Neonatal macrocephaly: cerebral primitive neuroectodermal tumor or neuroblastoma as an infrequent cause--a case report and review of the literature

We report a male term newborn presenting with a congenital macrocephaly 3.5 standard deviations above the median, with a wide and tense anterior fontanel, splayed calvarial sutures, and muscular hypotonia. Antenatal head circumferences were repeatedly below the median. A postnatal head ultrasound showed a large right intracerebral mass with right lateral ventricle compression, right temporal horn dilation, and right frontal horn enlargement with lateral displacement. Additional imaging by computed tomography scan and magnetic resonance imaging was performed. A decompression was performed and histology, immunohistochemistry, and molecular biology supported the diagnosis of a primitive neuroectodermal tumor. A MYCN gene amplification assay remained negative. The incidence of neonatal brain tumors is between 1.4 and 4.1/100,000 live births. Their most common presentation is macrocephaly, hydrocephalus, stillbirth, or diagnosis by pre- or postnatal imaging. Although hydrocephaly and intra- or extracranial hemorrhage are the most frequent causes of congenital macrocephaly, this should be initially investigated by head ultrasound. A suspected malignancy will be confirmed by histopathology, immunohistochemistry, and molecular biology

Pathophysiology of Perinatal Asphyxia in Humans and Animal Models

Perinatal asphyxia is caused by lack of oxygen delivery (hypoxia) to end organs due to an hypoxemic or ischemic insult occurring in temporal proximity to labor (peripartum) or delivery (intrapartum). Hypoxic–ischemic encephalopathy is the clinical manifestation of hypoxic injury to the brain and is usually graded as mild, moderate, or severe. The search for useful biomarkers to precisely predict the severity of lesions in perinatal asphyxia and hypoxic–ischemic encephalopathy (HIE) is a field of increasing interest. As pathophysiology is not fully comprehended, the gold standard for treatment remains an active area of research. Hypothermia has proven to be an effective neuroprotective strategy and has been implemented in clinical routine. Current studies are exploring various add-on therapies, including erythropoietin, xenon, topiramate, melatonin, and stem cells. This review aims to perform an updated integration of the pathophysiological processes after perinatal asphyxia in humans and animal models to allow us to answer some questions and provide an interim update on progress in this field.Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedFacultyResearcherOthe

Impact of study oximeter masking algorithm on titration of oxygen therapy in the canadian oxygen trial

OBJECTIVE: To compare oxygen saturations as displayed to caregivers on offset pulse oximeters in the 2 groups of the Canadian Oxygen Trial. STUDY DESIGN: In 5 double-blind randomized trials of oxygen saturation targeting, displayed saturations between 88% and 92% were offset by 3% above or below the true values but returned to true values below 84% and above 96%. During the transition, displayed values remained static at 96% in the lower and at 84% in the higher target group during a 3% change in true saturations. In contrast, displayed values changed rapidly from 88% to 84% in the lower and from 92% to 96% in the higher target group during a 1% change in true saturations. We plotted the distributions of median displayed saturations on days with >12 hours of supplemental oxygen in 1075 Canadian Oxygen Trial participants to reconstruct what caregivers observed at the bedside. RESULTS: The oximeter masking algorithm was associated with an increase in both stability and instability of displayed saturations that occurred during the transition between offset and true displayed values at opposite ends of the 2 target ranges. Caregivers maintained saturations at lower displayed values in the higher than in the lower target group. This differential management reduced the separation between the median true saturations in the 2 groups by approximately 3.5%. CONCLUSIONS: The design of the oximeter masking algorithm may have contributed to the smaller-than-expected separation between true saturations in the 2 study groups of recent saturation targeting trials in extremely preterm infants

Prediction of late death or disability at age 5 years using a count of 3 neonatal morbidities in very low birth weight infants

OBJECTIVE To evaluate bronchopulmonary dysplasia (BPD), serious brain injury, and severe retinopathy of prematurity (ROP) as predictors of poor long-term outcome in very low birth weight infants. STUDY DESIGN We examined the associations between counts of the 3 morbidities and long-term outcomes in 1514 of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long-term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more of the following disabilities: motor impairment, cognitive impairment, behavior problems, poor general health, deafness, and blindness. RESULTS BPD, serious brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants, respectively. Each of the 3 morbidities was similarly and independently correlated with poor 5-year outcome. Rates of death or disability (95% CI) in children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%), 22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively. CONCLUSIONS In very low birth weight infants who survive to 36 weeks PMA, a count of BPD, serious brain injury, and severe ROP predicts the risk of a late death or survival with disability at 5 years

Prevention and 18-month outcomes of serious pulmonary hemorrhage in extremely low birth weight infants: Results from the trial of indomethacin prophylaxis in preterms

OBJECTIVES. A patent ductus arteriosus is a risk factor for pulmonary hemorrhage; however, despite halving the incidence of patent ductus arteriosus, indomethacin prophylaxis did not reduce the rate of pulmonary hemorrhage in the Trial of Indomethacin Prophylaxis in Preterms. Inclusion of mild bleeds after trauma to the upper airways may have masked a beneficial drug effect. Using the Trial of Indomethacin Prophylaxis in Preterms database, we studied the effect of prophylactic indomethacin on the prevention of serious hemorrhages in extremely low birth weight infants. We also compared the 18-month outcomes of infants with and without a serious pulmonary bleed. METHODS. Pulmonary hemorrhage was classified as serious when it was treated with increased ventilator support, a higher concentration of oxygen, or transfusion of blood products. The cumulative risk for serious pulmonary hemorrhage was estimated for the first week of life and for the entire NICU stay. Poor outcome at a corrected age of 18 months was death or survival with cerebral palsy, cognitive delay, blindness, and/or deafness. RESULTS. A total of 123 (10.2%) of 1202 infants developed a serious pulmonary hemorrhage. During week 1, prophylactic indomethacin reduced the risk for serious pulmonary hemorrhage by 35%; however, during the entire NICU stay, the risk for such hemorrhages was decreased by only 23%. A reduced risk for patent ductus arteriosus explained 80% of the beneficial effect of prophylactic indomethacin on serious pulmonary bleeds. The risks for death or for survival with neurosensory impairment were doubled after a serious pulmonary hemorrhage. CONCLUSIONS. Extremely low birth weight infants with serious pulmonary hemorrhage have an increased risk for poor long-term outcome. Prophylactic indomethacin reduces the rate of early serious pulmonary hemorrhage, mainly through its action on patent ductus arteriosus. Prophylactic indomethacin is less effective in preventing serious pulmonary hemorrhages that occur after the first week of life. Copyrigh

Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants

Importance Extremely preterm infants may experience intermittent hypoxemia or bradycardia for many weeks after birth. The prognosis of these events is uncertain. Objective To determine the association between intermittent hypoxemia or bradycardia and late death or disability. Design, Setting, and Participants Post hoc analysis of data from the inception cohort assembled for the Canadian Oxygen Trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel, including 1019 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days who were born between December 2006 and August 2010 and survived to a postmenstrual age of 36 weeks. Follow-up assessments occurred between October 2008 and August 2012. Exposures Episodes of hypoxemia (pulse oximeter oxygen saturation <80%) or bradycardia (pulse rate <80/min) for 10 seconds or longer. Values were sampled every 10 seconds within 24 hours after birth until at least 36 weeks’ postmenstrual age. Main Outcomes and Measures The primary outcome was a composite of death after 36 weeks’ postmenstrual age, motor impairment, cognitive or language delay, severe hearing loss, or bilateral blindness at 18 months’ corrected age. Secondary outcomes were motor impairment, cognitive or language delay, and severe retinopathy of prematurity. Results Downloaded saturation and pulse rate data were available for a median of 68.3 days (interquartile range, 56.8-86.0 days). Mean percentages of recorded time with hypoxemia for the least and most affected 10% of infants were 0.4% and 13.5%, respectively. Corresponding values for bradycardia were 0.1% and 0.3%. The primary outcome was ascertained for 972 infants and present in 414 (42.6%). Hypoxemic episodes were associated with an estimated increased risk of late death or disability at 18 months of 56.5% in the highest decile of hypoxemic exposure vs 36.9% in the lowest decile (modeled relative risk, 1.53; 95% CI, 1.21-1.94). This association was significant only for prolonged hypoxemic episodes lasting at least 1 minute (relative risk, 1.66; 95% CI, 1.35-2.05 vs for shorter episodes, relative risk, 1.01; 95% CI, 0.77-1.32). Relative risks for all secondary outcomes were similarly increased after prolonged hypoxemia. Bradycardia did not alter the prognostic value of hypoxemia. Conclusions and Relevance Among extremely preterm infants who survived to 36 weeks’ postmenstrual age, prolonged hypoxemic episodes during the first 2 to 3 months after birth were associated with adverse 18-month outcomes. If confirmed in future studies, further research on the prevention of such episodes is needed

Respiratory syncytial virus-neutralizing serum antibody titers in infants following palivizumab prophylaxis with an abbreviated dosing regimen

<div><p>Background</p><p>Monthly injections of palivizumab during the respiratory syncytial virus (RSV) season in at-risk infants reduces RSV-associated hospitalizations. However, the additive effect of naturally acquired immunity remains unclear. The objective of this study was to assess total neutralizing serum antibodies (NAb) against RSV in at-risk infants who had received an abbreviated course of palivizumab prophylaxis.</p><p>Methods</p><p>Serum samples were collected from infants enrolled in the RSV Immunoprophylaxis Program in British Columbia, Canada over 2 consecutive RSV seasons (2013 to 2015). Infants in this program had received an abbreviated course of palivizumab in accordance with the provincial guidelines. Data were compared to adults and infants less than 12 months of age who did not receive palivizumab. Anti-RSV NAb titers were measured using an RSV microneutralization assay.</p><p>Findings</p><p>Infants who received palivizumab had anti-RSV NAb titers at the end of the RSV season that persisted beyond what is expected from the pharmacokinetics of palivizumab alone. Moreover, 54% of the control infants who did not receive palivizumab and all tested adults had protective anti-RSV NAb titers.</p><p>Conclusions</p><p>Based on our observations, we hypothesize that naturally acquired NAb provide additive protection, which may significantly reduce the need for additional doses of palivizumab in infants at risk of severe RSV infections.</p></div

Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity

CONTEXT: Very preterm infants are prone to apnea and have an increased risk of death or disability. Caffeine therapy for apnea of prematurity reduces the rates of cerebral palsy and cognitive delay at 18 months of age. OBJECTIVE: To determine whether neonatal caffeine therapy has lasting benefits or newly apparent risks at early school age. DESIGN, SETTING, AND PARTICIPANTS: Five-year follow-up from 2005 to 2011 in 31 of 35 academic hospitals in Canada, Australia, Europe, and Israel, where 1932 of 2006 participants (96.3%) had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial between 1999 and 2004. A total of 1640 children (84.9%) with birth weights of 500 to 1250 g had adequate data for the main outcome at 5 years. MAIN OUTCOME MEASURES: Combined outcome of death or survival to 5 years with 1 or more of motor impairment (defined as a Gross Motor Function Classification System level of 3 to 5), cognitive impairment (defined as a Full Scale IQ<70), behavior problems, poor general health, deafness, and blindness. RESULTS: The combined outcome of death or disability was not significantly different for the 833 children assigned to caffeine from that for the 807 children assigned to placebo (21.1% vs 24.8%; odds ratio adjusted for center, 0.82; 95% CI, 0.65-1.03; P = .09). The rates of death, motor impairment, behavior problems, poor general health, deafness, and blindness did not differ significantly between the 2 groups. The incidence of cognitive impairment was lower at 5 years than at 18 months and similar in the 2 groups (4.9% vs 5.1%; odds ratio adjusted for center, 0.97; 95% CI, 0.61-1.55; P = .89). CONCLUSION: Neonatal caffeine therapy was no longer associated with a significantly improved rate of survival without disability in children with very low birth weights who were assessed at 5 years