A total of 189 infants with a BW < 1000 gm were born at the Mount Sinai Hospital between August 1, 2004 and July 31, 2009. Of those patients, 14 patients with major congenital anomalies and 37 who died at age < 48 hours of life were excluded from the analysis.
Data from the remaining 138 patients were reviewed. Among those 138 patients, 26 died before discharge. Seven of those 26 died at age ≤ 7 days of life. The causes of death for those 26 patients were mainly respiratory failure due to extremely immature lungs (13/26). Other causes of death include NEC or sepsis (9/26), severe IVH (2/26), and twin to twin transfusion (2/26). Of the 112 babies who survived to discharge, 32 (28.6%) did not develop a hemodynamically significant PDA (the DA closed spontaneously). The remaining 80 patients (71.4%) were diagnosed with a hemodynamically significant PDA and received at least one course of COI. Among the 80 patients who received COI treatment for a PDA, 26 (32.5%) infants closed their PDA after one course of COI. One infant had her PDA ligated after the failure of one course of COI to achieve ductal closure due to significant side effects of COI usage. The remaining 53 patients received a second course of COI and 16 of these patients (30.2%) closed their PDA after the second course of COI. Therefore, there were a total of 37 of 80 patients (46.2%) whose DA remained clinically significant after 2 courses of COI treatment. PDAs were ligated in 22 out of these 37 patients after the second course and the other 15 babies received a third course of COI. Among the 15 infants who received a third course, 6 (40%) closed their PDA and the remaining 9 infants underwent PDA ligation. Therefore, a total of 32/80 (40%) underwent surgical ligation of the PDA. Most of the ligations were performed in the second or third week of life.
Detailed analysis was done on those 112 patients who survived to discharge. The demographics of infants with vs. those without hemodynamically significant PDAs are shown in Table . The babies with hemodynamically significant PDAs were less mature, had lower birth weights, higher CRIB II scores, higher OI, and received more fluid during the first 3 days of life. The overall outcomes for babies with hemodynamically significant PDAs were worse, as evidenced by an older age at extubation, reaching full enteral feeds later, and having a longer duration of hospitalization. Furthermore, the babies with hemodynamically significant PDAs had a higher incidence of CLD and ROP.
Demographics of the ELBW infants who survived to discharge
In order to ascertain whether these adverse outcomes in the babies with hemodynamically significant PDA might be attributable to the pre-existing risk factors of lower birth weight, lower gestational age, higher CRIB II scores, and higher OIs in these infants, we performed a multivariable logistic regression analysis. Since both birth weight and gestational age are included in the CRIB II score, logistic regression with CLD as the clinical outcome adjusted for CRIB II and OI was performed. This analysis reveals an adjusted odds ratio for CLD in those with vs. those without PDA of 1.10 (95% confidence interval [CI]: 0.37 - 3.30, P = 0.867). Similarly, the adjusted odds ratio for ROP in those with vs. those without symptomatic PDA is 3.20 (95% CI: 0.93 - 11.10, P = 0.065). These data suggest that the observed difference in CLD and ROP in babies with hemodynamically significant PDA vs. those without can be explained by the babies with hemodynamically significant PDA being less mature, having a lower birth weight, and being sicker as indicated by higher CRIB II scores and OI. Furthermore, multivariable regression analysis shows that a hemodynamically significant PDA did not add significantly to either CRIB II score or gestational age alone as a predictor of age at extubation or age at discharge. However, a multivariable regression analysis shows that the addition of a hemodynamically significant PDA to either CRIB II (R2 increases from 0.176 to 0.234 by addition of PDA to the model, p = 0.006) or gestational age (R2 increases from 0.195 to 0.232 by addition of PDA to the model, p = 0.025) improves a regression model for predicting age at full feeds. Presence of a hemodynamically significant PDA prolongs the time to full feeds by 8.0 ± 2.8 days in the multivariable model with CRIB II score and by 6.8 ± 3.0 days in the model with gestational age.
Among the 80 patients who received COI treatment for PDA, 26 (32.5%) infants closed their PDA after one course of COI. The comparisons of the infants whose DA closed with 1st course vs. who did not close with 1st course are presented in Table . As shown in the Table , other than the babies whose PDA was closed with the first course of COI being slightly more mature than those whose PDA did not close, none of the factors that we examined distinguished infants who responded to one course COI vs. those who did not.
Comparisons of the ELBW infants whose DA closed with 1st course of COI vs. who did not close with 1st course
The baseline characteristics of infants whose PDA closed with either one course or two courses of COI vs. those whose DA remained patent after 2nd course of COI are presented in Table . The babies whose PDA closed with either one or two courses of COI were slightly more mature than those who had persistent hemodynamically significant PDA but were otherwise not different (we excluded the baby whose PDA was ligated after the first course of COI). As is shown in Table , the incidence of CLD in infants whose DA remained patent after two courses of COI was almost twice that of babies whose DA closed with either one or two courses of COI. Furthermore, logistic regression analysis shows that, when compared to those whose PDA was successfully closed with the first or second course of COI, after adjusting for CRIB II score, OI, intubation for more than 2 days, and culture proven later onset bacteremia, the odds ratio of having CLD for surviving babies with persistent hemodynamically significant PDA is 3.24 (95% CI: 1.07 - 9.81, p = 0.038). Adding PDA ligation as a potential confounder did not improve the logistic model. These data demonstrate that failure of closure of PDA after 2 courses of COI is a significant risk factor for development of CLD in ELBW infants.
Baseline characteristic of the ELBW infants whose DA was closed after 2nd course COI vs. those whose DA remained patent after 2nd course
Outcomes of the ELBW infants whose DA was closed after 2nd course COI vs. those whose DA remained patent after 2nd course
Table shows a comparison of infants with PDA which closed with one (n = 26), two (n = 16), or three (n = 6) courses of COI vs. those who underwent surgical ligation after failure of one (n = 1), two (n = 22), or three (n = 9) courses of COI. Other than the fact that babies whose DAs were ligated received more courses of COI, neither the risk factors nor the outcomes we examined distinguished the babies who underwent ligation from those who did not.
Comparisons of ELBW infants with PDA closed by COI treatment vs. those with PDA who failed medical treatment and underwent surgical ligation