Prospective observational study of early respiratory management in preterm neonates less than 35 weeks of gestation.

BACKGROUND: Current guidelines for management of respiratory distress syndrome (RDS) recommend continuous positive airway pressure (CPAP) as the primary mode of respiratory support even in the most premature neonates, reserving endotracheal intubation (ETI) for rescue surfactant or respiratory failure. The incidence and timing of ETI in practice is poorly documented. METHODS: In 27 Level III NICUs in the US (n = 19), Canada (n = 3) and Poland (n = 5), demographics and baseline characteristics, respiratory support modalities including timing of ETI, administration of surfactant and caffeine/other methylxanthines, and neonatal morbidities were prospectively recorded in consecutive preterm neonates following written parental consent. Infants were divided into three groups according to gestational age (GA) at birth, namely 26-28, 29-32 and 33-34 weeks. Statistical comparisons between groups were done using Chi-Square tests. RESULTS: Of 2093 neonates (US = 1507, 254 Canada, 332 Poland), 378 (18%) were 26-28 weeks gestational age (GA), 835 (40%) were 29-32 weeks, and 880 (42%) were 33-34 weeks. Antenatal steroid use was 81% overall, and approximately 89% in neonates ≤32 weeks. RDS incidence and use of ventilatory or supplemental oxygen support were similar across all sites. CPAP was initiated in 43% of all infants, being highest in the 29-32-week group, with a lower proportion in other GA categories (p < 0.001). The overall rate of ETI was 74% for neonates 26-28 weeks (42% within 15 min of birth, 49% within 60 min, and 57% within 3 h), 33% for 29-32 weeks (13 16 and 21%, respectively), and 16% for 33-34 weeks (5, 6 and 8%, respectively). Overall intubation rates and timing were similar between countries in all GAs. Rates within each country varied widely, however. Across US sites, overall ETI rates in 26-28-week neonates were 30-60%, and ETI within 15 min varied from 0 to 83%. Similar within 15-min variability was seen at Polish sites (22-67%) in this GA, and within all countries for 29-32 and 33-34-week neonates. CONCLUSION: Despite published guidelines for management of RDS, rate and timing of ETI varies widely, apparently unrelated to severity of illness. The impact of this variability on outcome is unknown but provides opportunities for further approaches which can avoid the need for ETI.

Achieving and maintaining lung volume in the preterm infant: from the first breath to the NICU.

The main goal for the neonatologist is to facilitate the adaptation to extra-uterine life during initial transition, while minimizing lung injury opening and protecting the premature lung from the first breath onwards. An appropriate management from birth should lead to the achievement of an early functional residual capacity (FRC), and the following steps should aim at maintaining an adequate lung volume. To date, different strategies are available to optimize fetal-neonatal transition and promote lung recruitment. New ventilation approaches, such as sustained lung inflation (SLI) and "open lung strategy", well-established ventilation techniques with a more tailored application and less invasive modalities to administer surfactant have been recently introduced in clinical practice with promising results. CONCLUSIONS: given the current status of neonatal care, it seems that lung injury and BPD could be reduced with multiple strategies starting early in the delivery room. Literature underlines the importance of a respiratory tailored management of preterm infants from birth and during the whole NICU stay. What is Known: • Experimental and clinical studies have shown that the transition from fetal to adult type cardiorespiratory circulation needs an adequate lung ventilation. An appropriate management in the delivery room should lead to the achievement of an early FRC, and through the following steps, the neonatologist should aim at maintaining an adequate lung volume. • Literature underlines the importance of a respiratory tailored management of preterm infants during the whole NICU stay to maintain the benefits of a successful postnatal adaption. What is New: • Herewith, we describe the most relevant and recent interventions which can be performed from the delivery room to the NICU stay to guarantee an adequate tradition to postnatal life and an effective cardiorespiratory stability.

A pharmacoeconomic analysis of in-hospital costs resulting from reintubation in preterm infants treated with lucinactant, beractant, or poractant alfa.

OBJECTIVES: Reintubation and subsequent mechanical ventilation (MV) in preterm infants after surfactant replacement therapy are associated with excess morbidity and mortality and likely increase in-hospital costs. Specific surfactant therapy selection for prevention of respiratory distress syndrome (RDS) in preterm infants receiving conventional MV may impact not only clinical outcomes but also pharmacoeconomic outcomes. METHODS: We conducted a pharmacoeconomic analysis of the impact of surfactant selection and reintubation and subsequent MV of preterm infants on health care resource utilization. Rates of reintubation and duration of MV after reintubation were determined from 1546 preterm infants enrolled in two surfactant trials comparing lucinactant to beractant and poractant alfa. Hospital costs were obtained from a 2010 US database from 1564 preterm infants with RDS, with a direct cost of $2637 per day for MV in the neonatal intensive care unit. Cost of reintubation by study and treatment was estimated as the incidence of reintubation multiplied by days on MV therapy after reintubation multiplied by cost per day for direct MV costs, standardized per 100 surfactant-treated infants. RESULTS: There were no differences between studies or treatment groups in the overall extubation rate. Average MV duration following reintubation was similar between groups in both trials; however, reintubation rates were significantly lower (p<0 05) for infants treated with lucinactant than for those receiving beractant or poractant alfa. The observed differences in reintubation rates resulted in a projected cost saving of $160,013 to $252,203 per 100 infants treated with lucinactant versus animal-derived surfactants. CONCLUSIONS: In this analysis, higher reintubation rates following successful extubation in preterm infants receiving animal-derived surfactant preparations significantly increased estimated in-hospital costs, primarily due to excess costs associated with MV. This analysis suggests that surfactant selection may have a significant pharmacoeconomic impact on cost of patient care. Additional cost assessment of potential reduction in reintubation-associated morbidity is warranted.

A pilot, randomized, controlled clinical trial of lucinactant, a peptide-containing synthetic surfactant, in infants with acute hypoxemic respiratory failure.

OBJECTIVE: Inhibition of surfactant function and abnormal surfactant synthesis lead to surfactant dysfunction in children with acute hypoxemic respiratory failure. We evaluated whether intratracheal lucinactant, a synthetic, peptide-containing surfactant, was safe and well-tolerated in infants with acute hypoxemic respiratory failure, and assessed its effects on clinical outcomes. METHODS AND MAIN RESULTS: Infants ≤ 2 yrs of age with acute hypoxemic respiratory failure were enrolled in a phase II, double-blind, multinational, placebo-controlled randomized trial across 36 pediatric intensive care units. Infants requiring mechanical ventilation with persistent hypoxemia meeting acute lung injury criteria were randomized to receive intratracheal lucinactant (175 mg/kg) or air placebo. One retreatment was allowed 12-24 hrs after initial dosing if hypoxemia persisted. Peri-dosing tolerability of intratracheal lucinactant and adverse experiences were assessed. Mechanical ventilation duration was analyzed using analysis of variance. The Cochran-Mantel-Haenszel test was used for categorical variables.We enrolled 165 infants (84 lucinactant; 81 placebo) with acute hypoxemic respiratory failure. There were no significant differences in baseline subject characteristics, with the exception of a lower positive end-expiratory pressure and higher tidal volume in placebo subjects. The incidence of transient peri-dosing bradycardia and desaturation was significantly higher in the lucinactant treatment group. There were no statistical differences between groups for other adverse events or mortality. Oxygenation improved in infants randomized to receive lucinactant as indicated by fewer second treatments (67% lucinactant vs. 81% placebo, p = .02) and a trend in improvement in partial pressure of oxygen in arterial blood to fraction of inspired oxygen from eligibility to 48 hrs after dose (p = .06). There was no significant reduction in duration of mechanical ventilation with lucinactant (geometric least square means: 4.0 days lucinactant vs. 4.5 days placebo; p = .254). In a subset of infants (n = 22), the duration of mechanical ventilation in children with acute lung injury (partial pressure of oxygen in arterial blood to fraction of inspired oxygen >200) was significantly shorter with lucinactant (least square means: 2.4 days lucinactant vs. 4.3 days placebo; p = .006). CONCLUSIONS: In mechanically ventilated infants with acute hypoxemic respiratory failure, treatment with intratracheal lucinactant appeared to be generally safe. An improvement in oxygenation and a significantly reduced requirement for retreatment suggests that lucinactant might improve lung function in infants with acute hypoxemic respiratory failure.

Animal-derived surfactants for the treatment and prevention of neonatal respiratory distress syndrome: summary of clinical trials.

INTRODUCTION: Available literature suggests that the advantage of animal-derived surfactants over first-generation synthetic agents derives from the presence of surface-active proteins and their phospholipid content. Here we summarize the results of clinical trials comparing animal-derived surfactant preparations with other animal-derived surfactants and with both first-and second-generation synthetic surfactants. METHODS: Published clinical trials of comparisons of animal-derived surfactants were summarized and compared. Comparisons emphasized differences in (1) key surfactant components attributed with efficacy and (2) differences in published outcomes. RESULTS: For the most important outcomes, mortality and chronic lung disease, currently available natural surfactants are essentially similar in efficacy. When examining secondary outcomes (pneumothorax, ventilator weaning, and need for supplemental oxygen), it appears that both calfactant and poractant have an advantage over beractant. The weight of the evidence, especially for study design and secondary outcomes, favors the use of calfactant. However, the superiority of poractant over beractant, when the higher initial dose of poractant is used, strengthens the case for use of poractant as well. CONCLUSIONS: Clinical trials suggest that the higher surfactant protein-B content in calfactant, and perhaps the higher phospholipid content in poractant (at higher initial dose), are the factors that most likely confer the observed advantage over other surfactant preparations.

Postnatal dexamethasone therapy and cerebral tissue volumes in extremely low birth weight infants.

OBJECTIVE: Our goal was to relate postnatal dexamethasone therapy in extremely low birth weight infants (birth weight of < or = 1000 g) to their total and regional brain volumes, as measured by volumetric MRI performed at term-equivalent age. METHODS: Among 53 extremely low birth weight infants discharged between June 1 and December 31, 2003, 41 had high-quality MRI studies; 30 of those infants had not received postnatal steroid treatment and 11 had received dexamethasone, all after postnatal age of 28 days, for a mean duration of 6.8 days and a mean cumulative dose of 2.8 mg/kg. Anatomic brain MRI scans obtained at 39.5 weeks (mean) postmenstrual age were segmented by using semiautomated and manual, pretested, scoring algorithms to generate three-dimensional cerebral component volumes. Volumes were adjusted according to postmenstrual age at MRI. RESULTS: After controlling for postmenstrual age at MRI, we observed a 10.2% smaller total cerebral tissue volume in the dexamethasone-treated group, compared with the untreated group. Cortical tissue volume was 8.7% smaller in the treated infants, compared with untreated infants. Regional volume analysis revealed a 20.6% smaller cerebellum and a 19.9% reduction in subcortical gray matter in the dexamethasone-treated infants, compared with untreated infants. In a series of regression analyses, the reductions in total cerebral tissue, subcortical gray matter, and cerebellar volumes associated with dexamethasone administration remained significant after controlling not only for postmenstrual age but also for bronchopulmonary dysplasia and birth weight. CONCLUSIONS: We identified smaller total and regional cerebral tissue volumes in extremely low birth weight infants treated with relatively conservative regimens of dexamethasone. These volume deficits may be the structural antecedents of neuromotor and cognitive abnormalities reported after postnatal dexamethasone treatment.

Longitudinal assessment of heart rate variability in very low birth weight infants during their NICU stay.

BACKGROUND: Maturation of the autonomic nervous system has not been studied in high-risk very low birth weight (VLBW) infants in the first few weeks of life. AIM: To characterize developmental changes in autonomic nervous system activity of high-risk VLBW infants from 23 to 38 weeks post-menstrual age by measuring heart rate variability (HRV). STUDY DESIGN AND SUBJECTS: In this prospective cohort study 38 infants admitted to Children's Memorial Hermann Hospital NICU were longitudinally followed weekly or biweekly. Heart period data were recorded while infants were resting in active sleep. OUTCOME MEASURES: Growth of spectral power of HRV in low-frequency (0.05-0.25 Hz) and high-frequency (0.25-1.00 Hz) bands was modeled with linear mixed-effects models. The high-frequency power provides a measure of respiratory sinus arrhythmia (RSA). RESULTS: Low-frequency power increases with post-menstrual age, and intubated infants have lower HRV. The increase in low-frequency power is faster (0.50+/-0.12 dB/week) than the increase in RSA (0.17+/-0.09 dB/week). CONCLUSION: This longitudinal data exhibits developmental maturation of the RSA and of the low-frequency power of HRV in high-risk VLBW infants.

Evidence-based management of infants with congenital diaphragmatic hernia.

The mortality rate associated with congenital diaphragmatic hernia (CDH) varies widely between centers and remains relatively high despite widespread use of new therapeutic modalities. Many of these have been implemented without properly controlled studies. Over the past 10 to 15 years, only 9 randomized trials enrolling a total of approximately 250 infants with CDH have been published. The limited evidence available suggests that better outcomes are observed by delivering infants with CDH at experienced centers, by delaying surgical repair until hemodynamic and respiratory stability is achieved, and by the judicious utilization of nonaggressive mechanical ventilation and permissive hypercapnea. Other therapeutic modalities, such as high frequency oscillatory ventilation, inhaled nitric oxide, and ECMO, may provide additional advantages for selected infants. There is a dire need to establish networks of centers that manage enough infants with CDH, to conduct appropriately sized randomized trials that can answer some of the critical questions about the management and long-term outcome of these infants.

Regulation of human pulmonary surfactant protein gene expression by 1alpha,25-dihydroxyvitamin D3.

1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] has been reported to stimulate lung maturity, alveolar type II cell differentiation, and pulmonary surfactant synthesis in rat lung. We hypothesized that 1,25(OH)(2)D(3) stimulates expression of surfactant protein-A (SP-A), SP-B, and SP-C in human fetal lung and type II cells. We found that immunoreactive vitamin D receptor was detectable in fetal lung tissue and type II cells only when incubated with 1,25(OH)(2)D(3). 1,25(OH)(2)D(3) significantly decreased SP-A mRNA in human fetal lung tissue but did not significantly decrease SP-A protein in the tissue. In type II cells, 1,25(OH)(2)D(3) alone had no significant effect on SP-A mRNA or protein levels but reduced SP-A mRNA and protein in a dose-dependent manner when the cells were incubated with cAMP. SP-A mRNA levels in NCI-H441 cells, a nonciliated bronchiolar epithelial (Clara) cell line, were decreased in a dose-dependent manner in the absence or presence of cAMP. 1,25(OH)(2)D(3) had no significant effect on SP-B mRNA levels in lung tissue but increased SP-B mRNA and protein levels in type II cells incubated in the absence or presence of cAMP. Expression of SP-C mRNA was unaffected by 1,25(OH)(2)D(3) in lung tissue incubated +/- cAMP. These results suggest that regulation of surfactant protein gene expression in human lung and type II cells by 1,25(OH)(2)D(3) is not coordinated; 1,25(OH)(2)D(3) decreases SP-A mRNA and protein levels in both fetal lung tissue and type II cells, increases SP-B mRNA and protein levels only in type II cells, and has no effect on SP-C mRNA levels.

A multicenter, randomized, masked, comparison trial of lucinactant, colfosceril palmitate, and beractant for the prevention of respiratory distress syndrome among very preterm infants.

BACKGROUND AND OBJECTIVE: Evidence suggests that synthetic surfactants consisting solely of phospholipids can be improved through the addition of peptides, such as sinapultide, that mimic the action of human surfactant protein-B (SP-B). A synthetic surfactant containing a mimic of SP-B may also reduce the potential risks associated with the use of animal-derived products. Our objective was to compare the efficacy and safety of a novel synthetic surfactant containing a functional SP-B mimic (lucinactant; Discovery Laboratories, Doylestown, PA) with those of a non-protein-containing synthetic surfactant (colfosceril palmitate; GlaxoSmithKline, Brentford, United Kingdom) and a bovine-derived surfactant (beractant; Abbott Laboratories, Abbott Park, IL) in the prevention of neonatal respiratory distress syndrome (RDS) and RDS-related death. METHODS: We assigned randomly (double-masked) 1294 very preterm infants, weighing 600 to 1250 g and of < or =32 weeks gestational age, to receive colfosceril palmitate (n = 509), lucinactant (n = 527), or beractant (n = 258) within 20 to 30 minutes after birth. Primary outcome measures were the rates of RDS at 24 hours and the rates of death related to RDS during the first 14 days after birth. All-cause mortality rates, bronchopulmonary dysplasia (BPD) rates, and rates of other complications of prematurity were prespecified secondary outcomes. Primary outcomes, air leaks, and causes of death were assigned by an independent, masked, adjudication committee with prespecified definitions. The study was monitored by an independent data safety monitoring board. RESULTS: Lucinactant reduced significantly the incidence of RDS at 24 hours, compared with colfosceril (39.1% vs 47.2%; odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.52-0.89). There was no significant difference in comparison with beractant (33.3%). However, lucinactant reduced significantly RDS-related mortality rates by 14 days of life, compared with both colfosceril (4.7% vs 9.4%; OR: 0.43; 95% CI: 0.25-0.73) and beractant (10.5%; OR: 0.35; 95% CI: 0.18-0.66). In addition, BPD at 36 weeks postmenstrual age was significantly less common with lucinactant than with colfosceril (40.2% vs 45.0%; OR: 0.75; 95% CI: 0.56-0.99), and the all-cause mortality rate at 36 weeks postmenstrual age was lower with lucinactant than with beractant (21% vs 26%; OR: 0.67; 95% CI: 0.45-1.00). CONCLUSIONS: Lucinactant is a more effective surfactant preparation than colfosceril palmitate for the prevention of RDS. In addition, lucinactant reduces the incidence of BPD, compared with colfosceril palmitate, and decreases RDS-related mortality rates, compared with beractant. Therefore, we conclude that lucinactant, the first of a new class of surfactants containing a functional protein analog of SP-B, is an effective therapeutic option for preterm infants at risk for RDS.

Interaction of an artificial surfactant in human pulmonary epithelial cells.

Surfaxin (lucinactant), a peptide-based surfactant consisting of dipalmitoylphosphatidylcholine (DPPC) plus KL(4) (sinapultide) (a synthetic peptide modeled after human surfactant protein-B), is effective in treating respiratory distress syndrome in preterm infants. Our goal was to determine the uptake and effects of Surfaxin on human pulmonary type II cells isolated from fetal tissue and other lung cell types. Based on previous published reports, we hypothesized that this exogenous synthetic surfactant would have little effect on type II cell surfactant-related physiological features. Human type II cells and A549 and NCI-H441 adenocarcinoma cells incorporated (3)H-KL(4) and (14)C-DPPC components in Surfaxin, but with different kinetics. Fractionation of NCI-H441 and A549 cellular components indicated that the highest specific activity of (3)H-KL(4) was present in the 18,000g cellular fraction (which contains vesicles and lysosomes). The number of lamellar bodies (LBs) appears to increase in human type II cells incubated in the presence of Surfaxin when visualized by light microscopy, while LB structure (determined by electron microscopy) was not altered. Expression of endogenous surfactant protein (SP-A, SP-B, and SP-C) mRNA levels in human type II cells was not altered by the presence of Surfaxin. We conclude that while human type II cells and other lung cell types can incorporate the components of Surfaxin, the surfactant-related physiological functions of these cells are not altered.

Randomized, controlled trial of slow versus rapid feeding volume advancement in preterm infants.

OBJECTIVES: To determine whether infants who are fed initially and advanced at 30 mL/kg per day (intervention) take fewer days to get to full feedings than those who are fed initially and advanced at 20 mL/kg per day (control), without increasing their incidence of feeding complications and necrotizing enterocolitis (NEC). We also examined whether these infants regain birth weight earlier, have fewer days of intravenous fluids, and a have shorter hospital stay. METHODS: A randomized, controlled, single-center trial was conducted in a Neonatal Intensive Care Unit of a community-based county hospital in Houston, Texas. Infants between 1000 and 2000 g at birth, gestational age < or =35 weeks, and weight appropriate for gestational age were allocated randomly to feedings of expressed human milk or Enfamil formula starting and advanced at either 30 mL/kg per day or 20 mL/kg per day. Infants remained in the study until discharge or development of stage > or =IIA NEC. RESULTS: A total of 155 infants were enrolled: 72 infants in the intervention group and 83 in the control group. Infants in the intervention group achieved full-volume feedings sooner (7 vs 10 days, median), regained birth weight faster (11 vs 13 days, median), and had fewer days of intravenous fluids (6 vs 8 days, median). Three infants in the intervention group and 2 control infants developed NEC for an overall incidence of 3.2% (relative risk: 1.73; 95% confidence interval: 0.30-10.06). CONCLUSION: Among infants between 1000 and 2000 g at birth, starting and advancing feedings at 30 mL/kg per day seems to be a safe practice and results in fewer days to reach full-volume feedings than using 20 mL/kg per day. This intervention also leads to faster weight gain and fewer days of intravenous fluids.

Surfactant replacement therapy on ECMO does not improve outcome in neonates with congenital diaphragmatic hernia.

BACKGROUND PURPOSE: Respiratory failure in neonates with congenital diaphragmatic hernia (CDH) may in part be caused by a primary or secondary surfactant deficiency. Knowledge of the optimal approach to surfactant replacement in neonates with CDH and respiratory failure is limited. The aim of this study was to determine if surfactant replacement on extracorporeal membrane oxygenation (ECMO) results in improved outcomes in neonates > or =35 weeks' gestation with unrepaired CDH. METHODS: Using the CDH Study Group Registry, the authors identified 448 neonates with CDH who were > or =35 weeks' gestation, had no major anomalies, were treated with ECMO within the first 7 days of life, and underwent repair on or after ECMO therapy. Patients in 2 groups were compared: group 1 (- Surf, n = 334) consisted of patients who received no surfactant and group 2 (+ Surf, n = 114) consisted of patients who received at least 1 dose of surfactant while on ECMO. An analysis of all patients in both groups was performed. Additionally, subgroup analyses stratified by gestational age were performed for patients 351/7 to 366/7 weeks' gestation and for patients > or =37 weeks' gestation. Primary end-points for the study were survival and length of ECMO run. Secondary end-points were length of intubation, need for supplemental oxygen at 30 days of life, and at discharge to home. Demographic, clinical, and outcome variables were examined using Fisher's Exact tests for categorical variables and using unpaired t tests for continuous variables. Odds ratios were calculated for categorical end-point variables. RESULTS: Demographic and clinical variables were similar between groups. Analyses of aggregate data showed no significant differences between groups in length of ECMO run, survival, number of days intubated, and percent of patients requiring supplemental oxygen at 30 days or discharge. Subgroup stratification by gestational age did not show significant differences between groups in any of the outcome variables. CONCLUSIONS: The data from this study suggest that surfactant replacement on ECMO for neonates with congenital diaphragmatic hernia does not provide significant benefit in the infant's clinical course with respect to survival, length of ECMO course, length of intubation, or subsequent need for supplemental oxygen.

Surfactant does not improve survival rate in preterm infants with congenital diaphragmatic hernia.

BACKGROUND: Use of exogenous surfactant in congenital diaphragmatic hernia (CDH) patients is routine in many centers. The authors sought to determine the impact of surfactant use in the premature infant with CDH. METHODS: Data on liveborn infants with CDH from participating institutions were collected prospectively. Surfactant use and timing and outcome data were analyzed retrospectively. The authors evaluated the prenatal diagnosis patients as well. The outcome variable was survival to discharge. Odds ratios with confidence intervals were calculated. RESULTS: Five hundred ten infants less than 37 weeks' gestation were entered in the CDH registry. Infants with severe anomalies (n = 80) were excluded. Information on surfactant use was available for 424 patients. Infants receiving surfactant (n = 209) had a greater odds of death than infants not receiving surfactant (n = 215, odds ratio, 2.17, 95% CI: 1.5 to 3.2; P <.01). In prenatally diagnosed infants with immediate distress, there was a trend toward worse survival rates among those receiving surfactant at 1 hour (52 patients) versus those that did not (93 patients; odds ratio, 1.93, 95% CI: 0.96 to 3.9; P <.07). CONCLUSIONS: Surfactant, as currently used, is associated with a lower survival rate in preterm infants with CDH. The use of surfactant replacement in premature infants with CDH can be recommended only within the context of a randomized clinical trial.

Risk factors predicting vasopressor use after patent ductus arteriosus ligation.

Ligation of the patent ductus arteriosus (PDA) is sometimes complicated by postoperative hypotension requiring vasopressor(s). It is unclear which infants are at risk for this complication. We conducted a retrospective and prospective cohort study to identify risk factors predicting vasopressor use after PDA ligation. Our patients were infants < 37 weeks of gestation who underwent PDA ligation. The primary outcome was the use of vasopressor(s) within 72 hours after PDA ligation, defined as beginning vasopressor(s) or increasing the dose of vasopressor(s). Thirty-two of 100 (32%) study infants required vasopressor(s) after PDA ligation. Infants who had lower birth weights, lower gestational ages, higher ventilator support, or whose mothers had received antenatal steroids had a higher risk of vasopressor use. Infants who required vasopressor(s) were at increased risk of dying before 36 weeks postmenstrual age. Lower birth weight, lower gestational age, and higher respiratory support define a high-risk subgroup of patients in whom the prophylactic administration of vasopressor(s) could be studied.