Neurodevelopmental Outcome Of Infants Research Articles

The impact of early tracheostomy on neurodevelopmental outcomes of infants with severe bronchopulmonary dysplasia exposed to postnatal corticosteroids.

To compare the cognitive, language and motor scores of infants with severe BPD exposed to postnatal corticosteroids (PCS) and had early (ET), late (LT) or no tracheostomy (NT). Retrospective study was designed to compare the developmental outcomes of 71 infants born between 2010 and 2017 with severe BPD exposed to PCS and had ET (≤122 days), LT (>122 days), or NT. Cognitive scores were lower in LT versus NT and ET (p = 0.050); motor scores were worse in LT versus NT and ET (p = 0.004). Dexamethasone use was higher in LT versus NT and ET (p = 0.040). Adjusted for PCS, odds for major cognitive impairment were 90% less in ET versus LT. Trend for improved language and motor outcomes was seen in ET versus LT. Infants with severe BPD exposed to PCS and had ET had significantly better cognitive, and trend toward improved language and motor outcomes.

Predicting fetal alcohol spectrum disorders in preschool-aged children from early life factors.

Early life factors, including parental sociodemographic characteristics, pregnancy exposures, and physical and neurodevelopmental features measured in infancy are associated with fetal alcohol spectrum disorders (FASD). The objective of this study was to evaluate the performance of a classifier model for diagnosing FASD in preschool-aged children from pregnancy and infancy-related characteristics. We analyzed a prospective pregnancy cohort in Western Ukraine enrolled between 2008 and 2014. Maternal and paternal sociodemographic factors, maternal prenatal alcohol use and smoking behaviors, reproductive characteristics, birth outcomes, infant alcohol-related dysmorphic and physical features, and infant neurodevelopmental outcomes were used to predict FASD. Data were split into separate training (80%: n = 245) and test (20%: n = 58; 11 FASD, 47 no FASD) datasets. Training data were balanced using data augmentation through a synthetic minority oversampling technique. Four classifier models (random forest, extreme gradient boosting [XGBoost], logistic regression [full model] and backward stepwise logistic regression) were evaluated for accuracy, sensitivity, and specificity in the hold-out sample. Of 306 children evaluated for FASD, 61 had a diagnosis. Random forest models had the highest sensitivity (0.54), with accuracy of 0.86 (95% CI: 0.74, 0.94) in hold-out data. Boosted gradient models performed similarly, however, sensitivity was less than 50%. The full logistic regression model performed poorly (sensitivity = 0.18 and accuracy = 0.65), while stepwise logistic regression performed similarly to the boosted gradient model but with lower specificity. In a hold-out sample, the best performing algorithm correctly classified six of 11 children with FASD, and 44 of 47 children without FASD. As early identification and treatment optimize outcomes of children with FASD, classifier models from early life characteristics show promise in predicting FASD. Models may be improved through the inclusion of physiologic markers of prenatal alcohol exposure and should be tested in different samples.

Can perioperative electroencephalogram and adverse hemodynamic events predict neurodevelopmental outcomes in infants with congenital heart disease?

ObjectiveThe study objective was to characterize preoperative and postoperative continuous electroencephalogram metrics and hemodynamic adverse events as predictors of neurodevelopment in congenital heart disease infants undergoing cardiac surgery. MethodsFrom 2010 to 2021, 320 infants underwent congenital heart disease surgery at our institution, of whom 217 had perioperative continuous electroencephalogram monitoring and were included in our study. Neurodevelopment was assessed in 76 patients by the Bayley Scales of Infant and Toddler Development, 3rd edition, consisting of cognitive, communication, and motor scaled scores. Patient and procedural factors, including hemodynamic adverse events, were included by means of the likelihood of covariate selection in our predictive model. Median (25th, 75th percentile) follow-up was 1.03 (0.09, 3.44) years with 3 (1, 6) Bayley Scales of Infant and Toddler Development, 3rd Edition evaluations per patient. ResultsMedian age at index surgery was 7 (4, 23) days, and 81 (37%) were female. Epileptiform discharges, encephalopathy, and abnormality (lethargy and coma) were more prevalent on postoperative continuous electroencephalograms, compared with preoperative continuous electroencephalograms (P < .005). In 76 patients with Bayley Scales of Infant and Toddler Development, 3rd edition evaluations, patients with diffuse abnormality (P = .009), waveform discontinuity (P = .007), and lack of continuity (P = .037) on preoperative continuous electroencephalogram had lower cognitive scores. Patients with synchrony (P < .005) on preoperative and waveform continuity (P = .009) on postoperative continuous electroencephalogram had higher fine motor scores. Patients with postoperative adverse events had lower cognitive (P < .005) and gross motor scores (P < .005). ConclusionsPhenotypic patterns of perioperative continuous electroencephalogram metrics are associated with late-term neurologic injury in infants with congenital heart disease requiring surgery. Continuous electroencephalogram metrics can be integrated with hemodynamic adverse events in a predictive algorithm for neurologic impairment.

Abstract 14028: Stroke Location, White Matter Disconnections, and Neurodevelopmental Outcomes in Infants With Congenital Heart Disease

Objectives: Infants with congenital heart disease (CHD) are at risk for stroke, although associations with neurodevelopmental outcomes have varied. In adults with stroke, location and altered structural connectivity (disconnections) have been linked to neurologic symptoms. We assessed whether stroke (1) location and (2) white matter disconnections are related to neurodevelopment in infants with CHD. Methods: Infants underwent pre- and post-operative brain MRI in prospective studies at 3 centres (UBC, UCSF, SickKids) and completed 18-month neurodevelopmental assessments using Bayley Scales with separate motor and cognitive composites. Adverse outcomes were defined as composite score &lt;85. Strokes were manually segmented. Voxel-wise lesion symptoms maps (VLSM) were used to assess relationships between lesion location and neurodevelopment. Disconnectomes were generated using stroke segmentations as seeds for tractography and diffusion MRI from healthy controls. Voxel-wise disconnectome-symptoms maps (VDSM) of associations between structural disconnections and neurodevelopment were developed. Results: 50 infants with strokes had neurodevelopmental outcomes data. Most strokes were small (&lt;1/3 of arterial territory; n= 33) and in the left MCA territory (Fig 1A). However, strokes in the right basal ganglia and adjacent central white matter were most strongly associated with adverse motor and cognitive outcomes (Fig 1B). White matter disconnections extended beyond areas of injury (Fig 1C); these were extensive even in small strokes. Disconnections of tracts passing through the right basal ganglia were most strongly associated with adverse motor and cognitive outcomes (Fig 1D). Conclusions: Strokes involving the basal ganglia, particularly in the right hemisphere, were associated with worse motor and cognitive outcomes in infants with CHD. These data draw increasing attention to the right hemisphere in early-life stroke and neurodevelopment.

Neurodevelopmental Outcomes in Infants Screened for Retinopathy of Prematurity

Preterm infants screened for retinopathy of prematurity (ROP) are at risk for heterogenous neurodevelopment outcomes that are difficult to predict. To characterize the potential association between socioeconomic and clinical risk factors and neurodevelopmental outcomes in a diverse, multicenter cohort of premature neonates screened for ROP. This was a retrospective cohort study using electronic medical records and US Census Bureau income data. This study was performed at academic (University of California, Los Angeles [UCLA] Mattel Children's Hospital and UCLA Santa Monica Hospital), community (Cedars-Sinai Medical Center), and LA county (Harbor-UCLA Medical Center) neonatal intensive care units. Participants included infants who met American Academy of Pediatrics guidelines for ROP screening and had records from at least 1 Bayley Scales of Infant and Toddler Development (BSID) neurodevelopment assessment between 0 and 36 months of adjusted age. Data analyses were conducted from January 1, 2011, to September 1, 2022. Demographic and clinical information, proxy household income, and health insurance type were collected as risk factors. Neurodevelopmental outcomes in the cognitive, language, and motor domains measured via BSID were the primary outcomes. A total of 706 infants (mean [SD] age, 28.6 [2.4] weeks; 375 male [53.1%]) met inclusion criteria. In a multivariable model, which included adjustments for birth weight, sex, insurance type, intraventricular hemorrhage (IVH), and age at assessment, public health insurance was associated with a 4-fold increased risk of moderate to severe neurodevelopmental impairment (NDI) in cognitive and language domains (cognitive, odds ratio [OR], 3.65; 95% CI, 2.28-5.86; P = 8.1 × 10-8; language, OR, 3.96; 95% CI, 2.61-6.02; P = 1.0 × 10-10) and a 3-fold increased risk in the motor domain (motor, OR, 2.60; 95% CI, 1.59-4.24; P = 1.4 × 10-4). In this adjusted model, clinical factors that were associated with an increased risk of moderate to severe NDI included lower birth weight, diagnosis of IVH, male sex, and older age at time of Bayley assessment. In unadjusted analyses, infants who received either laser or anti-VEGF treatment, compared with infants without treatment-requiring ROP, had lower BSID scores in multiple domains at 0 to 12 months, 12 to 24 months, and 24 to 36 months (DATA). In the multivariable model, treatment type was no longer associated with worse neurodevelopmental outcomes in any domain. Study results suggest an association between public insurance type and NDI in a diverse population screened for ROP, indicating the complexities of neurodevelopment. This study also supports the early neurodevelopmental safety of anti-VEGF treatment, as anti-VEGF therapy was not found to be independently associated with worse NDI in any domain.

Use of the Motor Optimality Score-Revised (MOS-R) to predict neurodevelopmental outcomes in infants with congenital anomalies

AimsTo describe the Motor Optimality Score-Revised (MOS-R) in infants with congenital anomalies requiring major surgery in the neonatal period; and to determine the predictive validity of the MOS-R, including specific movement and postural patterns, for neurodevelopmental outcomes at 3 years of age. MethodA retrospective cohort study of 201 infants born with congenital anomalies requiring surgery in the neonatal period (mean gestational age 38.2 weeks, SD 2.2). MOS-R completed using the pre-recorded General Movements Assessment (GMA) videos taken at 12 to 14 weeks post-term age (mean 12.45, SD 1.54). Developmental outcomes were assessed at 3 years of age (38.13 months, SD 1.76) using the Bayley Scales of Infant and Toddler Development (3rd ed). ResultThe mean score for the MOS-R was 21.85 (SD 5.16), with scores ranging from 6 to 28. Fifty-six infants (27.9 %) scored within the optimal range (25–28) with only 12 % demonstrating a normal movement character. A MOS-R total score of <21 was identified as the best performing cut-off to predict a mild, moderate or severe delay or CP diagnosis with sensitivity 0.39 (95 % CI: 0.25, 0.54) and specificity 0.86 (95 % CI: 0.80, 0.91), and an area under the ROC curve of 0.63. Outcome at 3 years was significantly associated with the MOS-R total (p < 0.01) and the subscales for observed movement patterns (p < 0.01) and age adequate repertoire (p = 0.02). ConclusionThe MOS-R may be an effective tool to use in addition to existing assessments to identify infants who are at risk of adverse developmental outcomes. Our study found that a MOS-R of <21 identified infants who would benefit from referral to early intervention.

OP08.01: Ultrasound findings showing chronic placental abruption associated with adverse neurodevelopmental outcomes in infants

OP08.01: Ultrasound findings showing chronic placental abruption associated with adverse neurodevelopmental outcomes in infants

Neurodevelopmental Outcome of Infants with Transient Hypothyroxinemia of Prematurity in a Newborn Intensive Care Unit

The aim of this study was to evaluate neurological development of infants with transient premature hypothyroxinemia (THOP). This prospective study included newborns who were born between 28-36 weeks of gestation (GW) and were admitted to the neonatal intensive care unit. Newborns exposed to maternal thyroid disease, or with severe intracranial problems, and congenital anomalies were excluded. Infants with THOP were the study group and those without THOP formed the control group. The study group was subdivided into those receiving levothyroxine replacement (5 μg/kg/day) and those who were untreated. Neonatal demographics, and morbidities, including respiratory distress syndrome, bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) were evaluated. The Ages and Stages Questionnaire (ASQ) and ASQ:Social-Emotional (ASQ:SE) developmental screening tests were administered to the entire study population at the corrected age of two years. Seventy infants were included in this study, 40 of whom had THOP. The mean GW was 34.4±3.8 weeks in the study group and 37.2±2.3 weeks in controls (p=0.69). Mean overall birth weight was 1640±428 g. Levothyroxine replacement was started in 12/40 infants (30%). The groups were similar in terms of demographic characteristics. Rates of BPD and ROP were higher in the treated group (p=0.01). ASQ and ASQ:SE results did not differ between groups (p=0.75), nor did these scores differ between infants with THOP who did or did not receive levothyroxine (p=0.14). Although levothyroxine replacement therapy was associated with increased rates of BPD and ROP, this treatment did not appear to improve long-term neurological outcomes in this small group of infants with THOP. Prospective controlled studies with much larger sample sizes are needed to clarify the role of levothyroxine replacement in THOP.

Apgar Score and Neurodevelopmental Outcomes at Age 5 Years in Infants Born Extremely Preterm

The Apgar score is used worldwide as an assessment tool to estimate the vitality of newborns in their first minutes of life. Its applicability to estimate neurodevelopmental outcomes in infants born extremely preterm (EPT; <28 weeks' gestation) is not well established. To investigate the association between the Apgar score and neurodevelopmental outcomes in infants born EPT. This cohort study was conducted using data from the Effective Perinatal Intensive Care in Europe-Screening to Improve Health in Very Preterm Infants in Europe (EPICE-SHIPS) study, a population-based cohort in 19 regions of 11 European countries in 2011 to 2012. Clinical assessments of cognition and motor function at age 5 years were performed in infants born EPT and analyzed in January to July 2023. Apgar score at 5 minutes of life categorized into 4 groups (0-3, 4-6, 7-8, and 9-10 points). Cognitive and motor outcomes were assessed using the Wechsler Preschool and Primary Scale of Intelligence test of IQ derived from locally normed versions by country and the Movement Assessment Battery for Children-Second Edition. Parents additionally provided information on communication and problem-solving skills using the Ages and Stages Questionnaire, third edition (ASQ-3). All outcomes were measured as continuous variables. From the total cohort of 4395 infants born EPT, 2522 infants were live born, 1654 infants survived to age 5 years, and 996 infants (478 females [48.0%]) followed up had at least 1 of 3 outcome measures. After adjusting for sociodemographic variables, perinatal factors, and severe neonatal morbidities, there was no association of Apgar score with IQ, even for scores of 3 or less (β = -3.3; 95% CI, -10.5 to 3.8) compared with the score 9 to 10 category. Similarly, no association was found for ASQ-3 (β = -2.1; 95% CI, -24.6 to 20.4). Congruent results for Apgar scores of 3 or less were obtained for motor function scores for all children (β = -4.0; 95% CI, -20.1 to 12.1) and excluding children with a diagnosis of cerebral palsy (β = 0.8, 95% CI -11.7 to 13.3). This study found that low Apgar scores were not associated with longer-term outcomes in infants born EPT. This finding may be associated with high interobserver variability in Apgar scoring, reduced vitality signs and poorer responses to resuscitation after birth among infants born EPT, and the association of more deleterious exposures in the neonatal intensive care unit or of socioeconomic factors with greater changes in outcomes during the first 5 years of life.

Longitudinal cohort study investigating neurodevelopmental and socioemotional outcomes in school-entry aged children after open heart surgery in Australia and New Zealand: the NITRIC follow-up study protocol

IntroductionDespite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile...

Neurodevelopmental Outcomes of Infants after Neonatal Surgical Intervention for Tetralogy of Fallot or Pulmonary Atresia

To determine the 2-year neurodevelopmental outcomes for survivors of neonatal cardiac surgery for the most common right ventricular outflow tract obstructive lesions: tetralogy of Fallot and pulmonary atresia with a ventricular septal defect. A single-center consecutive cohort of 77 children underwent neonatal surgery for tetralogy of Fallot or pulmonary atresia with a ventricular septal defect at ≤6weeks of age between 2006 and 2017. The patients underwent a multidisciplinary neurodevelopmental assessment at 18-24months of age. Survivor outcomes were compared by univariable and multivariable analyses. The 2-year mortality was 7.8% (6/77) with a postoperative in-hospital mortality of 3.9% (3/77). Freedom from reintervention by cardiac catheterization or surgical intervention at 2years was 36%. Functional and neurodevelopmental assessment for 69 of 71 survivors was completed at a mean age of 22.6 ± 4.0 months using the Bayley Scales of Infant and Toddler Development III. The mean neurodevelopmental outcome scores were 83.4 ± 16.5 for cognitive skills, 82.2 ± 18.7 for language skills, and 81.4 ± 18.1 for motor skills. Cognitive, language, and motor delay, defined as a score of <70, was identified in 25%, 25%, and 23% of patients, respectively. Multivariable analyses for factors associated with worse neurodevelopmental outcomes identified chromosomal anomalies (P<.001) and postoperative complications (P<.03). Cyanotic tetralogy of Fallot and pulmonary atresia with ventricular septal defect requiring neonatal repair showed similar 2-year neurodevelopmental outcomes below normative values and a high prevalence of cognitive, ,language and motor delays.

Survival and early neurodevelopmental outcomes in infants born at extreme prematurity in a tertiary neonatal centre in Hong Kong

We report the first study conducted in Hong Kong looking at survival and neurodevelopmental outcomes of extremely preterm infants (EPI), which includes information on primary school entry. Survival rate to discharge in our single centre cohort was 65.9%. Surviving EPIs were at risk of developmental delay (48.4%), as well as psychiatric and behavioural disorders, necessitating referral to special education services. Nevertheless, the vast majority (90.2%) of EPIs in our cohort are able to attend mainstream primary schools.

Ultrasonographic Estimation of Ventricular Volume in Infants Born Preterm with Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled Early Versus Late Ventricular Intervention Study (ELVIS) Trial

To study the potential role of ventricular volume (VV) estimation in the management of posthemorrhagic ventricular dilatation related to the need for ventriculoperitoneal (VP)-shunt insertion and 2-year neurodevelopmental outcome in infants born preterm. We included 59 patients from the Early vs Late Ventricular Intervention Study from 4 participating centers. VV was manually segmented in 209 3-dimensional ultrasound scans and estimated from 2-dimensional ultrasound linear measurements in a total of 1226 ultrasounds. We studied the association of both linear measurements and VV to the need for VP shunt and 2-year neurodevelopmental outcome in the overall cohort and in the 29 infants who needed insertion of a reservoir. We used general estimating equations to account for repeated measures per individual. Maximum pre-reservoir VV (β coefficient=0.185, P=.0001) and gestational age at birth (β =-0.338; P=.0001) were related to the need for VP shunt. The estimated optimal single VV measurement cut point of 17cm3 correctly classified 79.31% with an area under the curve of 0.76 (CI 95% 0.74-0.79). Maximum VV (β=0.027; P=.012) together with VP shunt insertion (β =3.773; P=.007) and gestational age (β =-0.273; P=.0001) were related to cognitive outcome at 2years. Maximum ventricular index and anterior horn width before reservoir insertion were independently associated with the need of VP shunt and the proposed threshold groups in the Early vs Late Ventricular Intervention Study trial were associated with long-term outcome. Pre-reservoir VV measurements were associated with the need for VP-shunt insertion and 2-year cognitive outcome among infants born preterm with posthemorrhagic ventricular dilatation. ISRCTN43171322.

Does Growth Velocity Affect Associations between Birth Weight and Neurodevelopment for Infants Born Very Preterm?

To determine how neonatal growth velocity affects the association between birth weight and neurodevelopmental outcomes in infants born preterm. This study is a secondary analysis of the Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants (MOBYDIck) randomized multicenter trial conducted in breastfed infants born at <29weeks of gestation, whose mothers were supplemented with docosahexaenoic acid or placebo during the neonatal period. Neurodevelopmental outcomes were assessed at 18-22months of corrected age using the Bayley-III cognitive and language composite scores. The role of neonatal growth velocity was assessed with causal mediation and linear regression models. Subgroup analyses were stratified by birth weight z-score categories (<25th, ≥25th-≤75th, and >75th percentiles). Neurodevelopmental outcomes were available for 379 children (mean gestational age, 26.7± 1.5 weeks). Growth velocity partially mediated the relationships between birth weight and cognitive (β=-1.1; 95% CI, -2.2 to -0.02; P=.05) and language scores (β=-2.1; 95% CI, -3.3 to -0.8; P=.002). An increase by 1g/kg/day in growth velocity was associated with an increase by 1.1 point in the cognitive score (95% CI, -0.03 to 2.1; P=.06) and 1.9 point in the language score (95% CI, 0.7 to 3.1; P=.001), after adjustment for birth weight z-score. For children with birth weight<25th percentile, a 1g/kg/day increase in growth velocity was associated with an increase by 3.3 points in the cognitive score (95% CI, 0.5 to 6.0; P=.02) and 4.1 points in the language score (95% CI, 1.3 to 7.0; P=.004). Postnatal growth velocity mediated the relationship between birth weight and neurodevelopmental performance, with larger effects for children with lower birth weight. Clinicaltrials.gov identifier: NCT02371460.

A 12-month follow-up of infant neurodevelopmental outcomes of prenatal opioid exposure and polysubstance use

BackgroundPrenatal opioid exposure has been associated with developmental deficits during infancy, but the literature is limited by simple group comparisons and lack of appropriate controls. Previously published research with the current sample documented unique associations between prenatal opioid exposure and developmental outcomes at three and six months, but less is known about associations later in infancy. MethodThe current study examined pre- and postnatal opioid and polysubstance exposure as predictors of parent-reported developmental status at 12 months of age. Participants were 85 mother-child dyads, oversampled for mothers taking opioid treatment medications during pregnancy. Maternal opioid and polysubstance use were reported using the Timeline Follow-Back Interview during the third trimester of pregnancy or up to one month postpartum and updated through the child's first year of life. Seventy-eight dyads participated in a 12-month assessment, including 68 with parent-reported developmental status on Ages and Stages Questionnaire. ResultsAt 12 months, average developmental scores fell within normal ranges and prenatal opioid exposure was not significantly related to any developmental outcomes. However, more prenatal alcohol exposure was significantly related to worse problem-solving scores, and this relationship remained after controlling for adjusted age and other substance exposure. ConclusionAlthough findings await replication with larger samples and more comprehensive measures, results suggest that unique developmental risks of prenatal opioid exposure may not persist through the first year of life. Effects of prenatal exposure to co-occurring teratogens, such as alcohol, may become apparent as children exposed to opioids develop.

Efficacy of very early interventions on neurodevelopmental outcomes for infants and toddlers at increased likelihood of or diagnosed with autism: A systematic review and meta-analysis.

The aim of this systematic review was to determine the efficacy of very early interventions for infants and toddlers at increased likelihood of or diagnosed with autism for autism symptomatology, developmental outcomes and/or neurocognitive markers. Eight databases were searched (14 April 2022) with inclusion criteria: (i) RCTs with care as usual (CAU) comparison group, (ii) participants at increased likelihood of or diagnosed with autism and aged <24 months corrected age (CA), (iii) parent-mediated and/or clinician directed interventions, and (iv) outcome measures were autism symptomatology, cognition, language, adaptive skills, or neurocognitive assessments (EEG and eye tracking). Quality was assessed using Risk of Bias 2 and GRADE. Nineteen publications from 12 studies reported on 715 infants and toddlers. There was low to moderate certainty evidence that clinician-assessed outcomes did not show significant treatment effects for: autism symptomatology (ADOS CSS: MD -0.08, 95% CI -0.61, 0.44, p = 0.75), cognitive outcome (Mullen Scales of Early Learning-Early Learning Composite (MSEL-ELC): SMD 0.05, 95% CI -0.19, 0.29, p = 0.67), receptive language (MSEL-Receptive Language: SMD 0.04, 95% CI -0.21, 0.3, p = 0.74) or expressive language (MSEL-Expressive Language: SMD 0.06, 95% CI -0.1, 0.23, p = 0.45). Neurocognitive outcomes (EEG and eye tracking) were heterogeneous, with inconsistent findings. There is low to moderate certainty evidence that very early interventions have limited impact on neurodevelopmental outcomes by age 3 years.

Assessment of Neurodevelopment in Infants With and Without Exposure to Asymptomatic or Mild Maternal SARS-CoV-2 Infection During Pregnancy

Associations between prenatal SARS-CoV-2 exposure and neurodevelopmental outcomes have substantial public health relevance. A previous study found no association between prenatal SARS-CoV-2 infection and parent-reported infant neurodevelopmental outcomes, but standardized observational assessments are needed to confirm this finding. To assess whether mild or asymptomatic maternal SARS-CoV-2 infection vs no infection during pregnancy is associated with infant neurodevelopmental differences at ages 5 to 11 months. This cohort study included infants of mothers from a single-site prospective cross-sectional study (COVID-19 Mother Baby Outcomes [COMBO] Initiative) of mother-infant dyads and a multisite prospective cohort study (Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 in Pregnancy and Infancy [ESPI]) of pregnant individuals. A subset of ESPI participants was subsequently enrolled in the ESPI COMBO substudy. Participants in the ongoing COMBO study were enrolled beginning on May 26, 2020; participants in the ESPI study were enrolled from May 7 to November 3, 2021; and participants in the ESPI COMBO substudy were enrolled from August 2020 to March 2021. For the current analysis, infant neurodevelopment was assessed between March 2021 and June 2022. A total of 407 infants born to 403 mothers were enrolled (204 from Columbia University Irving Medical Center in New York, New York; 167 from the University of Utah in Salt Lake City; and 36 from the University of Alabama in Birmingham). Mothers of unexposed infants were approached for participation based on similar infant gestational age at birth, date of birth, sex, and mode of delivery to exposed infants. Maternal symptomatic or asymptomatic SARS-CoV-2 infection. Infant neurodevelopment was assessed using the Developmental Assessment of Young Children, second edition (DAYC-2), adapted for telehealth assessment. The primary outcome was age-adjusted standard scores on 5 DAYC-2 subdomains: cognitive, gross motor, fine motor, expressive language, and receptive language. Among 403 mothers, the mean (SD) maternal age at delivery was 32.1 (5.4) years; most mothers were of White race (240 [59.6%]) and non-Hispanic ethnicity (253 [62.8%]). Among 407 infants, 367 (90.2%) were born full term and 212 (52.1%) were male. Overall, 258 infants (63.4%) had no documented prenatal exposure to SARS-CoV-2 infection, 112 (27.5%) had confirmed prenatal exposure, and 37 (9.1%) had exposure before pregnancy or at an indeterminate time. In adjusted models, maternal SARS-CoV-2 infection during pregnancy was not associated with differences in cognitive (β = 0.31; 95% CI, -2.97 to 3.58), gross motor (β = 0.82; 95% CI, -1.34 to 2.99), fine motor (β = 0.36; 95% CI, -0.74 to 1.47), expressive language (β = -1.00; 95% CI, -4.02 to 2.02), or receptive language (β = 0.45; 95% CI, -2.15 to 3.04) DAYC-2 subdomain scores. Trimester of exposure and maternal symptom status were not associated with DAYC-2 subdomain scores. In this study, results of a novel telehealth-adapted observational neurodevelopmental assessment extended a previous finding of no association between prenatal exposure to maternal SARS-CoV-2 infection and infant neurodevelopment. Given the widespread and continued high prevalence of COVID-19, these data offer information that may be helpful for pregnant individuals who experience asymptomatic or mild SARS-CoV-2 infections.

A Scoping Review of Cerebral Doppler Arterial Waveforms in Infants.

Cerebral Doppler ultrasound has been an important tool in pediatric diagnostics and prognostics for decades. Although the Doppler spectrum can provide detailed information on cerebral perfusion, the measured spectrum is often reduced to simple numerical parameters. To help pediatric clinicians recognize the visual characteristics of disease-associated Doppler spectra and identify possible areas for future research, a scoping review of primary studies on cerebral Doppler arterial waveforms in infants was performed. A systematic search in three online bibliographic databases yielded 4898 unique records. Among these, 179 studies included cerebral Doppler spectra for at least five infants below 1 y of age. The studies describe variations in the cerebral waveforms related to physiological changes (43%), pathology (62%) and medical interventions (40%). Characteristics were typically reported as resistance index (64%), peak systolic velocity (43%) or end-diastolic velocity (39%). Most studies focused on the anterior (59%) and middle (42%) cerebral arteries. Our review highlights the need for a more standardized terminology to describe cerebral velocity waveforms and for precise definitions of Doppler parameters. We provide a list of reporting variables that may facilitate unambiguous reports. Future studies may gain from combining multiple Doppler parameters to use more of the information encoded in the Doppler spectrum, investigating the full spectrum itself and using the possibilities for long-term monitoring with Doppler ultrasound.

Impact of cardiac surgical timing on the neurodevelopmental outcomes of newborns with Complex congenital heart disease (CHD).

More than half of infants with complex congenital heart disease (CHD) will have a neurodevelopmental disorder of multifactorial causes. The preoperative period represents a time-window during which neonates with complex CHD are in a state of hypoxia and hemodynamic instability, which fosters the emergence of brain injuries and, thus, affects early brain networks and neurodevelopmental outcomes. Currently, there is no consensus regarding the optimal age for cardiac surgery in terms of neurodevelopmental outcomes, and its definition is a real challenge. Our aim is to determine the relationship between cardiac surgical timing and long-term neurodevelopmental outcomes for various types of complex CHD. We hypothesize that earlier surgical timing could represent a neuroprotective strategy that reduces perioperative white matter injuries (WMIs) and postoperative morbidity, leading to improved neurodevelopmental outcomes in infants with complex CHD. Firstly, our prospective study will allow us to determine the correlation between age at the time of surgery (days of life) and neurodevelopmental outcomes at 24 months. We will then analyze the correlation between age at surgery and (i) the incidence of WMIs (through pre- and postoperative MRIs), (ii) postoperative morbidity, and (iii) the duration of the hospital stay. This research protocol was registered in the Clinical Trial Registry (National Clinical Trial: NCT04733378). This project aims to help launch the first Neurocardiac Investigation Clinic in Marseille - AP-HM - to propose an overall personalized monitoring and treatment program for patients operated on for complex CHD.

How well does neonatal neuroimaging correlate with neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy?

BackgroundIn newborns with hypoxic-ischemic encephalopathy (HIE), the correlation between neonatal neuroimaging and the degree of neurodevelopmental impairment (NDI) is unclear.MethodsInfants with HIE enrolled in a randomized controlled trial underwent neonatal MRI/MR spectroscopy (MRS) using a harmonized protocol at 4–6 days of age. The severity of brain injury was measured with a validated scoring system. Using proportional odds regression, we calculated adjusted odds ratios (aOR) for the associations between MRI/MRS measures of injury and primary ordinal outcome (i.e., normal, mild NDI, moderate NDI, severe NDI, or death) at age 2 years.ResultsOf 451 infants with MRI/MRS at a median age of 5 days (IQR 4.5–5.8), outcomes were normal (51%); mild (12%), moderate (14%), severe NDI (13%); or death (9%). MRI injury score (aOR 1.06, 95% CI 1.05, 1.07), severe brain injury (aOR 39.6, 95% CI 16.4, 95.6), and MRS lactate/n-acetylaspartate (NAA) ratio (aOR 1.6, 95% CI 1.4,1.8) were associated with worse primary outcomes. Infants with mild/moderate MRI brain injury had similar BSID-III cognitive, language, and motor scores as infants with no injury.ConclusionIn the absence of severe injury, brain MRI/MRS does not accurately discriminate the degree of NDI. Given diagnostic uncertainty, families need to be counseled regarding a range of possible neurodevelopmental outcomes.ImpactHalf of all infants with hypoxic-ischemic encephalopathy (HIE) enrolled in a large clinical trial either died or had neurodevelopmental impairment at age 2 years despite receiving therapeutic hypothermia.Severe brain injury and a global pattern of brain injury on MRI were both strongly associated with death or neurodevelopmental impairment.Infants with mild or moderate brain injury had similar mean BSID-III cognitive, language, and motor scores as infants with no brain injury on MRI.Given the prognostic uncertainty of brain MRI among infants with less severe degrees of brain injury, families should be counseled regarding a range of possible neurodevelopmental outcomes.