Neurological outcomes in neonates treated with therapeutic hypothermia: challenges in a developing country.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) affects 1.5 newborns per 1 thousand term live births. Therapeutic hypothermia (TH) does not prevent all adverse outcomes. The experience with TH is still limited in Latin America. In Rio de Janeiro, Hospital Universitário Pedro Ernesto treats neonates with HIE since 2017 using the servo-controlled system. OBJECTIVE: To describe the frequency of epilepsy, altered neurological exam, and neurodevelopmental delay at 12 months of age in patients treated with TH in a reference hospital in Rio de Janeiro and to evaluate the possible risk associations with clinical data and data from complementary exams. METHODS: We evaluated medical records from the Neonatal Intensive Care Unit hospitalization and from first evaluation recorded at 12 months of age in the High-Risk Neonate Follow-up Outpatient Sevice. RESULTS: A total of 30 subjects were included in the study. We found epilepsy in 18.2% of the patients, altered neurological exam in 40.9%, and neurodevelopmental delay in 36.4%. We also found a significant relationship between altered magnetic resonance imaging scan and subsequent altered neurological exam. Our findings are in line with those of the international literature, which shows that adverse outcomes are still observed, even when TH is applied. Brazilian data shows our limited access to complementary exams. The rate of loss to follow-up was of 26.6%, probably due to the coronavirus disease 2019 (COVID-19) pandemic and to unfavorable socioeconomic conditions. More time for prospective follow-up and protocol adjustments should contribute to improve our data. CONCLUSION: High incidences of epilepsy, altered neurological exams, and neurodevelopmental delay were found, despite the use of TH. A more efficient use of resources is needed, as well as measures such as early intervention.

ANTECEDENTES: A encefalopatia hipóxico-isquêmica (EHI) afeta 1,5 a cada mil nascidos vivos a termo. A hipotermia terapêutica (HT) não previne todos os desfechos negativos. A experiência com HT ainda é limitada na América Latina. No Rio de Janeiro, o Hospital Universitário Pedro Ernesto trata neonatos com EHI desde 2017 usando o sistema servo-controlado. OBJETIVO: Relatar a frequência de epilepsia, de alteração em exame neurológico e de atraso no desenvolvimento neuropsicomotor aos 12 meses de idade nos pacientes submetidos a HT em um hospital de referência no estado do Rio de Janeiro e avaliar as associações de risco com dados clínicos e de exames complementares. MéTODOS: Foi feita análise de dados do prontuário médico da internação na UTI Neonatal e da primeira avaliação registrada a partir de 12 meses completos de idade no Ambulatório de Seguimento de Recém-Nascido de Alto Risco. RESULTADOS: Ao todo, 30 pacientes foram incluídos. As frequências de epilepsia, de alteração em exame neurológico e de atraso no desenvolvimento neuropsicomotor aos 12 meses de idade foram, respectivamente, de 18,2%, 40,9% e 36,4%. Observamos relação significativa entre alteração na ressonância magnética e posterior alteração no exame neurológico. Nossos achados corroboram a literatura internacional, em que desfechos desfavoráveis ocorrem mesmo aplicando-se HT. Dados brasileiros mostram a limitação da disponibilidade dos exames complementares. Houve perda de seguimento de 26,6%, provavelmente pela pandemia da doença do coronavírus 2019 (coronavirus disease 2019, COVID-19, em inglês) e condições socioeconômicas desfavoráveis. Mais tempo de seguimento e ajustes no protocolo devem contribuir para melhorar nossos dados. CONCLUSãO: Foram encontradas elevadas incidências de epilepsia, de exame neurológico alterado e de atraso no neurodesenvolvimento, apesar da HT. Faz-se necessário uso mais eficiente dos recursos disponíveis, bem como de medidas como intervenção precoce.

[The impact of congenital heart disease on neurodevelopment]. / El impacto de las cardiopatías congénitas en el neurodesarrollo.

It is estimated that about 1 in 100 live births has a congenital heart disease (CHD). Cognitive deficit, academic difficulties, and behavioral abnormalities, in combination, represent the most common morbidity affecting quality of life in survivors with CHD. Developmental dysfunction results from a complex interaction between patient-specific factors such as genetic susceptibility, cardiac diagnosis, fetal development, and environmental factors such as preoperative events, supportive techniques during surgical repair, postoperative events, socioeconomic status. A comprehensive neurodevelopmental assessment in all children with CHD is critical to identify any need for intervention early and provide the support needed to optimize their long-term development.

Se estima que aproximadamente 1 de cada 100 nacidos vivos presenta una cardiopatía congénita (CC). El déficit cognitivo, las dificultades académicas y anomalías conductuales, en combinación, representan la morbilidad más común que afecta la calidad de vida en sobrevivientes con CC. La disfunción del desarrollo resulta de una interacción compleja entre factores específicos del paciente como susceptibilidad genética, tipo de cardiopatía, desarrollo fetal y factores ambientales tales como eventos preoperatorios, técnicas de apoyo durante la reparación quirúrgica, eventos posoperatorios, estatus socioeconómico. Una evaluación integral del neurodesarrollo en todos los niños con CC es fundamental para identificar tempranamente cualquier necesidad de intervención y proporcionar el apoyo necesario para optimizar su desarrollo a largo plazo.

Risk of alterations in neurodevelopment in infants and preschool children with cancer.

BACKGROUND: Some cancer survivors experience difficulties with concentration, attention, and memory; however, there are no studies on neurodevelopment in patients under 5 years of age who are undergoing cancer treatment. Our aim was to evaluate neurodevelopment in cancer patients under 5 years of age using the Early Development Instrument (EDI) test, considering factors such as nutritional status, type of cancer, and treatment effect. METHODS: A cross-sectional study was conducted from February 2018 to March 2019. Patients with cancer diagnoses outside the central nervous system in any phase of cancer treatment were included. RESULTS: A total of 45 patients were included. Regarding fine motor skills, 28% of patients with retinoblastoma and 23% of patients with leukemia or lymphoma had a risk of developmental delay compared to 0% of patients with solid tumors (p = 0.025). The final results showed that 19 (42.2%) patients had normal neurodevelopment (gray), 7 (15.5%) had a delay in neurodevelopment (light gray), and 19 (42.2%) had a risk of developmental delay (black). Regarding developmental delay, 52% of patients in the leukemia and lymphoma group, 71% in the retinoblastoma group, and 23% in the solid tumor group presented developmental delay (p = 0.06). CONCLUSIONS: The risk of delay and lag in neurodevelopment is common in cancer patients under 5 years of age undergoing treatment. However, more studies are required to evaluate the effect of treatment on this group of patients as it may be affected by various factors.

INTRODUCCIÓN: En algunos pacientes supervivientes de cáncer se presentan dificultades de concentración, atención y memoria, sin embargo no hay estudios en relación al neurodesarrollo en pacientes menores de 5 años que se encuentran en tratamiento oncológico. Por lo que el objetivo fue valorar el neurodesarrollo en pacientes con cáncer durante el tratamiento oncológico mediante la prueba EDI tomando en cuenta diversos factores como su estado nutricional, tipo de cancer, y el efecto del tratamiento. MÉTODOS: Se realizó un estudio transversal, de febrero de 2018 a marzo de 2019. Se incluyeron pacientes mayores de 1 año y menores de 5 años con diagnóstico de cáncer fuera del sistema nervioso central, en tratamiento oncológico. RESULTADOS: Se incluyeron 45 pacientes. En el área motor fina el 28% de los pacientes con retinoblastoma y 23% con leucemias y linfomas se encontraron en rojo (retraso) en comparación con 0% de los pacientes con tumores sólidos (p = 0.025). En el resultado global se encontró que 19 (42.2%) pacientes tuvieron neurodesarrollo normal (gris), 7 (15.5%) rezago en el neurodesarrollo (gris claro) y 19 (42.2%) con riesgo de retraso en el desarrollo (negro). De los pacientes que presentaron riesgo de retraso el 52% fueron del grupo de leucemias y linfomas, el 71% en el grupo de retinoblastoma y el 23% del grupo de tumores sólidos (p = 0.06). CONCLUSIONES: La presencia de riesgo de retraso y rezago en el neurodesarrollo es frecuente en menores de 5 años con diagnóstico de cáncer. Se requieren más estudios, para evaluar el efecto del tratamiento en este grupo de pacientes, ya que pueden influir diversos factores.

Assessment of newborn neuropsychomotor development born with exposure to SARS-CoV-2 in the perinatal period using the Bayley III scale at 6 months of age.

OBJECTIVE: This study aimed to evaluate the Neuropsychomotor Development (NPMD) of newborns exposed to SARS-CoV-2 in the perinatal period using the Bayley III scale at 6 months of age. METHODS: Childcare appointments were scheduled for the included newborns in the study. During the 6-month consultation, the Screening Test for Bayley III Scale and, based on it, children were classified as "low risk", "moderate risk" or "high risk" in the domains: of cognitive, receptive language, expressive language, fine motor, and gross motor. Those classified as "moderate risk"; or "high risk" received guidance about NPMD stimuli and were instructed to maintain follow-up. RESULTS: Only 13 (37.1 %) of the newborns were classified as low risk in receptive language and 18 (51.4 %) in gross motor skills, with the domains most affected. Prematurity was a risk for cognitive incompetence (moderate risk/high-risk classification) (coefficient: 1.89, Odds Ratio = 6.7, 95 % CI 1.3‒35, p = 0.02). Lower birth weight that 2.500g had a similar effect on cognitive incompetence (coefficient: 1.9, Odds Ratio = 6.2, 95 % CI 1.2‒32.2, p = 0.02). Exclusive breastfeeding at hospital discharge (n = 8) was protective for incompetence (high risk/moderate risk) in the language domain (coefficient -2.14, OR = 0.12, 95 % CI 0.02‒0.71, p = 0.02). CONCLUSIONS: The children included in the study must be monitored and their development monitored in order to clarify whether there is a relationship between the delay in NPMD and perinatal exposure to COVID-19, as delays were observed in these preliminary results.

Is neurodevelopment impaired in Brazilian children with intestinal failure on prolonged parenteral nutrition? A single center study.

PURPOSE: To assess the neurodevelopment outcomes of children younger than 42 months of age with intestinal failure (IF) using prolonged parenteral nutrition (PN) followed by a Pediatric Multidisciplinary Intestinal Rehabilitation Program from a public tertiary hospital in Brazil. METHODS: Bayley III scale was administered in children aged 2 to 42 months with IF and receiving PN for more than 60 days. Composite scores in cognitive, motor, and language domains were analyzed. Developmental delay was defined as a performance 2 standard deviations (SD) below the average at the 3 domains. Association between Bayley III composite scores and clinical variables related to IF were tested. RESULTS: Twenty-four children with median (IQR) age of 17.5 months (9-28.5) were studied, 58.3% were male. Developmental delay was found in 34%, 33% and 27% of the patients in cognitive, motor, and language domains, respectively. There was no significant association between the Bayley-III composite scores and length of hospitalization, prematurity, and number of surgical procedures with anesthesia. CONCLUSION: The study demonstrated impairments in the cognitive, motor and language domains in approximately one-third of young patients with IF on prolonged PN.

Neurodevelopmental delay in children exposed to maternal SARS-CoV-2 in-utero.

It is unclear if SARS CoV-2 infection during pregnancy is associated with adverse neurodevelopmental repercussions to infants. We assessed pediatric neurodevelopmental outcomes in children born to mothers with laboratory-confirmed SARS CoV-2 infection during pregnancy. Neurodevelopmental outcomes of in-utero exposed children were compared to that of pre-pandemic control children in Los Angeles (LA), CA, USA and Rio de Janeiro, Brazil. Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), the gold standard tool for evaluating neurodevelopment until 36 months of age and Ages and Stages Questionnaires (ASQ-3), a frequently used screening instrument for evaluating neurodevelopment in this same age group were the assessment tools used. Developmental delay (DD) was defined as having a score < - 2 SD below the norm (< 70) in at least one of three Bayley-III domains, (cognitive, motor or language) or a score below the cut-off (dark zone) in at least one of five ASQ-3 domains (communication, gross motor, fine motor, problem solving, personal-social). Exposed children were born between April 2020 and December 2022 while control children were born between January 2016 to December 2019. Neurodevelopmental testing was performed in 300 children total: 172 COVID-19 exposed children between 5-30 months of age and 128 control children between 6-38 months of age. Bayley-III results demonstrated that 12 of 128 exposed children (9.4%) had DD versus 2 of 128 controls (1.6%), p = 0.0007. Eight of 44 additional exposed children had DD on ASQ-3 testing. Fully, 20 of 172 exposed children (11.6%) and 2 of 128 control children (1.6%), p = 0.0006 had DD. In Rio, 12% of exposed children versus 2.6% of controls, p = 0.02 had DD. In LA, 5.7% of exposed children versus 0 controls, p = 0.12 had DD. Severe/critical maternal COVID-19 predicted below average neurodevelopment in the exposed cohort (OR 2.6, 95% CI 1.1-6.4). Children exposed to antenatal COVID-19 have a tenfold higher frequency of DD as compared to controls and should be offered neurodevelopmental follow-up.

[Environmental factors influencing developmental disorders]. / Factores ambientales que influyen en los trastornos del desarrollo.

Neurodevelopmental disorders have been associated with multiple causes especially, genetic a nd environmental -nutritional, infectious, toxic, traumatic and psychosocial stress among others- that in general do not operate alone, but interact with each other. Of special interest is to identify the mechanism(s) that lead to these disorders. Inflammation and epigenetic changes may play a common end for many forms of environmental risk.

Los trastornos del neurodesarrollo, se han asociado con múltiples causas, especialmente genéticas y ambientales ­nutricionales, infecciosas, tóxicas, traumáticas y estrés psicosocial, entre otras­ que en general interactúan entre sí. De especial interés es identificar el/los factores que contribuyen a estos trastornos. Factores ambientales que están relacionados con inflamación y cambios epigenéticos pueden ser una vía común final.

High-Risk Neighborhoods and Neurodevelopmental Outcomes in Infants Born Preterm.

OBJECTIVE: To study the association between neighborhood risk and moderate to severe neurodevelopmental impairment (NDI) at 22-26 months corrected age in children born at <34 weeks of gestation. We hypothesized that infants born preterm living in high-risk neighborhoods would have a greater risk of NDI and cognitive, motor, and language delays. STUDY DESIGN: We studied a retrospective cohort of 1291 infants born preterm between 2005 and 2016, excluding infants with congenital anomalies. NDI was defined as any one of the following: a Bayley Scales of Infant and Toddler Development-III Cognitive or Motor composite score <85, bilateral blindness, bilateral hearing impairment, or moderate-severe cerebral palsy. Maternal addresses were geocoded to identify census block groups and create high-risk versus low-risk neighborhood groups. Bivariate and regression analyses were run to assess the impact of neighborhood risk on outcomes. RESULTS: Infants from high-risk (n = 538; 42%) and low-risk (n = 753; 58%) neighborhoods were compared. In bivariate analyses, the risk of NDI and cognitive, motor, and language delays was greater in high-risk neighborhoods. In adjusted regression models, the risks of NDI (OR, 1.43; 95% CI, 1.04-1.98), cognitive delay (OR, 1.62; 95% CI, 1.15-2.28), and language delay (OR, 1.58; 95% CI, 1.15-2.16) were greater in high-risk neighborhoods. Breast milk at discharge was more common in low-risk neighborhoods and was protective of NDI in regression analysis. CONCLUSIONS: High neighborhood risk provides an independent contribution to preterm adverse NDI, cognitive, and language outcomes. In addition, breast milk at discharge was protective. Knowledge of neighborhood risk may inform the targeted implementation of programs for socially disadvantaged infants.

Neurodevelopmental Outcome of Children with Congenital Heart Disease: A Cohort Study from Infancy to Preschool Age.

OBJECTIVE: To characterize the neuropsychological outcome of children with congenital heart disease (CHD) at age 5 years; the stability of cognitive and language abilities across childhood; and to identify early neurodevelopmental markers of neuropsychological outcomes in these children. STUDY DESIGN: Five-year-old children (n = 55) with complex CHD were assessed using standardized and comprehensive neuropsychological measures. Stability of language and cognitive performance was assessed by comparing standardized scores between ages 1, 2, and 5 years old. Association between 5-year-old skills and scores obtained in early childhood was studied to identify potential early markers of preschool performance. Receiver operating characteristic curves were used to evaluate the classification accuracy of Bayley Scales of Infant Development, Third Edition scales in identifying later impairments. RESULTS: At age 5 years, our cohort obtained scores significantly below the norms on most developmental domains, with 35% to 65% of participants showing impaired short-term/working memory, attention, and preacademic skills. Developmental patterns measured between ages 1 and 5 years were different for cognitive and language domains, with a decline with age for cognitive functioning and stable results for expressive language. The Bayley Scales of Infant Development, Third Edition language scores at age 2 years provided a good predictive value in identifying children with impaired language at age 5 years. CONCLUSIONS: In our cohort, we found a high prevalence of impairments affecting higher-order cognitive domains. Although language difficulties can be detected as early as 2 years of age, other neuropsychological impairments, such as attention and pre-academic skills, only appear later during development, which reinforces the need for long-term monitoring and systematic assessment before school entry.

Behavioral Health Diagnoses in Youth with Differences of Sex Development or Congenital Adrenal Hyperplasia Compared with Controls: A PEDSnet Study.

OBJECTIVE: To evaluate the odds of a behavioral health diagnosis among youth with differences of sex development (DSD) or congenital adrenal hyperplasia (CAH) compared with matched controls in the PEDSnet database. STUDY DESIGN: All youth with a diagnosis of DSD (n = 1216) or CAH (n = 1647) and at least 1 outpatient encounter were extracted from the PEDSnet database and propensity-score matched on 8 variables (1:4) with controls (n = 4864 and 6588, respectively) using multivariable logistic regression. The likelihood of having behavioral health diagnoses was examined using generalized estimating equations. RESULTS: Youth with DSD had higher odds of a behavioral health diagnosis (OR, 1.7; 95% CI, 1.4-2.1; P < .0001) and neurodevelopmental diagnosis (OR, 1.7; 95% CI, 1.4, 2.0; P < .0001) compared with matched controls. Youth with CAH did not have an increased odds of a behavioral health diagnosis (OR, 1.0; 95% CI, 0.9, 1.1; P = .9) compared with matched controls but did have higher odds of developmental delay (OR, 1.8; 95% CI, 1.4, 2.4; P < .0001). CONCLUSIONS: Youth with DSD diagnosis have higher odds of a behavioral health or neurodevelopmental diagnosis compared with matched controls. Youth with CAH have higher odds of developmental delay, highlighting the need for screening in both groups.

Health surveillance and development of children with congenital Zika Virus syndrome: an integrative literature review.

OBJECTIVE: To identify scientific knowledge about the attention to health surveillance and development of Brazilian children under the age of three years involving the Congenital Zika virus (ZIKV) Syndrome. DATA SOURCES: This is an integrative literature review of primary studies with Brazilian children under three years of age from 2015 to 2019. The searches were carried out in the databases Latin American and Caribbean Literature in Health Sciences (LILACS), US National Library of Medicine (PubMed), Cumulative Index to Nursing and Allied Health Literature (CINAHL), SCOPUS and Web of Science. It was carried out by crossing the keywords in English (child, child development and Zika virus) and in Portuguese (criança, desenvolvimento infantil e Zika vírus), with the combination of the Boolean operator "AND". DATA SYNTHESIS: The knowledge produced is related to the specific health and development problems of children affected by the Congenital ZIKV Syndrome, with clinical characteristics, care demands, multiprofessional performance, health monitoring and surveillance needs. CONCLUSIONS: This integrative review synthesized scientific knowledge by adding aspects that reinforce the relevance of appropriate approaches to assess and care for children, linked to the engagement of caregivers, the need to document, evaluate and track the situations of children in early childhood and long-term, management coordination of care and its challenges in the context of primary health care.

POTENTIAL RISK OF BRAIN DAMAGE AND POOR DEVELOPMENTAL OUTCOMES IN CHILDREN PRENATALLY EXPOSED TO SARS-COV-2: A SYSTEMATIC REVIEW.

OBJECTIVE: To perform a systematic literature review to analyze existing data on the neurological effects of coronavirus on newborns. DATA: sources: We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and searched the PubMed and Embase platforms for the keywords [brain damage OR pregnancy OR developmental outcomes] and [coronavirus OR SARS-CoV-2 OR SARS-CoV OR MERS-CoV] between January 1, 2000 and June 1, 2020. DATA: synthesis: Twenty-three reports described the course of pregnant women exposed to SARS-CoV-2, SARS-CoV, or MERS-CoV during the gestational period, eight to SARS-CoV-2, eight to SARS-CoV, and seven to MERS-CoV. No data were found on abnormalities in brain development or on a direct link between the virus and neurological abnormalities in the human embryo, fetus, or children. Spontaneous miscarriage, stillbirth, and termination of pregnancy were some complications connected with SARS/MERS-CoV infection. SARS-CoV-2 is not currently associated with complications in the gestational period. CONCLUSIONS: The literature has no data associating exposure to coronavirus during pregnancy with brain malformations and neurodevelopmental disorders. However, despite the lack of reports, monitoring the development of children exposed to SARS-CoV-2 is essential given the risk of complications in pregnant women and the potential neuroinvasive and neurotropic properties found in previous strains.

Child Mouthing of Soil and Contaminated Fomites and Unimproved Sanitation are Associated with Subsequent Poor Child Developmental Outcomes in Urban Bangladesh (CHoBI7 Program).

OBJECTIVE: To evaluate the relationship between mouthing of soil and living in unsanitary conditions and child cognitive development in urban Bangladesh. STUDY DESIGN: This prospective cohort study of 224 children under 5 years of age was conducted in urban Dhaka, Bangladesh. Developmental outcomes were assessed by communication, fine motor, gross motor, personal social, problem solving, and combined developmental scores measured by the Extended Ages and Stages Questionnaire (EASQ) at a 12-month follow-up visit. RESULTS: Children who had caregiver reports of puting soil in their mouths at the majority of surveillance visits had significantly lower combined EASQ Z scores (coefficient, -0.53; 95% CI, -0.83 to -0.22) at the 12-month follow-up visit. Children who had caregiver reports of putting visibly dirty objects in their mouths at the majority of visits had significantly lower combined EASQ Z scores (-0.50; 95% CI, -0.79 to -0.22). Children in households with unimproved sanitation had significantly lower combined EASQ Z scores (-0.63; 95% CI, -1.11 to -0.16). CONCLUSIONS: Children found to frequently put soil and visibly dirty objects in their mouths, and those who resided in households using unimproved sanitation, had lower subsequent cognitive developmental outcomes. These findings demonstrate the importance of interventions targeting child mouthing behaviors and sanitation infrastructure to decrease exposure to fecal pathogens and improve child cognitive developmental outcomes.

Developmental Service Referrals and Utilization Among Young Children in Protective Custody.

Children in foster care are at high risk for developmental delay. In this retrospective cohort study of young children presenting to a foster care clinic, 77% were not receiving developmental services and 75% failed developmental screening. Of those potentially eligible, 60% were not referred for developmental services.

Limitations of Conventional Magnetic Resonance Imaging as a Predictor of Death or Disability Following Neonatal Hypoxic-Ischemic Encephalopathy in the Late Hypothermia Trial.

OBJECTIVE: To investigate if magnetic resonance imaging (MRI) is an accurate predictor for death or moderate-severe disability at 18-22 months of age among infants with neonatal encephalopathy in a trial of cooling initiated at 6-24 hours. STUDY DESIGN: Subgroup analysis of infants ≥36 weeks of gestation with moderate-severe neonatal encephalopathy randomized at 6-24 postnatal hours to hypothermia or usual care in a multicenter trial of late hypothermia. MRI scans were performed per each center's practice and interpreted by 2 central readers using the Eunice Kennedy Shriver National Institute of Child Health and Human Development injury score (6 levels, normal to hemispheric devastation). Neurodevelopmental outcomes were assessed at 18-22 months of age. RESULTS: Of 168 enrollees, 128 had an interpretable MRI and were seen in follow-up (n = 119) or died (n = 9). MRI findings were predominantly acute injury and did not differ by cooling treatment. At 18-22 months, death or severe disability occurred in 20.3%. No infant had moderate disability. Agreement between central readers was moderate (weighted kappa 0.56, 95% CI 0.45-0.67). The adjusted odds of death or severe disability increased 3.7-fold (95% CI 1.8-7.9) for each increment of injury score. The area under the curve for severe MRI patterns to predict death or severe disability was 0.77 and the positive and negative predictive values were 36% and 100%, respectively. CONCLUSIONS: MRI injury scores were associated with neurodevelopmental outcome at 18-22 months among infants in the Late Hypothermia Trial. However, the results suggest caution when using qualitative interpretations of MRI images to provide prognostic information to families following perinatal hypoxia-ischemia. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00614744.

Rates of Developmental Coordination Disorder in Children Born Very Preterm.

OBJECTIVE: To examine the stability of developmental coordination disorder (DCD) throughout childhood in children born very preterm and term. Further, in the very preterm group, to compare perinatal variables and neurobehavioral outcomes at 13 years of age for children with persisting DCD and those with typical motor development. STUDY DESIGN: Prospective study of 180 very preterm and 73 term-born children assessed at 5, 7, and/or 13 years of age using the Movement Assessment Battery for Children, with scores ≤16th percentile used to classify DCD. Children with cerebral palsy or an IQ of <80 were excluded. RESULTS: Children born very preterm had increased odds for DCD at 5 (OR, 5.53; 95% CI, 2.53-12.0; P < .001), 7 (OR, 3.63; 95% CI, 1.43-9.18; P = .06), and 13 years (OR, 4.34; 95% CI, 1.61-11.7; P = .004) compared with term-born children. The rates of DCD in very preterm children reduced from 47.9% at 5 years of age, to 28.5% at 7 years and 27.8% at 13 years of age (OR per year of age, 0.81; 95% CI, 0.75-0.87; P < .001), but less so for term-born children (15.3%, 10.0%, and 8.5% at 5, 7, and 13-years respectively [OR, 0.91; 95% CI, 0.75-1.09; P = .31]). Within the very preterm group at 13 years of age, there was evidence that children with persisting DCD performed poorer across several cognitive domains compared with children with typical motor development, with differences in the order of 0.5-1.0 SD. CONCLUSIONS: Although the rates of DCD decreased across middle childhood for both groups, the odds for DCD were consistently higher for very preterm children compared with term, with important implications for cognitive functioning in the very preterm group.

Neurodevelopmental and Growth Outcomes of Extremely Preterm Infants with Short Bowel Syndrome.

OBJECTIVE: To determine if preterm infants with surgical necrotizing enterocolitis (sNEC) or spontaneous intestinal perforation (SIP) with short bowel syndrome (SBS) have worse neurodevelopmental and growth outcomes than those with sNEC/SIP without SBS, and those with no necrotizing enterocolitis, SIP, or SBS. STUDY DESIGN: We undertook a retrospective analysis of prospectively collected data from infants born between 22 and 26 weeks of gestation in the National Institute of Child Health and Human Development Neonatal Research Network centers from January 1, 2008, to December 31, 2016. Survivors were assessed at 18-26 months corrected age by standardized neurologic examination and Bayley Scales of Infant and Toddler Development, Third Edition. The primary outcome was moderate-severe neurodevelopmental impairment. Growth was assessed using World Health Organization z-score standards. Adjusted relative risks were estimated using modified Poisson regression models. RESULTS: Mortality was 32%, 45%, and 21% in the 3 groups, respectively. Eighty-nine percent of survivors were seen at 18-26 months corrected age. Moderate-severe neurodevelopmental impairment was present in 77% of children with SBS compared with 62% with sNEC/SIP without SBS (adjusted relative risk, 1.22; 95% CI, 1.02-1.45; P = .03) and 44% with no necrotizing enterocolitis, SIP, or SBS (adjusted relative risk, 1.60; 95% CI, 1.37-1.88; P < .001). Children with SBS had lowcognitive, language, and motor scores than children with sNEC/SIP without SBS. At follow-up, length and head circumference z-scores remained more than 1 SD below the mean for children with SBS. CONCLUSIONS: Preterm infants with sNEC/SIP and SBS had increased risk of adverse neurodevelopmental outcomes at 18-26 months corrected age and impaired growth compared with peers with sNEC/SIP without SBS or without any of these conditions.

Association between Transport Risk Index of Physiologic Stability in Extremely Premature Infants and Mortality or Neurodevelopmental Impairment at 18 to 24 Months.

OBJECTIVES: To examine the association between mortality or neurodevelopmental impairment at 18-24 months of corrected age and the Transport Risk Index of Physiologic Stability (TRIPS) score on admission to the neonatal intensive care unit (NICU) in extremely premature infants. STUDY DESIGN: Retrospective cohort study of extremely premature infants (inborn and outborn) born at 22-28 weeks of gestational age and admitted to NICUs in the Canadian Neonatal Network between April 2009 and September 2011. TRIPS scores and clinical data were collected from the Canadian Neonatal Network database. Follow-up data at 18-24 months of corrected age were retrieved from the Canadian Neonatal Follow-Up Network database. Neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development, Edition III. The primary outcome was death or significant neurodevelopmental impairment at 18-24 months of corrected age. The secondary outcomes were individual components of the Bayley Scales of Infant and Toddler Development, Edition III assessment. RESULTS: A total of 1686 eligible infants were included. A TRIPS score of ≥20 on admission to the NICU was significantly associated with mortality (aOR 2.71 [95% CI, 2.02-3.62]) and mortality or significant neurodevelopmental impairment (aOR 1.91 [95% CI, 1.52-2.41]) at 18-24 months of corrected age across all gestational age groups of extremely premature infants. CONCLUSION: The TRIPS score on admission to the NICU can be used as an adjunctive, objective tool for counselling the parents of extremely premature infants early after their admission to the NICU.

Functional Outcomes among a Cohort of Children in Northeastern Brazil Meeting Criteria for Follow-Up of Congenital Zika Virus Infection.

Following the large outbreak of Zika virus in the Western Hemisphere, many infants have been born with congenital Zika virus infection. It is important to describe the functional outcomes seen with congenital infections to allow for their recognition and appropriate interventions. We evaluated 120 children conceived during the 2015-2016 Zika virus outbreak in Paraíba, Brazil, who were approximately 24 months old, to assess functional outcomes. All children met either anthropometric criteria or laboratory criteria suggestive of possible congenital Zika virus infection. We collected results of previous medical evaluations, interviewed parents, and performed physical examinations and functional assessments, for example, the Hammersmith Infant Neurological Examination (HINE). We compared patterns of neurologic outcomes and developmental delay at age 24 months by whether children met anthropometric or laboratory criteria, or both. Among children meeting both criteria, 60% (26/43) were multiply affected (had severe motor impairment, severe developmental delay, and suboptimal HINE scores), compared with 5% (3/57) meeting only laboratory criteria and none (0/20) meeting only anthropometric criteria. Of the remaining 91 children, 49% (45) had developmental delay, with more severe delay seen in children meeting both criteria. Although children meeting physical and laboratory criteria for potential congenital Zika virus infection were more severely affected, we did identify several children with notable adverse neurologic outcomes and developmental delay with no physical findings but potential laboratory evidence of Zika virus infection. Given this, all children who were potentially exposed in utero to Zika virus should be monitored in early childhood for deficits to allow for early intervention.

Poor maternal nutritional status before and during pregnancy is associated with suspected child developmental delay in 2-year old Brazilian children.

Inadequate pre-pregnancy BMI and gestational weight gain (GWG) have been associated with sub-optimal child development. We used data from the 2015 Pelotas (Brazil) Birth Cohort Study. Maternal anthropometry was extracted from antenatal/hospital records. BMI (kg/m2) and GWG (kg) adequacy were classified according to WHO and IOM, respectively. Development was evaluated using the INTER-NDA assessment tool for 3,776 children aged 24 months. Suspected developmental delay (SDD) was defined as <10th percentile. Associations between maternal exposures and child development were tested using linear and logistic regressions. Mediation for the association between BMI and child development through GWG was tested using G-formula. Sex differences were observed for all child development domains, except motor. Maternal pre-pregnancy underweight increased the odds of SDD in language (OR: 2.75; 95%CI: 1.30-5.80), motor (OR: 2.28; 95%CI: 1.20-4.33), and global (OR: 2.14; 95% CI: 1.05-4.33) domains for girls; among boys, excessive GWG was associated with SDD in language (OR: 1.59; 95%CI: 1.13-2.24) and cognition (OR: 1.59; 95%CI: 1.15-2.22). Total GWG suppressed the association of pre-pregnancy BMI with percentiles of global development in the entire sample. Maternal underweight and excessive GWG were negatively associated with development of girls and boys, respectively. The association of pre-pregnancy BMI with global child development was not mediated by GWG, irrespective of child's sex.