1. Introduction
Open arterial duct is a complication in preterm infants and requires treatment because of its associated complications. The arterial duct naturally closes functionally on the first day of life [1]. Indeed, the anatomical closure of this duct usually occurs in the first week. The openness of the pulmonary artery also enhances the resistance of the pulmonary arteries in the long run. Therefore, treating this disease is extremely important due to its numerous complications [2]. There is a large body of literature on pharmacotherapy for open arterial ducts; however, the effects of oral ibuprofen versus injectable ibuprofen are contradictory and limited, requiring further investigations. The present study aimed to evaluate the effects of oral ibuprofen on the closure of the open artery duct and the role of some factors, like age at delivery and birth weight.
2. Materials & Methods 
This quasi-experimental study was performed on 40 premature infants with open ductus arteriosus. The inclusion criteria were the age below 28 days and no other contraindications to ibuprofen, including renal impairment, active non-pulmonary hemorrhage, and thrombocytopenia in preterm infants. Furthermore, parental dissatisfaction and some congenital malformations, a history of nonsteroidal anti-inflammatory drug use during maternal pregnancy, the presence of hydrops fetalis, and increased pulmonary hypertension were the exclusion criteria of this study. The diagnostic criteria for open arterial duct were using cardiac echocardiography, i.e., included in the study. These preterm infants were then treated with oral ibuprofen at a dose of 10 mg on the first day and 5 mg/kg/day on the second and third days. After the end of treatment and on the fourth day, diagnostic echocardiography was re-performed; in case of no recovery, ibuprofen was given another course with the same conditions, and the arterial canal healing was evaluated. Furthermore, a 95% confidence level was considered for the tests, and the analysis was performed by STATA.
3. Results
Of the total participants in the study, 62.5% (n=25) were boys, and the rest were girls. The mean birth weight of preterm infants equaled 0.639 g; the lowest weight of preterm infants was 750 g. Furthermore, the mean gestational age was 30.4 weeks. Descriptive information about the preterm infants participating in the study is displayed in Table 1.


Table 2 presents the results of comparing the mean gestational age and birth weight between the periods of ibuprofen use.


The mean gestational age of infants who underwent two courses of ibuprofen was 26.8 weeks, i.e., lower than infants who took one course of ibuprofen. However, this difference was not significant.
Moreover, the mean birth weight in infants who took two periods of ibuprofen equaled 1298.1 g, i.e., lower than infants who took one episode of ibuprofen, although this difference was not significant. This table also suggests the relationship between ibuprofen consumption periods and multiple births and delivery methods. Based on these results, the frequency of singleton as well as a cesarean delivery method was higher in infants who took a course of ibuprofen; however, this difference was not significant.
4. Discussion & Conclusion
Premature babies are at greater risk for open arterial ducts. Prolonged exposure to the disease can be harmful and associated with infant mortality. The lack of arterial duct closure, the so-called arterial duct, is among the problems in a premature baby. They remain open in 87% and 64% of babies born under 28 weeks and between 27-28 weeks, respectively [1]. Initially, treatment with indomethacin was considered the standard management for this condition; however, its use was restricted due to its high renal adverse effects. 
Moreover, studies evaluated the benefits of early closure of the open artery (or even prevention) with ibuprofen [3, 4]. The present study findings indicated that all cases of preterm neonates with open arterial flow improved after consuming different doses of ibuprofen. Most preterm infants recovered with one course, while other preterm infants recovered with two courses. Furthermore, preterm infants with less weight required further ibuprofen treatment. Infants whose maternal gestational age was lower required more ibuprofen treatment. Besides, there was no significant relationship between episodes of ibuprofen use and type of delivery, and multiple births. The present study data were consistent with those of similar studies [1, 3, 5, 6]. These results support the use of ibuprofen to close the open arterial duct and confirm the present study results. Based on the obtained data, ibuprofen can be used to close an open arterial canal in all preterm infants with the disorder; however, some preterm infants require repetition of ibuprofen. Therefore, this medicine can be used as a suitable drug in treating this group of preterm infants.

Ethical Considerations
Compliance with ethical guidelines
This study was approved by the Ethics Committee of Arak University of Medical Sciences (Code: IR.ARAKMU.REC.1396.265).

Funding
This article was extracted from the professional doctoral dissertation of the first author in the Department of Pediatrics, School of Medicine, Arak University of Medical Sciences. 

Authors' contributions
Research methodology: Yazdan Ghandi, Maryam Beheshtifar, and Parsa Yousefi Chaijan; Data analysis: Maryam Beheshtifar; Drafting and review of the text: All authors.

Conflicts of interest
The authors declared no conflicts of interest.

Acknowledgements
The authors would like to appreciate the Clinical Research Development Center of Amirkabir Hospital in Arak.


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