Cognitive and motor function of neurologically impaired extremely low birth weight children

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1 Original Article Cognitive and motor function of neurologically impaired extremely low birth weight children Janine Bernardo MD MPH 1, Harriet Friedman MA 2, Nori Minich BS 2, H Gerry Taylor PhD 2, Deanne Wilson-Costello MD 2, Maureen Hack MD 2 J Bernardo, H Friedman, N Minich, HG Taylor, D Wilson- Costello, M Hack. Cognitive and motor function of neurologically impaired extremely low birth weight children. Paediatr Child Health 2015;20(6):e Background: Rates of neurological impairment among extremely low birth weight children (ELBW [<1 kg]) have decreased since 2000; however, their functioning is unexamined. Objective: To compare motor and cognitive functioning of ELBW children with neurological impairment, including cerebral palsy and severe hypotonia/hypertonia, between two periods: 1990 to 1999 (n=83) and 2000 to 2005 (n=34). Methods: Measures of function at 20 months corrected age included the Mental and Psychomotor Developmental Indexes of the Bayley Scales of Infant Development and the Gross Motor Functional Classification System as primary outcomes and individual motor function items as secondary outcomes. Results: Analysis failed to reveal significant differences for the primary outcomes, although during 2000 to 2005, sitting significantly improved in children with neurological impairment (P=0.003). Conclusion: Decreases in rates of neurological impairment among ELBW children have been accompanied by a suggestion of improved motor function, although cognitive function has not changed. Key Words: Cerebral palsy; Cognitive function; Motor function; Neurologically impaired; Premature infant Cerebral palsy (CP) is the most common form of chronic motor disability associated with preterm birth. Originally defined as a disorder of movement and posture (1), CP is now considered to include a wider range of disruptions in neurological function that affect movement and posture, and may also be accompanied by disturbances in cognition, sensation, perception and behaviour (2). Neurological impairment of preterm children typically includes CP and less defined motor dysfunction, such as hypotonia and hypertonia, which are considered according to some as a milder form of CP. We previously reported that extremely low birth weight (ELBW [<1 kg]) children treated at our tertiary perinatal care centre in Cleveland, Ohio had improved rates of survival, along with reductions in neurodevelopmental impairment (3). Rates of CP declined from 13% to 5% between 1990 to 1999 and 2000 to 2002, with decreases in neurodevelopmental impairment between the two periods from 35% to 23%, respectively. We suggested that the improved neurodevelopmental outcomes were due to therapeutic changes, which included an increase in antenatal steroid use, decreases in postnatal steroid use, rates of sepsis and periventricular hemorrhage. Decreased rates of CP among preterm children have similarly been reported in Canada (4), Europe (5) and Australia (6). La fonction cognitive et motrice d enfants d extrême petit poids à la naissance présentant une atteinte neurologique HISTORIQUE : Les taux d atteinte neurologique chez les enfants d extrême petit poids à la naissance (EPPN [<1 kg]) ont diminué depuis Cependant, le fonctionnement de ces enfants n a pas fait l objet d examens. OBJECTIF : Comparer le fonctionnement moteur et cognitif des enfants d EPPN ayant une atteinte neurologique, y compris la paralysie cérébrale et l hypotonie et l hypertonie graves, pendant deux périodes : de 1990 à 1999 (n=83) et de 2000 à 2005 (n=34). MÉTHODOLOGIE : Les mesures de la fonction à 20 mois d âge corrigé incluaient les résultats cliniques primaires grâce aux indices de développement mental et psychomoteur de l échelle Bayley du développement des nourrissons et au système de classification de la motricité brute, et les résultats cliniques secondaires grâce aux éléments de la fonction motrice individuelle. RÉSULTATS : L analyse n a pu révéler de différences significatives dans les résultats cliniques primaires, même si entre 2000 et 2005, la position assise s est considérablement améliorée chez les enfants ayant une atteinte neurologique (P=0,003). CONCLUSION : La diminution des taux d atteinte neurologique chez les enfants d EPPN s accompagne de la suggestion d une amélioration de la fonction motrice, même si la fonction cognitive n a pas changé. There is little evidence regarding improvements in motor and cognitive functioning among preterm children with neurological impairment (7,8). We thus wanted to examine whether there have been changes in cognitive and motor functioning at 20 months corrected age among ELBW children born at our perinatal centre who developed a neurological impairment, defined as CP, or severe hypotonia or hypertonia. The periods of study included 1990 to 1999 (period I) and 2000 to 2005 (period II). Methods Participants The population included 749 ELBW infants born in period I and 417 born in period II, free of major congenital malformations who were delivered at MacDonald Hospital for Women (Cleveland, Ohio). Five hundred eight children (68%) in period I and 304 (73%) in period II survived, of whom 460 (91%) and 272 (90%), respectively, received neurodevelopmental assessments at 20 months corrected age including the Bayley Scales of Infant Development (BSID) (9,10). During period I, 83 children (18%) developed neurological impairment including 60 (13%) with CP (mean ± SD age 20±2 months) and 23 (5%) with hypo and/or hypertonia (19±2 months of age). During period II, 34 children (13%) developed neurological impairment, of whom 19 (7%) 1 Cleveland Clinic Lerner College of Medicine of Case Western Reserve University; 2 Department of Pediatrics, University Hospitals of Cleveland Case Medical Center, Cleveland, Ohio, USA Correspondence: Janine Bernardo, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, 9500 Euclid Avenue, NA21 Cleveland, Ohio 44195, Telephone , fax , jpb111@case.edu Accepted for publication February 27, Pulsus Group Inc. All rights reserved e33

2 Bernardo et al Table 1 Comparison of maternal, perinatal, birth data and neonatal risk factors (n=83) I (n=34) had CP (20±2 months of age) and 15 (6%) had hypo- and/or hypertonia (21±3 months of age). These children, with neurological impairments, constituted the study population. Design Neonatal care was rendered according to established guidelines during the periods of study (11). As previously reported, sociodemographic, birth and perinatal data were recorded at the time of neonatal discharge (3). Maternal information included age, marital status, education and race. Perinatal data included antenatal steroid therapy and mode of delivery. Birth data included birth weight, gestational age, small for gestational age (12), multiple births and sex. Neonatal risk factors included severe ultrasound abnormality (including grade III or IV periventricular hemorrhage, periventricular leukomalacia or ventricular dilation), septicemia, meningitis, hyperbilirubinemia (maximum bilirubin >0.1 g/l), bronchopulmonary dysplasia (oxygen dependence at 36 weeks corrected age) and postnatal steroid therapy. The children were followed as part of the ongoing neonatal high-risk follow-up program and seen sequentially during the first year and then at 20 months corrected age, at which time the BSID and a neurological assessment were performed (13). One developmental specialist and a neonatologist, who were specially trained and certified by the National Institute of Child Health and Human Development and unaware of the child s history, performed the neurological and BSID testing (14). Neurological impairment included CP and severe hypotonia and/or hypertonia. CP was defined as a persistent disorder of movement and posture attributable to a nonprogressive disorder of the brain and categorized as (n=60) I (n=23) I (n=15) Maternal data Age, years, mean ± SD 28±6 29±7 28±6 30±7 29±6 27±6 Marital status: married, n (%) 40 (48) 14 (41) 30 (50) 8 (42) 10 (44) 6 (40) Education >High school 34 (42) 13 (38) 23 (38) 8 (42) 11 (50) 5 (33) High school 41 (50) 16 (47) 35 (58) 9 (47) 6 (27) 7 (47) <High school 7 (9) 5 (15) 2 (3) 2 (11) 5 (23) 3 (20) Race, Black 48 (58) 22 (65) 34 (57) 12 (63) 14 (61) 10 (67) Perinatal data Antenatal steroid therapy 38 (46) 26 (77)** 22 (37) 15 (79)** 16 (70) 11 (73) Cesarean section 45 (54) 15 (44) 33 (55) 7 (37) 12 (52) 8 (53) Birth data Birth weight, g, mean ± SD 799± ±147* 813± ± ± ±139 Gestational age, weeks, mean ± SD 26±2 25±2 26±2 25±2 26±1 25±2 Small for gestational age 14 (17) 9 (27) 9 (15) 4 (21) 5 (22) 5 (33) Multiple births 17 (21) 12 (35) 11 (18) 7 (37) 6 (26) 5 (33) Male sex 43 (52) 15 (44) 32 (53) 7 (37) 11 (48) 8 (53) Neonatal risk factors Severe ultrasound abnormalities 46 (55) 16 (47) 39 (65) 14 (74) 7 (30) 2 (13) Septicemia 50 (60) 13 (38)* 33 (55) 9 (47) 17 (74) 4 (27)** Meningitis 8 (10) 2 (6) 4 (7) 2 (11) 4 (17) 0 (0) Hyper-bilirubinemia 11 (13) 7 (21) 8 (13) 5 (26) 3 (13) 2 (13) Bronchopulmonary dysplasia 47 (57) 18 (53) 29 (49) 11 (58) 18 (78) 7 (47)* Postnatal steroid therapy 64 (77) 8 (24)*** 44 (73) 5 (26)*** 20 (87) 3 (20)*** Data presented as n (%) unless otherwise indicated. 2 SD below mean value; Grade III or IV periventricular hemorrhage, periventricular leukomalacia or ventricular dilation at discharge; Maximum bilirubin >0.1 g/l. *P<0.05; **P<0.01; ***P<0.001 spastic diplegia, unilateral spastic CP, triplegia or quadriplegia (1). Children with a lesser increase or decrease in muscle tone, which may be characterized according to some as CP, were defined as having hypotonia and/or hypertonia (13). This usually included truncal hypotonia and hypo- or hypertonia of the extremities. Criteria for enrollment in physical therapy did not differ between the two time periods. Function of the children at 20 months corrected age was measured according to the Mental Developmental Index (MDI), the Psychomotor Developmental Index (PDI) of the BSID and the Gross Motor Function Classification System (GMFCS). Children born before 1992 were administered the original BSID I and those born between 1992 to 2005 were administered the BSID II (9,10). Because the BSID II results in lower scores than the BSID I, a correction factor was applied to the BSID I to provide greater comparability of scores. The correction was based on published differences found in a sample of 200 children given both tests in counterbalanced order (10). Infants who had severe motor or cognitive impairment and considered untestable based on the developmental specialist s clinical judgment were assigned a score of 50. Because children born after 2005 were tested using the BSID III, period II extended only to The differences across the two periods in attainment of individual motor milestones were examined using records extracted from the BSID psychomotor assessment at 20 months corrected age. Functional items included head control, sitting, rolling/turning, crawling/creeping, grasping, standing and walking. Head control was defined as holding the head unsupported while upright in the midline for 15 s. Sitting was categorized as either sitting independently (sitting unsupported 30 s), sitting with support or unable e34

3 Cognitive and motor function in ELBW children Table 2 Comparison of mental and psychomotor developmental indexes Neurological impairment CP Hypo/hypertonia (n=83) I (n=34) to sit. The ability to roll/turn was present if the child was able to roll from their back to their abdomen without assistance. Crawling and creeping were considered present if the child had a prewalking progression with movement forward, whether on their abdomen or hands and knees, respectively. Grasping included a fine pincer grasp, gross grasp and inability to grasp. A fine pincer grasp was defined as the ability to grasp objects between a finger and thumb. A gross grasp included both a partial pincer grasp (thumb opposition but less refined as fine pincer) and a rake/palmer grasp (scoop pellets). Standing was defined as either standing independently without support, standing with support or unable to stand. Walking was categorized as walking independently (three or more steps forward with no assistance, even if the gait was uncoordinated), walking with support and unable to walk. The GMFCS assessments of motor functioning were not performed at MacDonald Hospital for Women before Therefore, skill level was assigned from the motor items of the BSID 20-month report retrospectively (15). The GMFCS included skill levels zero to five ranging from normal to severely abnormal, as outlined by Palisano et al (15). The BSID report does not specify quality of walking, therefore the normal and possible level 1 categories were unable to be distinguished from one another. Statistical analysis Demographic, perinatal and neonatal descriptors were compared between the two periods of study. To limit the number of comparisons, the major focus was on trends across the two periods for the total neurological impairment sample in the three primary measures of outcome: the MDI, PDI and GMFCS. Secondary analyses were conducted to explore these trends for the CP and hypotonia/hypertonia subgroups separately, as well as trends across the periods in the individual motor items for the total sample and the CP and hypotonia/hypertonia subgroups. The Student s t test or Mann-Whitney U test was used for continuous variables, and χ 2 test for categorical variables. Outcomes were compared using logistic and ordinal regression for categorical measures, adjusting for sex, race and maternal education. Because of the multiple milestones examined, a more conservative α level of 0.01 was used in assessing the significance of differences. Outcomes did not differ in adjusted versus unadjusted analyses, therefore only unadjusted data are presented. (n=60) (n=23) (n=15) Mental developmental index score Range * 35 (42) 8 (24) 29 (48) 7 (37) 6 (26) 1 (7) (30) 15 (44) 17 (28) 6 (32) 8 (35) 9 (60) (15) 8 (24) 8 (13) 3 (16) 4 (17) 5 (33) (13) 3 (9) 6 (10) 3 (16) 5 (22) 0 (0) Psychomotor developmental index score n=81 n=33 n=58 n=18 Range (72) 17 (52) 50 (86) 13 (72) 8 (35) 4 (27) (22) 10 (30) 7 (12) 4 (22) 11 (48) 6 (40) (4) 5 (15) 1 (2) 1 (6) 2 (9) 4 (27) 85 2 (3) 1 (3) 0 (0) 0 (0) 2 (9) 1 (7) Data presented as n (%) unless otherwise indicated. *In period I (1990 to 1999), six of the children with cerebral palsy (CP) and one child with hypotonia/hypertonia had hearing impairment and mental developmental index (MDI) scores <50. In period II (2000 to 2005), one child with CP and one child with hypotonia/hypertonia had hearing impairment and an MDI score <50. In period I, 10 children with CP and one child with hypotonia/hypertonia had hearing impairment and psychomotor developmental index (PDI) scores < 50. In period II, one child with CP and one child with hypotonia/hypertonia had hearing impairment and PDI scores <50. The outcomes listed above did not differ significantly between the time periods The present study was approved by the Institutional Review Board of the University Hospitals of Cleveland and Case Medical Center and signed consent was obtained from parents. Results Table 1 presents a comparison of the sociodemographic data, birth data and peri-and neonatal risk factors between the two periods. For the total neurological impairment group and the CP subgroup, rates of antenatal steroid use were significantly higher. For all three groups, the rates of postnatal steroid therapy were significantly lower during period II, compared with period I. Additionally, among the neurologically impaired and hypo/hypertonia groups, rates of septicemia were significantly lower during period II. Among the hypo/ hypertonia group, rates of bronchopulmonary dysplasia were significantly lower in period II. There were no other significant differences in neonatal risk factors. Of the children with CP during period I, 14 (23%) had unilateral spastic CP, 25 (42%) diplegia, two (3%) triplegia and 19 (32%) quadriplegia. During period II, these rates were three (16%), eight (42%), two (11%) and six (32%), respectively (P=0.603). Unilateral or bilateral blindness occurred in one quadriplegic child in period I and two in period II (P=0.603). Deafness, defined as requiring a hearing aid, was present during period I in 15 children (18%) including four with hypo/hypertonia, three with unilateral spastic CP, seven with diplegia and one with quadriplegia. During period II, deafness was present in two children (6%) including one hypo/ hypertonic infant and one hemiplegic infant (P=0.146). Cognitive and motor functioning Table 2 presents a comparison of the BSID MDI and PDI scores. There were no differences between periods among the infants in the total neurological impairment group or in the CP or hypo/hypertonia subgroups. Of note, when the total neurologically impaired group was considered, more infants during period I than during period II were assigned a score of 50 on the PDI (58 of 83 [72%] versus 17 of 34 [52%]; P=0.040). For the MDI scores, these rates were 35 of 83 (42%) versus eight of 34 (24%) (P=0.058) for periods I and II, respectively. e35

4 Bernardo et al Table 3 Gross motor function classification system scores (n=76) Table 4 Comparison of functional motor development items (n=77) I (n=32) I (n=33) Gross motor function classification system The GMFCS scores did not differ significantly between the two periods for the total neurologically impaired sample or for children in the CP or hypo/hypertonia subgroups (Table 3). Of note, for all measures the children defined as having hypo- or hypertonia functioned better than those defined as having CP. Functional motor items By comparing the functional motor items (Table 4) during period I versus period II, among the total neurologically impaired group there was a significant improvement in sitting independently (50 of 76 [66%] versus 29 of 31 [94%], P=0.003). Improvements in sitting bordered on significance for the CP subgroup (P= 0.014) with more children sitting independently and fewer sitting with support. This was not observed in the hypo/hypertonic subgroup, although the vast majority of children in this subgroup sat independently during both periods. None of the other functional motor items differed significantly between time periods. (n=55) (n=56) I (n=18) I (n=21) Level Normal/possible 27 (36) 16 (50) 12 (22) 6 (33) 15 (71) 10 (71) 1 10 (13) 4 (13) 6 (11) 3 (17) 4 (19) 1 (7) 2 3 (4) 2 (6) 3 (6) 1 (6) 0 (0) 1 (7) 3 12 (16) 6 (19) 11 (20) 5 (28) 1 (5) 1 (7) 4 9 (12) 0 (0) 8 (15) 0 (0) 1 (5) 0 (0) 5 15 (20) 4 (13) 15 (27) 3 (17) 0 (0) 1 (7) Data presented as n (%). The outcomes listed above did not differ significantly between the time periods (n=21) I (n=14) I (n=14) Functional item Head control Yes 77 (100) 31 (94) 56 (100% 17 (90) 21 (100) 14 (100) No 0 (0) 2 (6) 0 (0) 2 (11) Sitting n=76 n=31* n=55 n=17* n=21 n=14 Sits independently with object 50 (66) 29 (94) 29 (53) 15 (88) 21 (100) 14 (100) Supported/unable to sit 26 (34) 2 (6) 26 (47) 2 (12) 0 (0) 0 (0) Rolling/turning n=73 n=32 n=52 n=18 n=21 n=14 Yes 61 (84) 28 (88) 40 (77) 15 (83) 21 (100) 13 (93) No 12 (16) 4 (13) 12 (23) 3 (17) 0 (0) 1 (7) Crawling/creeping n=73 n=32 n=52 n=18 n=21 n=14 Yes 52 (71) 28 (88) 32 (62) 15 (83) 20 (95) 13 (93) No 21 (29) 4 (13) 20 (38) 3 (17) 1 (5) 1 (7) Grasping n=68 n=29 n=49 n=17 n=19 n=12 Fine pincer 27 (40) 11 (38) 14 (29) 5 (29) 13 (68) 6 (50) Gross grasp 35 (51) 15 (52) 29 (59) 9 (53) 6 (32) 6 (50) Unable to use hands to retrieve objects 6 (9) 3 (10) 6 (12) 3 (18) 0 (0) 0 (0) Standing n=77 n=33 n=56 n=19 n=21 n=14 Stands independently 29 (38) 19 (58) 13 (23) 8 (42) 16 (76) 11 (79) Stands with support/unable to stand 48 (62) 14 (42) 43 (77) 11 (58) 5 (24) 3 (21) Walking n=77 n=33 n=56 n=19 n=21 n=14 Walks independently 27 (35) 16 (49) 12 (21) 6 (32) 15 (71) 10 (71) Walks with support/unable to walk 50 (65) 17 (52) 44 (79) 13 (68) 6 (29) 4 (29) Data presented as n (%). *P<0.01 Discussion We sought to compare the cognitive and motor outcomes of neurologically impaired children between period I and period II through the present retrospective chart review. We previously reported a reduction in the rates of both CP and overall neurodevelopmental impairment from 1990 to 1999 to 2000 to 2002 together with increases in antenatal steroid use, decreases in postnatal steroid use, sepsis and severe intraventricular hemorrhage (3). However, in the present study that specifically examined neurologically impaired children, there were no differences in perinatal risk factors between periods I and II, with the exception of higher antenatal steroid therapy and lower postnatal steroid therapy in period II. We found no differences in cognitive or motor function based on the MDI, PDI and GMFCS scores between the two periods of study. More children tended to have scores >50 on the PDI in period II. Futhermore, in secondary analyses, we found higher rates of independent sitting during period II for the total sample of neurologically impaired children and a suggestion of improved sitting for the subgroup with CP. e36

5 Cognitive and motor function in ELBW children Two previous studies have reported improvement in motor function of neurologically impaired children (7,8). van Haastert et al (7), in the Netherlands, reported a decrease in the rates of CP and its severity, as measured by the GMFCS, after 1993 in children born <34 weeks gestation. Guerrot and Chadie et al (8) reported that despite no change in the rates of CP in a single-center neonatal intensive care unit in France, the overall rate of motor impairment between 2000 and 2005 among infants born <33 weeks gestation with mild motor retardation declined, although in their study motor impairment was not clearly defined (8). The present study is the first to examine possible changes in cognitive, as well as motor, function in neurologically impaired preterm children. Furthermore, we described motor function examination with a tri-fold approach including the BSID, motor functional items and the GMFCS. Vohr et al (16) postulated that given the range of gross motor skills, the neurological assessment of ELBW children is optimized using a combination of standard neurological examinations with measures of gross and fine motor function, including the BSID and GMFCS. Such an approach provides a more thorough and comprehensive view of the function of the children. One of the study s limitations is that the functional milestones of development and GMFCS assessments were collected retrospectively from the psychomotor indexes of the BSID with missing data on outcomes for a number of children. Because the study was performed at a single centre, the sample may not be representative of the broader ELBW population. Sample size was also small, particularly among the infants born during period II and those with hypo/ hypertonia, which limited the statistical power of the present study. The BSID, while not specifically designed to evaluate the function of visual and hearing impaired children, is widely used with these populations. We document the percentage of children with hearing References 1. Bax M. Terminology and classification of cerebral palsy. Dev Med Child Neurol 1964;6: Bax M, Goldstein M, Rosenbaum P, Leviton A. Proposed definition and classification of cerebral palsy. Dev Med Child Neurol 2005;47: Wilson-Costello D, Friedman H, Minich N, et al. Improved neurodevelopmental outcomes for extremely low birth weight infants in Pediatrics 2007;119: Robertson CM, Watt MJ, Yasui Y. Changes in the prevalence of cerebral palsy for children born very prematurely within a population-based program over 30 years. JAMA 2007;297: Platt MJ, Cans C, Johnson A, et al. Trends in cerebral palsy among infants of very low birthweight (<1500 g) or born prematurely (<32 wks) in 16 European centers: A database study. Lancet 2007;369: Doyle LW, Roberts G, Anderson PJ. 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Pediatrics 2001;108:e35 < org/cgi/ content/full/108/2/e35> (Accessed September 20, 2013). aids and visual impairment, but additional children with audiovisual impairment may not be diagnosed or not yet aided. Although caution has been advised in using the GMFCS in children under two years of age (15) it is, however being used (16,17). Finally, our study was based on the neurological examination and diagnosis of CP, hypotonicity or hypertonicity during the 20 month follow-up visit. Although work by Peralta-Carcelen et al (18) found that a diagnosis of CP was stable in 84% and 91% of children between 18 and 30 months of age, respectively, former studies have observed changes in the diagnosis of CP as children age, which may not predict later cognitive function (19,20, 21). Conclusions Larger, multicentre, prospective investigations examining motor and cognitive development in neurologically impaired infants are needed to determine whether our suggestion of improved motor function since 2000, as evidenced by improvements in sitting, has continued for more recent birth cohorts. The present findings point to the importance of further research investigating the effects of more recent changes in neonatal intensive care, on neurodevelopmental outcomes as a means to identify the effects of these changes and to clarify the nature of children s developmental impairment. Acknowledgements: The authors thank Bonnie Siner and Angelia Williams for their help in conducting this research. They also appreciate the Clinical and Translational Science Award UL1TR for its support of the RedCap Database. Previous work by Wilson- Costello et al was supported by grant M01RR00080, General Clinical Research Center and partially supported by grant HD21364 from the National Institute of Child Health and Human Development Neonatal Research Network. 13. Amiel-Tison C, Stewart AL. Follow-up studies in the first five years of life: A pervasive assessment of neurological function. Arch Dis Child 1989;64: Vohr BR, Wright LL, Dusick AM, et al. Neurodevelopmental and functional outcomes of extremely low birth weight infants in the national institute of child health and human development neonatal research network, Pediatrics 2000;105: Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B. Development and reliability of a system, to classiffy gross motor function in children with cerebral palsy. Dev Med Child Neural 1997;39: Vohr BR, Msall ME, Wilson D, Wright LL, McDonald S, Poole WK. Spectrum of gross motor function in extremely low birth weight children with cerebral palsy at 18 months of age. Pediatrics 2005;116: Schmidt B, Anderson PJ, Doyle LW, et al. Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity. JAMA 2012;307: Peralta-Carcelen M, Moses M, Adams-Chapman I, Gantz M, Vohr BR. Stability of neuromotor outcomes at 18 and 30 months of age after extremely low birth weight status. Pediatrics 2009;123: Nelson KB, Ellenberg JH. Children who outgrew cerebral palsy. Pediatrics 1982;69: Ford GW, Kitchen WH, Doyle LW, Rickards AL, Kelly E. Changing diagnosis of cerebral palsy in very low birthweight children. Am J Perinatol 1990;7: Hack M, Taylor HG, Drotar 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: e37