|Year : 2018 | Volume
| Issue : 1 | Page : 8-13
Short-term outcome of patent ductus arteriosus in the neonatal period
Salah R Zaher, Manal A.M Antonios, Adham O Badib, Mahmoud M.B Nadder
Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt
|Date of Web Publication||7-Sep-2018|
Manal A.M Antonios
Department of Pediatrics, Faculty of Medicine, Alexandria University, 55 Port Saied Street,
El-Shatby, 21646 Alexandria
Source of Support: None, Conflict of Interest: None
Background Patent ductus arteriosus (PDA) is a common problem in neonates. It has a very high incidence especially in infants weighing 1000 g or less reaching in some studies up to 60%.
Aim The current study aimed at assessing the short-term outcome of PDA in the first 28 days of neonatal life.
Patients and methods All neonates admitted to Alexandria University Children’s Hospital Newborn unit at El-Shatby were assessed (n=410). Two-hundred fifty were preterm and 160 were term. Sixty cases were proved by echocardiography to have PDA at day 4 including 47 preterm and 13 term neonates who were followed up at day 10 and day 28 to assess the outcome of PDA.
Results The incidence of PDA was 18.8 and 8.1% in the preterm and in the term babies, respectively. The incidence in preterm neonates 32 weeks of gestational age or less was 29.1% and in neonates weighting 1000 g or less was 36.6%. It was also noted that the lower the gestational age and birth weight, the higher the incidence of PDA. Females were more common to have PDA in the term group. On following up these cases, the closure rate at 10 days was 62.2% in the preterm in comparison with 61.5% in the term, but at 28 days, the closure rate was 94.4% in the preterm in comparison with 66.7% in the term. Ten cases were not given any medical treatment and their closure rate was 70%, and no cases developed heart failure. It was also noticed that the closure rate is higher in cases that received ibuprofen (72%) in comparison with paracetamol (60%) at the age of 10 days.
Conclusion PDA in the neonatal period is a very common cardiac malformation that frequently closes spontaneously. The rate of closure is higher among preterm, low-birth-weight and small-for-gestational-age babies.
Keywords: neonates, patent ductus arteriosus, preterm
|How to cite this article:|
Zaher SR, Antonios MA, Badib AO, Nadder MM. Short-term outcome of patent ductus arteriosus in the neonatal period. Alex J Pediatr 2018;31:8-13
|How to cite this URL:|
Zaher SR, Antonios MA, Badib AO, Nadder MM. Short-term outcome of patent ductus arteriosus in the neonatal period. Alex J Pediatr [serial online] 2018 [cited 2018 Nov 15];31:8-13. Available from: http://www.ajp.eg.net/text.asp?2018/31/1/8/240745
| Introduction|| |
Patent ductus arteriosus (PDA) is caused by failure of the ductus arteriosus to be closed after the first 48–96 h of life. PDA incidence is ∼1/2000 in term neonates, but ∼20–60% in premature infants, with the highest incidence in the youngest patients. The incidence in females is 2–3-folds higher than in males . The echocardiogram has emerged as the procedure of choice to confirm the diagnosis and to assess the functional significance of PDA. M-mode echocardiography can detect enlargement of the atrium and left ventricle caused by volume overload. Two-dimensional image reveals the geometry of the PDA, and color Doppler, a very sensitive modality, is frequently used to estimate the degree of ductal shunting. Even an extremely tiny (silent) PDA can be detected by a color flow signal entering the pulmonary artery near the origin of the left pulmonary artery .
PDA is more common in preterm owing to failure of closure mechanisms. There are multiple medications for treatment. In the past, indomethacin was the drug of choice, but recently, ibuprofen has emerged as the drug of choice with fewer side effects in comparison with indomethacin. Paracetamol is also under trials as a good alternative option ,,,. Failure of medical treatment in the presence of heart failure manifestations usually indicates the need for surgical ligation . The aim of the present research was to assess the short-term outcome of PDA in neonates admitted in the Neonatal Intensive Care Unit (NICU) at Alexandria University Children’s Hospital at El-Shatby, Egypt.
| Patients and methods|| |
The NICU of El-Shatby hospital affiliated to the Faculty of Medicine at University of Alexandria is considered a highly equipped tertiary care center providing service to four governorates. This unit admits an average of 1200–1300 cases annually.
An observational prospective cohort study was carried on all neonates over 72 h of age admitted to NICU at El-Shatby University Hospital during the period from 1 September 2015 to 31 December 2015. Neonates with complex congenital heart disease, neonates with duct dependent pulmonary circulation and neonates with duct dependent systemic circulation were excluded from the study.
Neonates verifying the inclusion and exclusion criteria were scanned by echocardiography for the presence of PDA after the age of 72 h using an echocardiography with a 3–8 MHZ transducer (model: HD, 11XE machine; Philips Yorba Linda, Reedsville, Pennsylvania, USA). Positive cases with PDA were managed according to the guidelines of management of PDA in neonatal period . All relevant parameters of the history, clinical examination findings, complications and treatment given were recorded. A follow-up echocardiographic study was performed at day 10 and 28 to assess the outcome of their PDA through the following parameters:
- The size of the pulmonary end of the PDA was assessed in the ductal view and/or suprasternal view using color Doppler echocardiography.
- The ratio of the left atrium to aortic root diameters was assessed by M-mode echocardiography in the left parasternal long axis view.
- A qualitative assessment of the left atrial and ventricular dilatation by two-dimensional echocardiography in the apical four-chamber view.
Data were collected and entered to the computer using Statistical Package for Social Science program for statistical analysis (version 21) . Data were entered as numerical or categorical, as appropriate. Kolmogorov–Smirnov test of normality revealed significance in the distribution of some variables, so the nonparametric statistics was adopted. Data were described using minimum, maximum, median, and interquartile range for not-normally distributed numerical data. Categorical variables were described using frequency and percentage of total. Comparisons were carried out between the studied independent not-normally distributed subgroups using Mann–Whitney U-test. χ2-test was used to test association between qualitative variables, and Student’s t-test for quantitative variables. Monte Carlo or Fisher’s exact test was carried out when indicated. An α level was set to 5%, with a significance level of 95%.
Compliance with ethical statement
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The University ethical committee approved the study design on June 2015. An informed consent was obtained from the parents or legal guardian of all patients.
| Results|| |
During the study period, 441 newborns were screened for exclusion criteria: 21 cases were excluded owing to other concomitant cardiac malformations, four newborns were suspected to have genetic diseases with dysmorphic facial features, and six parents refused to give an informed consent. The incidence of PDA in the present study was 18.8 and 8.1% in the preterm and term groups, respectively. Females were more common to have PDA in the term group, yet this difference was not proved to be statistically significant. The incidence in preterm neonates 32 weeks of gestational age or less was 29.1% and in neonates weighting 1000 g or less was 36.6%. It was also noted that the lower the gestational age and birth weight, the higher the incidence of PDA. These correlations were statistically significant (P˂0.001) as shown in [Table 1].
|Table 1 Comparison between neonates with and without PDA regarding sex, time of delivery, and birth weight|
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[Table 2] shows the comparison between preterm and term newborns with PDA regarding their initial assessment at day 4 of age. Pulmonary hypertension was statistically higher among term newborns compared with preterm ones (P=0.002). However, the PDA was found to be hemodynamically significant in the preterm group (P=0.015).
|Table 2 Comparison between preterm and term newborns with PDA regarding the clinical and echocardiographic findings at day 4 (initial assessment)|
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On following up these cases, the closure rate of the PDA at day 10 was found to be statistically insignificant: 62.2 and 61.5% in the preterm and the term groups, respectively. At day 28, the closure rate was higher in the preterm group compared with the term group (94.4 vs. 66.7%, respectively); still this difference was not statistically different (P=0.093). Unfortunately, intraventricular hemorrhage, shock, and mortality were significantly higher among preterm group ([Table 3])
| Discussion|| |
While designing this study, many questions were addressed. First, how frequent is PDA in the studied population? second, are PDAs present just in preterm infants and rarely to be present in the full-term infants? third, how frequent are silent PDAs at day 4? fourth, what are the outcomes of these PDAs according to the current treatment strategies? and what is the ultimate fate of these babies?
How frequent is PDA in the studied population?
PDA is defined as failure of closure of the duct by 48–96 h. This explains the variability in the incidence of PDA in different NICUs; either the diagnosis was after 48, 72, or 96 h. Another important factor was whether the diagnosis is based clinically by the presence of systolic murmur and wide pulse pressure or by echocardiography? The present study used the standardized technique − echocardiography − for diagnosis after 72 h on day 4, and 60 cases out of 410 were diagnosed as having PDA with an incidence rate of 18.8% for preterm and 8.1% for term newborns. The incidence was much higher in the preterm less than 32 weeks, reaching 29.1%, and cases weighing less than 1000 gram had PDA in 36.6%. It was found that the lower the gestational age, the higher the incidence of PDA (P=0.001), and the lower the weight, the higher the incidence in both groups preterm and term (P=0.017 and 0.015, respectively). It was also reported that females (76.9%) were more affected in the term group compared with males (23.1%) (P=0.021). However, there was no significant difference regarding sex in the preterm group (P=0.404).
In comparison with other published work, it was estimated in 2013 that the incidence of PDA may reach up to 60% in extremely low-birth-weight preterm neonates less than 28 weeks of gestational age . Another review article was published in 2013, which showed that the incidence of PDA ranges from 40 to 60% on the third day of life depending on the gestational age . Another review article published in 2011 stated that the incidence of PDA in the preterm weighting 501–1500 g is about one-third . In a review article in 2007, it was stated that the incidence of PDA in the preterm ranges from 20 to 60% according to the gestational age, day of examination, and the diagnostic criteria. In the same review article, it was mentioned that PDA is much more common in female term neonates for unknown causes with a ratio of 2 : 1 . The relatively low frequency of PDA reported in the present study compared with the worldwide records could be attributed to several causes. First, the numbers absolutely would have been much higher if the echocardiography was done after 48 h. Another important factor that altered the incidence was that many low-birth-weight infants actually died before the screening echocardiography was done.
Are PDAs present just in preterm infants and rarely to be present in the full-term?
Formerly, it was believed that PDA is not a disease of neonatal period in term infants. Inversely, the present study found that 8.1% of term cases had PDAs, 53.8% of them was proved to be hemodynamically significant either clinically or echocardiographically, and 15.4% of them developed heart failure. It should be put into consideration that these cases were not healthy full terms going home with their mothers but critically ill full terms requiring more than 3 days of NICU admission. The study recognized two important risk factors, pulmonary hypertension, with 69.2% of the term in comparison with 21.3% of the preterm group (P=0.002), and intraventricular hemorrhage, with 38.3% of the term and 4.3% of the preterm (P=0.004).
In a study published in 2010, they found 44 terms and near terms to have PDA. Approximately 52.2% developed heart failure manifestation (23 from 44) and ∼34% (15 from 44) required PDA ligation to improve their pulmonary symptoms .
How frequent are silent PDAs in day 4?
Formerly, physicians relied on the clinical data (the presence of systolic murmur and wide pulse pressure) either as solid diagnosis for PDA or as alerting signs to order echocardiography. In the present study, 34% of the preterm group had no systolic murmur whereas only 7.7% of term group on day 4, and were found to have PDA with screening echocardiography. A presumed explanation of this strange observation is that the audible murmur in the term group is the tricuspid regurgitation murmur of pulmonary hypertension.
A review article published in 2004 stated that echocardiography to all the preterm for the first week of life demonstrated a clinical delay in the diagnosis ranging from 1 to 4 days, and most of these delayed PDAs were hemodynamically significant. They also stated that clinical signs were specific but insensitive for the diagnosis of PDA. These findings were similar to the observations of Evans et al.  mentioned in the same review article.
What are the outcomes of these PDAs according to the current treatment strategies and what is the ultimate fate of these babies?
The rate of ductal closure was similar at day 10: 62.2% in the preterm group and 61.5% in term group. However, at day 28, the rate of closure was higher in the preterm group (94.4%) compared with the term group (66.7%).
Hemodynamically significant PDA is defined clinically by the presence of wide pulse pressure and echocardiographically by left-sided dilatation, left atrial aortic root ratio more than 1.4 and in the preterm if the size (mm) of the internal diameter of the pulmonary end of the ductus to the weight (kg) more than 1.4 . In the present study, PDAs of the preterm (87.2%) were found to be hemodynamically more significant than term infants (53.8%) (P=0.015). In the preterm group, 61.7% had wide pulse pressure, 76.6% had PDA size/weight ratio more than 1.4, 44.7% had left-sided dilatation and 38.3% had left atrium/aortic root ratio more than 1.4.
The final outcome of the cases was different in the two groups. Heart failure rates were 17% in the preterm and 15% of the full term. Approximately 80.9% of the preterm required ventilation and 61.5% of the term. It was also noticed that most of term patients were ventilated because of pulmonary hypertension. Intraventricular hemorrhage (IVH) was only present in premature group with a rate of 21.3%. Shock was much more common in the premature neonates (72.3– 30.8%) (P=0.009). Mortality also was much more common in the preterm (66.0%) than full terms (30.8%). Necrotizing enterocolitis and bronchopulmonary dysplasia were not well documented in the files, so they were not considered.These results parallel to other results all over the world. In a review article published in 2011, the incidence of IVH in was 9%. Another study included in the same review done by Van Overmeire found that the rate of IVH in ibuprofen treated PDA neonates was ∼16%. The mortality rate in one study included in this systemic review was 15% . A study published in 2015 in which 48 premature neonates less than 1500 g were studied, 28 of them had PDA, and 71.4% of them required mechanical ventilation in comparison with 50% of the neonates without PDA. In the same study, the incidence of IVH was 39.3% in comparison with 25% in cases without PDA . Another study was published in 2009 in which the mortality rate was much higher in PDA cases (n=41) than cases without PDA (n=260) (70.7 vs. 11.2%, respectively). In the same study, the rate of IVH in PDA cases was 34.1% in comparison with 14.2% in cases without PDA . In another study conducted over 39 preterm neonates aged 29 week or less, 29 (74%) of them had PDA, nine (36%) of them had heart failure manifestation on the age of 3–5 days and 16 (64%) had spontaneous closure without any medical intervention .
This study is not without limitations. This is a single-center study, which represents its actual practice and results could not be generalized. Another limitation is plenty of confounding factors that happen especially in the preterm (sepsis, respiratory distress syndrome, hypothermia, hypoglycemia, very low birth weight, and others) not only PDA that correlate to their outcomes. Finally, these observational analysis results would support an association between the studied risk factors of gestation and birth weight and the occurrence of PDA and not necessarily causation.
| Conclusion|| |
PDA is a very common malformation in preterm especially in the preterm weighting 1000 g or less. The lower the weight and the gestational age, the higher the incidence of PDA. Silent PDAs are common in the preterm neonates. Spontaneous closure of PDAs is a considerable option in both preterm and term babies. Clinical and echocardiographic assessment gives a good picture before deciding to close the PDA.
This research was supported by Alexandria Faculty of Medicine
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]