Clinical trial NCT05462301: Normal Reference Range for Neonatal Echocardiography
Official title: Normal Reference Range for Neonatal Echocardiography: a Multi-center, Prospective Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Echocardiography
Keywords: Neonatal Echocardiogram
Reference Ranges
Preterm Infants
Lead sponsor: Children's Hospital of Chongqing Medical University
Sponsor class: OTHER
Collaborators: name: Shanxi Provincial Maternity and Children's Hospital
name: Inner Mongolia Maternal and Child Health Care Hospital
name: Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
name: Ningxia Medical University
First posted: 2022-07-18
Enrollment: 1500
Sex: ALL
Minimum age (years): 1
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: healthy neonates and preterm Infants

Brief summary: Echocardiography is the main method of bedside examination of neonatal cardiac morphology, which can timely diagnose congenital heart disease and quantitatively assess its severity, but the diagnosis and evaluation process depends on the normal range of neonatal echocardiography.At present, there have been normal reference standards for echocardiography in children and adults at home and abroad, but there is no uniform standard for echocardiographic parameters in newborns, especially premature infants.This study intends to carry out a national multicenter, prospective, observational study to establish the reference range of echocardiography at different time periods after birth in newborns, and stratified according to gestational age, birth weight and gender, to conduct a more accurate hemodynamic assessment of clinically critically ill newborns and guide the treatment of critically ill newborns in real time.

Detailed description: Neonatal goal-directed echocardiography (TNE) performed by neonatologists has been increasingly applied to hemodynamic assessment in the NICU to guide critical neonatal treatment in real time. There are many detection indexes of TNE, which are closely related to neonatal weight, birth weight, postnatal age, race and other factors. Therefore, establishing neonatal echocardiographic reference ranges is essential for the development of TNE. At present, there have been normal reference standards for echocardiography in children and adults at home and abroad, but there is no uniform standard for echocardiographic parameters in newborns, especially premature infants. At present, there are many problems in establishing the reference range of neonatal echocardiography internationally, including the small sample size included in establishing the reference range, no premature infant standard for some parameters, the reference range is not stratified according to gender, etc. Moreover, the majority of current echocardiographic reference ranges are derived from studies in European and American populations and are not applicable to Asian patients. So far, reference ranges for neonatal echocardiography established based on high-quality clinical studies are still lacking, greatly affecting the use of echocardiography in neonatal intensive care units. Therefore, this study intends to carry out a national multicenter, prospective, observational study to establish the reference range of echocardiography at different time periods after birth in neonates, and stratify according to creatinine, birth weight and gender, providing a reference for the application of echocardiography in neonatal intensive care units, and providing an important basis for the development of TNE-centered neonatal hemodynamic comprehensive assessment program in the NICU.

1. Study Design and Process:

   This study is a multicenter, prospective, observational study. Neonatal bedside echocardiography was performed by a trained neonatology clinician or sonographer. Five time points were selected for neonatal echocardiography, namely, 1 day, 3 days, 7 days, 14 days, and 28 days after birth. The examination was completed in the quiet state of the newborn, and the measurement method was based on the American Guidelines and Standards for Echocardiography in Children and the American NICU Echocardiography Practice Guidelines. All ultrasound data were averaged over three or more cardiac cycles.
2. Sample Size Calculation:

   Each participating NICU will be required to enroll 300 infants (60 infants for each PNA timepoint) for a final sample size of 1500 "normal infants".
3. Statistical Methods:

   Data statistics were performed using SPSS 21.0 software. The data obtained for each of the ultrasound hemodynamic parameters were tested for normality. The measurement data conforming to normal distribution are expressed by mean ± standard deviation, and the measurement data with non-normal distribution are expressed by median (interquartile range). Spearman correlation analysis was used to compare the correlation between different indicators and postnatal, birth weight, birth weight and gender. The echocardiographic reference range of newborns at different time periods after birth was established by 95% confidence interval and stratified according to birth weight, birth weight and gender. P \< 0.05 was considered statistically significant.
4. Quality control:

At the beginning of the study, a cooperative group kick-off meeting will be organized to interpret the study protocol in detail. In addition, the online or offline training of the participating units will be carried out to further unify the parameter setting and data collection criteria of the ultrasound machine. Establish a WeChat group to answer questions related to this study at any time. During the process of the project, regular contact meetings within the cooperative group will be held to ensure that the investigators participating in the study will implement the protocol. During the study, the study site will assign a special person to review the completeness and correctness of the data submitted by each participating site.

Eligibility criteria: Inclusion Criteria:

* Outpatient or inpatient neonate
* Gestational age \> 30weeks and birthweight \> 1250 grams
* Appropriate for gestational age
* Without perinatal asphyxia
* Without skin lesion on the left chest wall
* with family informed consent for neonatal echocardiography

Exclusion Criteria:

* specialist cardiac ultrasound suggests congenital heart disease;
* PDA with hemodynamic abnormalities, defined as: PDA \> 1.5 mm (left-to-right shunt) and left atrial diameter/aortic root \> 1.5 or the need for the use of inotropes;
* invasive mechanical ventilation therapy,
* non-invasive mechanical ventilation with FiO2 \>0.3
* major anomalies
* blood culture-proven neonatal sepsis
* persistent pulmonary hypertension
* renal failure
* necrotizing enterocolitis ≥ stage II
* post surgery
* Maternal history of severe anemia, or prenatal massive bleeding

Primary outcomes:
measure: Changes in left atrial anteroposterior diameter with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
measure: Changes in interventricular septum thickness with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
measure: Changes in left ventricular posterior wall thickness at end diastole with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
measure: Changes in left ventricular end diastolic diameter with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
measure: Changes in left ventricular end systolic diameter with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
measure: Changes in right ventricular anteroposterior diameter at end diastole with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
measure: Changes in right ventricular outflow tract diameter with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
measure: Changes in left ventricular ejection fraction with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
Secondary outcomes:
measure: Changes in left ventricular outflow tract diameter with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
measure: Changes in main pulmonary artery diameter with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
measure: Changes in Inferior vena cava diameter with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
measure: Changes in Simpson 's method for measuring ejection fraction with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
Other outcomes:
measure: Changes in Aortic Velocity Time Integral（VTI）with increasing age
timeFrame: 5 time points (1 day, 3 days, 7 days, 14 days and 28 days after birth)
Locations:
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
state: Chongqing
Study officials:
affiliation: Children's Hospital of Chongqing Medical University
name: Wang Jianhui, Doctor
role: STUDY_DIRECTOR
References:
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citation: Kluckow M, Evans N. Superior vena cava flow in newborn infants: a novel marker of systemic blood flow. Arch Dis Child Fetal Neonatal Ed. 2000 May;82(3):F182-7. doi: 10.1136/fn.82.3.f182.
citation: Schmitz L, Stiller B, Pees C, Koch H, Xanthopoulos A, Lange P. Doppler-derived parameters of diastolic left ventricular function in preterm infants with a birth weight <1500 g: reference values and differences to term infants. Early Hum Dev. 2004 Feb;76(2):101-14. doi: 10.1016/j.earlhumdev.2003.11.003.
citation: Cosyns B, Lancellotti P. Normal reference values for echocardiography: a call for comparison between ethnicities. Eur Heart J Cardiovasc Imaging. 2016 May;17(5):523-4. doi: 10.1093/ehjci/jev353. Epub 2016 Mar 13. No abstract available.