Neurodevelopmental Follow-up Research Articles

Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy

BackgroundErythropoietin is neuroprotective in animal models of neonatal hypoxic-ischemic encephalopathy. We previously reported a phase I safety and pharmacokinetic study of erythropoietin in neonates. This article presents the neurodevelopmental follow-up of infants who were enrolled in the phase I clinical trial. MethodsWe enrolled 24 newborns with hypoxic-ischemic encephalopathy in a dose-escalation study. Patients received up to six doses of erythropoietin in addition to hypothermia. All infants underwent neonatal brain magnetic resonance imaging (MRI) reviewed by a single neuroradiologist. Moderate-to-severe neurodevelopmental disability was defined as cerebral palsy with Gross Motor Function Classification System levels III-V or cognitive impairment based on Bayley Scales of Infant Development II mental developmental index or Bayley III cognitive composite score. ResultsOutcomes were available for 22 of 24 infants, at mean age 22 months (range, 8-34 months). There were no deaths. Eight (36%) had moderate-to-severe brain injury on neonatal MRI. Moderate-to-severe disability occurred in one child (4.5%), in the setting of moderate-to-severe basal ganglia and/or thalamic injury. Seven infants with moderate-to-severe watershed injury exhibited the following outcomes: normal (three), mild language delay (two), mild hemiplegic cerebral palsy (one), and epilepsy (one). All 11 patients with a normal brain MRI had a normal outcome. ConclusionsThis study is the first to describe neurodevelopmental outcomes in infants who received high doses of erythropoietin and hypothermia during the neonatal period. The findings suggest that future studies are warranted to assess the efficacy of this new potential neuroprotective therapy.

Monitoring developmental risk and promoting success for children with congenital heart disease: Recommendations for cardiac neurodevelopmental follow-up programs.

Monitoring developmental risk and promoting success for children with congenital heart disease: Recommendations for cardiac neurodevelopmental follow-up programs.

PC.64 Audit of the Management and follow up of infants who received Therapeutic Hypothermia for Neonatal Encephalopathy in NHS Greater Glasgow and Clyde (GG&C) from January 2008 to December 2010

IntroductionNeonatal hypoxic-ischaemic encephalopathy (HIE) is the most common cause of long term neurological deficit in term and near-term infants. Controlled hypothermia has been available within tertiary level Neonatal Units in...

Telephone interviews and online questionnaires can be used to improve neurodevelopmental follow-up rates

BackgroundMaximising response rates to neurodevelopmental follow-up is a key challenge for paediatric researchers. We have investigated the use of telephone interviews and online questionnaires to improve response rates, reduce non-response bias, maintain data completeness and produce unbiased outcomes compared with postal questionnaires when assessing neurodevelopmental outcomes at 2 years.MethodsA prospective cohort study of babies born ≥32 weeks gestation. Neurodevelopmental outcomes were assessed at 2 years of age using a parent questionnaire completed via post, telephone or online. Relative Risks with 95% confidence intervals (RR; 95% CI) were calculated to identify participant characteristics associated with non-response and questionnaire response mode (postal vs. telephone/online). The proportion of missing data and prevalence of adverse outcomes was compared between response modes using generalized linear models.ResultsOffering telephone/online questionnaires increased the study response rate from 55% to 60%. Telephone/online responders were more likely to be non-white (RR 1.6; [95% CI 1.1, 2.4]), non-English speaking (1.6; [1.0, 2.6]) or have a multiple birth (1.6; [1.1, 2.3]) than postal responders. There were no significant differences in the prevalence of adverse neurodevelopmental outcomes between those who responded via post vs. telephone/online (1.1; [0.9, 1.4]). Where parents attempted all questionnaire sections, there were no significant differences in the proportion of missing data between response modes.ConclusionsWhere there is sufficient technology and resources, offering telephone interviews and online questionnaires can enhance response rates and improve sample representation to neurodevelopmental follow-up, whilst maintaining data completeness and unbiased outcomes.

Traumatic Perforation of the Lamina Cribrosa During Nasal Intubation of a Preterm Infant

Traumatic perforation of the lamina cribrosa and penetration of the brain occurred during nasotracheal intubation of a preterm infant requiring resuscitation. This rare complication is specifically associated with the nasal route of intubation. The complication resulted in significant morbidity. The infant developed an extensive intracranial hemorrhage and posthemorrhagic hydrocephalus that required ventricular drainage. We recommend that nasotracheal intubation be performed with utmost care. We confirm Cameron and Lupton's recommendation of using a small feeding tube over which to slide the endotracheal tube. Despite extensive iatrogenic damage, the patient's neurodevelopmental follow-up at 2 years 9 months appeared relatively mild.

Neurodevelopmental outcome in congenital diaphragmatic hernia: Evaluation, predictors and outcome.

To review the reported neurodevelopmental outcome of congenital diaphragmatic hernia (CDH) survivors, identify important predictors of developmental disabilities, and describe the pathophysiological mechanisms contributing to adverse outcome. A Medline search was performed for English-language articles cross-referencing CDH with pertinent search terms. Retrospective, prospective, and longitudinal follow-up studies were examined. The reference lists of identified articles were also searched. Neurodevelopmental dysfunction has been recognized as one of most common and potentially most disabling outcome of CDH. Intelligence appears to be in the low normal to mildly delayed range. Neuromotor dysfunction is common during early childhood. Behavioral problems, hearing impairment, and quality of life related issues are frequently encountered in older children and adolescence. Disease severity correlates with the degree of neurological dysfunction. Neurodevelopmental follow-up in CDH children should become standard of care to identify those who would benefit from early intervention services and improve neurological outcomes.

712: Behavioral and developmental outcome of neonates at 2 years of age after preterm prelabor rupture of membranes: follow up of the PPROMEXIL trial

We recently found that induction of labor (IoL) did not reduce the incidence of neonatal sepsis in women with preterm prelabor rupture of membranes (PPROM) between 34 and 37 weeks’ gestation.1,2 In this abstract, we report the neurodevelopmental and behavioral follow-up of these children at 2 years of age.

Association between Feeding Difficulties and Language Delay in Preterm Infants Using Bayley Scales of Infant Development-Third Edition

To evaluate the relationship between abnormal feeding patterns and language performance on the Bayley Scales of Infant Development-Third Edition at 18-22 months adjusted age among a cohort of extremely premature infants. This is a descriptive analysis of 1477 preterm infants born ≤ 26 weeks gestation or enrolled in a clinical trial between January 1, 2006 and March 18, 2008 at a National Institute of Child Health and Human Development Neonatal Research Network center who completed the 18-month neurodevelopmental follow-up assessment. At 18-22 months adjusted age, a comprehensive neurodevelopmental evaluation was performed by certified examiners including the Receptive and Expressive Language Subscales of the Bayley Scales of Infant Development-Third Edition and a standardized adjusted age feeding behaviors and nutritional intake. Data were analyzed using bivariate and multilevel linear and logistic regression modeling. Abnormal feeding behaviors were reported in 193 (13%) of these infants at 18-22 months adjusted age. Abnormal feeding patterns, days of mechanical ventilation, hearing impairment, and Gross Motor Functional Classification System level ≥ 2 each independently predicted lower composite language scores. At 18 months adjusted age, premature infants with a history of feeding difficulties are more likely to have language delay. Neuromotor impairment and days of mechanical ventilation are both important risk factors associated with these outcomes.

Neurodevelopmental follow-up results in very low birth weight premature infants and influential factors

Neurodevelopmental follow-up results in very low birth weight premature infants and influential factors

Optimizing Therapeutic Hypothermia for Neonatal Encephalopathy

Therapeutic hypothermia (TH) for neonatal encephalopathy is becoming widely available in clinical practice. The goal of this collaborative was to create and implement an evidence-based standard-of-care approach to neonatal encephalopathy, deliver consistent care, and optimize outcomes. The quality improvement process identified and used the Model for Improvement as a framework for improvement efforts. This was a Vermont Oxford Network Collaborative focused on optimizing TH in the treatment of neonatal encephalopathy. By using an evidence-based approach, Potentially Better Practices were developed by the topic expert, modified by the collaborative, and implemented at each hospital. These included the following: timely identification of at-risk infants, coordination with referring hospitals to ensure TH was available within 6 hours after birth, staff education for both local and referring hospitals, nonsedated MRI, incorporating amplitude-integrated EEG into a TH protocol, and ensuring standard neurodevelopmental follow-up of infants. Each center used these practices to develop a matrix for implementation. Local self-assessments directed the implementation and adaptation of the Potentially Better Practices at each center. Resources, based on common identified barriers, were developed and shared among the group. The implementation of a TH program to improve the consistency of care for patients in NICUs is feasible using standard-quality improvement methodology. The successful introduction of new interventions such as TH to the NICU culture requires a collaborative multidisciplinary team, use of a systematic quality improvement process, and perseverance.

Neonatal posterior cerebral artery stroke: clinical presentation, MRI findings, and outcome

To report the clinical presentation, magnetic resonance imaging (MRI) findings, and follow-up data of newborn infants with perinatal arterial ischemic stroke in the territory of the posterior cerebral artery (PCA). Data on 18 newborn infants from three neonatal intensive care units (11 males, seven females) with an MRI-confirmed PCA stroke were analysed and reported. Infants were born at a mean gestational age of 38.7 weeks (SD 3.4) with a mean birthweight of 3244g (SD 850). Fourteen infants presented with clinical seizures. Five of these had associated hypoxic-ischemic encephalopathy, four had hypoglycaemia, and five had neither hypoxic-ischemic encephalopathy nor hypoglycaemia. Subclinical seizures were present in one infant with hypoxic-ischemic encephalopathy and one with meningitis. One preterm infant presented with apnoeas and one had hypoxic-ischemic encephalopathy without seizures. Neurodevelopmental follow-up of 17 children at a median age of 36 months (SD 28, range 12-120mo) showed five with a global delay. Two children with additional injury developed postneonatal epilepsy and one child with extensive injury developed hemiplegia. A visual field defect was observed in nine children (six hemianopia, three quadrantanopia). In the 11 children with a second MRI at 3 months, the asymmetry of the optic radiation correlated with the development of a visual field deficit. Outcome after PCA stroke is fairly good, depending on additional brain injury. Follow-up is required, as subsequent visual field defects are frequently observed. Further research will be needed to clarify the role of hypoglycaemia in perinatal arterial ischemic stroke.

Neurodevelopmental Outcome Among Multiples and Singletons: A Regional Neonatal Intensive Care Unit's Experience in Turkey

The aim of this study was to compare the neurodevelopmental outcome at 12-18 months' corrected age between multiples and singleton preterm infants. We designed a prospective study of preterm infants (≤32 weeks gestation) born and hospitalized in the neonatal intensive care unit between November 2008 and November 2009, whose assessments were performed at 12-18 months' corrected age. Neurodevelopmental impairment was defined as the presence of any one of the following: moderate or severe cerebral palsy, severe bilateral hearing loss or bilateral blindness, mental developmental index score, or psychomotor developmental index score less than 70. Results were compared for both multiples and singleton infants. One hundred and fifty-nine multiples and 211 singleton infants were assessed at 12-18 months' corrected age. The neurodevelopmental outcome including all parameters at 12-18 months' corrected age in multiples was not significantly different from singleton preterm infants. Multiple gestation in preterm infants is not associated with an increased risk of neurodevelopmental impairment at 12-18 months' corrected age compared with singleton preterm infants. For further information, long term and high participation in neurodevelopmental follow-up and evaluation at pre-school age will be needed.

Clinical utility of corpus callosum measurements in head sonograms of preterm infants: a cohort study

ObjectiveTo assess the clinical usefulness of measurement of corpus callosum (CC) size in head ultrasound (HUS) to predict short-term neurodevelopmental (ND) outcomes in preterm infants. We hypothesised that including CC...

386 A Count of three Neonatal Morbidities may Substitute for Long-Term Neurodevelopmental follow-up in very Low Birth Weight (VLBW) Infants

BackgroundIn very preterm infants who survive to a postmenstrual age (PMA) of 36 weeks, a count of BPD, brain injury and severe ROP predicts the risk of a later death...

1231 Neurodevelopmental Outcome Among Multiples and Singletons: A Regional Neonatal Intensive Care Unit’s Experience in Turkey

ObjectiveThe aim of this study was to compare the neurodevelopmental outcome at 12–18 months’ corrected age between multiples and singleton preterm infants.MethodsWe designed a prospective study of preterm infants (≤32...

Long-term follow-up of children with congenital chylothorax

To the Editors: Congenital chylothorax, defined as the accumulation of lymphatic fluid in the pleural cavity, is a rare neonatal disorder. Nevertheless, congenital chylothorax represents the most common cause of pleural effusion in fetuses and newborns [1]. Due to the rarity of this disorder only a few case series are reported in the literature and current treatment recommendations are based on individual case reports or case series only [2–5]. The diagnosis of chylothorax is considered when pleural fluid triglyceride levels are >1.1 mmol·L−1 and total cell counts are >1,000 cells per mL with >80% lymphocytes. Without oral fat intake chylomicrons, which are often an indication for the diagnosis of chylothorax, are absent in the pleural fluid and distinction between chylous and non-chylous effusion might be difficult [6]. Long-term follow-up of children with congenital chylothorax, however, was documented in only four studies [7–10] and none included pulmonary function testing. We describe the clinical course and long-term outcome of infants with congenital chylothorax including neurodevelopmental follow-up and pulmonary function testing. In this study the data of all children who were documented in the local database of the Division of Neonatology (Paediatric Dept, Medical University of Graz, Graz, Austria) with the diagnosis of congenital chylothorax between January 1, 1995 and December …

Long-Term Neurodevelopmental Follow-Up of Children With Congenital Muscular Torticollis

Congenital muscular torticollis is a common condition, but long-term neurodevelopmental follow-up is lacking. This study reports on neurodevelopmental outcome of 68 children, aged 7 to 9 years, with a history of congenital muscular torticollis, excluding children with torticollis due to other conditions. Thirty-eight children were examined for presence of neurodevelopmental disorders. Telephone interview data were available for an additional 30 children. Of those examined, 22/38 (57.9%) had or were at risk for a developmental disorder (attention-deficit hyperactivity disorder (ADHD), developmental coordination disorder, language impairment, autistic spectrum disorder) on at least 1 of the assessments administered, 23/38 (60.5%) had received developmental treatment during childhood. One child, based on a telephone interview, had a history of developmental treatment. Therefore, 30/68 (44.1%) children of the total sample demonstrated a developmental delay/disorder, currently (22/68) or previously (8/68). Our findings suggest congenital muscular torticollis to be a significant risk factor for later neurodevelopmental conditions with disorders presenting at different stages of development.

Das chronisch kranke Kind in der Schule

Advances in medical treatment have led to an increase survival of children suffering from severe diseases. Often times, these children will develop a chronic disorder thereafter. The care of these children and families is a challenging task for primary care providers. Children with chronic disorders may manifest medical complications, but may also face psychosocial and neurodevelopmental sequelae. Psychological maladjustment may occur independent of the underlying medical condition and quality of life can be impaired. Interestingly, quality of life is better if rated by the children themselves than if judged by their parents. Obviously, children with a chronic condition of the central nervous system have a high prevalence of neurodevelopmental problems. However, neurodevelopmental problems may also occur frequently in children at risk for developmental sequelae. Among those are children born before 32. weeks of gestation, those after perinatal asphyxia and children with a severe congenital heart defect. The prevalence of these three conditions is equally high at around 1 in 100 newborns. All three groups may face mild neurodevelopmental problems, which typically present at school-age. Problems may constitute of motor and intellectual difficulties and specific deficits in visuomotor and executive functions and often occur in combination. It is therefore of outmost importance that aside from regular specialized neurodevelopmental follow-up visits, these children are being followed closely by their primary care provider to early assess psychosocial and neurodevelopmental difficulties. These need to be evaluated and treated in association with other health care specialists.

Clinical Research Informing Neonatal Care at the University Hospital of the West Indies: 50 Years Experience

Neonatology has rapidly grown over the past few years to its present status of a highly technologically driven specialty. Centres in resource restricted countries tend to adopt management guidelines from the developed world and integrate them into local practice. Although international neonatal practices have influenced neonatal care at the University Hospital of the West Indies (UHWI), over the past fifty years there has been local clinical research done at the hospital that has informed local practice. Causes of neonatal mortality have been documented and this has informed neonatal resuscitation practices, infection control policies and ventilatory support of premature infants. Changes in the incidence of various aetiologies of jaundice over the years have altered how jaundiced neonates are investigated and managed. Research on neonatal sepsis has informed antibiotic choices and treatment regimes. Studies on preterm infants have informed management polices on ensuring optimal thermal environment, on the timing of discharge and on neurodevelopmental follow-up. It is clear that clinical research at the UHWI has informed neonatal care at the institution over the past 50 years and it is hoped that it will continue to do so for the next 50 years and beyond.

Outcomes of extremely low birth weight infants given early high-dose erythropoietin

To evaluate long-term outcomes of 60 extremely low birth weight (ELBW) infants treated with or without three injections of high-dose erythropoietin (Epo). A retrospective analysis of anthropometric and neurodevelopmental outcome data comparing 30 ELBW infants enrolled in a phase I/II study examining the pharmacokinetics of high-dose Epo (500, 1000 and 2500 U/kg × 3 doses) administered to 30 concurrent controls. Birth characteristics and growth from 4 to 36 months were similar for untreated and Epo-treated patients. Multiple linear regression analysis of neurodevelopmental follow-up scores from 17/25 Epo-treated and 18/26 control infants identified that Epo correlated with improvement of cognitive (R=0.22, P=0.044) and motor (R=0.15, P=0.026) scores. No negative long-term effects of Epo treatment were evident. Retrospective analysis of the only available long-term follow-up data from ELBW infants given high-dose Epo treatment suggests that Epo treatment is safe and correlates with modest improvement of neurodevelopmental outcomes.