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To describe patterns of renal and hepatic injury in infants with hypoxic ischemic encephalopathy (HIE).Retrospective cohort of infants receiving therapeutic hypothermia for HIE was classified into groups based on organ injury: neither acute kidney injury (AKI) nor acute hepatic injury (AHI), isolated AKI, isolated AHI, or both AKI/AHI. Biomarkers and outcomes were described and analyzed.Among 188 infants, 55% had no AKI nor AHI, 7% had only AKI, 22% had only AHI and 16% had both AKI and AHI. Infants with both AKI/AHI had the highest mortality (47%) and worse outcomes, compared to other injury groups, although AKI/AHI was not significantly associated with mortality (hazard ratio 2.5; 95% CI 0.9-6.9), after accounting for severity of HIE. For surviving infants, biomarkers of organ injury, on average, normalized by discharge.Infants with HIE with both AKI/AHI have worse outcomes than infants with AKI or AHI alone.

Objective To compare treatment failure between: (1) infants treated with phenobarbital versus levetiracetam for first-line treatment and (2) infants treated with phenytoin versus levetiracetam for second-line treatment following phenobarbital. Study design This retrospective cohort study included infants with seizures receiving phenobarbital or levetiracetam as the initial anti-seizure medication. Treatment failure was defined as the need for additional anti-seizure medication within 24-72 h and compared using mixed-effect logistic regression after adjustment for confounding factors, including center. Results In this cohort of 6842 infants, the incidence of treatment failure was 31% vs. 38% in infants receiving first-line phenobarbital versus levetiracetam (adjusted OR: 0.70; 95% CI 0.58-0.84). There was no significant difference in second-line treatment failure (adjusted OR: 1.31; 95% CI 0.92-1.86). Conclusions First-line treatment of neonatal seizures with phenobarbital is associated with a lower rate of treatment failure than levetiracetam. There was no significant difference in second-line treatment failure.

Our hypothesis was that among infants with hypoxic-ischemic encephalopathy (HIE), venoarterial (VA), compared to venovenous (VV), extracorporeal membrane oxygenation (ECMO) is associated with an increased risk of mortality or intracranial hemorrhage (ICH). Retrospective cohort analysis of infants in the Children’s Hospitals Neonatal Database from 2010 to 2016 with moderate or severe HIE, gestational age ≥36 weeks, and ECMO initiation

To determine practice variation in the utilization of neuromonitoring modalities in neonatal extracorporeal membrane oxygenation (ECMO) patients across Level IV neonatal intensive care units (NICUs). Cross-sectional survey design using electronic surveys sent to site sponsors of a multicenter collaborative of 34 Level IV NICUs of the Children’s Hospitals Neonatal Consortium (CHNC) from June to August 2018. We had 22 survey respondents from CHNC ECMO centers. Twenty-seven percent of respondents routinely monitored for seizures using electroencephalogram. Cerebral near infrared spectroscopy was used by 50%. Head ultrasound was performed by 95% but the frequency, duration, and type of views varied. Post ECMO screening brain MRI prior to hospital discharge was routinely performed by 77% of respondents. A majority of centers (95%) performed neurodevelopmental follow-up after hospital discharge. There is variation in neuromonitoring practices in Level IV NICUs performing ECMO. Lack of evidence and clear outcome benefits has contributed to practice variation across institutions.

Background While intercenter variation (ICV) in anti-epileptic drug (AED) use in neonates with seizures has been previously reported, variation in AED practices across regional NICUs has not been specifically and systematically evaluated. This is important as these centers typically have multidisciplinary neonatal neurocritical care teams and protocolized approaches to treating conditions such as hypoxic ischemic encephalopathy (HIE), a population at high risk for neonatal seizures. To identify opportunities for quality improvement (QI), we evaluated ICV in AED utilization for neonates with HIE treated with therapeutic hypothermia (TH) across regional NICUs in the US. Methods Children’s Hospital Neonatal Database and Pediatric Health Information Systems data were linked for 1658 neonates ≥36 weeks’ gestation, > 1800 g birthweight, with HIE treated with TH, from 20 NICUs, between 2010 and 2016. ICV in AED use was evaluated using a mixed-effect regression model. Rates of AED exposure, duration, prescription at discharge and standardized AED costs per patient were calculated as different measures of utilization. Results Ninety-five percent (range: 83–100%) of patients with electrographic seizures, and 26% (0–81%) without electrographic seizures, received AEDs. Phenobarbital was most frequently used (97.6%), followed by levetiracetam (16.9%), phenytoin/fosphenytoin (15.6%) and others (2.4%; oxcarbazepine, topiramate and valproate). There was significant ICV in all measures of AED utilization. Median cost of AEDs per patient was $89.90 (IQR $24.52,$258.58). Conclusions Amongst Children’s Hospitals, there is marked ICV in AED utilization for neonatal HIE. Variation was particularly notable for HIE patients without electrographic seizures, indicating that this population may be an appropriate target for QI processes to harmonize neuromonitoring and AED practices across centers.

OBJECTIVES: To develop predictive models for death or neurodevelopmental impairment (NDI) after neonatal hypoxic-ischemic encephalopathy (HIE) from data readily available at the time of NICU admission (“early”) or discharge (“cumulative”). METHODS: In this retrospective cohort analysis, we used data from the Children’s Hospitals Neonatal Consortium Database (2010–2016). Infants born at ≥35 weeks’ gestation and treated with therapeutic hypothermia for HIE at 11 participating sites were included; infants without Bayley Scales of Infant Development scores documented after 11 months of age were excluded. The primary outcome was death or NDI. Multivariable models were generated with 80% of the cohort; validation was performed in the remaining 20%. RESULTS: The primary outcome occurred in 242 of 486 infants; 180 died and 62 infants surviving to follow-up had NDI. HIE severity, epinephrine administration in the delivery room, and respiratory support and fraction of inspired oxygen of 0.21 at admission were significant in the early model. Severity of EEG findings was combined with HIE severity for the cumulative model, and additional significant variables included the use of steroids for blood pressure management and significant brain injury on MRI. Discovery models revealed areas under the curve of 0.852 for the early model and of 0.861 for the cumulative model, and both models performed well in the validation cohort (goodness-of-fit χ2: P = .24 and .06, respectively). CONCLUSIONS: Establishing reliable predictive models will enable clinicians to more accurately evaluate HIE severity and may allow for more targeted early therapies for those at highest risk of death or NDI.

Objective This study was aimed to describe utilization of therapeutic hypothermia (TH) in neonates presenting with mild hypoxic-ischemic encephalopathy (HIE) and associated neurological injury on magnetic resonance imaging (MRI) scans in these infants. Study Design Neonates ≥ 36 weeks' gestation with mild HIE and available MRI scans were identified. Mild HIE status was assigned to hyper alert infants with an exaggerated response to arousal and mild HIE as the highest grade of encephalopathy recorded. MRI scans were dichotomized as “injury” versus “no injury.” Results A total of 94.5% (257/272) neonates with mild HIE, referred for evaluation, received TH. MRI injury occurred in 38.2% (104/272) neonates and affected predominantly the white matter (49.0%, n = 51). Injury to the deep nuclear gray matter was identified in (10.1%) 20 infants, and to the cortex in 13.4% (n = 14 infants). In regression analyses (odds ratio [OR]; 95% confidence interval [CI]), history of fetal distress (OR = 0.52; 95% CI: 0.28–0.99) and delivery by caesarian section (OR = 0.54; 95% CI: 0.31–0.92) were associated with lower odds, whereas medical comorbidities during and after cooling were associated with higher odds of brain injury (OR = 2.31; 95% CI: 1.37–3.89). Conclusion Majority of neonates with mild HIE referred for evaluation are being treated with TH. Odds of neurological injury are over two-fold higher in those with comorbidities during and after cooling. Brain injury predominantly involved the white matter. Key Points

Quantify antimicrobial therapy (AMT) use in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia (HIE/TH). Newborns with HIE/TH were identified from the Children’s Hospital Neonatal Database (CHND). Early infection (onset ≤7 days of life) was defined as “confirmed” (culture proven) or “suspected infection” (culture negative but treated) and compared with a “no infection” group. 1501/1534 (97.8%) neonates received AMT. 36 (2.3%) had confirmed, 255 (16.6%) suspected, and 1243 (81.0%) had no infection. The median (IQR) AMT duration was 13 (8–21), 8 (7–10), and 3 (3–7) days for the three groups, respectively (p

Purpose We describe the frequency and timing of withdrawal of life-support (WLS) in moderate or severe hypoxic-ischemic encephalopathy (HIE) and examine its associations with medical and sociodemographic factors. Procedures We undertook a secondary data analysis of a prospective multicenter data registry of regional level IV Neonatal Intensive Care Units participating in the Children's Hospitals Neonatal Database. Infants ≥36 weeks gestational age with HIE admitted to a Children's Hospitals Neonatal Database Neonatal Intensive Care Unit between 2010 and 2016, who underwent therapeutic hypothermia were categorized as (1) infants who died following WLST and (2) survivors with severe HIE (requiring tube feedings at discharge). Results Death occurred in 267/1,925 (14%) infants with HIE, 87.6% following WLS. Compared to infants with WLS (n = 234), the survived severe group (n = 74) had more public insurance (73% vs 39.3%, P = 0.00001), lower household income ($37,020 vs $41,733, P = 0.006) and fewer [20.3% vs 35.0%, P = 0.0212] were from the South. Among infants with WLS, electroencephalogram was performed within 24 hours in 75% and was severely abnormal in 64% cases; corresponding rates for MRI were 43% and 17%, respectively. Private insurance was independently associated with WLS, after adjustment for HIE severity and center. Conclusions In a multicenter cohort of infants with HIE, WLS occurred frequently and was associated with sociodemographic factors. The rationale for decision-making for WLS in HIE require further exploration.

Introduction Amplitude-integrated EEG (aEEG) monitoring is increasing in the neonatal population, but the safety and feasibility of performing aEEG in extremely preterm infants have not been systematically evaluated. Methods Inborn infants 230/7 – 286/7 weeks gestation or birth weight 401–1000 grams were eligible. Serial, six-hour aEEG recordings were obtained from first week of life until 36 weeks postmenstrual age. Adverse events were documented, and surveys evaluated the impact of the aEEGs on routine care. Success of performing aEEGs according to protocol and aEEG quality were assessed. Results 102 infants were enrolled, with 755 recordings performed. 83% of recordings were performed according to schedule, and 96% were without adverse event. Bedside nurses reported no interference with routine care for 89% of recordings. 92% of recordings had acceptable signal quality. Conclusions Serial aEEG monitoring is safe in preterm infants, with few adverse events and general acceptance by nursing staff.

The purpose of this study is to characterize the cytokine response of preterm newborns with surgical necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP) before surgical treatment and to relate these finding to intestinal disease (NEC vs. SIP).The study was a 14-month prospective, cohort study of neonates undergoing surgery or drainage for NEC or SIP or surgical ligation of patent ductus arteriosus (PDA). Multiplex cytokine detection technology was used to analyze six inflammatory markers: interleukin-2, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 β (IL-1β), interferon-gamma, and tumor necrosis factor-α (TNF-α).Patients with NEC had much higher median preoperative levels of IL-6 (NEC: 8,381 pg/mL; SIP: 36 pg/mL; PDA: 25 pg/mL, p 0.001), IL-8 (NEC: 18,438 pg/mL; SIP: 2,473 pg/mL; PDA: 1,110 pg/mL, p = 0.001), TNF-α (NEC: 161 pg/mL; SIP: 77 pg/mL; PDA: 71 pg/mL, p 0.001), and IL-1β (NEC: 85 pg/mL; SIP: 31 pg/mL; PDA: 24 pg/mL, p = 0.001). Patients with NEC totalis (NEC-totalis had the highest levels of IL-8 and were significantly different from infants with limited NEC (28,141 vs. 11,429 pg/mL, p = 0.03).Surgical NEC is a profoundly more proinflammatory disease than SIP. The cytokine profiles of patients with SIP are closer to those of a nonseptic surgical neonate.

Our objective was to evaluate the relationship between congenital gastrointestinal anomalies requiring neonatal surgery and neurodevelopmental outcome. Among the children born in metropolitan Atlanta during 1982–2001 who survived to age 1 year (N = 762,824), we identified children with congenital gastrointestinal anomalies via linkage with the Metropolitan Atlanta Congenital Defects Program and children who received special education services via linkage with the Special Education Database of Metropolitan Atlanta. Several modest increases in special education service use were observed among children with isolated congenital gastrointestinal anomalies; no association was statistically significant. Among children with Hirschsprung disease, gastroschisis, esophageal atresia, intestinal malrotation, bowel atresia, or imperforate anus who had multiple anomalies, we observed statistically significant increases in special education service use.

Postnatal ductal closure is stimulated by rising oxygen tension and withdrawal of vasodilatory mediators (prostaglandins, nitric oxide, adenosine) and by vasoconstrictors (endothelin-1, catecholamines, contractile prostanoids), ion channels, calcium flux, platelets, morphologic maturity, and a favorable genetic predisposition. A persistently patent ductus arteriosus (PDA) in preterm infants can have clinical consequences. Decreasing pulmonary vascular resistance, especially in extremely low gestational age newborns, increases left-to-right shunting through the ductus and increases pulmonary blood flow further, leading to interstitial pulmonary edema and volume load to the left heart. Potential consequences of left-to-right shunting via a hemodynamically significant patent ductus arteriosus (hsPDA) include increased risk for prolonged ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis or focal intestinal perforation, intraventricular hemorrhage, and death. In the last decade, there has been a trend toward less aggressive treatment of PDA in preterm infants. However, there is a subgroup of infants who will likely benefit from intervention, be it pharmacologic, interventional, or surgical: (1) prophylactic intravenous indomethacin in highly selected extremely low gestational age newborns with PDA (

Although cesarean deliveries frequently are performed for anomalous fetal conditions, available data do not always support a fetal benefit from this delivery management. The literature on cesarean delivery for anomalous infants reports insufficient information on comorbid neonatal conditions, so these complications are unknown in this population of newborns. In a minority of cases, a cesarean delivery is reasonable to prevent dystocia or optimize outcome. Areas for future investigation include prospective, randomized, controlled trials of prelabor cesarean compared with vaginal deliveries for myelomeningocele and anterior abdominal wall defects. The rarity of other lesions likely precludes randomized controlled trials.

The objective was to determine whether an elevated nucleated red blood cell count at birth after perinatal depression is associated with brain injury as measured by (1) proton magnetic resonance spectroscopy and (2) abnormal neurodevelopmental outcome at 30 months of age. The nucleated red blood cell counts from the first 24 hours of life were statistically analyzed in 33 term infants enrolled in a prospective study of the value of magnetic resonance imaging for the determination of neurodevelopmental outcome after perinatal depression. Nucleated red blood cell counts were elevated in 13/33 (39%). Abnormal outcome (19/33, 54%) was associated with Score for Neonatal Acute Physiology-Perinatal Extension (P = 0.04), decreased N-acetylaspartate to choline ratio in the basal ganglia (P = 0.009), and increased lactate to choline ratio in the basal ganglia (P = 0.02), but not with cord pH, Apgar score, or nucleated red blood cell value. In a logistic regression model, increasing nucleated red blood cell counts did not increase the odds of an abnormal outcome at 30 months of age (OR 1.02, P = 0.17). In a population of neonates with perinatal depression, the nucleated red blood cell count at birth does not correlate with magnetic resonance spectroscopy or 30-month neurodevelopmental outcome. The nucleated red blood cell count should not be used as a surrogate marker for subsequent brain injury.

Importance Reduced death and neurodevelopmental impairment among infants is a goal of perinatal medicine. Objective To assess the association between surgery during the initial hospitalization and death or neurodevelopmental impairment of very low-birth-weight infants. Design, Setting, and Participants A retrospective cohort analysis was conducted of patients enrolled in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database from 1998 through 2009 and evaluated at 18 to 22 months’ corrected age. Twenty-two academic neonatal intensive care units participated. Inclusion criteria were birth weight 401 to 1500 g, survival to 12 hours, and availability for follow-up. A total of 12 111 infants were included in analyses. Exposures Surgical procedures; surgery also was classified by expected anesthesia type as major (general anesthesia) or minor (nongeneral anesthesia). Main Outcomes and Measures Multivariable logistic regression analyses planned a priori were performed for the primary outcome of death or neurodevelopmental impairment and for the secondary outcome of neurodevelopmental impairment among survivors. Multivariable linear regression analyses were performed as planned for the adjusted mean scores of the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development, Second Edition, for patients born before 2006. Results A total of 2186 infants underwent major surgery, 784 had minor surgery, and 9141 infants did not undergo surgery. The risk-adjusted odds ratio of death or neurodevelopmental impairment for all surgery patients compared with those who had no surgery was 1.29 (95% CI, 1.08-1.55). For patients who had major surgery compared with those who had no surgery, the risk-adjusted odds ratio of death or neurodevelopmental impairment was 1.52 (95% CI, 1.24-1.87). Patients classified as having minor surgery had no increased adjusted risk. Among survivors who had major surgery compared with those who had no surgery, the adjusted risk of neurodevelopmental impairment was greater and the adjusted mean Bayley scores were lower. Conclusions and Relevance Major surgery in very low-birth-weight infants is independently associated with a greater than 50% increased risk of death or neurodevelopmental impairment and of neurodevelopmental impairment at 18 to 22 months’ corrected age. The role of general anesthesia is implicated but remains unproven.

White matter injury (WMI) is a known complication following neonatal heart surgery in term infants. In preterm infants, WMI has been associated with the degree of systemic inflammation. It is not known whether inflammation is an important mechanism of WMI as documented by magnetic resonance imaging (MRI) following neonatal heart surgery with cardiopulmonary bypass. Term neonates with congenital heart disease were enrolled in a prospective study with postoperative MRI. White matter injury was recorded by the number of T1 hyperintense foci with >5 foci consistent with significant WMI. Eleven candidate cytokine markers (INF-gamma, TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-13) were assayed preoperatively and daily for 5 days following surgery. Multiple clinical factors were recorded and correlated with WMI. Ninety-two subjects were enrolled in the study. The median age at surgery was 5 days (interquartile range 4-7 days). Compared with the presurgery level, there were statistically significant increases (p < 0.005) for 8 out of 11 inflammatory markers. In all, 64 postoperative MRIs were performed. No significant correlation was detected between WMI and clinical variables or inflammatory markers assessed immediately postoperative and on postoperative days 1 and 3, with exception of IL-1 beta on postoperative day 1. WMI correlates poorly with the systemic inflammatory response after congenital heart surgery and a number of herein measured clinical factors. WMI following neonatal heart surgery is a complex, still incompletely understood phenomenon that warrants continued investigation.

This report describes the case of a neonate who underwent fetal surgery for congenital diaphragmatic hernia (CDH) and pulmonary sequestration. His postnatal management was complicated by the additional diagnosis of transposition of the great arteries (TGA). TGA is particularly difficult to diagnose in the fetus. This triad has not previously been documented in the literature. Clinicians should have a high index of suspicion for associated anomalies, especially cardiac, when evaluating and counseling a pregnancy complicated by CDH.

Little is known about the outcomes of extremely low birth weight (ELBW) preterm infants with congenital heart defects (CHDs). The aim of this study was to assess the mortality, morbidity, and early childhood outcomes of ELBW infants with isolated CHD compared with infants with no congenital defects. Participants were 401–1,000 g infants cared for at National Institute of Child Health and Human Development Neonatal Research Network centers between January 1, 1998, and December 31, 2005. Neonatal morbidities and 18–22 months’ corrected age outcomes were assessed. Neurodevelopmental impairment (NDI) was defined as moderate to severe cerebral palsy, Bayley II mental or psychomotor developmental index

Recent evidence suggests that the current ILCOR guidelines regarding hypothermia for the treatment of neonatal encephalopathy need urgent revision. In 2005 when the current ILCOR guidelines were finalised one large (CoolCap trial, n = 235) and one small RCT (n = 67), in addition to pilot trials, had been published, and demonstrated that therapeutic hypothermia after perinatal asphyxia was safe. The CoolCap trial showed a borderline overall effect on death and disability at 18 months of age, but significant improvement in a large subset of infants with less severe electroencephalographic changes. Based on this and other available evidence, the 2005 ILCOR guidelines supported post resuscitation hypothermia in paediatric patients after cardiac arrest, but not after neonatal resuscitation. Subsequently, a whole body cooling trial supported by the NICHD reported a significant overall improvement in death or disability. Further large neonatal trials of hypothermia have stopped recruitment and their final results are likely to be published 2009–2011. Many important questions around the optimal therapeutic use of hypothermia remain to be answered. Nevertheless, independent meta-analyses of the published trials now indicate a consistent, robust beneficial effect of therapeutic hypothermia for moderate to severe neonatal encephalopathy, with a mean NNT between 6 and 8. Given that there is currently no other clinically proven treatment for infants with neonatal encephalopathy we propose that an interim advisory statement should be issued to support and guide the introduction of therapeutic hypothermia into routine clinical practice.

To compare changes in regional cerebral or flank oxygen saturation measured by near-infrared spectroscopy with changes in central venous oxygen saturation (ScvO2) and to determine clinical variables associated with these changes.Prospective observational cohort study.University tertiary care center, pediatric cardiac intensive care unit.Seventy postoperative congenital cardiac surgical patients (median age 0.3 yrs; interquartile range 0.02-0.46 yrs).None.We measured temporally correlated regional oxygen saturation (rSO2) with hematologic (hematocrit), biochemical (arterial blood gas, ScvO2, and lactate) and physiologic (temperature, heart rate, mean blood pressure, and pulse oximetry) variables in the first postoperative day. Cerebral and flank rSO2 were strongly correlated with ScvO2, in both cyanotic or acyanotic patients and single- or two-ventricle physiology with and without aortic arch obstruction (all p.001). However, individual values had wide limits of agreement on Bland-Altman analysis. The correlations of change in these measurements were weaker but still significant (all p.0001), again with wide limits of agreement. Similar direction of change in cerebral rSO2 and ScvO2 was present 64% (95% confidence interval, 55-73%) of the time. Change in arterial pressure of carbon dioxide (delta PaCO2) was associated with cerebral delta rSO2 (delta PaCO2 beta = 0.35, p.0001) but not flank delta rSO2 or delta ScvO2. A pattern of relative cerebral desaturation (flank rSO2cerebral rSO2) was noted in a majority of patients (81%) with two-site monitoring regardless of bypass method or age.Neither individual values nor changes in rSO2 are interchangeable measures of ScvO2 in postoperative pediatric cardiac patients. The unique relationship between changes in PaCO2 and cerebral rSO2 supports the hypothesis that cerebral near-infrared spectroscopy monitors regional cerebral oxygenation. Clinical application of this monitor must include recognition of the clinical variables that affect regional brain oxygenation.

OBJECTIVES. Newborns delivered before 28 weeks' gestation commonly have white matter lesions on MRI that are associated with adverse neurodevelopmental outcomes. Our objective was to determine the risk factors for MRI-detectable white matter injury in infants delivered before 28 weeks' gestation who were treated with prophylactic indomethacin.METHODS. This was a prospective cohort study conducted at the intensive care nursery at University of California San Francisco Children's Hospital. Patients included 57 premature newborns between 24 and 27 (+6 days) weeks' gestation at birth (October 1998 to October 2004). We identified perinatal and neonatal risk factors associated with moderate-severe “white matter injuries” (T1 signal abnormalities >2 mm or >3 areas of T1 abnormality) and moderate-severe “brain abnormality” (moderate-severe white matter injuries, any degree of ventriculomegaly, or severe intraventricular hemorrhage) on MRI. Infants were studied with MRI at 31.1 weeks’ postmenstrual age (median).RESULTS. Moderate-severe white matter injuries were detected in 12 (21%) of 53 preterm newborns, and 20 (35%) of 57 had moderate-severe brain abnormality. Prolonged indomethacin exposure was the only risk factor independently associated with a lower risk of white matter injury or brain abnormality, even when adjusting for the presence of a hemodynamically significant PDA, gestational age at birth, prenatal betamethasone, systemic infection, and days of mechanical ventilation.CONCLUSIONS. In this observational study, a longer duration of indomethacin exposure was associated with less white matter injury in infants delivered before 28 weeks' gestation. A randomized trial of prolonged indomethacin treatment is needed to determine whether indomethacin can decrease white matter injury and neurodevelopmental abnormalities.

Perinatal brain injury is a major contributor to perinatal morbidity and mortality, and a considerable number of these children will develop long term neurodevelopmental disabilities. Despite the severe clinical and socio-economic significance and the advances in neonatal care over the past twenty years, no therapy yet exists that effectively prevents or ameliorates detrimental neurodevelopmental effects in cases of perinatal/neonatal brain injury. Our objective is to review recent evidence in relation to the pervading hypothesis for targeting time-dependent molecular and cellular repair mechanisms in the developing brain. In addition we review several potential neuroprotective strategies specific to the developing nervous system, with a focus on erythropoietin (Epo) because of its potential role in protection as well as repair.

Objectives To determine if the incidence of sonographically detected cystic periventricular leukomalacia (PVL) and periventricular hemorrhagic infarction (PVHI) have changed over the past decade and to determine if a decline in cystic PVL was associated with a change in neurodevelopmental outcome. Study design Premature newborn infants admitted to our intensive care nursery from 1992 to 2002 were identified in a comprehensive nursery database. Premature newborn infants had routine neurosonography by means of a standardized protocol. Infants weighing ≤1500 g at birth surviving to nursery discharge were enrolled in a nursery follow-up clinic. Results Adjusting for gestational age, there was a significant decrease in cystic PVL from 1992 to 2002 (P = .003) without a concurrent decrease in PVHI (P = 0.5). Cystic PVL and PVHI accounted for only 9 of the 28 cases of cerebral palsy and 12 of 90 cases of abnormal Developmental Scores in infants weighing

Objective We describe a case of chronic pulmonary hypertension in a 7-wk-old infant with congenital diaphragmatic hernia and an oral teratoma. Our patient was dependent on low-dose inhaled nitric oxide and was still very unstable with systemic right ventricular pressures leading to frequent oxygen desaturations. We administered sildenafil therapy to stabilize the infant with discontinuation of inhaled nitric oxide. We describe successful discontinuation of the inhaled therapy as well as a period of stabilization and improvement with continued sildenafil administration. Design Case report. Setting Intensive care nursery in tertiary academic center. Patient A 7-wk-old infant with congenital diaphragmatic hernia who was mechanically ventilated from birth. Intervention Oral sildenafil 0.3 mg/kg/dose every 12 hrs. Measurements and results Right ventricular pressure (from tricuspid valve regurgitant flow) to systemic systolic arterial pressure was measured by echocardiogram. Right ventricular to systemic pressure ratio was marginally improved with the initiation of sildenafil therapy. Inhaled nitric oxide was successfully discontinued, and the patient clinically stabilized temporarily, but he ultimately succumbed to his pulmonary hypertension. Conclusion Sildenafil may be a useful therapy for chronic pulmonary hypertension in congenital diaphragmatic hernia, but further studies of safety and efficacy need to be performed.

Objectives. To evaluate the long-term neurodevelopmental outcome of infants who underwent cardiac surgery and required extracorporeal membrane oxygenation (ECMO) support, and to examine variables that predict death or disability in these patients.Methods. We studied all infants who had congenital heart disease and were supported postoperatively with ECMO from 1990 to 2001 at our institution (n = 53). Medical records were reviewed retrospectively to obtain clinical variables. Neurologic and age-appropriate developmental examinations occurred at ages 1, 1.5, 2.5, and 4.5 years. Median age at follow-up was 55 months (9–101). Cognitive outcome was defined as suspect when scores were between 1 and 2 SD below the mean for age and abnormal when scores were >2 SD below mean for age. Neuromotor outcome was defined as suspect when the patient manifested clumsiness, tremor, or mild tone and reflex changes without functional limitations, and abnormal when there were functional limitations.Results. In-hospital survival was 17 (32%) of 53. Of survivors, 14 (88%) of 16 are living and 1 patient was lost to follow-up. Of the 53 patients, 7 survived completely intact (13%). Seven (50%) of 14 patients had a normal cognitive outcome, 3 (21%) had a suspect cognitive outcome, and 4 (29%) were abnormal. Ten (72%) of 14 patients had a normal neuromotor outcome, 1 (7%) patient had a suspect neuromotor outcome, and 3 (21%) were abnormal. No survivor with an aortic cross-clamp time >40 minutes had a normal cognitive outcome. Nonsurvivors were more likely than survivors to have had cardiac arrest as an indication for ECMO (31% vs 6%), to have had a longer aortic cross-clamp time (mean 73 minutes vs 32 minutes), and to have required continuous arteriovenous hemofiltration (78% vs 35%). The age and weight at cannulation, gender, cardiac diagnosis, interval from surgery to ECMO, cardiopulmonary bypass time, diagnosis of sepsis or mediastinitis, and duration of ECMO were not significantly associated with survival.Conclusions. Although mortality was 68% in infants who had congenital heart disease and were treated with ECMO postoperatively, of those who survive to hospital discharge, 75% have a normal neuromotor outcome and 50% have a normal cognitive outcome. These high rates of mortality and disability suggest that increased attention be paid to neuroprotection in these complex disorders.

Previous studies have suggested a relationship between reproductive history, pregnancy and birth factors, and the risk of neuroblastoma. We conducted a case-control telephone interview study that included a total of 504 children under the age of 19 years with newly diagnosed neuroblastoma identified by two national collaborative clinical trials groups, the Children's Cancer Group and the Pediatric Oncology Group. A total of 504 controls, matched to cases on age, were identified by random digit dialing. Conditional logistic regression was used to estimate the matched odds ratio (OR) and 95% confidence interval (CI) with adjustment for household income, and maternal race and education. In addition, case subgroups defined by age at diagnosis, tumour MYCN oncogene amplification status, and stage were evaluated. A suggestive pattern of increased risk was seen for a greater number of prior pregnancies, history of previous miscarriages and induced abortions, with nearly a twofold increase in risk for two or more prior induced abortions (OR = 1.9, 95% CI [1.0,3.7]). No association was found for the following diseases or conditions during pregnancy: hepatitis, rubella, measles, mumps, chickenpox, mononucleosis, vaccinations, morning sickness, pre-eclampsia, bleeding, proteinuria, anaemia, urinary tract infections, heart disease, kidney disease, liver disease and diabetes. A weak association was found for hypertension during pregnancy. Several labour and delivery factors were related to an increased risk, including threatened miscarriage, anaesthetic during labour (specifically epidural) and caesarean delivery. We found associations between premature delivery (

To the Editor.— It has always been challenging to know when new therapies should be considered ready for use in practice. History has provided many contrasting examples of simple and effective treatments (such as phototherapy and antenatal steroids) that languished for decades before being adopted and treatments that were and often continue to be used well after they proved to be either useless or less effective than simpler alternatives. However, it is extremely difficult to understand why Kirpalani and colleagues1 are so concerned that some neonatologists are now choosing to offer therapeutic hypothermia on a compassionate basis. Neither these practitioners nor any official body have, to our knowledge, declared that hypothermia should be the standard of care. They, and several of the undersigned, helped develop the consensus of the 2005 National Institute of Child Health and Human Development workshop that hypothermia is an evolving (not unproven or experimental) therapy, with many questions around its optimal use.2 Thus, the underlying premise of their commentary is shaky. Three independent …