Association between Early Basal Ganglia and Thalami Perfusion Assessed by Color Doppler Ultrasonography and Brain Injury in Infants with Hypoxic-Ischemic Encephalopathy: A Prospective Cohort Study.

OBJECTIVE: To evaluate associations between neurologic outcomes and early measurements of basal ganglia (BG) and thalamic (Th) perfusion using color Doppler ultrasonography (CDUS) in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Prospective study of infants with mild (n = 18), moderate (n = 17), and severe HIE (n = 14) and controls (n = 17). Infants with moderate-severe HIE received therapeutic hypothermia (TH). CDUS was performed at 24-36 hours and brain magnetic resonance imaging (MRI) at a median of 10 days. Development was followed through 2.5-5 years. The primary outcome was the association between BG and Th perfusion and brain MRI injury. Secondary analyses focused on associations between perfusion measurements and admission neurologic examinations, MRI scores in infants treated with TH, and motor and sensory disability, or death. An exploratory analysis assessed the accuracy of BG and Th perfusion to predict brain MRI injury in infants treated with TH. RESULTS: Increased BG and Th perfusion on CDUS was observed in infants with severe MRI scores and those with significant motor and neurosensory disability or death through 2.5-5 years (P < .05). Infants with severe HIE showed increased BG and Th perfusion (P < .005) compared with infants with moderate HIE. No differences were identified between the between the control and mild HIE groups. Th perfusion ≥0.237 cm/second (Area under the curve of 0.824) correctly classified 80% of infants with severe MRI scores. CONCLUSIONS: Early dynamic CDUS of the BG and Th is a potential biomarker of severe brain injury in infants with HIE and may be a useful adjunct to currently used assessments.

An in-frame deletion affecting the critical acid loop of PPP2R5D is associated with a neonatal lethal form of PPP2R5D-related neurodevelopmental disorder.

Heterozygous pathogenic variants in PPP2R5D gene are associated with PPP2R5D-related neurodevelopmental disorder, a rare autosomal dominant condition, characterized by neurodevelopmental impairment in childhood, macrocephaly/megalencephaly, hypotonia, epilepsy, and dysmorphic features. Up-to-date, only approximately 100 cases have been published in the literature and the full phenotypic and genotypic spectrum have not yet been fully described. PPP2R5D gene encodes the B56δ subunit of the PP2A enzyme complex. We describe a neonatal form of PPP2R5D-related disorder with early infantile death, caused by a novel in-frame deletion causing loss of 8 amino acids and insertion of serine at position 201 (p.Phe194_Pro201delinsSer) of the B56δ subunit. This deletion is predicted to disrupt a critical acidic loop of amino acids important for binding other subunits of the PP2A enzyme complex, and harbors many of the residues previously reported to cause a mild-moderate form of this condition. This report describes a neonatal lethal presentation of the PPP2R5D-related neurodevelopmental disorder and provides additional evidence that disruption of the acidic loop is an important pathomechanism underlying PPP2R5D-related disorder.

Spontaneous resolution of post-hemorrhagic ventricular dilatation in preterm newborns and neurodevelopment.

BACKGROUND: We investigated the temporal evolution of post-hemorrhagic ventricular dilatation (PHVD) and compared neurodevelopmental impairments (NDI) in newborns with (Group 1) spontaneous resolution of PHVD, (Group 2) persistent PHVD without neurosurgical intervention, and (Group 3) progressive PHVD receiving neurosurgical intervention. METHODS: A multicenter retrospective cohort study of newborns born at ≤34 weeks with PHVD (ventricular index [VI] >97th centile for gestational age and anterior horn width [AHW] >6 mm) from 2012 to 2020. Severe NDI was defined as global developmental delay or cerebral palsy GMFCS III-V at 18 months. RESULTS: Of 88 survivors with PHVD, 39% had a spontaneous resolution, 17% had persistent PHVD without intervention, and 44% had progressive PHVD receiving intervention. The median time between PHVD diagnosis and spontaneous resolution was 14.0 days (IQR 6.8-32.3) and between PHVD diagnosis and first neurosurgical intervention was 12.0 days (IQR 7.0-22.0). Group 1 had smaller median maximal VI (1.8, 3.4, 11.1 mm above p97; p < 0.001) and AHW (7.2, 10.8, 20.3 mm; p < 0.001) than Groups 2 and 3. Neurodevelopmental outcome data were available for 82% of survivors. Group 1 had reduced severe NDI compared to Group 3 (15% vs 66%; p < 0.001). CONCLUSION: Newborns with PHVD without spontaneous resolution are at higher risk for impairments despite neurosurgical interventions, which may be due to larger ventricular dilatation. IMPACT: The natural evolution of post-hemorrhagic ventricular dilatation (PHVD) and developmental implications of spontaneous resolution are not well established. In this study, approximately one in three newborns with PHVD experienced spontaneous resolution and this subset of newborns had reduced rates of neurodevelopmental impairments. More prominent ventricular dilatation was associated with reduced rates of spontaneous resolution and increased rates of severe neurodevelopmental impairment among newborns with PHVD. Understanding clinically relevant time points in the evolution of PHVD and predictors of spontaneous resolution may help inform the discussion around the optimal timing for intervention and allow for more precise prognostication in this population.

Neurological implications of antenatal corticosteroids on late preterm and term infants: a scoping review.

The objective of this study was to synthesize the body of knowledge on the association between ACS exposure for risk of preterm birth and brain development in infants ultimately born late preterm and term. Three databases and eight conference proceedings were systematically searched (1972-2021). Selection criteria included ACS administration for risk of preterm delivery, cohort of late preterm and term infants, and assessment of brain development. Data on study characteristics, ACS administration, and neurological outcomes were extracted and qualitatively synthesized according to themes. Neurological outcomes of the included studies (n = 27) were grouped into four themes. The most common adverse outcomes were reduced neonatal head circumference, structural cortical differences on MRI, increased prevalence of psychiatric problems, and increased risk of neurodevelopmental delays in ACS-exposed late preterm and term infants. Our scoping review demonstrated that ACS exposure for risk of preterm delivery may have important neurological implications in infants ultimately born late preterm and term. Given that the existing research is at serious risk for bias, further research that accounts for confounders such as preterm labor, maternal stress, and the number of ACS courses is needed to better establish the long-term neurological effects of ACS on late preterm and term infants. IMPACT: Due to the difficulty in predicting preterm birth, approximately 40% of fetuses exposed to antenatal corticosteroids (ACS) are born at term (≥37 weeks' gestation). This scoping review summarizes the knowledge on the association between ACS exposure for risk of preterm birth and brain development in late preterm and term infants. The majority of studies reported that ACS exposure was associated with adverse brain development outcomes across various domains, such as reduced neonatal head circumference, cortical differences on MRI, and increased prevalence of psychiatric problems and neurodevelopmental delays in late preterm and term infants.

Incidence and risk factors for autism spectrum disorder among infants born <29 weeks' gestation.

Objective: This study was aimed to assess the incidence of and risk factors for autism spectrum disorder (ASD) among preterm infants born <29 weeks' gestational age (GA). Methods: A retrospective cohort study of infants born <29 weeks' GA admitted to two tertiary neonatal intensive care units (2009 to 2017) and followed ≥18 months corrected age (CA) at a neonatal follow-up clinic. The primary outcome was ASD, diagnosed using standardized testing or provisional diagnosis at ≥18 months CA. Patient data and 18-month CA developmental outcomes were obtained from the local Canadian Neonatal Follow Up Network database and chart review. Stepwise logistic regression assessed factors associated with ASD. Results: Among 300 eligible infants, 26 (8.7%) were diagnosed with confirmed and 21 (7.0%) with provisional ASD for a combined incidence of 15.7% (95% confidence interval [CI] 11.7 to 20.3). The mean follow-up duration was 3.9 ± 1.4 years and the mean age of diagnosis was 3.7 ± 1.5 years. Male sex (adjusted odds ratio [aOR] 4.63, 95% CI 2.12 to 10.10), small for gestational age status (aOR 3.03, 95% CI 1.02 to 9.01), maternal age ≥35 years at delivery (aOR 2.22, 95% CI 1.08 to 4.57) and smoking during pregnancy (aOR 5.67, 95% CI 1.86 to 17.29) were significantly associated with ASD. Among ASD infants with a complete 18-month CA developmental assessment, 46% (19/41) had no neurodevelopmental impairment (Bayley-III<70, deafness, blindness, or cerebral palsy). Conclusions: ASD is common among infants born <29 weeks' GA and possibly associated with identified risk factors. Such findings emphasize the importance of ASD evaluation among infants <29 weeks' GA and for continued reporting of developmental outcomes beyond 18-months of corrected age.

Location and Size of Preterm Cerebellar Hemorrhage and Childhood Development.

OBJECTIVE: To examine the association between cerebellar hemorrhage (CBH) size and location and preschool-age neurodevelopment in very preterm neonates. METHODS: Preterm magnetic resonance images of 221 very preterm neonates (median gestational age = 27.9 weeks) were manually segmented for CBH quantification and location. Neurodevelopmental assessments at chronological age 4.5 years included motor (Movement Assessment Battery for Children, 2nd Edition [MABC-2]), visuomotor integration (Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition), cognitive (Wechsler Primary and Preschool Scale of Intelligence, 3rd Edition), and behavioral (Child Behavior Checklist) outcomes. Multivariable linear regression models examined the association between CBH size and 4.5-year outcomes accounting for sex, gestational age, and supratentorial injury. Probabilistic maps assessed CBH location and likelihood of a lesion to predict adverse outcome. RESULTS: Thirty-six neonates had CBH: 14 (6%) with only punctate CBH and 22 (10%) with ≥1 larger CBH. CBH occurred mostly in the inferior aspect of the posterior lobes. CBH total volume was independently associated with MABC-2 motor scores at 4.5 years (ß = -0.095, 95% confidence interval = -0.184 to -0.005), with a standardized ß coefficient (-0.16) that was similar to that of white matter injury volume (standardized ß = -0.22). CBH size was similarly associated with visuomotor integration and externalizing behavior but not cognition. Voxelwise odds ratio and lesion-symptom maps demonstrated that CBH extending more deeply into the cerebellum predicted adverse motor, visuomotor, and behavioral outcomes. INTERPRETATION: CBH size and location on preterm magnetic resonance imaging were associated with reduced preschool motor and visuomotor function and more externalizing behavior independent of supratentorial brain injury in a dose-dependent fashion. The volumetric quantification and localization of CBH, even when punctate, may allow opportunity to improve motor and behavioral outcomes by providing targeted intervention. ANN NEUROL 2020;88:1095-1108.

Cerebral palsy after neonatal encephalopathy: do neonates with suspected asphyxia have worse outcomes?

AIM: We sought to investigate how brain injury and severity, and neurological subtype of cerebral palsy (CP) differed in term-born children with CP after neonatal encephalopathy, between those with suspected birth asphyxia and those without. METHOD: Using the Canadian CP Registry, which included 1001 children, those with CP born at ≥ 36 wks after moderate or severe neonatal encephalopathy, were dichotomized according to the presence or absence of suspected birth asphyxia. Gross Motor Function Classification System (GMFCS) scores, neurological subtypes, comorbidities, and magnetic resonance imaging findings were compared. RESULTS: Of the 147 term-born children with CP (82 males, 65 females; median age 37 months, interquartile range [IQR] 26-52.5) who after moderate or severe neonatal encephalopathy had the required outcome data, 61 (41%) met criteria for suspected birth asphyxia. They had a higher frequency of non-ambulatory GMFCS status (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.72-6.8), spastic quadriplegia (OR 2.8, 95% CI 1.4-5.6), non-verbal communication skills impairment (OR 4.2, 95% CI 2.0-8.6), isolated deep grey matter injury (OR 4.1, 95% CI 1.8-9.5), a lower frequency of spastic hemiplegia (OR 0.17, 95% CI 0.07-0.42), focal injury (OR 0.20; 95% CI 0.04-0.93), and more comorbidities (p=0.017) than those who did not meet criteria. INTERPRETATION: Term-born children who develop CP after neonatal encephalopathy with suspected birth asphyxia have a greater burden of disability than those without suspected birth asphyxia.

Cerebral Palsy after Neonatal Encephalopathy: How Much Is Preventable?

OBJECTIVES: To determine the expected proportion of term cerebral palsy (CP) after neonatal encephalopathy (NE) that could theoretically be prevented by hypothermia and elucidate the perinatal factors associated with CP after NE in those who do not meet currently used clinical criteria required to qualify for hypothermia ("cooling criteria"). STUDY DESIGN: Using the Canadian CP Registry, we categorized children born at ≥ 36 weeks with birth weight ≥ 1800 g with CP after moderate or severe NE according to the presence or absence of cooling criteria. Maternal, perinatal, postnatal, and placental factors were compared between the 2 groups. A number needed to treat of 8 (95% CI 6-17) to prevent one case of CP was used for calculations. RESULTS: Among the 543 term-born children with CP, 155 (29%) had moderate or severe NE. Sixty-four of 155 (41%) met cooling criteria and 91 of 155 (59%) did not. Shoulder dystocia was more common in those who did not meet cooling criteria (OR 8.8; 95% CI 1.1-71.4). Low birth weights (20% of all singletons), small placentas (42%), and chorioamnionitis (13%) were common in both groups. CONCLUSIONS: The majority of children with CP after NE did not meet cooling criteria. An estimated 5.1% (95% CI 2.4%-6.9%) of term CP after NE may be theoretically prevented with hypothermia. Considering shoulder dystocia as an additional criterion may help recognize more neonates who could potentially benefit from cooling. In all cases, a better understanding of the antenatal processes underlying NE is essential in reducing the burden of CP.

Corrected Age at Bayley Assessment and Developmental Delay in Extreme Preterms.

BACKGROUND AND OBJECTIVES: Research on outcomes of prematurity frequently examines neurodevelopment in the toddler years as an end point, but the age range at examination varies. We aimed to evaluate whether the corrected age (CA) at Bayley-III assessment is associated with rates of developmental delay in extremely preterm children. METHODS: This retrospective cohort study included children born at <29 weeks' gestation who were admitted in the Canadian Neonatal Network between 2009 and 2017. The primary outcomes were significant developmental delay (Bayley-III score <70 in any domain) and developmental delay (Bayley-III score <85 in any domain). To assess the association between CA at Bayley-III assessment and developmental delay, we compared outcomes between 2 groups of children: those assessed at 18 to 20 months' CA and 21-24 months. RESULTS: Overall, 3944 infants were assessed at 18-20 months' CA and 881 at 21-24 months. Compared with infants assessed at 18-20 months, those assessed at 21-24 months had higher odds of significant development delay (20.0% vs 12.5%; adjusted odds ratio, 1.75; 95% confidence interval [CI], 1.41-2.13) and development delays (48.9% vs 41.7%, adjusted odds ratio 1.33; 95% CI, 1.11-1.52). Bayley-III composite scores were on average 3 to 4 points lower in infants evaluated at 21-24 months' CA (for instance, adjusted mean difference and 95% CI for language: 3.49 [2.33-4.66]). Conversely, rates of cerebral palsy were comparable (4.6% vs 4.7%) between the groups. CONCLUSIONS: Bayley-III assessments performed at 21-24 months' CA were more likely to diagnose a significant developmental delay compared with 18- to 20-month assessments in extremely preterm children.

Response to Hydrocortisone in an Extremely Preterm Neonate With Late-Onset Sepsis, Meningoencephalitis, and Drug-Resistant Seizures.

Corticosteroids are commonly used in children with bacterial meningitis; however, there are very few data regarding possible utility in neonates, particularly those born premature. We describe our experience using hydrocortisone in the treatment of a girl born at 26 weeks, 6 days gestation. She had suffered profound brain injury following late onset group B streptococcus sepsis and meningitis, and developed drug-resistant seizures. Because seizures continued despite treatment with phenobarbital, phenytoin, levetiracetam, lacosamide, and midazolam, intravenous hydrocortisone was added. We observed a marked decrease in focal electrographic seizures within 2 days of initiation of hydrocortisone. This experience suggests that corticosteroids could be a treatment option for drug-resistant seizures and status epilepticus in preterm neonates, particularly those with bacterial meningitis.

Neurolathyrism in vapniarka: medical heroism in a concentration Camp.

Stories abound about the medical abuses that have come to define medicine and the "pseudo"-neurosciences in the Third Reich. Well known are the Nazi program of euthanasia and the neuroscientific publications that arose from it. Nevertheless, during this widespread perversion of medical practice and science, true medical heroics persisted, even in the concentration camps. In December 1942, inmates of Camp Vapniarka began experiencing painful lower extremity muscle cramps, spastic paraparesis, and urinary incontinence. In order to reduce the cost of feeding the 1200, mostly Jewish, inmates of Camp Vapniarka and surreptitiously hasten their deaths, the Nazi-affiliated Romanian officers of the camp had begun feeding them a diet high in Lathyrus sativus. L. sativus is the neurotoxin implicated in neurolathyrism, a degenerative disease of the upper motor neurons. Dr. Arthur Kessler, one of the camp's prisoners, eventually identified the source of the epidemic. Armed with this knowledge, the inmates collectively organized to halt its spread.

Imaging pattern of calvarial lesions in adults.

Calvarial lesions often present themselves as clinically silent findings on skull radiographs or as palpable masses that may cause localized pain or soreness. This review aims to explore the radiographic, computed tomography (CT), and magnetic resonance imaging (MRI) characteristics of calvarial neoplastic, inflammatory, and congenital lesions that are common in adults in order to facilitate a structured approach to their diagnosis and limit the differential diagnosis. In addition to reviewing the literature, we reviewed the records of 141 patients of the Montreal Neurological Institute and Hospital with radiologically documented calvarial lesions between 2001 and June 2009. CT is ideal for detecting bony lesions and is helpful in precisely localizing a lesion pre-surgically. MRI is best at identifying intradiploic lesions before they affect the cortical tables and is able to establish extraosseous involvement, especially when paramagnetic contrast is employed.

Early Clinical Features of Cerebral Palsy in Children Without Perinatal Risk Factors: A Scoping Review.

BACKGROUND: The early identification of cerebral palsy (CP) in the primary care context is often problematic and referral for diagnosis often delayed. This study aimed to identify clinical features associated with the early detection of CP that can be used by the primary care provider. METHODS: We performed a scoping review by searching six electronic databases. We included English language articles that addressed the diagnosis of CP and/or its differential diagnosis in children and ways of detecting CP before the diagnosis is established (i.e., early clinical signs of CP) via (1) questions on the patient's clinical history, (2) developmental screening and/or health questionnaires, or (3) physical or neurological examination. RESULTS: Included studies (n = 41; 27 overview studies and 14 original studies) were grouped into the three themes. Most of the overview articles relied on expert opinion, and all original studies included patients at high risk of developing CP. The most commonly identified features from each theme were early hand preference on clinical history, delayed or absent achievement of motor developmental milestones on developmental screening, and persistent primitive reflexes on neurological examination. CONCLUSIONS: Overall, the literature on the early observable clinical signs that should prompt referral for investigation of possible CP in the specific context of well-baby care surveillance was sparse and inconsistent. Further research should focus on evaluating the contribution of readily identifiable clinical features.

Trends in sex-specific differences in outcomes in extreme preterms: progress or natural barriers?

OBJECTIVE: To examine the differences and trends of outcomes of preterm boys and girls born at <29 weeks' gestation. DESIGN: A retrospective cohort study. SETTING: Data collected by the Canadian Neonatal Network. PATIENTS: Neonates born at <29 weeks' gestation between January 2007 and December 2016. MAIN OUTCOME MEASURES: We examined rate differences in mortality, major morbidities (bronchopulmonary dysplasia, severe brain injury, retinopathy of prematurity, necrotising enterocolitis and late-onset sepsis) and care practices (antenatal steroids, magnesium sulfate, maternal antibiotics, ventilation and surfactant administration) between boys and girls and evaluated trends in these rate differences over the study period. Our primary outcome was a composite of mortality and any one of the five morbidities. RESULTS: Our study included 8219 boys and 6934 girls with median gestational age of 26 (IQR 25-28) weeks. The composite of death or major morbidity was more common in boys (adjusted risk ratio 1.07, 95% CI 1.05 to 1.10) and remained higher in boys over the study period. The gap between boys and girls for mortality, however, decreased over time: the slope for boys was -0.043 (95% CI -0.071 to -0.015) and for girls was -0.012 (95% CI -0.045 to 0.020) (p=0.04). All other morbidities remained higher in boys. Care practices changed at similar rates between the sexes. CONCLUSION: The difference between the mortality rates for boys and girls decreased over the study period but the difference between rates of the major morbidities was unchanged. More research is needed to understand biological differences and outcome disparities.

Neonatal Infection in Children With Cerebral Palsy: A Registry-Based Cohort Study.

BACKGROUND: The goal of this study was to explore the association between neonatal infection and outcomes in children with cerebral palsy. METHODS: We conducted a retrospective cohort study using the Canadian CP Registry. Neonatal infection was defined as meeting one of the following criteria: (1) septicemia, (2) septic shock, or (3) administration of antibiotics for ≥10 days. Phenotypic profiles of children with cerebral palsy with and without an antecedent neonatal infection were compared. Subgroup analysis was performed, stratified by gestational age (term versus preterm). RESULTS: Of the 1229 registry participants, 505 (41.1%) were preterm, and 192 (15.6%) met the criteria for neonatal infection with 29% of preterm children having a neonatal infection compared with 6.5% in term-born children. Children with prior neonatal infection were more likely to have a white matter injury (odds ratio 2.2, 95% confidence interval 1.5 to 3.2), spastic diplegic neurological subtype (odds ratio 1.6, 95% confidence interval 1.1 to 2.3), and sensorineural auditory impairment (odds ratio 2.1, 95% confidence interval 1.4 to 3.3). Among preterm children, neonatal infection was not associated with a difference in phenotypic profile. Term-born children with neonatal infection were more likely to have spastic triplegia or quadriplegia (odds ratio 2.4, 95% confidence interval 1.3 to 4.3), concomitant white matter and cortical injury (odds ratio 4.1, 95% confidence interval 1.6 to 10.3), and more severe gross motor ability (Gross Motor Function Classification System IV to V) (odds ratio 2.6, 95% confidence interval 1.4 to 4.8) compared with preterm children. CONCLUSIONS: Findings suggest a role of systemic infection on the developing brain in term-born infants, and the possibility to develop targeted therapeutic and preventive strategies to reduce cerebral palsy morbidity.

Somatosensory evoked potentials in neonates with hypoxic-ischemic encephalopathy treated with hypothermia.

OBJECTIVE: Somatosensory evoked potentials (SEPs) are reported to have high positive predictive value (PPV) for neurodevelopmental impairment (NDI) in neonates with moderate or severe hypoxic-ischemic encephalopathy (HIE). Our objective was to assess if this predictive value remains high with the use of therapeutic hypothermia. METHODS: A cohort of HIE neonates treated with hypothermia was recruited between September 2008 and September 2010. SEPs were elicited after hypothermia and classified as bilateral absent N19, abnormal N19 (i.e., delayed or unilateral absent), or normal. Qualitative evaluation of MRI was also performed. The primary outcome was moderate or severe NDI around 2 years of age. RESULTS: SEPs were performed after hypothermia in 26 of 34 neonates submitted to hypothermia with adequate follow-up at a median day of life 11 (IQR 9, 13). Twenty-three (88%) had moderate encephalopathy. Eleven neonates (42%) had bilateral absent N19, 4 of whom had NDI, while fifteen neonates (58%) had either abnormal or normal N19, of whom only one had NDI. SEPs thus had a PPV of 0.36 (4/11) and a negative predictive value (NPV) of 0.93 (14/15). Eighteen neonates (69%) had brain injury on MRI. MRI thus had a PPV of 0.28 (5/18) and an NPV of 1.00 (8/8). CONCLUSIONS: Neonates with HIE treated with hypothermia with bilateral absent N19 potentials may have a better prognosis than reported in the pre-hypothermia era. MRI also had a low PPV and high NPV. SEPs should be interpreted with caution in this new population and need to be re-evaluated in larger studies.

Autism spectrum disorder in a term birth neonatal intensive care unit population.

BACKGROUND: Nonspecific perinatal risk factors have been revealed to be associated with the development of autism spectrum disorder. However, term at-risk infants, as a distinct population, are underrepresented in the literature. This study examines the incidence and neonatal risk factors for autism spectrum disorder in term neonatal intensive care unit survivors. METHODS: We performed a retrospective analysis from a single university-practice database of neonates admitted to the neonatal intensive care unit and followed by a single pediatric neurologist. Term infants (≥ 37 weeks), born between 1991 and 2011, with at least 2 years (or 1 year if found to be neurologically normal) of follow-up were included. Principle outcomes were autism spectrum disorder, cerebral palsy, global developmental delay, and epilepsy. RESULTS: One hundred eighty infants were included from a database of 564 neonates. Twelve (6.6%) developed autism spectrum disorder, 53 (29.4%) cerebral palsy, 77 (42.7%) global developmental delay, and 47 (26.1%) epilepsy. Seventy-one (39.4%) developed no adverse outcomes. Nine patients with autism spectrum disorder (75%) were diagnosed with at least one other adverse outcome. No neonatal or perinatal variables were evident to be significantly associated with later autism spectrum disorder. CONCLUSIONS: In term neonatal intensive care unit survivors, autism spectrum disorder occurs at a greater frequency than in the general population and often develops alongside comorbid conditions. This highlights the importance of screening term neonatal intensive care unit survivors for autism spectrum disorder, particularly when comorbidities are present.

Cooling in the real world: therapeutic hypothermia in hypoxic-ischemic encephalopathy.

BACKGROUND AND AIM: The benefits of therapeutic hypothermia have not been assessed from the perspective of the neurology clinic. We aimed to report the impact of the implementation of a local regional therapeutic hypothermia program on the neurodevelopmental outcomes of surviving hypoxic-ischemic encephalopathy (HIE) infants who were followed in the neonatal neurology clinic. METHODS: Retrospective analysis of term infants referred to the neonatal neurology clinic after having been diagnosed with HIE and meeting eligibility criteria for therapeutic hypothermia between March 1999 and June 2010. Therapeutic hypothermia was implemented in September 2008. Outcome measures were dichotomously defined as: normal or adverse, which included cerebral palsy, global developmental delay, and epilepsy. RESULTS: Thirty infants were included in the pre-therapeutic hypothermia group. Thirty-one infants received therapeutic hypothermia and 27 were adequately followed and included in the post-therapeutic hypothermia group. The frequency of an adverse outcome was significantly higher in the pre-therapeutic hypothermia infants (19/30 [63%] versus 4/27 [15%]; OR = 0.10; 95% CI, 0.03-0.37; P < 0.001). Neonatal clinical seizures were more frequent in the pre-therapeutic hypothermia group (P = 0.012). There were no differences regarding frequency of fetal distress, rate of caesarean sections, Apgar scores, need of resuscitation, cord/initial blood gases, and degrees of encephalopathy between the two groups. CONCLUSIONS: The implementation of a regional therapeutic hypothermia program in our institution has vastly reduced the observed neurological morbidity of surviving HIE infants followed in our neonatal neurology clinic. A similar change in outcomes of infants with HIE can be anticipated by other centers and other clinics adopting this therapy.

Predictors of outcome in term infants with neonatal seizures subsequent to intrapartum asphyxia.

The objective of this study was to define potential clinical prognostic factors for term infants with neonatal seizures subsequent to intrapartum asphyxia. The authors completed a retrospective analysis of 62 term infants with clinical neonatal seizures subsequent to intrapartum asphyxia. Logistic regression analysis was applied to determine the independent prognostic indicators of an adverse outcome. A total of 23 (37%) infants had a normal outcome, 34 (55%) survived with 1 or more neurodevelopmental impairments (23 cerebral palsy, 28 global developmental delay, 15 epilepsy, with 18 combination of two, and 9 all three), and 5 (8%) died. Six variables were associated with an adverse outcome, but only the presence of meconium aspiration, a low (≤ 3) 1-minute Apgar score, seizure type other than focal clonic, and moderately severely abnormal electroencephalography (EEG) background findings were independently associated with an adverse outcome. Signs of acute distress are predictors of adverse outcome, alongside seizure semiology and moderate to severe EEG background abnormalities.

Cerebral palsy, developmental delay, and epilepsy after neonatal seizures.

This study sought to identify clinical prognostic factors for cerebral palsy, global developmental delay, and epilepsy in term infants with neonatal seizures. We completed a retrospective analysis of 120 term infants who experienced clinical neonatal seizures at a single academic pediatric neurology practice. Logistic regression analysis determined the significant independent prognostic (P < 0.05) indicators of cerebral palsy, global developmental delay, and epilepsy. Fifty-four (45%) infants were never diagnosed with a neurodevelopmental abnormality, whereas 37 (31%) manifested cerebral palsy, 51 (43%) manifested global developmental delay, and 38 (32%) manifested epilepsy. Global developmental delay was present in 92% of the children who manifested spastic quadraparetic cerebral palsy. Seizure type, seizure onset, electroencephalographic background findings, and 5-minute Apgar scores constituted independent predictors of cerebral palsy. None of the children who manifested less than two predictors developed the disorder. For global developmental delay, predictors included method of delivery, seizure onset, electroencephalographic background findings, and etiology. Only one infant (2%) who manifested less than two predictors exhibited global developmental delay. For epilepsy, predictors included seizure type and administration of a second antiepileptic drug. Only one infant (3%) who manifested neither predictor developed the disease.