Persistent Ductus Arteriosus in Critically Ill Preterm Infants

Abstract

Introduction: Persistent ductus arteriosus (PDA) is found with increased incidence in preterm infants, significantly affecting neonatal morbidity and mortality rates. Aim: To evaluate the association between the presence of PDA and the severity of clinical condition at birth in critically ill preterm infants, with gestational ages (GA) ≤ 32 weeks and severe respiratory distress. Methods: All preterm infants with GA ≤ 32 weeks admitted to the neonatal intensive care unit (NICU) of the Clinical County Emergency Hospital, Sibiu between 1 January 2010 and 31 December 2015 were included in the study. These were categorized as Group 1 [Preterm infants with PDA; n=154] and Group 2 [Preterm infants without PDA; n=186]. Epidemiological and clinical data were collected in the National Registry for Respiratory Distress Syndrome for all children, and data related to prenatal period, clinical characteristics at birth i.e GA, weight, gender, Apgar scores, and clinical features such as resuscitation at birth, surfactant administration, need and duration of respiratory support, neonatal sepsis, complications associated with prematurity, and death, were analyzed. Results: Group 1 infants had significantly lower GA and birth weights, were more often out born (p=0.049, HR 1.69), and had significantly lower Apgar scores at 1 and 10 minutes (p=0.022, p=0.000). They presented a significantly higher need for surfactant administration (42.9% vs 24.7%, p<0.0001) and respiratory support (96.8% vs 90.3%, HR 3.19, p=0.019 for need of CPAP and 22.1% vs 10.8%, HR 2.35, p=0.004 for mechanical ventilation). Duration of respiratory support was also significantly higher in the Group 1 (7.6%±7.5 vs. 5.1±3.8 days, p<0.0001 for CPAP and 20.1±22.5 vs. 12.0±15.7 days, p<0.0001 for mechanical ventilation). Conclusion:In very preterm infants, PDA may be associated with a critical clinical condition leading to serious complications. The presence of PDA after the seventh day of life was associated with an increased need for respiratory support, both CPAP and mechanical ventilation, increased severity of the respiratory distress syndrome, requiring a longer duration of respiratory support, and increased the hospitalization length. In very preterm infants, PDA presence was also associated with a higher rate of severe complications and death, indicating the need for a careful and proper management of these critical cases in neonatal intensive care units.

Related Factors of Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-Analysis

“…It is a well-recognized fact that the incidence of PDA is inversely related to GA and BW of infants (15,18,(29)(30)(31)(32)(33)(34). The study of Koch et al (35) showed that with each additional week of GA, the probability of spontaneous closure of the DA increased by 1.5 times.…”

“…Our study confirms the results of prior meta-analysis (21), which supported a positive correlation between CA and PDA in preterm infants. On the one hand, CA is a definite risk factor for preterm birth (40,41), and on the other hand, some cytokines regarding inflammatory process result in some hemodynamic changes (18,21,42). Interestingly, another meta-analysis on the same theme revealed that it was the confounders (differences in GA and BW) that considerably influenced the association between CA and PDA, and even CA played a protective role in the occurrence of PDA by facilitating lung maturation and diminishing the use of surfactant and mechanical ventilation (20,43).…”

“…Left-to-right shunting across the DA results in pulmonary overcirculation and decreased systemic perfusion. "Diastolic steal" through the DA to the lungs reduces the blood supply to other organs, escalating the rate of IVH and NEC (18,49,(53)(54)(55)(56)(57)(58). The mechanism of RDS causing PDA is mainly related to hypoxemia, and pulmonary hyperperfusion resulting from PDA impairs surfactant production in the alveolar cells, which means the relationship between PDA and RDS is complex and bidirectional (15,18,23,49).…”

“…The mechanism of RDS causing PDA is mainly related to hypoxemia, and pulmonary hyperperfusion resulting from PDA impairs surfactant production in the alveolar cells, which means the relationship between PDA and RDS is complex and bidirectional (15,18,23,49). PDA can promote an interstitial and alveolar pulmonary edema and decreased lung compliance, and in turn, it gives rise to higher ventilator settings and prolonged ventilation duration, which has been implicated in the pathogenesis of BPD (18,49,54,(59)(60)(61)(62)(63). In recent studies, Clyman et al found that exposure to PDA increased risk of BPD only when the infants required at least 10 days of intubation, and the incidence of BPD (grades 2 and 3) was low in infants requiring less ventilatory support, regardless of whether PDA constricted or remained open for several weeks (64,65).…”

“…A growing body of evidence from recent articles has suggested that a few variables have a causal impact on PDA, notwithstanding some of which are still controversial (11)(12)(13)(14)(15)(16)(17)(18)(19). Although there have been several meta-analyses endeavoring to address these conflicting disputes, unfortunately, they focus only on certain one related factor of PDA (20)(21)(22)(23), while it is a multifactorial disease, and many factors play different roles in the pathophysiological process.…”