Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts 330


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 12  |  Issue : 2  |  Page : 59-63

“Clinical Profile of Neonates with Patent Ductus Arteriosus and Factors Predicting Prolonged Paracetamol Treatment and Outcome” – A retrospective Study


1 Department of Paediatrics, Father Muller Medical College, Mangaluru, Karnataka, India
2 Department of Paediatrics, A.J. Institute of Medical Sciences and Research Centre, Mangaluru, Karnataka, India

Date of Submission09-Dec-2020
Date of Acceptance07-Jan-2022
Date of Web Publication28-Feb-2022

Correspondence Address:
Dr. B K Praveen
Department of Paediatrics, Father Muller Medical College Hospital, Mangalore, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjmsr.mjmsr_52_20

Rights and Permissions
  Abstract 


Introduction: Patent ductus arteriosus (PDA) comprises 5%–10% of all congenital heart diseases, excluding premature infants. It is more common in females than in males. Clinical evidence of PDA appears in 45% of neonates with a birth weight of <1750 g and in about 80% of neonates with a birth weight of <1200 g. Significant PDA occurs in 15% of premature infants with a birth weight of <1750 g and in 40%–50% of those with a birth weight of <1500 g. Materials and Methods: The present study was a retrospective, observational, descriptive, record-based study conducted in the department of neonatology of our medical college from March 2015 to April 2020. All the clinical parameters, echo details, and treatment histories were obtained from the patients' case records and were analyzed. Results: In the present study, a total of 56 cases of hemodynamically significant PDA were evaluated. Thirty-seven of them had primary closure, 17 of them had secondary closure, and 2 of them had no closure. Conclusion: From the present study, we conclude that the larger the size of PDA, the longer is the duration for closure. The presence of complications such as pulmonary hemorrhage and prolonged ventilation were associated with delayed closure.

Keywords: Hemodynamically significant patent ductus arteriosus, paracetamol, patent ductus arteriosus


How to cite this article:
Shilpa K, Praveen B K, Alva P. “Clinical Profile of Neonates with Patent Ductus Arteriosus and Factors Predicting Prolonged Paracetamol Treatment and Outcome” – A retrospective Study. Muller J Med Sci Res 2021;12:59-63

How to cite this URL:
Shilpa K, Praveen B K, Alva P. “Clinical Profile of Neonates with Patent Ductus Arteriosus and Factors Predicting Prolonged Paracetamol Treatment and Outcome” – A retrospective Study. Muller J Med Sci Res [serial online] 2021 [cited 2022 Jun 26];12:59-63. Available from: https://www.mjmsr.net/text.asp?2021/12/2/59/338506




  Introduction Top


Patent ductus arteriosus (PDA) comprises 5%–10% of all congenital heart diseases, excluding premature neonates. It is more common in females than in males. Clinical evidence of PDA appears in 45% of neonates with a birth weight of <1750 g and in about 80% of neonates with a birth weight of <1200 g. Significant PDA occurs in 15% of premature infants with a birth weight of <1750 g and in 40%–50% of those with a birth weight of <1500 g.[1]

Based on the size of PDA, it is classified as large when the diameter is >3 mm, moderate when the diameter is between 1.5 mm and 3 mm, and small when the diameter is <1.5 mm.[2]

Risk factors for PDA include prematurity, respiratory distress syndrome, high volume of intravenous fluids in 1st week, sepsis, prolonged rupture of membranes, use of furosemide, male sex, and aminoglycoside antibiotics.[3]

PDA is associated with prolonged ventilation, risk of complications such as intraventricular hemorrhage, acute pulmonary hemorrhage, necrotizing enterocolitis, chronic lung disease, bronchopulmonary dysplasia, and increased mortality.[4]


  Materials and Methods Top


The present study was a retrospective observational, descriptive, record-based study conducted in the department of neonatology from March 2015 to April 2020. This study protocol was approved by the institutional ethics committee. Neonates admitted to neonatal intensive care unit (NICU) fulfilling the inclusion criteria were included in the study, i.e., the neonates with hemodynamically significant PDA requiring medical management to close the duct.

Hemodynamically significant PDA was defined as echo transductal diameter >1.5 mm with one of the following: ductal velocity of <2 m/s, antegrade main pulmonary artery diastolic flow >20 cm/s, LA: Ao root diameter ≥1.4, left ventricular/aortic root width ratio >2.2, E wave/A wave ratio >1, isovolumic relaxation time ≤ 45 ms, left ventricular stroke volume index <0.26, and retrograde diastolic flow >30% of forward flow. Intravenous paracetamol was used as first-line management to close PDA at a dose of 15 mg/kg once every 6 h.[5] Prolonged paracetamol treatment was defined as the requirement of paracetamol more than 3 days. For secondary closure of PDA, paracetamol was continued beyond 3 days instead of ibuprofen or indomethacin as paracetamol had lesser adverse effects in the form of NEC and ARF. A study by Babaei et al. favored longer duration of paracetamol.[6]

Neonates and their mothers necessary demographic, etiological, and clinical history investigations were collected in predesigned pro forma. Data collected were analyzed by frequency, percentage, and Chi-square test.

Two-dimensional (2D) Echo was done in all VLBW babies by 48 h of life. In neonates who weighed >1500 g, echo was performed if murmur was found on examination or were hemodynamically unstable on ventilation/CPAP. None of the babies received HHFNC. Beractant (Survanta) was used in standard doses in all babies, where surfactant was indicated as per the NICU protocol.

Outcomes were measured as primary closure rate and secondary closure rate. Primary closure was defined as the closure of PDA by 3 days of intravenous paracetamol at 15 mg/kg 6th hourly. Secondary closure was defined as the closure of PDA by 6 days of intravenous paracetamol at 15 mg/kg 6th hourly. No closure was defined as the nonclosure of PDA even after 6 days of intravenous paracetamol at 15 mg/kg 6th hourly.


  Results Top


Of 56 neonates, 38% of females and 62% of males had primary closure and 29% of females and 71% of males had secondary closure [Figure 1] and [Figure 2].
Figure 1: Demographic profile of hemodynamically significant patent ductus arteriosus

Click here to view
Figure 2: Distribution according to the gender

Click here to view


Of the 37 neonates with primary closure, 8 neonates (21.6%) had a birth weight <1000 g, 6 (16.2%) neonates had a weight from 1000 to 1500 g, 14 (37.8%) had a weight from 1500 to 2500 g, and 9 (24.3%) neonates weighed >2500 g. Of the 17 neonates with secondary closure, 7 neonates (41.2%) had weight <1000 g, 3 (17.6%) neonates had weight from 1000 to 1500 g, 5 (29.4%) neonates weighed between 1500–2500 g, and 2 (11.7%) neonates weighed >2500 g. Two neonates with nonclosure of PDA weighed >2500 g [Figure 3].
Figure 3: Distribution according to the weight

Click here to view


Among the 37 neonates of primary closure, 10.8% were <28 weeks, 29.7% were between 28 and 32 weeks, 35.1% were between 33 and 37 weeks, and 24.3% were term neonates. Among the 17 neonates of secondary closure, 17.6% were <28 weeks, 41.1% were between 28 and 32 weeks, 23% were between 33 and 37 weeks, and 17.6% were term neonates [Table 1] [Figure 4].
Figure 4: Distribution according to the gestational age

Click here to view
Table 1: Distribution according to the gestational age

Click here to view


Among 17 neonates with secondary closure, 13 (76.4%) neonates required invasive ventilation, and among the 37 neonates of primary closure, 23 (62.1%) neonates required invasive ventilation [Figure 5].
Figure 5: Distribution according to the need of ventilation

Click here to view


Of the 23 neonates of primary closure requiring invasive ventilation, 15 (65.2%) required prolonged ventilation for >3 days. Of the 13 neonates of secondary closure requiring invasive ventilation, all of them required prolonged ventilation of >3 days [Figure 6].
Figure 6: Distribution according to the duration of ventilation

Click here to view


Of 25 neonates with large PDA, 60% had primary closure, 32% had secondary closure, and 8% had no closure [Figure 7].
Figure 7: Patent ductus arteriosus closure in large patent ductus arteriosus

Click here to view


Of 31 neonates with moderate PDA, 71% had primary closure and 29% had secondary closure [Figure 8].
Figure 8: Patent ductus arteriosus closure in moderate patent ductus arteriosus

Click here to view


The complications associated with PDA included necrotizing enterocolitis (NEC), intraventricular hemorrhage, seizures, and pulmonary hemorrhage [Table 2]. The presence of pulmonary hemorrhage and prolonged ventilation were associated with delayed closure.
Table 2: Complications associated with patent ductus arteriosus

Click here to view


Outcomes

Of 72 neonates with hemodynamically significant PDA, 16 neonates were excluded. Nine neonates expired within 3 days of paracetamol therapy, 5 were discharged against medical advice, and 2 neonates were referred before the completion of day 3 of paracetamol therapy. Of the 56 neonates included in the study, 96.4% of neonates showed improvement with paracetamol treatment, 3.6% had no improvement in the form of nonclosure of PDA.


  Discussion Top


A total of 56 cases of PDA were included in our study from the last 5 years. In the present study, we found that 62% males and 71% males had primary and secondary closure, respectively, whereas 38% of females and 29% of females had primary and secondary closure, respectively, showing male preponderance for primary closure and female preponderance of secondary closure. In a study done by Sunil et al. in 36 neonates, 58.3% were male and 41.7% were females. PDA closure was evident in 25 (75%) by 2D echo after receiving IV paracetamol (15 mg/kg) 6th hourly for 3 days.[7]

In our study, 37 neonates had primary closure, 17 neonates had secondary closure, and 2 neonates had no closure. Hammerman et al. described five cases of successful closure of PDA with acetaminophen by the end of 3 days.[8] In a study done by Oncel et al., of the ten preterm neonates with successful closure of hemodynamically significant PDA (hsPDA), 7 (70%) had primary closure and 3 (30%) had secondary closure.[9]

Of 25 neonates with large PDA, 60% had primary closure, 32% had secondary closure, and 8% had no closure. Of 31 neonates with moderate PDA, 71% had primary closure, and 29% had secondary closure, suggesting more rates of primary closure. Thus, an increase in the size of PDA is associated with a longer duration of treatment for closure.

The complications noted in neonates with hsPDA in our study were NEC, intraventricular hemorrhage, seizures, and pulmonary hemorrhage. In our study, of the 23 neonates of primary closure requiring invasive ventilation, 15 (65.2%) neonates required prolonged ventilation for more than 3 days and all neonates of secondary closure requiring invasive ventilation required prolonged ventilation of more than 3 days. Thus, the prolonged need of ventilation was an important associated complication. Delayed closure of PDA in preterm can be associated with important complications such as severe RDS and prolonged need of assisted ventilation.[10]

Of the 56 neonates included in the study, 96.4% of neonates showed improvement with paracetamol treatment, 3.6% had no improvement in the form of nonclosure of PDA. In a study done by Homa Babaei et al. on 69 neonates with significant PDA, the overall PDA closure rate was 94.4%, with the primary closure in 75% of patients and secondary closure in 19.4%, and no closure in 5.6%.[6]

Limitations of the study

The study was a retrospective study. 2D echo on a daily basis would give a better knowledge of the exact duration taken for the ductus to close in these high-risk neonates on treatment.


  Conclusion Top


From the present study, we conclude that larger the size of PDA, delayed is the closure. Intravenous paracetamol is a good modality of treatment of PDA. Moreover, the presence of complications such as pulmonary hemorrhage and prolonged ventilation were associated with delayed closure.

A randomized control prospective study using a larger sample may throw better light on the usage of paracetamol instead of ibuprofen or indomethacin, which has more adverse effects on preterm babies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Park M, Salamat M. The Paediatric Cardiology Handbook. 7th ed. Elsevier health sciences, India 2020.  Back to cited text no. 1
    
2.
Arlettaz R. Echocardiographic evaluation of patent ductus arteriosus in preterm infants. Front Pediatr 2017;5:147.  Back to cited text no. 2
    
3.
Gillam-Krakauer M, Reese J. Diagnosis and management of patent ductus arteriosus. Neoreviews 2018;19:e394-402.  Back to cited text no. 3
    
4.
Allegaert K, Anderson B, Simons S, van Overmeire B. Paracetamol to induce ductus arteriosus closure: Is it valid? Arch Dis Child 2013;98:462-6.  Back to cited text no. 4
    
5.
Hamrick SE, Sallmon H, Rose AT, Porras D, Shelton EL, Reese J, et al. Patent ductus arteriosus of the preterm infant. Pediatrics 2020;146:e20201209.  Back to cited text no. 5
    
6.
Babaei H, Nemati R, Daryoshi H. Closure of patent ductusarteriosus with oral acetaminophen in preterm neonates: A randomized trial. Biomed Res Ther 2018;5:2034-44.  Back to cited text no. 6
    
7.
Sunil B. Patel S. Girish N. IV Paracetamol for closure of patent ductus arteriosus in preterm neonates admitted to a tertiary care centre. International Journal of Contemporary Pediatrics, 2018.v5,n2.294-8.  Back to cited text no. 7
    
8.
Hammerman C, Bin-Nun A, Markovitch E, Schimmel MS, Kaplan M, Fink D. Ductal closure with paracetamol: A surprising new approach to patent ductus arteriosus treatment. Pediatrics 2011;128:e1618-21.  Back to cited text no. 8
    
9.
Oncel MY, Yurttutan S, Degirmencioglu H, Uras N, Altug N, Erdeve O, et al. Intravenous paracetamol treatment in the management of patent ductus arteriosus in extremely low birth weight infants. Neonatology 2013;103:166-9.  Back to cited text no. 9
    
10.
Schena F, Francescato G, Cappelleri A, Picciolli I, Mayer A, Mosca F, et al. Association between hemodynamically significant patent ductus arteriosus and bronchopulmonary dysplasia. J Pediatr 2015;166:1488-92.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Materials and Me...
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed1257    
    Printed68    
    Emailed0    
    PDF Downloaded107    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]