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Brazilian Journal of Cardiovascular Surgery

Print version ISSN 0102-7638

Rev Bras Cir Cardiovasc vol.28 no.4 São José do Rio Preto Oct./Dec. 2013 



Indicators of surgical treatment of patent ductus arteriosus in preterm neonates in the first week of life



Renato BraulioI, MD, MSc; Cláudio Léo GelapeI, MD, PhD; Fátima Derlene da Rocha AraújoII, MD, MSc; Kelly Nascimento BrandãoII, MD; Luciana Drummond Guimarães AbreuII, MD; Paulo Henrique Nogueira CostaI, MD, MSc; Flávio Diniz CapanemaI, MD, PhD

IFederal University of Minas Gerais, School of Mediciney, Belo Horizonte, MG, Brazil
IIHospital Municipal Odilon Behrens, Department of Pediatrics, Belo Horizonte, Minas Gerais, Brazil

Correspondence address




OBJECTIVE: To identify clinical and echocardiographic indicators of the necessity for early surgical closure of patent ductus arteriosus in preterm neonates.
METHODS: The prospective study was conducted at the Neonatal Unit of Hospital Municipal Odilon Behrens between 2006 and 2010. The study population comprised 115 preterm neonates diagnosed with patent ductus arteriosus in the first week after birth, of whom 55 (group S) were submitted to clinical and or surgical closure and 60 (group NS) received non-surgical treatment. The parameters analyzed were birth weight, diameter of the ductus arteriosus (DAD), left atrial-to-aortic root diameter ratio (LA:Ao), the quotient of DAD2 and birth weight (mm2/kg), and ductal shunting.
RESULTS: The study population comprised 58 males and 57 females. The average birth weight of group S (924 ± 224.3 g) was significantly (P=0.049) lower than that of group NS (1012.3 ± 242.8 g). The probability of the preterm neonates being submitted to surgical closure was 62.1% (P=0.006) when the DAD2/birth weight index was > 5 mm2/kg, 72.2% (P=0.001) when the LA:Ao ratio was > 1.5, and 61.2% when ductal shunting was high (P=0.025).
CONCLUSION: The parameters DAD2/birth weight index > 5 mm2/kg, LA:Ao ratio > 1.5 and high ductal shunting were statistically significant indicators (P<0.05) of the need for surgical closure of patent ductus arteriosus in low birth weight preterm neonates. Moreover, when an LA:Ao ratio > 1.5 was associated with the occurrence of shock, the probability of surgical closure increased to 78.4%.

Descriptors: Ductus arteriosus, patent. Echocardiography. Infant, premature, diseases.




Patent ductus arteriosus (PDA) is a congenital heart problem that affects some neonates in which the ductus arteriosus, the blood vessel connecting the descending aorta and the pulmonary artery, fails to close after birth. Although the disorder can affect full-term infants, it is significantly more prevalent in preterm babies. The PDA in preterm neonates has been associated with increased morbidity and mortality if left uncorrected [1-3].

Correction of PDA in preterm neonates can be achieved via surgical methods (open surgery, video laparoscopy or endovascular approaches) or via clinical therapy [4-6]. The treatment of choice is the administration of nonsteroidal anti-inflammatory drugs (such as indomethacin and ibuprofen) that inhibit the prostaglandins known to keep the ductus arteriosus (DA) open [1]. In cases where clinical treatment fails, the DA can be closed by surgical ligation. However, while early closure of the DA improves the long-term cardiorespiratory functions of infants [2], the ideal time of application of the surgical procedure in preterm neonates remains somewhat controversial [3].

Although premature surgical closure of DA has received considerable attention in recent years, no definitive criteria of indication of this procedure have been established. The surgical indications most frequently applied appear to be related to the presence of heart anomalies (increased DA diameter and enlarged left atrium) and clinical signs such as shock, high parasternal systolic murmur and hyperdynamic precordium [7-9]. Considering that early surgical intervention can reduce morbidity and mortality among preterm neonates, it is of the utmost importance to recognize the signs and symptoms that support a surgical approach. Within this context, the aim of the present study was to identify the clinical and echocardiographic parameters that indicate the need for early surgical closure of PDA in preterm neonates who have been found unresponsive to, or unsuitable to receive, appropriate medication.



Details of the project were submitted to and approved by the Ethical Research Committee of the Hospital Municipal Odilon Behrens (CAAE 0012.0.216.000-06; FR99402; protocol no. 82/2006). The aims and objectives of the study were explained to the parents or legal guardians of the infants, and written informed consent was obtained prior to the commencement of the study. All procedures were conducted according to the ethical principles of research as embodied in the Declaration of Helsinki.

The prospective study was conducted at the Neonatal Unit of the Hospital Municipal Odilon Behrens between 2006 and 2010. Clinical and echocardiographic data of 215 preterm neonates (gestational age < 30 weeks) were analyzed and those diagnosed with PDA, according to the echocardiogram acquired on the 3rd or 4th day after birth, were selected for possible inclusion in the study. Neonates presenting congenital cardiovascular pathologies other than PDA (as determined by echocardiography using a Toshiba Nemio 30 ultrasound instrument) and infants who died during the first week after birth were excluded from the study. The final study population comprised 115 infants, all of whom received clinical treatment except for those who presented contraindications for ibuprofen therapy or PDA-induced shock. Sixty of the infants responded to the non-surgical treatment (group NS), while 55 were submitted to surgery for the correction of PDA (group S). The treatment with ibuprofen consisted of intravenous perfusion of three doses at 24 h intervals: 1st dose 10 mg/kg, 2nd and 3rd doses 5 mg/kg. The surgical technique applied to the S group involved left posterior thoracotomy in the third or fourth intercostal space via the triangle of auscultation, followed by extra pleural dissection of the DA and ligation with titanium clips under general anaesthesia [9,10].

The data assessed for all patients included birth weight, gestational age, clinical and echocardiographic signs of PDA in the first week after birth, treatment received to correct the defect (surgical or non-surgical), diameter of the DA (DAD), left atrial-to-aortic root diameter ratio (LA:Ao), the quotient of DAD2 and birth weight (mm2/kg), and ductal shunting. Shunting was evaluated on the parasternal short axis by color Doppler from the pattern and magnitude of shunt of the arterial canal in the direction of the pulmonary artery, and classified as: low (flow from the pulmonary branch up to the distal portion of the pulmonary artery), moderate (flow up to the mid-third of the pulmonary artery), and high (flow up to the proximal portion of the pulmonary artery and reaching the pulmonary valve). The diameter of the arterial canal was measured by two-dimensional echocardiography at the level of the pulmonary vein ostium.

Univariate analyzes of the clinical and echocardiographic data and their association with surgical closure was established using χ2 and Student t tests. Multivariate logistic regression analysis was performed in order to evaluate cross influences between the variables. Results were considered statistically significant at 5% probability (P<0.05). A receiver operating characteristic (ROC) curve was constructed for each of the variables in order to determine those that constituted good predictors for the outcome of interest (surgical indication). According to the ROC curves, the cut off points for the DAD2/birth weight index was 5 mm2/kg and that for the LA:Ao ratio was 1.5.



Of the 215 preterm neonates initially screened, 115 (53.5%) were diagnosed with PDA by echocardiography and included in the study. While the numbers of males (58/115; 50.4%) and females (57/115; 49.6%) in the study population were similar, the percentage of males submitted to surgical intervention (31/58; 53.4%) was higher than that of females (24/57; 42.1%), although the difference was not statistically significant (P=0.223).

The mean gestational ages of the preterm neonates in groups S and NS were 27.1 and 27.7 weeks, respectively, while the average birth weight of group S was significantly (P=0.049) lower than that of group NS (Table 1). Of the neonates presenting low birth weight in the total study population, more than half (57.7%) were in group S but, according to the ROC curve, birth weight was not a good predictor (P=0.107) of surgical closure. There was no significant difference (P=0.155) between the surgical and non-surgical groups regarding DAD, however, the two groups were significantly (P=0.010) different with respect to the index DAD2/birth weight (Table 1).

According to the percentage distributions shown in Table 2, preterm neonates with DAD2/birth weight index above 5 mm2/kg presented a 62.1% (P=0.006) probability of being submitted to surgical closure of PDA. Elevated probabilities of receiving surgical treatment for the correction of PDA were also associated with preterm neonates presenting LA:Ao ratios above 1.5 (72.2 % probability; P=0.001) or exhibiting high ductal shunting (61.2%; P=0.025). Mortality was not directly associated (P=0.151) with surgical closure, however, since the deaths of seven children from group S and of 13 children from group NS were caused by other factors including sepsis, complex congenital malformations and cerebral ventricular hemorrhage.



Multivariate logistic regression analysis of the predictors of surgical closure in 115 preterm neonates with PDA revealed that the variables LA:Ao ratio and ductal shunting were significant predictors of surgical closure (P=0.0315 and P=0.0370, respectively; Table 3). Moreover, the probability of surgical closure increased to 78.4% when the markers LA:Ao > 1.5 and shock were associated (Table 4).






In the present study, 47.8% (55/115) of the preterm neonates diagnosed with PDA required surgical closure. The necessity for surgical intervention is decided mainly on clinical and echocardiographic assessment, but this decision is not always straightforward, particularly in the case of borderline patients. The consideration of various parameters has been proposed in the selection of preterm neonates requiring early surgical correction of PDA in order to prevent future heart problems and to ensure better chances of survival. Tschuppert et al. [1] indicated that a DAD2/birth weight index > 9 mm2/kg and a LA:Ao ratio > 1.5 represented good predictors of the need for surgery. The cut-off points obtained in the present study agree partially with the earlier proposals in that the suggested LA:Ao ratio cut-off was similar (> 1.5) but that for the DAD2/birth weight index was much smaller (> 5 mm2/kg). Furthermore, our results indicated that high ductal shunting is a relevant prognostic marker for surgical closure. According to Chiruvolu et al. [7], high left-to-right shunting is very aggressive to preterm neonates because it induces pulmonary hypertension, pulmonary congestion and enlargement of heart chambers. A hemodynamically significant degree of ductal shunting may be a decisive factor in the choice of a surgical approach.

The sample size employed in the present study was larger than that reported in earlier studies, and this improved the precision of the statistical analysis of parameters. Thus, the results obtained herein may be considered appropriate for the construction a checklist to serve as a guideline for pediatricians and cardiologists when arriving at decisions regarding surgical closure of PDA. Obviously, meticulous medical assessment on a case by case basis, coupled with sound and prudent judgment, must always prevail in decision making. However, it is important to stress that, while the short- and long-term benefits of PDA closure have been demonstrated by numerous studies [1-3,7,8], delays in the treatment of PDA may lead to severe consequences for the neonate.



The parameters DAD2/birth weight index > 5 mm2/kg and LA:Ao ratio > 1.5 along with high ductal shunting are statistically significant indicators (P<0.05) of the need for surgical closure of PDA in low birth weight preterm neonates during the first week of life. The probability of surgical intervention when any of these factors are present is greater than 60%. Moreover, when the LA:Ao ratio > 1.5 is associated with the occurrence of shock, the probability of surgical closure increases to 78.4%.



1. Tschuppert S, Doell C, Arlettaz-Mieth R, Baenziger O, Rousson V, Balmer C, et al. The effect of ductal diameter on surgical and medical closure of patent ductus arteriosus in preterm neonates: size matters. J Thorac Cardiovasc Surg. 2008;135(1):78-82.         [ Links ]

2. Vida VL, Lago P, Salvatori S, Boccuzzo G, Padalino MA, Milanesi O, et al. Is there an optimal timing for surgical ligation of patent ductus arteriosus in preterm infants? Ann Thorac Surg. 2009;87(5):1509-15.         [ Links ]

3. Noori S, McCoy M, Friedlich P, Bright B, Gottipati V, Seri I, et al. Failure of ductus arteriosus closure is associated with increased mortality in preterm infants. Pediatrics. 2009;123(1):e138-44.         [ Links ]

4. Laborde F, Folliguet TA, Etienne PY, Carbognani D, Batisse A, Petrie J. Video-thoracoscopic surgical interruption of patent ductus arteriosus. Routine experience in 332 pediatric cases. Eur J Cardiothorac Surg. 1997;11(6):1052-5.         [ Links ]

5. Khelashvili V, Gogorishili I, Metreveli I, Tsintsadze A, Botsvadze T. Patent ductus arteriosus endovascular closure by amplatzer duct occluder. Georgian Med News. 2006;(134):19-22.         [ Links ]

6. Su PH, Chen JY, Su CM, Huang TC, Lee HS. Comparison of ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants. Pediatr Int. 2003;45(6):665-70.         [ Links ]

7. Chiruvolu A, Punjwani P, Ramaciotti C. Clinical and echocardiographic diagnosis of patent ductus arteriosus in premature neonates. Early Hum Dev. 2009;85(3):147-9.         [ Links ]

8. Afiune JY, Singer JM, Leone CR. Echocardiographic post-neonatal progress of preterm neonates with patent ductus arteriosus. J Pediatr (Rio J). 2005;81(6):454-60.         [ Links ]

9. Santos JLV, Braile DM, Ardito RV, Zaiantchick M, Soares MJF, Rade W, et al. Ligadura do canal arterial: técnica extrapleural. Rev Bras Cir Cardiovasc. 1992;7(1):14-21.         [ Links ]

10. Vicente WV, Rodrigues AJ, Ribeiro PJ, Evora PR, Menardi AC, Ferreira CA, et al. Dorsal minithoracotomy for ductus arteriosus clip closure in premature neonates. Ann Thorac Surg. 2004;77(3):1105-6.         [ Links ]



Correspondence address:
Renato Braulio
Hospital das Clínicas da UFMG
Av. Prof. Alfredo Balena, 110 - 5º andar - Santa Efigênia
Belo Horizonte, MG, Brazil - Zip code: 30130-100

Article received on August 1st, 2013
Article accepted on October 8th, 2013
No financial support.



Work carried out at Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG), Belo Horizonte, MG, Brazil and Hospital Municipal Odilon Behrens (HOB), Belo Horizonte, MG, Brazil.





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