DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY
ORIGINAL ARTICLE
Can preoperative cranial ultrasound predict early neurodevelopmental outcome in infants with congenital heart disease? BEATRICE LATAL 1,2 | CHRISTIAN KELLENBERGER 3 | ANASTASIA DIMITROPOULOS 1 CHRISTIAN BALMER 5 | INGRID BECK 1 | VERA BERNET 2,6
| CORNELIA HAGMANN 4 |
1 Child Development Center, University Children’s Hospital, Zurich; 2 Children’s Research Center, University Children’s Hospital Zurich, Zurich; 3 Paediatric Radiology, University Children’s Hospital, Zurich; 4 Clinic of Neonatology, University Hospital Zurich, Zurich; 5 Department of Cardiology, University Children’s Hospital Zurich, Zurich; 6 Department of Paediatric Intensive Care and Neonatology, University Children’s Hospital Zurich, Zurich, Switzerland. Correspondence to Beatrice Latal at Child Development Center, University Children’s Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland. E-mail: [email protected]
PUBLICATION DATA
Accepted for publication 14th December 2014. Published online 23rd January 2015. ABBREVIATIONS
BAS CHD cUS IVH MDI PDI PVL
Balloon-atrial septostomy Congenital heart disease Cranial ultrasound Intraventricular haemorrhage Mental developmental index Psychomotor developmental index Periventricular leukomalacia
AIM To determine the role of preoperative cranial ultrasound (cUS) in predicting neurodevelopmental outcome in infants undergoing bypass surgery for congenital heart disease (CHD). METHOD Prospective cohort study on 77 infants (44 males, 33 females) operated before 3 months of age (median age at surgery 10d [range 3–88d]) who received at least one preoperative cUS. Outcome at 1 year was assessed with a standardized neurological examination and the Bayley Scales of Infant Development II (mental developmental index [MDI]; psychomotor developmental index [PDI]). RESULTS Abnormalities on cUS were detected in 22 (29%) infants and consisted of diffuse brain oedema (n=12, 16%), periventricular white matter injury (n=5, 6%), ventricular dilatation (n=3, 4%), and intraventricular haemorrhage (IVH) (n=2, 3%). Infants undergoing balloon-atrial septostomy (BAS) had a higher rate of subsequent brain oedema than those without BAS (p=0.006). cUS abnormalities were not related to neurodevelopmental outcome. INTERPRETATION Preoperative cUS findings in infants undergoing bypass surgery for CHD occur rather frequently, consisting of mild lesions such as brain oedema or white matter changes. These findings, however, do not correlate with early neurodevelopmental outcome.
Survival rates after bypass surgery for congenital heart disease (CHD) have increased in the past few decades,1 but neurodevelopment and quality of life is often impaired.2–4 Studies have shown that infants may manifest neurobehavioural abnormalities before surgery and that these abnormalities are highly predictive of later outcome.5,6 Recently, cerebral abnormalities have been detected before surgery in almost half of all newborn infants with complex CHD using magnetic resonance imaging (MRI).7–10 Yet, in clinical practice cranial ultrasound (cUS) is the routinely used bedside tool to assess preoperative cerebral abnormalities in the term CHD population.11,12 In the preterm population, cUS has been shown to have a high sensitivity for cerebral injuries such as periventricular leukomalacia (PVL) and intraventricular haemorrhage (IVH), with a good predictive validity for major neurodevelopmental impairments.13,14 A recently published study on a large cohort of infants with CHD, however, demonstrated that cUS poorly correlated with MRI findings.15 In contrast, for infants with CHD undergoing bypass surgery, the validity of preoperative cUS in predicting neurodevelopmental outcome has not © 2015 Mac Keith Press
yet been determined. Thus, the aim of this study was to determine the association between preoperative cUS and neurodevelopmental outcome in infants undergoing bypass surgery.
METHOD Design This is a prospective cohort study performed at the University Children’s Hospital of Zurich, a paediatric tertiary care centre with 350 cardiac surgeries. All children in the study were recruited before the first open-heart surgery. The study was approved by the local ethics committee and written informed consent was obtained from the parents. Children were enrolled between August 2004 and July 2006, and between October 2007 and May 2008. Infants eligible for this analysis had their first bypass surgery at an age younger than 3 months of age. Surgical risk was determined using the Risk Adjustment for Congenital Heart Surgery-1 scoring system.16 Genetic comorbidities were screened for based on clinical suspicion. Demographic and perioperative variables were prospectively collected and entered into an SPSS database. DOI: 10.1111/dmcn.12701
639
Surgical management Cardiac surgery was performed by two paediatric cardiac surgeons. Alpha-stat blood gas management was routine. In most cardiac surgeries normothermic or mild hypothermic cardiopulmonary bypass surgery (rectal temperature 25mmHg, measured in the right radial artery. Cranial ultrasound cUS was obtained before the first open-heart surgery in all infants, but after a balloon-atrial septostomy (BAS) procedure if this procedure was necessary. cUS was performed in the six coronal and five sagittal planes with an Acuson Sequoia scanner (Siemens, Mountain View, CA, USA) using 8MHz vector and 15MHz linear-array transducers. In our institution, cUS is recommended for all infants undergoing bypass surgery before the age of 3 months. One experienced paediatric radiologist (CK) who was unaware of the clinical course of the infants reviewed all cUS to classify the findings as described. It was not deemed necessary to review the scans that were considered normal, as they had been reviewed by a senior paediatric radiologist as part of the clinical routine. cUS findings were classified as follows: white matter injuries (periventricular leukomalacia [PVL]) according to de Vries et al.,17 intraventricular haemorrhage (IVH) according to Papile,18 ventricular dilatation and/or ventricular asymmetry, and diffuse brain oedema. Diffuse brain oedema was defined as generalized increase in cerebral echogenicity with slit-like lateral ventricles and effacement of sulci.19 In infants with more than one abnormal finding, the most severe finding was coded. Eight infants (10%) had repeat cUS examinations (maximum 4). cUS findings were classified into normal and abnormal. A first categorization was made where all findings were coded as abnormal ‘any cUS abnormality’. A second categorization was made where only PVL and cerebral oedema were considered abnormal. Neurodevelopmental assessment Infants were examined by two developmental paediatricians from the Child Development Centre of the University Children’s Hospital Zurich (BL, AD). Examiners were not aware of the cUS findings, but were aware of the CHD diagnosis and clinical course. A standardized neurological assessment was performed before surgery if the infant was haemodynamically stable and at 1 year of age, at least 4 to 6 months after surgery. The assessment was modified after Prechtl and Beintema20 and resulted in a neurological severity score, which has been applied in infants with CHD.7 The following domains were graded from 0 to 3: posture, general movements, tone, primitive and muscle stretch reflexes, cranial nerves and reactivity/behaviour, 640 Developmental Medicine & Child Neurology 2015, 57: 639–644
• • • • •
What this paper adds Infants with congenital heart disease are at risk for preoperative cerebral abnormalities. Preoperative cranial ultrasound findings occur in around 30% of infants. Abnormalities consist of diffuse oedema or mild white matter injury. Infants undergoing balloon-atrial septostomy are at risk for cerebral oedema. Cranial ultrasound is not related to early neurodevelopmental outcome.
and a summary score ranging from 0 to 18 was created. At 1 year of age, the Bayley Scales of Infant Development II providing a mental developmental index (MDI) and a psychomotor developmental index (PDI)21 was administered.
Statistics Results are presented as median and ranges. Univariate analyses were performed using non-parametric tests. Comparisons between median MDI and PDI to test norms were performed using the Wilcoxon signed rank test. Correlation between variables was performed with the Spearman rank sign test. Associations between risk factors and outcome were analyzed using a univariate regression analysis with MDI, PDI and neuroscore as the dependent continuous variable. As genetic comorbidity was the strongest determinant of outcome, we excluded infants with a genetic comorbidity in the analysis of risk factors for poorer neurodevelopmental outcome. To determine the independent influence of risk factors on outcome, we performed a multiple linear regression analysis. We included variables based on their significant correlation with outcome in the univariate analysis or based on reports from the literature (sex, cyanotic CHD). Based on the research question of this article, we also included the variable preoperative cUS abnormalities. Thus, included variables were: any cUS abnormality; preoperative neuroscore; age at surgery; sepsis; length of ICU stay; male sex; and cyanotic heart defect. Analyses were performed using SPSS 19 (SPSS Inc., Chicago, IL, USA). RESULTS Patients During the study period, 99 infants were younger than 3 months at the time of the surgery. Of those, 77 had at least one preoperative cUS. Infants with a preoperative cUS had a higher surgical risk and were younger at surgery than those without a cUS (Table I). cUS was obtained at a median age of 3 days (range 0–83d). Surgery was performed at a median age of 10 days, 33 (43%) infants were operated within the first 7 days of age, 22 (28.5%) between 8 days and 28 days of age, and 22 (28.5%) were older than 28 days at the time of the surgery. cUS was performed at a median age of 1 day (0–5d) in the first group, at a median age of 3.5 days (0–19d) in the second group and at 33 days (1–83d) in the third group. Infants who had surgery within 1 month were all admitted to the neonatal intensive care unit and not discharged. Nine infants died postoperatively, one family moved away, and one child was placed in foster care and was not brought back for the 1-year examination. Thus, follow-up
Table I: Perinatal and cardiac variables for infants with and without preoperative cranial ultrasound Preoperative cUS n=77 n (%) Sex (male) Cyanotic CHD Univentricular CHD Genetic defect Prenatal diagnosis
Age at surgery (d) Surgical risk (RACHS-1) Apgar 1 Apgar 5 Apgar 10 Arterial cord blood pH Gestational age (wks) Birthweight (g)
44 55 11 19 21
No preoperative cUS n=21 n (%)
(57) (71) (14) (25) (27)
p-value
12 (57) 8 (38) 0 (0) 5 (24) 1 (5)
1.0 0.01 0.12 1.0 0.04
Median (range)
Median (range)
p-value
10 3 8 9 9 7.27 38.7 3180
63 2 8 9 10 7.25 39.3 3110
ORIGINAL ARTICLE
Can preoperative cranial ultrasound predict early neurodevelopmental outcome in infants with congenital heart disease? BEATRICE LATAL 1,2 | CHRISTIAN KELLENBERGER 3 | ANASTASIA DIMITROPOULOS 1 CHRISTIAN BALMER 5 | INGRID BECK 1 | VERA BERNET 2,6
| CORNELIA HAGMANN 4 |
1 Child Development Center, University Children’s Hospital, Zurich; 2 Children’s Research Center, University Children’s Hospital Zurich, Zurich; 3 Paediatric Radiology, University Children’s Hospital, Zurich; 4 Clinic of Neonatology, University Hospital Zurich, Zurich; 5 Department of Cardiology, University Children’s Hospital Zurich, Zurich; 6 Department of Paediatric Intensive Care and Neonatology, University Children’s Hospital Zurich, Zurich, Switzerland. Correspondence to Beatrice Latal at Child Development Center, University Children’s Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland. E-mail: [email protected]
PUBLICATION DATA
Accepted for publication 14th December 2014. Published online 23rd January 2015. ABBREVIATIONS
BAS CHD cUS IVH MDI PDI PVL
Balloon-atrial septostomy Congenital heart disease Cranial ultrasound Intraventricular haemorrhage Mental developmental index Psychomotor developmental index Periventricular leukomalacia
AIM To determine the role of preoperative cranial ultrasound (cUS) in predicting neurodevelopmental outcome in infants undergoing bypass surgery for congenital heart disease (CHD). METHOD Prospective cohort study on 77 infants (44 males, 33 females) operated before 3 months of age (median age at surgery 10d [range 3–88d]) who received at least one preoperative cUS. Outcome at 1 year was assessed with a standardized neurological examination and the Bayley Scales of Infant Development II (mental developmental index [MDI]; psychomotor developmental index [PDI]). RESULTS Abnormalities on cUS were detected in 22 (29%) infants and consisted of diffuse brain oedema (n=12, 16%), periventricular white matter injury (n=5, 6%), ventricular dilatation (n=3, 4%), and intraventricular haemorrhage (IVH) (n=2, 3%). Infants undergoing balloon-atrial septostomy (BAS) had a higher rate of subsequent brain oedema than those without BAS (p=0.006). cUS abnormalities were not related to neurodevelopmental outcome. INTERPRETATION Preoperative cUS findings in infants undergoing bypass surgery for CHD occur rather frequently, consisting of mild lesions such as brain oedema or white matter changes. These findings, however, do not correlate with early neurodevelopmental outcome.
Survival rates after bypass surgery for congenital heart disease (CHD) have increased in the past few decades,1 but neurodevelopment and quality of life is often impaired.2–4 Studies have shown that infants may manifest neurobehavioural abnormalities before surgery and that these abnormalities are highly predictive of later outcome.5,6 Recently, cerebral abnormalities have been detected before surgery in almost half of all newborn infants with complex CHD using magnetic resonance imaging (MRI).7–10 Yet, in clinical practice cranial ultrasound (cUS) is the routinely used bedside tool to assess preoperative cerebral abnormalities in the term CHD population.11,12 In the preterm population, cUS has been shown to have a high sensitivity for cerebral injuries such as periventricular leukomalacia (PVL) and intraventricular haemorrhage (IVH), with a good predictive validity for major neurodevelopmental impairments.13,14 A recently published study on a large cohort of infants with CHD, however, demonstrated that cUS poorly correlated with MRI findings.15 In contrast, for infants with CHD undergoing bypass surgery, the validity of preoperative cUS in predicting neurodevelopmental outcome has not © 2015 Mac Keith Press
yet been determined. Thus, the aim of this study was to determine the association between preoperative cUS and neurodevelopmental outcome in infants undergoing bypass surgery.
METHOD Design This is a prospective cohort study performed at the University Children’s Hospital of Zurich, a paediatric tertiary care centre with 350 cardiac surgeries. All children in the study were recruited before the first open-heart surgery. The study was approved by the local ethics committee and written informed consent was obtained from the parents. Children were enrolled between August 2004 and July 2006, and between October 2007 and May 2008. Infants eligible for this analysis had their first bypass surgery at an age younger than 3 months of age. Surgical risk was determined using the Risk Adjustment for Congenital Heart Surgery-1 scoring system.16 Genetic comorbidities were screened for based on clinical suspicion. Demographic and perioperative variables were prospectively collected and entered into an SPSS database. DOI: 10.1111/dmcn.12701
639
Surgical management Cardiac surgery was performed by two paediatric cardiac surgeons. Alpha-stat blood gas management was routine. In most cardiac surgeries normothermic or mild hypothermic cardiopulmonary bypass surgery (rectal temperature 25mmHg, measured in the right radial artery. Cranial ultrasound cUS was obtained before the first open-heart surgery in all infants, but after a balloon-atrial septostomy (BAS) procedure if this procedure was necessary. cUS was performed in the six coronal and five sagittal planes with an Acuson Sequoia scanner (Siemens, Mountain View, CA, USA) using 8MHz vector and 15MHz linear-array transducers. In our institution, cUS is recommended for all infants undergoing bypass surgery before the age of 3 months. One experienced paediatric radiologist (CK) who was unaware of the clinical course of the infants reviewed all cUS to classify the findings as described. It was not deemed necessary to review the scans that were considered normal, as they had been reviewed by a senior paediatric radiologist as part of the clinical routine. cUS findings were classified as follows: white matter injuries (periventricular leukomalacia [PVL]) according to de Vries et al.,17 intraventricular haemorrhage (IVH) according to Papile,18 ventricular dilatation and/or ventricular asymmetry, and diffuse brain oedema. Diffuse brain oedema was defined as generalized increase in cerebral echogenicity with slit-like lateral ventricles and effacement of sulci.19 In infants with more than one abnormal finding, the most severe finding was coded. Eight infants (10%) had repeat cUS examinations (maximum 4). cUS findings were classified into normal and abnormal. A first categorization was made where all findings were coded as abnormal ‘any cUS abnormality’. A second categorization was made where only PVL and cerebral oedema were considered abnormal. Neurodevelopmental assessment Infants were examined by two developmental paediatricians from the Child Development Centre of the University Children’s Hospital Zurich (BL, AD). Examiners were not aware of the cUS findings, but were aware of the CHD diagnosis and clinical course. A standardized neurological assessment was performed before surgery if the infant was haemodynamically stable and at 1 year of age, at least 4 to 6 months after surgery. The assessment was modified after Prechtl and Beintema20 and resulted in a neurological severity score, which has been applied in infants with CHD.7 The following domains were graded from 0 to 3: posture, general movements, tone, primitive and muscle stretch reflexes, cranial nerves and reactivity/behaviour, 640 Developmental Medicine & Child Neurology 2015, 57: 639–644
• • • • •
What this paper adds Infants with congenital heart disease are at risk for preoperative cerebral abnormalities. Preoperative cranial ultrasound findings occur in around 30% of infants. Abnormalities consist of diffuse oedema or mild white matter injury. Infants undergoing balloon-atrial septostomy are at risk for cerebral oedema. Cranial ultrasound is not related to early neurodevelopmental outcome.
and a summary score ranging from 0 to 18 was created. At 1 year of age, the Bayley Scales of Infant Development II providing a mental developmental index (MDI) and a psychomotor developmental index (PDI)21 was administered.
Statistics Results are presented as median and ranges. Univariate analyses were performed using non-parametric tests. Comparisons between median MDI and PDI to test norms were performed using the Wilcoxon signed rank test. Correlation between variables was performed with the Spearman rank sign test. Associations between risk factors and outcome were analyzed using a univariate regression analysis with MDI, PDI and neuroscore as the dependent continuous variable. As genetic comorbidity was the strongest determinant of outcome, we excluded infants with a genetic comorbidity in the analysis of risk factors for poorer neurodevelopmental outcome. To determine the independent influence of risk factors on outcome, we performed a multiple linear regression analysis. We included variables based on their significant correlation with outcome in the univariate analysis or based on reports from the literature (sex, cyanotic CHD). Based on the research question of this article, we also included the variable preoperative cUS abnormalities. Thus, included variables were: any cUS abnormality; preoperative neuroscore; age at surgery; sepsis; length of ICU stay; male sex; and cyanotic heart defect. Analyses were performed using SPSS 19 (SPSS Inc., Chicago, IL, USA). RESULTS Patients During the study period, 99 infants were younger than 3 months at the time of the surgery. Of those, 77 had at least one preoperative cUS. Infants with a preoperative cUS had a higher surgical risk and were younger at surgery than those without a cUS (Table I). cUS was obtained at a median age of 3 days (range 0–83d). Surgery was performed at a median age of 10 days, 33 (43%) infants were operated within the first 7 days of age, 22 (28.5%) between 8 days and 28 days of age, and 22 (28.5%) were older than 28 days at the time of the surgery. cUS was performed at a median age of 1 day (0–5d) in the first group, at a median age of 3.5 days (0–19d) in the second group and at 33 days (1–83d) in the third group. Infants who had surgery within 1 month were all admitted to the neonatal intensive care unit and not discharged. Nine infants died postoperatively, one family moved away, and one child was placed in foster care and was not brought back for the 1-year examination. Thus, follow-up
Table I: Perinatal and cardiac variables for infants with and without preoperative cranial ultrasound Preoperative cUS n=77 n (%) Sex (male) Cyanotic CHD Univentricular CHD Genetic defect Prenatal diagnosis
Age at surgery (d) Surgical risk (RACHS-1) Apgar 1 Apgar 5 Apgar 10 Arterial cord blood pH Gestational age (wks) Birthweight (g)
44 55 11 19 21
No preoperative cUS n=21 n (%)
(57) (71) (14) (25) (27)
p-value
12 (57) 8 (38) 0 (0) 5 (24) 1 (5)
1.0 0.01 0.12 1.0 0.04
Median (range)
Median (range)
p-value
10 3 8 9 9 7.27 38.7 3180
63 2 8 9 10 7.25 39.3 3110
