Neurodevelopmental Risks Research Articles

Brain Dysplasia Associated with Ciliary Dysfunction in Infants with Congenital Heart Disease

To test for associations between abnormal respiratory ciliary motion (CM) and brain abnormalities in infants with congenital heart disease (CHD) STUDY DESIGN: We recruited 35 infants with CHD preoperatively and performed nasal tissue biopsy to assess respiratory CM by videomicroscopy. Cranial ultrasound scan and brain magnetic resonance imaging were obtained pre- and/or postoperatively and systematically reviewed for brain abnormalities. Segmentation was used to quantitate cerebrospinal fluid and regional brain volumes. Perinatal and perioperative clinical variables were collected. A total of 10 (28.5%) patients with CHD had abnormal CM. Abnormal CM was not associated with brain injury but was correlated with increased extraaxial cerebrospinal fluid volume (P < .001), delayed brain maturation (P < .05), and a spectrum of subtle dysplasia including the hippocampus (P < .0078) and olfactory bulb (P < .034). Abnormal CM was associated with higher composite dysplasia score (P < .001), and both were correlated with elevated preoperative serum lactate (P < .001). Abnormal respiratory CM in infants with CHD is associated with a spectrum of brain dysplasia. These findings suggest that ciliary defects may play a role in brain dysplasia in patients with CHD and have the potential to prognosticate neurodevelopmental risks.

Court orders EPA to act on chlorpyrifos

EPA is under a court-ordered deadline to finalize a rule that would prohibit all agricultural uses of chlorpyrifos, a common organophosphate insecticide. The 9th U.S. Circuit Court of Appeals on Aug. 12 denied the agency’s request for an additional six months to finalize the rule. Such a delay is not justified “in light of the EPA’s history in the matter” and “the court’s previous extensions,” it said. The court did, however, give the agency another three months to finish the rule, setting a March 31, 2017, deadline. EPA proposed to ban all uses of chlorpyrifos on food in October 2015 in response to a 2007 petition from environmental groups. The agency says that it cannot ensure that combined exposure to the pesticide from food and drinking water is safe. Exposure to chlorpyrifos has been associated with neurodevelopmental risks in children. The pesticide industry and farm groups strongly oppose EPA’s proposal.

Project TENDR: Targeting Environmental Neuro-Developmental Risks The TENDR Consensus Statement.

Summary: Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. Approach: Leading scientific and medical experts, along with children’s health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children’s brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children’s risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. Conclusion: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential.

The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs.

A number of antiepileptic drugs (AEDs) have been confirmed as teratogens due to their association with an increased malformation rate. The majority of research to date does not find an association between prenatal exposure to monotherapy carbamazepine, lamotrigine or phenytoin and neurodevelopmental outcome in comparison to control children and noted higher abilities in comparison to children exposed to valproate; but further work is needed before conclusions can be drawn. Data for levetiracetam was limited to one study, as was the evidence for topiramate. Sodium valproate exposure appeared to carry a dose dependent risk to the developing brain, with evidence of reduced levels of IQ, poorer verbal abilities and increased rate of autistic spectrum disorder both in comparison to control children and children exposed to other AEDs. The severity of the neurodevelopmental deficits associated with prenatal exposure to valproate highlight the critical need to consider neurodevelopmental outcomes as a central aspect of teratological research.

Sides drawn over EPA proposal to ban chlorpyrifos

EPA’s plan to halt all agricultural uses of chlorpyrifos, a common organophosphate insecticide, to protect children from neurodevelopmental risks is drawing mixed reactions. The pesticide industry, farm groups, and USDA are criticizing the proposal because it relies on a single human epidemiological study. Environmental groups and some external EPA advisers, however, claim that current hazard assessment methods, which rely on measuring inhibition of the enzyme acetylcholinesterase in laboratory animals, fail to protect children. Agency advisers are urging EPA to consider all relevant data, including other epidemiology studies and animal toxicity data, to strengthen its assessment. Late last year, EPA proposed to ban all uses of chlorpyrifos on food, saying the agency cannot ensure that combined exposure to chlorpyrifos from food and drinking water is safe. If the agency finalizes the proposal, it will mark the first EPA ban of a pesticide on the basis of human epidemiology data rather

Short- and Long-Term Outcomes of Moderate and Late Preterm Infants.

Late (34-36 weeks' gestational age) and moderate (32-33(6/7) weeks' gestational age) preterm infants constitute approximately 84% of all preterm infants. Over the past few decades, there is increasing recognition that this population is at risk for short- and long-term morbidities and adverse outcomes. This article is an overview of the common clinical problems encountered by the clinician during the neonatal period among infants born even a few weeks early. Recent literature highlighting the long-term neurodevelopmental and health risks of those born moderately or late preterm is also summarized and discussed. Further research on the efficacy and benefits of specific therapies in this population is warranted.

Project Tendr: Targeting Environment And Neuro-Developmental Risks

Project TENDR, “Targeting Environment and Neuro-Developomental Risks,” was recently launched with the overarching goal to reduce the incidence of childhood conditions of autism spectrum disorder, intellectual disability, attention deficits, hyperactivity and other learning and neurodevelopmental disabilities. The U of California Davis MIND (Medical Investigations of Neurodevelopmental Disorders) Institute and the Learning Disabilities Association of America are leading this effort. Neurodevelopmental disorders rob children of their abilities to learn, engage in social activities, and lead productive lives. The rapid rise in their incidence in the last few decades underscores the pressing need for action. During the same period, a growing body of scientific evidence has produced robust evidence that environmental chemicals can play a significant role in these disorders. Project TENDR convened its organizing committee in fall 2014, and in spring of 2015, an expert elicitation process involving many ISEE members will define a set of chemical classes for which evidence of harm to neurodevelopment and widespread prevalence of exposure warrant action. In June 2015, Project TENDR will convene a group of 45 invited scientists, health providers and advocates for children's health and development with the goal to 1) collectively identify environmental chemicals with evidence and levels of exposure that warrant action to reduce children's risk of neurodevelopmental disorders, 2) craft recommendations aimed at reducing exposures to those chemical risk factors and promoting healthy brain development, to include changes in policy, clinical practice and behavior, and 3) prepare a dissemination and implementation plan for the recommendations. The American Academy of Pediatrics and the American College of Obstetrics &amp; Gynecology have joined. A report on the progress of these activities will be presented, along with the Consensus Statement and the draft recommendations.

A prospective investigation of neurodevelopmental risk factors for adult antisocial behavior combining official arrest records and self-reports

Neurodevelopmental deficits are postulated to play an important role in the etiology of persistent antisocial behavior (ASB). Yet it remains uncertain as to which particular deficits are most closely associated with ASB. We seek to advance this understanding using prospectively collected data from a birth cohort in which multiple indices of neurodevelopmental functioning and ASB were assessed. Participants (n = 2776) were members of the Providence, Rhode Island cohort of the Collaborative Perinatal Project. Information on demographic and neurodevelopmental variables was collected from pregnancy through age 7. When all offspring had reached 33 years of age an adult criminal record check was conducted. A subset of subjects also self-reported on their engagement in serious ASB. Bivariate logistic regression was used to examine the relationship between each neurodevelopmental factor and adult ASB and test whether associations varied depending on how ASB was ascertained. After controlling for background and contextual characteristics, maternal smoking during pregnancy, lower childhood verbal and performance IQ, and age 7 aggressive/impulsive behavior all significantly increased the odds of adult ASB. Associations were not modified by sex and did not depend on how ASB was assessed. However, while both males and Black participants were more likely to engage in ASB than their respective female and White counterparts, relationships were significantly stronger for official records than for self-reports. Results point to a particular subset of early neurodevelopmental risks for antisocial outcomes in adulthood. Findings also suggest that prior contradictory results are not due to the use of official records versus self-reported outcomes.

Beyond building better brains: bridging the docosahexaenoic acid (DHA) gap of prematurity.

Long chain polyunsaturated fatty acids (LCPUFA) including docosahexaenoic acid (DHA), are essential for normal vision and neurodevelopment. DHA accretion in utero occurs primarily in the last trimester of pregnancy to support rapid growth and brain development. Premature infants, born before this process is complete, are relatively deficient in this essential fatty acid. Very low birth weight (VLBW) infants remain deficient for a long period of time due to ineffective conversion from precursor fatty acids, lower fat stores, and a limited nutritional provision of DHA after birth. In addition to long- term visual and neurodevelopmental risks, VLBW infants have significant morbidity and mortality from diseases specific to premature birth, including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP). There is increasing evidence that DHA has protective benefits against these disease states. The aim of this article is to identify the unique needs of premature infants, review the current recommendations for LCPUFA provision in infants, and discuss the caveats and innovative new ways to overcome the DHA deficiency through postnatal supplementation, with the long term goal of improving morbidity and mortality in this at risk population.

Neurodevelopmental Risks of Pediatric Anesthesia: What Do We Know, and What Should We Do?

First demonstrated in 1846, general anesthesia remains a singular advance of modern medicine. Anesthesia for children has dramatically alleviated pain and stress in pediatric patients, and now permits surgical care of even the youngest and smallest infants. By the mid-20th century, however, it was first suggested adverse postoperative behaviors in children might be due, at least in part, to general anesthesia [1]. Subsequent studies demonstrated abnormal neuropathology and adverse behavioral changes in rodents following in utero exposure to volatile agents, and in 1999, data demonstrating widespread neuronal apoptosis in rat pups following postnatal exposure to anesthetics were first published [2]. The resultant debate in the medical literature regarding human relevance of such findings has been extensive, and dissemination of alarm over potential deleterious effects of pediatric anesthesia in the general media has been widespread. What do we know, and what should we do? Neuronal apoptosis, or programmed cell death, is a normal part of neurodevelopment. Up to 1% of neurons in a developing mammalian brain normally will be pruned via apoptosis after failing to meet anatomic or functional milestones. Numerous factors may dramatically increase this percentage, potentially inducing abnormal neuropathology and adverse clinical outcomes [3]. Untreated neonatal pain in animals is associated with increased neuronal apoptosis and sustained behavioral disturbances [4, 5], and even seemingly minor procedures in human infants such as neonatal circumcision are associated with increased subsequent pain behaviors if performed without anesthesia [6]. Provision of adequate analgesia during painful interventions attenuates abnormal neuropathology and adverse clinical outcomes [7, 8]: anesthetic exposure to treat pain is neuroprotective, not neurotoxic. Anesthetic agents are thought to induce apoptosis through γ-aminobutyric acid (GABA)–receptor agonism, N-methyl-D-aspartate (NMDA)–receptor antagonism, or both [9]. Such apoptosis is characterized histopathologically by breakdown of nuclear membranes and condensation of nuclear contents, and functionally by marked disruption of synaptogenesis [10]. All currently available general anesthetics possess some combination of GABA agonism and/or NMDA antagonism, and virtually all have been shown to cause enhanced apoptosis and subsequent behavioral disturbances in animals [11]. Most animal data to date derive from rodents, primarily rats, although available data from nonhuman primates are concordant. Immature animals of all species studied demonstrate increased neuronal apoptosis and subsequent abnormal behaviors following exposure to anesthetics. Anesthetic neurotoxicity, however, appears limited to a critical neurodevelopmental window, and to demonstrate threshold doses and durations [11–13]. Anesthetic exposure outside this critical neurodevelopmental window, or below threshold doses and durations, is not neurotoxic. Further, and of critical relevance to human surgical practice, neurotoxicity in S. R. Hays (*) Departments of Anesthesiology & Pediatrics, Vanderbilt University School of Medicine; Pediatric Anesthesia, Monroe Carell Jr. Children’s Hospital at Vanderbilt, 2200 Children’s Way, Suite 3115, Nashville, TN 37232-9070, USA e-mail: stephen.hays@Vanderbilt.Edu

Newly Postulated Neurodevelopmental Risks of Pediatric Anesthesia

Recent animal and human studies have raised concern that exposure to anesthetic agents in children may cause neuronal damage and be associated with adverse neurodevelopmental outcomes. Exposure of young animals to anesthetic agents above threshold doses and durations during a critical neurodevelopmental window in the absence of concomitant painful stimuli causes widespread neuronal apoptosis and subsequent abnormal behaviors. The relevance of such animal data to humans is unknown. Untreated neonatal pain and stress also are associated with enhanced neuronal death and subsequent maladaptive behaviors, which can be prevented by exposure to these same anesthetic agents. Retrospective observational human studies have suggested a dose-dependent association between multiple anesthetic exposures in early childhood and subsequent learning disability, the causality of which is unknown. Ongoing prospective investigations are underway, the results of which may clarify if and what neurodevelopmental risks are associated with pediatric anesthesia. No change in current practice is yet indicated.

Subclinical hypothyroidism and related biochemical entities in pregnancy: implications and management.

Subclinical hypothyroidism (SCH), thyroid autoimmunity and isolated maternal hypothyroxinaemia are diagnoses made on laboratory findings. The two former conditions are commonly identified in the general population, while the term isolated maternal hypothyroxinaemia was developed to highlight potential neurodevelopmental risks in progeny. Each entity has been associated with either obstetric, perinatal and/or child developmental harm in observational studies, although few interventional trials have been performed to guide diagnostic and therapeutic approaches. Once diagnosed, treatment of SCH is recommended by endocrine groups to limit potential risk, given that harm from appropriate therapy is unlikely. Screening for thyroid disorders in pregnancy has traditionally been controversial. Definitive trials are expected to report over coming years and updated consensus guidelines will hopefully resolve this issue.

Quantitative Analyses of Inhibitory Effects of Bisphenol A on Neural Stem-cell Migration Using a Neurosphere Assay in vitro

The large numbers of environmental chemicals that now exist have made assessing their neurodevelopmental risks challenging. In this study, we quantified neurodevelopmental toxicity of bisphenol A, using a neurosphere assay in vitro. Neurosphere was isolated from rat E16 mesencephalone. A neurosphere assay was carried out in the amine-coated plates. Cells emerged from the neurosphere and migrated along the radial axis from the sphere. The migrating populations comprised cells that were positive for nestin, microtubule-associated proteins, and glial fibrillary acidic protein. Exposure to bisphenol A inhibited cell migration and decreased proliferative cells in dose-dependent manner. Quantitative analyses revealed a linear function between the inhibition of migration and the logarithm of bisphenol A concentration (0-100 μM); the percent inhibition by 1 μM bisphenol A of migration was 35% (p<0.05). Thus, we showed for first time that bisphenol A inhibited migration as well as proliferation of neural stem cells in vitro and that a neurosphere assay in vitro is very useful to rapidly quantify neurodevelopmental toxicity of environmental chemicals.

Defining a Lowest Observable Adverse Effect Hair Concentrations of Mercury for Neurodevelopmental Effects of Prenatal Methylmercury Exposure Through Maternal Fish Consumption: A Systematic Review

Methylmercury is an environmental pollutant that can cause irreversible effects on the development of children. Although there is no doubt that high exposure can cause neurodevelopmental deficits, the threshold that will adversely affect the developing fetus is not well defined. Our objective was to systematically review the evidence of neurodevelopmental risks of methylmercury to the unborn child from maternal fish consumption to define the lowest observable adverse effect hair concentration (LOAEHC). A systematic review was conducted of all original research reporting on the effects of methylmercury on the human fetus. A literature search was undertaken using SCOPUS, Medline-Ovid, PubMed, Google Scholar, and EMBASE. Papers were selected based on the following inclusion criteria: 1) child neurodevelopmental outcome; 2) comparison groups; and 3) methylmercury exposure through fish consumption. Forty-eight publications met these inclusion criteria. Thirty articles reported on longitudinal studies and 18 were cross-sectional studies. Variations in study design precluded formal meta-analysis. Based on an evaluation of these studies, we defined the LOAEHC at 0.3 microg/g of maternal hair mercury. The longitudinal studies yielded a LOAEHC of 0.5 microg/g. In the clinical context, the majority of pregnant women consume mercury-containing fish in amounts that are lower than the LOAEHC defined in this study. However, the LOAEHC is in the same order of magnitude of mercury exposure that occurs in significant numbers of women. Hence, although it appears safe to suggest that eating the recommended types and amounts of fish poses no measurable risks for neurodevelopmental deficits, analysis of hair mercury content before pregnancy might be suggested because dietary modification can decrease body content and risk.

Neurodevelopmental Toxicity Risks Due to Occupational Exposure to Industrial Chemicals during Pregnancy

Exposure to neurotoxic chemicals is of particular concern when it occurs during early development. The immature brain is highly vulnerable prenatally and is therefore at risk due to occupational exposures incurred by pregnant women. A systematic search of the literature has been performed with emphasis on epidemiological studies on female workers and the neurodevelopment of their children. The majority of recent occupational studies focused on organic solvents and pesticides, which were associated with neurobehavioral impairments in the progeny. Additional evidence on environmental exposures demonstrates the vulnerability of the developing brain to substances like lead and methylmercury. Despite the evident hazards involved, the number of occupational cohort studies carried out in this field is very low. However, the lack of evidence for assumed neurotoxicants should not divert the attention by occupational health researchers and practitioners from the need to protect pregnant workers. Due to the vulnerability of the brain during early development, a precautionary approach to neurodevelopmental toxicity needs to be applied in occupational health.

Predictive validity of DSM‐IV and ICD‐10 criteria for ADHD and hyperkinetic disorder

The goal of this study was to compare the predictive validity of the two main diagnostic schemata for childhood hyperactivity - attention-deficit hyperactivity disorder (ADHD; Diagnostic and Statistical Manual- IV) and hyperkinetic disorder (HKD; International Classification of Diseases- 10th Edition). Diagnostic criteria for ADHD and HKD were used to classify 419 children ages 6 to 16 years referred to a clinic for behavioral problems into one of four groups: HKD, ADHD combined subtype (ADHD-C), ADHD hyperactive-impulsive subtype (ADHD-HI), ADHD inattentive subtype (ADHD-IA). These groups were compared on clinical characteristics including total symptom severity, overall impairment, exposure to psychosocial and neuro-developmental risks, family history of ADHD in first-degree family members, rate and type of comorbidity, intelligence, academic achievement, and on laboratory tests of motor response inhibition and working memory with each other and with normal controls (47). Of the 419 cases, there were 46 HKD (11.0%), 200 ADHD-C (47.7%), 60 ADHD-HI (14.3%) and 113 ADHD-IA (27.0%) cases. The HKD group had more symptoms and was more impaired on teachers' ratings than were the other groups. The ADHD-C and HKD groups had poorer inhibitory control than the ADHD-IA, ADHD-HI and control groups, and all four clinic groups showed inhibition deficit compared to controls. Groups did not differ in working memory. Compared to controls, the HKD, ADHD-C, ADHD-HI and ADHD-IA groups had higher familial risk of ADHD, greater psychosocial risk exposure, lower intellectual level and poorer academic attainment. However, we observed no differences among the clinic groups in these characteristics. Like earlier versions, ICD-10 and DSM-IV continue to delineate diagnostic entities with substantially different prevalence in clinic samples. However, HKD, ADHD-C, ADHD-IA and ADHD-HI groups overlap substantially in terms of important clinical characteristics, although HKD and ADHD-C may be somewhat more severe variants of the condition than ADHD-IA and ADHD-HI.

Outcomes among newborns with total serum Bilirubin levels of 25 mg per deciliter or more

. Newman, T.B., Liljestrand, P., Jeremy, R.J., Ferriero, D.M., Wu, Y.W., Hudes, E.S., Escobar, G.J. , ( 2006 ) , 354 , 1889 – 1900 . Background The neurodevelopmental risks associated with high total serum bilirubin levels in newborns are not well defined.Methods We identified 140 infants with neonatal total serum bilirubin levels of at least 25 mg per deciliter (428 µmol per litre) and 419 randomly selected controls from a cohort of 106 627 term and near‐term infants born from 1995 to 1998 in Kaiser Permanente hospitals in northern California. Data on outcomes were obtained from electronic records, interviews, responses to questionnaires and neurodevelopmental evaluations that had been performed in a blinded fashion.Results Peak bilirubin levels were between 25 and 29.9 mg per deciliter (511 µmol per litre) in 130 of the newborns with hyperbilirubinemia and 30 mg per deciliter (513 µmol per litre) or more in 10 newborns; treatment involved phototherapy in 136 cases and exchange transfusion in five. Follow‐up data to the age of at least 2 years were available for 132 of 140 children with a history of hyperbilirubinemia (94%) and 372 of 419 controls (89%) and included formal evaluation at a mean (±SD) age of 5.1 ± 0.12 years for 82 children (59%) and 168 children (40%) respectively. There were no cases of kernicterus. Neither crude nor adjusted scores on cognitive tests differed significantly between the two groups; on most tests, 95% confidence intervals excluded a 3‐point (0.2 SD) decrease in adjusted scores in the hyperbilirubinemia group. There was no significant difference between groups in the proportion of children with abnormal neurologic findings on physical examination or with documented diagnoses of neurologic abnormalities. Fourteen of the children with hyperbilirubinemia (17%) had ‘questionable’ or abnormal findings on neurologic examination, as compared with 48 controls (29%; P = 0.05; adjusted odds ratio, 0.47; 95% confidence interval, 0.23–0.98; P = 0.04). The frequencies of parental concern and reported behavioural problems also were not significantly different between the two groups. Within the hyperbilirubinemia group, those with positive direct antiglobulin tests had lower scores on cognitive testing but not more neurologic or behavioural problems.Conclusions When treated with phototherapy or exchange transfusion, total serum bilirubin levels in the range included in this study were not associated with adverse neurodevelopmental outcomes in infants born at or near term.

Outcomes among Newborns with Total Serum Bilirubin Levels of 25 mg per Deciliter or More

The neurodevelopmental risks associated with high total serum bilirubin levels in newborns are not well defined. We identified 140 infants with neonatal total serum bilirubin levels of at least 25 mg per deciliter (428 micromol per liter) and 419 randomly selected controls from a cohort of 106,627 term and near-term infants born from 1995 through 1998 in Kaiser Permanente hospitals in northern California. Data on outcomes were obtained from electronic records, interviews, responses to questionnaires, and neurodevelopmental evaluations that had been performed in a blinded fashion. Peak bilirubin levels were between 25 and 29.9 mg per deciliter (511 micromol per liter) in 130 of the newborns with hyperbilirubinemia and 30 mg per deciliter (513 micromol per liter) or more in 10 newborns; treatment involved phototherapy in 136 cases and exchange transfusion in 5. Follow-up data to the age of at least two years were available for 132 of 140 children with a history of hyperbilirubinemia (94 percent) and 372 of 419 controls (89 percent) and included formal evaluation at a mean (+/-SD) age of 5.1+/-0.12 years for 82 children (59 percent) and 168 children (40 percent), respectively. There were no cases of kernicterus. Neither crude nor adjusted scores on cognitive tests differed significantly between the two groups; on most tests, 95 percent confidence intervals excluded a 3-point (0.2 SD) decrease in adjusted scores in the hyperbilirubinemia group. There was no significant difference between groups in the proportion of children with abnormal neurologic findings on physical examination or with documented diagnoses of neurologic abnormalities. Fourteen of the children with hyperbilirubinemia (17 percent) had "questionable" or abnormal findings on neurologic examination, as compared with 48 controls (29 percent; P=0.05; adjusted odds ratio, 0.47; 95 percent confidence interval, 0.23 to 0.98; P=0.04). The frequencies of parental concern and reported behavioral problems also were not significantly different between the two groups. Within the hyperbilirubinemia group, those with positive direct antiglobulin tests had lower scores on cognitive testing but not more neurologic or behavioral problems. When treated with phototherapy or exchange transfusion, total serum bilirubin levels in the range included in this study were not associated with adverse neurodevelopmental outcomes in infants born at or near term.

Bronchopulmonary dysplasia: an enduring challenge.

1. Yvonne E. Vaucher, MD, MPH* 1. *Clinical Professor of Pediatrics, Division of Neonatology, University of California, San Diego, Calif. After completing this article, readers should be able to: 1. Describe the most common cause of chronic lung disease during infancy. 2. Explain the importance of a history of bronchopulmonary dysplasia throughout childhood. 3. Identify infants at high risk for developing bronchopulmonary dysplasia. 4. List the adverse effects associated with postnatal corticosteroids. Despite clinical advances in antepartum, intrapartum, and neonatal care, bronchopulmonary dysplasia (BPD) continues to challenge infants who have been in neonatal intensive care units and their caretakers. BPD is the most common cause of chronic respiratory disease during infancy and remains a major cause of long-term medical, pulmonary, and neurodevelopmental morbidity, increasing the cost of health care and the utilization of medical and educational resources throughout childhood. BPD is a clinical diagnosis, defined by oxygen dependence for a specific period of time after birth and accompanied by characteristic radiographic findings that correspond to anatomic abnormalities. Thus far, a precise physiologic definition of BPD is lacking. As the clinical presentation has evolved over the past 30 years, so has the definition. As originally described by Northway in the 1960s, the diagnosis of classic BPD was based on progressive radiographic changes in preterm infants who were treated for severe respiratory distress syndrome (RDS) immediately after birth and had prolonged ventilator and oxygen dependence. This form of BPD occurred in larger, relatively mature preterm infants, who required treatment with high-pressure mechanical ventilation and high concentrations of oxygen. Although the acute respiratory disease initially improved in these infants, oxygen requirements increased 7 to 10 days after birth and persisted for at least 28 days. The definition of BPD subsequently was modified by Bancalari to include preterm infants who had less severe RDS that initially required short-term mechanical ventilation, but who also developed persistent respiratory symptoms and an oxygen requirement for at least 28 days after birth …

Neonatal Society Abstracts

The use of neuroimaging, the General Movement Assessment (GMA), and the Hammersmith Infant Neurological Examination (HINE) to identify the risk of neurodevelopmental delay in early infancy is recommended.The aim of this study was to examine the predictive power of neuroimaging, GMA and HINE for neurodevelopmental delay and cerebral palsy (CP) in infants with hypoxic ischemic encephalopathy (HIE) who were treated with hypothermia.Retrospective cohort.This retrospective study included 47 (18 female and 29 male) infants who were treated with hypothermia due to HIE. Neonates with a diagnosis of HIE were followed and assessed using neuroimaging, GMA, HINE and the Bayley Scales of Infant and Toddler Development-II (Bayley II) between 3 m and 2 years of age.Out of the 47 infants with HIE, no fidgety movements were observed in 5 infants. The sensitivity and specificity in determining the psychomotor developmental index (PDI) score were 97% and 100%, respectively, for MRI; 92.9% and 100% for GMA; and 91.9% and 80% for the HINE. The sensitivity and specificity in determining the mental developmental index (MDI) score were 95% and 85.7%, respectively, for MRI; 90.5% and 80% for GMA; and 91.9% and 50% for HINE. The sensitivity and specificity in determining CP diagnosis at the age of 2 years were 83.3% and 95%, respectively, for MRI; 83.3% and 100% for GMA; and 83.3% and 87.8% for HINE.The interpretation of MRI, GMA, and HINE that are performed within the early period of life may be the gold standard for the early detection of neurodevelopmental risks in 2-year-old infants with HIE. Clinical implementation of these methods in the early period in the follow-up of these infants offers useful information for the early identification of neurodevelopmental risk and for planning early intervention.