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Cerebral oxygenation following preterm delivery
November 2015 Volume 167 Number 5
Read my mind — Paul G. Fisher, MD
Reporting “perceptions” — Thomas R. Welch, MD
Charting the course of young children with cystic fibrosis — Steven H. Abman, MD
Copyright ª 2015 by Elsevier Inc.
D
yslexia is a difficulty in reading unexpected in relation to intelligence. This language disorder likely is rooted in difficulties processing the sounds of speech and unawareness of phonemes, the smallest elements of sound. Perhaps 1 in 20 (or more) school children suffer from this learning disability; and most are not identified until third grade or later. Can dyslexia be identified as early as first grade? Does the gap been reading and intelligence change over time? In this issue of The Journal, Ferrer et al demonstrate that the gap can be seen as early as first grade, using a cohort of 414 children from the Connecticut Longitudinal Study. The gap persisted over time at a relatively constant difference. Dyslexia can be identified at the first grade. The authors make a strong plea for early identification of and intervention in young children at risk for dyslexia by kindergarten or even preschool. Although this is a laudable goal, definitive evidence that earlier intervention will result in superior outcomes is still limited. Identification of children before ages 3 or 4 years is not so straightforward, when children are not yet reading. Even at ages 5 or 6 years, pediatricians are not accustomed to screening for reading difficulties. Clearly greater awareness of dyslexia is needed along with research on which interventions will consistently lead to improvements when started at the earliest possible ages. Article page 1121< his issue of The Journal includes a study that is noteworthy for two very different reasons. Guise et al from the Oregon Health Sciences University remind us that health care often begins with the emergency medical services (EMS) system. Although the quality and safety of inpatient hospital care has been the subject of a wealth of initiatives and reports, there has been little work done examining the prevention of safety events and errors in the over one million pediatric EMS encounters annually. Although the report does not address the issue directly, it provides a nice map of several targets for safety studies in the pediatric prehospital environment. What also is noteworthy about the study is the approach. On its face, the study was accomplished by a survey of EMS providers to obtain their thoughts about potential causes of safety events. The Journal receives scores of manuscripts reporting such surveys, the bulk of which we do not publish. The article by Guise et al, however, is a model of how surveys can be designed and implemented to produce reliable results. From selection of the target population, to survey design and testing, to implementation and reporting, this article sets a standard by which such studies can be judged. Article page 1143<
T
I
n addition to aggressive monitoring of disease course and the use of novel strategies for respiratory and antimicrobial therapies, marked attention to the maintenance of excellent growth and nutrition has played a key role in improving long-term outcomes of children with cystic fibrosis (CF). CF centers play particular attention to changes in growth measurements as useful markers of nutrition and disease activity, leading to earlier and more rigorous evaluations and interventions. As such, the optimal care of young children with CF is highly dependent on the use of standardized growth 947
charts. In this study, Zhang et al analyzed data from 2587 children followed in the Cystic Fibrosis Foundation Patient Data Registry in order to compare differences in the classification of growth status of young children with CF as assessed by the World Health Organization (WHO) and Centers for Disease Control (CDC) growth percentiles. Currently, WHO standards often are followed up to 23.9 months, followed by the use of CDC references. Among several findings, this study reports that using weight status measures (weight-for-length and body mass index) at 24 months, 26% of children who were classified as normal growth using WHO references were underweight using CDC references. These findings are important to ensure greater understanding of the potential impact of changing growth standards on the interpretation of individual growth status, the impact on clinical practice, and to allow accurate comparisons between CF centers. These findings further set the stage to explore relationships between early nutritional interventions and long-term growth and pulmonary outcomes. Article page 1089<
Cerebral oxygenation following preterm delivery — Alan H. Jobe, MD, PhD
Warming up to the need for MRI after hypothermia — Paul G. Fisher, MD
948
T
he Neonatal Resuscitation Program (NRP) has progressed over 25 years from assumptions and professional opinion about resuscitation of the term infant to evidence-based recommendations for the initial support of both term and preterm infants. This evidence base has been developed by interested investigators using traditional and newer monitoring techniques to measure the transitions in oxygenation, cardiopulmonary function, and metabolism following birth. Supplemental oxygen can cause oxidant exposures that may cause long-term organ injury. As the monitoring has improved, the challenges are to learn if monitoring can change outcomes rather than simply improve physiologic variables that may not impact long-term outcomes. The report by Kenosi et al illustrates this point. They evaluated cerebral oxygenation immediately following delivery of preterm infants with the hypothesis that those infants that received >30% oxygen would have more brain regional oxygen saturations >85% and, thus, the possibility of oxidant injury relative to infants receiving <30%. They found no difference in >85% saturation values between the groups, but more of the infants receiving >30% oxygen had saturations <55%, indicating brain hypoxia. The infants requiring more oxygen had more lung immaturity and presumably a less mature cardiovascular adaptation to birth. This report demonstrates interesting but transient differences in cerebral oxygen saturations. But, the bigger challenge will be to evaluate if the differences are clinically relevant and if measurements of cerebral oxygen saturation are of value during delivery, beyond experimental studies. The physiology is fascinating, and more studies are required to identify which measurements can improve outcomes. Article page 1007<
A
number of clinical trials around the globe, including the Total Body Hypothermia for Neonatal Encephalopathy (TOBY), CoolCap, Infant Cooling Evaluation (ICE), and National Institute of Childhood Health and Human Development (NICHD) Neonatal Research Network (NRN) studies, have demonstrated that therapeutic hypothermia reduces the incidence of neonatal death and long-term neurodevelopmental disability among infants born with acute, moderate-to-severe neonatal encephalopathy, characterized by acidosis and low Apgar scores. Hypothermia has become a standard, though not panacea, for these at-risk newborns. As the implementation of hypothermia within 6 hours of birth has become widespread for perinatal asphyxia, what other practices should become standard? In this issue of The Journal, the NICHD NRN investigators report on the importance of neonatal brain magnetic resonance imaging (MRI) following rewarming to predict future outcome. MRIs were obtained in their trial at approximately 44 weeks postmenstrual age. A normal brain MRI had a sensitivity of 61% and positive predictive Vol. 167, No. 5
value (PPV) of 92% for normal outcome and intelligence quotient (IQ) $ 70 at age 6 to 7 years. However, MRI involvement of either basal ganglia, thalamus, anterior or posterior limb of the internal capsule, or an area of infarction, plus any additional cerebral lesions (or cerebral hemispheric devastation) had an 81% sensitivity and 70% PPV for death or IQ <70 at aged 6 to 7 years. These MRI patterns can be highly helpful to counsel the families of affected newborns. MRI following therapeutic hypothermia should now be a standard procedure. Article page 987<
Transfused RBC survival in very low birth weight infants — Alan H. Jobe, MD, PhD
November 2015
T
he textbook descriptions of red blood cell (RBC) survival are that newborn RBC survival is shorter than adult RBC for a number of reasons. Widness et al asked if RBC survival from transfused adult blood differed from autologous RBC in sick, very low birth weight infants. Their anticipation was that transfused adult RBC would survive longer than endogenous RBC in the circulation of the premature infant. They labeled adult RBC and autologous RBC from the preterm infants with different amounts of biotin and tracked transfused RBC survival over 7 weeks. They also tracked cells in some infants with mismatched Kidd antigen to verify the biotin labeling techniques did not change RBC survival. Interpretation of the experiment was complicated by repeated blood sampling and transfusions in this sick premature population. Nevertheless, RBC from adults and premature infants had similar survival rates for weeks after transfusion. This unanticipated result using high-resolution techniques challenges past information about the survival of the infant RBC. The circulatory environment of the very low birth weight infant is determining the survival of both autologous and adult RBC. The techniques used for this study could be profitability applied to learn more about RBC survival in other clinical settings in infants and children. Article page 1001<
949
Read my mind — Paul G. Fisher, MD
Reporting “perceptions” — Thomas R. Welch, MD
Charting the course of young children with cystic fibrosis — Steven H. Abman, MD
Copyright ª 2015 by Elsevier Inc.
D
yslexia is a difficulty in reading unexpected in relation to intelligence. This language disorder likely is rooted in difficulties processing the sounds of speech and unawareness of phonemes, the smallest elements of sound. Perhaps 1 in 20 (or more) school children suffer from this learning disability; and most are not identified until third grade or later. Can dyslexia be identified as early as first grade? Does the gap been reading and intelligence change over time? In this issue of The Journal, Ferrer et al demonstrate that the gap can be seen as early as first grade, using a cohort of 414 children from the Connecticut Longitudinal Study. The gap persisted over time at a relatively constant difference. Dyslexia can be identified at the first grade. The authors make a strong plea for early identification of and intervention in young children at risk for dyslexia by kindergarten or even preschool. Although this is a laudable goal, definitive evidence that earlier intervention will result in superior outcomes is still limited. Identification of children before ages 3 or 4 years is not so straightforward, when children are not yet reading. Even at ages 5 or 6 years, pediatricians are not accustomed to screening for reading difficulties. Clearly greater awareness of dyslexia is needed along with research on which interventions will consistently lead to improvements when started at the earliest possible ages. Article page 1121< his issue of The Journal includes a study that is noteworthy for two very different reasons. Guise et al from the Oregon Health Sciences University remind us that health care often begins with the emergency medical services (EMS) system. Although the quality and safety of inpatient hospital care has been the subject of a wealth of initiatives and reports, there has been little work done examining the prevention of safety events and errors in the over one million pediatric EMS encounters annually. Although the report does not address the issue directly, it provides a nice map of several targets for safety studies in the pediatric prehospital environment. What also is noteworthy about the study is the approach. On its face, the study was accomplished by a survey of EMS providers to obtain their thoughts about potential causes of safety events. The Journal receives scores of manuscripts reporting such surveys, the bulk of which we do not publish. The article by Guise et al, however, is a model of how surveys can be designed and implemented to produce reliable results. From selection of the target population, to survey design and testing, to implementation and reporting, this article sets a standard by which such studies can be judged. Article page 1143<
T
I
n addition to aggressive monitoring of disease course and the use of novel strategies for respiratory and antimicrobial therapies, marked attention to the maintenance of excellent growth and nutrition has played a key role in improving long-term outcomes of children with cystic fibrosis (CF). CF centers play particular attention to changes in growth measurements as useful markers of nutrition and disease activity, leading to earlier and more rigorous evaluations and interventions. As such, the optimal care of young children with CF is highly dependent on the use of standardized growth 947
charts. In this study, Zhang et al analyzed data from 2587 children followed in the Cystic Fibrosis Foundation Patient Data Registry in order to compare differences in the classification of growth status of young children with CF as assessed by the World Health Organization (WHO) and Centers for Disease Control (CDC) growth percentiles. Currently, WHO standards often are followed up to 23.9 months, followed by the use of CDC references. Among several findings, this study reports that using weight status measures (weight-for-length and body mass index) at 24 months, 26% of children who were classified as normal growth using WHO references were underweight using CDC references. These findings are important to ensure greater understanding of the potential impact of changing growth standards on the interpretation of individual growth status, the impact on clinical practice, and to allow accurate comparisons between CF centers. These findings further set the stage to explore relationships between early nutritional interventions and long-term growth and pulmonary outcomes. Article page 1089<
Cerebral oxygenation following preterm delivery — Alan H. Jobe, MD, PhD
Warming up to the need for MRI after hypothermia — Paul G. Fisher, MD
948
T
he Neonatal Resuscitation Program (NRP) has progressed over 25 years from assumptions and professional opinion about resuscitation of the term infant to evidence-based recommendations for the initial support of both term and preterm infants. This evidence base has been developed by interested investigators using traditional and newer monitoring techniques to measure the transitions in oxygenation, cardiopulmonary function, and metabolism following birth. Supplemental oxygen can cause oxidant exposures that may cause long-term organ injury. As the monitoring has improved, the challenges are to learn if monitoring can change outcomes rather than simply improve physiologic variables that may not impact long-term outcomes. The report by Kenosi et al illustrates this point. They evaluated cerebral oxygenation immediately following delivery of preterm infants with the hypothesis that those infants that received >30% oxygen would have more brain regional oxygen saturations >85% and, thus, the possibility of oxidant injury relative to infants receiving <30%. They found no difference in >85% saturation values between the groups, but more of the infants receiving >30% oxygen had saturations <55%, indicating brain hypoxia. The infants requiring more oxygen had more lung immaturity and presumably a less mature cardiovascular adaptation to birth. This report demonstrates interesting but transient differences in cerebral oxygen saturations. But, the bigger challenge will be to evaluate if the differences are clinically relevant and if measurements of cerebral oxygen saturation are of value during delivery, beyond experimental studies. The physiology is fascinating, and more studies are required to identify which measurements can improve outcomes. Article page 1007<
A
number of clinical trials around the globe, including the Total Body Hypothermia for Neonatal Encephalopathy (TOBY), CoolCap, Infant Cooling Evaluation (ICE), and National Institute of Childhood Health and Human Development (NICHD) Neonatal Research Network (NRN) studies, have demonstrated that therapeutic hypothermia reduces the incidence of neonatal death and long-term neurodevelopmental disability among infants born with acute, moderate-to-severe neonatal encephalopathy, characterized by acidosis and low Apgar scores. Hypothermia has become a standard, though not panacea, for these at-risk newborns. As the implementation of hypothermia within 6 hours of birth has become widespread for perinatal asphyxia, what other practices should become standard? In this issue of The Journal, the NICHD NRN investigators report on the importance of neonatal brain magnetic resonance imaging (MRI) following rewarming to predict future outcome. MRIs were obtained in their trial at approximately 44 weeks postmenstrual age. A normal brain MRI had a sensitivity of 61% and positive predictive Vol. 167, No. 5
value (PPV) of 92% for normal outcome and intelligence quotient (IQ) $ 70 at age 6 to 7 years. However, MRI involvement of either basal ganglia, thalamus, anterior or posterior limb of the internal capsule, or an area of infarction, plus any additional cerebral lesions (or cerebral hemispheric devastation) had an 81% sensitivity and 70% PPV for death or IQ <70 at aged 6 to 7 years. These MRI patterns can be highly helpful to counsel the families of affected newborns. MRI following therapeutic hypothermia should now be a standard procedure. Article page 987<
Transfused RBC survival in very low birth weight infants — Alan H. Jobe, MD, PhD
November 2015
T
he textbook descriptions of red blood cell (RBC) survival are that newborn RBC survival is shorter than adult RBC for a number of reasons. Widness et al asked if RBC survival from transfused adult blood differed from autologous RBC in sick, very low birth weight infants. Their anticipation was that transfused adult RBC would survive longer than endogenous RBC in the circulation of the premature infant. They labeled adult RBC and autologous RBC from the preterm infants with different amounts of biotin and tracked transfused RBC survival over 7 weeks. They also tracked cells in some infants with mismatched Kidd antigen to verify the biotin labeling techniques did not change RBC survival. Interpretation of the experiment was complicated by repeated blood sampling and transfusions in this sick premature population. Nevertheless, RBC from adults and premature infants had similar survival rates for weeks after transfusion. This unanticipated result using high-resolution techniques challenges past information about the survival of the infant RBC. The circulatory environment of the very low birth weight infant is determining the survival of both autologous and adult RBC. The techniques used for this study could be profitability applied to learn more about RBC survival in other clinical settings in infants and children. Article page 1001<
949