Objective:Lung ultrasound (LUS) has been used in the diagnosis of neonatal respiratory distress syndrome(RDS) successfully, but there have been no multicenter prospective studies to verify its reliability or determine how to grade RDS with LUS findings.This study aimed to discuss the necessity and feasibility of using LUS findings to determine RDS grades through a multicenter prospective study.Methods:Every researcher participated in the National Neonatal Lung Ultrasound Training Course and receiving 3-6 months of lung ultrasound system training at the National Neonatal Lung Ultrasound Training Center.Patients between June 2018 and May 2020 who met the RDS ultrasound diagnostic criteria and had full available clinical data were included in this study.The LUS examination was completed immediately after the patients were admitted to the hospital.Some of them also underwent chest X-ray examination.Arterial blood gas analysis was completed immediately before or after the LUS ultrasound examination.RDS grading was performed according to the LUS findings and whether the patient had serious complications.Results:A total of 275 qualifying cases were included in this study, which included 220 premature infants and 55 full-term infants, and the primary RDS occurred in 117 cases (42.5%), and secondary RDS occurred in 158 cases (57.5%). LUS manifestations of RDS patients can be divided into three categories: (1)A ground-glass opacity sign: which could be found among 50 infants when they were admitted to the hospital (that was, at their first LUS examination). Twenty-eight of these infants were considered to have wet lungs and were not sent for special management on admission, but LUS showed typical snowflake-like lung consolidation within 0.5 to 4 hours.Twenty-two of them were given mechanical ventilation with exogenous pulmonary surfactant; Eighteen cases were controlled within 6-12 hours, but the lung lesions became more severe in the other 4 infants (due to severe intrauterine infection). (2)Snowflake-like lung consolidations: the first LUS on admission showed typical snowflake-like lung consolidation involving areas ranging from 1-2 intercostal spaces to 12 lung divisions in 204 cases.Thirty-eight infants among them the lung consolidation only had involvement of 1-2 intercostal spaces at the time of admission; Fifteen of them received invasive respiratory support and recovered within 4-12 hours.Twelve patients received noninvasive respiratory support; Seven of them recovered, while five cases developed severe lung illness.The remaining 11 patients who were not given any form of ventilator support developed severe conditions within 1-4 hours.Thirty of them showed snowflake signs involving 12 lung regions at admission.The remaining 136 patients had lung consolidation degree between the two degree above condition.(3)Snowflake-like sign with complications: Twenty-one patients had severe complications such as pneumothorax, pulmonary hemorrhage or/and persistent pulmonary hypertension of the newborn or large area atelectasis, etc, although snowflake lung consolidation did not involve all lung regions.Conclusion:(1) LUS is reliable and accurate for diagnosing RDS.RDS has the same characteristics on ultrasound for both preterm and full-term infants, both primary and secondary RDS.(2) To facilitate the management of RDS, it is necessary to classify RDS according to the ultrasound findings and the presence of severe complications.(3) Based on the results of this study, it is recommended that RDS can be divided into mild, moderate and severe degrees.The exact standards for grading are as follows: Mild RDS: the early stage of RDS, in which lung consolidation shows as a ground-glass opacity sign on ultrasound; Moderate RDS: lung consolidation shows a snowflake sign on ultrasound, not all of the lung fields are involved; Severe RDS meets one or more of the following criteria: lung consolidation shows as a snowflake sign on ultrasound and all lung regions are involved, or regardless of its degree and extent, lung consolidation has caused serious complications, such as pulmonary hemorrhage, pneumothorax, persistent pulmonary hypertension of the newborn, or/and a large area of pulmonary atelectasis.