We demonstrated a high level of diagnostic accuracy using quantitative LUS scores for predicting the respiratory support needs of newborns with transient tachypnea. An LUS can be used to accurately predict the different respiratory support needed. The higher the score, the more powerful the support needed. These results were not influenced by the GA within the age range of the enrolled population.
Transient tachypnea of the newborn (TTN) is the frequent cause of respiratory distress syndrome in premature newborns. In recent decades, the preterm birth rate has increased, mostly due to a rise in late preterm births (
17). A recent study showed that more than half of infants with TTN required respiratory support (
18). Non-invasive or mechanical ventilation respiratory support may be administered to reduce respiratory distress during TTN. In addition, respiratory support might improve the clearance of lung liquid, reducing the effort required to breathe and therefore reducing respiratory distress (
1). The meta-analysis showed insufficient evidence to establish the benefits and harms of noninvasive respiratory support in the management of newborn transient tachypnea. Continuous positive airway pressure (CPAP) remains the most noninvasive respiratory support in the NICU. In a meta-analysis including preterm infants requiring respiratory support, NIPPV proved to be more efficient than CPAP for reducing the need for intubation (
19). As a result, an increasing number of doctors in our NICU favored NIPPV instead of CPAP in infants with respiratory distress. Therefore, we did include infants with CPAP respiratory support due to the limited utilization.
Ultrasonography is a safe, inexpensive and accurate diagnostic tool. It provides real-time, quick and minimally invasive information without significant biological hazards. Lung ultrasonography (LUS) has been successfully used to diagnose neonatal disease. A previous study showed that the sensitivity and specificity of LUS for the diagnosis of TTN were 76.7% and 100%, respectively. After transfer to the NICU, this intervention can be conducted, distinguishing it from other critical lung diseases and facilitating proper initial treatment. LUS has already become a point-care tool for identifying respiratory illness and providing intervention guides. However, these descriptive findings are more qualitative in content. In recent years, lung ultrasound has been widely used to diagnose neonatal lung diseases. B lines can reflect the degree of pulmonary interstitial edema, but the utility of lung ultrasound scores by counting the number of B-lines in the assessment of severity is controversial. Min Zhao proposed using the neonatal LUS score to predict extravascular lung water, and the results showed that the lung ultrasound score can semiquantitatively evaluate the extravascular lung water content (
20).
The early-preterm neonate may suffer from various respiratory disorders due to different degrees of surfactant insufficiency. With the current study, this population was excluded because an LUS is more useful in infants (even late-preterm infants) than in more mature neonates > 37 weeks’ GA. This is likely because of the homogeneity of the preterm population, which is predominantly affected by TTPN. Infants with RDS or pneumonia were excluded from our study. Our aim was to verify whether an LUS was accurate enough for predicting in the higher GAs.
According to the previous LUS scoring systems, there are two methods of zoning, one that uses 12 zones and one that uses 6 zones. The 12-zone score was selected for this study. First, the infants in this study were late preterm babies, so the body surface area was limited. Second, previous studies revealed that the upper and lower areas showed different LUS phenomena in TTN (
21). Each side of the lung was divided into three areas (anterior, lateral and posterior), and every area was also divided into upper and lower sections. Therefore, 12 zones were recorded. Each area was assigned a score ranging from 0 to 3 (0 = normal lung pattern with A line, lung sliding and less than three B lines, 3= extended consolidations, with poor lung aeration) (
7). However, this LUS scoring system was used to assess lung aeration in neonates with RDS or bronchopulmonary dysplasia, so the authors did not assess posterior lung zones (
22). Unlike diffuse inflammatory lung diseases, such as MAS or BPD, neonates with TTN always showed increases in their extravascular lung water content. The LUS scan excluded lung consolidation, so the previous lung scoring system was not useful in the assessment of TTN. We modified the previous LUS scoring systems because confluent B-lines and compact B-lines are commonly observed in infants with diffuse alveolar edema, and consolidation was not observed. In another previous study, the posterior zone was never scanned by the LUS protocol because the population was almost all early-preterm infants (
20). In this study, the posterior zone was also scanned, providing more information about LUS scores.
In this prospective study, every lung area was scanned to assess the TTN severity of infants during NICU admission using quantitative LUS scores. Several LUS findings were utilized in the diagnosis of TTN in our study, such as confluent B-line, double lung point, compact B-line and white lung (
7). Our study shows that LUS scores are correlated with severe conditions of TTN. Neonates with higher LUS scores required more advanced respiratory support. Li et al. (
6) revealed that the LUS score after birth decreased with respiratory support. In comparison with the neonates in the control group, the LUS score of the TTN group was significantly higher. Our study showed that affected neonates with higher scores always developed respiratory distress due to the accumulation of fluid in the lungs and needed assisted respiratory support. It also displayed an early positive correlation between LUS scores and PaCO
2 of the ABG results and a negative correlation between PaO
2, SaO
2 and the scores; however, the correlation was not significant because the sample size was not adequate. Our study indicated that infants with higher LUS scores experienced severe TTN and needed appropriate respiratory support. If the scores drastically increased, mechanical ventilation should probably be provided. Another study showed that LUS scores had a greater decrease after birth in the infants that needed TTN in comparison with the control group. In infants with TTN, the scores were significantly associated with the respiratory severity scores (RSSs) (
6). In another study, quantitative ultrasound texture analysis of the fetal lung was conducted. It could predict neonatal respiratory morbidity in preterm infants, the accuracy of which was almost 86.5%. Furthermore, its positive and negative likelihood ratios were 6.5 and 0.3, respectively (
23).
TTN is a neonatal disease related to multiple risk factors, and it is mainly attributed to fluid clearance failure and epithelial Na+ channel abnormalities (
1). Some infants with hypoxemia and respiratory failure have increased the need for ventilation support in the NICU (
18). Several studies were conducted to identify some clues that may help to predict the severity of the disease and need for different respiratory support. Kahvecioglu et al. (
18) demonstrated that a positive correlation was found between the arterial blood gas result (pH < 7.30), ratio of PaO2/% inspired O
2 < 1.2 and the need for ventilator support. In our study, we revealed that the LUS score was significantly correlated with the severity of clinical respiratory conditions after admission. In this study, a new LUS scoring system was proposed. The ROC analysis suggested that this new scoring system could be better for evaluating the severity of TTN. Infants with a higher LUS score (> 6 units) might be provided noninvasive ventilation support; moreover, an LUS score over 11 units might be a good predictor of the need to provide NIPPV ventilation. Because few infants were included in the MV group, how to use the LUS score to predict mechanical ventilation was not analyzed.
In this study, only one doctor conducted the LUS procedure, and different operators’ biases were minimized. However, there are also some limitations in this research. First, the sample size was smaller than that in other studies. For a more significant result, we need to include more infants who meet the criteria. Second, the double-blind condition was not conducted in this study, as the physician who performed the LUS scan recognized the neonatal clinical condition and mode of respiratory support. Nonetheless, if the operator had knowledge of the relevant clinical data and respiratory modes, the LUS score was likely to be misestimated by experimenter bias. Finally, TTN was diagnosed by typical clinical indications and the result of ultrasound scan and was not diagnosed pathologically, as it is difficult to find rare conditions, such as alveolar capillary dysplasia with misalignment of pulmonary veins, alveolar growth disorders, etc., which are usually evaluated by high-resolution CT.
LUS is a dynamic, point-of-care tool in addition to the available tools that dramatically decrease neonates’ exposure to radiation. It offers increased sensitivity in capturing evidence of pulmonary edema and evaluating the clinical effectiveness of follow-up. In this study, the LUS check results on admission can reveal the respiratory conditions of patients with TTN disease accurately. The LUS will be a good predictor for the decision on the respiratory mode needed.