A neonatal illness severity score, The Score for Neonatal Acute Physiology-II (SNAP-II), predicts neurodevelopmental impairments at two years of age among children born extremely preterm. We sought to evaluate to what extent SNAP-II is predictive of cognitive and other neurodevelopmental impairments at 10 years of age.
In a cohort of 874 children born before 28 weeks of gestation, we prospectively collected clinical, physiologic and laboratory data to calculate SNAP-II for each infant. When the children were 10 years old, examiners who were unaware of the child’s medical history assessed neurodevelopmental outcomes, including neurocognitive, gross motor, social and communication functions, diagnosis and treatment of seizures or attention deficit hyperactivity disorder (ADHD), academic achievement, and quality of life. We used logistic regression to adjust for potential confounders.
An undesirably high SNAP-II (⩾30), present in 23% of participants, was associated with an increased risk of cognitive impairment (IQ, executive function, language ability), adverse neurological outcomes (epilepsy, impaired gross motor function), behavioral abnormalities (attention deficit disorder and hyperactivity), social dysfunction (autistic spectrum disorder) and education-related adversities (school achievement and need for educational supports. In analyses that adjusted for potential confounders, Z-scores ⩽−1 on 11 of 18 cognitive outcomes were associated with SNAP-II in the highest category, and 6 of 18 were associated with SNAP-II in the intermediate category. Odds ratios and 95% confidence intervals ranged from 1.4 (1.01, 2.1) to 2.1 (1.4, 3.1). Similarly, 2 of the 8 social dysfunctions were associated with SNAP-II in the highest category, and 3 of 8 were associated with SNAP-II in the intermediate category. Odds ratios and 95% confidence intervals were slightly higher for these assessments, ranging from 1.6 (1.1, 2.4) to 2.3 (1.2, 4.6).
Among very preterm newborns, physiologic derangements present in the first 12 postnatal hours are associated with dysfunctions in several neurodevelopmental domains at 10 years of age. We are unable to make inferences about causality.
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Richardson DK, Gray JE, McCormick MC, Workman K, Goldmann DA . Score for Neonatal Acute Physiology: a physiologic severity index for neonatal intensive care. Pediatrics 1993; 91 (3): 617–623.
Richardson DK, Corcoran JD, Escobar GJ, Lee SK . SNAP-II and SNAPPE-II: simplified newborn illness severity and mortality risk scores. J Pediatr 2001; 138 (1): 92–100.
Escobar GJ, Shaheen SM, Breed EM, Botas C, Greene JD, Yoshida CK et al. Richardson score predicts short-term adverse respiratory outcomes in newborns >/=34 weeks gestation. J Pediatr 2004; 145 (6): 754–760.
Chien LY, Whyte R, Thiessen P, Walker R, Brabyn D, Lee SK . Snap-II predicts severe intraventricular hemorrhage and chronic lung disease in the neonatal intensive care unit. J Perinatol 2002; 22 (1): 26–30.
Carvalho PR, Moreira ME, Sa RA, Lopes LM . SNAPPE-II application in newborns with very low birth weight: evaluation of adverse outcomes in severe placental dysfunction. J Perinat Med 2011; 39 (3): 343–347.
Hagadorn JI, Richardson DK, Schmid CH, Cole CH . Cumulative illness severity and progression from moderate to severe retinopathy of prematurity. J Perinatol 2007; 27 (8): 502–509.
Fortes Filho JB, Dill JC, Ishizaki A, Aguiar WW, Silveira RC, Procianoy RS . Score for Neonatal Acute Physiology and Perinatal Extension II as a predictor of retinopathy of prematurity: study in 304 very-low-birth-weight preterm infants. Ophthalmologica 2009; 223 (3): 177–182.
Dammann O, Naples M, Bednarek F, Shah B, Kuban KC, O'Shea TM et al. SNAP-II and SNAPPE-II and the risk of structural and functional brain disorders in extremely low gestational age newborns: the ELGAN study. Neonatology 2010; 97 (2): 71–82.
Dammann O, Shah B, Naples M, Bednarek F, Zupancic J, Allred EN et al. Interinstitutional variation in prediction of death by SNAP-II and SNAPPE-II among extremely preterm infants. Pediatrics 2009; 124 (5): e1001–e1006.
Hack M, Taylor HG, Drotar D, Schluchter M, Cartar L, Wilson-Costello D et al. Poor predictive validity of the Bayley Scales of Infant Development for cognitive function of extremely low birth weight children at school age. Pediatrics 2005; 116 (2): 333–341.
Potharst ES, Houtzager BA, van Sonderen L, Tamminga P, Kok JH, Last BF et al. Prediction of cognitive abilities at the age of 5 years using developmental follow-up assessments at the age of 2 and 3 years in very preterm children. Dev Med Child Neurol 2012; 54 (3): 240–246.
Roberts G, Anderson PJ, Doyle LW . The stability of the diagnosis of developmental disability between ages 2 and 8 in a geographic cohort of very preterm children born in 1997. Arch Dis Child 2010; 95 (10): 786–790.
Aylward GP . Neurodevelopmental outcomes of infants born prematurely. J Dev Behav Pediatrics JDBP 2014; 35 (6): 394–407.
Aylward GP . Cognitive and neuropsychological outcomes: more than IQ scores. Ment Retard Dev Disabl Res Rev 2002; 8 (4): 234–240.
O'Shea TM, Allred EN, Dammann O, Hirtz D, Kuban KC, Paneth N et al. The ELGAN study of the brain and related disorders in extremely low gestational age newborns. Early Hum Dev 2009; 85 (11): 719–725.
Elliott CD . Differential Ability Scales, 2nd edn. Pearson: San Antonio, TX, USA, 2007.
Carrow-Woolfolk E . Oral and Written Language Scales: Written Expression Scale Manual. American Guidance Service: Circle Pines, MN, 1996.
Korkman M, Kemp S . NEPSY: A Developmental Neuropsychological Assessment. The Psychological Corporation: New York, NY, USA, 1998.
Korkman KKU, Kemp S . NEPSY II: Clinical and interpretative manual, 2007b ed. Psychological Corporation: San Antonio, TX, USA, 2007.
Wechsler D . The Wechsler Individual Achievement Test-III. Pearson Assessment: UK, 2009.
Palisano RJ, Rosenbaum P, Bartlett D, Livingston MH . Content validity of the expanded and revised Gross Motor Function Classification System. Dev Med Child Neurol 2008; 50 (10): 744–750.
Constantino JN GC . Social Responsiveness Scale, Second Edition (SRS-2). Western Psychological Services: Los Angeles, CA, USA, 2012.
Rutter M, Bailey A, Lord C . The Social Communication Questionnaire – Manual. Western Psychological Services: Los Angeles, CA, USA, 2003.
Rutter M, Le Couteur A, Lord C . Autism Diagnostic Interview – Revised. Western Psychological Services: Los Angeles, CA, USA, 2003.
Risi S, Lord C, Gotham K, Corsello C, Chrysler C, Szatmari P et al. Combining information from multiple sources in the diagnosis of autism spectrum disorders. J Am Acad Child Adolesc Psychiatry 2006; 45 (9): 1094–1103.
Lord CRM, DiLavore PC . Autism diagnostic observation schedule, second edition: ADOS™-2. Western Psychological Services: Torrance, CA, USA, 2012.
Gadow K.D. SJ . Child Symptom Inventory–4 Screening and Norms Manual. Checkmate Plus: Stony Brook, NY, USA, 2002.
Sprafkin J, Gadow KD, Salisbury H, Schneider J, Loney J . Further evidence of reliability and validity of the Child Symptom Inventory-4: parent checklist in clinically referred boys. J Clin Child Adolesc Psychol 53; 2002; 31 (4): 513–524.
Ikeda E, Hinckson E, Krageloh C . Assessment of quality of life in children and youth with autism spectrum disorder: a critical review. Qual Life Res 2014; 23 (4): 1069–1085.
Varni JW, Seid M, Rode CA . The PedsQL: measurement model for the pediatric quality of life inventory. Med Care 1999; 37 (2): 126–139.
Anderson PJ . Neuropsychological outcomes of children born very preterm. Semin Fetal Neonatal Med 2014; 19 (2): 90–96.
Batton B, Li L, Newman NS, Das A, Watterberg KL, Yoder BA et al. Early blood pressure, antihypotensive therapy and outcomes at 18-22 months' corrected age in extremely preterm infants. Arch Dis Childhood Fetal Neonatal Ed 2016; 101 (3): F201–F206.
Kuint J, Barak M, Morag I, Maayan-Metzger A . Early treated hypotension and outcome in very low birth weight infants. Neonatology 2009; 95 (4): 311–316.
du Plessis AJ . The role of systemic hemodynamic disturbances in prematurity-related brain injury. J Child Neurol 2009; 24 (9): 1127–1140.
Arduini A, Escobar J, Vento M, Escrig R, Quintas G, Sastre J et al. Metabolic adaptation and neuroprotection differ in the retina and choroid in a piglet model of acute postnatal hypoxia. Pediatr Res 2014; 76 (2): 127–134.
Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR . The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics 2000; 106 (4): 659–671.
Wood NS, Marlow N, Costeloe K, Gibson AT, Wilkinson AR . Neurologic and developmental disability after extremely preterm birth. EPICure Study Group. N Engl J Med 2000; 343 (6): 378–384.
Back SA, Craig A, Kayton RJ, Luo NL, Meshul CK, Allcock N et al. Hypoxia-ischemia preferentially triggers glutamate depletion from oligodendroglia and axons in perinatal cerebral white matter. J Cereb Blood Flow Metab 2007; 27 (2): 334–347.
Greisen G, Vannucci RC . Is periventricular leucomalacia a result of hypoxic-ischaemic injury? Hypocapnia and the preterm brain. Biol Neonate 2001; 79 (3-4): 194–200.
Limperopoulos C, Bassan H, Kalish LA, Ringer SA, Eichenwald EC, Walter G et al. Current definitions of hypotension do not predict abnormal cranial ultrasound findings in preterm infants. Pediatrics 2007; 120 (5): 966–977.
Saugstad OD, Aune D . Optimal oxygenation of extremely low birth weight infants: a meta-analysis and systematic review of the oxygen saturation target studies. Neonatology 2014; 105 (1): 55–63.
Manja V, Lakshminrusimha S, Cook DJ . Oxygen saturation target range for extremely preterm infants: a systematic review and meta-analysis. JAMA Pediatr 2015; 169 (4): 332–340.
Logan JW, O'Shea TM, Allred EN, Laughon MM, Bose CL, Dammann O et al. Early postnatal hypotension and developmental delay at 24 months of age among extremely low gestational age newborns. Arch Dis Child Fetal Neonatal Ed 2011; 96 (5): F321–F328.
Logan JW, O'Shea TM, Allred EN, Laughon MM, Bose CL, Dammann O et al. Early postnatal hypotension is not associated with indicators of white matter damage or cerebral palsy in extremely low gestational age newborns. J Perinatol 2011; 31 (8): 524–534.
Barrington KJ . Management during the first 72 h of age of the periviable infant: an evidence-based review. Semin Perinatol 2014; 38 (1): 17–24.
Carlo WA . Gentle ventilation: the new evidence from the SUPPORT, COIN, VON, CURPAP, Colombian network, and neocosur network trials. Early Hum Dev 2012; 88 (Suppl 2): S81–S83.
Dempsey E, Pammi M, Ryan AC, Barrington KJ . Standardised formal resuscitation training programmes for reducing mortality and morbidity in newborn infants. Cochrane Database Syst Rev 2015; 9: CD009106.
Kapadia VS, Chalak LF, Sparks JE, Allen JR, Savani RC, Wyckoff MH . Resuscitation of preterm neonates with limited versus high oxygen strategy. Pediatrics 2013; 132 (6): e1488–e1496.
Laptook AR, Watkinson M . Temperature management in the delivery room. Semin Fetal Neonatal Med 2008; 13 (6): 383–391.
Perlman JM, Wyllie J, Kattwinkel J, Atkins DL, Chameides L, Goldsmith JP et al. Neonatal resuscitation: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Pediatrics 2010; 126 (5): e1319–e1344.
Laughon M, Bose C, Allred E, O'Shea TM, Van Marter LJ, Bednarek F et al. Factors associated with treatment for hypotension in extremely low gestational age newborns during the first postnatal week. Pediatrics 2007; 119 (2): 273–280.
Smith PB, Ambalavanan N, Li L, Cotten CM, Laughon M, Walsh MC et al. Approach to infants born at 22 to 24 weeks' gestation: relationship to outcomes of more-mature infants. Pediatrics 2012; 129 (6): e1508–e1516.
Joseph RM, O'Shea TM, Allred EN, Heeren T, Hirtz D, Jara H et al. Neurocognitive and academic outcomes at age 10 years of extremely preterm newborns. Pediatrics. e-pub ahead of print 22 March 2016. doi: 10.1542/peds.2015-4343.
Johnson S, Hennessy E, Smith R, Trikic R, Wolke D, Marlow N . Academic attainment and special educational needs in extremely preterm children at 11 years of age: the EPICure study. Arch Dis Child Fetal Neonatal Ed 2009; 94 (4): F283–F289.
Rysavy MA, Li L, Bell EF, Das A, Hintz SR, Stoll BJ et al. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med 2015; 372 (19): 1801–1811.
Marlow N, Wolke D, Bracewell MA, Samara M . Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med 2005; 352 (1): 9–19.
Plomgaard AM, Hagmann C, Alderliesten T, Austin T, van Bel F, Claris O et al. Brain injury in the international multicenter randomized SafeBoosC phase II feasibility trial: cranial ultrasound and magnetic resonance imaging assessments. Pediatr Res 2016; 79 (3): 466–472.
Gray JE, Richardson DK, McCormick MC, Goldmann DA . Coagulase-negative staphylococcal bacteremia among very low birth weight infants: relation to admission illness severity, resource use, and outcome. Pediatrics 1995; 95 (2): 225–230.
Barton SK, Tolcos M, Miller SL, Christoph-Roehr C, Schmolzer GM, Moss TJ et al. Ventilation-induced brain injury in preterm neonates: a review of potential therapies. Neonatology 2016; 110 (2): 155–162.
Shah DK, Doyle LW, Anderson PJ, Bear M, Daley AJ, Hunt RW et al. Adverse neurodevelopment in preterm infants with postnatal sepsis or necrotizing enterocolitis is mediated by white matter abnormalities on magnetic resonance imaging at term. J Pediatr 2008 153 2 (170-5): 5 e1.
Lee I, Neil JJ, Huettner PC, Smyser CD, Rogers CE, Shimony JS et al. The impact of prenatal and neonatal infection on neurodevelopmental outcomes in very preterm infants. J Perinatol 2014; 34 (10): 741–747.
Alshaikh B, Yee W, Lodha A, Henderson E, Yusuf K, Sauve R . Coagulase-negative staphylococcus sepsis in preterm infants and long-term neurodevelopmental outcome. J Perinatol 2014; 34 (2): 125–129.
Dammann O, Leviton A . Brain damage in preterm newborns: might enhancement of developmentally regulated endogenous protection open a door for prevention? Pediatrics 1999; 104 (3 Pt 1): 541–550.
Zwicker JG, Grunau RE, Adams E, Chau V, Brant R, Poskitt KJ et al. Score for neonatal acute physiology-II and neonatal pain predict corticospinal tract development in premature newborns. Pediatric Neurology 2013; 48 (2): 123–9 e1.
Leviton A, Kuban KC, Allred EN, Fichorova RN, O'Shea TM, Paneth N . Early postnatal blood concentrations of inflammation-related proteins and microcephaly two years later in infants born before the 28th post-menstrual week. Early Hum Dev. 2011; 87 (5): 325–330.
O'Shea TM, Allred EN, Kuban KC, Dammann O, Paneth N, Fichorova R et al. Elevated concentrations of inflammation-related proteins in postnatal blood predict severe developmental delay at 2 years of age in extremely preterm infants. J Pediatr 2012; 160 (3): 395–401 e4.
Kuban KC, O'Shea TM, Allred EN, Paneth N, Hirtz D, Fichorova RN et al. Systemic inflammation and cerebral palsy risk in extremely preterm Infants. J Child Neurol 2014; 29 (12): 1692–1698.
O'Shea TM, Joseph RM, Kuban KC, Allred EN, Ware J, Coster T et al. Elevated blood levels of inflammation-related proteins are associated with an attention problem at age 24 mo in extremely preterm infants. Pediatr Res 2014; 75 (6): 781–787.
Brochu ME, Girard S, Lavoie K, Sebire G . Developmental regulation of the neuroinflammatory responses to LPS and/or hypoxia-ischemia between preterm and term neonates: An experimental study. J Neuroinflammation 2011; 8: 55.
Leviton A, Allred EN, Kuban KC, Dammann O, Fichorova RN, O'Shea TM et al. Blood protein concentrations in the first two postnatal weeks associated with early postnatal blood gas derangements among infants born before the 28th week of gestation. the ELGAN study. Cytokine 2011; 56 (2): 392–398.
Avila C, Willins JL, Jackson M, Mathai J, Jabsky M, Kong A et al. Usefulness of two clinical chorioamnionitis definitions in predicting neonatal infectious outcomes: a systematic review. Am J Perinatol 2015; 32 (11): 1001–1009.
Stoll BJ, Hansen NI, Sanchez PJ, Faix RG, Poindexter BB, Van Meurs KP et al. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics 2011; 127 (5): 817–826.
De Felice C, Toti P, Parrini S, Del Vecchio A, Bagnoli F, Latini G et al. Histologic chorioamnionitis and severity of illness in very low birth weight newborns. Pediatr Crit Care Med 2005; 6 (3): 298–302.
Bersani I, Thomas W, Speer CP . Chorioamnionitis—the good or the evil for neonatal outcome? J Matern Fetal Neonatal Med 2012; 25 (Suppl 1): 12–16.
Chau V, McFadden DE, Poskitt KJ, Miller SP . Chorioamnionitis in the pathogenesis of brain injury in preterm infants. Clin Perinatol 2014; 41 (1): 83–103.
Chau V, Poskitt KJ, McFadden DE, Bowen-Roberts T, Synnes A, Brant R et al. Effect of chorioamnionitis on brain development and injury in premature newborns. Ann Neurol 2009; 66 (2): 155–164.
Roescher AM, Timmer A, Erwich JJ, Bos AF . Placental pathology, perinatal death, neonatal outcome, and neurological development: a systematic review. PloS One 2014; 9 (2): e89419.
Arnold CC, Kramer MS, Hobbs CA, McLean FH, Usher RH . Very low birth weight: a problematic cohort for epidemiologic studies of very small or immature neonates. Am J Epidemiol 1991; 134 (6): 604–613.
This study was supported by grants from the National Institute of Neurologic Disorders and Stroke (5U01NS040069-05, 2R01NS040069-06A2), The National Eye Institute (1-R01-EY021820-01) and the National Institute of Child Health and Human Development (5P30HD018655-34). The authors thank the parents, families and collaborators who contributed to this project, without whom this project would not have been possible. The primary author would also like to acknowledge Dr Leif Nelin and colleagues at Nationwide Children’s Hospital for their ongoing support of his academic interests.
The authors declare no conflict of interest.
Supplementary Information accompanies the paper on the Journal of Perinatology website
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Logan, J., Dammann, O., Allred, E. et al. Early postnatal illness severity scores predict neurodevelopmental impairments at 10 years of age in children born extremely preterm. J Perinatol 37, 606–614 (2017). https://doi.org/10.1038/jp.2016.242
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