TY - JOUR
T1 - Early Neurodevelopmental Outcomes Following Exposure to General Anesthesia in Infancy
T2 - EGAIN, a Prospective Cohort Study
AU - Bong, Choon Looi
AU - Ho, Duncun
AU - Allen, John Carson
AU - Lim, Gillian Si-Min
AU - Tan, Hong-Kuang
AU - Broekman, Birit F P
AU - Fabila, Teddy
AU - Reddy, Satish
AU - Koh, Woon-Puay
AU - Swee-Kim Tan, Josephine
AU - Meaney, Michael
AU - Rifkin-Graboi, Anne
N1 - Funding Information: The authors thank the Estate of Tan Sri Khoo Teck Puat and SingHealth Foundation for funding support; the National University of Singapore; all staff in the Neurodevelopment Research Unit, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*Star), for their support in conducting the neurodevelopmental follow-up; the Departments of Pediatric Anesthesia and Pediatric Surgery at KK Women’s and Children’s Hospital for their support in patient recruitment; Ms Michelle Ren and Ms Siti Nur Diyanah and for their administrative assistance; and the GUSTO Study group for their collaboration. The GUSTO study group includes Allan Sheppard, Amutha Chinnadurai, Anne Eng Neo Goh, Anne Rifkin-Graboi, Anqi Qiu, Arijit Biswas, Bee Wah Lee, Birit F.P. Broekman, Boon Long Quah, Borys Shuter, Chai Kiat Chng, Cheryl Ngo, Choon Looi Bong, Christiani Jeyakumar Henry, Cornelia Yin Ing Chee, Yam Thiam Daniel Goh, Doris Fok, Fabian Yap, George Seow Heong Yeo, Helen Chen, Hugo P S van Bever, Iliana Magiati, Inez Bik Yun Wong, Ivy Yee-Man Lau, Jeevesh Kapur, Jenny L. Richmond, Jerry Kok Yen Chan, Joanna D. Holbrook, Joshua J. Gooley, Keith M. Godfrey, Kenneth Kwek, Kok Hian Tan, Krishnamoorthy Niduvaje, Leher Singh, Lin Su, Lourdes Mary Daniel, Lynette P Shek, Marielle V. Fortier, Mark Hanson, Mary Foong-Fong Chong, Mary Rauff, Mei Chien Chua, Michael Meaney, Mya Thway Tint, Neerja Karnani, Ngee Lek, Oon Hoe Teoh, P. C. Wong, Peter D. Gluckman, Pratibha Agarwal, Rob M. van Dam, Salome A. Rebello, Seang-Mei Saw, Shang Chee Chong, Shirong Cai, Shu-E Soh, Sok Bee Lim, Chin-Ying Stephen Hsu, Victor Samuel Rajadurai, Walter Stunkel, Wee Meng Han, Wei Pang, Yap-Seng Chong, Yin Bun Cheung, Yiong Huak Chan, and Yung Seng Lee. Funding Information: This study is sponsored by the Estate of Tan Sri Khoo Teck Puat and Singhealth Foundation, as well as supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC), Singapore-NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A∗STAR), Singapore. Funding Information: This study is sponsored by the Estate of Tan Sri Khoo Teck Puat and Singhealth Foundation, as well as supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore—NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. Publisher Copyright: Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2023/10/1
Y1 - 2023/10/1
N2 - BACKGROUND: General anesthesia (GA) is known to worsen neural outcomes in animals, but human research assessing early-life GA exposure and neurodevelopment show inconsistent findings. We investigated the effects of a single GA exposure for minor surgery on the neurodevelopment of healthy children at multiple time-points, using clinical assessments along with behavioral and neurophysiological measures rarely used in human research.METHODS: GA-exposed children were a prospective cohort of 250 full-term, healthy infants who underwent GA for minor surgery before 15 months. Nonexposed children were from a separate cohort of similar age, sex, ethnicity, and maternal education. In both cohorts, clinical measures (Bayley Scales of Infant and Toddler Development-III [BSID-III] and Child Behavior Checklist [CBCL1½-5]) were assessed at 24 months, and experimental tests (memory and attentional) and neurophysiology (event-related potentials) at 6 and 18 months.RESULTS: At 24 months, there were no differences between GA-exposed and nonexposed children in the cognitive, language, motor, and socioemotional domains of the BSDI-III; however, GA-exposed children had poorer parental-reported scores in BSID-III general adaptability (94.2 vs. 99.0 [mean difference, 4.77; 97.3% confidence interval, -9.29, -0.24]; P=0.020) and poorer internalizing behavior scores on CBCL1½-5 (52.8 vs. 49.4 [mean difference, 3.35; 97.3% confidence interval, 0.15-6.55]; P=0.021). For experimental measures, GA-exposed children showed differences in 4 tests at 6 and 18 months.CONCLUSIONS: GA-exposed children did not differ from unexposed children in cognitive, language or motor outcomes at 24 months, but exhibited poorer parent-reported behavior scores. Differences in infant behavior and neurophysiology were detected at 6 and 18 months. Neurophysiological assessments may complement clinically relevant assessments to provide greater insights into neurodevelopment following early GA exposure.
AB - BACKGROUND: General anesthesia (GA) is known to worsen neural outcomes in animals, but human research assessing early-life GA exposure and neurodevelopment show inconsistent findings. We investigated the effects of a single GA exposure for minor surgery on the neurodevelopment of healthy children at multiple time-points, using clinical assessments along with behavioral and neurophysiological measures rarely used in human research.METHODS: GA-exposed children were a prospective cohort of 250 full-term, healthy infants who underwent GA for minor surgery before 15 months. Nonexposed children were from a separate cohort of similar age, sex, ethnicity, and maternal education. In both cohorts, clinical measures (Bayley Scales of Infant and Toddler Development-III [BSID-III] and Child Behavior Checklist [CBCL1½-5]) were assessed at 24 months, and experimental tests (memory and attentional) and neurophysiology (event-related potentials) at 6 and 18 months.RESULTS: At 24 months, there were no differences between GA-exposed and nonexposed children in the cognitive, language, motor, and socioemotional domains of the BSDI-III; however, GA-exposed children had poorer parental-reported scores in BSID-III general adaptability (94.2 vs. 99.0 [mean difference, 4.77; 97.3% confidence interval, -9.29, -0.24]; P=0.020) and poorer internalizing behavior scores on CBCL1½-5 (52.8 vs. 49.4 [mean difference, 3.35; 97.3% confidence interval, 0.15-6.55]; P=0.021). For experimental measures, GA-exposed children showed differences in 4 tests at 6 and 18 months.CONCLUSIONS: GA-exposed children did not differ from unexposed children in cognitive, language or motor outcomes at 24 months, but exhibited poorer parent-reported behavior scores. Differences in infant behavior and neurophysiology were detected at 6 and 18 months. Neurophysiological assessments may complement clinically relevant assessments to provide greater insights into neurodevelopment following early GA exposure.
KW - event-related potentials
KW - general anesthesia
KW - infant neurodevelopment
KW - neurodevelopment
UR - http://www.scopus.com/inward/record.url?scp=85144082356&partnerID=8YFLogxK
U2 - https://doi.org/10.1097/ANA.0000000000000857
DO - https://doi.org/10.1097/ANA.0000000000000857
M3 - Article
C2 - 35613046
SN - 0898-4921
VL - 35
SP - 394
EP - 405
JO - Journal of Neurosurgical Anesthesiology
JF - Journal of Neurosurgical Anesthesiology
IS - 4
ER -