Indomethacin-Responsive Patent Ductus Arteriosus in an Extremely Preterm Infant at 8 Weeks Postnatal Age

To the Editor: The ability of indomethacin in effecting patent ductus arteriosus (PDA) closure decreases with postnatal age [1, 2]. Here, we describe a patient where a hemodynamically significant PDA closed after indomethacin therapy at 8 wk postnatal age (34 wk postconceptual age). A 27-wk, 690 g newborn receiving mechanical ventilation developed a hemodynamically significant PDA (size 1.7 mm and LA/Ao ratio 2.1) on Day 3 of life. Oral ibuprofen courses, delayed due to sepsis with thrombocytopenia, administered on Days 10 and 13, were ineffective in closing the PDA (2.2 mm, LA/Ao 1.89). Intravenous indomethacin courses were given on Days 17 and 24. The PDA constricted (1.2 mm) by Day 26, and closed on Day 31. By this time, the baby had been extubated, and the sepsis treated. On Day 40, the baby had pulmonary bleeding and needed mechanical ventilation. Echocardiography revealed a hemodynamically significant PDA (2.6 mm, LA/Ao 1.6), and a third standard 3-dose course of indomethacin was administered. The PDA was confirmed closed on Day 43. Extubation to continuous positive airway pressure (CPAP) was successful at this stage. However, the ductus reopened on Day 46 (3.4 mm, La/Ao ratio 1.7). Thereafter, a 7-day course of low-dose indomethacin (0.1 mg/kg) was given. The PDA was documented to have closed on Day 52 of life and the baby remained stable thereafter and even improved beyond need of supplemental oxygen. Surgical ligation was withheld due to parental wishes, the extreme prematurity and low weight of the baby, incipient chronic lung disease (CLD), need for intubation and risk of prolonged ventilation for the surgery and its potentially hazardous complications. None of the known adverse effects associated with indomethacin therapy, namely, oliguria, thrombocytopenia or intestinal dysfunction, were encountered. The decreased effectiveness of prostaglandin synthesis inhibitors like indomethacin with increasing postnatal age may be due to a reduced role of prostaglandin in ductal patency and increased nitric oxide production in the ductal wall with increasing postnatal age [1]. Extremely premature infants have PDAs that are less sensitive to indomethacin, and unresponsive beyond 8 wk postnatal age according to Pacifici [2]. Achanti et al. also found indomethacin ineffective for ductal closure at 8 wk postnatal age [3]. McCarthy et al. have reported unsuccessful pharmacotherapy beyond 33 wk postconceptual age [4]. However, Sterniste et al. reported effective ductal closure with indomethacin in an ELBW infant at 11 wk postnatal age [5]. Our report demonstrates that although PDA in extremely premature babies can reopen after standard pharmacotherapy with indomethacin, it may still remain responsive to further doses even at an advanced postnatal age, and without any significant side-effects. It may therefore be worth attempting pharmacotherapy in similar cases, before opting for surgical treatment and its associated set of morbidities.