43% female, mean age 3.2 years). Of these, 38 (21%) were classified as ZIKV-positive (+), 111 (61%) ZIKV-negative (-), 31 (17%) ZIKV-possible, and 3 (2%) ZIKV-indeterminate. ZIKV(+) cases and higher composite MSEL scores clustered in more densely populated areas (Figure 1). ZIKV(+) serostatus was associated with higher MSEL composite (increase in log score 0.09, P = 0.003) and subdomain scores: fine motor (0.13, P = 0.011), visual reception (0.15, P = 0.002), receptive language (0.09, P = 0.041), gross motor (0.14, P = 0.09), and expressive language (0.09, P = 0.058) (Figure 2). Of the 78 children (43%) with 2015–2016 samples, 46 (59%) remained ZIKV(−), 16 (21%) seroconverted from ZIKV(−) or possible/indeterminate to ZIKV(+), and 16 (21%) were indeterminate when enrolled in the ZIKV study. ZIKV seroconversion was associated with higher composite (0.13, P = 0.02) MSEL scores compared with ZIKV(−).ConclusionIn this exploratory analysis, post-natal ZIKV infection was not associated with adverse ND outcomes in children age 1–5 years. Overall, ZIKV(+) status was associated with higher average ND scores than ZIKV(−), and scores decreased with age for most children, independent of ZIKV status. The correlation of ZIKV(+) status and higher MSEL scores may be confounded by geographic-related factors or other confounders. NIAID Contract HHSN272201300015I Task Order HHSN27200013 (Co-PIs: FMM & EJA). DisclosuresFlor M. Munoz, M.D, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor - Royalties, Other Financial or Material Support.

846. Postnatally Acquired Zika Virus (ZIKV) Infection in Infants and Young Children in Guatemala: Serologic and Neurodevelopmental (ND) Evaluation

BackgroundDiagnosing ZIKV infection in children in dengue (DENV) endemic regions is challenging. The kinetics and effects of maternal Ab on infant infection responses remain unknown, as do the ND effects of ZIKV acquired in early life.MethodsThis is a population-based prospective cohort study in infant–mother pairs and children <5 years in a rural DENV endemic area of Guatemala evaluating the incidence and ND outcomes of postnatally cquired ZIKV infection. Subjects were followed 1 year for symptoms of flavivirus-like illness (FLI), serologic and virologic evidence of ZIKV or DENV infection and ND outcomes. ZIKV and DENV neutralizing antibodies (NAb) were measured at enrollment and longitudinally. Subjects were classified as ZIKV- or DENV-infected based on NAb. Specimens from acute illnesses were tested for viral RNA by rRT-PCR. ND was assessed at enrollment and longitudinally using an adapted Mullen Scales of Early Learning (MSEL).ResultsIn total, 1,371 subjects (374 children 1–5 years, 500 infants, 497 mothers) were enrolled from June 2017 to July 2018. Among 1,335 evaluable subjects, 7.6% (101) had serologic evidence of recent ZIKV infection (NAb >500 or >100 and DENV-neg); 13.2% (176) were DENV-pos only; 44.8% (598) were ZIKV-neg (NAb15 −<100) or low (<500) ZIKV and DENV NAb, suggesting prior flavivirus infection or cross-reactivity (Figures 1 and 2). ZIKV infection alone was more prevalent in children 1–5 years, while infants’ serologic pattern was similar to that of their mothers. One child ZIKV seroconverted. In 391 FLI episodes (67 children 1–5 years and 215 infants with fever, rash, myalgia, and conjunctivitis; 109 mothers with fever, myalgia, and joint pain), acute DENV infections, but not ZIKV, were identified by rRT-PCR. MSEL scores were similar to US norms in infants <12 m (composite mean 94.8, SD 11.9), but lower in children 1–5 years in all domains (mean 75.1, SD 17.4, P < 0.0001) (Figure 3).ConclusionSerologic evidence of recent ZIKV infection, but no acute ZIKV, was documented in young children in Guatemala. Infant seroreactivity derives from prior maternal infection and DENV cross-reactivity. Observed substantial differences in ND scores between infants and children 1–5 years challenge the ability to isolate the potential effects of ZIKV infection in early life. NIAID Contract HHSN272201300015I Task Order HHSN27200013. FMM and EJA Co-PIs. DisclosuresFlor M. Munoz, MD, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor: Royalties, Other Financial or Material Support.

Child development, growth and microbiota: follow-up of a randomized education trial in Uganda

Undernutrition impairs child development outcomes and growth. In this follow-up study of an open cluster-randomized intervention trial we examined the effects of an education package delivered to mothers in rural Uganda on their children's development, growth and gut microbiota at 36 months of age.The parental trial included 511 mother-child pairs recruited when the children were 6-8 months. In that trial, a nutrition, stimulation and hygiene education was delivered to mothers in the intervention group while the control group received routine health care. A follow-up sample of 155 pairs (intervention n = 77, control n = 78) were re-enrolled when the children were 24 months. Developmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development (BSID-III) composite scores for cognitive (primary endpoint), language and motor development. Development outcomes were also evaluated using the Ages and Stages Questionnaire (ASQ) and the Mullen Scales of Early Learning (MSEL). Other outcomes included growth and gut microbiota composition.The demographic characteristics were not different (P > 0.05) between the intervention and control groups and similar to those of the parental study. The intervention group had higher BSID-III scores than controls, with mean difference 10.13 (95% confidence interval (CI): 3.31-17.05, P = 0.002); 7.59 (1.62-13.66, P = 0.01); 9.00 (2.92-15.40, P = 0.005), for cognitive, language and motor composite scores, respectively. An improvement in the intervention compared to the control group was obtained for both the ASQ and the MSEL scores. The mean difference in height-for-age z-score was higher in the intervention compared to the control group: 0.50 (0.25-0.75, P = 0.0001). Gut microbiota composition did not differ significantly between the two study groups.The maternal education intervention had positive effects on child development and growth at three years, but did not alter gut microbiota composition. This intervention may be applicable in other low-resource settings.ClinicalTrials.gov registration number NCT02098031.

Adaptation of the Mullen Scales of Early Learning for use among infants aged 5‐ to 24‐months in rural Gambia

Infants in low‐resource settings are at heightened risk for compromised cognitive development due to a multitude of environmental insults in their surroundings. However, the onset of adverse outcomes and trajectory of cognitive development in these settings is not well understood. The aims of the present study were to adapt the Mullen Scales of Early Learning (MSEL) for use with infants in a rural area of The Gambia, to examine cognitive development in the first 24‐months of life and to assess the association between cognitive performance and physical growth. In Phase 1 of this study, the adapted MSEL was tested on 52 infants aged 9‐ to 24‐months (some of whom were tested longitudinally at two time points). Further optimization and training were undertaken and Phase 2 of the study was conducted, where the original measures were administered to 119 newly recruited infants aged 5‐ to 24‐months. Infant length, weight and head circumference were measured concurrently in both phases. Participants from both phases were split into age categories of 5–9 m (N = 32), 10–14 m (N = 92), 15–19 m (N = 53) and 20–24 m (N = 43) and performance was compared across age groups. From the ages of 10–14 m, Gambian infants obtained lower MSEL scores than US norms. Performance decreased with age and was lowest in the 20–24 m old group. Differential onsets of reduced performance were observed in the individual MSEL domains, with declines in visual perception and motor performance detected as early as at 10–14 months, while reduced language scores became evident after 15–19 months of age. Performance on the MSEL was significantly associated with measures of growth.

Transitivity Types Predict Communicative Abilities in Infants at Risk of Autism*

Abstract To examine predictors of preschool language abilities, thirty-seven infants at high risk for Autism Spectrum Disorder (ASD) were recorded longitudinally from 5-14 months as they interacted with their caregivers and toys at home. Triadic interactions were coded, categorized as transitive, intransitive or vacuously transitive, and then related to the MacArthur Bates Communicative Development Inventory (CDI-III) and the Mullen Scales of Early Learning (MSEL) at 36 months. The results show that prior to 14 months, early transitive interactions correlate positively and intransitive interactions correlate negatively with CDI-III and MSEL scores at 36 months. By categorizing interactions between 5-14 months by transitivity, we have demonstrated that recurring triadic patterns can predict communicative abilities at 36 months.

Prenatal exposure to organophosphate esters and cognitive development in young children in the Pregnancy, Infection, and Nutrition Study

Organophosphate esters (OPEs) are a class of chemicals commonly used as flame retardants and plasticizers. OPEs are applied to a wide variety of consumer products and have a propensity to leach from these products. Consequently, OPEs are ubiquitous contaminants in many human environments and human exposure is pervasive. Accumulating evidence suggests that OPEs are capable of interfering with childhood cognitive development through both neurologic- and endocrine-mediated mechanisms. However, observational evidence of cognitive effects is limited. We used data collected in the third phase of the Pregnancy, Infection, and Nutrition Study to investigate cognitive effects of prenatal exposure to OPEs. In a spot prenatal maternal urine sample, we measured the following OPE metabolites: diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl phosphate) (BDCIPP), isopropyl-phenyl phenyl phosphate (ip-PPP), and 1-hydroxyl-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP). We assessed children's language and multi-faceted and overall cognitive development between two and three years of age using the MacArthur-Bates Communicative Development Inventories (MB-CDI) and the Mullen Scales of Early Learning (MSEL). We used linear regression to estimate the change in children's scores on these developmental assessments per interquartile range (IQR) increase in log-transformed, specific-gravity-corrected prenatal OPE metabolite concentrations, adjusted for maternal age, education, income, race/ethnicity, BMI, and child's sex. A total of 149 children had both OPE metabolite measurements and MB-CDI scores, and 227 children had both OPE metabolite measurements and MSEL scores. We observed that higher concentrations of ip-PPP (ng/ml) were associated with lower scores on the MSEL Cognitive Composite Score (β = −2.61; 95% CI: −5.69, 0.46), and separately on two of the four MSEL Scales that comprise the Cognitive Composite, specifically the Fine Motor Scale (β = −3.08; 95% CI: −5.26, −0.91) and the Expressive Language Scale (β = −1.21; 95% CI: −2.91, 0.49). We similarly observed that prenatal ip-PPP concentrations were inversely associated with age-standardized scores on the MB-CDI Vocabulary assessment (β = −1.19; 95% CI: −2.53, 0.16). Other OPE metabolites were not strongly associated with performance on either assessment. Our results suggest that isopropylated triarylphosphate isomers, the presumed parent compounds of ip-PPP, may adversely impact cognitive development, including fine motor skills and early language abilities. Our study contributes to the growing body of observational evidence that suggests prenatal exposure to OPEs may adversely affect cognitive development.

Adapting and translating the Mullen Scales of Early Learning for the South African context.

BackgroundSouth African speech-language therapists have identified the need for culturally valid and sensitive assessment tools that can accommodate multiple languages and cover a reasonable age range. The Mullen Scales of Early Learning (MSEL) extend from birth to 68 months, contain five separate subscales including receptive language, expressive language, gross motor, fine motor and visual reception scale, are straightforward to administer and have been successfully used in other African countries, such as Uganda. It also identifies a child’s strengths and weaknesses and provides a solid foundation for intervention planning.ObjectivesThis research aimed to demonstrate the appropriateness and usefulness of the translated and culturally and linguistically adapted MSEL across four South African languages (Afrikaans, isiZulu, Setswana and South African English) through two sub-aims: (1) to describe differences, if any, in MSEL performance across language groups and (2) to describe differences, if any, in MSEL performance between age groups.MethodA total of 198 typically developing children between the ages of 21 and 68 months spread across the four language groups were individually assessed with the culturally and linguistically adapted and translated MSEL.ResultsA one-way analysis of variance (ANOVA) showed no statistically significant differences between the four language groups for total MSEL scores. A Welch’s one-way ANOVA showed that the total MSEL scores were significantly different between age groups.ConclusionThe translation and adaptation of the MSEL was successful and did not advantage or disadvantage children based on their home language, implying that linguistic equivalence was achieved. The MSEL results differed between age groups, suggesting that the measure was also successful in differentiating the performance of children at different developmental levels.

In utero pyrethroid pesticide exposure and child cognitive development from 6 to 36 months in the MARBLES longitudinal cohort

Introduction: Pyrethroid (PYR) pesticides have neurotoxicological properties but little is known about the effects of in utero exposure on child development. We assessed the relation or in utero PYR exposure and child cognitive development from 6-36 months. Methods: Mother-child pairs (n=132) in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) cohort were examined. MARBLES enrolls pregnant women who already had a child with autism spectrum disorder (ASD) and, therefore are at increased risk (up to 20%) for having another child who will develop ASD. Maternal urine samples comprising an individual spot urine and a pooled sample of three individual spot urine samples, from each of the latter two trimesters were analyzed for PYR metabolite 3-phenoxybenzoic acid (3PBA). For 9 mothers we analyzed all samples, without pooling, to study intra-pregnancy variability. The intraclass correlation coefficient (ICC) from these 9 moms and total number of urine samples for each pregnancy were used to compute weights for linear regression models of child cognition using the Mullen Scales of Early Learning (MSEL) a norm referenced cognitive measure. Results: Median 3PBA concentration in the variability study was 0.63 ng/ml with an ICC = 0.65 for specific gravity-adjusted 3PBA. In all 132 moms, median 3PBA concentration was 0.83 ng/ml. After applying weights to 3PBA concentration and adjusting for specific gravity, mom’s age at delivery, child’s sex, and season of conception, we found significantly lower MSEL scores at 6 months (β= -0.55, p-value 0.002). Lower scores were also observed for MSEL at 12, 24 and 36 months but these results were not significant. Conclusion: This may be the first study to show an association with in utero PYR pesticide exposure and decreased cognitive development at 6 months. These are preliminary findings and results will be updated with a larger sample and more rigorous measurement error modeling approaches.

The Mullen scales of early learning: ceiling effects among preschool children

Two cognitive tests were administered to typically developing children (36–67 months): the Mullen Scales of Early Learning (MSEL), which is appropriate for very young children and thus often used in research with atypical samples (e.g., children with Autism Spectrum Disorder), and the Kaufman Assessment Battery for Children (K-ABC). This was done in order to re-examine possible MSEL ceiling effects in a new sample and achieve a more in-depth understanding of these ceiling effects, if indeed present. Results indicated that among children ranging in age from 51 to 68 months, MSEL scores were significantly lower than K-ABC scores, and that with increasing age the number of children who completed the MSEL without establishing a ceiling level increased. Our results indicated that the MSEL scores are affected by ceiling effects and, therefore, the test underestimates cognitive abilities among older and more cognitively able children.