Introduction
Neonatal respiratory distress syndrome (NRDS) is the most common respiratory system disease in premature babies, particularly those born before 28 weeks of gestation [
1,
2]. It is caused by dysfunction of effective ventilation in neonates due to the lack of pulmonary surfactant (PS), or the immature development of the lung [
3,
4]. Because of the formation of hyaline membrane in the pathophysiology of this disease, it is also called neonatal pulmonary hyaline membrane disease [
5].The disease causes a progressive worsening of inspiratory dyspnea. NRDS patients may experience rapid breathing, grunting sounds while breathing, and flaring nostrils, they may also have a bluish tint to their skin due to inadequate oxygenation [
6].NRDS has a high morbidity rate, 5% of near-term infants are affected, 30% of infants who had a gestational age of less than 30 weeks are affected, and 60% of premature infants who had a gestational age of less than 28 weeks are affected [
7]. Many premature infants also die because of NRDS [
8]. Severe NRDS can lead to neonatal respiratory failure(NRF), which is defined as decreased oxygen saturation and oxygen partial pressure (PO2), or the need for endotracheal intubation and mechanical ventilation [
9]. NRF is likely to occur after NRDS for a period of time under the induction of various causes, affecting the development of children's circulatory system, nervous system, metabolism and other aspects, and even cause a serious impact on the prognosis of newborns [
10].
At present, prenatal use of dexamethasone to promote fetal lung development and maturation [
11], postpartum PS supplementation [
12], and effective ventilation therapy [
13] have reduced the incidence of NRDS, and also changed its severity and typical manifestations. However, NRDS remains the most common respiratory disease in preterm infants in the neonatal intensive care unit (NICU), and there are many cases of NRDS leading to NRF [
14]. Therefore, being able to identify the cases with a high probability of developing NRF in NRDS patients is helpful for early medical intervention, and is of great significance for improving the prognosis of children.
Predictive models have been previously developed for neonatal respiratory distress syndrome in both preterm and late-preterm infants, as well as for predicting other complications associated with NRDS [
15,
16]. Nevertheless, a predictive model for respiratory failure within the context of neonatal respiratory distress syndrome has yet to be established. A newborn refers to an infant who is in the initial 28 days of life after birth. during this neonatal period, infants diagnosed with NRDS are at a high risk of developing NRF. As such, this study aims to investigate the likelihood of NRF occurrence among neonates diagnosed with NRDS at both day 1 and day 28 after birth and then establishing a predictive model for the development of NRF in NRDS.
Discussion
NRF secondary to NRDS is not uncommon, it may occur after NRDS for a period of time after the onset of NRDS, especially when combined with multiple risk factors. We performed a large sample multi-risk factor analysis, and indicated Gestational age < 28 weeks, pH, PO2, PCO2, Hb, Blood culture, infection, Neonatal intracranial Hemorrhage, PS, parenteral nutrition and respiratory support as independent risk factors for NRF in NRDS patients. These results were used to construct a nomogram for estimating the NRF risk in NRDS patients within day 1 and day 28 during hospitalization. The validity of our nomogram model was determined using multiple indicators, including AUC, calibration curves and decision-curve analysis. In this study, we constructed a more comprehensive model based on a combination of various risk factors, to better predict the risk of NRF in patients with NRDS.
We found that most of the secondary NRF in NRDS patients occurred within one day [
29]. This is also consistent with the clinical features of NRDS, which is a progressive worsening of dyspnea that develops gradually after birth, therefore most NRDS patients typically develop respiratory failure within 1 day. Premature infants with a gestational age of less than 28 weeks are at an increased risk of developing NRF following NRDS. This is primarily due to the fact that premature infants exhibit underdeveloped lungs, insufficient production of surface-active substances, and compromised immunity, which collectively increase the likelihood of disease progression and exacerbation2. In addition, we found that infection-related factors were also closely related to neonatal respiratory failure secondary to NRDS, including clear presence of infection-related symptoms, or positive microbial tests such as blood culture and CSF culture, which may be due to the decreased activity and increased degradation of PS caused by inflammatory mediators [
30]. At the same time, inflammation can cause mechanical damage to type II alveolar epithelial cells, and further reduce the secretion of PS [
31]. Thus, patients with pathogen cultures detected during the first time should receive clinical attention. Antimicrobial agents should include all possibly present pathogenic bacteria in the initial stage of anti-infective therapy.
In terms of treatment, parenteral nutrition increases the risk of NRF, which may be associated with infection due to parenteral nutrition, or increased pulmonary circulation due to excessive fluid intake [
32]. Therefore, rational parenteral nutrition and fluid management are critical in patients with NRDS. At the same time, the use of noninvasive ventilation and Surfactant replacement can effectively reduce the occurrence of NRF. Noninvasive ventilation techniques, like nasal Continuous Positive Airway Pressure (nCPAP), offer positive end-expiratory pressure to NRDS patients. This aids in consistently expanding the alveoli, enhancing gas exchange, and subsequently mitigating the risk of NRF. As the respiratory distress in NRDS patients stems from a PS deficiency, replenishing PS further reduces the likelihood of NRF [
33].
Blood gas analysis is an important laboratory test index in neonatal respiratory management. Our study found that pH, PO2 and PCO2 are of great importance to NRF [
10]. These indicators can not only reflect the occurrence of NRF, but also be used as risk factors to early judge NRF secondary to NRDS, and remind us to carry out early intervention. Our findings revealed a significant association between reduced hemoglobin levels and disease development, potentially attributed to inadequate oxygenation among anemic children. Furthermore, the impact of intracranial hemorrhage on disease onset may be related to the central nervous system's role in respiratory regulation.
Clinical predictive models can be used to study the relationship between future outcome events and baseline status in patients [
34]. They can integrate the results of traditional analyses, simplify them with more intuitive and convincing presentations, and predict the probability of certain outcome events with a scoring system [
35]. NRDS is the most common respiratory disease in preterm infants. NRF caused by NRDS can be followed by multiple organ dysfunctions, which has a great impact on the prognosis of preterm infants. At present, the risk factors of respiratory failure secondary to NRDS have not been well studied. Therefore, the establishment of this prediction model has important clinical significance for early identification of NRF in patients with NRDS. Our doctors can use the scoring results of the model to communicate with the family members of the neonate, help them understand the severity of the child's condition, work out a treatment plan together, improve the degree of cooperation, and prevent the occurrence of NRF to the greatest extent. However, the predictive ability of this nomogram may be improved by considering other potential important factors that we were not able to obtain from the MIMIC-IV database, such as maternal factors during pregnancy, perinatal medication and detailed insights into the parameters associated with non-invasive ventilation. And although the number of patients included was large, this study is a single-center study, and lacks external validation.
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