Clinical trial NCT03629093: Neurodevelopment of Infants Exposed to General Anesthesia: a Multi-center Investigation
Official title: General Anesthesia Exposed Infants Neurodevelopment Investigation: a Multi-center Prospective Cohort Study United in Shanghai
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: General Anesthetics Toxicity
Neurodevelopment
Infant
Keywords: General anesthesia
Infant
Neurodevelopment
Postoperative
the Gesell Developmental Inventory
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Children's Medical Center
name: Children's Hospital of Fudan University
name: Shanghai Children's Hospital
name: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
First posted: 2018-08-14
Enrollment: 1000
Sex: ALL
Minimum age (years): 4
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Eligible infants scheduled for elective surgeries under general anesthesia will be recruited in six medical centers in Shanghai, China. The medical centers include Huashan Hospital Fudan University, Shanghai Children's Medical Center, Children's Hospital of Fudan University, Children's Hospital of Shanghai, Shanghai Tenth People's Hospital, and Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University.

Brief summary: Numerous preclinical evidence has confirmed that most commonly-used general anesthetics can affect neurodevelopment of young animals adversely, causing both structural defect of brain and cognitive impairment. However, it is unclear at present whether such effect would also occur to children exposed to general anesthesia in their early life. Several observational clinical studies and one interventional clinical trial indicated that short-time general anesthesia less than 80 minutes might be safe to cognitive development. Concerning long-time and/or multiple anesthesia exposure, some studies supported its association with long-term cognitive defects, while other studies did not. These studies are mainly retrospective or ambirectional researches. We have designed a prospective, multicenter cohort study to examine the neurodevelopment of infants exposed to anesthesia before age 2 in the first year after surgery, and compare the neurodevelopment status of infants exposed to anesthesia less than 3 hours and those more than 3 hours. The Gesell Developmental Inventory (GDI) and several neuropsychological testing batteries will be used. The anticipated outcome of the study will add reliable evidence from Asians to elucidate the relationship of anesthesia and long-term neurodevelopment of infants.


Eligibility criteria: Inclusion Criteria:

* Apgar score ≥ 8 at birth
* ASA level Ⅰ\~Ⅲ
* Obtained written consent form from the infants' parents or guardians

Exclusion Criteria:

* Postmenstrual age ≤ 44 weeks, or postmenstrual age ≥ 144 weeks
* Severe cardiac, pulmonary, or neurologic disease
* Severe obstructive sleep apnea hypopnea syndrome
* History of dystocia and/or hypoxic ischemic encephalopathy
* Gestational age at birth ≤32 weeks
* Any known or suspected chromosomal abnormalities, abnormal development of vision or hearing, neurodevelopment retardation, or other known acquired or congenital abnormalities that might affect neurodevelopment
* Significant cardiovascular surgery, significant ENT surgery, or neurosurgery
* Malignant diseases that may reduce survival
* Taking part in other clinical trials in the last 3 months or at present

Primary outcomes:
measure: Change of the developmental quotient of the Gesell Developmental Inventory
timeFrame: From baseline before anesthesia to 1 year after anesthesia
Secondary outcomes:
measure: Change of the standardized score of the five domains of the Gesell Developmental Inventory
timeFrame: From baseline before anesthesia to 1 year after anesthesia
measure: Change of the standardized score of the Social Maturity Scale
timeFrame: From baseline before anesthesia to 1 year after anesthesia
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital Fudan University
state: Shanghai
Study officials:
affiliation: Huashan Hospital
name: Ying-Wei Wang, M.D., Ph.D.
role: STUDY_DIRECTOR
References:
citation: Davidson AJ, Disma N, de Graaff JC, Withington DE, Dorris L, Bell G, Stargatt R, Bellinger DC, Schuster T, Arnup SJ, Hardy P, Hunt RW, Takagi MJ, Giribaldi G, Hartmann PL, Salvo I, Morton NS, von Ungern Sternberg BS, Locatelli BG, Wilton N, Lynn A, Thomas JJ, Polaner D, Bagshaw O, Szmuk P, Absalom AR, Frawley G, Berde C, Ormond GD, Marmor J, McCann ME; GAS consortium. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet. 2016 Jan 16;387(10015):239-50. doi: 10.1016/S0140-6736(15)00608-X. Epub 2015 Nov 4.
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citation: Sun LS, Li G, Miller TL, Salorio C, Byrne MW, Bellinger DC, Ing C, Park R, Radcliffe J, Hays SR, DiMaggio CJ, Cooper TJ, Rauh V, Maxwell LG, Youn A, McGowan FX. Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood. JAMA. 2016 Jun 7;315(21):2312-20. doi: 10.1001/jama.2016.6967.
citation: Warner DO, Zaccariello MJ, Katusic SK, Schroeder DR, Hanson AC, Schulte PJ, Buenvenida SL, Gleich SJ, Wilder RT, Sprung J, Hu D, Voigt RG, Paule MG, Chelonis JJ, Flick RP. Neuropsychological and Behavioral Outcomes after Exposure of Young Children to Procedures Requiring General Anesthesia: The Mayo Anesthesia Safety in Kids (MASK) Study. Anesthesiology. 2018 Jul;129(1):89-105. doi: 10.1097/ALN.0000000000002232.