Definitions of bronchopulmonary dysplasia and long-term outcomes of extremely preterm infants in Korean Neonatal Network.

New definitions for bronchopulmonary dysplasia (BPD) have recently been suggested, and an accurate diagnosis, including severity classification with proper definition, is crucial to identify high-risk infants for appropriate interventions. To determine whether recently suggested BPD definitions can better predict long-term outcomes of BPD in extremely preterm infants (EPIs) than the original BPD definition, BPD was classified with severity 1, 2, and 3 using three different definitions: definition A (original), National Institute of Child Health and Human Development (NICHD) definition in 2001; definition B, the modified NICHD 2016 definition (graded by the oxygen concentration and the respiratory support at 36 weeks' postmenstrual age [PMA]); and definition C, the modified Jensen 2019 definition (graded by the respiratory support at 36 weeks' PMA). We evaluated 1050 EPIs using a national cohort. Whereas EPIs with grade 2 or 3 BPD as per definition A did not show any increase in the risk, EPIs with BPD diagnosed by definition B and C showed significantly increased risk for poor outcomes, such as respiratory mortality and morbidities, neurodevelopmental delay, and growth restriction at 18-24 months of corrected age. The recently suggested definition and severity grading better reflects long-term childhood morbidities than the original definition in EPIs.

Duration of Resuscitation at Birth, Mortality, and Neurodevelopment: A Systematic Review.

CONTEXT: The International Liaison Committee on Resuscitation Neonatal Life Support Task Force reviewed evidence for the duration of cardiopulmonary resuscitation (CPR) for newborns immediately after birth. OBJECTIVE: To summarize evidence for ongoing CPR on the outcomes of survival, neurodevelopment, and the composite of survival without moderate or severe neurodevelopmental impairment (NDI). DATA SOURCES: Medline, Embase, Evidence-Based Medicine Reviews, Cumulative Index to Nursing and Allied Health Literature, and Scientific Electronic Library Online were searched between inception and February 29, 2020. STUDY SELECTION: Two independent reviewers selected studies of newborns with at least 10 minutes of asystole, bradycardia, or pulseless electrical activity for which CPR is indicated. DATA EXTRACTION: Two independent reviewers extracted data and appraised the risk of bias. RESULTS: In 16 eligible studies, researchers reported outcomes of 579 newborns born between 1982 and 2017. Within individual studies, 2% to 100% of infants survived to last follow-up (hospital discharge through 12 years). Summarized across studies, 237 of 579 (40.9%) newborns survived to last follow-up. In 13 studies, researchers reported neurodevelopmental outcomes of 277 newborns. Of these, 30 of 277 (10.8%) survived without moderate or severe impairment, and 240 of 277 (87%) met the composite outcome of death or NDI (191 died and 49 survived with moderate or severe impairment). LIMITATIONS: There was very low certainty of evidence because of risk of bias and inconsistency. CONCLUSIONS: Infants with ongoing CPR at 10 minutes after birth are at high risk for mortality and neurodisability, but survival without moderate or severe NDI is possible. One specified duration of CPR is unlikely to uniformly predict survival or survival without neuroimpairment.

Trends in Mental Health Presentations to a Paediatric Emergency Department.

Aims This study aimed to analyse trends in mental health presentations to the Emergency Department (ED), which anecdotally had increased over the past decade. Methods The ED's electronic 'Symphony' system was used to identify the annual number of presentations categorised as having a mental health complaint from 2006-2017. A detailed analysis was performed on presentations over a one-year period. Results The number of presentations increased from 69 in 2006 to a peak of 432 in 2016 (526% increase). The overall admission rate was 33.3%(n=99), while 52.5%(n=156) of presentations occurred outside of standard working hours. Similar increases were documented by other ED's worldwide, and the WHO estimate that neuropsychiatric disorders will become one of the top five causes of morbidity, mortality and disability among children by 2020. Conclusion With the number of mental health presentations dramatically increasing, carefully designed and integrated strategies are required to pro-actively tackle this growing epidemic.

Association of Antenatal Corticosteroids and Magnesium Sulfate Therapy With Neurodevelopmental Outcome in Extremely Preterm Children.

OBJECTIVE: To test the primary hypothesis that extremely preterm children antenatally exposed to both magnesium sulfate and antenatal corticosteroids have a lower rate of severe neurodevelopmental impairment or death compared with those exposed to antenatal corticosteroids alone. METHODS: This was a prospective observational study of children born at 22 0/7-26 6/7 weeks of gestation from 2011 to 2014 at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network hospitals (N=3,093). The primary outcome was severe neurodevelopmental impairment or death at 18-26 months of corrected age follow-up based on exposure to antenatal corticosteroids and magnesium sulfate or antenatal corticosteroids alone. Secondary outcomes included components of severe neurodevelopmental impairment by exposure group and comparisons of severe neurodevelopmental impairment or death between children exposed to both antenatal corticosteroids and magnesium sulfate with those exposed to magnesium sulfate alone or to neither antenatal corticosteroids nor magnesium sulfate. Logistic regression models adjusted for background characteristics. RESULTS: Children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of severe neurodevelopmental impairment or death (813/2,239, 36.3%) compared with those exposed to antenatal corticosteroids alone (225/508, 44.3%; adjusted odds ratio [aOR] 0.73; 95% CI 0.58-0.91), magnesium sulfate alone (47/89, 53%; aOR 0.49; 95% CI 0.29-0.82), or neither therapy (121/251; 48.2%; aOR 0.66, 95% CI 0.49-0.89). Similarly, children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of death compared with either or neither therapy, but the rate of severe neurodevelopmental impairment among survivors did not differ between exposure groups. CONCLUSION: In children born between 22 0/7 and 26 6/7 weeks of gestation, exposure to both antenatal corticosteroids and magnesium sulfate was associated with lower rates of severe neurodevelopmental impairment or death and death compared with exposure to antenatal corticosteroids alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00063063.

Outcome of Very Preterm Infants With Early Optimal Nutrition Strategy: A Comparative Cohort Study.

BACKGROUND: Aggressive nutrition may benefit early growth; nevertheless, effects on neurodevelopmental outcomes are unclear. We planned a descriptive analytical study to compare survival without neurodevelopment disability (NDD) at 1 year in 2 groups during 2 time epochs-before and after implementation of early optimal nutrition strategies. NDD was defined as any one of the following: mental and/or motor development quotient < 85 at 12 months of age, corrected for prematurity; Denver Developmental Screening Test abnormal/suspect in even 1 domain out of the 4 domains; seizures; requirement of hearing aid; or blindness in 1 or both eyes. We also compared mortality, survival without bronchopulmonary dysplasia, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), intraventricular hemorrhage, periventricular leukomalacia, sepsis, metabolic bone disease (MBD), and extrauterine growth restriction (EUGR). METHODS: Preterm neonates born between 27 and 32 weeks' gestation were included. The prospective study group (AO) was recruited after implementation of early optimal nutrition policy. The comparative retrospective cohort (BO) received nutrition based on clinicians' decisions. Both groups were followed up using a structured plan till 1 year corrected age. RESULTS: 137 neonates were enrolled in AO and 151 in the BO cohort. There was no statistically significant difference in survival without NDD at 1 year-75.5% in AO vs 72.1% in BO, odds ratio 0.84 (95% CI 0.5-1.6). Babies who received early optimal nutrition had less NEC, EUGR, and ROP requiring laser therapy but more MBD. CONCLUSION: There was no difference in survival without NDD in early optimal nutrition cohort compared to the cohort before implementation of the nutrition strategy. Short-term benefits themselves may justify the need for early optimal nutrition.

Neurodevelopmental Outcomes of Preterm Infants With Retinopathy of Prematurity by Treatment.

OBJECTIVE: Among extremely preterm infants, we evaluated whether bevacizumab therapy compared with surgery for retinopathy of prematurity (ROP) is associated with adverse outcomes in early childhood. METHODS: This study was a retrospective analysis of prospectively collected data on preterm (22-26 + 6/7 weeks' gestational age) infants admitted to the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers who received bevacizumab or surgery exclusively for ROP. The primary outcome was death or severe neurodevelopmental impairment (NDI) at 18 to 26 months' corrected age (Bayley Scales of Infant and Toddler Development, Third Edition cognitive or motor composite score <70, Gross Motor Functional Classification Scale level ≥2, bilateral blindness or hearing impairment). RESULTS: The cohort (N = 405; 214 [53%] boys; median [interquartile range] gestational age: 24.6 [23.9-25.3] weeks) included 181 (45%) infants who received bevacizumab and 224 (55%) who underwent ROP surgery. Infants treated with bevacizumab had a lower median (interquartile range) birth weight (640 [541-709] vs 660 [572.5-750] g; P = .02) and longer durations of conventional ventilation (35 [21-58] vs 33 [18-49] days; P = .04) and supplemental oxygen (112 [94-120] vs 105 [84.5-120] days; P = .01). Death or severe NDI (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.94 to 2.14) and severe NDI (aOR 1.14; 95% CI 0.76 to 1.70) did not differ between groups. Odds of death (aOR 2.54 [95% CI 1.42 to 4.55]; P = .002), a cognitive score <85 (aOR 1.78 [95% CI 1.09 to 2.91]; P = .02), and a Gross Motor Functional Classification Scale level ≥2 (aOR 1.73 [95% CI 1.04 to 2.88]; P = .04) were significantly higher with bevacizumab therapy. CONCLUSIONS: In this multicenter cohort of preterm infants, ROP treatment modality was not associated with differences in death or NDI, but the bevacizumab group had higher mortality and poor cognitive outcomes in early childhood. These data reveal the need for a rigorous appraisal of ROP therapy.

Outcome of vein of Galen malformation presenting in the neonatal period.

OBJECTIVE: Vein of Galenaneurysmal malformation (VGAM) is a rare but important congenital malformation presenting to neonatal intensive care units (NICUs), and with a change from surgical to endovascular management, survival for this condition has improved. However, there is little reported about the medical management decisions of infants with this condition and the associated long-term neurodevelopmental outcomes. We aim to report a single centre experience of both acute treatment and long-term outcomes of VGAM for those infants admitted to our NICU soon after birth. DESIGN: Retrospective cohort study over a 15-year period from 2001 to 2015 inclusive. SETTING: A quaternary NICU at The Royal Children's Hospital, Melbourne, Australia. PARTICIPANTS: 24 newborn infants referred for management of VGAM. There were no eligibility criteria set for this study; all presenting infants were included. INTERVENTIONS: None. MAIN OUTCOMES MEASURES: Clinical neuroimaging data were gathered. Surviving children were formally assessed with a battery of tests administered by a neuropsychologist and occupational therapist/physiotherapist at various ages across early to middle childhood. RESULTS: Fifteen neonates with VGAM did not survive beyond their NICU admission. 10 of these were not offered endovascular intervention. Of the nine surviving infants, only one had a normal neurodevelopmental outcome. CONCLUSIONS: The mortality of VGAM presenting in the neonatal period was high, and rates of normal neurodevelopmental outcome for survivors were low. These findings contribute to our understanding of which neonates should be treated and highlights the importance of providing clinical neurodevelopmental follow-up to survivors beyond their infant years.

Neurodevelopmental disorder in children believed to have isolated mild ventriculomegaly prenatally.

OBJECTIVE: To estimate the prevalence of specific neurodevelopmental disorders in children believed to have isolated mild ventriculomegaly (IMV) prenatally in the second trimester of pregnancy, in order to optimize the counseling process. METHODS: This was a nationwide registry-based study including all singleton pregnancies that had first- and second-trimester ultrasound scans in the period 1st January 2008 to 1st October 2014, identified in the Danish Fetal Medicine Database and local clinical databases in Denmark. All fetuses diagnosed prenatally with IMV (measurement of the atrium of the lateral ventricles, 10.0-15.0 mm) between 18 and 22 weeks' gestation were followed up in national patient registers until the age of 2-7 years. Information was obtained on the diagnoses of intellectual disability, cerebral palsy, autism spectrum disorder, epilepsy and impaired psychomotor development. Neurodevelopmental disorders were compared between those with postnatally confirmed IMV and a reference population of children in the same age range. RESULTS: Of a cohort of 292 046 fetuses, 133 were found to have apparent IMV on the second-trimester scan for fetal malformations. In 11 cases, long-term follow-up was not possible owing to termination of pregnancy, spontaneous miscarriage, neonatal death or loss to follow-up. Of the 122 liveborn children followed up until 2-7 years, 15 were identified as having an additional abnormality while 107 were confirmed postnatally to have IMV. Of these 107 children, the diagnosis of a neurodevelopmental disorder was registered in six (5.6%), corresponding to an odds ratio of 2.64 (95% CI, 1.16-6.02), as compared with the reference population. The diagnoses were autism spectrum disorder, epilepsy and impaired psychomotor development. None of these 107 children was diagnosed with intellectual disability or cerebral palsy. CONCLUSIONS: Our results show that a confirmed diagnosis of IMV was associated with an increased risk of a neurodevelopmental disorder, as compared with the reference population, but the absolute risk was low and there were no cases of intellectual disability or cerebral palsy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Trastorno del desarrollo neurológico en fetos con sospecha de ventriculomegalia leve aislada prenatal OBJETIVO: Estimar la prevalencia de trastornos específicos del desarrollo neurológico en fetos con sospecha de ventriculomegalia leve aislada (IMV, por sus siglas en inglés) prenatal en el segundo trimestre del embarazo, a fin de optimizar el proceso de asesoramiento. MÉTODOS: Este estudio estuvo basado en un registro nacional que incluyó todos los embarazos con feto único a los que se les hizo ecografías en el primer y segundo trimestre entre el 1 de enero de 2008 y el 1 de octubre de 2014, identificados en la Base de Datos Danesa de Medicina Fetal y en las bases de datos clínicas locales en Dinamarca. Todos los fetos diagnosticados prenatalmente con IMV (por medición de la aurícula de los ventrículos laterales, 10,0-15,0 mm) entre las semanas de gestación 18 y 22 fueron monitoreados en los registros nacionales de pacientes hasta la edad de 2-7 años. Se obtuvo información sobre los diagnósticos de discapacidad intelectual, parálisis cerebral, trastornos del espectro autista, epilepsia y trastornos del desarrollo psicomotor. Se compararon los trastornos del desarrollo neurológico entre aquellos con IMV confirmada después del nacimiento y una población de referencia de niños en el mismo rango de edad. RESULTADOS: De una cohorte de 292 046 fetos, se encontró que 133 tenían IMV aparente en la ecografía del segundo trimestre realizada para detectar malformaciones fetales. El seguimiento a largo plazo no fue posible en 11 casos debido a la interrupción del embarazo, el aborto espontáneo, la muerte del recién nacido o el abandono del monitoreo. De los 122 niños nacidos vivos a los que se les dio seguimiento hasta los 2-7 años, se identificó a 15 con una anomalía adicional, mientras que a 107 se les confirmó postnatalmente que tenían IMV. De estos 107 niños, se registró el diagnóstico de un trastorno del desarrollo neurológico en seis (5,6%), lo que corresponde a una razón de momios de 2,64 (IC 95%: 1,16-6,02), en comparación con la población de referencia. Los diagnósticos fueron trastornos del espectro autista, epilepsia y trastornos del desarrollo psicomotor. Ninguno de estos 107 niños fue diagnosticado con discapacidad intelectual o parálisis cerebral. CONCLUSIONES: Nuestros resultados muestran que un diagnóstico confirmado de IMV se asoció con un mayor riesgo de trastorno del desarrollo neurológico, en comparación con la población de referencia, pero que el riesgo absoluto fue bajo y no hubo casos de discapacidad intelectual o parálisis cerebral.

Changes in long-term prognosis with increasing postnatal survival and the occurrence of postnatal morbidities in extremely preterm infants offered intensive care: a prospective observational study.

BACKGROUND: Decisions regarding provision of intensive care and post-discharge follow-up for infants born extremely preterm (<28 weeks' gestation) are based on the risks of mortality and neurodevelopmental disability. We aimed to elucidate the changes in probability of three outcomes (death, survival with major disability, and survival without major disability) with postnatal age in extremely preterm infants offered intensive care, and the effect of postnatal events on the probability of survival without major disability. METHODS: In this prospective observational study, we used data from three geographical cohorts composed of all extremely preterm livebirths offered intensive care at birth during three distinct periods (1991-92, 1997, and 2005) in Victoria, Australia. Participants were assessed at 8 years' corrected age for major neurodevelopmental disability, defined as moderate or severe cerebral palsy, general intelligence more than 2 SDs below term-born control means, blindness, or deafness. Probabilities of outcomes conditional on survival to different postnatal ages were calculated by logistic regression. Multivariable logistic regression was used to assess factors predictive of survival with major disability. FINDINGS: 751 (82%) of 915 extremely preterm livebirths free of lethal anomalies were offered intensive care, of whom 546 (73%) survived to age 8 years. Of the 499 survivors assessed, 86 (17%) had a major disability. With increasing gestational age at birth or days of postnatal survival, the probability of death decreased and of survival without major disability increased. By contrast, the probability of survival with major disability varied little with gestational age or postnatal survival. In survivors, major disability was associated with the occurrence of four important postnatal events: grade 3 or 4 intraventricular haemorrhage (odds ratio 2·61 [95% CI 1·11-6·15]), cystic periventricular leukomalacia (9·17 [3·57-23·53]), postnatal corticosteroid use (1·99 [1·03-3·85]), and surgery (2·78 [1·51-5·13]). 241 survivors (48%) had no major postnatal events during the newborn period, and had the lowest prevalence of major disability (17 participants [7%]). The probability of survival without major disability decreased with increasing number of major events (0·93 [0·89-0·96] for no events vs 0·31 [0·11-0·59] for three or more events). INTERPRETATION: Long-term prognosis in terms of death and major neurodevelopmental disability changes rapidly after birth for extremely preterm infants. Counselling of families and post-discharge planning should be individualised to changing circumstances following birth. FUNDING: National Health and Medical Research Council of Australia.

Closing the medical mortality gap in patients with major psychiatric conditions.

This article discusses options for closing the mortality gap between the general population and people with major psychiatric conditions such as psychosis, autism, learning disability and dementia. Most of the mortality (85%) involves physical disease, with most deaths occurring in general hospitals or care homes, so is relevant to all doctors. The main focus of psychiatric treatments has been to reduce suicide, although there is no evidence that they achieve this. This article calls for psychiatrists to collaborate with medical colleagues to help reduce excess deaths from physical causes. The practicalities of combined physical and mental health monitoring and prescribing clinics are discussed, based on experience in Whitby. Potential national solutions are summarized including options for smoking cessation, sugar restriction, nutritional supplementation and flu vaccination.

Association of admission temperature and death or adverse neurodevelopmental outcomes in extremely low-gestational age neonates.

OBJECTIVE: Preterm infants are at higher risk of developing hypothermia and complications from cold stress, resulting in high mortality and short-term morbidity. Our objective is to evaluate the association between admission temperatures of extremely low-gestational age neonates (ELGAN) (<29 weeks') and adverse short-term neurodevelopmental outcomes. STUDY DESIGN: In this retrospective study, we included ELGAN admitted to NICUs across Canada between April 2009 and September 2011, who underwent neurodevelopmental assessment at 18-21 months' corrected age. RESULTS: Of 2739 infants with a complete data set identified during the study period, 968 (35.3%) had admission temperatures ≤36.4 °C (hypothermia group), 1489 (54.5%) had temperature of 36.5-37.2 °C (normothermia group), and 282 (10.3%) had hyperthermia (≥37.3 °C). Their mean birth weight was 823 ± 230 g, 944 ± 227 g and 927 ± 223 g, respectively (p < 0.01). More than 50% of infants born at 23-24 weeks were in the hypothermic group compared to 28.5-36.1% at higher gestational ages. We found 39.5% of infants in the hypothermic group had primary composite outcome of death or severe neurodevelopmental impairment (sNDI). Multivariate logistic regression revealed an increased adjusted odd of primary composite outcome (OR = 1.32; 95% CI = [1.05, 1.66]) in the hypothermic group, compared to infants with normothermia on admission. CONCLUSIONS: In our cohort of ELGAN, hypothermia on admission was associated with increased risk of death or sNDI.

Outcome of fetuses with prenatal diagnosis of isolated severe bilateral ventriculomegaly: systematic review and meta-analysis.

OBJECTIVE: To quantify from the published literature survival and neurodevelopmental outcome of fetuses with prenatally detected isolated severe bilateral ventriculomegaly. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched electronically. Only cases with a prenatal diagnosis of apparently isolated severe ventriculomegaly and postnatal neurodevelopmental assessment were selected and included. Severe ventriculomegaly was defined as enlargement of the ventricular atria, with a diameter of greater than 15 mm in the transventricular plane. All cases in which the investigators were unable to detect associated structural abnormality, chromosomal abnormality or fetal infection, and in which the ventriculomegaly was therefore regarded as apparently isolated, were included. Those for which the etiology was identified prenatally were excluded, whereas those with postnatal identification of the underlying cause were not excluded, since this information was not available prenatally. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for cohort studies. Pregnancy outcomes such as termination, stillbirth, neonatal survival and developmental outcome of the baby, were recorded. The degree of disability was classified as no, mild or severe disability. Statistical assessment was performed by meta-analysis of proportions to combine data, weighting the studies using the inverse variance method and a random-effects model. Proportions and CIs were reported. RESULTS: Eleven studies including 137 fetuses were found. Twenty-seven pregnancies underwent termination and were excluded. The remaining 110 fetuses with apparently isolated severe ventriculomegaly for which continuation of pregnancy was intended, form the study population. Overall quality assessed using NOS for cohort studies was good. Survival was reported in 95/110 (pooled proportion 87.9% (95% CI, 75.6-96.2%)) cases. In 15/110 (pooled proportion 12.1% (95% CI, 3.8-24.4%)), either stillbirth or neonatal demise was reported. No disability was reported in 41/95 survivors (pooled proportion 42.2% (95% CI, 27.5-57.6%)). However, 17/95 showed mild/moderate disability (pooled proportion 18.6% (95% CI, 7.2-33.8%)) and 37/95 were reported to have severe disability (pooled proportion 39.6% (95% CI, 30.0-50.0%)). CONCLUSIONS: Four-fifths of fetuses with severe ventriculomegaly survive and, of these, just over two-fifths show normal neurodevelopment. The overall survivors without disability account for more than one third of the total. Given that many cases undergo termination of pregnancy and require longer follow-up in order to detect subtle abnormalities, mortality and prevalence of developmental delay may be even higher than that reported in this paper. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Development and Validation of an Empiric Tool to Predict Favorable Neurologic Outcomes Among PICU Patients.

OBJECTIVES: To create a novel tool to predict favorable neurologic outcomes during ICU stay among children with critical illness. DESIGN: Logistic regression models using adaptive lasso methodology were used to identify independent factors associated with favorable neurologic outcomes. A mixed effects logistic regression model was used to create the final prediction model including all predictors selected from the lasso model. Model validation was performed using a 10-fold internal cross-validation approach. SETTING: Virtual Pediatric Systems (VPS, LLC, Los Angeles, CA) database. PATIENTS: Patients less than 18 years old admitted to one of the participating ICUs in the Virtual Pediatric Systems database were included (2009-2015). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 160,570 patients from 90 hospitals qualified for inclusion. Of these, 1,675 patients (1.04%) were associated with a decline in Pediatric Cerebral Performance Category scale by at least 2 between ICU admission and ICU discharge (unfavorable neurologic outcome). The independent factors associated with unfavorable neurologic outcome included higher weight at ICU admission, higher Pediatric Index of Morality-2 score at ICU admission, cardiac arrest, stroke, seizures, head/nonhead trauma, use of conventional mechanical ventilation and high-frequency oscillatory ventilation, prolonged hospital length of ICU stay, and prolonged use of mechanical ventilation. The presence of chromosomal anomaly, cardiac surgery, and utilization of nitric oxide were associated with favorable neurologic outcome. The final online prediction tool can be accessed at https://soipredictiontool.shinyapps.io/GNOScore/. Our model predicted 139,688 patients with favorable neurologic outcomes in an internal validation sample when the observed number of patients with favorable neurologic outcomes was among 139,591 patients. The area under the receiver operating curve for the validation model was 0.90. CONCLUSIONS: This proposed prediction tool encompasses 20 risk factors into one probability to predict favorable neurologic outcome during ICU stay among children with critical illness. Future studies should seek external validation and improved discrimination of this prediction tool.

Congenital neurodevelopmental anomalies in pediatric and young adult cancer.

Congenital anomalies that are diagnosed in at least 120,000 US infants every year are the leading cause of infant death and contribute to disability and pediatric hospitalizations. Several large-scale epidemiologic studies have provided substantial evidence of an association between congenital anomalies and cancer risk in children, suggesting potential underlying cancer-predisposing conditions and the involvement of developmental genetic pathways. Electronic medical records from 1,107 pediatric, adolescent, and young adult oncology patients were reviewed. The observed number (O) of congenital anomalies among children with a specific pediatric cancer subtype was compared to the expected number (E) of anomalies based on the frequency of congenital anomalies in the entire study population. The O/E ratios were tested for significance using Fisher's exact test. The Kaplan-Meier method was used to compare overall and neurological malignancy survival rates following tumor diagnosis. Thirteen percent of patients had a congenital anomaly diagnosis prior to their cancer diagnosis. When stratified by congenital anomaly subtype, there was an excess of neurological anomalies among children with central nervous system tumors (O/E = 1.56, 95%CI 1.13-2.09). Male pediatric cancer patients were more likely than females to have a congenital anomaly, particularly those <5 years of age (O/E 1.35, 95%CI 0.97-1.82). Our study provides additional insight into the association between specific congenital anomaly types and pediatric cancer development. Moreover, it may help to inform the development of new screening policies and support hypothesis-driven research investigating mechanisms underlying tumor predisposition in children with congenital anomalies.

Restricted Ventilation Associated with Reduced Neurodevelopmental Impairment in Preterm Infants.

BACKGROUND AND OBJECTIVE: Restrictive use of invasive mechanical ventilation (IMV) in preterm infants reduces the risk of bronchopulmonary dysplasia (BPD). Our objective was to determine its effect on neurodevelopmental impairment (NDI) at 24 months' corrected age (CA). METHODS: This retrospective single-center cohort study included all patients with a gestational age <30 weeks born in 2004/2005 (epoch 1) and 2010/2011 (epoch 2). In epoch 2, we introduced a policy of restriction on IMV and liberalized the use of respiratory stimulants in the delivery room and neonatal intensive care. Data on patient characteristics, respiratory management, short-term outcomes, mortality, BPD, and NDI at 24 months' CA were collected. RESULTS: Four hundred and four preterm infants were included. Compared to those in epoch 1, infants in epoch 2 were less likely to be intubated and the duration of IMV was shorter. Other noninvasive adjuvant therapies such as caffeine, doxapram, and nasal ventilation were more often used during epoch 2. There was a trend to less BPD in epoch 2 compared to epoch 1 (17 vs. 23%, adjusted OR = 0.75, 95% CI: 0.48, 1.16). Mortality did not change over time. The combined outcome death or NDI at 24 months' CA was significantly lower in epoch 2 compared to epoch 1 (24.7 vs. 33.9%, adjusted OR = 0.71, 95% CI: 0.53, 0.97). CONCLUSIONS: Restricted use of IMV is feasible in preterm infants and might be associated with a reduced risk of the combined outcome death or NDI at 24 months' CA. Larger studies are needed to confirm these findings.

Oxygen Saturation Targets in Preterm Infants and Outcomes at 18-24 Months: A Systematic Review.

CONTEXT: The optimal oxygen saturation target for extremely preterm infants remains unclear. OBJECTIVE: To systematically review evidence evaluating the effect of lower (85%-89%) versus higher (91%-95%) pulse oxygen saturation (Spo2) target on mortality and neurodevelopmental impairment (NDI) at 18 to 24 months. DATA SOURCES: Electronic databases and all published randomized trials evaluating lower versus higher Spo2 target in preterm infants. STUDY SELECTION: A total of 2896 relevant citations were identified; 5 trials were included in the final analysis. DATA EXTRACTION: Data from 5 trials were analyzed for quality of evidence and risk of bias. LIMITATIONS: Limitations include heterogeneity in age at enrollment and comorbidities between trials and change in oximeter algorithm midway through 3 trials. RESULTS: There was no difference in the incidence of primary outcome (death/NDI at 18-24 months) in the 2 groups; risk ratio,1.05, 95% confidence interval 0.98-1.12, P = .18. Mortality before 18 to 24 months was higher in the lower-target group (risk ratio,1.16, 95% confidence interval 1.03-1.31, P = .02). Rates of NDI and severe visual loss did not differ between the 2 groups. Proportion of time infants spent outside the target range while on supplemental oxygen ranged from 8.2% to 27.4% <85% and 8.1% to 22.4% >95% with significant overlap between the 2 groups. CONCLUSIONS: There was no difference in primary outcome between the 2 Spo2 target groups. The collective data suggest that risks associated with restricting the upper Spo2 target limit to 89% outweigh the benefits. The quality of evidence was moderate. We speculate that a wider target range (lower alarm limit, 89% and upper, 96%) may increase time spent within range, but the safety profile of this approach remains to be determined.

Comparison of two common aEEG classifications for the prediction of neurodevelopmental outcome in preterm infants.

Neurodevelopmental outcome after prematurity is crucial. The aim was to compare two amplitude-integrated EEG (aEEG) classifications (Hellström-Westas (HW), Burdjalov) for outcome prediction. We recruited 65 infants ≤32 weeks gestational age with aEEG recordings within the first 72 h of life and Bayley testing at 24 months corrected age or death. Statistical analyses were performed for each 24 h section to determine whether very immature/depressed or mature/developed patterns predict survival/neurological outcome and to find predictors for mental development index (MDI) and psychomotor development index (PDI) at 24 months corrected age. On day 2, deceased infants showed no cycling in 80% (HW, p = 0.0140) and 100% (Burdjalov, p = 0.0041). The Burdjalov total score significantly differed between groups on day 2 (p = 0.0284) and the adapted Burdjalov total score on day 2 (p = 0.0183) and day 3 (p = 0.0472). Cycling on day 3 (HW; p = 0.0059) and background on day 3 (HW; p = 0.0212) are independent predictors for MDI (p = 0.0016) whereas no independent predictor for PDI was found (multiple regression analyses). CONCLUSION: Cycling in both classifications is a valuable tool to assess chance of survival. The classification by HW is also associated with long-term mental outcome. What is Known: •Neurodevelopmental outcome after preterm birth remains one of the major concerns in neonatology. •aEEG is used to measure brain activity and brain maturation in preterm infants. What is New: •The two common aEEG classifications and scoring systems described by Hellström-Westas and Burdjalov are valuable tools to predict neurodevelopmental outcome when performed within the first 72 h of life. •Both aEEG classifications are useful to predict chance of survival. The classification by Hellström-Westas can also predict long-term outcome at corrected age of 2 years.

Association of Antenatal Corticosteroids With Mortality, Morbidity, and Neurodevelopmental Outcomes in Extremely Preterm Multiple Gestation Infants.

IMPORTANCE: Little is known about the effects of antenatal corticosteroids (ANS) on extremely preterm multiples. OBJECTIVE: To examine if use of ANS is associated with improvement in major outcomes in extremely preterm multiples. DESIGN, SETTING, AND PARTICIPANTS: Infants with a gestational age between 22 and 28 weeks born at a National Institute of Child Health and Human Development Neonatal Research Network center were studied between January 1998 and December 2013. Generalized estimating equation models were used to generate adjusted relative risks (aRR) controlling for important maternal and neonatal variables. EXPOSURE: Antenatal corticosteroids. MAIN OUTCOMES AND MEASURES: In-hospital mortality and the composite outcome of neurodevelopmental impairment at 18 to 22 months' corrected age or death before assessment. RESULTS: A total of 6925 multiple-birth infants were studied; 5775 of 6925 (83.4%) were twins, and 4276 (61.7%) were white. Of the total study population, 6094 (88%) were born to women who received ANS. In-hospital mortality was lower among infants with exposure to ANS vs no exposure (aRR = 0.87; 95% CI, 0.78-0.96). Neurodevelopmental impairment or death was not significantly lower among those exposed to ANS vs no exposure (aRR = 0.93; 95% CI, 0.84-1.03). Other adverse outcomes that occurred less frequently among infants of women receiving ANS included severe intraventricular hemorrhage (aRR = 0.68; 95% CI, 0.58-0.78) and the combined outcomes of necrotizing enterocolitis or death and severe intraventricular hemorrhage or death. Subgroup analyses indicated that exposure to ANS was associated with a lower risk of mortality and a lower composite of neurodevelopmental impairment or mortality among nonsmall for gestational age multiples (aRR = 0.82; 95% CI, 0.74-0.92; and aRR = 0.89; 95% CI, 0.80-0.98, respectively) and a higher risk among small for gestational age multiples (aRR = 1.40; 95% CI, 1.02-1.93; and aRR = 1.62; 95% CI, 1.22-2.16, respectively). Antenatal corticosteroids were associated with higher neurodevelopmental impairment or mortality among multiple-birth infants of mothers with diabetes (aRR = 1.55; 95% CI, 1.00-2.38) but not among infants of mothers without diabetes (aRR = 0.91; 95% CI, 0.83-1.01). CONCLUSIONS AND RELEVANCE: Compared with no exposure, exposure to ANS was associated with a lower risk of mortality in extremely preterm multiples, with no significant differences in the composite of neurodevelopmental impairment or death. Future research should investigate the increased risks of mortality and the composite of neurodevelopmental impairment or death associated with exposure to corticosteroids among small for gestational age multiples.