In this study, 90 premature infants with BW between 600-1250g and GA between 23-29 wks who received prophylactic surfactant were entered into a prospective, randomized, controlled trial to receive either ICN (0.1 mg/Kg/dose) or sham (S) at < 24 H following birth and again every 24 H for a total of six doses to prevent a patent ductus arteriosus (PDA). Echocardiograms (ECHO) were performed on day 1 prior to ICN or S and again on day 7, 24 H after the last dose. Hemodynamically significant PDAs were confirmed with a routine ECHO and these non-responders (NRs) were treated with standard ICN or ligation. Serum ICN levels were obtained at the following times: 24 H after the initial dose in all patients, 24 H after dose 6(steady-state) in responders (Rs), and in NRs when a symptomatic PDA was confirmed. 43 infants received ICN (BW=915±209gm, GA=26.4±1.6wks) and 47 received S (BW=879±202gm, GA=26.4±1.8wks), p=not significant. Nine of 43 (21%) ICN-treated infants were NRs compared with 22 of 47 (47%) S-treated infants (P<0.018). Results from the 43 ICN-treated patients are summarized below:Table

Table 1
Full size table

At the mean time NRs became symptomatic and needed treatment with standard ICN or ligation (26.3H), their mean ICN level was not significantly different than the Rs mean ICN level 24 H after dose 1. At steady-state, Rs achieved a mean ICN level of 0.64 ± 0.32 mcg/ml.

We conclude that, in general, prophylactic low-dose ICN promotes ductal closure in this population. These data suggest that smaller, more premature infants will more likely be non-responders to low-dose prophylactic ICN (0.1 mg/kg/dose) and will require a different dosing regimen to elicit ductal closure.