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Using the Alberta Infant Motor Scale to early identify very low-birth-weight infants with cystic periventricular leukomalacia
Brain & Development 35 (2013) 32–37 www.elsevier.com/locate/braindev
Original article
Using the Alberta Infant Motor Scale to early identify very low-birth-weight infants with cystic periventricular leukomalacia Lin-Yu Wang a,b, Yu-Lin Wang c, Shan-Tair Wang d, Chao-Ching Huang b,e,⇑ b
a Department of Pediatrics, Chei-Mei Medical Center, Tainan, Taiwan Institute of Clinical Medicine, National Cheng Kung University, College of Medicine, Tainan, Taiwan c Department of Rehabilitation, Chei-Mei Medical Center, Tainan, Taiwan d Department of Medical Research, Chiayi Christian Hospital, Chiayi, Taiwan e Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan
Received 20 March 2011; received in revised form 11 August 2011; accepted 31 August 2011
Abstract We examined whether the Alberta Infant Motor Scale (AIMS) is able to identify very low-birth-weight (VLBW) preterm infants with cystic periventricular leukomalacia (PVL) as early as 6 months of corrected age. Longitudinal follow-up AIMS assessments were done at 6, 12, and 18 months old for 35 VLBW infants with cystic PVL (cPVL+), 70 VLBW infants without cystic PVL (cPVL ), and 76 term infants (healthy controls: HC). Corrected age was used for the preterm infants. The cPVL+ group had significantly lower prone, supine and sitting subscales at age 6, 12, and 18 months than the cPVL group (all p < 0.05). The cPVL group showed significantly lower supine, prone, sitting, and standing subscales than the HC group only at age 6 months. At age 6 months, the areas under the receiver operator curve used to discriminate the cPVL+ infants from cPVL infants were 0.82 ± 0.04 for prone, 0.93 ± 0.02 for supine, 0.83 ± 0.05 for sitting, and 0.62 ± 0.07 for standing. The AIMS may help early identify VLBW infants with cystic PVL at age 6 months old. Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. Keywords: Very low birth weight; Cystic periventricular leukomalacia; Cerebral palsy
1. Introduction Great improvements in neonatal intensive care during the last decade have raised the survival rate for very low birth weight (VLBW) preterm infants, those with a birth body weight (bbw) (<1500 g) [1,2]. Of VLBW infants who survive, 15% have cerebral palsy, and 50% have significant cognitive, behavioral, and attentional deficits that require special education [3–6]. Periventricular leukomalacia (PVL) is the most common brain injury in premature infants and it often devel⇑ Corresponding author at: Department of Pediatrics, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan 704, Taiwan. Tel.: +886 6 235 3535; fax: +886 6 236 6584. E-mail address: [email protected] (C.-C. Huang).
ops into cerebral palsy in later life [7–9]. PVL is characterized by focal necrosis in developing cerebral white matter dorsal and lateral to the external angles of the lateral ventricle as a result of hypoxic-ischemic or infection insults [7,10]. Focal necrosis can be macroscopic in size, include the loss of cellular elements (preoligodendrocytes and axons), lead to the formation of cysts, and be visualized using cranial ultrasonography [6,11]. In this particular area, the corticospinal tracts innervating muscles in the lower extremities descend from their origin in the motor cortex through the white matter and into the internal capsule [10]. Depending on the extent and severity of the white-matter damage, infants with PVL develop different degrees of progressive motor deficits and disabilities several months after birth [7,10].
0387-7604/$ - see front matter Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2011.08.012
L.-Y. Wang et al. / Brain & Development 35 (2013) 32–37
An important aspect of the pediatrician’s evaluation of a high-risk infant is using developmental screening tools that provide information about its developmental status and making recommendations for early intervention for high-risk infants. Early intervention is more effective for high-risk children than for children with identified disabilities [12–16]. To help identify these high-risk infants as early as possible, a developmental screening tool for early prediction is necessary. One assessment tool particularly useful for monitoring gross motor developmental change in infants during the first 18 months of life is the Alberta Infant Motor Scale (AIMS) [17]. The AIMS is designed to examine, discriminate, and evaluate the spontaneous movement of infants from term age through independent walking, which is also useful for monitoring gross motor developmental change in infants during the first 18 months of life [17]. The AIMS demonstrates a high degree of correlation with the gross motor scale of the Bayley Scale of Infant Development (BSID) when the tests are applied on high-risk infants with motor delays [16]. The AIMS follows the principles of dynamical motor systems by observing infants as they move into and out of four positions: prone, supine, sitting, and standing. In contrast to the BSID that requires trained psychologists to administer with, the testing procedures of AIMS are administered by observation only and can be completed within 20 min, which is more feasible for clinicians than BSID. The AIMS has been widely used to assess gross motor development in normal term infants [17–19], atrisk infants [20], infants with cerebral palsy [21], and very preterm infants [22–24]. Jeng et al. [24] observed that the AIMS provided reliable and valid measurement that was useful evaluating the gross motor function of Taiwanese preterm infants from birth to corrected age 18 months. They also demonstrated the AIMS scores correlated with the Bayley Motor Scale scores at 6 and 12 months corrected age. Most studies [20,22–24] report that motor development in preterm infants differs from that in term infants. However, there are relatively few studies that compare the gross motor development between VLBW infants with and those without cystic PVL in the first 18 months of life [21,22]. More important, whether the AIMS is able to identify VLBW infants with cystic PVL as early as 6 months of corrected age remains unknown. 2. Methods 2.1. Participants The institutional review board approved this study and informed consent was obtained. VLBW preterm (gestational age 627 weeks) infants were recruited from the neonatal intensive care unit at six tertiary hospitals in Southern Taiwan from 01 June 2000 through 31
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May 2006. The selection criteria were (1) a bbw <1500 g, (2) born at one of six tertiary hospitals in southern Taiwan, (3) no genetic syndromes and no congenital brain malformations, (4) no intraventricular or intracerebral hemorrhage, (5) no transient periventricular hyperechoic lesion, and (6) survived until discharge. Real-time ultrasound examinations were done with 7.5- and 5 MHz sector and linear transducers (Toshiba America Medical Systems, Inc., Tustin, CA). Multiple images were obtained in the coronal and sagittal planes, with the anterior fontanel used as an acoustic window. Cranial ultrasound images were taken within 72 h of birth, either weekly or every second week and at discharge from the neonatal intensive care unit. We divided the participants into three groups: cPVL+ = pre-term infants with cystic PVL, cPVL = pre-term infants without cystic PVL, and healthy controls: (HC) = full-term infants (gestational age, 37–42 weeks). The cPVL+ group consisted of infants with increased echogenicity in the periventricular region; they had developed cysts, which were confirmed using serial cranial ultrasound examinations. Infants who developed cysts of 5 mm or more in diameter in the periventricular white matter were diagnosed by a pediatric neurologist as having cystic PVL. HC group infants were from wellchild clinics; they met inclusion criteria 2–6 and participated with their parents’ signed written consent. 2.2. Instruments and procedures HC group infants were recruited at age 6 months, and additional follow-up visits were made every 6 months until age 18 months. VLBW preterm infants in each hospital were enrolled monthly, and case files were established, including sociodemographic data, perinatal conditions, and hospital courses. When the VLBW infants were discharged, the case manager arranged the first follow-up visit at a corrected age of 6 months. Additional follow-up visits were made every 6 months until a corrected age of 18 months. During each visit for the three group infants, a pediatrician did a growth evaluation and physical and neuromotor examinations. The AIMS gross motor developmental assessment was administered by physiotherapists experienced with the instrument [17]. The assessments were scheduled at each hospital’s Pediatric Developmental Follow-up Clinic for within 1 week of each child’s becoming 6, 12, and 18 months of age. Corrected ages were used for preterm infants. Two physiotherapists took part in assessing each infant’s gross motor assessment; both were experienced in infant motor development follow-up, and both had been trained to administer the AIMS. Both evaluators assessed each of the infants at the same time, independently, and blinded to each other. The AIMS is designed to measure motor skills from birth to independent walking. It consists of 58 items
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divided into four subscales: prone (21 items), supine (nine items), sitting (12 items), and standing (16 items). Each test item is specifically described in terms of the weight-bearing surface of the body, the posture necessary to achieve the gross motor skill, and the antigravity or voluntary movement performed by the infant in the position. Spontaneous movements of the infants were observed by the physical therapists. Each item must be completed in order to receive a score. “Key descriptors”, which must be observed to give credit to the item, are provided on the score sheet. The manual provides more details for proper scoring. The total raw score, which is the sum of the positional item scores, ranges from 0 to 58. The higher the score, the more mature the child’s gross motor pattern. The instrument has acceptable levels of reliability and validity when used with preterm Taiwanese infants [24]. 2.3. Data analysis SPSS 10.0 for Windows was used for statistical analysis. v2 and Fisher’s exact tests were used to compare demographic characteristics at birth and neonatal morbidity. The gross motor developmental patterns in all three groups were evaluated at three time points: 6, 12, and 18 months postnatal. A repeated measures analysis of variance (ANOVA) was used to examine the effects of age and group on the infants’ motor performance. When a significant difference was found, a post hoc comparison using Scheffe’s method identified the different pairs. Significance was set at p < 0.05. Continuous data are means ± standard deviation (SD), unless otherwise indicated. The area under the receiver operator curve (ROC) was calculated to identify the most useful subscale within AIMS to detect the VLBW infants with cystic PVL at the corrected age of 6 and 12 months [25]. The area under the ROC curve is the probability of correctively classifying a pair of a VLBW infant with and that without cystic PVL using a subscale.
3. Results 3.1. Diagnosis Cystic PVL was diagnosed at a mean age of 28 days (range, 21–60 days). None of the infants in cPVL+ group had intraventricular hemorrhage. 3.2. Participant characteristics One of the 36 infants in the cPVL+ group was excluded because she developed a grade IV intraventricular hemorrhage during the study; two of the 72 infants in the cPVL group were excluded because they were lost to follow-up; and one of the 77 infants in the HC group was excluded because of an incomplete followup record. The mean gestational age, mean bbw, and Apgar scores at 1 and 5 min were all significantly larger in HC group infants than in cPVL+ and cPVL group infants (p < 0.001). There were no significant differences in gender, bbw, gestational age, or Apgar score 1 and 5 min Apgar scores between the cPVL+ and cPVL group infants (Table 1). Although there were nearly twice as many boys as girls (23/12) in the cPVL+ group, that difference was not significant according to a v2 test. There were no significant differences in the incidence of sepsis, bronchopulmonary dysplasia, or patent ductus arteriosus between the two preterm groups. 3.3. Neurodevelopmental outcome Gross motor developmental patterns were evaluated at three time points of corrected age: at 6, 12, and 18 months old. A repeated measures ANOVA was used to examine the effects of age (time) and group (two groups of preterm infants and one group of term infants) on the prone, supine, sitting, and standing AIMS subscales. There were significant differences for the prone, supine, sitting, standing subscales and total
Table 1 Clinical characteristics of the infants in the study. Characteristic
cPVL+ group n = 35
cPVL group n = 70
HC group n = 76
Gestational age (weeks)a Birth body weight (g)a Male/female Apgar score (1 min)a Apgar score (5 min)a Sepsis (%) Bronchopulmonary disease (%) Patent ductus arteriosis (%)
28.5 ± 2.0 1201 ± 181 23/12 4.7 ± 2.0 7.0 ± 1.3 25.7 14.2 32.2
28.6 ± 2.2 1124 ± 223 32/38 4.8 ± 1.8 7.0 ± 1.5 26.3 14.8 30.7
39.0 ± 3.9 3342 ± 451 36/40 7.9 ± 0.3 9.0 ± 0.0 0 0 0
cPVL+ group, very low birth weight preterm infants with cystic periventricular leukomalacia; cPVL group, very low birth weight preterm infants without cystic periventricular leukomalacia; HC group, healthy full-term infants (gestational age, 37–42 weeks). a Significant difference between the cPVL+, cPVL and HC group infants (p < 0.001) analysis of variance (ANOVA) and then the Tukey Honestly Significant Difference post hoc tests.
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Table 2 Alberta Infant Motor Scale (AIMS) subscales and total scores by group at 6, 12, and 18 months old. AIMS subscales and total scores
n
6 months old Mean (SD)
12 months old Mean (SD)
18 months old Mean (SD)
Group effect p-value
Time effect p-value
Interaction effect p-value
Prone cPVL+ group cPVL group HC group
35 70 76
5.23 (1.68)a,b 7.79 (2.11)c 10.18 (2.67)
7.70 (2.30)a,b 20.10 (2.06) 20.72 (1.09)
9.86 (2.70)a,b 20.87 (0.64) 21.00 (0.00)
<0.001 – –
<0.001 – –
<0.001 – –
Supine cPVL+ group cPVL group HC group
35 70 76
4.23 (0.99)a,b 6.88 (1.33)c 7.97 (1.02)
6.27 (1.79)a,b 8.97 (0.17) 9.00 (0.00)
7.00 (1.88)a,b 9.00 (0.00) 9.00 (0.00)
<0.001 – –
<0.001 – –
<0.001 – –
Sitting cPVL+ group cPVL group HC group
35 70 76
2.96 (1.15)a,b 4.85 (1.59)c 6.37 (2.06)
5.12 (2.20)a,b 11.50 (1.15) 11.99 (0.11)
6.49 (2.57)a,b 11.94 (0.23) 12.00 (0.00)
<0.001 – –
<0.001 – –
<0.001 – –
Standing cPVL+ group cPVL group HC group
35 70 76
1.92 (0.69)b 2.24 (0.58)c 3.62 (2.11)
2.88 (1.24)a,b 10.94 (2.54)c 13.54 (2.00)
4.57 (2.76)a,b 15.33 (1.84) 15.99 (0.11)
<0.001 – –
<0.001 – –
<0.001 – –
Total score cPVL+ group cPVL group HC group
35 70 76
14.54 (2.97)a,b 21.52 (4.38)c 28.14 (5.17)
22.61 (7.35)a,b 51.51 (5.07)c 55.25 (2.42)
28.66 (9.80)a,b 57.14 (2.52) 57.99 (0.11)
<0.001
<0.001
<0.001
cPVL+ group, very low-birth-weight preterm infants with cystic periventricular leukomalacia; cPVL group, very low-birth-weight preterm infants without cystic periventricular leukomalacia; HC group, healthy full-term infants (gestational age, 37–42 weeks); SD, standard deviation. Data were compared using repeated measurement analysis of variance (ANOVA), followed by post hoc comparisons by Scheffe’s method. There were significant (all p < 0.05) differences between the groups for prone, supine, sitting and standing subscales, and total scores. a cPVL+ vs. cPVL . b cPVL+ vs. HC group. c cPVL vs. HC group.
scores of the AIMS assessed across ages (all p < 0.001), between groups (all p < 0.001), and for the interaction effect (all p < 0.001) (Table 2). The sequential changes of gross motor performance of the three groups at age 6, 12, and 18 months is shown in Fig. 1. At 6 months old, the cPVL+ group infants showed significantly lower supine, prone, and sitting subscales than the cPVL group infants (all p < 0.05) (Fig. 1 and Table 2). The cPVL group infants also had significantly lower supine, prone, sitting, and standing subscales than the HC group infants (all p < 0.05). At 12 months old, the cPVL+ group infants had significantly lower supine, prone, sitting, and standing subscales than the cPVL group infants (all p < 0.05). The cPVL group infants differed from the HC group infants only at the standing subscale. At 18 months old, the cPVL+ group infants had significantly lower supine, prone, sitting, and standing subscales than the cPVL group infants (all p < 0.05). In contrast, there were no significant differences in any subscale between the cPVL and the HC group infants. The cPVL+ group infants had significantly lower prone, supine and sitting subscales at 6, 12, and 18 months corrected age than the cPVL group infants. The area under the ROC curve was used to clarify the most useful AIMS subscale that could be used to
discriminate the cPVL+ preterm infants from the cPVL preterm infants at the corrected age 6 and 12 months. The areas under the ROC curves for prone, supine, sitting, and standing subscale were (mean ± standard error of mean) 0.82 ± 0.04, 0.93 ± 0.02, 0.83 ± 0.05, and 0.62 ± 0.07, respectively, at the corrected age 6 months; and 1.00 ± 0.00, 0.97 ± 0.03, 0.99 ± 0.01, and 0.98 ± 0.01, respectively, at age 12 months. This ROC curve analysis result indicated that although the prone, supine, sitting, and standing subscale at age 12 months were higher than the respective subscale at age 6 months, the supine subscale is the most useful subscale to discriminate the cPVL+ preterm infants from the cPVL preterm infants as early as 6 months old. Pediatric neurologists diagnosed all 35 cPVL+ group infants as having cerebral palsy at 24 months old. Topographic classification showed that 28/35 infants had spastic diplegia, 6/35 had quadriplegia, and 1/35 had hemiplegia. All cPVL group infants developed normally. 4. Discussion The AIMS has been widely used, but a gross motor developmental profile of VLBW preterm infants with
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Fig. 1. AIMS total and subscale scores over time for VLBW preterm infants with cystic PVL (cPVL+ group), VLBW preterm infants without cystic PVL (cPVL group) and healthy full-term controls (HC). Summary subscales are given for (A) prone, (B) supine, (C) sitting, (D) standing, and (E) total scores. Values are means ± SEM. The high scores indicate better performance. a: cPVL+ vs. cPVL group (p < 0.05); b: cPVL+ vs. HC group (p < 0.05); c: cPVL vs. HC group (p < 0.05).
cystic PVL has not been previously published. We report, for VLBW preterm infants with and without cystic PVL and healthy full-term infants from 6 to 18 months old, the longitudinal development of gross motor function on four AIMS subscales and total score. The healthy full-term infants had the best gross motor performance, and the VLBW preterm infants with cystic PVL had the worst. The 6-month-old infants in both VLBW preterm groups had significant differences in supine, prone, and sitting scores that persisted up to 18 months old. The ROC curve analysis indicated that supine is the most useful subscale to identify VLBW preterm infants with cystic PVL as early as 6 months corrected age. This finding indicates that cystic PVL had consistent negative effects on gross motor functions beginning as early as 6 months old. Most premature infants with PVL are asymptomatic. If symptoms occur, they are usually subtle, such as decreased tone in the lower extremities, increased tone in the neck extensors, apnea, bradycardia, irritability, etc. [7]. However; it is often difficult to identify PVL based on the infant’s physical or behavioral characteristics. The AIMS can be used to identify cystic PVL in VLBW preterm infants as young as 6 months old. Cystic PVL contributes to the development of cerebral palsy [26–30]. Consistent with these observations, all VLBW preterm infants with cystic PVL in our study were later diagnosed with cerebral palsy at 2 years old. Thus, early identification of cystic PVL in VLBW preterm infants is important for beginning early rehabilitation and for obtaining a good effect on the plasticity of the premature brain. The VLBW preterm infants without cystic PVL caught up with the development of healthy full-term infants by the time they were 18 months old. However, it took much longer for the VLBW preterm infants to stand. Early intervention targeting primarily the standing capacity of VLBW preterm infants without cystic PVL may accelerate their gross motor maturation. Our data support the results of a report [31] that walking is delayed in VLBW preterm infants. Early standing requires a high degree of coordinated postural stability and mobility of the neck, trunk, shoulders, and legs [32–35]. Therefore, younger VLBW premature infants rarely have high scores on the AIMS standing subscale. The lower standing scores in younger VLBW premature infants may also be attributed to the short gestational age and complicated hospitalization course, especially respiratory distress, sepsis, and necrotizing enterocolitis. In conclusion, VLBW preterm infants with cystic PVL had low AIMS scores at 6, 12, and 18 months old. There were significant differences in supine, prone, and sitting scores between the VLBW preterm infants with and without cystic PVL, especially at 6 months old. AIMS supine subscale is most useful to discriminate the VLBW infants with cystic PVL from those without
L.-Y. Wang et al. / Brain & Development 35 (2013) 32–37
cystic PVL as early as 6 months old. VLBW preterm infants with cystic PVL are at higher risk for motor disability and delayed gross motor milestones as early as 6 months older than are VLBW preterm infants without PVL. VLBW preterm infants without cystic PVL had AIMS scores lower than those of healthy full-term infants at 6 months old, but they caught up with the development of healthy full-term infants by the time they were 18 months old. Using the AIMS to assess gross motor development may assist pediatricians in identifying VLBW preterm infants with PVL as early as 6 months old, and in formulating plans for early therapeutic intervention.
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Original article
Using the Alberta Infant Motor Scale to early identify very low-birth-weight infants with cystic periventricular leukomalacia Lin-Yu Wang a,b, Yu-Lin Wang c, Shan-Tair Wang d, Chao-Ching Huang b,e,⇑ b
a Department of Pediatrics, Chei-Mei Medical Center, Tainan, Taiwan Institute of Clinical Medicine, National Cheng Kung University, College of Medicine, Tainan, Taiwan c Department of Rehabilitation, Chei-Mei Medical Center, Tainan, Taiwan d Department of Medical Research, Chiayi Christian Hospital, Chiayi, Taiwan e Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan
Received 20 March 2011; received in revised form 11 August 2011; accepted 31 August 2011
Abstract We examined whether the Alberta Infant Motor Scale (AIMS) is able to identify very low-birth-weight (VLBW) preterm infants with cystic periventricular leukomalacia (PVL) as early as 6 months of corrected age. Longitudinal follow-up AIMS assessments were done at 6, 12, and 18 months old for 35 VLBW infants with cystic PVL (cPVL+), 70 VLBW infants without cystic PVL (cPVL ), and 76 term infants (healthy controls: HC). Corrected age was used for the preterm infants. The cPVL+ group had significantly lower prone, supine and sitting subscales at age 6, 12, and 18 months than the cPVL group (all p < 0.05). The cPVL group showed significantly lower supine, prone, sitting, and standing subscales than the HC group only at age 6 months. At age 6 months, the areas under the receiver operator curve used to discriminate the cPVL+ infants from cPVL infants were 0.82 ± 0.04 for prone, 0.93 ± 0.02 for supine, 0.83 ± 0.05 for sitting, and 0.62 ± 0.07 for standing. The AIMS may help early identify VLBW infants with cystic PVL at age 6 months old. Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. Keywords: Very low birth weight; Cystic periventricular leukomalacia; Cerebral palsy
1. Introduction Great improvements in neonatal intensive care during the last decade have raised the survival rate for very low birth weight (VLBW) preterm infants, those with a birth body weight (bbw) (<1500 g) [1,2]. Of VLBW infants who survive, 15% have cerebral palsy, and 50% have significant cognitive, behavioral, and attentional deficits that require special education [3–6]. Periventricular leukomalacia (PVL) is the most common brain injury in premature infants and it often devel⇑ Corresponding author at: Department of Pediatrics, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan 704, Taiwan. Tel.: +886 6 235 3535; fax: +886 6 236 6584. E-mail address: [email protected] (C.-C. Huang).
ops into cerebral palsy in later life [7–9]. PVL is characterized by focal necrosis in developing cerebral white matter dorsal and lateral to the external angles of the lateral ventricle as a result of hypoxic-ischemic or infection insults [7,10]. Focal necrosis can be macroscopic in size, include the loss of cellular elements (preoligodendrocytes and axons), lead to the formation of cysts, and be visualized using cranial ultrasonography [6,11]. In this particular area, the corticospinal tracts innervating muscles in the lower extremities descend from their origin in the motor cortex through the white matter and into the internal capsule [10]. Depending on the extent and severity of the white-matter damage, infants with PVL develop different degrees of progressive motor deficits and disabilities several months after birth [7,10].
0387-7604/$ - see front matter Ó 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2011.08.012
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An important aspect of the pediatrician’s evaluation of a high-risk infant is using developmental screening tools that provide information about its developmental status and making recommendations for early intervention for high-risk infants. Early intervention is more effective for high-risk children than for children with identified disabilities [12–16]. To help identify these high-risk infants as early as possible, a developmental screening tool for early prediction is necessary. One assessment tool particularly useful for monitoring gross motor developmental change in infants during the first 18 months of life is the Alberta Infant Motor Scale (AIMS) [17]. The AIMS is designed to examine, discriminate, and evaluate the spontaneous movement of infants from term age through independent walking, which is also useful for monitoring gross motor developmental change in infants during the first 18 months of life [17]. The AIMS demonstrates a high degree of correlation with the gross motor scale of the Bayley Scale of Infant Development (BSID) when the tests are applied on high-risk infants with motor delays [16]. The AIMS follows the principles of dynamical motor systems by observing infants as they move into and out of four positions: prone, supine, sitting, and standing. In contrast to the BSID that requires trained psychologists to administer with, the testing procedures of AIMS are administered by observation only and can be completed within 20 min, which is more feasible for clinicians than BSID. The AIMS has been widely used to assess gross motor development in normal term infants [17–19], atrisk infants [20], infants with cerebral palsy [21], and very preterm infants [22–24]. Jeng et al. [24] observed that the AIMS provided reliable and valid measurement that was useful evaluating the gross motor function of Taiwanese preterm infants from birth to corrected age 18 months. They also demonstrated the AIMS scores correlated with the Bayley Motor Scale scores at 6 and 12 months corrected age. Most studies [20,22–24] report that motor development in preterm infants differs from that in term infants. However, there are relatively few studies that compare the gross motor development between VLBW infants with and those without cystic PVL in the first 18 months of life [21,22]. More important, whether the AIMS is able to identify VLBW infants with cystic PVL as early as 6 months of corrected age remains unknown. 2. Methods 2.1. Participants The institutional review board approved this study and informed consent was obtained. VLBW preterm (gestational age 627 weeks) infants were recruited from the neonatal intensive care unit at six tertiary hospitals in Southern Taiwan from 01 June 2000 through 31
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May 2006. The selection criteria were (1) a bbw <1500 g, (2) born at one of six tertiary hospitals in southern Taiwan, (3) no genetic syndromes and no congenital brain malformations, (4) no intraventricular or intracerebral hemorrhage, (5) no transient periventricular hyperechoic lesion, and (6) survived until discharge. Real-time ultrasound examinations were done with 7.5- and 5 MHz sector and linear transducers (Toshiba America Medical Systems, Inc., Tustin, CA). Multiple images were obtained in the coronal and sagittal planes, with the anterior fontanel used as an acoustic window. Cranial ultrasound images were taken within 72 h of birth, either weekly or every second week and at discharge from the neonatal intensive care unit. We divided the participants into three groups: cPVL+ = pre-term infants with cystic PVL, cPVL = pre-term infants without cystic PVL, and healthy controls: (HC) = full-term infants (gestational age, 37–42 weeks). The cPVL+ group consisted of infants with increased echogenicity in the periventricular region; they had developed cysts, which were confirmed using serial cranial ultrasound examinations. Infants who developed cysts of 5 mm or more in diameter in the periventricular white matter were diagnosed by a pediatric neurologist as having cystic PVL. HC group infants were from wellchild clinics; they met inclusion criteria 2–6 and participated with their parents’ signed written consent. 2.2. Instruments and procedures HC group infants were recruited at age 6 months, and additional follow-up visits were made every 6 months until age 18 months. VLBW preterm infants in each hospital were enrolled monthly, and case files were established, including sociodemographic data, perinatal conditions, and hospital courses. When the VLBW infants were discharged, the case manager arranged the first follow-up visit at a corrected age of 6 months. Additional follow-up visits were made every 6 months until a corrected age of 18 months. During each visit for the three group infants, a pediatrician did a growth evaluation and physical and neuromotor examinations. The AIMS gross motor developmental assessment was administered by physiotherapists experienced with the instrument [17]. The assessments were scheduled at each hospital’s Pediatric Developmental Follow-up Clinic for within 1 week of each child’s becoming 6, 12, and 18 months of age. Corrected ages were used for preterm infants. Two physiotherapists took part in assessing each infant’s gross motor assessment; both were experienced in infant motor development follow-up, and both had been trained to administer the AIMS. Both evaluators assessed each of the infants at the same time, independently, and blinded to each other. The AIMS is designed to measure motor skills from birth to independent walking. It consists of 58 items
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divided into four subscales: prone (21 items), supine (nine items), sitting (12 items), and standing (16 items). Each test item is specifically described in terms of the weight-bearing surface of the body, the posture necessary to achieve the gross motor skill, and the antigravity or voluntary movement performed by the infant in the position. Spontaneous movements of the infants were observed by the physical therapists. Each item must be completed in order to receive a score. “Key descriptors”, which must be observed to give credit to the item, are provided on the score sheet. The manual provides more details for proper scoring. The total raw score, which is the sum of the positional item scores, ranges from 0 to 58. The higher the score, the more mature the child’s gross motor pattern. The instrument has acceptable levels of reliability and validity when used with preterm Taiwanese infants [24]. 2.3. Data analysis SPSS 10.0 for Windows was used for statistical analysis. v2 and Fisher’s exact tests were used to compare demographic characteristics at birth and neonatal morbidity. The gross motor developmental patterns in all three groups were evaluated at three time points: 6, 12, and 18 months postnatal. A repeated measures analysis of variance (ANOVA) was used to examine the effects of age and group on the infants’ motor performance. When a significant difference was found, a post hoc comparison using Scheffe’s method identified the different pairs. Significance was set at p < 0.05. Continuous data are means ± standard deviation (SD), unless otherwise indicated. The area under the receiver operator curve (ROC) was calculated to identify the most useful subscale within AIMS to detect the VLBW infants with cystic PVL at the corrected age of 6 and 12 months [25]. The area under the ROC curve is the probability of correctively classifying a pair of a VLBW infant with and that without cystic PVL using a subscale.
3. Results 3.1. Diagnosis Cystic PVL was diagnosed at a mean age of 28 days (range, 21–60 days). None of the infants in cPVL+ group had intraventricular hemorrhage. 3.2. Participant characteristics One of the 36 infants in the cPVL+ group was excluded because she developed a grade IV intraventricular hemorrhage during the study; two of the 72 infants in the cPVL group were excluded because they were lost to follow-up; and one of the 77 infants in the HC group was excluded because of an incomplete followup record. The mean gestational age, mean bbw, and Apgar scores at 1 and 5 min were all significantly larger in HC group infants than in cPVL+ and cPVL group infants (p < 0.001). There were no significant differences in gender, bbw, gestational age, or Apgar score 1 and 5 min Apgar scores between the cPVL+ and cPVL group infants (Table 1). Although there were nearly twice as many boys as girls (23/12) in the cPVL+ group, that difference was not significant according to a v2 test. There were no significant differences in the incidence of sepsis, bronchopulmonary dysplasia, or patent ductus arteriosus between the two preterm groups. 3.3. Neurodevelopmental outcome Gross motor developmental patterns were evaluated at three time points of corrected age: at 6, 12, and 18 months old. A repeated measures ANOVA was used to examine the effects of age (time) and group (two groups of preterm infants and one group of term infants) on the prone, supine, sitting, and standing AIMS subscales. There were significant differences for the prone, supine, sitting, standing subscales and total
Table 1 Clinical characteristics of the infants in the study. Characteristic
cPVL+ group n = 35
cPVL group n = 70
HC group n = 76
Gestational age (weeks)a Birth body weight (g)a Male/female Apgar score (1 min)a Apgar score (5 min)a Sepsis (%) Bronchopulmonary disease (%) Patent ductus arteriosis (%)
28.5 ± 2.0 1201 ± 181 23/12 4.7 ± 2.0 7.0 ± 1.3 25.7 14.2 32.2
28.6 ± 2.2 1124 ± 223 32/38 4.8 ± 1.8 7.0 ± 1.5 26.3 14.8 30.7
39.0 ± 3.9 3342 ± 451 36/40 7.9 ± 0.3 9.0 ± 0.0 0 0 0
cPVL+ group, very low birth weight preterm infants with cystic periventricular leukomalacia; cPVL group, very low birth weight preterm infants without cystic periventricular leukomalacia; HC group, healthy full-term infants (gestational age, 37–42 weeks). a Significant difference between the cPVL+, cPVL and HC group infants (p < 0.001) analysis of variance (ANOVA) and then the Tukey Honestly Significant Difference post hoc tests.
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Table 2 Alberta Infant Motor Scale (AIMS) subscales and total scores by group at 6, 12, and 18 months old. AIMS subscales and total scores
n
6 months old Mean (SD)
12 months old Mean (SD)
18 months old Mean (SD)
Group effect p-value
Time effect p-value
Interaction effect p-value
Prone cPVL+ group cPVL group HC group
35 70 76
5.23 (1.68)a,b 7.79 (2.11)c 10.18 (2.67)
7.70 (2.30)a,b 20.10 (2.06) 20.72 (1.09)
9.86 (2.70)a,b 20.87 (0.64) 21.00 (0.00)
<0.001 – –
<0.001 – –
<0.001 – –
Supine cPVL+ group cPVL group HC group
35 70 76
4.23 (0.99)a,b 6.88 (1.33)c 7.97 (1.02)
6.27 (1.79)a,b 8.97 (0.17) 9.00 (0.00)
7.00 (1.88)a,b 9.00 (0.00) 9.00 (0.00)
<0.001 – –
<0.001 – –
<0.001 – –
Sitting cPVL+ group cPVL group HC group
35 70 76
2.96 (1.15)a,b 4.85 (1.59)c 6.37 (2.06)
5.12 (2.20)a,b 11.50 (1.15) 11.99 (0.11)
6.49 (2.57)a,b 11.94 (0.23) 12.00 (0.00)
<0.001 – –
<0.001 – –
<0.001 – –
Standing cPVL+ group cPVL group HC group
35 70 76
1.92 (0.69)b 2.24 (0.58)c 3.62 (2.11)
2.88 (1.24)a,b 10.94 (2.54)c 13.54 (2.00)
4.57 (2.76)a,b 15.33 (1.84) 15.99 (0.11)
<0.001 – –
<0.001 – –
<0.001 – –
Total score cPVL+ group cPVL group HC group
35 70 76
14.54 (2.97)a,b 21.52 (4.38)c 28.14 (5.17)
22.61 (7.35)a,b 51.51 (5.07)c 55.25 (2.42)
28.66 (9.80)a,b 57.14 (2.52) 57.99 (0.11)
<0.001
<0.001
<0.001
cPVL+ group, very low-birth-weight preterm infants with cystic periventricular leukomalacia; cPVL group, very low-birth-weight preterm infants without cystic periventricular leukomalacia; HC group, healthy full-term infants (gestational age, 37–42 weeks); SD, standard deviation. Data were compared using repeated measurement analysis of variance (ANOVA), followed by post hoc comparisons by Scheffe’s method. There were significant (all p < 0.05) differences between the groups for prone, supine, sitting and standing subscales, and total scores. a cPVL+ vs. cPVL . b cPVL+ vs. HC group. c cPVL vs. HC group.
scores of the AIMS assessed across ages (all p < 0.001), between groups (all p < 0.001), and for the interaction effect (all p < 0.001) (Table 2). The sequential changes of gross motor performance of the three groups at age 6, 12, and 18 months is shown in Fig. 1. At 6 months old, the cPVL+ group infants showed significantly lower supine, prone, and sitting subscales than the cPVL group infants (all p < 0.05) (Fig. 1 and Table 2). The cPVL group infants also had significantly lower supine, prone, sitting, and standing subscales than the HC group infants (all p < 0.05). At 12 months old, the cPVL+ group infants had significantly lower supine, prone, sitting, and standing subscales than the cPVL group infants (all p < 0.05). The cPVL group infants differed from the HC group infants only at the standing subscale. At 18 months old, the cPVL+ group infants had significantly lower supine, prone, sitting, and standing subscales than the cPVL group infants (all p < 0.05). In contrast, there were no significant differences in any subscale between the cPVL and the HC group infants. The cPVL+ group infants had significantly lower prone, supine and sitting subscales at 6, 12, and 18 months corrected age than the cPVL group infants. The area under the ROC curve was used to clarify the most useful AIMS subscale that could be used to
discriminate the cPVL+ preterm infants from the cPVL preterm infants at the corrected age 6 and 12 months. The areas under the ROC curves for prone, supine, sitting, and standing subscale were (mean ± standard error of mean) 0.82 ± 0.04, 0.93 ± 0.02, 0.83 ± 0.05, and 0.62 ± 0.07, respectively, at the corrected age 6 months; and 1.00 ± 0.00, 0.97 ± 0.03, 0.99 ± 0.01, and 0.98 ± 0.01, respectively, at age 12 months. This ROC curve analysis result indicated that although the prone, supine, sitting, and standing subscale at age 12 months were higher than the respective subscale at age 6 months, the supine subscale is the most useful subscale to discriminate the cPVL+ preterm infants from the cPVL preterm infants as early as 6 months old. Pediatric neurologists diagnosed all 35 cPVL+ group infants as having cerebral palsy at 24 months old. Topographic classification showed that 28/35 infants had spastic diplegia, 6/35 had quadriplegia, and 1/35 had hemiplegia. All cPVL group infants developed normally. 4. Discussion The AIMS has been widely used, but a gross motor developmental profile of VLBW preterm infants with
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Fig. 1. AIMS total and subscale scores over time for VLBW preterm infants with cystic PVL (cPVL+ group), VLBW preterm infants without cystic PVL (cPVL group) and healthy full-term controls (HC). Summary subscales are given for (A) prone, (B) supine, (C) sitting, (D) standing, and (E) total scores. Values are means ± SEM. The high scores indicate better performance. a: cPVL+ vs. cPVL group (p < 0.05); b: cPVL+ vs. HC group (p < 0.05); c: cPVL vs. HC group (p < 0.05).
cystic PVL has not been previously published. We report, for VLBW preterm infants with and without cystic PVL and healthy full-term infants from 6 to 18 months old, the longitudinal development of gross motor function on four AIMS subscales and total score. The healthy full-term infants had the best gross motor performance, and the VLBW preterm infants with cystic PVL had the worst. The 6-month-old infants in both VLBW preterm groups had significant differences in supine, prone, and sitting scores that persisted up to 18 months old. The ROC curve analysis indicated that supine is the most useful subscale to identify VLBW preterm infants with cystic PVL as early as 6 months corrected age. This finding indicates that cystic PVL had consistent negative effects on gross motor functions beginning as early as 6 months old. Most premature infants with PVL are asymptomatic. If symptoms occur, they are usually subtle, such as decreased tone in the lower extremities, increased tone in the neck extensors, apnea, bradycardia, irritability, etc. [7]. However; it is often difficult to identify PVL based on the infant’s physical or behavioral characteristics. The AIMS can be used to identify cystic PVL in VLBW preterm infants as young as 6 months old. Cystic PVL contributes to the development of cerebral palsy [26–30]. Consistent with these observations, all VLBW preterm infants with cystic PVL in our study were later diagnosed with cerebral palsy at 2 years old. Thus, early identification of cystic PVL in VLBW preterm infants is important for beginning early rehabilitation and for obtaining a good effect on the plasticity of the premature brain. The VLBW preterm infants without cystic PVL caught up with the development of healthy full-term infants by the time they were 18 months old. However, it took much longer for the VLBW preterm infants to stand. Early intervention targeting primarily the standing capacity of VLBW preterm infants without cystic PVL may accelerate their gross motor maturation. Our data support the results of a report [31] that walking is delayed in VLBW preterm infants. Early standing requires a high degree of coordinated postural stability and mobility of the neck, trunk, shoulders, and legs [32–35]. Therefore, younger VLBW premature infants rarely have high scores on the AIMS standing subscale. The lower standing scores in younger VLBW premature infants may also be attributed to the short gestational age and complicated hospitalization course, especially respiratory distress, sepsis, and necrotizing enterocolitis. In conclusion, VLBW preterm infants with cystic PVL had low AIMS scores at 6, 12, and 18 months old. There were significant differences in supine, prone, and sitting scores between the VLBW preterm infants with and without cystic PVL, especially at 6 months old. AIMS supine subscale is most useful to discriminate the VLBW infants with cystic PVL from those without
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cystic PVL as early as 6 months old. VLBW preterm infants with cystic PVL are at higher risk for motor disability and delayed gross motor milestones as early as 6 months older than are VLBW preterm infants without PVL. VLBW preterm infants without cystic PVL had AIMS scores lower than those of healthy full-term infants at 6 months old, but they caught up with the development of healthy full-term infants by the time they were 18 months old. Using the AIMS to assess gross motor development may assist pediatricians in identifying VLBW preterm infants with PVL as early as 6 months old, and in formulating plans for early therapeutic intervention.
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