Pediatric Neurology 52 (2015) 192e197
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Original Article
Corpus Callosum and Motor Development in Healthy Term Infants Chaw-Liang Chang MD a, b, Kun-Long Hung MD c, d, Yi-Chen Yang MS b, Che-Sheng Ho MD e, f, Nan-Chang Chiu MD e, f, * a
Department of Pediatrics, Cathay General Hospital, Hsinchu, Taiwan Center for Medical Education and Research, Cathay General Hospital, Hsinchu, Taiwan c Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan d School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan e Department of Pediatrics, MacKay Children’s Hospital, Taipei, Taiwan f Mackay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan b
abstract BACKGROUND: Corpus callosum atrophy has been associated with cognitive and motor deficits in elderly people. However, the role of the corpus callosum in infant development is unclear. The aim of this study was to assess the impact of corpus callosum size on motor development in infants. METHODS: We investigated cerebral ultrasonograms performed on healthy infants aged 4 to 6 months. The correlation between the development of rolling over and corpus callosum size was calculated for determining odds ratios. Covariates, including gestational age, sex, age in months, and head circumference were tested using logistic regression. RESULTS: We investigated 244 cerebral ultrasonograms performed on term infants from 2009 to 2011. The percentage of rolling over development in the examined infants increased with age (47.8%, 78.4%, and 97.5% at ages 4, 5, and 6 months, respectively). There was no significant difference in the development of rolling over between male (67.9%) and female (73.6%) children or among different gestational age groups. After the other covariates in the logistic model were adjusted, only age and corpus callosum size (length and thickness) were significantly associated with the development of rolling over: 3.86 times the odds (confidence interval, 2.1 to 7.0) for age in months, 1.14 times the odds (confidence interval, 1.0 to 1.3) for corpus callosum length, and 3.92 times the odds (confidence interval, 1.6 to 9.6) for corpus callosum thickness. CONCLUSIONS: Corpus callosum size is positively associated with the development of rolling over in healthy term infants, independent of the gestational age, sex, age, and head circumference. Keywords: corpus callosum, motor development, rolling over, cerebral ultrasound, infant
Pediatr Neurol 2015; 52: 192-197 Ó 2015 Elsevier Inc. All rights reserved.
Introduction
The corpus callosum (CC) is the largest white matter structure in the human brain, connecting the cortical regions of both hemispheres. It plays a crucial role in interhemispheric integration and is responsible for normal
Article History: Received August 8, 2014; Accepted in final form October 9, 2014 * Communications should be addressed to: Dr. Chiu; Department of Pediatrics; MacKay Children’s Hospital; 92, Section 2, Zhongshan North Road; Taipei 10449, Taiwan. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2014.10.012
communication and cooperation between the two hemispheres. The CC is one of the few white matter tracts that can be discretely identified, showing equally sharp images in computed tomography, magnetic resonance imaging (MRI), and ultrasonography. The CC has been the focus of many studies, but only few studies have investigated the role of the CC in infant motor development. A correlation between CC thickness and the intelligence quotient has been demonstrated in adults and adolescents.1,2 Tissue loss in the CC has been associated with various types of cognitive decline and motor impairment such as Alzheimer’s disease,3 intellectual disability,4 stroke,1 traumatic brain injury,5 multiple sclerosis,6
C.-L. Chang et al. / Pediatric Neurology 52 (2015) 192e197
temporal lobe and frontal lobe epilepsy,7,8 deficient auditory language comprehension,9 dyslexia,10 Down syndrome,11 Huntington disease,12,13 and human immunodeficiency virus and/or AIDS.14 Corpus callosal atrophy has also been linked to disorders such as schizophrenia,15,16 Tourette syndrome,17 bipolar disorder,18,19 post-traumatic stress disorder,20 autism,21 obsessivecompulsive disorder,22 and attention-deficit hyperactivity disorder.23 Most studies on the CC in children have focused on autism and preterm children and adolescents. Several studies conducted on preterm children have suggested that those born prematurely have a smaller CC size later in life compared with those born at term.24-27 Studies on extremely preterm individuals have described the importance of the CC in neuropsychologic development; reduced CC size has been correlated with low intelligence quotient,28-30 poor motor performance,24 and language31 and neuropsychologic impairment.26,29 Although the importance of the CC has been recognized in the neuropsychologic development of prematurely born children and adolescents, the role of the CC in motor development of term infants was still unclear. The aim of this study was to clarify the correlation between the CC and motor development in healthy term infants.
193
FIGURE 1. On the midsagittal plane, the length of the corpus callosum was measured from the most anterior aspect of the genu to the most posterior aspect of the splenium (between the two arrows).
Materials and Methods Selection criteria
Variables
We analyzed cerebral ultrasound examinations performed on 4- to 6month-old healthy term infants (gestational age, 37 to 42 weeks) from January 2009 to December 2011. All cerebral ultrasound scans were performed by the same pediatric neurologist. We chose rolling over (supine to prone) as a marker of infant motor development because rolling over is the first prominent motor development that could be easily recognized by parents and have a clear cut of its occurrence. Ultrasound examinations conducted in winter (mean temperature below 20 C, including December to March) were excluded because of heavy clothing, which might hinder the development of rolling over. Infants born prematurely and term infants with major malformations or known syndromes with developmental implications were also excluded. The status of rolling over (supine to prone) development was asked before performing the cerebral ultrasound examination. Those with uncertain rolling over status record were excluded. The study was approved by the Institutional Review Board of the Cathay General Hospital, and the requirement of informed consent was waived.
The variables for the analysis included age, sex, gestational age, head circumference, and CC size. Head circumference is a measurement of the circumference of the head, around the occiput of the skull to the most anterior portion of the frontal bone. Head circumference was measured immediately before each cerebral ultrasound examination. Rolling over was defined as rolling from the supine to the prone position.
Measuring the CC The cerebral ultrasound scans were performed using a Siemens Sonoline G60S real-time scanner with a multifrequency high-resolution transducer 5.0P10 (4 to 6.5 MHz). Sagittal and coronal views were obtained from the anterior fontanelle in each examination. CC length was measured on midsagittal view and was delineated superiorly by the sulcus of the CC and the cingulate gyrus and inferiorly by the hypoechoic pericallosal cisterns (cavum septi pellucidi and cavum vergae). In this plane, CC length was measured from the most anterior aspect of the genu to the most posterior aspect of the splenium (length between the anterior- and posterior-most points of the CC; Fig 1).32,33 The thickness of the CC was measured at the midcoronal plane. The anterior midbody portion of the CC appeared as a hypoechogenic band between two echogenic lines, bordered superiorly by the interhemispheric echogenic midline, laterally by the frontal horns of the lateral ventricles, and inferiorly by the anechoic cavum septum pellucidum or echogenic septum pellucidum (Fig 2).33
FIGURE 2. On the midcoronal plane, a hypoechogenic corpus callosum band between two echogenic lines was measured according to thickness (between the two arrows).
194
C.-L. Chang et al. / Pediatric Neurology 52 (2015) 192e197
Statistical analysis Statistical analyses were performed using the Statistics Analysis System version 9.2 (SAS Institute Inc, Cary, NC). The proportion and characteristics of all individuals are presented as a number (%) and mean with standard deviation. The chi-square test of independence was used for categorical variables and t test for continuous variables between baseline characteristics and rolling over development. We calculated odds ratios to compare the CC size (both thickness and length) with the development of rolling over. Logistic regression analysis was performed to analyze categorical and continuous variables for rolling over development. The categorical variable was sex, and the continuous variables were gestational age (weeks), age (months), head circumference (cm), CC length (mm), and CC thickness (mm). We calculated the odds ratio and 95% confidence intervals (CIs) to assess whether the observed distribution of examined factors was statistically different between participants with and without the development of rolling over, adjusted for different variables. Statistical analysis was performed by a statistician blinded to patient group assignment. The level of statistical significance for all analyses was set at P < 0.05 by using two-tailed comparison.
and 6 months, respectively, in the nonrolling over group (Fig 3A). The mean CC length was 52.8 4.4 mm and 49.6 1.3 mm in the rolling over and nonrolling over groups, respectively, which was statistically different (P < 0.0001; Table 1). The mean CC thickness increased with age in the rolling over group (2.7, 3.0, and 3.3 mm at ages 4, 5, and 6 months, respectively), but no such change was observed in the nonrolling over group (2.5, 2.8, and 2.4 mm at ages 4, 5, and 6 months, respectively; Fig 3B). The mean CC thickness was 3.0 0.6 mm in the rolling over group and 2.5 0.4 mm in the nonrolling over group, which was also statistically different (P < 0.0001; Table 1). To further clarify the relationship between variables, four models were run for the logistic regression. After adjustment for the other covariates in the logistic models, in models 1 to 4 (Table 2), only age and CC size (length and thickness) were significantly associated with the development of rolling over: 3.86 times the odds (CI, 2.1 to 7.0) for age in months, 1.14 times the odds (CI, 1.0 to 1.3) for CC
Results
We analyzed 244 cerebral ultrasound examinations preformed on healthy term infants aged 4 to 6 months from January 2009 to December 2011. The overall percentage of rolling over development was 70.5%. The percentage of rolling over development increased with age (47.8%, 78.4%, and 97.5% at ages 4, 5, and 6 months, respectively). There were no significant difference in rolling over development between male and female infants (P ¼ 0.33) or among different gestational age groups (P ¼ 0.61). Age, head circumference, and CC size (length and thickness) were significantly associated with the development of rolling over (P < 0.0001; Table 1). The mean CC length increased with age: 51.4, 52.2, and 54.0 mm at ages 4, 5, and 6 months, respectively, in the rolling over group and 49.3, 50.8, and 51.3 mm at ages 4, 5, TABLE 1. Characteristics of Infants
Characteristics
Total
Rolling (þ) Rolling () P Value
Total infants, n (%) Age, n (%) 4 mo old 5 mo old 6 mo old Sex, n (%) Male Female Gestational age, n (%) 37 wk 38 wk 39 wk 40 wk S41 wk Head circumference, mean (SD) (cm) Corpus callosum, mean (SD) (mm) Length Thickness
244
172 (70.5)
113 51 80
54 (47.8) 40 (78.4) 78 (97.5)
59 (52.2)
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Original Article
Corpus Callosum and Motor Development in Healthy Term Infants Chaw-Liang Chang MD a, b, Kun-Long Hung MD c, d, Yi-Chen Yang MS b, Che-Sheng Ho MD e, f, Nan-Chang Chiu MD e, f, * a
Department of Pediatrics, Cathay General Hospital, Hsinchu, Taiwan Center for Medical Education and Research, Cathay General Hospital, Hsinchu, Taiwan c Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan d School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan e Department of Pediatrics, MacKay Children’s Hospital, Taipei, Taiwan f Mackay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan b
abstract BACKGROUND: Corpus callosum atrophy has been associated with cognitive and motor deficits in elderly people. However, the role of the corpus callosum in infant development is unclear. The aim of this study was to assess the impact of corpus callosum size on motor development in infants. METHODS: We investigated cerebral ultrasonograms performed on healthy infants aged 4 to 6 months. The correlation between the development of rolling over and corpus callosum size was calculated for determining odds ratios. Covariates, including gestational age, sex, age in months, and head circumference were tested using logistic regression. RESULTS: We investigated 244 cerebral ultrasonograms performed on term infants from 2009 to 2011. The percentage of rolling over development in the examined infants increased with age (47.8%, 78.4%, and 97.5% at ages 4, 5, and 6 months, respectively). There was no significant difference in the development of rolling over between male (67.9%) and female (73.6%) children or among different gestational age groups. After the other covariates in the logistic model were adjusted, only age and corpus callosum size (length and thickness) were significantly associated with the development of rolling over: 3.86 times the odds (confidence interval, 2.1 to 7.0) for age in months, 1.14 times the odds (confidence interval, 1.0 to 1.3) for corpus callosum length, and 3.92 times the odds (confidence interval, 1.6 to 9.6) for corpus callosum thickness. CONCLUSIONS: Corpus callosum size is positively associated with the development of rolling over in healthy term infants, independent of the gestational age, sex, age, and head circumference. Keywords: corpus callosum, motor development, rolling over, cerebral ultrasound, infant
Pediatr Neurol 2015; 52: 192-197 Ó 2015 Elsevier Inc. All rights reserved.
Introduction
The corpus callosum (CC) is the largest white matter structure in the human brain, connecting the cortical regions of both hemispheres. It plays a crucial role in interhemispheric integration and is responsible for normal
Article History: Received August 8, 2014; Accepted in final form October 9, 2014 * Communications should be addressed to: Dr. Chiu; Department of Pediatrics; MacKay Children’s Hospital; 92, Section 2, Zhongshan North Road; Taipei 10449, Taiwan. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2014.10.012
communication and cooperation between the two hemispheres. The CC is one of the few white matter tracts that can be discretely identified, showing equally sharp images in computed tomography, magnetic resonance imaging (MRI), and ultrasonography. The CC has been the focus of many studies, but only few studies have investigated the role of the CC in infant motor development. A correlation between CC thickness and the intelligence quotient has been demonstrated in adults and adolescents.1,2 Tissue loss in the CC has been associated with various types of cognitive decline and motor impairment such as Alzheimer’s disease,3 intellectual disability,4 stroke,1 traumatic brain injury,5 multiple sclerosis,6
C.-L. Chang et al. / Pediatric Neurology 52 (2015) 192e197
temporal lobe and frontal lobe epilepsy,7,8 deficient auditory language comprehension,9 dyslexia,10 Down syndrome,11 Huntington disease,12,13 and human immunodeficiency virus and/or AIDS.14 Corpus callosal atrophy has also been linked to disorders such as schizophrenia,15,16 Tourette syndrome,17 bipolar disorder,18,19 post-traumatic stress disorder,20 autism,21 obsessivecompulsive disorder,22 and attention-deficit hyperactivity disorder.23 Most studies on the CC in children have focused on autism and preterm children and adolescents. Several studies conducted on preterm children have suggested that those born prematurely have a smaller CC size later in life compared with those born at term.24-27 Studies on extremely preterm individuals have described the importance of the CC in neuropsychologic development; reduced CC size has been correlated with low intelligence quotient,28-30 poor motor performance,24 and language31 and neuropsychologic impairment.26,29 Although the importance of the CC has been recognized in the neuropsychologic development of prematurely born children and adolescents, the role of the CC in motor development of term infants was still unclear. The aim of this study was to clarify the correlation between the CC and motor development in healthy term infants.
193
FIGURE 1. On the midsagittal plane, the length of the corpus callosum was measured from the most anterior aspect of the genu to the most posterior aspect of the splenium (between the two arrows).
Materials and Methods Selection criteria
Variables
We analyzed cerebral ultrasound examinations performed on 4- to 6month-old healthy term infants (gestational age, 37 to 42 weeks) from January 2009 to December 2011. All cerebral ultrasound scans were performed by the same pediatric neurologist. We chose rolling over (supine to prone) as a marker of infant motor development because rolling over is the first prominent motor development that could be easily recognized by parents and have a clear cut of its occurrence. Ultrasound examinations conducted in winter (mean temperature below 20 C, including December to March) were excluded because of heavy clothing, which might hinder the development of rolling over. Infants born prematurely and term infants with major malformations or known syndromes with developmental implications were also excluded. The status of rolling over (supine to prone) development was asked before performing the cerebral ultrasound examination. Those with uncertain rolling over status record were excluded. The study was approved by the Institutional Review Board of the Cathay General Hospital, and the requirement of informed consent was waived.
The variables for the analysis included age, sex, gestational age, head circumference, and CC size. Head circumference is a measurement of the circumference of the head, around the occiput of the skull to the most anterior portion of the frontal bone. Head circumference was measured immediately before each cerebral ultrasound examination. Rolling over was defined as rolling from the supine to the prone position.
Measuring the CC The cerebral ultrasound scans were performed using a Siemens Sonoline G60S real-time scanner with a multifrequency high-resolution transducer 5.0P10 (4 to 6.5 MHz). Sagittal and coronal views were obtained from the anterior fontanelle in each examination. CC length was measured on midsagittal view and was delineated superiorly by the sulcus of the CC and the cingulate gyrus and inferiorly by the hypoechoic pericallosal cisterns (cavum septi pellucidi and cavum vergae). In this plane, CC length was measured from the most anterior aspect of the genu to the most posterior aspect of the splenium (length between the anterior- and posterior-most points of the CC; Fig 1).32,33 The thickness of the CC was measured at the midcoronal plane. The anterior midbody portion of the CC appeared as a hypoechogenic band between two echogenic lines, bordered superiorly by the interhemispheric echogenic midline, laterally by the frontal horns of the lateral ventricles, and inferiorly by the anechoic cavum septum pellucidum or echogenic septum pellucidum (Fig 2).33
FIGURE 2. On the midcoronal plane, a hypoechogenic corpus callosum band between two echogenic lines was measured according to thickness (between the two arrows).
194
C.-L. Chang et al. / Pediatric Neurology 52 (2015) 192e197
Statistical analysis Statistical analyses were performed using the Statistics Analysis System version 9.2 (SAS Institute Inc, Cary, NC). The proportion and characteristics of all individuals are presented as a number (%) and mean with standard deviation. The chi-square test of independence was used for categorical variables and t test for continuous variables between baseline characteristics and rolling over development. We calculated odds ratios to compare the CC size (both thickness and length) with the development of rolling over. Logistic regression analysis was performed to analyze categorical and continuous variables for rolling over development. The categorical variable was sex, and the continuous variables were gestational age (weeks), age (months), head circumference (cm), CC length (mm), and CC thickness (mm). We calculated the odds ratio and 95% confidence intervals (CIs) to assess whether the observed distribution of examined factors was statistically different between participants with and without the development of rolling over, adjusted for different variables. Statistical analysis was performed by a statistician blinded to patient group assignment. The level of statistical significance for all analyses was set at P < 0.05 by using two-tailed comparison.
and 6 months, respectively, in the nonrolling over group (Fig 3A). The mean CC length was 52.8 4.4 mm and 49.6 1.3 mm in the rolling over and nonrolling over groups, respectively, which was statistically different (P < 0.0001; Table 1). The mean CC thickness increased with age in the rolling over group (2.7, 3.0, and 3.3 mm at ages 4, 5, and 6 months, respectively), but no such change was observed in the nonrolling over group (2.5, 2.8, and 2.4 mm at ages 4, 5, and 6 months, respectively; Fig 3B). The mean CC thickness was 3.0 0.6 mm in the rolling over group and 2.5 0.4 mm in the nonrolling over group, which was also statistically different (P < 0.0001; Table 1). To further clarify the relationship between variables, four models were run for the logistic regression. After adjustment for the other covariates in the logistic models, in models 1 to 4 (Table 2), only age and CC size (length and thickness) were significantly associated with the development of rolling over: 3.86 times the odds (CI, 2.1 to 7.0) for age in months, 1.14 times the odds (CI, 1.0 to 1.3) for CC
Results
We analyzed 244 cerebral ultrasound examinations preformed on healthy term infants aged 4 to 6 months from January 2009 to December 2011. The overall percentage of rolling over development was 70.5%. The percentage of rolling over development increased with age (47.8%, 78.4%, and 97.5% at ages 4, 5, and 6 months, respectively). There were no significant difference in rolling over development between male and female infants (P ¼ 0.33) or among different gestational age groups (P ¼ 0.61). Age, head circumference, and CC size (length and thickness) were significantly associated with the development of rolling over (P < 0.0001; Table 1). The mean CC length increased with age: 51.4, 52.2, and 54.0 mm at ages 4, 5, and 6 months, respectively, in the rolling over group and 49.3, 50.8, and 51.3 mm at ages 4, 5, TABLE 1. Characteristics of Infants
Characteristics
Total
Rolling (þ) Rolling () P Value
Total infants, n (%) Age, n (%) 4 mo old 5 mo old 6 mo old Sex, n (%) Male Female Gestational age, n (%) 37 wk 38 wk 39 wk 40 wk S41 wk Head circumference, mean (SD) (cm) Corpus callosum, mean (SD) (mm) Length Thickness
244
172 (70.5)
113 51 80
54 (47.8) 40 (78.4) 78 (97.5)
59 (52.2)
