Predicting Factors of INSURE Failure in Low Birth Weight Neonates with RDS; A Logistic Regression Model

Document Type: Original Article


1 Assistant Professor, Pediatrics Department, Faculty of Medicine, Baqiyatallah University of Medical Science, Tehran, Iran

2 Baqiyatallah university of medical sciences

3 Assistant Professor, Pediatrics Department, Faculty of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran

4 Pediatrics Department, Faculty of Medicine, Birjand University of Medical Science, Tehran, Iran

5 Students Research Committee, Baqiyatallah University of Medical Science, Tehran, Iran


Background:Respiratory Distress syndrome is the most common respiratory disease in premature neonate and the most important cause of death among them. We aimed to investigate factors to predict successful or failure of INSURE method as a therapeutic method of RDS.
Methods:In a cohort study,45 neonates with diagnosed RDS and birth weight lower than 1500g were included and they underwent INSURE followed by NCPAP(Nasal Continuous Positive Airway Pressure). The patients were divided into failure or successful groups and factors which can predict success of INSURE were investigated by logistic regression in SPSS 16th version.
Results:29 and16 neonates were observed in successful and failure groups, respectively. Birth weight was the only variable with significant difference between two groups (P=0.002). Finally logistic regression test showed that birth weight is only predicting factor for success (P: 0.001, EXP[β]: 0.009, CI [95%]: 1.003-0.014) and mortality (P: 0.029, EXP[β]: 0.993, CI [95%]: 0.987-0.999) of neonates treated with INSURE method.
Conclusion:Predicting factors which affect on success rate of INSURE can be useful for treating and reducing charge of neonate with RDS and the birth weight is one of the effective factor on INSURE Success in this study.



Respiratory Distress Syndrome (RDS) (1) or Hyaline Membrane Disease (HMD) (2) is the most common respiratory disorder in premature infants and the leading cause of their mortality. The disease, which is caused by the deficiency of alveolar surfactant, is also referred to as preterm neonatal respiratory distress (3). Thus, 60% of infants who are less than 30 weeks old, and 42% of infants with birth weights lower than 1500g are affected by the disease (1).

The syndrome appears immediately after birth or within a few hours later. It normally manifests with cyanosis, moaning and retraction of intercostals of muscles. Consequently, the patient might develop respiratory failure which is assessed with scoring of the respiratory distress severity (RDS score), lung radiography and blood

gas analysis (Arterial Blood Gas: ABG) (2).

The diagnosis is confirmed by a combination of clinical signs of the disease, gestational age, ruling out other causes of respiratory distress and the chest x-ray view, including "Ground Glass" and "Air Bronchogram" (1). The risk factors of the disease include gestational age, birth weight, maternal diabetes and perinatal asphyxia; the gestational age and birth weight are two important factors with an adverse effect on the incidence and severity of the symptoms (1, 2).

The disorder is progressive and its severity increases during the first two days of the life. If it is not treated appropriately, mortality will occur due to progressive hypoxemia and breathing failure. Therefore, several different studies have been conducted on the pathophysiology of the disease. In 1929, the effect of surfactant on lung maturation was determined, and for the first time, the use of surfactant in infants with HMD was successfully reported in 1980 (3). The treatment of RDS is based on respiratory support and surfactant administration. Meanwhile, methods of respiratory support, mechanical ventilation and Nasal Continuous Positive Airway Pressure (NCPAP) are more widely known now due to their efficiency in the reduction of the disease mortality (4, 5).

The symptoms caused by using the invasive mechanical ventilation resulted in the designing of a variety of strategies in order to reduce the need for Mechanical Ventilation (MV) (5). The early use of NCPAP and surfactant has proven to be effective in reducing the need for mechanical ventilation and diminishing the side effects (6). Early use of NCPAP, even without the use of surfactants, has also contributed to improving the prognosis of infants with RDS (7, 8). Several studies have been done and different therapeutic strategies were introduced for surfactant administration and the use of CPAP. Among those strategies, the INSURE method is a very useful and effective approach which results in reducing the need for mechanical ventilation, diminishing side effects and hospital stay duration and its costs (9-11).

The present study was designed to investigate the effective factors in predicting the success or failure of INSURE method in infants with respiratory distress syndrome in the group with the body weight of less than 1,500 grams, via the MV method in the Neonatal Intensive Care Units (NICU) of Mofid Hospital and Mahdieh Hospital from 2009 to 2010.


Material and Method

This was a cohort study in which the infants born in 2009 and 2010 in Mofid Hospital and Mahdieh Hospital in Tehran, Iran were enrolled upon parental consent. The infants with RDS weighing less than 1500 grams whose disease was confirmed by their medical history, clinical findings and chest radiograph, and had also been hospitalized for up to 48 hours after their birth, were enrolled in this study. Furthermore, infants with any congenital malformations, anomaly in the lung structure, chromosomal abnormality or any evidence of sepsis and congenital heart disease were excluded from the study.

Finally, 45 patients were enrolled and received INSURE treatment protocol with surfactant administration (Intratracheal Suspension of Survanta, Beractant, Columbus, Ohio, US) with a dosage of 100mg/kg, which had been heated to the temperature of 37 °C. Afterwards, they received NCPAP with the pressure of 4 cm of water.

Based on their response to the treatment, the patients were divided into two groups: success and failure. The infants with no RDS symptoms, normal ABG and Chest X-Ray examination interpretation were placed in the success group. If they showed no signs of respiratory distress, with Fio2 <0-40, Positive End Expiratory Pressure (PEEP) 50mmHg and PH> 7.25 in their arterial blood gas, they would be separated from NCPAP and placed under Oxygen-Hoods.

In contrast, in infants who had oxygen saturation of less than 85% with PaCO2> 60mmHg, PaO2

Statistical analysis was done using SPSS software, version 16. In addition, independent and paired t-Student test, ANOVA, Wilcoxon, Mann-Whitney and the regression model were applied for this experiment which were considered statistically significant with P < 0.05. In the logistic regression test, it should be noted that the variables with results of P

Figure1. Flow-chart of the study


Successful; 29 (64.4%) cases

Failure; 16(35.5%) cases

Survived; 29 (100%) cases

Dead; no one


INSURE + N.CPAP; 45 cases

Survived; 11 (68.75%) cases

Dead; 5 (31.25%) cases

regression model power, a variable per 15 subjects was added to the model. In other words, having the sample size of 45 subjects, three variables were evaluated for each time of the model testing. In total, the most influential variables were added to the final model and their impact on the success rate of INSURE method was specified.

This study was done upon the approval of the Scientific and Ethical Committee of Beheshti University of Medical Sciences, Tehran, Iran. The reports on various stages of the project were presented to the concerned authority. Moreover, all interventions were done after obtaining informed consent from the the infants’ parents imposing no additional costs on the patients.



Fourty-five patients were included in the study. twenty-five of them (55.5%) were male. A total of 6 patients (13.3%) were born through Normal Vaginal Delivery (NVD). Of all the patients, 31 neonates (68.8%) were born from nulliparous women. The average birth weight of the patients was equal to 1171 ± 218 g and their average age at birth was equivalent to 29.60 ± 2.28 weeks.

 The demographic, para-clinical and clinical values are shown in Table 1. According to Table 1, there was no significant difference between the male and female cases in either the succes or the failure group. Also, no significant difference was observed between the two groups regarding the method of delivery and age at birth. However, a significant difference was noted on the birth weight between the two groups (P = 0.002). Thus, from the patients with weighing less than 1000 g, one was placed in the success group and 8 were placed in the failure group. Among the patients with a birth weight between 1000-1250 grams, 12 and 5 patients were placed in the success and failure group respectively. Of the patients with a birth weight between 1250-1500 g, 16 patients were placed in the uccess group and 3 in the failure group. Moreover, no significant differences were observed regarding the age at birth between different categories (P = 0.465) (

No significant difference was seen among other demographic, clinical and para-clinical values between the two groups (Table 1). The variables with P



The results of our study indicate that multiple factors can be involved in the success or failure of INSURE method in treating infants with RDS. In the current study, a total of 45 children were examined, of which 29 patients (64.4%) were placed in the success group and the rest were placed in the failure group. The birth weight was one of the factors influencing the success level of the method.

Most of the previous studies had focused on comparing the effectiveness of INSURE method with other methods of treatment, and only a small number of studies have examined the predictors of success in using INSURE method (12-14). For instance, in Cherif et al. study conducted on 70 infants, it was concluded that the arterial partial pressure of CO2, a/A pO2 and extreme degree of radiology are among the factors affecting the success rate of this method (15). Our findings are consistent with the aforementioned study. Thus, significant changes can be observed between the success and the failure group. However, by univariate analysis in the study mentioned, it was found that in addition to the birth weight, other factors such as small size, serum hemoglobin level < 14 g/dL as well as Clinical Risk Index for Babies (CRIB) score> 4 are also involved in success rate. Following Logistic Regression Analysis, it was found that out of the four factors, only the CRIB score> 4 factor is effective on the success rate, which was not mentioned in our study; probably due to the differences in the number of patients. The point lacking in the above-mentioned study and our study is that the gestational age (GA) is not raised as a predictor of success, which is consistent with previous studies suggesting that the low birth weight is a factor for the incidence of respiratory distresses (16, 17).

In another study conducted by Dani et al., it was claimed that such factors as birth weight < 750 g, PO2/FiO2 <218, and a/ApO2

Furthermore, in a related study by Afjeh et al. in 2010, it was reported that several factors are associated with the complications and success rate of INSURE method in low birth weight infants. However, the study mentioned above was a cross-sectional study, while the present study was performed in order to predict the success factors or eliminate the underlying confounding factors using regression models, which were not mentioned in the other study (19). Given the efficacy of INSURE method, which will make it the method of choice for the treatment of neonatal RDS in the near future, it will be able to predict the success and failure factors of the procedure and as well as attempt to remove the causes of failure which can significantly influence the effectiveness of treatments associated with reduced costs.



We would like to humbly thank all the nurses and staff of Mofid Hospital and Mahdieh Hospital.

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