CONGENITAL

HEART DISEASE

The Timing of Spontaneous Closure of the Ductus Arteriosus in Infants with Respiratory Distress Syndrome Mark D. Reller, MD, Michael A. Colasurdo, MD, Mary J. Rice, MD, and Robert W. McDonald, RCPT, RDMS

Previous studies evaluating the incidence of patent ductus arteriosus have not made a distinction between physiologic ductal patency and abnormally persistent ductus arteriosus. However, it has recently been shown that healthy premature infants without respiratory distress syndrome (RDS) undergo spontaneous closure of the ductus arteriosus in the flrst 4 days of life at times comparable to full-term infants. Thus, ductal patency within this time frame would appear to be physiologic. Although sick premature infants are well recognized to be at risk for ductal shunting, the purpose of this investigation was to evaluate systematically the actual impact that RDS has on duration of ductal shunting by assessing the timing of spontaneous functional closure. The presence of ductal shunting was evaluated using echocardiographic color flow Doppler techniques. Thirty-six premature infants (30 to 37 weeks gestational age) were evaluated. By the fourth day of life, only 4 of 36 (11.1%) of the infants continued to have evidence of ductal patency. The remainder of the infants underwent spontaneous functional closure of the ductus arteriosus at times comparable to healthy infants without RDS. For most infants 230 weeks gestation, uncomplicated RDS does not alter the usual timing of functional ductal closure. (Am J Cardiol 1990;66:75-78)

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revious studies evaluating the incidence of ductal shunting in premature infants with respiratory distress syndrome (RDS) have generally included the entire spectrum of neonatal respiratory illnesses.’ 6 These studies have invariably included infants with other complicating problems, such as birth asphyxia, that can independently affect both the natural history of RDS and the incidence of ductal shunting. An additional important problem is that in most studies assessing the incidence of patent ductus arteriosus with RDS, the background incidence of “normal” or physiologic ductal patency has not been taken into account. As such, previous studies of premature infants have not made a distinction between physiologic ductal patency and abnormally persistent ductus arteriosus. In a recent study evaluating healthy premature infants, we have established that essentially all healthy infants of 230 weeks gestation undergo spontaneous functional closure of the ductus arteriosus by the fourth day of life.’ Based on these data, ductal patency within this time frame would appear to be physiologic for both preterm and full-term infants. The current study prospectively evaluates the specific impact of RDS on the duration of ductal shunting using echocardiographic color flow Doppler studies. By comparing these results to those obtained previously in healthy premature infants, our goal was to assess the incremental risk that uncomplicated RDS poses on the natural history of physiologic ductal shunting and the timing of functional closure. METHODS

From the Department of Pediatrics, Oregon Health Sciences University, Portland, Oregon. Manuscript received November 13, 1989; revised manuscript received and accepted February 26, 1990. Address for reprints: Mark D. Reller, MD, Department of Pediatrics, Oregon Health Sciences University, 3 I8 1 Southwest Sam Jackson Park Road, Portland, Oregon 97201.

This investigation involved 27 premature infants delivered at the Oregon Health Sciences University Hospital as well as 11 outborn infants who were referred to the Neonatal Intensive Care Unit in the first 12 hours of life. The study protocol was approved by the Institutional Review Board. Infants were enrolled over a lomonth period between February 23 and December 12, 1988. Criteria for inclusion into this study were: (1) gestational age between 30 and 37 weeks (confirmed by a neonatal modified Ballard examination); (2) birth weights that were appropriate for gestational age; (3) infants felt to have a clinical illness consistent with RDS with documented oxygen requirements to maintain normal arterial p0~ or systemic arterial saturation (assessed by oximetry), and chest x-ray appearance consistent with RDS (i.e., diffuse granular pattern). Infants were excluded from the study if they had: (1) evidence THE AMERICAN

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of congenital malformation including congenital heart disease; (2) birth asphyxia defined as a 5-minute Apgar score 15 or any pH 17.10 in the first 2 hours of life; (3) suspected neonatal sepsis defined as a “septic” appearance (i.e., poor perfusion) or leukopenia in conjunction with maternal risk factors for neonatal sepsis (i.e., fever, prolonged rupture of membranes); or (4) any chest x-ray appearance suggesting an alternative respiratory illness (i.e., asymmetric infiltrates, patchy or coarse infiltrates, pleural effusion or pulmonary interstitial emphysema). Thus, the goal of the study was to enroll premature infants who had uncomplicated RDS. For infants meeting inclusion criteria, signed parental consent for participation was obtained. Thirty-eight infants met these criteria. Infants enrolled in this investigation were managed by the attending neonatal staff in the usual manner. Infants requiring intubation were managed using standard positive pressure ventilation. Ventilator adjustments and alteration of inspired oxygen concentration was made using arterial blood gases and standard oximetry techniques. No infant in this study was administered artiticial surfactant. One member of our group (MAC) performed a daily cardiac examination for evidence of clinical ductal shunting. Both he and the neonatal staff were blinded to the results of our echocardiographic

evaluations. If the neonatal staff had clinical concerns regarding patency of the ductus arteriosus, standard channels of cardiology consultation were obtained. On initiation of the investigational protocol, a complete 2-dimensional echocardiographic study was performed to exclude congenital cardiac anomalies. All subsequent studies were limited to high parasternal and suprasternal notch imaging to best visualize the entire length of the ductus arteriosus (Figure 1).‘-14 For detection of left-to-right ductal shunting, color flow Doppler imaging was used (Figure 2). With this extremely sensitive tool, ductal flow is noted to originate near the orilice of the left pulmonary artery and even small shunts are easily detectable.7J3-*9 The echocardiograms were obtained with the use of Hewlett-Packard model HP77020A color flow ultrasound imaging system. The 2-dimensional images and color flow Doppler signals were obtained with a 5 MHz short-focus transducer. The 2-dimensional and color flow Doppler images were recorded on a videocassette recorder (Panasonic). For all infants after the initial complete echo-color flow Doppler evaluation, daily sequential ductal shunt flow studies were obtained at roughly 24-hour intervals following the same protocol of our previous study in healthy preterm infants.’ For all infants, the first study was performed within the first 16 hours of life (mean f standard deviation 10 f 3 hours). For the entire group, the mean ages on days 2,3 and 4 were 33 f 8, 58 f 7 and 82 f 7 hours, respectively. The daily studies were continued until no shunt flow could be detected on 2 successive days, signifying that functional closure of the ductus arteriosus had occurred. Functional closure was defined as occurring on the first day that no shunt flow was detected. RESULTS

FIGURE 1. Reprermtatn

m e image of ths “chctai obtainsdfromthe~astemainotch.Rotethatthe~ a&nosus(PDA)isvi~asanex~ofthemain pahomuy artery (MPA) and is bcatsd supehr puhmwy art&PA). The hctus is partially relativetothedimensionoftlwdeseendingaorta(DsAo).

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Thirty-eight infants met entrance criteria for this study. Of these, 1 was withdrawn because of unsuspected congenital cardiac disease diagnosed at the time of the initial echocardiographic evaluation (this patient had total anomalous pulmonary venous connection). The remaining 37 patients were divided into 2 groups by severity of RDS. Group 1 infants required endotracheal intubation and ventilatory assistance (20). Group 2 infants required either oxygen therapy only (14) or transient (

The timing of spontaneous closure of the ductus arteriosus in infants with respiratory distress syndrome.

Previous studies evaluating the incidence of patent ductus arteriosus have not made a distinction between physiologic ductal patency and abnormally pe...
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