How to cite this article: Juárez-Domínguez G, Iglesias-Leboreiro J, Rendón-Macías ME, Bernardez-Zapata I, Patiño-Bahena EJ, Agami-Micha S, Ortega-García KL, Torres-Palomino G, Delgado-Franco D. Echocardiographic screening vs. symptomatic diagnosis for patent ductus arteriosus in preterms. Rev Med Inst Mex Seguro Soc. 2015 Mar-Apr;53(2):136-41.
Received: April 15th 2014
Accepted: September 23rd 2014
Gabriela Juárez-Domínguez,a José Iglesias-Leboreiro,a,b Mario Enrique Rendón-Macías,a,c Isabel Bernardez-Zapata,a,b Emilia Josefina Patiño-Bahena,d Sion Agami-Micha,a Karla Leticia Ortega-García,a Gregory Torres-Palomino,c Dagoberto Delgado-Francoc
aFacultad Mexicana de Medicina, División de postgrado Universidad La Salle
bUnidad de Cuidados Intensivos Neonatales, Hospital Español de México
cUnidad de Investigación en Epidemiología Clínica Hospital de Pediatría Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social
dServicio de Cardiología, Hospital Español de México
Distrito Federal, México
Communication with: Gabriela Juárez-Domínguez
Telephone: (55) 2729 4818
Background: The persistence of ductus arteriosus, the aim of this study is to evaluate the possible benefit in the treatment for ductus closure when a early (less tan 72 hours of life) echocardiographic screening is done versus when the echocardiographic diagnosis is realized only in present of associated symptoms.
Methods: Preterm without malformation followed by two strategies: patent ductus arteriosus (PDA) screening or echocardiographic study on suspected PDA for symptoms (control group). We analized the ductus characteristics, the presence of pulmonary hypertension and the treatments for their closure. We analize the result in relation of the premature age as: late preterm (34 to 36 gestational age weeks), moderate (30 to 33) and extreme (< 30).
Results: There was no diference in the proportion of newborns diagnosed with PDA among the strategies (screening 18.6 % [101/543] vs 18.1 % [55/304], p = 0.92). In the control group, 53 % were diagnosed after 72 hours of life. There were no differences in realtion of the ductus characteristic among the groups. The closure treatment were similar in the two strategies among the moderate and late preterm, but was more aggressive in the control group in the extreme preterms.
Conclusion: The echocardiographic screening for PDA in extreme preterm newborns reduce the time to detect it, and allow to give less agressive treatment. We do not recommend their use in moderate o late preterm newborn.
Keywords: Screening; Ductus arteriosusm; Preterm; Echocardiography
Patent ductus arteriosus (PDA) is the most common disease in infants, its frequency varies from 53% for preterm infants < 34 weeks, up to 65% in those < 26 weeks.1,2 This lack of closure or persistence generates a blood short circuit from left to right that increases pulmonary flow. Its presence can generate few symptoms or be associated with edema and/or pulmonary hemorrhage.1,2 In particular in preterm infants < 30 weeks of gestation it is associated with the development of bronchopulmonary dysplasia, pulmonary hypertension, ventricular hemorrhage, and necrotizing enterocolitis.5,9
At present, treatment ranges from general ventilation and fluid control measures, to the use of drugs that inhibit cyclooxygenase (indomethacin or ibuprofen), to surgical closure.2,7,10 Success can be determined by various factors, one of which is the time at which its existence is detected. Therefore, some neonatal care centers have proposed screening for it in all neonates admitted to treatment,5,6,8 especially for premature infants < 1500 grams.5 This approach has been supported by the availability of echocardiography in neonatal treatment, which can be done even by a trained neonatologist.3,5 Previous experiences have shown that this approach reduces some postnatal complications.6,12 However, recent studies question the use of unnecessary drug treatments given the possibility of spontaneous closures of the PDA, with the potential side effects inherent to medications.4,7
Therefore, this study shows the experience of our service with respect to management observed with these two approaches: diagnosis of PDA via echocardiographic screening, versus diagnosis made only when suspected by clinical data.
During the period from January 1, 2007 to June 1, 2011 the records of all preterm infants < 37 weeks gestation admitted to the neonatal intensive care unit (NICU) of our hospital were reviewed. These infants were treated by two possible strategies regarding the diagnosis of PDA. One group was treated by doctors who performed screening by echocardiography before the newborn had 72 hours of life. In those, one pediatric cardiologist performed a Doppler continuous pulsed color two-dimensional (2D) echocardiography (brands En Visor de Phillips and Alfa 6 from Aloka) with parasternal cuts short, long, chambers 4 and 5, as well as suprasternal with special emphasis on the PDA. In the cut axis the flow from the aorta to the pulmonary artery was determined, in which the aorto-pulmonary gradient was estimated. Pulmonary arterial pressure was obtained from the difference between the gradient and the systemic systolic blood pressure. In the suprasternal projection the size and diameter of the conduct was determined, as well as confirmation of the gradient.
The other strategy only differed in that the echocardiographic evaluation, with the same procedural characteristics, was done only at the request of the neonatologist in charge of the child based on the presence of symptoms associated with PDA (tachycardia, hyperdynamic precordium, systolic murmur, bounding pulses, fall or decrease in mean blood pressure, diastolic hypotension, tachypnea, apnea, cardiomegaly, hepatomegaly, increased ventilatory and/or oxygen requirements).2
Information was collected about treatment received for the closure of the ductus arteriosus, which could be: nonpharmacological (electrolyte, ventilation, and nutrition control); pharmacological (indomethacin, ibuprofen, or both), and surgical (whether after, or not, having received medication treatment). The therapeutic decision was determined by the physician responsible for the minor. For the group of diagnosis by symptoms it was established if this was done before or after 72 hours of life.
Patients were grouped according to their preterm gestational age: late (34 to 36/6 weeks of gestation [GW]), moderate (30 to 33/6 GW) and extreme (<30 GW).
In both groups (screening and symptomatology) the proportions of patients with PDA were determined, for this the number of patients confirmed by echocardiography in each group was divided by the total. The proportions were reported in percentages.
For categorical variables simple frequencies and percentages were obtained. In quantitative measures the medians were calculated with their maximum and minimum values.
Comparisons were made between the screening group versus those diagnosed with symptoms before 72 hours of life (early) and versus those after 72 hours or more (late). For comparisons between proportions Chi-squared or Fisher’s exact test was used according to the number of available data, and for the quantitative data the Mann-Whitney test was used.
Analyses were performed using the statistical program SPSS version 20 and statistical significance level was considered a p-value less than 0.05.
During the study period, there were a total of 847 newborns admitted to intensive care. As shown in Figure I, in 543 (64.1%) the screening for patent ductus arteriosus (PDA) was done. Of the remainder (304) only 55 (18.1%) were studied with echocardiography because of clinical suspicion, in all cases its presence was confirmed.
Figure 1 Flow chart of detection or diagnosis of patent ductus arteriosus by strategy used in each patient. PDA = patent ductus arteriosus; NICU = neonatal intensive care unit
We found no differences in the percentage of confirmed cases of PDA between the strategies (screening 18.6% versus suspicion 18.1%, chi-squared 0.03, 2 df, p = 0.92). However, with respect to time of diagnosis, for 52.7% (29/55) of cases, diagnostic because of symptoms was performed after 72 hours of life (Table I).
|Table I Frequency of patent ductus arteriosus found by search strategy and age group|
(≤ 72 h)
≤ 72 h vs.> 72 h
|n = 543||n = 304||n = 26||n = 29|
|Late (34; 36/6 GW)||23/293 (7.8%)||21/199 (10.5%)||14 (70%)||7 (30%)|
|Moderate (30; 33/6 GW)||50/168 (29.7%)||15/86 (17.4%)||7 (46.6%)||8 (53.4%)|
|Extreme (< 30 GW)||28/82 (34.1%)||19/19 (100%)||5 (26.3%)||14 (73.6%)|
|Total||101/543 (18.6%)||55/304 (18.1%)|
By analyzing the strategies according to the gestational age group (Table I) in late preterm the screenings found 7.8% of PDA, a figure very similar to 10% by suspicion (chi-squared 0.71, 2 df, p = 0.49). And for 35% (7/20) of those detected by suspicion, diagnosis time was set after 72 hours of life.
For the moderately premature, the screening detected more infants with PDA (29.7% vs. 17.4%, chi-squared of 3.7, 2 df, p = 0.053), while avoiding diagnoses after 72 hours as was the case in more than half (53.4%) of those detected by the presence of symptoms.
The most striking difference was for the extremely premature. For them, although detection was similar between screening and diagnosis by early symptoms (34.1% vs. 26.3%), the screening prevented the appearance of this condition in subsequent days, unlike in the group with symptoms where everyone presented patent ductus arteriosus during hospitalization. (34.1% vs. 100%, Fisher’s two-tailed exact test, p < 0.0001) (Table I).
The evaluation of the conditions of the ductus arteriosus was analyzed by gestational age group. Table II presents conditions in the late preterm infants. In them a higher proportion of infants with pulmonary hypertension was observed in the group detected by screening, although the difference was statistically significant only in late diagnosis. Conditions of the conduit in its diameter, gradient, and flow showed no difference between groups.
|Table II Echocardiographic characteristics by diagnosis method of patent ductus arteriosus in late preterm infants (= 43)|
≤ 72 hours
≤ 72 hours
> 72 hours
|n = 23||n = 13||n = 7|
|Duct diameter (mm)||2 (0.1-3)||2 (1-2) *||1 (1-3) *|
|Gradient (mmHg)||7 (0-33)||2 (0-32) *||0 (0-32) *|
|Pulmonary arterial pressure (mmHg)||46 (22-64)||39 (24-72) *||29 (25-52) *|
|Comparison against screening group, Mann-WhitneyUtest *p> 0.05.
Comparison against screening group, Fisher's exact test, one tail?p> 0.05 ‡p= 0.03.
Comparison against screening group,
chi-squared test §p> 0.05
For the moderate preterm group (30-33 GW), the only difference found was the presence of a higher pulmonary gradient in infants detected by suspicion after 72 hours of life, although only half of them had pulmonary hypertension (Table III). In the extremely premature, the presence of a greater gradient of flow was observed in those diagnosed by clinical data after 72 hours of life (Table IV). Unlike the moderately premature, in this group all those diagnosed by clinical data before 72 hours of life presented figures of pulmonary hypertension.
|Table III Echocardiographic features according to diagnosis method of patent ductus arteriosus in moderately preterm infants (= 65)|
≤ 72 hours
≤ 72 hours
> 72 hours
|n = 50||n = 7||n = 8|
|Duct diameter (mm)||1 (0.2-3)||2 (1-3) *||2 (0.4-2) *|
|Gradient (mmHg)||3 (0-37)||6 (0-22) *||25 (0-36)?|
|Pulmonary arterial pressure (mmHg)||43 (13-80)||47 (19-71) *||25 (15-65) *|
|Comparison against screening group, Mann-Whitney U test *p> 0.05.?p= 0.03
Comparison against screening group, Fisher's exact test, one tail ‡p> 0.05
Comparison against screening group,
chi-squared test §p> 0.05
|Table IV Echocardiographic characteristics by diagnosis method of patent ductus arteriosus in extremely preterm infants = 47)|
|Search ≤ 72 hours||Suspected early ≤ 72 hours||Suspected late > 72 hours|
|n = 28||n = 5||n = 14|
|Duct diameter||1 (0.3-3)||1 (1-2)*||1.5 (0.2-2)*|
|Gradient (mmHg)||2 (0-26)||1 (0-11)*||12.5 (0-29)?|
|Pulmonary arterial pressure (mmHg)||35 (16-60)||42 (32-49)*||32 (25-60)*|
|Comparison against screening group, Mann-Whitney U test *p> 0.05.?p= 0.05.
Comparison against screening group, Fisher's exact test, one tail ‡p> 0.05.
Comparison against screening group,
chi-squared test §p> 0.05.
As for the treatment received (Table V), we note that of the late preterm detected by screening, none required any pharmacological or surgical treatment, only ventilation and electrolyte control. In this gestational group, in those detected by symptoms, three needed medication treatment and even one of those diagnosed after 72 hours of life required surgical closure.
In the moderately premature with PDA, none required surgical closure, and pharmacological closure was performed in a similar ratio between those detected by screening and those diagnosed by symptoms (Table V). In the extreme preterm infants no differences were observed in the treatment received for the closure of the patent ductus arteriosus among those detected by screening and those diagnosed by clinical data by suspicion. The most surgical closures were seen in this age group.
|Table V treatments according to method of diagnosis of the persistence of patent ductus arteriosus|
|Management||Search ≤ 72 hours||Suspected early ≤ 72 hours||Suspected late > 72 hours|
|Late (= 43)||n = 23||n = 13||n = 7|
|No pharmacological or surgical||23 (100%)||11 (84.6%)||6 (85.7%)|
|Pharmacological||0||1 (7.7%)||1 (14.3%)|
|Pharmacological and surgical||0||1 (7.7%)||0|
|Search against suspected < 72 h, Fisherp= 0.12; search against suspected ≥ 72 h, Fisherp= 0.23|
|Moderate (= 65)||n = 50||n = 7||n = 8|
|No pharmacological or surgical||45 (90%)||6 (85.7%)||6 (75%)|
|Pharmacological||5 (10%)||1 (14.3%)||2 (25%)|
|Search against suspected < 72 h, Fisherp= 1.00; search against suspected ≥ 72 h, Fisherp= 0.24|
|Ends (= 48)||n = 28||n = 6||n = 14|
|No pharmacological or surgical||45 (82.1%)||5 (83.1%)||10 (71.4%)|
|Pharmacological||5 (10.7%)||1 (16.7%)||1 (7.1%)|
|Pharmacological and surgical||2 (7.1%)||0||2 (14.3%)|
|Search against suspected < 72 h, Fisher p= 1.00; search against suspected ≥ 72 h, Fisher p= 0.59|
Our data show that for both the late and the moderate preterm, conducting a screening for the detection of PDA appears not to be a more efficient approach than detection for treatment of its closure, rather only when data exist to suspect its presence. This is supported by the fact that the proportion of infants detected was very similar and the therapeutic approach was not significantly different. The only difference might be the time of treatment, which, in the absence of major complications or the presence of some irreversible ones, does not justify the cost of screening. Moreover, since echocardiography is a noninvasive and safe procedure, its use can give different information on neonatal hemodynamics and thereby justify its performance.3,5,8
The currently recommended approach to surveillance with management by hemodynamic and ventilatory support without the use of drugs could prevent the unwarranted use of these drugs for closure.7,11 Therefore, echocardiography could serve more as a tool for continuous assessment and to support decision-making when the data on pulmonary repercussions point to PDA.6,8
On the other hand, our data support doing PDA screening in the extremely premature. For them, previous studies like ours show that the frequency of this condition is very high.8 Furthermore, as was observed in this study, it appears that all patients at some point in their follow-up could present PDA, particularly if there is not close management hemodynamic, ventilatory, and electrolyte conditions. This group is where there is still controversy over very early detection, given the possibility that medication treatment may begin early. We note that strict and conservative management of fluid and ventilation can encourage the closure when detected, or possibly prevent its opening associated with hypoxia2,4,12 and sepsis events.11,12 Furthermore, a diagnosis of PDA after five days of life is associated with a lower rate of response to closure with medication.12
A current advantage of echocardiography is its availability in different NICU, where they can be done by trained neonatologists, which reduces costs and time associated with requesting support from a pediatric cardiologist. Concerning the latter, we do not rule out their support for other cases associated with heart disease or questions about their management.
The study has several strengths, such as being a prospective study in a relatively large population (N = 847) of premature infants. In addition, the echocardiographic studies were conducted by a single expert cardiologist to avoid interobserver variability or lack of consistency due to inexperience. Echocardiographic diagnostic criteria were specific and consistent with those internationally recommended.2,5,6
There are several limitations to this study. Firstly, the study is observational and not randomized, so different confounding factors between groups could not be controlled. Although this was not tested, it is likely that infants treated by a medical group would have had differences in the risks of presenting PDA. There are currently proposals for randomized, double-blind studies to further evaluate this suggestion.6 Second, although the sample was large, PDA cases were few and therefore some conclusions of the treatment could not be confirmed by lack of statistical power. The criteria for treatment decision might not be the same among medical groups, since there was not consensus or preset protocols. Finally, this experiment took place in a private care center, so extrapolating it to centers with other conditions should be done with caution.
Based on our data we consider it advisable to perform echocardiography screening for PDA for all extremely premature newborns before 72 hours of life. Detection can improve management and prevent later reopening or association with other complications.
In moderate and late preterm infants PDA screening by echocardiography does not seem to impact diagnosis and treatment, so we highly recommend that it be done only with clinical suspicion.
Conflict of interest statement: The authors have completed and submitted the form translated into Spanish for the declaration of potential conflicts of interest of the International Committee of Medical Journal Editors, and none were reported in relation to this article.