- Email: [email protected]
Filtered sunlight noninferior to conventional phototherapy
Translating Best Evidence into Best Care EDITOR’S NOTE: Studies for this issue were identified using the Clinical Queries feature of PubMed, “hand” searching JAMA Pediatrics, Pediatrics, and The Journal of Pediatrics, and from customized EvidenceUpdates alerts. EBM PEARL: THE 95% CONFIDENCE INTERVAL (CI), PART 1: The 95% CI for an effect measure (eg, a treatment effect, an adverse effect, a likelihood ratio) is a range of possible values in which the “true” effect has a 95% chance of residing. The effect measured in an experiment is the most likely “true” effect, with all the others contained in the 95% CI less likely and following a Gaussian curve around the measured effect. The 95% CI also is a measure of precision, where precision is a measure of uncertainty associated with the effect measure. The higher the precision, the more certainty, the closer the upper and lower 95% CI limits are to each other, and the “tighter” they are around the effect measure. If the 95% CI contains the value of no difference between experimental groups, the 2 groups are not statistically different from each other. LITERATURE SEARCH PEARL: CITATION INDICES: A citation index is a bibliographic database that has many uses. The two most used indices in the health sciences are Scopus (scopus.com) and Web of Science (wokinfo.com). The classic use of a citation index is to identify which later articles cited earlier articles. Other uses include identifying articles published by a particular researcher, the number times an article is cited by other articles, and the number of times one researcher’s articles are cited by other researchers’ articles. Another a popular use is calculation of the journal Impact Factor, a measure of the how often the average article in a journal has been cited in a particular year. One journal can compare its Impact Factor with other journals in its field. Finally, citation indices can measure the h-index, a type of Impact Factor for individual researchers, which measures both productivity and scientific influence (based on number of citations). —Jordan Hupert, MD
Filtered sunlight noninferior to conventional phototherapy Slusher TM, Olusanya BO, Vreman HJ, Brearley AM, Vaucher YE, Lund TC, et al. A Randomized Trial of Phototherapy with Filtered Sunlight in African Neonates. N Engl J Med. 2015;373:1115-24. Question Among term or near-term neonates, what is the efficacy of filtered sunlight, compared with conventional phototherapy, in hyperbilirubinemia resolution? Design Randomized, controlled, noninferiority trial. Setting Maternity hospital in Lagos, Nigeria. Participants Term and late-preterm neonates. Intervention Filtered sunlight compared with conventional phototherapy. Outcomes Bilirubin increase of less than 0.2 mg/dl/hr or a serum bilirubin decrease. 10% noninferiority margin. Main Results Filtered sunlight was efficacious on 93% (95% CI, 89 to 96) of treatment days that could be evaluated, as compared with 90% (95% CI, 86 to 93) for conventional phototherapy. Conclusions Filtered sunlight was noninferior to conventional phototherapy. Commentary Photons emitted by blue-to-green light (450 to 490 nm) can photo-alter bilirubin molecules, which deposit in the subcutaneous tissue and/or circulate in the
vascular space.1,2 The bioengineering novelty of this study was to take advantage of known principles of physics to filter the broad spectrum of sunlight using select windowtinting films to transmit only safe and efficacious blue light to lower total bilirubin levels. The investigators constructed special annexes that allowed for maternal care of their newborns with jaundice while being exposed to filtered sunlight phototherapy. A trans-disciplinary approach bridged challenges collecting data, adhering to a study design, and attaining data integrity. Clinicians and researchers should be attentive to these important technical and organizational issues. More importantly, effective replication and safe implementation of this novel approach in community settings require the clinical resources described by Slusher et al. Families of newborns at risk for acute bilirubin encephalopathy may require emergency access to exchange transfusion. However, in many countries, these families are not able to access well-organized, modern perinatal health services. Thus, there is a need to implement, as well as to encourage effective and preventive phototherapy at, or adjacent to, the local community birthing facility. At the same time, systems must be developed for timely transport to regionalized, expert, newborn care at perinatal centers. Vinod K. Bhutani, MD Stanford University School of Medicine Stanford, California 341
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References 1. Maisels MJ, McDonagh AF. Phototherapy for neonatal jaundice. N Engl J Med 2008;358:920-8. 2. Bhutani VK, Committee on Fetus and Newborn, American Academy of Pediatrics. Phototherapy to prevent severe neonatal hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2011; 128:e1046-52.
Volume 170 In a previous meta-analysis, Morgan et al observed delayed introduction of progressive enteral feeds beyond four days did not reduce the incidence of NEC in VLBW infants.3 Clinical trials including extremely low birth weight (<1000 g) and infants with growth restriction will enhance our understanding of feeding-advancement rate effects on NEC incidence. Based on this meta-analysis, it would be reasonable to advance enteral feeds by 30-40 ml/kg/day in clinically stable VLBW infants. Sachin Amin, MD University of Illinois at Chicago Chicago, Illinois
Rapid feed advancement appears protective in very low birth weight infants Morgan J, Young L, McGuire W. Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev 2015;10:CD001241. Question Among very preterm (<32 weeks gestation) or very low birth weight (VLBW) infants (<1500 g), what is the therapeutic efficacy of slow, compared with fast enteral feed advancement, in decreasing the incidence and mortality of necrotizing enterocolitis (NEC)? Design Meta-analysis of 9 randomized or quasi-randomized controlled trials. Setting North America, India, Turkey and South Africa. Participants Very preterm or VLBW infants.
References 1. Patole SK, de Klerk N. Impact of standardized feeding regimens on incidence of neonatal necrotising enterocolitis: a systematic review and metaanalysis of observational studies. Arch Dis Child Fetal Neonatal Ed 2005; 90:F147-51. 2. Fallon EM, Nehra D, Potemkin AK, Gura KM, Simpser E, Compher C. A.S.P.E.N. clinical guidelines: nutrition support of neonatal patients at risk for necrotizing enterocolitis. JPEN J Parenter Enteral Nutr 2012;36: 506-23. 3. Morgan J, Young L, McGuire W. Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev 2014;12:CD001970.
Intervention Slow (15-24 ml/kg/day) vs fast (30-40 ml/kg/ day) enteral feed advancement. Outcomes Incidence of NEC and mortality. Main results There was no statistically significant difference in the incidence of NEC: absolute risk increase (ARI), 0.4% (95% CI, -2.9% to 3.6%), or all-cause mortality: ARI, 2.8% (95% CI, -2.7% to 8.3%). Slow feed advancement was associated with delayed establishment of full enteral nutrition by one to five days, and increased risk of invasive infection: ARI, 7.3% (95% CI, 0.8% to 13.8%), number needed to harm, 14 (95% CI, 8 to 100).
Air pollutants associated with astrocytoma and medulloblastoma Danysh HE, Mitchell LE, Zhang K, Scheurer ME, Lupo PJ. Traffic-related air pollution and the incidence of childhood central nervous system tumors: Texas, 2001-2009. Pediatr Blood Cancer. 2015;62:1572-8. Question What is the association among children with central nervous system (CNS) tumors and traffic-related air pollution?
Conclusions Fast advancement of feeds was not associated with increased incidence of NEC or death, and was protective against invasive infection in very preterm or VLBW infants.
Design Retrospective, population-based study.
Commentary Necrotizing enterocolitis is the most common gastrointestinal emergency in preterm infants and is typically associated with high rates of morbidity and mortality. In this feeding-advancement meta-analysis, most infants were more than 1000 g at birth. As very sick infants were excluded in 3 trials, as well as infants with intrauterine growth restriction, the conclusions of this study may not be applicable to infants most at risk for NEC. Patole et al found that centers with standardized feeding regimens had lower incidence of NEC.1 This effect of standardized feeding regimens may have been due to increased awareness and early detection and management of stage 1 NEC, and not to variations in the regimen. Other factors affecting NEC incidence include breast feeding (protective)2 and continuous versus bolus feeds.
Participants <15 years old, residing in Texas during 20012009.
342
Setting Texas.
Intervention Exposure and cancer linkage based on the Texas Cancer Registry and the 2005 US Environmental Protection Agency’s Assessment System for Population Exposure Nationwide. Outcomes CNS tumors diagnosed 2001-2009. Main Results Medium and medium-high 1,3-butadiene concentrations had higher astrocytoma incidence rates: adjusted incidence rate ratio (aIRR), 1.46 (95% CI, 1.05 to 2.01) and 1.69 (95% CI, 1.22 to 2.33), respectively, compared with low concentrations. Medium diesel particulate matter concentrations had higher astrocytoma and medulloblastoma incidence rates: aIRR, 1.42 (95% CI, 1.05 to 1.94) and
CURRENT BEST EVIDENCE
March 2016 aIRR, 1.46 (95% CI, 1.01 to 2.12), respectively, compared with low concentrations. Conclusions Air pollutants are associated with childhood astrocytoma and medulloblastoma. Commentary This study adds further evidence to potential risk factors of CNS tumors in children. Currently, the only established environmental risk factor is ionizing radiation.1 Only a few studies previously investigated specific childhood CNS tumors in relation to traffic related air pollution.2,3 The study by Danysh et al includes a sufficiently large number of cases to investigate the major histologic types. The strongest evidence of an association was found for astrocytomas (other than juvenile pilocytic astrocytoma), and the strongest associations, though not statistically significant, were found for primitive neuroectodermal tumors. These findings must be interpreted with caution. Exposure was measured at the level of census tracts and may only poorly reflect children’s actual exposure levels. The failure to account for changes in census tract population levels over the study period may also have biased results. Nonetheless, the results point to potential etiologic differences between childhood CNS tumor phenotypes and could indicate that, in some children, etiology is related to traffic emissions. Ben Daniel Spycher, PhD University of Bern Bern, Switzerland
References 1. Johnson KJ, Cullen J, Barnholtz-Sloan JS, Ostrom QT, Langer CE, Turner MC, et al. Childhood brain tumor epidemiology: a brain tumor epidemiology consortium review. Cancer Epidemiol Biomarkers Prev 2014;23:2716-36. 2. Ghosh JK, Heck JE, Cockburn M, Su J, Jerrett M, Ritz B. Prenatal exposure to traffic-related air pollution and risk of early childhood cancers. Am J Epidemiol 2013;178:1233-9. 3. Heck JE, Wu J, Lombardi C, Qiu J, Meyers TJ, Wilhelm M, et al. Childhood cancer and traffic-related air pollution exposure in pregnancy and early life. Environ Health Perspect 2013;121:1385-91.
Participants Neonates at risk for neonatal hypoglycemia: maternal diabetes, preterm (gestational age of <37 weeks), or weight (<10th percentile or <2500 g) (>90th percentile or >4500 g). Staff intermittently measured blood glucose. Glucose monitors continuously monitoring interstitial glucose concentrations were masked to clinical staff. Intervention Bayley Scales of Infant Development III and tests of executive and visual function. Outcomes Neurosensory impairment and processing difficulty at 2 years old. Main Results Hypoglycemia, treated to maintain a blood glucose concentration of at least 47 mg/dl, was not associated with neurosensory impairment: risk ratio, 0.95 (95% CI, 0.75 to 1.20) or processing difficulty: risk ratio, 0.92 (95% CI, 0.56 to 1.51). Conclusions Neonatal hypoglycemia was not associated with an adverse neurologic outcome when treatment was provided to maintain a blood glucose concentration of at least 47 mg/dl. Commentary The Children with Hypoglycaemia and their Later Development (CHYLD) Study demonstrated that by setting the glucose treatment goal to 47 mg/dl and closely monitoring and rapidly treating hypoglycemia, long-term neurologic outcomes were equal among those who had hypoglycemia and those who did not. However, that does not mean there was no risk of adverse neurosensory outcome in this at-risk group. Fourteen of 33 (42%) children with unrecognized hypoglycemia and 45/108 (42%) with recognized hypoglycemia had an adverse neurosensory outcome. One may reasonably ask if it is the risk factors for the development of hypoglycemia rather than the hypoglycemia itself that resulted in the adverse outcome or indeed if the hypoglycemia is a marker of impaired metabolic adaptation in infants already at risk for adverse outcomes. This study, in conjunction with two other studies,1,2 demonstrated that there is no clear answer to whether physiologic transitional hypoglycemia, pathologic transient, or persistent hypoglycemia in atrisk babies are the same in terms of neurologic outcome. For now, the recommendations3 to maintain the glucose levels >50 mg/dl in at-risk babies are safe until further evidence is obtained.
Neonates at risk for hypoglycemia: associated neurological outcomes McKinlay CJ, Alsweiler JM, Ansell JM, Anstice NS, Chase JG, Gamble GD, et al. Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years. N Engl J Med. 2015;373: 1507-18. Question Among neonates at risk for hypoglycemia and treated to maintain a glucose at least 47 mg/dl, what is the association of hypoglycemia with adverse neurological outcomes at 2 years old? Design Prospective cohort. Setting Waikato Hospital, Hamilton, New Zealand.
Paul S. Thornton, MB, BCh Cook Children’s Medical Center Fort Worth, Texas
References 1. Harris DL, Alsweiler JM, Ansell JM, Gamble GD, Thompson B, Wouldes TA, et al. Outcome at 2 years after dextrose gel treatment for neonatal hypoglycemia: follow-up of a randomized trial. J Pediatr 2016; 170:54-9. 2. Kaiser IR, Bai S, Gibson N, Holland G, Lin TM, Swearingen CJ, et al. Association Between Transient Newborn Hypoglycemia and Fourth-Grade Achievement Test Proficiency: A Population-Based Study. JAMA Pediatr 2015;169:913-21. 343
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3. Thornton PS, Stanley CA, De Leon D, Harris DL, Haymond M, Hussain K, et al. Recommendations from the Pediatric Endocrine Society For Evaluation And Management Of Persistent Hypoglycemia In Neonates, Infants, And Children. J Pediatr 2015; 166:1520-5.
Dyslexia identified early and persists into adolescence Ferrer E, Shaywitz BA, Holahan JM, Marchione KE, Michaels R, Shaywitz SE. Achievement Gap in Reading Is Present as Early as First Grade and Persists through Adolescence. J Pediatr. 2015;167:1121-5. Question Among children with dyslexia, what is the prognosis for normal reading attainment, compared with children without dyslexia? Design Prospective cohort of the Connecticut Longitudinal Study (CLS). Setting Connecticut public school system. Participants Children, kindergarten through 12th grade. Intervention Measures of reading and IQ. Outcomes Reading scores and verbal IQ. Main Results As early as first grade, compared with typical readers, readers with dyslexia had lower reading scores and verbal IQ, and their trajectories over time never converge with those of typical readers. Conclusions The achievement gap between typical readers and readers with dyslexia is evident as early as first grade, and this gap persists into adolescence. Commentary Longitudinal studies about dyslexia are rare. The CLS is a longitudinal, population-based study, in contrast to the temporally-limited clinical studies dominating the dyslexia field. The CLS, initiated in 1983, followed 445 children for more than 20 years. This in itself was a notable
344
Volume 170 achievement, which has influenced international dyslexia research in many ways, not the least of which is that it found almost as many girls as boys developed dyslexia. In the current study, Ferrer et al demonstrated persistent reading and verbal IQ differences between a group with identified dyslexia and controls. However, because the study used data collected more than 20 years ago, updated research findings should have been incorporated into the current study’s design. For instance, recent research points to the multifactorial etiology of dyslexia, showing that the achievement gap between typical readers and those who develop dyslexia can be seen earlier than first grade, as is pointed out in the study.1 The present study refers to a very high prevalence (17%-21%) of schoolage children affected by dyslexia. This is not in line with current views, which differentiate between “false dyslexia,” explained by environmental factors, and “true dyslexia,” explained by constitutional factors.2 In the international literature, reading impairment is generally observed to ameliorate over time, and writing problems persist through adulthood.3 Using the “true dyslexia” definition, which includes writing difficulties, would alter the sampling criteria and lead to a lower “true dyslexia” occurrence rate. Thus, one may debate the criteria used for dyslexia identification in the present study. Turid Helland, PhD University of Bergen Bergen, Norway
References 1. van Bergen E, van der Leij A, de Jong PF. The intergenerational multiple deficit model and the case of dyslexia. Front Hum Neurosci 2014;8:346. 2. Frith U. Paradoxes in the definition of dyslexia. Dyslexia 1999;5:192-214. 3. Berninger VW, Nielsen KH, Abbott RD, Wijsman E, Raskind W. Writing problems in developmental dyslexia: Under-recognized and undertreated. J Sch Psychol 2008;46:1-21.
Filtered sunlight noninferior to conventional phototherapy Slusher TM, Olusanya BO, Vreman HJ, Brearley AM, Vaucher YE, Lund TC, et al. A Randomized Trial of Phototherapy with Filtered Sunlight in African Neonates. N Engl J Med. 2015;373:1115-24. Question Among term or near-term neonates, what is the efficacy of filtered sunlight, compared with conventional phototherapy, in hyperbilirubinemia resolution? Design Randomized, controlled, noninferiority trial. Setting Maternity hospital in Lagos, Nigeria. Participants Term and late-preterm neonates. Intervention Filtered sunlight compared with conventional phototherapy. Outcomes Bilirubin increase of less than 0.2 mg/dl/hr or a serum bilirubin decrease. 10% noninferiority margin. Main Results Filtered sunlight was efficacious on 93% (95% CI, 89 to 96) of treatment days that could be evaluated, as compared with 90% (95% CI, 86 to 93) for conventional phototherapy. Conclusions Filtered sunlight was noninferior to conventional phototherapy. Commentary Photons emitted by blue-to-green light (450 to 490 nm) can photo-alter bilirubin molecules, which deposit in the subcutaneous tissue and/or circulate in the
vascular space.1,2 The bioengineering novelty of this study was to take advantage of known principles of physics to filter the broad spectrum of sunlight using select windowtinting films to transmit only safe and efficacious blue light to lower total bilirubin levels. The investigators constructed special annexes that allowed for maternal care of their newborns with jaundice while being exposed to filtered sunlight phototherapy. A trans-disciplinary approach bridged challenges collecting data, adhering to a study design, and attaining data integrity. Clinicians and researchers should be attentive to these important technical and organizational issues. More importantly, effective replication and safe implementation of this novel approach in community settings require the clinical resources described by Slusher et al. Families of newborns at risk for acute bilirubin encephalopathy may require emergency access to exchange transfusion. However, in many countries, these families are not able to access well-organized, modern perinatal health services. Thus, there is a need to implement, as well as to encourage effective and preventive phototherapy at, or adjacent to, the local community birthing facility. At the same time, systems must be developed for timely transport to regionalized, expert, newborn care at perinatal centers. Vinod K. Bhutani, MD Stanford University School of Medicine Stanford, California 341
THE JOURNAL OF PEDIATRICS
www.jpeds.com
References 1. Maisels MJ, McDonagh AF. Phototherapy for neonatal jaundice. N Engl J Med 2008;358:920-8. 2. Bhutani VK, Committee on Fetus and Newborn, American Academy of Pediatrics. Phototherapy to prevent severe neonatal hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2011; 128:e1046-52.
Volume 170 In a previous meta-analysis, Morgan et al observed delayed introduction of progressive enteral feeds beyond four days did not reduce the incidence of NEC in VLBW infants.3 Clinical trials including extremely low birth weight (<1000 g) and infants with growth restriction will enhance our understanding of feeding-advancement rate effects on NEC incidence. Based on this meta-analysis, it would be reasonable to advance enteral feeds by 30-40 ml/kg/day in clinically stable VLBW infants. Sachin Amin, MD University of Illinois at Chicago Chicago, Illinois
Rapid feed advancement appears protective in very low birth weight infants Morgan J, Young L, McGuire W. Slow advancement of enteral feed volumes to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev 2015;10:CD001241. Question Among very preterm (<32 weeks gestation) or very low birth weight (VLBW) infants (<1500 g), what is the therapeutic efficacy of slow, compared with fast enteral feed advancement, in decreasing the incidence and mortality of necrotizing enterocolitis (NEC)? Design Meta-analysis of 9 randomized or quasi-randomized controlled trials. Setting North America, India, Turkey and South Africa. Participants Very preterm or VLBW infants.
References 1. Patole SK, de Klerk N. Impact of standardized feeding regimens on incidence of neonatal necrotising enterocolitis: a systematic review and metaanalysis of observational studies. Arch Dis Child Fetal Neonatal Ed 2005; 90:F147-51. 2. Fallon EM, Nehra D, Potemkin AK, Gura KM, Simpser E, Compher C. A.S.P.E.N. clinical guidelines: nutrition support of neonatal patients at risk for necrotizing enterocolitis. JPEN J Parenter Enteral Nutr 2012;36: 506-23. 3. Morgan J, Young L, McGuire W. Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev 2014;12:CD001970.
Intervention Slow (15-24 ml/kg/day) vs fast (30-40 ml/kg/ day) enteral feed advancement. Outcomes Incidence of NEC and mortality. Main results There was no statistically significant difference in the incidence of NEC: absolute risk increase (ARI), 0.4% (95% CI, -2.9% to 3.6%), or all-cause mortality: ARI, 2.8% (95% CI, -2.7% to 8.3%). Slow feed advancement was associated with delayed establishment of full enteral nutrition by one to five days, and increased risk of invasive infection: ARI, 7.3% (95% CI, 0.8% to 13.8%), number needed to harm, 14 (95% CI, 8 to 100).
Air pollutants associated with astrocytoma and medulloblastoma Danysh HE, Mitchell LE, Zhang K, Scheurer ME, Lupo PJ. Traffic-related air pollution and the incidence of childhood central nervous system tumors: Texas, 2001-2009. Pediatr Blood Cancer. 2015;62:1572-8. Question What is the association among children with central nervous system (CNS) tumors and traffic-related air pollution?
Conclusions Fast advancement of feeds was not associated with increased incidence of NEC or death, and was protective against invasive infection in very preterm or VLBW infants.
Design Retrospective, population-based study.
Commentary Necrotizing enterocolitis is the most common gastrointestinal emergency in preterm infants and is typically associated with high rates of morbidity and mortality. In this feeding-advancement meta-analysis, most infants were more than 1000 g at birth. As very sick infants were excluded in 3 trials, as well as infants with intrauterine growth restriction, the conclusions of this study may not be applicable to infants most at risk for NEC. Patole et al found that centers with standardized feeding regimens had lower incidence of NEC.1 This effect of standardized feeding regimens may have been due to increased awareness and early detection and management of stage 1 NEC, and not to variations in the regimen. Other factors affecting NEC incidence include breast feeding (protective)2 and continuous versus bolus feeds.
Participants <15 years old, residing in Texas during 20012009.
342
Setting Texas.
Intervention Exposure and cancer linkage based on the Texas Cancer Registry and the 2005 US Environmental Protection Agency’s Assessment System for Population Exposure Nationwide. Outcomes CNS tumors diagnosed 2001-2009. Main Results Medium and medium-high 1,3-butadiene concentrations had higher astrocytoma incidence rates: adjusted incidence rate ratio (aIRR), 1.46 (95% CI, 1.05 to 2.01) and 1.69 (95% CI, 1.22 to 2.33), respectively, compared with low concentrations. Medium diesel particulate matter concentrations had higher astrocytoma and medulloblastoma incidence rates: aIRR, 1.42 (95% CI, 1.05 to 1.94) and
CURRENT BEST EVIDENCE
March 2016 aIRR, 1.46 (95% CI, 1.01 to 2.12), respectively, compared with low concentrations. Conclusions Air pollutants are associated with childhood astrocytoma and medulloblastoma. Commentary This study adds further evidence to potential risk factors of CNS tumors in children. Currently, the only established environmental risk factor is ionizing radiation.1 Only a few studies previously investigated specific childhood CNS tumors in relation to traffic related air pollution.2,3 The study by Danysh et al includes a sufficiently large number of cases to investigate the major histologic types. The strongest evidence of an association was found for astrocytomas (other than juvenile pilocytic astrocytoma), and the strongest associations, though not statistically significant, were found for primitive neuroectodermal tumors. These findings must be interpreted with caution. Exposure was measured at the level of census tracts and may only poorly reflect children’s actual exposure levels. The failure to account for changes in census tract population levels over the study period may also have biased results. Nonetheless, the results point to potential etiologic differences between childhood CNS tumor phenotypes and could indicate that, in some children, etiology is related to traffic emissions. Ben Daniel Spycher, PhD University of Bern Bern, Switzerland
References 1. Johnson KJ, Cullen J, Barnholtz-Sloan JS, Ostrom QT, Langer CE, Turner MC, et al. Childhood brain tumor epidemiology: a brain tumor epidemiology consortium review. Cancer Epidemiol Biomarkers Prev 2014;23:2716-36. 2. Ghosh JK, Heck JE, Cockburn M, Su J, Jerrett M, Ritz B. Prenatal exposure to traffic-related air pollution and risk of early childhood cancers. Am J Epidemiol 2013;178:1233-9. 3. Heck JE, Wu J, Lombardi C, Qiu J, Meyers TJ, Wilhelm M, et al. Childhood cancer and traffic-related air pollution exposure in pregnancy and early life. Environ Health Perspect 2013;121:1385-91.
Participants Neonates at risk for neonatal hypoglycemia: maternal diabetes, preterm (gestational age of <37 weeks), or weight (<10th percentile or <2500 g) (>90th percentile or >4500 g). Staff intermittently measured blood glucose. Glucose monitors continuously monitoring interstitial glucose concentrations were masked to clinical staff. Intervention Bayley Scales of Infant Development III and tests of executive and visual function. Outcomes Neurosensory impairment and processing difficulty at 2 years old. Main Results Hypoglycemia, treated to maintain a blood glucose concentration of at least 47 mg/dl, was not associated with neurosensory impairment: risk ratio, 0.95 (95% CI, 0.75 to 1.20) or processing difficulty: risk ratio, 0.92 (95% CI, 0.56 to 1.51). Conclusions Neonatal hypoglycemia was not associated with an adverse neurologic outcome when treatment was provided to maintain a blood glucose concentration of at least 47 mg/dl. Commentary The Children with Hypoglycaemia and their Later Development (CHYLD) Study demonstrated that by setting the glucose treatment goal to 47 mg/dl and closely monitoring and rapidly treating hypoglycemia, long-term neurologic outcomes were equal among those who had hypoglycemia and those who did not. However, that does not mean there was no risk of adverse neurosensory outcome in this at-risk group. Fourteen of 33 (42%) children with unrecognized hypoglycemia and 45/108 (42%) with recognized hypoglycemia had an adverse neurosensory outcome. One may reasonably ask if it is the risk factors for the development of hypoglycemia rather than the hypoglycemia itself that resulted in the adverse outcome or indeed if the hypoglycemia is a marker of impaired metabolic adaptation in infants already at risk for adverse outcomes. This study, in conjunction with two other studies,1,2 demonstrated that there is no clear answer to whether physiologic transitional hypoglycemia, pathologic transient, or persistent hypoglycemia in atrisk babies are the same in terms of neurologic outcome. For now, the recommendations3 to maintain the glucose levels >50 mg/dl in at-risk babies are safe until further evidence is obtained.
Neonates at risk for hypoglycemia: associated neurological outcomes McKinlay CJ, Alsweiler JM, Ansell JM, Anstice NS, Chase JG, Gamble GD, et al. Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years. N Engl J Med. 2015;373: 1507-18. Question Among neonates at risk for hypoglycemia and treated to maintain a glucose at least 47 mg/dl, what is the association of hypoglycemia with adverse neurological outcomes at 2 years old? Design Prospective cohort. Setting Waikato Hospital, Hamilton, New Zealand.
Paul S. Thornton, MB, BCh Cook Children’s Medical Center Fort Worth, Texas
References 1. Harris DL, Alsweiler JM, Ansell JM, Gamble GD, Thompson B, Wouldes TA, et al. Outcome at 2 years after dextrose gel treatment for neonatal hypoglycemia: follow-up of a randomized trial. J Pediatr 2016; 170:54-9. 2. Kaiser IR, Bai S, Gibson N, Holland G, Lin TM, Swearingen CJ, et al. Association Between Transient Newborn Hypoglycemia and Fourth-Grade Achievement Test Proficiency: A Population-Based Study. JAMA Pediatr 2015;169:913-21. 343
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3. Thornton PS, Stanley CA, De Leon D, Harris DL, Haymond M, Hussain K, et al. Recommendations from the Pediatric Endocrine Society For Evaluation And Management Of Persistent Hypoglycemia In Neonates, Infants, And Children. J Pediatr 2015; 166:1520-5.
Dyslexia identified early and persists into adolescence Ferrer E, Shaywitz BA, Holahan JM, Marchione KE, Michaels R, Shaywitz SE. Achievement Gap in Reading Is Present as Early as First Grade and Persists through Adolescence. J Pediatr. 2015;167:1121-5. Question Among children with dyslexia, what is the prognosis for normal reading attainment, compared with children without dyslexia? Design Prospective cohort of the Connecticut Longitudinal Study (CLS). Setting Connecticut public school system. Participants Children, kindergarten through 12th grade. Intervention Measures of reading and IQ. Outcomes Reading scores and verbal IQ. Main Results As early as first grade, compared with typical readers, readers with dyslexia had lower reading scores and verbal IQ, and their trajectories over time never converge with those of typical readers. Conclusions The achievement gap between typical readers and readers with dyslexia is evident as early as first grade, and this gap persists into adolescence. Commentary Longitudinal studies about dyslexia are rare. The CLS is a longitudinal, population-based study, in contrast to the temporally-limited clinical studies dominating the dyslexia field. The CLS, initiated in 1983, followed 445 children for more than 20 years. This in itself was a notable
344
Volume 170 achievement, which has influenced international dyslexia research in many ways, not the least of which is that it found almost as many girls as boys developed dyslexia. In the current study, Ferrer et al demonstrated persistent reading and verbal IQ differences between a group with identified dyslexia and controls. However, because the study used data collected more than 20 years ago, updated research findings should have been incorporated into the current study’s design. For instance, recent research points to the multifactorial etiology of dyslexia, showing that the achievement gap between typical readers and those who develop dyslexia can be seen earlier than first grade, as is pointed out in the study.1 The present study refers to a very high prevalence (17%-21%) of schoolage children affected by dyslexia. This is not in line with current views, which differentiate between “false dyslexia,” explained by environmental factors, and “true dyslexia,” explained by constitutional factors.2 In the international literature, reading impairment is generally observed to ameliorate over time, and writing problems persist through adulthood.3 Using the “true dyslexia” definition, which includes writing difficulties, would alter the sampling criteria and lead to a lower “true dyslexia” occurrence rate. Thus, one may debate the criteria used for dyslexia identification in the present study. Turid Helland, PhD University of Bergen Bergen, Norway
References 1. van Bergen E, van der Leij A, de Jong PF. The intergenerational multiple deficit model and the case of dyslexia. Front Hum Neurosci 2014;8:346. 2. Frith U. Paradoxes in the definition of dyslexia. Dyslexia 1999;5:192-214. 3. Berninger VW, Nielsen KH, Abbott RD, Wijsman E, Raskind W. Writing problems in developmental dyslexia: Under-recognized and undertreated. J Sch Psychol 2008;46:1-21.