Correlation between the Closure Time of Patent Ductus Arteriosus in Preterm Infants and Long-Term Neurodevelopmental Outcome

Abstract

In patent ductus arteriosus (PDA) in preterm infants, the relationship between treatment timing and long-term developmental prognosis remains unclear. The purpose of this study was to clarify the relationship between the age in days when ductus arteriosus closure occurred and long-term development. Preterm infants with a birth weight of less than 1500 g who were admitted to our NICU over a period of 9 years (2011–2019) and were diagnosed with PDA were included. A new version of the K-type developmental test for corrected ages of 1.5 and 3 years was used as an index of development. The relationship between the duration of PDA and the developmental index was evaluated using Pearson’s correlation coefficient, and multiple regression analysis was performed. Development quotient (DQ) at the ages of 1.5 and 3 years showed a correlation with the PDA closure date and the standard deviation (SD) value of the term birth weight. Multiple regression analysis showed a positive correlation of the DQ at 1.5 and 3 years with the SD value of the term birth weight and a negative correlation with the PDA closure date. In addition, a stronger correlation was found in the “posture/motor” sub-item at 3 years. On the other hand, the analysis including preterm infants without PDA showed that preterm infants with PDA closure on the 6th day or later after birth had a significantly lower 3-year-old DQ than preterm infants with a PDA exposure within 5 days. In conclusion, it is suggested that the decrease in cerebral blood flow due to PDA in preterm infants has an adverse effect on long-term neurodevelopment. Appropriate interventions, including surgical treatment for PDA in preterm infants without delay, ideally within 5 days of birth, may be effective in improving the developmental prognosis.

Who Still Gets Ligated? Reasons for Persistence of Surgical Ligation of the Patent Ductus Arteriosus Following Availability of Transcatheter Device Occlusion for Premature Neonates

“…The current state of the field is centered on understanding overall trends of definitive procedural closure [1][2][3], comparing short-and long-term outcomes between surgical ligation a device occlusion [12,32], and exploring a prospective outcomes-based randomized controlled trial (PIVOTAL NCT05547165) to determine the effectiveness of treatments for the "high-risk" premature infants with a hsPDA. In comparison to device closure, infants undergoing surgical ligation have more respiratory instability with a greater need for high-frequency ventilation after the procedure [15,21], take longer to wean to extubation, have a higher incidence of post-closure cardiac compromise (aka low cardiac output syndrome) [15,19,33,34], have longer intensive care and hospital lengths of stay, higher costs [13], and increased mortality [13,21].…”

“…Surgical ligation rates of the patent ductus arteriosus (PDA) have declined over the past two decades in premature infants [1][2][3][4][5][6][7]. Contemporary evidence suggests that the temporal shifts away from surgical ligation rates resulted from the appreciation that spontaneous closure of the ductus occurred more frequently than once expected [8,9] and negative associations with adverse neonatal and neurodevelopmental outcomes [9][10][11][12]. The trend has been more pronounced since the 2019 United States Food and Drug Administration (FDA) approval of a transcatheter device to occlude the PDA in premature infants with the rapid increase in institutions capable of performing device closures [1][2][3].…”