Giving parents support: a randomized trial of peer support for parents after NICU discharge.

BACKGROUND: Peer support during inpatient hospitalization has been recommended for NICU parents and can improve maternal mental health. Less is known about the impact of peer support after NICU discharge on parental mental health and infant healthcare utilization. METHODS: Three hundred families of infants approaching discharge from a Level IV NICU were randomized to receive a care notebook (control) or care notebook plus peer support for 12 months (intervention). Participants reported on measures of stress, depression, anxiety, self-efficacy, and infant healthcare utilization. Analysis compared outcomes between control and treatment groups. RESULTS: Parental depression, anxiety, stress, and self-efficacy improved significantly for all participants, yet there were no differences between control and intervention groups. Infant ED visits, hospitalizations, immunization status, and developmental status at 12 months did not differ between groups. CONCLUSIONS: Peer support after NICU discharge did not improve self-reported parental mental health measures or infant healthcare utilization. CLINICAL TRIAL REGISTRATION: NCT02643472.

Serial plasma biomarkers of brain injury in infants with neonatal encephalopathy treated with therapeutic hypothermia.

BACKGROUND: Neonatal encephalopathy (NE) is a major cause of long-term neurodevelopmental disability in neonates. We evaluated the ability of serially measured biomarkers of brain injury to predict adverse neurological outcomes in this population. METHODS: Circulating brain injury biomarkers including BDNF, IL-6, IL-8, IL-10, VEGF, Tau, GFAP, and NRGN were measured at 0, 12, 24, 48, 72, and 96 h of cooling from 103 infants with NE undergoing TH. The biomarkers' individual and combinative ability to predict death or severe brain injury and adverse neurodevelopmental outcomes beyond 1 year of age was assessed. RESULTS: Early measurements of inflammatory cytokines IL-6, 8, and 10 within 24 HOL (AUC = 0.826) and late measurements of Tau from 72 to 96 HOL (AUC = 0.883, OR 4.37) were accurate in predicting severe brain injury seen on MRI. Late measurements of Tau were predictive of adverse neurodevelopmental outcomes (AUC = 0.81, OR 2.59). CONCLUSIONS: Tau was consistently a predictive marker for brain injury in neonates with NE. However, in the first 24 HOL, IL-6, 8, and 10 in combination were most predictive of death or severe brain injury. The results of this study support the use of a serial biomarker panel to assess brain injury over the time course of disease in NE. IMPACT: While recent studies have evaluated candidate brain injury biomarkers, no biomarker is in current clinical use. This study supports the use of a serial biomarker panel for ongoing assessment of brain injury neonates with NE. In combination, IL6, IL8, and IL10 in the first 24 h of cooling were more predictive of brain injury by MRI than each cytokine alone. Individually, Tau was overall most consistently predictive of adverse neurological outcomes, particularly when measured at or after rewarming.

Early Versus Late Brain Magnetic Resonance Imaging after Neonatal Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia.

OBJECTIVE: To evaluate the agreement in brain injury findings between early and late magnetic resonance imaging (MRI) in newborn infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia and to compare the ability of early vs late MRI to predict early neurodevelopmental outcomes. STUDY DESIGN: This was a prospective longitudinal study of 49 patients with hypoxic-ischemic encephalopathy who underwent therapeutic hypothermia and had MRI performed at both <7 and ≥7 days of age. MRIs were reviewed by an experienced neuroradiologist and assigned brain injury severity scores according to established systems. Scores for early and late MRIs were assessed for agreement using the kappa statistic. The ability of early and late MRI scores to predict death or developmental delay at 15-30 months of age was assessed by logistic regression analyses. RESULTS: Agreement between the early and late MRI was substantial to near perfect (k > 0.75, P < .001) across MRI scoring systems. In cases of discrepant scoring, early MRI was more likely to identify severe injury when compared with late MRI. Early MRI scores were more consistently predictive of adverse outcomes compared with late MRI. CONCLUSIONS: The results of this study suggest that a single MRI performed in the first week after birth is adequate to assess brain injury and offer prognostic information in this high-risk population.

Exploratory Assessment of the Relationship Between Hemoglobin Volume Phase Index, Magnetic Resonance Imaging, and Functional Outcome in Neonates with Hypoxic-Ischemic Encephalopathy.

BACKGROUND/OBJECTIVE: Near-infrared spectroscopy (NIRS)-based measures of cerebral autoregulation (CAR) can potentially identify neonates with hypoxic-ischemic encephalopathy (HIE) who are at greatest risk of irreversible brain injury. However, modest predictive abilities have precluded previously described metrics from entering clinical care. We previously validated a novel autoregulation metric in a piglet model of induced hypotension called the hemoglobin volume phase index (HVP). The objective of this study was to evaluate the clinical ability of the HVP to predict adverse outcomes neonates with HIE. METHODS: This is a prospective study of neonates with HIE who underwent therapeutic hypothermia (TH) at a level 4 neonatal intensive care unit (NICU). Continuous cerebral NIRS and mean arterial blood pressure (MAP) from indwelling arterial catheters were measured during TH and through rewarming. Multivariate autoregressive process was used to calculate the coherence between MAP and the sum total of the oxy- and deoxygenated Hb densities (HbT), a surrogate measure of cerebral blood volume (CBV). The HVP was calculated as the cosine-transformed phase shift at the frequency of maximal MAP-HbT coherence. Brain injury was assessed by neonatal magnetic resonance imaging (MRI), and developmental outcomes were assessed by the Bayley Scales of Infant Development (BSID-III) at 15-30 months. The ability of the HVP to predict (a) death or severe brain injury by MRI and (b) death or significant developmental delay was assessed using logistic regression analyses. RESULTS: In total, 50 neonates with moderate or severe HIE were monitored. Median HVP was higher, representing more dysfunctional autoregulation, in infants who had adverse outcomes. After adjusting for sex and encephalopathy grade at presentation, HVP at 21-24 and 24-27 h of life predicted death or brain injury by MRI (21-24 h: OR 8.8, p = 0.037; 24-27 h: OR 31, p = 0.011) and death or developmental delay at 15-30 months (21-24 h: OR 11.8, p = 0.05; 24-27 h: OR 15, p = 0.035). CONCLUSIONS: Based on this pilot study of neonates with HIE, HVP merits further study as an indicator of death or severe brain injury on neonatal MRI and neurodevelopmental delay in early childhood. Larger studies are warranted for further clinical validation of the HVP to evaluate cerebral autoregulation following HIE.

Parental Depression Symptoms at Neonatal Intensive Care Unit Discharge and Associated Risk Factors.

OBJECTIVE: To investigate the prevalence and risk factors associated with parental depressive symptoms at neonatal intensive care unit (NICU) discharge and determine the relationships among depressive symptoms, stress, and social support. STUDY DESIGN: Parents participating in the Giving Parents Support trial (n = 300) were surveyed before NICU discharge. Depressive symptoms, stress, and social support were assessed using the Center for Epidemiological Studies Depression Scale (CESD-10), Parental Stressor Scale: Neonatal Intensive Care Unit (PSS:NICU), Perceived Stress Scale (PSS-10), and Multidimensional Scale of Perceived Social Support (MSPSS). Regression analyses examined relationships among depressive symptoms, stress, social support, and parent/infant factors. RESULTS: At NICU discharge, 45% of parents reported depressive symptoms and 43% reported elevated perceived stress. Increased odds of elevated depressive symptoms were associated with older gestational age (P = .02), female infant (P = .02), and longer length of stay (P = .045). Odds of depression were 7.87 (95% CI, 2.15-28.75) for parents of infants with gestational age ≥37 weeks compared with gestational age <28 weeks. Parental NICU stress was higher in younger parents (P < .01). Depressive symptoms were positively associated with parental stress. Each 1-point increase in PSS:NICU score was associated with a 2.1-point (95% CI, 1.6-2.9; P < .001) increase in CESD-10 score. Social support was inversely associated with depressive symptoms. CONCLUSION: The prevalence of depressive symptoms in parents at NICU discharge was high, even among parents of term infants. Older gestational age, greater parental stress, and lower levels of social support were strong correlates of depressive symptoms. Strategies to support parents, including depression screening, stress reduction strategies, and mental health referrals, are needed.

Plasma and Cerebrospinal Fluid Candidate Biomarkers of Neonatal Encephalopathy Severity and Neurodevelopmental Outcomes.

OBJECTIVES: To identify candidate biomarkers in both plasma and cerebrospinal fluid (CSF) that are associated with neonatal encephalopathy severity measured by encephalopathy grade, seizures, brain injury by magnetic resonance imaging (MRI), and neurodevelopmental outcomes at 15-30 months. STUDY DESIGN: A retrospective cohort study of plasma (N = 155, day of life 0-1) and CSF (n = 30, day of life 0-7) from neonates with neonatal encephalopathy and healthy neonates born at term (N = 30, ≥36 weeks of gestation) was conducted. We measured central nervous system necrosis (glial fibrillary acidic protein [GFAP], neurogranin [NRGN], tau), inflammatory (interleukin [IL]-6, IL-8, IL-10), and trophic (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor) proteins. Clinical outcomes were Sarnat scores of encephalopathy, seizures, MRI scores, and Bayley Scales of Infant and Toddler Development III at 15-30 months. RESULTS: Plasma NRGN, tau, IL-6, IL-8, and IL-10 were greater, whereas BDNF and vascular endothelial growth factor were lower in patients with neonatal encephalopathy vs controls. In plasma, tau, GFAP, and NRGN were directly and BDNF inversely associated with encephalopathy grade. IL-6 was inversely related to seizures. Tau was directly related to MRI abnormalities. Tau was inversely associated with Bayley Scales of Infant and Toddler Development III cognitive and motor outcomes. In CSF, NRGN was inversely associated with cognitive, motor, and language measures. GFAP, IL-6, and IL-10 were inversely related to cognitive and motor outcomes. IL-8 was inversely related to motor outcomes. CSF candidate biomarkers showed no significant relationships with encephalopathy grade, seizures, or MRI abnormalities. CONCLUSIONS: Plasma candidate biomarkers predicted encephalopathy severity, seizures, MRI abnormalities, and neurodevelopmental outcomes at 15-30 months.

The Giving Parents Support Study: A randomized clinical trial of a parent navigator intervention to improve outcomes after neonatal intensive care unit discharge.

Parents of infants hospitalized in a neonatal intensive care unit (NICU) experience increased anxiety and stress, which may persist after discharge. The rationale and design of a randomized clinical trial assessing the impact of a 1-year, post-discharge, peer support intervention (parent navigation) on parental mental health and infant health care utilization is described. Qualitative methods guided the adaptation of an existing parent support program to target emotional and resource-related needs of NICU families. Approximately 300 parent-infant dyads were enrolled at discharge and randomized to either receive a care notebook (control group) or a parent navigator and a care notebook (intervention group). We aim to determine if the parent navigator intervention: 1) increases self-efficacy and decreases stress in parents, 2) decreases overall levels of anxiety and depression in parents, 3) decreases infant hospitalizations and emergency department visits, and 4) increases adherence to infant vaccination recommendations during 1 year of follow-up. Standardized, self-reported psychological scales to assess parent depression, anxiety, self-efficacy and social support were administered at baseline (NICU discharge) and at 1-week, 1-, 3-, 6- and 12-month intervals. Infant immunization status and health care utilization during the study period were also assessed. This paper reviews challenges and successes during implementation. If this intervention improves outcomes, NICUs may choose to provide similar parent navigation services for infants and families transitioning from the NICU to home. This study was registered with ClinicalTrials.gov (NCT02643472) on December 31, 2015.

Evolution of Amplitude-Integrated Electroencephalogram as a Predictor of Outcome in Term Encephalopathic Neonates Receiving Therapeutic Hypothermia.

OBJECTIVES: This study aims to evaluate the ability of (1) a novel amplitude-integrated electroencephalogram (aEEG) background evolution classification system; and (2) specific hour of life (HOL) cut points when observation of aEEG normalization and development of cycling can predict adverse neurological outcomes in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Continuous aEEG data of term neonates with HIE were reviewed for background pattern and aEEG cycling from start of monitoring through rewarming. Infants were classified by overall background evolution pattern. Adverse outcomes were defined as death or severe magnetic resonance imaging injury, as well as developmental outcomes in a subset of patients. aEEG characteristics were compared between outcome groups by multivariate regression models, likelihood ratios (LR), and receiver operating characteristic (ROC) curve analyses. RESULTS: Overall, 80 infants receiving therapeutic hypothermia met the inclusion criteria. Background evolution pattern seemed to distinguish outcome groups more reliably than background pattern at discrete intervals in time (LR: 43.9, p value < 0.001). Infants who did not reach discontinuous background by 15.5 HOL, cycling by 45.5 HOL, and normalization by 78 HOL were most likely to have adverse outcomes. CONCLUSION: Evolution of aEEG in term neonates with HIE may be more useful for predicting outcome than evaluating aEEG at discrete intervals in time.

Conducting an investigator-initiated randomized double-blinded intervention trial in acute decompensation of inborn errors of metabolism: Lessons from the N-Carbamylglutamate Consortium.

Organic acidemias and urea cycle disorders are ultra-rare inborn errors of metabolism characterized by episodic acute decompensation, often associated with hyperammonemia, resulting in brain edema and encephalopathy. Retrospective reports and translational studies suggest that N-carbamylglutamate (NCG) may be effective in reducing ammonia levels during acute decompensation in two organic acidemias, propionic and methylmalonic acidemia (PA and MMA), and in two urea cycle disorders, carbamylphosphate synthetase 1 and ornithine transcarbamylase deficiency (CPSD and OTCD). We established the 9-site N-carbamylglutamate Consortium (NCGC) in order to conduct two randomized double-blind, placebo-controlled trials of NCG in acute hyperammonemia of PA, MMA, CPSD and OTCD. Conducting clinical trials is challenging in any disease, but poses unique barriers and risks in the ultra-rare disorders. As the number of clinical trials in orphan diseases increases, evaluating the successes and opportunities for improvement in such trials is essential. We summarize herein the design, methods, experiences, challenges and lessons from the NCGC-conducted trials.

Perioperative Near-Infrared Spectroscopy Monitoring in Neonates With Congenital Heart Disease: Relationship of Cerebral Tissue Oxygenation Index Variability With Neurodevelopmental Outcome.

OBJECTIVES: To evaluate the value of perioperative cerebral near-infrared spectroscopy monitoring using variability analysis in the prediction of neurodevelopmental outcomes in neonates undergoing surgery for congenital heart disease. DESIGN: Retrospective cohort study. SETTING: Urban, academic, tertiary-care children's hospital. PATIENTS: Neonates undergoing surgery with cardiopulmonary bypass for congenital heart disease. INTERVENTIONS: Perioperative monitoring of continuous cerebral tissue oxygenation index by near-infrared spectroscopy and subsequent neurodevelopmental testing at 6, 15, and 21 months of age. MEASUREMENTS AND MAIN RESULTS: We developed a new measure, cerebral tissue oxygenation index variability, using the root mean of successive squared differences of averaged 1-minute cerebral tissue oxygenation index values for both the intraoperative and first 24-hours postoperative phases of monitoring. There were 62 neonates who underwent cerebral tissue oxygenation index monitoring during surgery for congenital heart disease and 44 underwent subsequent neurodevelopmental testing (12 did not survive until testing and six were lost to follow-up). Among the 44 monitored patients who underwent neurodevelopmental testing, 20 (45%) had abnormal neurodevelopmental indices. Patients with abnormal neurodevelopmental indices had lower postoperative cerebral tissue oxygenation index variability when compared with patients with normal indices (p = 0.01). Adjusting for class of congenital heart disease and duration of deep hypothermic circulatory arrest, lower postoperative cerebral tissue oxygenation index variability was associated with poor neurodevelopmental outcome (p = 0.02). CONCLUSIONS: We found reduced postoperative cerebral tissue oxygenation index variability in neonatal survivors of congenital heart disease surgery with poor neurodevelopmental outcomes. We hypothesize that reduced cerebral tissue oxygenation index variability may be a surrogate for impaired cerebral metabolic autoregulation in the immediate postoperative period. Further research is needed to investigate clinical implications of this finding and opportunities for using this measure to drive therapeutic interventions.

Cerebral tissue oxygenation index and lactate at 24 hours postoperative predict survival and neurodevelopmental outcome after neonatal cardiac surgery.

IMPORTANCE: There are no well-established noninvasive biomarkers for identifying patients at risk for poor outcome after surgery for congenital heart disease. Few studies have assessed prognostic accuracy of cerebral tissue oxygenation index (cTOI) measured by near infrared spectroscopy (NIRS). OBJECTIVE: To assess the utility of noninvasive NIRS monitoring as a predictor of outcomes after neonatal cardiac surgery through measurement of cTOI. To examine the utility of noninvasive NIRS monitoring in combination with lactate concentration and inotropic score in prediction of outcomes after neonatal cardiac surgery. DESIGN: Prospective longitudinal cohort study. SETTING: Operating room and cardiac intensive care unit, Children's National Heart Institute. PARTICIPANTS: Seventy-five patients with complex congenital heart disease undergoing surgical repair within first month of life. EXPOSURE: Cerebral TOI, blood lactate, and inotropic scores were measured preoperative, intraoperative and up to 24 hours postoperative. MAIN OUTCOME MEASURES: Postoperative mortality and neurodevelopmental outcome assessed by the Bayley Scales of Infant Development (BSID II). Mental and motor scores were obtained at 6, 15, and 21 months. Good outcome was defined as survival and BSID mental and motor scores ≥70 points. Poor outcome was defined as death or BSID scores <70 at most recent follow-up. RESULTS: Cohort of 75 patients prospectively followed including 40 patients with single ventricle and 35 with two ventricles. Four patients died before discharge and ten died within 21 months. Seven patients were lost to follow-up. Among survivors with follow-up (n = 54), BSID was abnormal in 25 (46%). Patients with poor outcome (n = 39) had lower mean cTOI 60 minutes off-CPB (48% vs. 58%, P = .003) and 24 hours postoperative (49% vs. 59%, P < .001), higher lactate (8.2 vs. 5.0 mmol/L, P = .005) and higher inotropic scores (10 vs. 6, P = .02) at 24 hours postoperative. ROC analysis indicated that cTOI had moderate predictive accuracy of outcome (AUC = 0.751, P < .001). Multivariable regression analysis confirmed that predictive accuracy was improved using both cTOI and lactate at 24 hours postoperative (AUC = 0.813, 95% CI: 0.705-0.921, P < .001) with optimal cutoff values <58% and >7.4 mmol/L, respectively (sensitivity = 95%). CONCLUSION: Cerebral TOI combined with lactate at 24 hours postoperative are accurate non-invasive predictive biomarkers of patient survival and neurodevelopmental outcome in neonates with CHD undergoing cardiac surgery.

Neonatal neurobehavior after therapeutic hypothermia for hypoxic ischemic encephalopathy.

BACKGROUND: Perinatal hypoxic ischemic encephalopathy (HIE) is a major cause of neurodevelopmental impairment including cerebral palsy and intellectual disability. Brain magnetic resonance imaging is the gold standard for acute assessment of cerebral injury in HIE. Limited data are available regarding the significance of clinically manifested neurobehavioral impairments in the neonatal period. AIM: To evaluate brain structure-function relationships in newborns with HIE using diffusion tensor imaging (DTI) and the NICU Network Neurobehavioral Scale (NNNS). STUDY DESIGN: Prospective observational study with secondary longitudinal component. SUBJECTS: Forty-five newborns (62% male) with HIE referred for therapeutic hypothermia who underwent MRI and neurobehavioral assessment prior to discharge. OUTCOME MEASURES: DTI was performed at median age of 8 days (range 5-16) and NNNS at median 12 days of life (range 5-20, postmenstrual age 40±2 weeks). Developmental assessment with the Bayley Scales of Infant Development-II was performed at median age of 21.6 months (range 20.8-30.6). RESULTS: Significant associations were observed between DTI corticospinal tract integrity and NNNS neuromotor performance in HIE newborns. Neonatal neuromotor performance was also related to later early childhood motor outcomes. CONCLUSIONS: NNNS performed after therapeutic hypothermia in newborns with HIE can identify neuromotor abnormalities that are related to microstructural brain injury in the corticospinal tract and later motor outcomes in early childhood. These data support the NNNS as a valid early functional assessment of perinatal brain injury.

Regional Brain Biometrics at Term-Equivalent Age and Developmental Outcome in Extremely Low-Birth-Weight Infants.

OBJECTIVE: This study aims to evaluate individual regional brain biometrics and their association with developmental outcome in extremely low-birth-weight (ELBW) infants. STUDY DESIGN: This is a retrospective study evaluating term-equivalent magnetic resonance imaging (TE-MRI) from 27 ELBW infants with known developmental outcomes beyond 12 months corrected age. Regional biometric measurements were performed by a pediatric neuroradiologist blinded to outcome data. Measures included biparietal width, transcerebellar diameter (TCD), deep gray matter area (DGMA), ventricular dilatation, corpus callosum, and interhemispheric distance. The relationship between regional biometrics and Bayley-II developmental scores were evaluated with linear regression models. RESULTS: The study cohort had an average±standard deviation birth weight of 684±150 g, gestational age of 24.6±2 weeks and 48% males. DGMA was significantly associated with both cognitive and motor outcomes. Significant associations were also observed between TCD and corpus callosum splenium with cognitive and motor outcomes, respectively. Other biometric measures were not associated with outcome (p>0.05). DGMA<10.26 cm2 was highly specific for poor motor and cognitive outcome. CONCLUSION: TE-MRI biometrics reflecting impaired deep gray matter, callosal, and cerebellar size is associated with worse early childhood cognitive and motor outcomes. DGMA may be the most robust single biometric measure to predict adverse developmental outcome in preterm survivors.

White matter tract integrity and developmental outcome in newborn infants with hypoxic-ischemic encephalopathy treated with hypothermia.

AIM: To determine whether corpus callosum (CC) and corticospinal tract (CST) diffusion tensor imaging (DTI) measures relate to developmental outcome in encephalopathic newborn infants after therapeutic hypothermia. METHOD: Encephalopathic newborn infants enrolled in a longitudinal study underwent DTI after hypothermia. Parametric maps were generated for fractional anisotropy, mean, radial, and axial diffusivity. CC and CST were segmented by DTI-based tractography. Multiple regression models were used to examine the association of DTI measures with Bayley-II Mental (MDI) and Psychomotor Developmental Index (PDI) at 15 months and 21 months of age. RESULTS: Fifty-two infants (males n=32, females n=20) underwent DTI at median age of 8 days. Two were excluded because of poor magnetic resonance imaging quality. Outcomes were assessed in 42/50 (84%) children at 15 months and 35/50 (70%) at 21 months. Lower CC and CST fractional anisotropy were associated with lower MDI and PDI respectively, even after controlling for gestational age, birth weight, sex, and socio-economic status. There was also a direct relationship between CC axial diffusivity and MDI, while CST radial diffusivity was inversely related to PDI. INTERPRETATION: In encephalopathic newborn infants, impaired microstructural organization of the CC and CST predicts poorer cognitive and motor performance respectively. Tractography provides a reliable method for early assessment of perinatal brain injury.

Biomarkers S100B and neuron-specific enolase predict outcome in hypothermia-treated encephalopathic newborns*.

OBJECTIVES: To evaluate if serum S100B protein and neuron-specific enolase measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy. DESIGN: Prospective longitudinal cohort study. SETTING: A level IV neonatal ICU in a freestanding children's hospital. PATIENTS: Term newborns with moderate to severe neonatal encephalopathy referred for therapeutic hypothermia during the study period. INTERVENTIONS: Serum neuron-specific enolase and S100B were measured at 0, 12, 24, and 72 hours of hypothermia. MEASUREMENTS AND MAIN RESULTS: Of the 83 infants enrolled, 15 (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development-II at 15 months. Outcomes were assessed in 49 of 68 survivors (72%) at a mean age of 15.2 ± 2.7 months. Neurodevelopmental outcome was classified by Bayley Scales of Infant Development-II Mental Developmental Index and Psychomotor Developmental Index scores, reflecting cognitive and motor outcomes, respectively. Four-level outcome classifications were defined a priori: normal = Mental Developmental Index/Psychomotor Developmental Index within 1 SD (> 85), mild = Mental Developmental Index/Psychomotor Developmental Index less than 1 SD (70-85), moderate/severe = Mental Developmental Index/Psychomotor Developmental Index less than 2 SD (< 70), or died. Elevated serum S100B and neuron-specific enolase levels measured during hypothermia were associated with increasing outcome severity after controlling for baseline and socioeconomic characteristics in ordinal regression models. Adjusted odds ratios for cognitive outcome were 2.5 (95% CI, 1.3-4.8) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase, and for motor outcome, 2.6 (95% CI, 1.2-5.6) for S100B and 2.1 (95% CI, 1.2-3.6) for neuron-specific enolase. CONCLUSIONS: Serum S100B and neuron-specific enolase levels in babies with neonatal encephalopathy are associated with neurodevelopmental outcome at 15 months. These putative biomarkers of brain injury may help direct care during therapeutic hypothermia.

International telemedicine consultations for neurodevelopmental disabilities.

BACKGROUND: A telemedicine program was developed between the Children's National Medical Center (CNMC) in Washington, DC, and the Sheikh Khalifa Bin Zayed Foundation in the United Arab Emirates (UAE). A needs assessment and a curriculum of on-site training conferences were devised preparatory to an ongoing telemedicine consultation program for children with neurodevelopmental disabilities in the underserved eastern region of the UAE. MATERIALS AND METHODS: Weekly telemedicine consultations are provided by a multidisciplinary faculty. Patients are presented in the UAE with their therapists and families. Real-time (video over Internet protocol; average connection, 768 kilobits/s) telemedicine conferences are held weekly following previews of medical records. A full consultation report follows each telemedicine session. RESULTS: Between February 29, 2012 and June 26, 2013, 48 weekly 1-h live interactive telemedicine consultations were conducted on 48 patients (28 males, 20 females; age range, 8 months-22 years; median age, 5.4 years). The primary diagnoses were cerebral palsy, neurogenetic disorders, autism, neuromuscular disorders, congenital anomalies, global developmental delay, systemic disease, and epilepsy. Common comorbidities were cognitive impairment, communication disorders, and behavioral disorders. Specific recommendations included imaging and DNA studies, antiseizure management, spasticity management including botulinum toxin protocols, and specific therapy modalities including taping techniques, customized body vests, and speech/language and behavioral therapy. Improved outcomes reported were in clinician satisfaction, achievement of therapy goals for patients, and requests for ongoing sessions. CONCLUSIONS: Weekly telemedicine sessions coupled with triannual training conferences were successfully implemented in a clinical program dedicated to patients with neurodevelopmental disabilities by the Center for Neuroscience at CNMC and the UAE government. International consultations in neurodevelopmental disabilities utilizing telemedicine services offer a reliable and productive method for joint clinical programs.

Sleep wake cycling and neurodevelopmental outcome in very low birth weight infants.

BACKGROUND: Although the maturation of sleep wake cycling (SWC) in premature infants has been described, its value in predicting neurodevelopmental outcome (NDO) is yet to be known. OBJECTIVE: To examine the relationship between NDO and SWC evaluated by amplitude integrated electroencephalogram (aEEG) in very low birth weight (VLBW) infants. STUDY DESIGN: VLBW infants (<1500 grams and ≤34 weeks gestational age) were enrolled in a prospective study. Two channel 12-hour aEEG recordings were completed at 34 weeks postmenstrual age (PMA) and SWC scores were assigned. NDO was measured by the Bayley's Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) at 9 and 18 months corrected age (CA). RESULTS: Eighty-four of the 103 enrolled infants had an aEEG completed at 34 weeks PMA. At 9 months CA, in linear regression models, MDI was significantly associated with severe intraventricular hemorrhage (IVH) and SWC score, while PDI was associated with GA and SWC score. At 18 months CA, these associations lost significance. CONCLUSIONS: At 34 weeks PMA, all VLBW premature infants demonstrate some degree of SWC on aEEG. Maturation of SWC at 34 weeks PMA is not associated with gestational age, however may relate to early NDO. Further studies are needed to evaluate this relationship.

Neurodevelopmental deficits among infants and toddlers with sickle cell disease.

OBJECTIVE: Neurodevelopmental deficits are among the serious complications of sickle cell disease (SCD). However, few studies have prospectively evaluated neurodevelopmental deficits in very young children with SCD. We analyzed baseline neurodevelopmental data from a cohort of 80 infants and toddlers with SCD to identify primary disease-related events and sociodemographic risk factors associated with early developmental delay. METHODS: This is an analysis of baseline date of a 4-year mixed, cross-sectional/longitudinal study. Full-term children at age 3.5 years or younger with SCD (any genotype) were eligible. Neurodevelopmental evaluations (Bayley II) were conducted at ages 9, 15, 21, 30, and 40 months. Demographics, hematologic variables, and medical events were obtained. RESULTS: Significant neurodevelopmental deficits were evident: 17.5% scoring >2SD below the mean on Bayley Mental Index or Motor Index. Odds ratio of significant developmental delay was >9 times more likely among those who had experienced vaso-occlusive pain episodes, after controlling for socioeconomic status (SES), gender, pneumonia/acute chest syndrome, and hemoglobin concentration. Male gender was also a risk factor for developmental delay. CONCLUSIONS: Early cognitive and motor delays were present in young children with SCD, with higher prevalence among those who had experienced pain crises. Increased vulnerability of male gender is consistent with other at-risk populations but has not been previously addressed in SCD research. Furthermore, these delays are not sufficiently explained by lower SES. Significant developmental delay in children with SCD may go unrecognized by primary care practices, medical specialty clinics, or parents. The importance of routine neurodevelopmental assessment for children with chronic medical conditions is clear.