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Sengupta A, Gauvreau K, Sadhwani A, Butler SC, Newburger JW, Del Nido PJ, Nathan M. Impact of Residual Lesion Severity on Neurodevelopmental Outcomes Following Congenital Heart Surgery in Infancy and Childhood. Pediatr Cardiol 2024; 45:1676-1691. [PMID: 37543999 DOI: 10.1007/s00246-023-03248-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 07/20/2023] [Indexed: 08/08/2023]
Abstract
Children with congenital heart disease are at increased risk of neurodevelopmental delay throughout their lifespan. This risk is exacerbated following congenital heart surgery (CHS) in infancy. However, there are few modifiable risk factors for postoperative neurodevelopmental delay. In this study, we assessed the Residual Lesion Score (RLS), a quality assessment metric that evaluates residual lesion severity following CHS, as a predictor of neurodevelopmental delay. This was a single-center, retrospective review of patients who underwent CHS from 01/2011 to 03/2021 and post-discharge neurodevelopmental evaluation from 12 to 42 months of age using the Bayley Scales of Infant Development, 3rd Edition (BSID-III). RLS was assigned per published criteria: RLS 1, no residua; RLS 2, minor residua; and RLS 3, major residua or pre-discharge reintervention. Associations between RLS and BSID-III scores, as well as trends in neurodevelopmental outcomes over time, were evaluated. Of 517 patients with median age at neurodevelopmental testing of 20.0 (IQR 18.0-22.7) months, 304 (58.8%), 146 (28.2%), and 67 (13.0%) were RLS 1, 2, and 3, respectively. RLS 3 patients had significantly lower scaled scores in the cognitive, receptive, and expressive communication, and fine and gross motor domains, compared with RLS 1 patients. Multivariable models accounted for 21.5%-31.5% of the variation in the scaled scores, with RLS explaining 1.4-7.3% of the variation. In a subgroup analysis, RLS 3 patients demonstrated relatively fewer gains in cognitive, expressive communication, and gross motor scores over time (all p < 0.05). In conclusion, RLS 3 patients are at increased risk for neurodevelopmental delay, warranting closer follow-up and greater developmental support for cognitive, language, and motor skills soon after surgery.
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Affiliation(s)
- Aditya Sengupta
- Department of Cardiac Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
| | - Kimberlee Gauvreau
- Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
- Department of Cardiology, Boston Children's Hospital, Boston, MA, USA
| | - Anjali Sadhwani
- Department of Psychiatry and Behavioral Sciences, Harvard Medical School, Boston, MA, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Samantha C Butler
- Department of Psychiatry and Behavioral Sciences, Harvard Medical School, Boston, MA, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Jane W Newburger
- Department of Cardiology, Boston Children's Hospital, Boston, MA, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Pedro J Del Nido
- Department of Cardiac Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA
- Department of Surgery, Harvard Medical School, Boston, MA, USA
| | - Meena Nathan
- Department of Cardiac Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA
- Department of Surgery, Harvard Medical School, Boston, MA, USA
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Liu Y, Hu L, Zhu M, Zhong J, Fu M, Yang M, Cheng S, Wang Y, Mo X, Yang M. Disrupted White Matter Topology Organization in Preschool Children with Tetralogy of Fallot. Brain Behav 2024; 14:e70153. [PMID: 39576237 PMCID: PMC11583477 DOI: 10.1002/brb3.70153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 09/20/2024] [Accepted: 10/26/2024] [Indexed: 11/24/2024] Open
Abstract
BACKGROUND Cognitive impairment is the most common long-term complication in children with congenital heart disease (CHD) and is closely related to the brain network. However, little is known about the impact of CHD on brain network organization. This study aims to investigate brain structural network properties that may underpin cognitive deficits observed in children with Tetralogy of Fallot (TOF). METHODS In this prospective study, 29 preschool-aged children diagnosed with TOF and 19 without CHD (non-CHD) were enrolled. Participants underwent diffusion tensor imaging (DTI) scans alongside cognitive assessment using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-fourth edition (WPPSI-IV). We constructed a brain structural network based on DTI and applied graph analysis methodology to investigate alterations in diverse network topological properties in TOF compared with non-CHD. Additionally, we explored the correlation between brain network topology and cognitive performance in TOF. RESULTS Although both TOF and non-CHD exhibited small-world characteristics in their brain networks, children with TOF significantly demonstrated increased characteristic path length and decreased clustering coefficient, global efficiency, and local efficiency compared with non-CHD (p < 0.05). Regionally, reduced nodal betweenness and degree were found in the left cingulate gyrus, and nodal efficiency was decreased in the right precentral gyrus and cingulate gyrus, left inferior frontal gyrus (triangular part), and insula (p < 0.05). Furthermore, a positive correlation was identified between local efficiency and cognitive performance (p < 0.05). CONCLUSION This study elucidates a disrupted brain structural network characterized by impaired integration and segregation in preschool TOF, correlating with cognitive performance. These findings indicated that the brain structural network may be a promising imaging biomarker and potential target for neurobehavioral interventions aimed at improving brain development and preventing lasting impairments across the lifetime.
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Affiliation(s)
- Yuting Liu
- Department of Radiology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Liang Hu
- Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Meijiao Zhu
- Department of Radiology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Jingjing Zhong
- Department of Radiology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Mingcui Fu
- Department of Radiology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Mingwen Yang
- Department of Radiology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Shuting Cheng
- Department of Radiology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Ying Wang
- Department of Radiology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Xuming Mo
- Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Ming Yang
- Department of Radiology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
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Hofer J, Blum M, Wiltsche R, Deluggi N, Holzinger D, Fellinger J, Tulzer G, Blum G, Oberhuber R. Research gaps in the neurodevelopmental assessment of children with complex congenital heart defects: a scoping review. Front Pediatr 2024; 12:1340495. [PMID: 38846331 PMCID: PMC11155449 DOI: 10.3389/fped.2024.1340495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 04/15/2024] [Indexed: 06/09/2024] Open
Abstract
Background Children with congenital heart defects (CHD) are at risk for a range of developmental disabilities that challenge cognition, executive functioning, self-regulation, communication, social-emotional functioning, and motor skills. Ongoing developmental surveillance is therefore key to maximizing neurodevelopmental outcome opportunities. It is crucial that the measures used cover the spectrum of neurodevelopmental domains relevant to capturing possible predictors and malleable factors of child development. Objectives This work aimed to synthesize the literature on neurodevelopmental measures and the corresponding developmental domains assessed in children aged 1-8 years with complex CHD. Methods PubMed was searched for terms relating to psycho-social, cognitive and linguistic-communicative outcomes in children with CHD. 1,380 papers with a focus on complex CHD that reported neurodevelopmental assessments were identified; ultimately, data from 78 articles that used standardized neurodevelopmental assessment tools were extracted. Results Thirty-nine (50%) of these excluded children with syndromes, and 9 (12%) excluded children with disorders of intellectual development. 10% of the studies were longitudinal. The neurodevelopmental domains addressed by the methods used were: 53% cognition, 16% psychosocial functioning, 18% language/communication/speech production, and 13% motor development-associated constructs. Conclusions Data on social communication, expressive and receptive language, speech motor, and motor function are underrepresented. There is a lack of research into everyday use of language and into measures assessing language and communication early in life. Overall, longitudinal studies are required that include communication measures and their interrelations with other developmental domains.
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Affiliation(s)
- Johannes Hofer
- Research Institute for Developmental Medicine, Johannes Kepler University of Linz, Linz, Austria
- Institute of Neurology of Senses and Language, Hospital of St. John of God, Linz, Austria
| | - Marina Blum
- Research Institute for Developmental Medicine, Johannes Kepler University of Linz, Linz, Austria
| | - Regina Wiltsche
- Research Institute for Developmental Medicine, Johannes Kepler University of Linz, Linz, Austria
| | - Nikoletta Deluggi
- Research Institute for Developmental Medicine, Johannes Kepler University of Linz, Linz, Austria
| | - Daniel Holzinger
- Research Institute for Developmental Medicine, Johannes Kepler University of Linz, Linz, Austria
- Institute of Neurology of Senses and Language, Hospital of St. John of God, Linz, Austria
- Institute of Linguistics, University of Graz, Graz, Austria
| | - Johannes Fellinger
- Research Institute for Developmental Medicine, Johannes Kepler University of Linz, Linz, Austria
- Institute of Neurology of Senses and Language, Hospital of St. John of God, Linz, Austria
- Division of Social Psychiatry, University Clinic for Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Gerald Tulzer
- Department of Pediatric Cardiology, Children’s Heart Center Linz, Kepler University Hospital, Linz, Austria
| | - Gina Blum
- Research Institute for Developmental Medicine, Johannes Kepler University of Linz, Linz, Austria
| | - Raphael Oberhuber
- Research Institute for Developmental Medicine, Johannes Kepler University of Linz, Linz, Austria
- Department of Pediatric Cardiology, Children’s Heart Center Linz, Kepler University Hospital, Linz, Austria
- Department of Inclusive Education, University of Education Upper Austria, Linz, Austria
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Butler SC, Rofeberg V, Wypij D, Ferreira R, Singer J, Stopp C, Wood L, Ware J, Newburger JW, Sadhwani A. Inpatient Screening for Early Identification of Developmental Risk in Infants with Congenital Heart Defects. J Pediatr 2023; 263:113687. [PMID: 37611735 DOI: 10.1016/j.jpeds.2023.113687] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 07/10/2023] [Accepted: 08/16/2023] [Indexed: 08/25/2023]
Abstract
OBJECTIVE To assess the utility of an inpatient standardized developmental screener for early identification of developmental risk in infants with a congenital heart defect (CHD). STUDY DESIGN This was a retrospective, observational study with convenience sample of postoperative infants with CHD (aged 3-12 months) who underwent neurodevelopmental screening with the Bayley Scales of Infant and Toddler Development Screening Test, Third Edition (Bayley-III Screener) just before discharge. Follow-up testing included outpatient Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) (12-42 mo). RESULTS The Bayley-III Screener was administered to 325 infants at a median of 5 months, 8 days (IQR 3 months, 28 days, to 7 months, 17 days). Infants scored below age expectations on the Gross Motor (79%), Fine Motor (63%), Receptive Communication (50%), Expressive Communication (38%), and Cognitive (38%) domains. In each domain, children with CHD had greater rates of scores below expectations than the normative sample (each P <.001). The odds of scoring in a greater risk category were increased for infants with genetic syndromes and longer length of hospital stay across all domains. The outpatient Bayley-III (n = 74, 23% follow-up) was completed at a median of 19 months, 9 days (IQR: 17 months, 3 days, to 23 months, 37 days). Individuals falling in greater-risk categories on their initial Bayley-III Screener were significantly more likely to have worse performance on their follow-up outpatient Bayley-III (each domain P < .01). CONCLUSIONS Inpatient standardized neurodevelopmental screening provides important clinical utility in identifying infants at risk for developmental concern, allows for provision of recommendations for developmental services, and potentially overcomes barriers often noted in returning for outpatient post-discharge assessments.
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Affiliation(s)
- Samantha C Butler
- Department of Psychiatry and Behavioral Services, Boston Children's Hospital, Boston, MA; Department of Psychiatry, Harvard Medical School, Boston, MA.
| | - Valerie Rofeberg
- Department of Cardiology, Boston Children's Hospital, Boston, MA
| | - David Wypij
- Department of Cardiology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Raquel Ferreira
- Department of Cardiology, Boston Children's Hospital, Boston, MA
| | - Jayne Singer
- Department of Psychiatry and Behavioral Services, Boston Children's Hospital, Boston, MA; Department of Psychiatry, Harvard Medical School, Boston, MA
| | - Christian Stopp
- Department of Cardiology, Boston Children's Hospital, Boston, MA
| | - Laura Wood
- Department of Psychiatry and Behavioral Services, Boston Children's Hospital, Boston, MA; Department of Psychiatry, Harvard Medical School, Boston, MA; Division of General Pediatrics, Intermountain Healthcare, Salt Lake City, UT
| | - Janice Ware
- Department of Psychiatry and Behavioral Services, Boston Children's Hospital, Boston, MA; Department of Psychiatry, Harvard Medical School, Boston, MA
| | - Jane W Newburger
- Department of Cardiology, Boston Children's Hospital, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA
| | - Anjali Sadhwani
- Department of Psychiatry and Behavioral Services, Boston Children's Hospital, Boston, MA; Department of Psychiatry, Harvard Medical School, Boston, MA
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Schmitt KRL, Sievers LK, Hütter A, Abdul-Khaliq H, Poryo M, Berger F, Bauer UMM, Helm PC, Pfitzer C. New Insights into the Education of Children with Congenital Heart Disease with and without Trisomy 21. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:2001. [PMID: 38004050 PMCID: PMC10673200 DOI: 10.3390/medicina59112001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 11/01/2023] [Accepted: 11/07/2023] [Indexed: 11/26/2023]
Abstract
Background and Objectives: Patients with congenital heart disease (CHD), especially as a concomitant syndromal disease of trisomy 21 (T21), are at risk for impaired neurodevelopment. This can also affect these patients' education. However, there continues to be a research gap in the educational development of CHD patients and T21 CHD patients. Materials and Methods: In total, data from 2873 patients from the German National Register for Congenital Heart Defects were analyzed. The data are based on two online education surveys conducted among patients registered in the National Register for Congenital Heart Defects (2017, 2020). Results: Of 2873 patients included (mean age: 14.1 ± 4.7 years, 50.5% female), 109 (3.8%) were identified with T21 (mean age: 12.9 ± 4.4 years, 49.5% female). T21 CHD participants had a high demand for early specific interventions (overall cohort 49.1%; T21 cohort 100%). T21 CHD children more frequently attended special schools and, compared to non-trisomy 21 (nT21) CHD patients, the probability of attending a grammar school was reduced. In total, 87.1% of nT21 CHD patients but 11% of T21 CHD patients were enrolled in a regular elementary school, and 12.8% of T21 CHD patients could transfer to a secondary school in contrast to 35.5% of nT21 CHD patients. Most of the T21 CHD patients were diagnosed with psychiatric disorders, e.g., learning, emotional, or behavioral disorders (T21 CHD patients: 82.6%; nT21 CHD patients: 31.4%; p < 0.001). Conclusions: CHD patients are at risk for impaired academic development, and the presence of T21 is an aggravating factor. Routine follow-up examinations should be established to identify developmental deficits and to provide targeted interventions.
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Affiliation(s)
- Katharina R. L. Schmitt
- Department of Congenital Heart Disease—Pediatric Cardiology, Deutsches Herzzentrum der Charité, Augustenburger Platz 1, 13353 Berlin, Germany; (K.R.L.S.); (F.B.)
- Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
- Competence Network for Congenital Heart Defects, 13353 Berlin, Germany;
| | - Laura K. Sievers
- Department of Internal Medicine I, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany;
| | - Alina Hütter
- Department of Congenital Heart Disease—Pediatric Cardiology, Deutsches Herzzentrum der Charité, Augustenburger Platz 1, 13353 Berlin, Germany; (K.R.L.S.); (F.B.)
- Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
| | - Hashim Abdul-Khaliq
- Department of Pediatric Cardiology, Saarland University Medical Center, 66421 Homburg, Germany; (H.A.-K.); (M.P.)
| | - Martin Poryo
- Department of Pediatric Cardiology, Saarland University Medical Center, 66421 Homburg, Germany; (H.A.-K.); (M.P.)
| | - Felix Berger
- Department of Congenital Heart Disease—Pediatric Cardiology, Deutsches Herzzentrum der Charité, Augustenburger Platz 1, 13353 Berlin, Germany; (K.R.L.S.); (F.B.)
- Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
- Competence Network for Congenital Heart Defects, 13353 Berlin, Germany;
| | - Ulrike M. M. Bauer
- Competence Network for Congenital Heart Defects, 13353 Berlin, Germany;
- National Register for Congenital Heart Defects, 13353 Berlin, Germany
| | - Paul C. Helm
- National Register for Congenital Heart Defects, 13353 Berlin, Germany
| | - Constanze Pfitzer
- Department of Congenital Heart Disease—Pediatric Cardiology, Deutsches Herzzentrum der Charité, Augustenburger Platz 1, 13353 Berlin, Germany; (K.R.L.S.); (F.B.)
- Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
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Chiperi LE, Huţanu A, Tecar C, Muntean I. Serum Markers of Brain Injury in Pediatric Patients with Congenital Heart Defects Undergoing Cardiac Surgery: Diagnostic and Prognostic Role. Clin Pract 2023; 13:1253-1265. [PMID: 37887089 PMCID: PMC10605074 DOI: 10.3390/clinpract13050113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 09/28/2023] [Accepted: 10/16/2023] [Indexed: 10/28/2023] Open
Abstract
Introduction: The objectives of this study were to assess the role of neuromarkers like glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), protein S100 (pS100), and neuron-specific enolase (NSE) as diagnostic markers of acute brain injury and also as prognostic markers for short-term neurodevelopmental impairment. Methods: Pediatric patients with congenital heart defects (CHDs) undergoing elective cardiac surgery were included. Neurodevelopmental functioning was assessed preoperatively and 4-6 months postoperatively using the Denver Developmental Screening Test II. Blood samples were collected preoperatively and postoperatively. During surgery, regional cerebral tissue oxygen saturation was monitored using near-infrared spectroscopy (NIRS). Results: Forty-two patients were enrolled and dichotomized into cyanotic and non-cyanotic groups based on peripheric oxygen saturation. Nineteen patients (65.5%) had abnormal developmental scores in the non-cyanotic group and eleven (84.6%) in the cyanotic group. A good diagnostic model was observed between NIRS values and GFAP in the cyanotic CHD group (AUC = 0.7). A good predicting model was observed with GFAP and developmental scores in the cyanotic CHD group (AUC = 0.667). A correlation was found between NSE and developmental quotient scores (r = 0.09, p = 0.046). Conclusions: From all four neuromarkers studied, only GFAP was demonstrated to be a good diagnostic and prognostic factor in cyanotic CHD patients. NSE had only prognostic value.
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Affiliation(s)
- Lacramioara Eliza Chiperi
- Clinic of Pediatric Cardiology, Emergency Institute for Cardiovascular Diseases and Heart Transplant, 540136 Targu Mures, Romania
- Doctoral School, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Adina Huţanu
- Department of Laboratory Medicine, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania;
- Laboratory of Humoral Immunology, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania
| | - Cristina Tecar
- Department of Neurosciences, Iuliu Hatieganu University of Medicine and Pharmacy, 400129 Cluj-Napoca, Romania
| | - Iolanda Muntean
- Clinic of Pediatric Cardiology, Emergency Institute for Cardiovascular Diseases and Heart Transplant, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania;
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Kataria-Hale J, Gollins L, Bonagurio K, Blanco C, Hair AB. Nutrition for Infants with Congenital Heart Disease. Clin Perinatol 2023; 50:699-713. [PMID: 37536773 DOI: 10.1016/j.clp.2023.04.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
Perioperative malnutrition in infants with congenital heart disease can lead to significant postnatal growth failure and poor short- and long-term outcomes. A standardized approach to nutrition is needed for the neonatal congenital heart disease population, taking into consideration the type of cardiac lesion, the preoperative and postoperative period, and prematurity. Early enteral feeding is beneficial and should be paired with parenteral nutrition to meet the fluid and nutrient needs of the infant.
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Affiliation(s)
- Jasmeet Kataria-Hale
- Department of Pediatrics, Division of Neonatology, Mission Hospital, 509 Biltmore Avenue, Asheville, NC 28801, USA
| | - Laura Gollins
- Department of Pediatrics, Division of Neonatology, Baylor College of Medicine, Texas Children's Hospital, 6621 Fannin Street, MC: A5590, Houston, TX 77030, USA
| | - Krista Bonagurio
- University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - Cynthia Blanco
- University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - Amy B Hair
- Department of Pediatrics, Division of Neonatology, Baylor College of Medicine, Texas Children's Hospital, 6621 Fannin Street, MC: A5590, Houston, TX 77030, USA.
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Feng J, Zhang Y, Zhang J, Liu T, Ma L, Zou M, Chen W, Chen X, Li J. Evaluation of neurodevelopmental impairments and risk factors in children following cardiac surgery: The first cohort from China. JTCVS OPEN 2023; 14:462-471. [PMID: 37425439 PMCID: PMC10328831 DOI: 10.1016/j.xjon.2023.03.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 03/01/2023] [Accepted: 03/08/2023] [Indexed: 07/11/2023]
Abstract
Objective Neurodevelopmental impairment has been realized as the most common complication in children with congenital heart disease undergoing cardiac surgery during the past 30 years. But little attention has been paid to this problem in China. The potential risk factors for adverse outcomes include demographic, perioperative, and socioeconomic factors, which are vastly different in China compared with the developed countries in previous reports. Methods Four hundred twenty-six patients (aged 35.9 ± 18.6 months) at about 1- to 3-year follow-up after cardiac surgery were prospectively enrolled from March 2019 to February 2022. Griffiths Mental Development Scales-Chinese was used to evaluate the quotients of overall development and 5 subscales of the child's locomotor, language, personal-social, eye-hand coordination, and performance skills. Demographic, perioperative, socioeconomic, and feeding type during the first year of life (breastfeeding, mixed, or never breastfeeding) were examined to identify the risk factors for adverse neurodevelopmental outcomes. Results Mean scores were 90.0 ± 15.5 for development quotient, 92.3 ± 19.4 for locomotor, 89.6 ± 19.2 for personal-social, 85.5 ± 21.7 for language, 90.3 ± 17.2 for eye-hand coordination, and 92 ± 17.1 for performance subscales. For the entire cohort, the impairment in at least 1 subscale was found in 76.1% of the cohort (>1 SD below population mean) with 50.1% being severe (>2 SDs below the mean). The significant risk factors included prolonged hospital stay, peak level of postoperative C-reactive protein, socioeconomic status, and never breastfeeding or mixed feeding. Conclusions Neurodevelopmental impairment is substantial in terms of incidence and severity in children with congenital heart disease undergoing cardiac surgery in China. Risk factors contributing to the adverse outcomes included prolonged hospital stay, early postoperative inflammatory response, socioeconomic status, and never breastfeeding or mixed feeding. There is an urgent need for standardized follow-up and neurodevelopmental assessment in this special group of children in China.
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Affiliation(s)
- Jinqing Feng
- Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
- Clinical Physiology Laboratory, Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Yani Zhang
- Department of Neurology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Jinyuan Zhang
- School of Health Management, Guangzhou Medical University, Guangzhou, China
| | - Techang Liu
- Heart Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Li Ma
- Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
- Heart Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Minghui Zou
- Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
- Heart Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Wenxiong Chen
- Department of Neurology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Xinxin Chen
- Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
- Heart Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Jia Li
- Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
- Clinical Physiology Laboratory, Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China
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Ramonfaur D, Zhang X, Garza AP, García-Pons JF, Britton-Robles SC. Hypoplastic Left Heart Syndrome: A Review. Cardiol Rev 2023; 31:149-154. [PMID: 35349498 DOI: 10.1097/crd.0000000000000435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Hypoplastic left heart syndrome is a rare and poorly understood congenital disorder featuring a univentricular myocardium, invariably resulting in early childhood death if left untreated. The process to palliate this congenital cardiomyopathy is of high complexity and may include invasive interventions in the first week of life. The preferred treatment strategy involves a staged correction with 3 surgical procedures at different points in time. The Norwood procedure is usually performed within the first weeks of life and aims to increase systemic circulation and relieve pulmonary vascular pressure. This procedure is followed by the bidirectional Glenn and the Fontan procedures in later life, which offer to decrease stress in the ventricular chamber. The prognosis of children with this disease has greatly improved in the past decades; however, it is still largely driven by multiple modifiable and nonmodifiable variables. Novel and clever alternatives have been proposed to improve the survival and neurodevelopment of these patients, although they are not used as standard of care in all centers. The neurodevelopmental outcomes among these patients have received particular attention in the last decade in light to improve this very limiting associated comorbidity that compromises quality of life.
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Affiliation(s)
- Diego Ramonfaur
- From the Division of Postgraduate Medical Education, Harvard Medical School, Boston, MA
| | - Xiaoya Zhang
- From the Division of Postgraduate Medical Education, Harvard Medical School, Boston, MA
| | - Abraham P Garza
- Departamento de Medicina, Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, México
| | - José Fernando García-Pons
- División de Ciencias de la Salud, Departamento de Medicina y Nutrición, Universidad de Guanajuato, Guanajuato, México
| | - Sylvia C Britton-Robles
- Departamento de Medicina, Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, México
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Schmithorst V, Ceschin R, Lee V, Wallace J, Sahel A, Chenevert TL, Parmar H, Berman JI, Vossough A, Qiu D, Kadom N, Grant PE, Gagoski B, LaViolette PS, Maheshwari M, Sleeper LA, Bellinger DC, Ilardi D, O’Neil S, Miller TA, Detterich J, Hill KD, Atz AM, Richmond ME, Cnota J, Mahle WT, Ghanayem NS, Gaynor JW, Goldberg CS, Newburger JW, Panigrahy A. Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study. Diagnostics (Basel) 2023; 13:1604. [PMID: 37174995 PMCID: PMC10178603 DOI: 10.3390/diagnostics13091604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 04/25/2023] [Accepted: 04/27/2023] [Indexed: 05/15/2023] Open
Abstract
Patients with hypoplastic left heart syndrome who have been palliated with the Fontan procedure are at risk for adverse neurodevelopmental outcomes, lower quality of life, and reduced employability. We describe the methods (including quality assurance and quality control protocols) and challenges of a multi-center observational ancillary study, SVRIII (Single Ventricle Reconstruction Trial) Brain Connectome. Our original goal was to obtain advanced neuroimaging (Diffusion Tensor Imaging and Resting-BOLD) in 140 SVR III participants and 100 healthy controls for brain connectome analyses. Linear regression and mediation statistical methods will be used to analyze associations of brain connectome measures with neurocognitive measures and clinical risk factors. Initial recruitment challenges occurred that were related to difficulties with: (1) coordinating brain MRI for participants already undergoing extensive testing in the parent study, and (2) recruiting healthy control subjects. The COVID-19 pandemic negatively affected enrollment late in the study. Enrollment challenges were addressed by: (1) adding additional study sites, (2) increasing the frequency of meetings with site coordinators, and (3) developing additional healthy control recruitment strategies, including using research registries and advertising the study to community-based groups. Technical challenges that emerged early in the study were related to the acquisition, harmonization, and transfer of neuroimages. These hurdles were successfully overcome with protocol modifications and frequent site visits that involved human and synthetic phantoms.
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Affiliation(s)
- Vanessa Schmithorst
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Floor 2, Pittsburgh, PA 15224, USA
| | - Rafael Ceschin
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Floor 2, Pittsburgh, PA 15224, USA
- Department of Biomedical Informatics, University of Pittsburgh School, 5607 Baum Blvd., Pittsburgh, PA 15206, USA
| | - Vincent Lee
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Floor 2, Pittsburgh, PA 15224, USA
| | - Julia Wallace
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Floor 2, Pittsburgh, PA 15224, USA
| | - Aurelia Sahel
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Floor 2, Pittsburgh, PA 15224, USA
| | - Thomas L. Chenevert
- Michigan Medicine Department of Radiology, University of Michigan, 1500 E Medical Center Dr., Ann Arbor, MI 48109, USA
| | - Hemant Parmar
- Michigan Medicine Department of Radiology, University of Michigan, 1500 E Medical Center Dr., Ann Arbor, MI 48109, USA
| | - Jeffrey I. Berman
- Department of Radiology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA
| | - Arastoo Vossough
- Department of Radiology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA
| | - Deqiang Qiu
- Department of Radiology and Imaging Sciences, Children’s Healthcare of Atlanta, Emory University, 1364 Clifton Rd, Atlanta, GA 30322, USA
| | - Nadja Kadom
- Department of Radiology and Imaging Sciences, Children’s Healthcare of Atlanta, Emory University, 1364 Clifton Rd, Atlanta, GA 30322, USA
| | - Patricia Ellen Grant
- Children’s Hospital Boston, Fetal-Neonatal Neuroimaging and Developmental Science Center (FNNDSC), 300 Longwood Avenue, Boston, MA 02115, USA
| | - Borjan Gagoski
- Department of Radiology, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA
| | - Peter S. LaViolette
- Department of Radiology, Medical College of Wisconsin, 9200 W Wisconsin Avenue, Milwaukee, WI 53226, USA
| | - Mohit Maheshwari
- Department of Radiology, Medical College of Wisconsin, 9200 W Wisconsin Avenue, Milwaukee, WI 53226, USA
| | - Lynn A. Sleeper
- Department of Cardiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
- Department of Pediatrics, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
| | - David C. Bellinger
- Cardiac Neurodevelopmental Program, Department of Neurology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
| | - Dawn Ilardi
- Department of Neuropsychology, Children’s Healthcare of Atlanta, 1400 Tullie Road NE, Atlanta, GA 30329, USA
| | - Sharon O’Neil
- Children’s Hospital Los Angeles, Neuropsychology Core of the Saban Research Institute, 4661 Sunset Blvd., Los Angeles, CA 90027, USA
| | - Thomas A. Miller
- Division of Pediatric Cardiology, Department of Pediatrics, University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT 84132, USA
| | - Jon Detterich
- Division of Pediatric Cardiology, Children’s Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027, USA
| | - Kevin D. Hill
- Division of Pediatric Cardiology, Department of Pediatrics, Duke University School of Medicine, 7506 Hospital North, DUMC Box 3090, Durham, NC 27710, USA
| | - Andrew M. Atz
- Division of Pediatric Cardiology, Medical University of South Carolina, 96 Jonathan Lucas St. Ste. 601, MSC 617, Charleston, SC 29425, USA
| | - Marc E. Richmond
- Program for Pediatric Cardiomyopathy, Heart Failure, and Transplantation, New York-Presbyterian Morgan Stanley Children’s Hospital, 3959 Broadway MSCH North, 2nd Floor, New York, NY 10032, USA
| | - James Cnota
- Fetal Heart Program, Cincinnati Children’s, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
| | - William T. Mahle
- Division of Pediatric Cardiology, Children’s Healthcare of Atlanta, 1400 Tullie Rd NE Suite 630, Atlanta, GA 30329, USA
| | - Nancy S. Ghanayem
- Section of Pediatric Critical Care, Department of Pediatrics, Comer Children’s Hospital, University of Chicago Medicine, 5721 S. Maryland Avenue, Chicago, IL 60637, USA
- Department of Pediatrics, Medical College of Wisconsin Section of Pediatric Critical Care, 9000 W. Wisconsin Avenue MS 681, Milwaukee, WI 53226, USA
| | - J. William Gaynor
- Heart Failure and Transplant Program, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA
| | - Caren S. Goldberg
- Department of Pediatrics, Division of Cardiology, C.S. Mott Children’s Hospital, 1540 E Hospital Dr #4204, Ann Arbor, MI 48109, USA
| | - Jane W. Newburger
- Department of Cardiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
| | - Ashok Panigrahy
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Floor 2, Pittsburgh, PA 15224, USA
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11
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Schmithorst V, Ceschin R, Lee V, Wallace J, Sahel A, Chenevert T, Parmar H, Berman JI, Vossough A, Qiu D, Kadom N, Grant PE, Gagoski B, LaViolette P, Maheshwari M, Sleeper LA, Bellinger D, Ilardi D, O’Neil S, Miller TA, Detterich J, Hill KD, Atz AM, Richmond M, Cnota J, Mahle WT, Ghanayem N, Gaynor W, Goldberg CS, Newburger JW, Panigrahy A. Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.04.12.23288433. [PMID: 37131744 PMCID: PMC10153324 DOI: 10.1101/2023.04.12.23288433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Patients with hypoplastic left heart syndrome who have been palliated with the Fontan procedure are at risk for adverse neurodevelopmental outcomes, lower quality of life, and reduced employability. We describe the methods (including quality assurance and quality control protocols) and challenges of a multi-center observational ancillary study, SVRIII (Single Ventricle Reconstruction Trial) Brain Connectome. Our original goal was to obtain advanced neuroimaging (Diffusion Tensor Imaging and Resting-BOLD) in 140 SVR III participants and 100 healthy controls for brain connectome analyses. Linear regression and mediation statistical methods will be used to analyze associations of brain connectome measures with neurocognitive measures and clinical risk factors. Initial recruitment challenges occurred related to difficulties with: 1) coordinating brain MRI for participants already undergoing extensive testing in the parent study, and 2) recruiting healthy control subjects. The COVID-19 pandemic negatively affected enrollment late in the study. Enrollment challenges were addressed by 1) adding additional study sites, 2) increasing the frequency of meetings with site coordinators and 3) developing additional healthy control recruitment strategies, including using research registries and advertising the study to community-based groups. Technical challenges that emerged early in the study were related to the acquisition, harmonization, and transfer of neuroimages. These hurdles were successfully overcome with protocol modifications and frequent site visits that involved human and synthetic phantoms. Trial registration number ClinicalTrials.gov Registration Number: NCT02692443.
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Affiliation(s)
- Vanessa Schmithorst
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Ave, Floor 2, Pittsburgh, PA 15224 USA
| | - Rafael Ceschin
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Ave, Floor 2, Pittsburgh, PA 15224 USA
- Department of Biomedical Informatics, University of Pittsburgh School, 5607 Baum Blvd, Pittsburgh, PA 15206-3701 USA
| | - Vince Lee
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Ave, Floor 2, Pittsburgh, PA 15224 USA
| | - Julia Wallace
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Ave, Floor 2, Pittsburgh, PA 15224 USA
| | - Aurelia Sahel
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Ave, Floor 2, Pittsburgh, PA 15224 USA
| | - Thomas Chenevert
- Department of Radiology, Michigan Medicine, University of Michigan, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109 USA
| | - Hemant Parmar
- Department of Radiology, Michigan Medicine, University of Michigan, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109 USA
| | - Jeffrey I. Berman
- Department of Radiology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104, USA
| | - Arastoo Vossough
- Department of Radiology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104, USA
| | - Deqiang Qiu
- Department of Radiology and Imaging Sciences, Children’s Healthcare of Atlanta, Emory University, 1364 Clifton Rd, Atlanta, GA 30322 USA
| | - Nadja Kadom
- Department of Radiology and Imaging Sciences, Children’s Healthcare of Atlanta, Emory University, 1364 Clifton Rd, Atlanta, GA 30322 USA
| | - Patricia Ellen Grant
- Fetal-Neonatal Neuroimaging and Developmental Science Center (FNNDSC), Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115 USA
| | - Borjan Gagoski
- Department of Radiology, Children’s Hospital Boston, 300 Longwood Ave, Boston, MA 02115 USA
| | - Peter LaViolette
- Department of Radiology, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA
| | - Mohit Maheshwari
- Department of Radiology, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA
| | - Lynn A. Sleeper
- Department of Cardiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115
- Department of Pediatrics, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115 USA
| | - David Bellinger
- Cardiac Neurodevelopmental Program, Department of Neurology, Boston, Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115 USA
| | - Dawn Ilardi
- Department of Neuropsychology, Children’s Healthcare of Atlanta, 1400 Tullie Road NE, Atlanta, GA 30329
| | - Sharon O’Neil
- Neuropsychology Core of the Saban Research Institute, Children’s Hospital Los Angeles, 4661 Sunset Blvd., Los Angeles, CA 90027 USA
| | - Thomas A. Miller
- Division of Pediatric Cardiology, Department of Pediatrics, University of Utah, School of Medicine, 30 N 1900 E, Salt Lake City, UT 84132 USA
| | - Jon Detterich
- Division of Pediatric Cardiology, Children’s Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027 USA
| | - Kevin D. Hill
- Division of Pediatric Cardiology, Department of Pediatrics, Duke University, School of Medicine, 7506 Hospital North, DUMC Box 3090, Durham, NC 27710 USA
| | - Andrew M. Atz
- Division of Pediatric Cardiology, Medical University of South Carolina, 96 Jonathan Lucas St. Ste. 601, MSC 617, Charleston, SC 29425 USA
| | - Marc Richmond
- Program for Pediatric Cardiomyopathy, Heart Failure, and Transplantation, New York-Presbyterian Morgan Stanley Children’s Hospital, 3959 Broadway MSCH North, 2 Floor, New York, NY 10032 USA
| | - James Cnota
- Fetal Heart Program, Cincinnati Children’s, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3026 USA
| | - William T. Mahle
- Division of Pediatric Cardiology, Children’s Healthcare of Atlanta, 1400 Tullie Rd NE Suite 630, Atlanta, GA 30329
| | - Nancy Ghanayem
- Section of Pediatric Critical Care, Department of Pediatrics, University of Chicago Medicine, Comer Children’s Hospital, 5721 S. Maryland Ave., Chicago, IL 60637 USA
- Section of Pediatric Critical Care, Department of Pediatrics, Medical College of Wisconsin, 9000 W. Wisconsin Ave. MS 681, Milwaukee, WI 53226 USA
| | - William Gaynor
- Heart Failure and Transplant Program, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104 USA
| | - Caren S. Goldberg
- Department of Pediatrics, Division of Cardiology, C.S. Mott Children’s Hospital, 1540 E Hospital Dr #4204, Ann Arbor, MI 48109 USA
| | - Jane W. Newburger
- Department of Cardiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115
| | - Ashok Panigrahy
- Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Ave, Floor 2, Pittsburgh, PA 15224 USA
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Pfitzer C, Sievers LK, Hütter A, Khaliq HA, Poryo M, Berger F, Bauer UMM, Helm PC, Schmitt KRL. Microcephaly is associated with impaired educational development in children with congenital heart disease. Front Cardiovasc Med 2022; 9:917507. [PMID: 36277771 PMCID: PMC9584804 DOI: 10.3389/fcvm.2022.917507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 09/02/2022] [Indexed: 11/13/2022] Open
Abstract
Objectives This study aims to evaluate the school careers of patients with congenital heart disease (CHD) and microcephaly. Methods An exploratory online survey was conducted on patients from a previous study on somatic development in children with CHD in 2018 (n = 2818). A total of 750 patients participated in the online survey (26.6%). This publication focuses on 91 patients (12.1%) diagnosed with CHD and microcephaly who participated in the new online survey. Results Microcephaly was significantly associated with CHD severity (p < 0.001). Microcephalic patients suffered from psychiatric comorbidity two times as often (67.0%) as non-microcephalic patients (29.8%). In particular, the percentage of patients with developmental delay, intellectual debility, social disability, learning disorder, or language disorder was significantly increased in microcephalic CHD patients (p < 0.001). A total of 85.7% of microcephalic patients and 47.6% of non-microcephalic patients received early interventions to foster their development. The school enrollment of both groups was similar at approximately six years of age. However, 89.9% of non-microcephalic but only 51.6% of microcephalic patients were enrolled in a regular elementary school. Regarding secondary school, only half as many microcephalic patients (14.3%) went to grammar school, while the proportion of pupils at special schools was eight times higher. Supportive interventions, e.g., for specific learning disabilities, were used by 52.7% of microcephalic patients and 21.6% of non-microcephalic patients. Conclusion Patients with CHD and microcephaly are at high risk for impaired educational development. Early identification should alert clinicians to provide targeted interventions to optimize the developmental potential.
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Affiliation(s)
- Constanze Pfitzer
- Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany,Berlin Institute of Health (BIH), Berlin, Germany,DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
| | - Laura K. Sievers
- Department of Internal Medicine I., Christian-Albrechts-University and University Hospital Schleswig-Holstein, Kiel, Germany,*Correspondence: Laura K. Sievers
| | - Alina Hütter
- Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany
| | - Hashim-Abdul Khaliq
- Department of Pediatric Cardiology, Saarland University Medical Center, Homburg, Germany
| | - Martin Poryo
- Department of Pediatric Cardiology, Saarland University Medical Center, Homburg, Germany
| | - Felix Berger
- Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany,DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany,Department of Pediatric Cardiology, Charite – Universitaetsmedizin Berlin, Berlin, Germany
| | - Ulrike M. M. Bauer
- National Register for Congenital Heart Defects, Berlin, Germany,Competence Network for Congenital Heart Defects, Berlin, Germany
| | - Paul C. Helm
- National Register for Congenital Heart Defects, Berlin, Germany,Competence Network for Congenital Heart Defects, Berlin, Germany
| | - Katharina R. L. Schmitt
- Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany,DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
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Abstract
The most common comorbidities in children with congenital heart disease (CHD) are neurodevelopmental impairments, particularly in areas of executive function, memory and attention. Limited studies have demonstrated similar impairments in CHD adults although no studies have screened specifically for mild cognitive impairment and dementia. Methods We performed a prospective cross-sectional study of CHD patients, ages 30-65 years, who were coming for clinic visits. We administered the Mini-Mental State Exam (MMSE), and scores were compared with population norms adjusted by age and education level. Results A total of 125 patients were recruited (55% male). The median age was 40 years (range 30-65). More than a half (80%) had some college education or advanced degrees. Adjusting for age and education, CHD participants scored significantly lower than the general population (median 1 point lower, p<0.001) on the MMSE. The greatest impairments occurred in recall and orientation. Five percent of the total cohort met the general threshold for mild cognitive impairment (MMSE < 24). Clinical factors associated with this degree of cognitive impairment were duration of cyanosis (p=0.005) and decreased systemic ventricular function (p=0.003). Conclusions Our pilot study showed that, when adjusted for age and education level, CHD adults had significantly lower MMSE scores than the general population, with 5% meeting criteria for mild cognitive impairment. These findings suggest that subtle and early cognitive changes are present in the adult CHD population. Further studies are needed to investigate those changes that might influence long-term outcomes in the adult CHD population.
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14
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Tran NN, Votava-Smith JK, Wood JC, Panigrahy A, Wee CP, Borzage M, Kumar SR, Murray PM, Brecht ML, Paquette L, Brady KM, Peterson BS. Cerebral oxygen saturation and cerebrovascular instability in newborn infants with congenital heart disease compared to healthy controls. PLoS One 2021; 16:e0251255. [PMID: 33970937 PMCID: PMC8109808 DOI: 10.1371/journal.pone.0251255] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 04/22/2021] [Indexed: 11/18/2022] Open
Abstract
Objective Infants with Congenital Heart Disease (CHD) are at risk for developmental delays, though the mechanisms of brain injury that impair development are unknown. Potential causes could include cerebral hypoxia and cerebrovascular instability. We hypothesized that we would detect significantly reduced cerebral oxygen saturation and greater cerebrovascular instability in CHD infants compared to the healthy controls. Methods We performed a secondary analysis on a sample of 43 term infants (28 CHD, 15 healthy controls) that assessed prospectively in temporal cross-section before or at 12 days of age. CHD infants were assessed prior to open-heart surgery. Cerebral oxygen saturation levels were estimated using Near-Infrared Spectroscopy, and cerebrovascular stability was assessed with the response of cerebral oxygen saturation after a postural change (supine to sitting). Results Cerebral oxygen saturation was 9 points lower in CHD than control infants in both postures (β = -9.3; 95%CI = -17.68, -1.00; p = 0.028), even after controlling for differences in peripheral oxygen saturation. Cerebrovascular stability was significantly impaired in CHD compared to healthy infants (β = -2.4; 95%CI = -4.12, -.61; p = 0.008), and in CHD infants with single ventricle compared with biventricular defects (β = -1.5; 95%CI = -2.95, -0.05; p = 0.04). Conclusion CHD infants had cerebral hypoxia and decreased cerebral oxygen saturation values following a postural change, suggesting cerebrovascular instability. Future longitudinal studies should assess the associations of cerebral hypoxia and cerebrovascular instability with long-term neurodevelopmental outcomes in CHD infants.
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Affiliation(s)
- Nhu N. Tran
- Institute for the Developing Mind, The Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
- Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
- * E-mail:
| | - Jodie K. Votava-Smith
- Division of Cardiology, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
- Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - John C. Wood
- Division of Cardiology, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
- Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Ashok Panigrahy
- University of Pittsburgh Medical Center, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
- Department of Pediatric Radiology, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
| | - Choo Phei Wee
- Department of Preventive Medicine, Southern California Clinical and Translational Science Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
| | - Matthew Borzage
- Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
- Division of Neonatology, Department of Pediatrics, Fetal and Neonatal Institute, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
| | - S. Ram Kumar
- Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
- Division of Cardiothoracic Surgery, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
| | - Paula M. Murray
- Institute for Nursing and Interprofessional Research, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
| | - Mary-Lynn Brecht
- School of Nursing, University of California, Los Angeles, Los Angeles, California, United States of America
| | - Lisa Paquette
- Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
- Division of Neonatology, Department of Pediatrics, Fetal and Neonatal Institute, Children’s Hospital Los Angeles, Los Angeles, California, United States of America
| | - Kenneth M. Brady
- Lurie Children’s Hospital of Chicago, Anesthesiology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America
| | - Bradley S. Peterson
- Department of Psychiatry, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
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15
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Tran NN, Tran M, Lopez J, Ogbaa M, Votava-Smith JK, Brady KM. Near-Infrared Spectroscopy: Clinical Use in High-Risk Neonates. Neonatal Netw 2021; 40:73-79. [PMID: 33731373 DOI: 10.1891/0730-0832/11-t-678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/06/2020] [Indexed: 11/25/2022]
Abstract
In this review, we describe the near-infrared spectroscopy (NIRS) technology and its clinical use in high-risk neonates in critical care settings. We searched databases (e.g., PubMed, Google Scholar, EBSCOhost) to find studies describing the use of NIRS on critically ill and high-risk neonates. Near-infrared spectroscopy provides continuous noninvasive monitoring of venous oxygen saturation. It uses technology similar to pulse oximetry to measure the oxygen saturation of hemoglobin in a tissue bed to describe the relative delivery and extraction of oxygen. Near-infrared spectroscopy can be a valuable bedside tool to provide clinicians indirect evidence of perfusion. It may prompt early interventions that promote oxygen delivery, which can improve high-risk neonatal outcomes.
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16
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Sananes R, Goldberg CS, Newburger JW, Hu C, Trachtenberg F, Gaynor JW, Mahle WT, Miller T, Uzark K, Mussatto KA, Pizarro C, Jacobs JP, Cnota J, Atz AM, Lai WW, Burns KM, Milazzo A, Votava-Smith J, Brosig CL, on behalf of the PHN investigators. Six-Year Neurodevelopmental Outcomes for Children With Single-Ventricle Physiology. Pediatrics 2021; 147:peds.2020-014589. [PMID: 33441486 PMCID: PMC7849196 DOI: 10.1542/peds.2020-014589] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/27/2020] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES To determine if neurodevelopmental deficits in children with single-ventricle physiology change with age and early developmental scores predict 6-year outcomes. METHODS In the Single Ventricle Reconstruction Trial, Bayley Scales of Infant Development, Second Edition, were administered at 14 months of age, and parents completed the Behavior Assessment System for Children, Second Edition (BASC-2) annually from the ages of 2 to 6 years. Scores were classified as average, at risk, or impaired. We calculated sensitivities, specificities, and positive and negative predictive values of earlier tests on 6-year outcomes. RESULTS Of 291 eligible participants, 244 (84%) completed the BASC-2 at 6 years; more Single Ventricle Reconstruction participants than expected on the basis of normative data scored at risk or impaired on the BASC-2 Adaptive Skills Index at that evaluation (28.7% vs 15.9%; P < .001). Children with Adaptive Skills Composite scores <2 SD below the mean at the age of 6 were more likely to have had delayed development at 14 months, particularly on the Psychomotor Development Index (sensitivity of 79%). However, the positive predictive value of the 14-month Mental Development Index and Psychomotor Development Index for 6-year BASC-2 Adaptive Scores was low (44% and 36%, respectively). Adaptive Skills Composite score impairments at the age of 6 were poorly predicted by using earlier BASC-2 assessments, with low sensitivities at the ages of 3 (37%), 4 (48%), and 5 years (55%). CONCLUSIONS Many children with hypoplastic left heart syndrome who have low adaptive skills at the age of 6 years will not be identified by screening at earlier ages. With our findings, we highlight the importance of serial evaluations for children with critical congenital heart disease throughout development.
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Affiliation(s)
- Renee Sananes
- Department of Pediatrics and Labatt Family Heart Centre, Hospital for Sick Children, University of Toronto, Toronto, Canada;
| | - Caren S. Goldberg
- Department of Pediatrics, Michigan Medicine, Medical School, University of Michigan, Ann Arbor, Michigan
| | - Jane W. Newburger
- Department of Cardiology, Boston Children’s Hospital and Department of Pediatrics, Harvard Medical School, Harvard University, Boston, Massachusetts
| | - Chenwei Hu
- New England Research Institutes, Watertown, Massachusetts
| | | | - J. William Gaynor
- Division of Pediatric Cardiothoracic Surgery, Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - William T. Mahle
- Department of Pediatrics, Children’s Healthcare of Atlanta, Emory University, Atlanta, Georgia
| | - Thomas Miller
- Department of Pediatrics, Primary Children’s Hospital, University of Utah, Salt Lake City, Utah;,Division of Pediatric Cardiology, Maine Medical Center, Portland, Maine
| | - Karen Uzark
- Department of Pediatrics, Michigan Medicine, Medical School, University of Michigan, Ann Arbor, Michigan
| | | | - Christian Pizarro
- Department of Surgery, Nemours Cardiac Center, Alfred I du Pont Hospital for Children, Wilmington, Delaware
| | | | - James Cnota
- Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
| | - Andrew M. Atz
- Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
| | - Wyman W. Lai
- Children’s Heart Institute, Children’s Hospital of Orange County, Orange, California
| | | | - Angelo Milazzo
- Department of Pediatrics, School of Medicine, Duke University, Durham, North Carolina;,Department of Pediatrics, East Carolina University, Greenville, North Carolina;,Department of Pediatrics, Wake Forest University, Winston-Salem, North Carolina; and
| | - Jodie Votava-Smith
- Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, California
| | - Cheryl L. Brosig
- Pediatrics, Herma Heart Institute, Children’s Wisconsin and Medical College of Wisconsin, Milwaukee, Wisconsin
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Dahl CM, Kroupina M, Said SM, Somani A. Case Report: Traumatic Stress and Developmental Regression: An Unintended Consequence of Complex Cardiac Care. Front Pediatr 2021; 9:790066. [PMID: 35004546 PMCID: PMC8739888 DOI: 10.3389/fped.2021.790066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 12/06/2021] [Indexed: 11/28/2022] Open
Abstract
This brief case report outlines a novel approach to supporting the development of a pediatric complex cardiac care patient. Patient X is a 19-month old patient who spent 5.5 months in hospital and underwent multiple surgeries including heart transplantation. This case report explores the impacts of his condition and care on his development and family functioning within the framework of an integrated care model. This case report is uniquely complimented by outpatient neurodevelopmental follow up, dyadic trauma-informed intervention and use of telemedicine allowing for a deeper understanding of the family adaptation that provide novel insight into long-term trajectory beyond discharge. Throughout care Patient X met criteria for both a traumatic stress disorder and global developmental delay. This case study highlights the threat complex care poses to neurodevelopment, pediatric mental health and family dynamics as well as opportunities for intervention.
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Affiliation(s)
- Claire M Dahl
- Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States
| | - Maria Kroupina
- Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States
| | - Sameh M Said
- Division of Pediatric Cardiovascular Surgery, Masonic Children's Hospital, Minneapolis, MN, United States.,Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, United States
| | - Arif Somani
- Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States
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18
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Pfitzer C, Buchdunger LA, Helm PC, Blickle MJ, Rosenthal LM, Ferentzi H, Berger F, Bauer UMM, Schmitt KRL. Education of Children With Cyanotic Congenital Heart Disease After Neonatal Cardiac Surgery. Ann Thorac Surg 2020; 112:1546-1552. [PMID: 33075323 DOI: 10.1016/j.athoracsur.2020.07.072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 07/10/2020] [Accepted: 07/14/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND The aim of the study was to evaluate the educational achievement of patients diagnosed with univentricular heart physiology (UVHP) or transposition of the great arteries (TGA) after neonatal cardiac surgery. METHODS An exploratory online survey was performed with patients registered with the National Register for Congenital Heart Defects in Germany. For this publication, a subgroup analysis was conducted among patients diagnosed with TGA (n = 173; 36.3%) and UVHP (n = 304; 63.7%). RESULTS Median age of the sample at school enrollment was 6 years (range, 5-8 years). The majority were enrolled at a standard elementary school (n = 368 of 477; 77.1%), although patients with UVHP were enrolled significantly more often at a special needs school (n = 52 of 304; 17.1%, TGA patients n = 11/ of 173; 6.4%, P < .001). A total of 45.8% (n = 66 of 144) of the patients graduated with a high school diploma. A substantial number of patients had been diagnosed with behavioral or learning disorders (TGA patients n = 63 of 173 [36.4%], UVHP patients n = 148 of 304 [48.7%]) and received early supportive therapy or remedial teaching before (TGA patients n = 89 of 173 [51.4%], UVHP patients n = 209 of 304 [68.8%]) and/or during their school careers (TGA patients n = 54 of 173 [31.2%], UVHP patients n = 120 of 304 [39.5%]). CONCLUSIONS A large proportion of patients who underwent neonatal cardiac surgery graduated with a high school diploma. These results are of great importance to congenital heart defect patients, affected families, and treating physicians. Nevertheless, study participants, especially patients with UVHP, face some academic challenges. We conclude that long-term follow-up examinations and regular developmental assessments may be beneficial.
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Affiliation(s)
- Constanze Pfitzer
- Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Germany; Berlin Institute of Health, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany.
| | | | - Paul C Helm
- National Register for Congenital Heart Defects, DZHK (German Centre for Cardiovascular Research), Berlin, Germany
| | - Maximilian J Blickle
- Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Germany
| | - Lisa-Maria Rosenthal
- Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Germany
| | - Hannah Ferentzi
- Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Germany
| | - Felix Berger
- Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany; Department of Pediatric Cardiology, Charité- Universitaetsmedizin Berlin, Germany
| | - Ulrike M M Bauer
- National Register for Congenital Heart Defects, DZHK (German Centre for Cardiovascular Research), Berlin, Germany; Competence Network for Congenital Heart Defects, DZHK (German Centre for Cardiovascular Research), Berlin, Germany
| | - Katharina R L Schmitt
- Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany
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White BR, Rogers LS, Kirschen MP. Recent advances in our understanding of neurodevelopmental outcomes in congenital heart disease. Curr Opin Pediatr 2019; 31:783-788. [PMID: 31693588 PMCID: PMC6852883 DOI: 10.1097/mop.0000000000000829] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Patients with congenital heart disease (CHD) suffer from a pattern of neurodevelopmental abnormalities including deficits in language and executive function. In this review, we summarize recent studies that examine these outcomes, their risk factors, possible biomarkers, and attempts to develop therapeutic interventions. RECENT FINDINGS The latest literature has highlighted the role of genetics in determining neurologic prognosis, as we have increased our understanding of potentially modifiable perioperative risk factors. The role of potentially neurotoxic medical therapies has become more salient. One recent focus has been how neurodevelopment affects quality of life and leads to a high prevalence of mental illness. Neuroimaging advances have provided new insights into the pathogenesis of deficits. SUMMARY Although many risk factors in CHD are not modifiable, there is promise for interventions to improve neurodevelopmental outcomes in patients with CHD. Biomarkers are needed to better understand the timing and prognosis of injury and to direct therapy. Research into psychosocial interventions is urgently needed to benefit the many survivors with CHD.
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Affiliation(s)
- Brian R. White
- Division of Pediatric Cardiology, Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania
| | - Lindsay S. Rogers
- Division of Pediatric Cardiology, Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania
| | - Matthew P. Kirschen
- Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania
- Department of Neurology, The Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania
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20
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Romanowicz J, Leonetti C, Dhari Z, Korotcova L, Ramachandra SD, Saric N, Morton PD, Bansal S, Cheema A, Gallo V, Jonas RA, Ishibashi N. Treatment With Tetrahydrobiopterin Improves White Matter Maturation in a Mouse Model for Prenatal Hypoxia in Congenital Heart Disease. J Am Heart Assoc 2019; 8:e012711. [PMID: 31331224 PMCID: PMC6761654 DOI: 10.1161/jaha.119.012711] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 06/24/2019] [Indexed: 01/05/2023]
Abstract
Background Reduced oxygen delivery in congenital heart disease causes delayed brain maturation and white matter abnormalities in utero. No treatment currently exists. Tetrahydrobiopterin (BH4) is a cofactor for neuronal nitric oxide synthase. BH4 availability is reduced upon NOS activation, such as during hypoxic conditions, and leads to toxin production. We hypothesize that BH4 levels are depleted in the hypoxic brain and that BH4 replacement therapy mitigates the toxic effects of hypoxia on white matter. Methods and Results Transgenic mice were used to visualize oligodendrocytes. Hypoxia was introduced during a period of white matter development equivalent to the human third trimester. BH4 was administered during hypoxia. BH4 levels were depleted in the hypoxic brain by direct quantification (n=7-12). The proliferation (n=3-6), apoptosis (n=3-6), and developmental stage (n=5-8) of oligodendrocytes were determined immunohistologically. Total oligodendrocytes increased after hypoxia, consistent with hypoxia-induced proliferation seen previously; however, mature oligodendrocytes were less prevalent in hypoxia, and there was accumulation of immature oligodendrocytes. BH4 treatment improved the mature oligodendrocyte number such that it did not differ from normoxia, and accumulation of immature oligodendrocytes was not observed. These results persisted beyond the initial period of hypoxia (n=3-4). Apoptosis increased with hypoxia but decreased with BH4 treatment to normoxic levels. White matter myelin levels decreased following hypoxia by western blot. BH4 treatment normalized myelination (n=6-10). Hypoxia worsened sensory-motor coordination on balance beam tasks, and BH4 therapy normalized performance (n=5-9). Conclusions Suboptimal BH4 levels influence hypoxic white matter abnormalities. Repurposing BH4 for use during fetal brain development may limit white matter dysmaturation in congenital heart disease.
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Affiliation(s)
- Jennifer Romanowicz
- Children's National Heart InstituteChildren's National Health SystemWashingtonDC
| | - Camille Leonetti
- Children's National Heart InstituteChildren's National Health SystemWashingtonDC
- Center for Neuroscience ResearchChildren's National Health SystemWashingtonDC
| | - Zaenab Dhari
- Children's National Heart InstituteChildren's National Health SystemWashingtonDC
- Center for Neuroscience ResearchChildren's National Health SystemWashingtonDC
| | - Ludmila Korotcova
- Children's National Heart InstituteChildren's National Health SystemWashingtonDC
- Center for Neuroscience ResearchChildren's National Health SystemWashingtonDC
| | - Shruti D. Ramachandra
- Children's National Heart InstituteChildren's National Health SystemWashingtonDC
- Center for Neuroscience ResearchChildren's National Health SystemWashingtonDC
| | - Nemanja Saric
- Children's National Heart InstituteChildren's National Health SystemWashingtonDC
- Center for Neuroscience ResearchChildren's National Health SystemWashingtonDC
| | - Paul D. Morton
- Children's National Heart InstituteChildren's National Health SystemWashingtonDC
- Center for Neuroscience ResearchChildren's National Health SystemWashingtonDC
| | - Shivani Bansal
- Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonDC
| | - Amrita Cheema
- Lombardi Comprehensive Cancer CenterGeorgetown University Medical CenterWashingtonDC
| | - Vittorio Gallo
- Center for Neuroscience ResearchChildren's National Health SystemWashingtonDC
| | - Richard A. Jonas
- Children's National Heart InstituteChildren's National Health SystemWashingtonDC
- Center for Neuroscience ResearchChildren's National Health SystemWashingtonDC
| | - Nobuyuki Ishibashi
- Children's National Heart InstituteChildren's National Health SystemWashingtonDC
- Center for Neuroscience ResearchChildren's National Health SystemWashingtonDC
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21
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Pfitzer C, Helm PC, Blickle MJ, Rosenthal LM, Berger F, Abdul-Khaliq H, Bauer UMM, Schmitt KRL. Educational achievement of children with congenital heart disease: Promising results from a survey by the German National Register of Congenital Heart Defects. Early Hum Dev 2019; 128:27-34. [PMID: 30448707 DOI: 10.1016/j.earlhumdev.2018.11.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Revised: 05/29/2018] [Accepted: 11/02/2018] [Indexed: 10/27/2022]
Abstract
BACKGROUND Survival rates of children with congenital heart disease (CHD) have increased significantly in the decade. There is now increased interest in the long-term outcome and quality of life of these children. AIMS To assess the educational achievement of patients with CHD in Germany. STUDY DESIGN Cross-sectional study using an online survey. The recruitment of study participants was carried out via the database of the German National Register for Congenital Heart Defects (NRCHD). SUBJECTS Patients born between 1992 and 2011 were enrolled in the study. For 2609 study participants (female = 1870 (71.7%); 1072 (41.1%) patients; 1537 (58.9%) parents), who participated in the survey, detailed information regarding the underlying CHD diagnosis and clinical data was available. OUTCOME MEASURES Age at enrollment, secondary school form, school year repetition, school degree. RESULTS The large majority of study participants were enrolled at a conventional elementary school (83.4%) and started school at the age of 6 years or below (73.3%). In total 45.7% of graduated study participants graduated with the qualification necessary to study at any university. In terms of analysis of the different CHD severity subgroups 57.3% of patients with a mild CHD, 47.5% with a moderate CHD and only 35.1% suffering from a severe CHD attained a high school diploma. CONCLUSIONS In our study, the majority of participating CHD patients had a standard school career. These initial results are of great importance to affected families and treating physicians as they show that, in general, a normal school career is possible for all CHD patients.
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Affiliation(s)
- Constanze Pfitzer
- Department of Congenital Heart Disease - Paediatric Cardiology, Deutsches Herzzentrum Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany.
| | - Paul C Helm
- National Register for Congenital Heart Defects, DZHK (German Centre for Cardiovascular Research), Berlin, Germany
| | - Maximilian J Blickle
- Department of Congenital Heart Disease - Paediatric Cardiology, Deutsches Herzzentrum Berlin, Germany
| | - Lisa-Maria Rosenthal
- Department of Congenital Heart Disease - Paediatric Cardiology, Deutsches Herzzentrum Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany
| | - Felix Berger
- Department of Congenital Heart Disease - Paediatric Cardiology, Deutsches Herzzentrum Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany; Department of Paediatric Cardiology, Charite - Universitaetsmedizin Berlin, Germany
| | - Hashim Abdul-Khaliq
- Department of Paediatric Cardiology, University Hospital Homburg Saar, Germany
| | - Ulrike M M Bauer
- National Register for Congenital Heart Defects, DZHK (German Centre for Cardiovascular Research), Berlin, Germany; Competence Network for Congenital Heart Defects, DZHK (German Centre for Cardiovascular Research), Berlin, Germany
| | - Katharina R L Schmitt
- Department of Congenital Heart Disease - Paediatric Cardiology, Deutsches Herzzentrum Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany
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22
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Andresen B, Døhlen G, Diep LM, Lindberg H, Fosse E, Andersen MH. Psychosocial and clinical outcomes of percutaneous versus surgical pulmonary valve implantation. Open Heart 2018; 5:e000758. [PMID: 30018768 PMCID: PMC6045705 DOI: 10.1136/openhrt-2017-000758] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 02/21/2018] [Accepted: 03/06/2018] [Indexed: 11/23/2022] Open
Abstract
Objective This prospective non-randomised study was performed to compare the psychosocial function and clinical outcomes following surgical and percutaneous implantation of a pulmonary valve at 3 months and 1 year after treatment. Methods All patients were consecutively admitted for treatment by either method from June 2011 to October 2014. The data of 20 patients treated with the percutaneous technique and 14 patients treated with open heart surgery were compared. Psychosocial function was measured by the Achenbach System of Empirically Based Assessment (ASEBA). We used linear mixed-effect models to investigate group changes between the psychosocial function and clinical data of 34 patients with congenital pulmonary valve disease. Results A significant difference in favour of the percutaneous pulmonary valve implantation group was observed regarding the ASEBA scores, specifically in the Thought problems subscale at 1 year (p=0.015), Attention problems subscale at 3 months (p=0.016) and 1 year (p=0.007) after treatment. After adjustment for the right ventricle to pulmonary artery pressure gradient at 3 months, a significant change in the Attention problems subscale (p=0.038) was noted in the percutaneous group. The New York Heart Association functional score significantly improved in both groups. The measured right ventricle to pulmonary artery pressure gradient was reduced significantly in both groups at 1 year. Conclusions Both methods led to significant clinical improvement. Thought and attention problems such as intrusive behaviour significantly decreased only in patients who underwent the percutaneous procedure. Complications as reintervention, bleeding and arrhythmia were only observed in the open surgery group.
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Affiliation(s)
- Brith Andresen
- Intervention Centre, Oslo University Hospital, Oslo, Norway.,Department of Cardiothoracic Surgery, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Gaute Døhlen
- Department of Pediatric Cardiology, Oslo University Hospital, Oslo, Norway
| | - Lien My Diep
- Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway
| | - Harald Lindberg
- Department of Cardiothoracic Surgery, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Erik Fosse
- Intervention Centre, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Marit Helen Andersen
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.,Department of Transplant Medicine, Oslo University Hospital, Oslo, Norway.,Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
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23
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Wong P, Denburg A, Dave M, Levin L, Morinis JO, Suleman S, Wong J, Ford-Jones E, Moore AM. Early life environment and social determinants of cardiac health in children with congenital heart disease. Paediatr Child Health 2018; 23:92-95. [PMID: 29686491 PMCID: PMC5905484 DOI: 10.1093/pch/pxx146] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Congenital heart disease is a significant cause of infant mortality. Epidemiology and social context play a crucial role in conditioning disease burden and modulating outcomes, while diagnosis and treatment remain resource intensive. This review will address the role of social demographics, environmental exposure, epigenetics and nutrition in the aetiology of congenital heart disease. We then discuss the determinant effect of social factors on the provision and outcomes of care for congenital heart disease and implications for practice. It is our hope that enhanced knowledge of the intersection of social determinants of health and congenital heart disease will facilitate effective preventative strategies at the individual and population levels to optimize heart health outcomes across the life course.
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Affiliation(s)
- Peter Wong
- Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario
| | | | - Malini Dave
- Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario
| | - Leo Levin
- Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario
| | - Julia Orkin Morinis
- Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario
| | - Shazeen Suleman
- Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario
| | - Jonathan Wong
- Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario
| | - Elizabeth Ford-Jones
- Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario
| | - Aideen M Moore
- Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario
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24
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Kasmi L, Calderon J, Montreuil M, Geronikola N, Lambert V, Belli E, Bonnet D, Kalfa D. Neurocognitive and Psychological Outcomes in Adults With Dextro-Transposition of the Great Arteries Corrected by the Arterial Switch Operation. Ann Thorac Surg 2018; 105:830-836. [DOI: 10.1016/j.athoracsur.2017.06.055] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Revised: 06/18/2017] [Accepted: 06/21/2017] [Indexed: 11/29/2022]
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Puri K, Warshak CR, Habli MA, Yuan A, Sahay RD, King EC, Divanovic A, Cnota JF. Fetal somatic growth trajectory differs by type of congenital heart disease. Pediatr Res 2018; 83:669-676. [PMID: 29261645 DOI: 10.1038/pr.2017.275] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 10/14/2017] [Indexed: 02/06/2023]
Abstract
BackgroundThe growth trajectories of common measurements, including estimated fetal weight (EFW), head circumference (HC), and abdominal circumference (AC), in fetuses with congenital heart disease (CHD) have not been described for different cardiac lesions. We hypothesized that (i) fetuses with CHD have differential growth in utero, and (ii) different categories of CHD demonstrate different in utero growth curves.MethodsWe performed a retrospective observational cohort study of pregnancies with known fetal CHD seen from January 2000 to June 2013. For analysis, the infants were divided into single ventricle (SV), biventricular conotruncal, d-transposition of great arteries (d-TGA), biventricular septal defects (SD; including atrial, ventricular, and atrioventricular SD), and all others (Other).ResultsA total of 194 newborns met inclusion criteria. There was significant differential growth of EFW in all CHD types, except d-TGA, starting with low z-scores before 25 weeks gestation, improving toward normal around 30-32 weeks gestation, and then again differential growth with advancing gestation. SV and SD groups had significant differential growth of HC starting early in gestation and linearly progressing negative z-scores with advancing gestation.ConclusionWe observed differences in the fetal growth curves throughout gestation for the major categories of CHD, including significant differential growth in even "simple" CHD, such as SD.
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Affiliation(s)
- Kriti Puri
- The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Carri R Warshak
- Maternal-Fetal Medicine at the Cincinnati Fetal Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Mounira A Habli
- Department of Obstetrics and Gynecology, Good Samaritan Hospital, Cincinnati, Ohio
| | - Amy Yuan
- Department of Obstetrics and Gynecology, Good Samaritan Hospital, Cincinnati, Ohio
| | - Rashmi D Sahay
- Department of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Eileen C King
- Department of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Allison Divanovic
- The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - James F Cnota
- The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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Abstract
OBJECTIVE Children with hypoplastic left heart syndrome are at a risk for neurodevelopmental delays. Current guidelines recommend systematic evaluation and management of neurodevelopmental outcomes with referral for early intervention services. The Single Ventricle Reconstruction Trial represents the largest cohort of children with hypoplastic left heart syndrome ever assembled. Data on life events and resource utilisation have been collected annually. We sought to determine the type and prevalence of early intervention services used from age 1 to 4 years and factors associated with utilisation of services. METHODS Data from 14-month neurodevelopmental assessment and annual medical history forms were used. We assessed the impact of social risk and geographic differences. Fisher exact tests and logistic regression were used to evaluate associations. RESULTS Annual medical history forms were available for 302 of 314 children. Greater than half of the children (52-69%) were not receiving services at any age assessed, whereas 20-32% were receiving two or more therapies each year. Utilisation was significantly lower in year 4 (31%) compared with years 1-3 (with a range from 40 to 48%) (p<0.001). Social risk factors were not associated with the use of services at any age but there were significant geographic differences. Significant delay was reported by parents in 18-43% of children at ages 3 and 4. CONCLUSION Despite significant neurodevelopmental delays, early intervention service utilisation was low in this cohort. As survival has improved for children with hypoplastic left heart syndrome, attention must shift to strategies to optimise developmental outcomes, including enrolment in early intervention when merited.
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Verma RK, Keller D, Grunt S, Bigi S, Weisstanner C, Wiest R, Gralla J, Hutter D, Wagner B. Decreased oxygen saturation levels in neonates with transposition of great arteries: Impact on appearance of cerebral veins in susceptibility-weighted imaging. Sci Rep 2017; 7:15471. [PMID: 29133891 PMCID: PMC5684390 DOI: 10.1038/s41598-017-15591-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 10/27/2017] [Indexed: 12/24/2022] Open
Abstract
Purpose of this study was to investigate a potential correlation between the pattern of cerebral veins (CV) on susceptibility-weighted imaging (SWI) and blood oxygen saturation, as well as preoperative brain injury, in neonates with transposition of the great arteries (TGA). Eleven neonates with TGA underwent MRI preoperatively, including SWI, T1- and T2-weighted scans. Images were retrospectively evaluated and appearance of CV was graded from 0 (normal appearance) to 3 (severe prominent appearance). White matter injuries (WMI) and strokes were analysed. Results were correlated with preductal arterial oxygen saturation. As findings one subject showed a normal CV appearance (grade 0) whereas 10 showed pathological prominent CV (grades 1–3); median 2. Mean oxygen saturation ranged between 67.5% and 89.0% (median 81.0%). CV grade and mean oxygen saturation correlated significantly (p = 0.011). WMI were absent in 5 cases, mild in 4, and moderate in 2 cases. We conclude, that SWI has the potential to be used to estimate the current hypoxic burden on brain tissue in TGA newborns by assessing the prominence of the CV.
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Affiliation(s)
- Rajeev Kumar Verma
- University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland. .,Institute of Radiology and Neuroradiology, Tiefenau Hospital, Division Stadt, Inselgroup, Bern, Switzerland.
| | - Desislava Keller
- University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland
| | - Sebastian Grunt
- University Department of Pediatrics, Division of Pediatric Neurology, Development and Rehabilitation, Inselspital, University of Bern, Bern, Switzerland
| | - Sandra Bigi
- University Department of Pediatrics, Division of Pediatric Neurology, Development and Rehabilitation, Inselspital, University of Bern, Bern, Switzerland
| | - Christian Weisstanner
- University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland
| | - Roland Wiest
- University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland
| | - Jan Gralla
- University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, University of Bern, Bern, Switzerland
| | - Damian Hutter
- University Department of Pediatrics, Division of Pediatric Cardiology, Inselspital, University of Bern, Bern, Switzerland
| | - Bendicht Wagner
- University Department of Pediatrics, Division of Pediatric Intensive Care Medicine, Inselspital Bern, University of Bern, Bern, Switzerland
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Lauridsen MH, Uldbjerg N, Henriksen TB, Petersen OB, Stausbøl-Grøn B, Matthiesen NB, Peters DA, Ringgaard S, Hjortdal VE. Cerebral Oxygenation Measurements by Magnetic Resonance Imaging in Fetuses With and Without Heart Defects. Circ Cardiovasc Imaging 2017; 10:e006459. [DOI: 10.1161/circimaging.117.006459] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 09/29/2017] [Indexed: 11/16/2022]
Affiliation(s)
- Mette H. Lauridsen
- From Pediatrics and Adolescent Medicine, Neonatal and Intensive Care Unit (M.H.L., T.B.H.), Department of Obstetrics and Gynecology (N.U., O.B.P.), Department of Pediatrics, Perinatal Epidemiology Research Unit (T.B.H., N.B.M.), Department of Radiology (B.S.-G.), and Department of Cardio-Thoracic and Vascular Surgery (V.E.H.), Aarhus University Hospital, Denmark; Institute for Clinical Medicine (M.H.L., N.U., S.R., V.E.H.) and the MR Research Centre (S.R.), Aarhus University, Denmark; and Department
| | - Niels Uldbjerg
- From Pediatrics and Adolescent Medicine, Neonatal and Intensive Care Unit (M.H.L., T.B.H.), Department of Obstetrics and Gynecology (N.U., O.B.P.), Department of Pediatrics, Perinatal Epidemiology Research Unit (T.B.H., N.B.M.), Department of Radiology (B.S.-G.), and Department of Cardio-Thoracic and Vascular Surgery (V.E.H.), Aarhus University Hospital, Denmark; Institute for Clinical Medicine (M.H.L., N.U., S.R., V.E.H.) and the MR Research Centre (S.R.), Aarhus University, Denmark; and Department
| | - Tine B. Henriksen
- From Pediatrics and Adolescent Medicine, Neonatal and Intensive Care Unit (M.H.L., T.B.H.), Department of Obstetrics and Gynecology (N.U., O.B.P.), Department of Pediatrics, Perinatal Epidemiology Research Unit (T.B.H., N.B.M.), Department of Radiology (B.S.-G.), and Department of Cardio-Thoracic and Vascular Surgery (V.E.H.), Aarhus University Hospital, Denmark; Institute for Clinical Medicine (M.H.L., N.U., S.R., V.E.H.) and the MR Research Centre (S.R.), Aarhus University, Denmark; and Department
| | - Olav B. Petersen
- From Pediatrics and Adolescent Medicine, Neonatal and Intensive Care Unit (M.H.L., T.B.H.), Department of Obstetrics and Gynecology (N.U., O.B.P.), Department of Pediatrics, Perinatal Epidemiology Research Unit (T.B.H., N.B.M.), Department of Radiology (B.S.-G.), and Department of Cardio-Thoracic and Vascular Surgery (V.E.H.), Aarhus University Hospital, Denmark; Institute for Clinical Medicine (M.H.L., N.U., S.R., V.E.H.) and the MR Research Centre (S.R.), Aarhus University, Denmark; and Department
| | - Brian Stausbøl-Grøn
- From Pediatrics and Adolescent Medicine, Neonatal and Intensive Care Unit (M.H.L., T.B.H.), Department of Obstetrics and Gynecology (N.U., O.B.P.), Department of Pediatrics, Perinatal Epidemiology Research Unit (T.B.H., N.B.M.), Department of Radiology (B.S.-G.), and Department of Cardio-Thoracic and Vascular Surgery (V.E.H.), Aarhus University Hospital, Denmark; Institute for Clinical Medicine (M.H.L., N.U., S.R., V.E.H.) and the MR Research Centre (S.R.), Aarhus University, Denmark; and Department
| | - Niels B. Matthiesen
- From Pediatrics and Adolescent Medicine, Neonatal and Intensive Care Unit (M.H.L., T.B.H.), Department of Obstetrics and Gynecology (N.U., O.B.P.), Department of Pediatrics, Perinatal Epidemiology Research Unit (T.B.H., N.B.M.), Department of Radiology (B.S.-G.), and Department of Cardio-Thoracic and Vascular Surgery (V.E.H.), Aarhus University Hospital, Denmark; Institute for Clinical Medicine (M.H.L., N.U., S.R., V.E.H.) and the MR Research Centre (S.R.), Aarhus University, Denmark; and Department
| | - David A. Peters
- From Pediatrics and Adolescent Medicine, Neonatal and Intensive Care Unit (M.H.L., T.B.H.), Department of Obstetrics and Gynecology (N.U., O.B.P.), Department of Pediatrics, Perinatal Epidemiology Research Unit (T.B.H., N.B.M.), Department of Radiology (B.S.-G.), and Department of Cardio-Thoracic and Vascular Surgery (V.E.H.), Aarhus University Hospital, Denmark; Institute for Clinical Medicine (M.H.L., N.U., S.R., V.E.H.) and the MR Research Centre (S.R.), Aarhus University, Denmark; and Department
| | - Steffen Ringgaard
- From Pediatrics and Adolescent Medicine, Neonatal and Intensive Care Unit (M.H.L., T.B.H.), Department of Obstetrics and Gynecology (N.U., O.B.P.), Department of Pediatrics, Perinatal Epidemiology Research Unit (T.B.H., N.B.M.), Department of Radiology (B.S.-G.), and Department of Cardio-Thoracic and Vascular Surgery (V.E.H.), Aarhus University Hospital, Denmark; Institute for Clinical Medicine (M.H.L., N.U., S.R., V.E.H.) and the MR Research Centre (S.R.), Aarhus University, Denmark; and Department
| | - Vibeke E. Hjortdal
- From Pediatrics and Adolescent Medicine, Neonatal and Intensive Care Unit (M.H.L., T.B.H.), Department of Obstetrics and Gynecology (N.U., O.B.P.), Department of Pediatrics, Perinatal Epidemiology Research Unit (T.B.H., N.B.M.), Department of Radiology (B.S.-G.), and Department of Cardio-Thoracic and Vascular Surgery (V.E.H.), Aarhus University Hospital, Denmark; Institute for Clinical Medicine (M.H.L., N.U., S.R., V.E.H.) and the MR Research Centre (S.R.), Aarhus University, Denmark; and Department
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29
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Nattel SN, Adrianzen L, Kessler EC, Andelfinger G, Dehaes M, Côté-Corriveau G, Trelles MP. Congenital Heart Disease and Neurodevelopment: Clinical Manifestations, Genetics, Mechanisms, and Implications. Can J Cardiol 2017; 33:1543-1555. [PMID: 29173597 DOI: 10.1016/j.cjca.2017.09.020] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Revised: 09/27/2017] [Accepted: 09/27/2017] [Indexed: 10/18/2022] Open
Abstract
Children with congenital heart disease (CHD) are at increased risk of neurodevelopmental disorders (NDDs) and psychiatric conditions. These include cognitive, adaptive, motor, speech, behavioural, and executive functioning deficits, as well as autism spectrum disorder and psychiatric conditions. Structural and functional neuroimaging have demonstrated brain abnormalities in young children with CHD before undergoing surgical repair, likely as a result of an in utero developmental insult. Surgical factors do not seem to play a significant role in neurodevelopmental outcomes. Specific genetic abnormalities, particularly copy number variants, have been increasingly implicated in both CHD and NDDs. Variations in genes involved in apolipoprotein E (APOE) production, the Wnt signalling pathway, and histone modification, as well as in the 1q21.1, 16p13.1-11, and 8p23.1 genetic loci, have been associated with CHD and NDDs and are important targets for future research. Understanding these associations is important for risk stratification, disease classification, improved screening, and pharmacologic management of individuals with CHD.
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Affiliation(s)
- Sarah N Nattel
- Department of Psychiatry, Albert Einstein College of Medicine and Seaver Autism Center at Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Laura Adrianzen
- Department of Psychiatry, Seaver Autism Center at Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | | | - Gregor Andelfinger
- Department of Pediatrics, University of Montreal and Ste-Justine Hospital University Centre, Montreal, Quebec, Canada
| | - Mathieu Dehaes
- Department of Radiology, Radio-oncology, and Nuclear Medicine, University of Montreal and Ste-Justine Hospital University Centre, Montreal, Quebec, Canada
| | - Gabriel Côté-Corriveau
- Department of Radiology, Radio-oncology, and Nuclear Medicine, University of Montreal and Ste-Justine Hospital University Centre, Montreal, Quebec, Canada
| | - M Pilar Trelles
- Department of Psychiatry, Seaver Autism Center at Icahn School of Medicine at Mount Sinai, New York, New York, USA.
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30
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Pironkova RP, Giamelli J, Seiden H, Parnell VA, Gruber D, Sison CP, Kowal C, Ojamaa K. Brain injury with systemic inflammation in newborns with congenital heart disease undergoing heart surgery. Exp Ther Med 2017; 14:228-238. [PMID: 28672919 PMCID: PMC5488503 DOI: 10.3892/etm.2017.4493] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 01/13/2017] [Indexed: 12/03/2022] Open
Abstract
The potential role of systemic inflammation on brain injury in newborns with congenital heart disease (CHD) was assessed by measuring levels of central nervous system (CNS)-derived proteins in serum prior to and following cardiac surgery. A total of 23 newborns (gestational age, 39±1 weeks) with a diagnosis of CHD that required cardiac surgery with cardiopulmonary bypass (CPB) were enrolled in the current study. Serum samples were collected immediately prior to surgery and 2, 24 and 48 h following CPB, and serum levels of phosphorylated neurofilament-heavy subunit (pNF-H), neuron-specific enolase (NSE) and S100B were analyzed. Systemic inflammation was assessed by measuring serum concentrations of complement C5a and complement sC5b9, and the following cytokines: Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL12p70, interferon γ and tumor necrosis factor (TNF)-α. Analysis of cord blood from normal term deliveries (n=26) provided surrogate normative values for newborns. pNF-H and S100B were 2.4- to 2.8-fold higher (P<0.0001) in patient sera than in cord blood prior to surgery and remained elevated following CPB. Pre-surgical serum pNF-H and S100B levels directly correlated with interleukin (IL)-12p70 (ρ=0.442, P<0.05). pNF-H was inversely correlated with arterial pO2 prior to surgery (ρ=−0.493, P=0.01) and directly correlated with arterial pCO2 post-CPB (ρ=0.426, P<0.05), suggesting that tissue hypoxia and inflammation contribute to blood brain barrier (BBB) dysfunction and neuronal injury. Serum IL12p70, IL-6, IL-8, IL-10 and TNF-α levels were significantly higher in patients than in normal cord blood and levels of these cytokines increased following CPB (P<0.001). Activation of complement was observed in all patients prior to surgery, and serum C5a and sC5b9 remained elevated up to 48 h post-surgery. Furthermore, they were correlated (P<0.05) with low arterial pO2, high pCO2 and elevated arterial pressure in the postoperative period. Length of mechanical ventilation was associated directly with post-surgery serum IL-12p70 and IL-8 concentrations (P<0.05). Elevated serum concentrations of pNF-H and S100B in neonates with CHD suggest BBB dysfunction and CNS injury, with concurrent hypoxemia and an activated inflammatory response potentiating this effect.
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Affiliation(s)
- Rossitza P Pironkova
- Division of Pediatric Cardiology, Department of Pediatrics, Cohen Children's Medical Center of New York at Northwell Health, New Hyde Park, NY 11040, USA
| | - Joseph Giamelli
- Division of Pediatric Cardiology, Department of Pediatrics, Cohen Children's Medical Center of New York at Northwell Health, New Hyde Park, NY 11040, USA
| | - Howard Seiden
- Division of Pediatric Cardiology, Department of Pediatrics, Cohen Children's Medical Center of New York at Northwell Health, New Hyde Park, NY 11040, USA
| | - Vincent A Parnell
- Division of Pediatric Cardiothoracic Surgery, Department of Pediatrics, Cohen Children's Medical Center of New York at Northwell Health, New Hyde Park, NY 11040, USA
| | - Dorota Gruber
- Division of Pediatric Cardiology, Department of Pediatrics, Cohen Children's Medical Center of New York at Northwell Health, New Hyde Park, NY 11040, USA.,Department of Pediatrics, Hofstra Northwell School of Medicine, Hempstead, NY 11549, USA
| | - Cristina P Sison
- Biostatistics Unit, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY 11030, USA.,Department of Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY 11549, USA
| | - Czeslawa Kowal
- Center for Musculoskeletal and Autoimmune Diseases, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY 11030, USA
| | - Kaie Ojamaa
- Division of Pediatric Cardiology, Department of Pediatrics, Cohen Children's Medical Center of New York at Northwell Health, New Hyde Park, NY 11040, USA.,Department of Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY 11549, USA.,Center for Immunology and Inflammation, The Feinstein Institute for Medical Research, Northwell Health, Manhasset, NY 11030, USA
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31
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Morton PD, Ishibashi N, Jonas RA. Neurodevelopmental Abnormalities and Congenital Heart Disease: Insights Into Altered Brain Maturation. Circ Res 2017; 120:960-977. [PMID: 28302742 PMCID: PMC5409515 DOI: 10.1161/circresaha.116.309048] [Citation(s) in RCA: 139] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 12/14/2016] [Accepted: 12/15/2016] [Indexed: 01/14/2023]
Abstract
In the past 2 decades, it has become evident that individuals born with congenital heart disease (CHD) are at risk of developing life-long neurological deficits. Multifactorial risk factors contributing to neurodevelopmental abnormalities associated with CHD have been identified; however, the underlying causes remain largely unknown, and efforts to address this issue have only recently begun. There has been a dramatic shift in focus from newly acquired brain injuries associated with corrective and palliative heart surgery to antenatal and preoperative factors governing altered brain maturation in CHD. In this review, we describe key time windows of development during which the immature brain is vulnerable to injury. Special emphasis is placed on the dynamic nature of cellular events and how CHD may adversely impact the cellular units and networks necessary for proper cognitive and motor function. In addition, we describe current gaps in knowledge and offer perspectives about what can be done to improve our understanding of neurological deficits in CHD. Ultimately, a multidisciplinary approach will be essential to prevent or improve adverse neurodevelopmental outcomes in individuals surviving CHD.
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Affiliation(s)
- Paul D Morton
- From the Center for Neuroscience Research and Children's National Heart Institute, Children's National Health System, Washington, DC
| | - Nobuyuki Ishibashi
- From the Center for Neuroscience Research and Children's National Heart Institute, Children's National Health System, Washington, DC.
| | - Richard A Jonas
- From the Center for Neuroscience Research and Children's National Heart Institute, Children's National Health System, Washington, DC.
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32
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Effect of congenital heart disease on 4-year neurodevelopment within multiple-gestation births. J Thorac Cardiovasc Surg 2017; 154:273-281.e2. [PMID: 28320512 DOI: 10.1016/j.jtcvs.2017.02.022] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Revised: 02/03/2017] [Accepted: 02/13/2017] [Indexed: 11/20/2022]
Abstract
OBJECTIVES We sought to assess the effect of congenital heart disease requiring infant surgery with cardiopulmonary bypass on neurodevelopmental outcomes and growth at 4 years of age, while matching for gestational age, socioeconomic status, maternal gestational conditions, home environment, and parental intelligence by studying multiple-gestation births. METHODS We performed within-family comparison of 14 multiple-gestation births in which 1 child had congenital heart disease requiring surgery with cardiopulmonary bypass at ≤6 months of age. Between 4 and 5 years of age, a comprehensive neurodevelopmental assessment was performed. Paired comparisons were conducted between siblings with and without heart defects using a series of nonparametric tests. RESULTS On average, the children qualified as late preterm (mean gestational age 35.4 ± 2.6 weeks). At an average age of 4.8 ± 0.1 years, children with congenital heart disease weighed less than their siblings (median weight for age z score -0.4 vs 0.1, P = .02) and had worse performance for cognition (median full-scale IQ 99 vs 109, P = .02) and fine motor skills (median Wide Range Assessment of Visual Motor Ability, Fine Motor score 94.5 vs 107.5, P < .01). CONCLUSIONS After controlling for socioeconomic status, home environment, parental intelligence, and gestational factors by using multiple-gestation births, congenital heart disease requiring surgery with cardiopulmonary bypass at ≤6 months of age is associated with lower weight, cognitive abilities and fine motor skills at 4 years of age.
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33
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Browne JV, Martinez D, Talmi A. Infant Mental Health (IMH) in the Intensive Care Unit: Considerations for the Infant, the Family and the Staff. ACTA ACUST UNITED AC 2016. [DOI: 10.1053/j.nainr.2016.09.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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McKechnie AC, Pridham K, Tluczek A. Walking the "Emotional Tightrope" From Pregnancy to Parenthood: Understanding Parental Motivation to Manage Health Care and Distress After a Fetal Diagnosis of Complex Congenital Heart Disease. JOURNAL OF FAMILY NURSING 2016; 22:74-107. [PMID: 26704535 DOI: 10.1177/1074840715616603] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
Advances in medical technology account for increasingly more couples receiving fetal diagnoses of complex congenital heart disease. Theory on internal working models of caregiving during parenting transitions informed this prospective, exploratory study. Data included conjoint interviews and measures of anxiety, trauma, and depression collected from six couples after diagnosis and after birth. Severity of illness was described using infant health records. Directed content analysis furthered understanding of the caregiving motivation to manage health care that included three categories of parental efforts: (a) to determine expectations of health care providers, (b) to reconcile illness- and non-illness-related care, and (c) to express agency as a parent. Synthesis of qualitative findings transformed into categorical ratings with parents' levels of distress resulted in two profiles characterizing types of internal working models. Findings extend theory on internal working models of caregiving and offer direction for future research regarding parental management of health care for their chronically ill offspring. Implications for practice with families are offered.
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Abstract
OBJECTIVE To evaluate the family psycho-social outcomes of children with Down syndrome and atrioventricular septal defect, and examine the impact of these variables on the child's neurodevelopmental outcome. METHODS This was a cross-sectional study that consisted of 57 children with Down syndrome - 20 cases and 37 controls - of ~12-14 months of age. In both groups, we assessed the development of the child, the quality of the child's home environment, and parenting stress. RESULTS Compared with the Down syndrome without CHD group, the atrioventricular septal defect group revealed lower scores in all developmental domains, less optimal home environments, and higher parental stress. Significant differences in development were seen in the areas of cognition (p=0.04), expressive language (p=0.05), and gross motor (p<0.01). The Home Observation for Measurement of the Environment revealed significant differences in emotional and verbal responsiveness of the mother between the two groups. The Parenting Stress Index revealed that the Down syndrome with atrioventricular septal defect group had a significantly higher child demandingness subdomain scores compared with the Down syndrome without CHD group. CONCLUSIONS The diagnosis of a CHD in addition to the diagnosis of Down syndrome may provide additional stress to the child and parents, elevating parental concern and disrupting family dynamics, resulting in further neurodevelopmental deficits. Finding that parental stress and home environment may play a role in the neurodevelopmental outcomes may prompt new family-directed interventions and anticipatory guidance for the families of children with Down syndrome who have a CHD.
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Changes in Motor Development During a 4-Year Follow-up on Children With Univentricular Heart Defects. Pediatr Phys Ther 2016; 28:446-51. [PMID: 27661239 DOI: 10.1097/pep.0000000000000298] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To compare changes in motor development from 1 to 5 years of age among 18 children with hypoplastic left heart syndrome and 12 with univentricular heart to 42 children without heart defect. METHODS Motor development was assessed with the Alberta Infant Motor Scale and Movement Assessment Battery for Children (Movement ABC). RESULTS Children with hypoplastic left heart syndrome or univentricular heart had significantly lower scores on the Alberta Infant Motor Scale test at the age of 1 and on the Movement ABC test at the age of 5 years compared with controls. Children with clear abnormalities on brain magnetic resonance imaging had lower scores compared with those with normal images or mild changes, and their relative motor scores decreased during follow-up. CONCLUSIONS Some children with univentricular heart defects may benefit from physiotherapeutic interventions to support their motor development.
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Mussatto KA, Hoffmann R, Hoffman G, Tweddell JS, Bear L, Cao Y, Tanem J, Brosig C. Risk Factors for Abnormal Developmental Trajectories in Young Children With Congenital Heart Disease. Circulation 2015; 132:755-61. [PMID: 26304667 DOI: 10.1161/circulationaha.114.014521] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND Children with congenital heart disease are at risk for developmental delay. This study sought to identify early risk factors for abnormal developmental trajectories in children with congenital heart disease. METHODS AND RESULTS Children with congenital heart disease at high risk for developmental delay, without known genetic abnormality, and with ≥3 assessments by the use of the Bayley Scales of Infant and Toddler Development, Third Edition, were studied. Logistic regression was used to assess the impact of patient and clinical factors on cognitive, language, and motor score trajectories; classified as: average or improved if all scores were ≥85 (<1 standard deviation below the mean) or increased to ≥85 and never decreased; or abnormal if all scores were <85, fell to <85 and never improved, or fluctuated above and below 85. Data on 131 children with 527 Bayley Scales of Infant and Toddler Development, Third Edition assessments were analyzed. Subject age was 5.5 to 37.4 months. Overall, 56% had cognitive, language, and motor development in the average range. Delays occurred in single domains in 23%. Multiple domains were delayed in 21%. More cardiac surgeries, longer hospital stay, poorer linear growth, and tube feeding were associated with worse outcomes in all domains (P<0.05). In the multivariable model, the need for tube feeding was a risk factor for having an abnormal developmental trajectory (odds ratio, 5.1-7.9). Minority race and lack of private insurance had significant relationships with individual domains. CONCLUSIONS Longitudinal developmental surveillance identified early factors that can help quantify the risk of developmental delay over time. Strategies to improve modifiable factors and early therapeutic intervention can be targeted to children at highest risk.
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Affiliation(s)
- Kathleen A Mussatto
- From Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee (K.A.M., J.T.); and Departments of Pediatrics (R.H., L.B., Y.C., C.B.), Anesthesiology (G.H.), and Surgery (J.S.T.), Medical College of Wisconsin, Milwaukee.
| | - Raymond Hoffmann
- From Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee (K.A.M., J.T.); and Departments of Pediatrics (R.H., L.B., Y.C., C.B.), Anesthesiology (G.H.), and Surgery (J.S.T.), Medical College of Wisconsin, Milwaukee
| | - George Hoffman
- From Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee (K.A.M., J.T.); and Departments of Pediatrics (R.H., L.B., Y.C., C.B.), Anesthesiology (G.H.), and Surgery (J.S.T.), Medical College of Wisconsin, Milwaukee
| | - James S Tweddell
- From Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee (K.A.M., J.T.); and Departments of Pediatrics (R.H., L.B., Y.C., C.B.), Anesthesiology (G.H.), and Surgery (J.S.T.), Medical College of Wisconsin, Milwaukee
| | - Laurel Bear
- From Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee (K.A.M., J.T.); and Departments of Pediatrics (R.H., L.B., Y.C., C.B.), Anesthesiology (G.H.), and Surgery (J.S.T.), Medical College of Wisconsin, Milwaukee
| | - Yumei Cao
- From Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee (K.A.M., J.T.); and Departments of Pediatrics (R.H., L.B., Y.C., C.B.), Anesthesiology (G.H.), and Surgery (J.S.T.), Medical College of Wisconsin, Milwaukee
| | - Jena Tanem
- From Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee (K.A.M., J.T.); and Departments of Pediatrics (R.H., L.B., Y.C., C.B.), Anesthesiology (G.H.), and Surgery (J.S.T.), Medical College of Wisconsin, Milwaukee
| | - Cheryl Brosig
- From Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee (K.A.M., J.T.); and Departments of Pediatrics (R.H., L.B., Y.C., C.B.), Anesthesiology (G.H.), and Surgery (J.S.T.), Medical College of Wisconsin, Milwaukee
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38
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Hoffman GM, Brosig CL, Bear LM, Tweddell JS, Mussatto KA. Effect of Intercurrent Operation and Cerebral Oxygenation on Developmental Trajectory in Congenital Heart Disease. Ann Thorac Surg 2015; 101:708-16. [PMID: 26542436 DOI: 10.1016/j.athoracsur.2015.08.059] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2015] [Revised: 07/13/2015] [Accepted: 08/21/2015] [Indexed: 11/18/2022]
Abstract
BACKGROUND Children with congenital heart disease are at increased risk of abnormal neurodevelopment (ND). Demographic and perioperative physiologic factors have both been associated with developmental outcome. The acute physiologic effect of a surgical procedure, anesthesia, and hospitalization may offset any potential advantage gained from anatomic correction and circulatory palliation. The specific risk/benefit balance on ND outcome of the insult of the operation, offset by the benefit of improved anatomy and physiology, has not been addressed. We therefore sought to identify interval procedural and physiologic factors assessed at outpatient ND evaluation visits that were associated with outcome. METHODS The study included children with congenital heart disease at high risk for impaired ND performance with at least three ND assessments using the Bayley Scales of Infant Development-III during the first 3 years of life. The number of cardiac procedures, duration of hospitalization, feeding status, height, weight, and arterial, cerebral, and somatic oxygen saturations by near-infrared spectroscopy were recorded at each visit and used as predictors of language, motor, and cognitive composite scores and slopes (change over time) in general linear models. RESULTS Data on 178 children derived from 632 visits (median, 4 visits/child) were analyzed, with ages at first and last assessment of 7.7 and 30.2 months. Fifty-one had 1 ventricle (1V), 88 had 2 ventricles, and 39 had genetic syndrome conditions. Motor performance increased with age in all diagnostic categories. Cognitive and language performance increased with age in 1V patients but exhibited no significant change in 2-ventricle and genetic syndrome groups. At the first visit, 1V patients performed less well than 2-ventricle patients in the motor domain, but the rate of improvement was higher for 1V patients; by 24 months, there were no differences, and both groups were normal in all domains. Performance in genetic syndrome patients was below normal in all domains at the first visit and did not improve. Higher arterial saturation and narrower arterial-cerebral and arterial-somatic near-infrared spectroscopy saturation differences were associated with better or improving motor performance. Incremental cardiopulmonary bypass time, cumulative hospital length of stay, and tube feedings were risk factors in all domains. Total and incremental times for deep hypothermic circulatory arrest, extracorporeal membrane oxygenation, total open and total surgical procedures, and birth weight were not risk factors. CONCLUSIONS Patient physiologic status assessed by cerebral and somatic near-infrared spectroscopy is associated with ND performance. Incremental surgical procedures are not associated with ND performance when adjusted for cardiopulmonary bypass time and physiologic status. Treatment strategies that target improved physiologic status may also improve ND outcome.
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Affiliation(s)
- George M Hoffman
- Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee, Wisconsin; Departments of Pediatric Anesthesiology, Pediatrics, and Pediatric Critical Care Medicine, Cardiology, and Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin.
| | - Cheryl L Brosig
- Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee, Wisconsin; Departments of Pediatric Anesthesiology, Pediatrics, and Pediatric Critical Care Medicine, Cardiology, and Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Laurel M Bear
- Departments of Pediatric Anesthesiology, Pediatrics, and Pediatric Critical Care Medicine, Cardiology, and Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - James S Tweddell
- Herma Heart Center, Children's Hospital of Wisconsin, Milwaukee, Wisconsin; Departments of Pediatric Anesthesiology, Pediatrics, and Pediatric Critical Care Medicine, Cardiology, and Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
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Korotcova L, Kumar S, Agematsu K, Morton PD, Jonas RA, Ishibashi N. Prolonged White Matter Inflammation After Cardiopulmonary Bypass and Circulatory Arrest in a Juvenile Porcine Model. Ann Thorac Surg 2015; 100:1030-7. [PMID: 26228605 DOI: 10.1016/j.athoracsur.2015.04.017] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Revised: 03/27/2015] [Accepted: 04/01/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND White matter (WM) injury is common after neonatal cardiopulmonary bypass (CPB). We have demonstrated that the inflammatory response to CPB is an important mechanism of WM injury. Microglia are brain-specific immune cells that respond to inflammation and can exacerbate injury. We hypothesized that microglia activation contributes to WM injury caused by CPB. METHODS Juvenile piglets were randomly assigned to 1 of 3 CPB-induced brain insults (1, no-CPB; 2, full-flow CPB; 3, CPB and circulatory arrest). Neurobehavioral tests were performed. Animals were sacrificed 3 days or 4 weeks postoperatively. Microglia and proliferating cells were immunohistologically identified. Seven analyzed WM regions were further categorized into 3 fiber connections (1, commissural; 2, projection; 3, association fibers). RESULTS Microglia numbers significantly increased on day 3 after CPB and circulatory arrest, but not after full-flow CPB. Fiber categories did not affect these changes. On post-CPB week 4, proliferating cell number, blood leukocyte number, interleukin (IL)-6 levels, and neurologic scores had normalized. However, both full-flow CPB and CPB and circulatory arrest displayed significant increases in the microglia number compared with control. Thus brain-specific inflammation after CPB persists despite no changes in systemic biomarkers. Microglia number was significantly different among fiber categories, being highest in association and lowest in commissural connections. Thus there was a WM fiber-dependent microglia reaction to CPB. CONCLUSIONS This study demonstrates prolonged microglia activation in WM after CPB. This brain-specific inflammatory response is systemically silent. It is connection fiber-dependent which may impact specific connectivity deficits observed after CPB. Controlling microglia activation after CPB is a potential therapeutic intervention to limit neurologic deficits after CPB.
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Affiliation(s)
- Ludmila Korotcova
- Children's National Heart Institute, Children's National Medical Center, Washington, DC; Center for Neuroscience Research, Children's National Medical Center, Washington, DC
| | - Sonali Kumar
- George Washington University School of Medicine and Health Science, Washington, DC
| | - Kota Agematsu
- Children's National Heart Institute, Children's National Medical Center, Washington, DC; Center for Neuroscience Research, Children's National Medical Center, Washington, DC
| | - Paul D Morton
- Children's National Heart Institute, Children's National Medical Center, Washington, DC; Center for Neuroscience Research, Children's National Medical Center, Washington, DC
| | - Richard A Jonas
- Children's National Heart Institute, Children's National Medical Center, Washington, DC; Center for Neuroscience Research, Children's National Medical Center, Washington, DC; George Washington University School of Medicine and Health Science, Washington, DC
| | - Nobuyuki Ishibashi
- Children's National Heart Institute, Children's National Medical Center, Washington, DC; Center for Neuroscience Research, Children's National Medical Center, Washington, DC; George Washington University School of Medicine and Health Science, Washington, DC.
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Morton PD, Ishibashi N, Jonas RA, Gallo V. Congenital cardiac anomalies and white matter injury. Trends Neurosci 2015; 38:353-63. [PMID: 25939892 PMCID: PMC4461528 DOI: 10.1016/j.tins.2015.04.001] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Revised: 04/01/2015] [Accepted: 04/02/2015] [Indexed: 12/17/2022]
Abstract
Cardiac abnormalities are the most common birth defects. Derangement of circulatory flow affects many vital organs; without proper supply of oxygenated blood, the brain is particularly vulnerable. Although surgical interventions have greatly reduced mortality rates, patients often suffer an array of neurological deficits throughout life. Neuroimaging provides a macroscopic assessment of brain injury and has shown that white matter (WM) is at risk. Oligodendrocytes and myelinated axons have been identified as major targets of WM injury, but still little is known about how congenital heart anomalies affect the brain at the cellular level. Further integration of animal model studies and clinical research will define novel therapeutic targets and new standards of care to prevent developmental delay associated with cardiac abnormalities.
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Affiliation(s)
- Paul D Morton
- Center for Neuroscience Research and Children's National Heart Institute, Children's National Medical Center, Washington, DC 20010, USA
| | - Nobuyuki Ishibashi
- Center for Neuroscience Research and Children's National Heart Institute, Children's National Medical Center, Washington, DC 20010, USA
| | - Richard A Jonas
- Center for Neuroscience Research and Children's National Heart Institute, Children's National Medical Center, Washington, DC 20010, USA
| | - Vittorio Gallo
- Center for Neuroscience Research and Children's National Heart Institute, Children's National Medical Center, Washington, DC 20010, USA.
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Panigrahy A, Schmithorst VJ, Wisnowski JL, Watson CG, Bellinger DC, Newburger JW, Rivkin MJ. Relationship of white matter network topology and cognitive outcome in adolescents with d-transposition of the great arteries. NEUROIMAGE-CLINICAL 2015; 7:438-48. [PMID: 25685710 PMCID: PMC4318874 DOI: 10.1016/j.nicl.2015.01.013] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Revised: 12/25/2014] [Accepted: 01/23/2015] [Indexed: 12/16/2022]
Abstract
Patients with congenital heart disease (CHD) are at risk for neurocognitive impairments. Little is known about the impact of CHD on the organization of large-scale brain networks. We applied graph analysis techniques to diffusion tensor imaging (DTI) data obtained from 49 adolescents with dextro-transposition of the great arteries (d-TGA) repaired with the arterial switch operation in early infancy and 29 healthy referent adolescents. We examined whether differences in neurocognitive functioning were related to white matter network topology. We developed mediation models revealing the respective contributions of peri-operative variables and network topology on cognitive outcome. Adolescents with d-TGA had reduced global efficiency at a trend level (p = 0.061), increased modularity (p = 0.012), and increased small-worldness (p = 0.026) as compared to controls. Moreover, these network properties mediated neurocognitive differences between the d-TGA and referent adolescents across every domain assessed. Finally, structural network topology mediated the neuroprotective effect of longer duration of core cooling during reparative neonatal cardiac surgery, as well as the detrimental effects of prolonged hospitalization. Taken together, worse neurocognitive function in adolescents with d-TGA is mediated by global differences in white matter network topology, suggesting that disruption of this configuration of large-scale networks drives neurocognitive dysfunction. These data provide new insights into the interplay between perioperative factors, brain organization, and cognition in patients with complex CHD.
Network topology mediates neurocognitive outcomes in congenital heart disease. Network topology mediates the neuroprotective effect of hypothermia on cognition. Network topology mediates the effect of prolonged hospitalization on cognition.
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Affiliation(s)
- Ashok Panigrahy
- Department of Pediatric Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, CA, USA
- Department of Radiology and Bioinformatics, University of Pittsburgh, Pittsburgh, CA, USA
- Department of Radiology, Children's Hospital Los Angeles, CA, USA
- Brain and Creativity Institute, University of Southern California, CA, USA
- Correspondence to: Department of Pediatric Radiology, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Tel: +1 412 692 5510; fax: +1 412 864 8622.
| | - Vincent J. Schmithorst
- Department of Pediatric Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, CA, USA
| | - Jessica L. Wisnowski
- Department of Pediatric Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, CA, USA
- Department of Radiology, Children's Hospital Los Angeles, CA, USA
- Brain and Creativity Institute, University of Southern California, CA, USA
| | - Christopher G. Watson
- Department of Neurology, Boston Children's Hospital, Boston, MA, USA
- Graduate Program for Neuroscience, Boston University, Boston, MA, USA
| | | | - Jane W. Newburger
- Department of Cardiology, Boston Children's Hospital, Boston, MA, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - Michael J. Rivkin
- Department of Neurology, Boston Children's Hospital, Boston, MA, USA
- Department of Psychiatry, Boston Children's Hospital, Boston, MA, USA
- Department of Radiology, Boston Children's Hospital, Boston, MA, USA
- Department of Neurology, Harvard Medical School, Boston, MA, USA
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Neurodevelopment and behavior after transcatheter versus surgical closure of secundum type atrial septal defect. J Pediatr 2015; 166:31-8. [PMID: 25282067 DOI: 10.1016/j.jpeds.2014.08.039] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Revised: 06/19/2014] [Accepted: 08/20/2014] [Indexed: 02/01/2023]
Abstract
OBJECTIVE To assess the neuropsychological and behavioral profiles of school-aged children treated for atrial septal defect, secundum type (ASD-II) with open-heart surgery or catheterization. STUDY DESIGN Patients (n = 48; mean age, 9 years, 3 months) and a matched healthy group (mean age, 9 years, 2 months) were evaluated with a shortened intelligence scale (Wechsler Intelligence Scale for Children, third edition, Dutch version) and a developmental neuropsychological test battery (Developmental Neuropsychological Assessment, second edition, Dutch version). Parents completed behavioral checklists (Achenbach Child Behavior Checklist for Children aged 6-18). Hospitalization variables were retrieved from medical files for studying associations with long-term neurodevelopment. RESULTS Compared with the healthy matched controls, patients treated for ASD-II had significantly lower scores on subtasks underlying such Developmental Neuropsychological Assessment, second edition, Dutch version domains as Attention and Executive Functioning, Language, Working Memory, Sensorimotor Functioning, Social Cognition, and Visuospatial Information Processing. Only subtle differences, mainly in Visuospatial Information Processing, were found between the surgical repair and transcatheter repair groups. Socioeconomic status, longer hospital stay, and larger defect size were associated with neurocognitive outcome measures. Parents of patients reported more thought problems, posttraumatic stress problems, and lower school performance compared with parents of healthy peers. CONCLUSION After treatment for ASD-II, children display a range of neuropsychologic difficulties that may increase their risk for learning problems and academic underachievement. Differences related to treatment were not found. Our results suggest that neurodevelopmental and behavioral follow-up at school age is warranted in this group.
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Minimizing the risk of preoperative brain injury in neonates with aortic arch obstruction. J Pediatr 2014; 165:1116-1122.e3. [PMID: 25306190 PMCID: PMC4624274 DOI: 10.1016/j.jpeds.2014.08.066] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2013] [Revised: 06/19/2014] [Accepted: 08/28/2014] [Indexed: 12/28/2022]
Abstract
OBJECTIVE To determine whether prenatal diagnosis lowers the risk of preoperative brain injury by assessing differences in the incidence of preoperative brain injury across centers. STUDY DESIGN From 2 prospective cohorts of newborns with complex congenital heart disease studied by preoperative cerebral magnetic resonance imaging, one cohort from the University Medical Center Utrecht (UMCU) and a combined cohort from the University of California San Francisco (UCSF) and University of British Columbia (UBC), patients with aortic arch obstruction were selected and their imaging and clinical course reviewed. RESULTS Birth characteristics were comparable between UMCU (n = 33) and UCSF/UBC (n = 54). Patients had a hypoplastic aortic arch with either coarctation/interruption or hypoplastic left heart syndrome. In subjects with prenatal diagnosis, there was a significant difference in the prevalence of white matter injury (WMI) between centers (11 of 22 [50%] at UMCU vs 4 of 30 [13%] at UCSF/UBC; P < .01). Prenatal diagnosis was protective for WMI at UCSF/UBC (13% prenatal diagnoses vs 50% postnatal diagnoses; P < .01), but not at UMCU (50% vs 46%, respectively; P > .99). Differences in clinical practice between prenatally diagnosed subjects at UMCU vs UCSF/UBC included older age at surgery, less time spent in the intensive care unit, greater use of diuretics, less use of total parenteral nutrition (P < .01), and a greater incidence of infections (P = .01). In patients diagnosed postnatally, the prevalence of WMI was similar in the 2 centers (46% at UMCU vs 50% at UCSF/UBC; P > .99). Stroke prevalence was similar in the 2 centers regardless of prenatal diagnosis (prenatal diagnosis: 4.5% at Utrecht vs 6.7% at UCSF/UBC, P = .75; postnatal diagnosis: 9.1% vs 13%, respectively, P > .99). CONCLUSION Prenatal diagnosis can be protective for WMI, but this protection may be dependent on specific clinical management practices that differ across centers.
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Neurologic and psycho-intellectual outcome related to structural brain imaging in adolescents and young adults after neonatal arterial switch operation for transposition of the great arteries. J Thorac Cardiovasc Surg 2014; 148:2190-9. [DOI: 10.1016/j.jtcvs.2013.10.087] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Revised: 09/23/2013] [Accepted: 10/06/2013] [Indexed: 11/21/2022]
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Mulkey SB, Ou X, Ramakrishnaiah RH, Glasier CM, Swearingen CJ, Melguizo MS, Yap VL, Schmitz ML, Bhutta AT. White matter injury in newborns with congenital heart disease: a diffusion tensor imaging study. Pediatr Neurol 2014; 51:377-83. [PMID: 25160542 PMCID: PMC4147255 DOI: 10.1016/j.pediatrneurol.2014.04.008] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Revised: 04/04/2014] [Accepted: 04/05/2014] [Indexed: 11/28/2022]
Abstract
BACKGROUND Brain injury is observed on cranial magnetic resonance imaging preoperatively in up to 50% of newborns with congenital heart disease. Newer imaging techniques such as diffusion tensor imaging provide sensitive measures of the white matter integrity. The objective of this study was to evaluate the diffusion tensor imaging analysis technique of tract-based spatial statistics in newborns with congenital heart disease. METHODS Term newborns with congenital heart disease who would require surgery at less than 1 month of age were prospectively enrolled (n = 19). Infants underwent preoperative and postoperative brain magnetic resonance imaging with diffusion tensor imaging. Tract-based spatial statistics, an objective whole-brain diffusion tensor imaging analysis technique, was used to determine differences in white matter fractional anisotropy between infant groups. Term control infants were also compared with congenital heart disease infants. Postmenstrual age was equivalent between congenital heart disease infant groups and between congenital heart disease and control infants. RESULTS Ten infants had preoperative brain injury, either infarct or white matter injury, by conventional brain magnetic resonance imaging. The technique of tract-based spatial statistics showed significantly lower fractional anisotropy (P < 0.05, corrected) in multiple major white matter tracts in the infants with preoperative brain injury compared with infants without preoperative brain injury. Fractional anisotropy values increased in the white matter tracts from the preoperative to the postoperative brain magnetic resonance imaging correlating with brain maturation. Control infants had higher fractional anisotropy in multiple white matter tracts compared with infants with congenital heart disease. CONCLUSION Tract-based spatial statistics is a valuable diffusion tensor imaging analysis technique that may have better sensitivity in detecting white matter injury compared with conventional brain magnetic resonance imaging in term newborns with congenital heart disease.
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Affiliation(s)
- Sarah B. Mulkey
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Xiawei Ou
- Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | | | - Charles M. Glasier
- Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | | | - Maria S. Melguizo
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Vivien L. Yap
- Department of Pediatrics, New York Presbyterian Weill Cornell Medical College, New York, NY, USA
| | - Michael L. Schmitz
- Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Adnan T. Bhutta
- Department of Pediatrics, University of Maryland, Baltimore, MD, USA
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Gaynor JW, Kim DS, Arrington CB, Atz AM, Bellinger DC, Burt AA, Ghanayem NS, Jacobs JP, Lee TM, Lewis AB, Mahle WT, Marino BS, Miller SG, Newburger JW, Pizarro C, Ravishankar C, Santani AB, Wilder NS, Jarvik GP, Mital S, Russell MW. Validation of association of the apolipoprotein E ε2 allele with neurodevelopmental dysfunction after cardiac surgery in neonates and infants. J Thorac Cardiovasc Surg 2014; 148:2560-6. [PMID: 25282659 DOI: 10.1016/j.jtcvs.2014.07.052] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Revised: 06/27/2014] [Accepted: 07/12/2014] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Apolipoprotein E (APOE) genotype is a determinant of neurologic recovery after brain ischemia and traumatic brain injury. The APOE ε2 allele has been associated with worse neurodevelopmental (ND) outcome after repair of congenital heart defects (CHD) in infancy. Replication of this finding in an independent cohort is essential to validate the observed genotype-phenotype association. METHODS The association of APOE genotype with ND outcomes was assessed in a combined cohort of patients with single-ventricle CHD enrolled in the Single Ventricle Reconstruction and Infant Single Ventricle trials. ND outcome was assessed at 14 months using the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. Stepwise multivariable regression was performed to develop predictive models for PDI and MDI scores. RESULTS Complete data were available for 298 of 435 patients. After adjustment for preoperative and postoperative covariates, the APOE ε2 allele was associated with a lower PDI score (P = .038). Patients with the ε2 allele had a PDI score approximately 6 points lower than those without the risk allele, explaining 1.04% of overall PDI variance, because the ε2 allele was present in only 11% of the patients. There was a marginal effect of the ε2 allele on MDI scores (P = .058). CONCLUSIONS These data validate the association of the APOE ε2 allele with adverse early ND outcomes after cardiac surgery in infants, independent of patient and operative factors. Genetic variants that decrease neuroresilience and impair neuronal repair after brain injury are important risk factors for ND dysfunction after surgery for CHD.
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Affiliation(s)
- J William Gaynor
- Division of Cardiothoracic Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pa.
| | - Daniel Seung Kim
- Departments of Medicine (Division of Medical Genetics) and Genome Sciences, University of Washington School of Medicine, Seattle, Wash
| | | | - Andrew M Atz
- Division of Pediatric Cardiology, Medical University of South Carolina, Charleston, SC
| | - David C Bellinger
- Department of Neurology, Boston Children's Hospital, Boston, Mass, and Department of Neurology, Harvard Medical School, Boston, Mass
| | - Amber A Burt
- Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, Wash
| | - Nancy S Ghanayem
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis
| | - Jeffery P Jacobs
- Johns Hopkins Children's Heart Institute, All Children's Hospital and Florida Hospital for Children, St Petersburg, Fla
| | - Teresa M Lee
- Department of Pediatrics, Columbia University Medical Center, New York, NY
| | - Alan B Lewis
- Children's Hospital Los Angeles, Los Angeles, Calif
| | | | - Bradley S Marino
- Ann and Robert F. Lurie Children's Hospital of Chicago, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Stephen G Miller
- Division of Pediatric Oncology, Duke University Medical Center, Durham, NC
| | - Jane W Newburger
- Department of Cardiology, Boston Children's Hospital, Boston, Mass
| | - Christian Pizarro
- Nemours Cardiac Center, Alfred I. Dupont Hospital for Children, Wilmington, Del
| | - Chitra Ravishankar
- Division of Pediatric Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pa
| | - Avni B Santani
- Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pa
| | - Nicole S Wilder
- Department of Anesthesia, University of Michigan Medical School, Ann Arbor, Mich
| | - Gail P Jarvik
- Departments of Medicine (Division of Medical Genetics) and Genome Sciences, University of Washington School of Medicine, Seattle, Wash
| | - Seema Mital
- Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
| | - Mark W Russell
- Department of Pediatrics and Communicable Diseases (Division of Pediatric Cardiology), University of Michigan Medical School, Ann Arbor, Mich
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Oofuvong M, Geater AF, Chongsuvivatwong V, Chanchayanon T, Worachotekamjorn J, Sriyanaluk B, Saefung B, Nuanjun K. Comparison of intelligence, weight and height in children after general anesthesia with and without perioperative desaturation in non-cardiac surgery: a historical and concurrent follow-up study. SPRINGERPLUS 2014; 3:164. [PMID: 25674447 PMCID: PMC4320222 DOI: 10.1186/2193-1801-3-164] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2014] [Accepted: 03/21/2014] [Indexed: 11/10/2022]
Abstract
Purpose To determine whether perioperative desaturation (PD) in preschool children undergoing non-cardiac surgery is associated with subsequent impairment of intelligence or subsequent change in age-specific weight and height percentile. Method A historical-concurrent follow-up study was conducted in children aged ≤ 60 months who underwent general anesthesia (GA) for non-cardiac surgery between January 2008 and December 2011 at Songklanagarind Hospital. Children who developed PD (PD group) and children who did not develop perioperative respiratory events (no-PRE group) were matched on sex, age, year of having index GA, type of surgery and choice of anesthesia. The children’s age-specific weight and height percentile and intelligence quotient (IQ) scores by Standford Binet-LM or Wechsler Intelligence Scale for Children, 3rd edition 12–60 months after GA were compared using Student’s t- test and Wilcoxon’s rank sum test. Multivariate linear regression models for standardized IQ and multivariate mixed effects linear regression models for the change of age-specific weight and height percentile from the time of index GA to the time of IQ test were performed to identify independent predictors. The coefficients and 95% confidence intervals (CI) were displayed and considered significant if the F test p-values were < 0.05. Results Of 103 subjects in each group (PD vs no-PRE), there were no statistically significant differences in IQ (94.7 vs 98.3, p = 0.13), standardized IQ (−0.1 vs 0.1, p = 0.14) or age-specific weight percentile (38th vs 63th, p = 0.06). However, age-specific height percentile in the PD group at the time of IQ test was significantly lower (38th vs 50th, p = 0.02). In the multivariate analysis, PD was not a significant predictor for standardized IQ (coefficient: −0.06, 95% CI: −0.3, 0.19, p = 0.57), change in age-specific weight percentile (coefficient: 4.66, 95% CI: −2.63, 11.95, p = 0.21) or change in age-specific height percentile (coefficient: −1.65, 95% CI: −9.74, 6.44, p = 0.69) from the time of index GA to the time of IQ test after adjusting for family and anesthesia characteristics. Conclusion Our study could not demonstrate any serious effect of PD on subsequent intelligence or on the change in age-specific weight and height percentile of children after non-cardiac surgery. Electronic supplementary material The online version of this article (doi:10.1186/2193-1801-3-164) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Maliwan Oofuvong
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla, 90112 Thailand
| | - Alan Frederick Geater
- Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Songkhla, 90112 Thailand
| | | | - Thavat Chanchayanon
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla, 90112 Thailand
| | - Juthamas Worachotekamjorn
- Division of Child Development, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, 90112 Thailand
| | - Bussarin Sriyanaluk
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla, 90112 Thailand
| | - Boonthida Saefung
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla, 90112 Thailand
| | - Kanjana Nuanjun
- Department of Anesthesiology, Faculty of Medicine, Prince of Songkla University, Songkhla, 90112 Thailand
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Andropoulos DB, Ahmad HB, Haq T, Brady K, Stayer SA, Meador MR, Hunter JV, Rivera C, Voigt RG, Turcich M, He CQ, Shekerdemian LS, Dickerson HA, Fraser CD, McKenzie ED, Heinle JS, Easley RB. The association between brain injury, perioperative anesthetic exposure, and 12-month neurodevelopmental outcomes after neonatal cardiac surgery: a retrospective cohort study. Paediatr Anaesth 2014; 24:266-74. [PMID: 24467569 PMCID: PMC4152825 DOI: 10.1111/pan.12350] [Citation(s) in RCA: 140] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/17/2013] [Indexed: 12/22/2022]
Abstract
BACKGROUND Adverse neurodevelopmental outcomes are observed in up to 50% of infants after complex cardiac surgery. We sought to determine the association of perioperative anesthetic exposure with neurodevelopmental outcomes at age 12 months in neonates undergoing complex cardiac surgery and to determine the effect of brain injury determined by magnetic resonance imaging (MRI). METHODS Retrospective cohort study of neonates undergoing complex cardiac surgery who had preoperative and 7-day postoperative brain MRI and 12-month neurodevelopmental testing with Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Doses of volatile anesthetics (VAA), benzodiazepines, and opioids were determined during the first 12 months of life. RESULTS From a database of 97 infants, 59 met inclusion criteria. Mean ± sd composite standard scores were as follows: cognitive = 102.1 ± 13.3, language = 87.8 ± 12.5, and motor = 89.6 ± 14.1. After forward stepwise multivariable analysis, new postoperative MRI injury (P = 0.039) and higher VAA exposure (P = 0.028) were associated with lower cognitive scores. ICU length of stay (independent of brain injury) was associated with lower performance on all categories of the Bayley-III (P < 0.02). CONCLUSIONS After adjustment for multiple relevant covariates, we demonstrated an association between VAA exposure, brain injury, ICU length of stay, and lower neurodevelopmental outcome scores at 12 months of age. These findings support the need for further studies to identify potential modifiable factors in the perioperative care of neonates with CHD to improve neurodevelopmental outcomes.
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Affiliation(s)
- Dean B. Andropoulos
- Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA,Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA,Pediatric Cardiovascular Anesthesiology, Texas Children’s Hospital, Houston, TX, USA
| | - Hasan B. Ahmad
- Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA,Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA,Edward Via College of Osteopathic Medicine, Blacksburg, VA, USA
| | - Taha Haq
- Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA,Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Ken Brady
- Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA,Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA,Pediatric Cardiovascular Anesthesiology, Texas Children’s Hospital, Houston, TX, USA
| | - Stephen A. Stayer
- Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA,Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA,Pediatric Cardiovascular Anesthesiology, Texas Children’s Hospital, Houston, TX, USA
| | - Marcie R. Meador
- Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA,Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA,Pediatric Cardiovascular Anesthesiology, Texas Children’s Hospital, Houston, TX, USA
| | - Jill V. Hunter
- Department of Radiology, Baylor College of Medicine, Houston, TX, USA,Pediatric Neuroradiology, Texas Children’s Hospital, Houston, TX, USA
| | - Carlos Rivera
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA,Pediatric Neurology, Texas Children’s Hospital, Houston, TX, USA
| | - Robert G. Voigt
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA,Developmental Pediatrics, Texas Children’s Hospital, Houston, TX, USA
| | - Marie Turcich
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA,Developmental Pediatrics, Texas Children’s Hospital, Houston, TX, USA
| | - Cathy Q. He
- Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA,Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - Lara S. Shekerdemian
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA,Pediatric Critical Care, Texas Children’s Hospital, Houston, TX, USA
| | - Heather A. Dickerson
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA,Pediatric Cardiology, Texas Children’s Hospital, Houston, TX, USA
| | - Charles D. Fraser
- Department of Surgery, Baylor College of Medicine, Houston, TX, USA,Congenital Heart Surgery, Texas Children’s Hospital, Houston, TX, USA
| | - E. Dean McKenzie
- Department of Surgery, Baylor College of Medicine, Houston, TX, USA,Congenital Heart Surgery, Texas Children’s Hospital, Houston, TX, USA
| | - Jeffrey S. Heinle
- Department of Surgery, Baylor College of Medicine, Houston, TX, USA,Congenital Heart Surgery, Texas Children’s Hospital, Houston, TX, USA
| | - R. Blaine Easley
- Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA,Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA,Pediatric Cardiovascular Anesthesiology, Texas Children’s Hospital, Houston, TX, USA
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Mussatto KA, Hoffmann RG, Hoffman GM, Tweddell JS, Bear L, Cao Y, Brosig C. Risk and prevalence of developmental delay in young children with congenital heart disease. Pediatrics 2014; 133:e570-7. [PMID: 24488746 PMCID: PMC3934337 DOI: 10.1542/peds.2013-2309] [Citation(s) in RCA: 174] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND AND OBJECTIVE Children with congenital heart disease (CHD) are at risk for developmental delay (DD). Changes in cognitive, language, and motor skills in early childhood have not been described. We report the results of a structured approach using longitudinal testing to identify problems and ensure early intervention in accordance with published guidelines. METHODS Bayley Scales of Infant Development, Third Edition, were used to assess cognitive, language, and motor skills in 99 children with CHD. Subjects were evaluated 3 to 6 times in the first 3 years of life. DD was defined as scores >1 SD below the population mean. RESULTS Cardiac anatomy was single ventricle (1V) in 34 subjects and 2 ventricles (2V) in 65. Medical comorbidities were present in 21% and genetic syndromes in 19%. Most subjects (75%) had DD in ≥1 area at ≥1 assessments. Subjects with 1V anatomy had equivalent outcomes to those with 2V. Cognitive and language scores declined in subjects with genetic syndromes but were stable and within the average range for subjects with 1V and 2V. Motor scores improved for subjects with 1V and 2V but remained low for those with genetic syndromes. In addition to age, need for supplemental tube feeding, longer cardiopulmonary bypass time, and shorter time since last hospitalization were significant predictors of developmental outcomes. CONCLUSIONS DDs in young children with CHD are both common and dynamic. Providers should encourage longitudinal surveillance for children with CHD because exposure to risk and prevalence of DD change over time.
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Affiliation(s)
- Kathleen A. Mussatto
- Herma Heart Center, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin; and,Medical College of Wisconsin, Milwaukee, Wisconsin
| | | | - George M. Hoffman
- Herma Heart Center, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin; and,Medical College of Wisconsin, Milwaukee, Wisconsin
| | - James S. Tweddell
- Herma Heart Center, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin; and,Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Laurel Bear
- Herma Heart Center, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin; and,Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Yumei Cao
- Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Cheryl Brosig
- Herma Heart Center, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin; and,Medical College of Wisconsin, Milwaukee, Wisconsin
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50
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Zampi JD, Hirsch-Romano JC, Goldstein BH, Shaya JA, Armstrong AK. Hybrid approach for pulmonary atresia with intact ventricular septum: Early single center results and comparison to the standard surgical approach. Catheter Cardiovasc Interv 2014; 83:753-61. [DOI: 10.1002/ccd.25181] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Revised: 08/06/2013] [Accepted: 08/25/2013] [Indexed: 12/26/2022]
Affiliation(s)
- Jeffrey D. Zampi
- Division of Pediatric Cardiology; Department of Pediatrics; University of Michigan; Ann Arbor Michigan
| | - Jennifer C. Hirsch-Romano
- Division of Pediatric Cardiac Surgery; Department of Surgery; University of Michigan; Ann Arbor Michigan
| | - Bryan H. Goldstein
- The Heart Institute; Cincinnati Children's Hospital Medical Center; Cincinnati Ohio
| | | | - Aimee K. Armstrong
- Division of Pediatric Cardiology; Department of Pediatrics; University of Michigan; Ann Arbor Michigan
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