Seizures after initiation of rewarming in cooled infants with hypoxic ischaemic encephalopathy.

BACKGROUND: Seizures after initiation of rewarming from therapeutic hypothermia for neonatal encephalopathy are well recognised but not easy to predict. METHODS: A secondary analysis was performed of NEOLEV2 trial data, a multicentre randomised trial of levetiracetam versus phenobarbital for neonatal seizures. Enrolled infants underwent continuous video EEG (cEEG) monitoring. The trial data were reviewed for 42 infants with seizures during therapeutic hypothermia and 118 infants who received therapeutic hypothermia but had no seizures on cEEG. RESULTS: Overall, 112 of 160 (70%) had cEEG monitoring continued until rewarming was completed. Of the 42 infants with prior seizures, there were 30 infants with valid cEEG available and seizures occurred following the initiation of rewarming in 8 (26.6%). For the 118 seizure-naive infants, 82 (69.5%) continued cEEG until either rewarming was completed or 90 h of age and none had documented seizures. CONCLUSION: Overall, just over a quarter of infants with prior seizures had cEEG evidence of at least one seizure in the 24 h after initiation of rewarming but no seizure-naive infant had cEEG evidence of seizure(s) on rewarming. Critically, by reporting the two groups separately, the data can provide guidance on the duration of EEG monitoring. IMPACT: Infants with hypoxic ischaemic encephalopathy who have cEEG evidence of seizures during therapeutic hypothermia have a significant risk of further seizures on rewarming. For infants with hypoxic ischaemic encephalopathy but no cEEG evidence of seizures during therapeutic hypothermia, there is very little risk of de novo seizures. Ongoing work utilising large cohorts may generate EEG criteria that refine estimates of risk for rewarming seizures. Based on current experience, if seizures have occurred during therapeutic hypothermia for hypoxic ischaemic encephalopathy, the EEG monitoring should be continued during rewarming and for 12 h thereafter to minimise the risk of missing an event.

Use of Pulse Oximetry Pulsatility Index Screening for Critical Congenital Heart Disease.

OBJECTIVE: This study aimed to compare oximetry data (pre- and postductal oxygen saturation [SpO2], pre- and postductal pulsatility index [PI]) in healthy newborns (≥35 weeks' gestational age) to infants who have critical congenital heart disease (CCHD). STUDY DESIGN: This is a retrospective analysis of data obtained from electronic medical records, recorded as part of routine pulse oximetry screening (POS) for CCHD in infants born between the years 2013 and 2020. Testing was performed at 24 ± 2 hours of life. Data were analyzed to detect differences in pre- and postductal SpO2 and pre- and postductal PI in healthy newborns compared with infants who have CCHD. Newborns were excluded from analysis if they: (1) had a prenatal diagnosis of CCHD in the medical record, (2) had previously been admitted to the neonatal intensive care unit, or (3) had failed POS but were found no CCHD by diagnostic echocardiography. RESULTS: A total of 88,754 healthy newborns had received POS between the years 2013 and 2020. Of the 88,736 newborn records available for analysis,18 newborns were diagnosed with CCHD. Eight were identified by POS before discharge and 10 were diagnosed after discharge. Infants diagnosed with CCHD by POS had lower pre- and postductal SpO2 compared with normal infants. Their postductal PI was significantly lower. Infants who had CCHD that was not identified by POS had similar pre- and postductal SpO2 values, but their postductal PI was lower. Using a postductal PI cutoff of 1.21 had a receiver operating curve of area under the curve 0.77 (95% confidence interval: 0.672, 0.869) with 74% sensitivity and 61% specificity. CONCLUSION: In our large cohort of infants born in San Diego County, the postductal PI is lower in infants with CCHD. Given that PI is routinely displayed on every pulse oximeter and the high morbidity of missed CCHD, PI should be incorporated into routine CCHD screening. KEY POINTS: · Postductal PI is lower in newborn who presented later with congenital heart disease.. · Postductal PI cut-off of 1.21 may help practitioners determine if a newborn is at risk for CCHD.. · This large cohort study demonstrates that a low PI can detect additional CCHD cases..

Identifying Ways to Fix Outcome Disparities among Outborns Needing Therapeutic Hypothermia.

OBJECTIVE: This study examined patterns of care after birth in newborns treated with therapeutic hypothermia to identify remediable causes for the poorer outcomes observed in outborn infants. STUDY DESIGN: This was a secondary analysis of 150 newborns (68 outborn) prospectively enrolled at our center in the Vermont Oxford Neonatal Encephalopathy Registry from January 2008 to October 2016. RESULTS: The 5-minute Apgar's score and cord pH value did not differ, but cord blood gases were obtained far less frequently in outborns (p = 0.002). Outborns needed more chest compressions (p = 0.01) and epinephrine (p = 0.04), and had more brain injury on neuroimaging (p = 0.05). Outborns took longer to reach target hypothermia temperature (p < 0.0001). CONCLUSION: The lack of cord gas values and longer time to reach target temperature observed in the outborns are two observed differences in care that can be potentially remedied by providing education and resources at delivering hospitals in rapid identification of hypothermia candidates, though further research is needed to define the effects of such measures. Possible solutions are also discussed here.

Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: There are no US Food and Drug Administration-approved therapies for neonatal seizures. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain. Levetiracetam has proven efficacy and an excellent safety profile in older patients; therefore, there is great interest in its use in neonates. However, randomized studies have not been performed. Our objectives were to study the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment of neonatal seizures. METHODS: The study was a multicenter, randomized, blinded, controlled, phase IIb trial investigating the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment for neonatal seizures of any cause. The primary outcome measure was complete seizure freedom for 24 hours, assessed by independent review of the EEGs by 2 neurophysiologists. RESULTS: Eighty percent of patients (24 of 30) randomly assigned to phenobarbital remained seizure free for 24 hours, compared with 28% of patients (15 of 53) randomly assigned to levetiracetam (P < .001; relative risk 0.35 [95% confidence interval: 0.22-0.56]; modified intention-to-treat population). A 7.5% improvement in efficacy was achieved with a dose escalation of levetiracetam from 40 to 60 mg/kg. More adverse effects were seen in subjects randomly assigned to phenobarbital (not statistically significant). CONCLUSIONS: In this phase IIb study, phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures. Higher rates of adverse effects were seen with phenobarbital treatment. Higher-dose studies of levetiracetam are warranted, and definitive studies with long-term outcome measures are needed.

Assessing the Feasibility of Providing a Real-Time Response to Seizures Detected With Continuous Long-Term Neonatal Electroencephalography Monitoring.

PURPOSE: Continuous video electroencephalography (cEEG) monitoring is the recommended gold standard of care for at-risk neonates but is not available in many Neonatal Intensive Care Units (NICUs). To conduct a randomized treatment trial of levetiracetam for the first-line treatment of neonatal seizures (the NEOLEV2 trial), we developed a monitoring infrastructure at five NICUs, implementing recent technological advancements to provide continuous video EEG monitoring and real-time response to seizure detection. Here, we report on the feasibility of providing this level of care. METHODS: Twenty-five key informant interviews were conducted with study neurologists, neonatologists, coordinators, and EEG technicians from the commercial EEG monitoring company Corticare. A general inductive approach was used to analyze these qualitative data. RESULTS: A robust infrastructure for continuous video EEG monitoring, remote review, and real-time seizure detection was established at all sites. At the time of this survey, 260 babies had been recruited and monitored for 2 to 6 days. The EEG technician review by the commercial EEG monitoring company was reassuring to families and neonatologists and led to earlier detection of seizures but did not reduce work load for neurologists. Neurologists found the automated neonatal seizure detector algorithm provided by the EEG software company Persyst useful, but the accuracy of the algorithm was not such that it could be used without review by human expert. Placement of EEG electrodes to initiate monitoring, especially after hours, remains problematic. CONCLUSIONS: Technological advancements have made it possible to provide at-risk neonates with continuous video EEG monitoring, real-time detection of and response to seizures. However, this standard of care remains unfeasible in usual clinical practice. Chief obstacles remain starting a recording and resourcing the real-time specialist review of suspect seizures.

Evidence-based skin care in preterm infants.

Most guidelines on neonatal skin care emphasize issues pertaining to healthy, term infants. Few address the complex task of skin barrier maintenance in preterm, very preterm, and extremely preterm infants. Here, we provide an evidence-based review of the literature on skin care of preterm neonates. Interestingly, the stratum corneum does not fully develop until late in the third trimester, and as such, the barrier function of preterm skin is significantly compromised. Numerous interventions are available to augment the weak skin barrier of neonates. Plastic wraps reduce the incidence of hypothermia while semipermeable and transparent adhesive dressings improve skin quality and decrease the incidence of electrolyte abnormalities. Tub bathing causes less body temperature variability than sponge bathing and can be performed as infrequently as once every four days without increasing bacterial colonization of the skin. Topical emollients, particularly sunflower seed oil, appear to reduce the incidence of skin infections in premature neonates-but only in developing countries. In developed countries, studies indicate that topical petrolatum ointment increases the risk of candidemia and coagulase-negative Staphylococcus infection in the preterm population, perhaps by creating a milieu similar to occlusive dressings. For preterm infants with catheters, povidone-iodine and chlorhexidine are comparably effective at preventing catheter colonization. Further studies are necessary to examine the safety and efficacy of various skin care interventions in premature infants with an emphasis placed on subclassifying the patient population. In the interim, it may be beneficial to develop guidelines based on the current body of evidence.

Point-of-care glucose analysis in neonates using modified quinoprotein glucose dehydrogenase.

BACKGROUND: Asymptomatic hypoglycemia in neonates may contribute to neurologic deficits during development. Whole-blood glucose sensors are often imprecise and inaccurate at the low glucose concentrations found in neonates. SUBJECTS AND METHODS: In this study, a glucose sensor using a mutated glucose dehydrogenase that does not cross-react significantly with maltose was evaluated at three pediatric centers. Blood samples (n=575) from infants less than 30 days of age (hematocrit 23-70%) were analyzed using six reagent lots on three ACCU-CHEK(®) meters (Roche Diagnostics, Indianapolis, IN): the Inform II, Performa, and Aviva. Reference glucose level was determined in duplicate in perchloric acid extracts using a coupled hexokinase procedure. RESULTS: Imprecision of glucose measurement using stable control materials ranged from 2.0% to 3.1% (coefficient of variation) using the glucose meters and from 0.8% to 5.3% (coefficient of variation) in perchloric acid-treated controls. The difference between meter glucose values and reference values showed a slight dependence on hematocrit from 23% to 70% (r=-0.391, P<0.001) but not in the typical range of neonatal hematocrit from 45% to 70% (r=-0.036, P=0.239). Linear regression of the aggregated results yielded the following relationship: Meter glucose=0.99×Reference Glucose+0.04; r(2)=0.976; Syx=0.249. Receiver-operator characteristic analysis of the data using 2.2 mmol/L as the reference threshold for hypoglycemia yielded an area under the curve value of 0.993. All infants with a glucose level of <2.2 mmol/L were detected (100% sensitivity) when the meter glucose value was below 2.8 mmol/L. CONCLUSIONS: These data indicate that the modified ACCU-CHEK chemistry may be used effectively in neonatal settings to detect clinically significant hypoglycemia.

Safety and effectiveness of meropenem in infants with suspected or complicated intra-abdominal infections.

BACKGROUND: Intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial with excellent activity against pathogens associated with intra-abdominal infections. The purpose of this study was to determine the safety and effectiveness of meropenem in young infants with suspected or complicated intra-abdominal infections. METHODS: Preterm and term infants <91 days of age with suspected or confirmed intra-abdominal infections hospitalized in 24 neonatal intensive care units were studied in an open-label, multiple-dose study. Adverse events and serious adverse events were collected through 3 and 30 days following the last meropenem dose, respectively. Effectiveness was assessed by 3 criteria: death, bacterial cultures, and presumptive clinical cure score. RESULTS: Of 200 subjects enrolled in the study, 99 (50%) experienced an adverse event, and 34 (17%) had serious adverse events; no adverse events were probably or definitely related to meropenem. The most commonly reported adverse events were sepsis (6%), seizures (5%), elevated conjugated bilirubin (5%), and hypokalemia (5%). Only 2 of the serious adverse events were determined to be possibly related to meropenem (isolated ileal perforation and an episode of fungal sepsis). Effectiveness was evaluable in 192 (96%) subjects, and overall treatment success was 84%. CONCLUSIONS: Meropenem was well tolerated in this cohort of critically ill infants, and the majority of infants treated with meropenem met the definition of therapeutic success. CLINICAL TRIALS REGISTRATION: NCT00621192.

Population pharmacokinetics of meropenem in plasma and cerebrospinal fluid of infants with suspected or complicated intra-abdominal infections.

BACKGROUND: Suspected or complicated intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial agent with excellent activity against pathogens associated with intra-abdominal infections in this population. The purpose of this study was to determine the pharmacokinetics (PK) of meropenem in young infants as a basis for optimizing dosing and minimizing adverse events. METHODS: Premature and term infants <91 days old hospitalized in 24 neonatal intensive care units were studied. Limited PK sampling was performed following single and multiple doses of meropenem 20 to 30 mg/kg of body weight every 8 to 12 hours based on postnatal and gestational age at birth. Population and individual patient (Bayesian) PK parameters were estimated using NONMEM. RESULTS: In this study, 200 infants were enrolled and received the study drug. Of them, 188 infants with 780 plasma meropenem concentrations were analyzed. Their median (range) gestational age at birth and postnatal age at PK evaluation were 28 (23-40) weeks and 21 (1-92) days, respectively. In the final PK model, meropenem clearance was strongly associated with serum creatinine and postmenstrual age (clearance [L/h/kg] = 0.12*[(0.5/serum creatinine)**0.27]*[(postmenstrual age/32.7)**1.46]). Meropenem concentrations remained >4 µg/mL for 50% of the dose interval and >2 µg/mL for 75% of the dose interval in 96% and 92% of patients, respectively. The estimated penetration of meropenem into the cerebrospinal fluid was 70% (5-148). CONCLUSIONS: Meropenem dosing strategies based on postnatal and gestational age achieved therapeutic drug exposure in almost all infants.

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.)

Meropenem pharmacokinetics, pharmacodynamics, and Monte Carlo simulation in the neonate.

BACKGROUND: Hospitalized neonates are exposed to antibiotic-resistant bacterial pathogens and develop nosocomial infections. Limited data are available regarding the neonatal pharmacokinetics of meropenem, a broad spectrum carbapenem antibiotic. METHODS: Neonates <2 months of age received a single dose of meropenem at 10 or 20 mg/kg. Meropenem serum concentrations were measured at specified times during the 24 hours postinfusion. Population pharmacokinetics (PPK) were evaluated using NONMEM. Using Monte Carlo simulation (MCS), the probability of pharmacokinetic-pharmacodynamic target attainment was evaluated by computer modeling from predictions extrapolated from PPK data, using "virtual" dosing regimens of 10, 20, and 40 mg/kg administered every 8 or 12 hours against community- and hospital-acquired pathogens. RESULTS: Thirty-seven neonates were enrolled, 22 were born at <36 weeks (range, 23-41 weeks) gestational age. Meropenem clearance was greater in neonates with older chronologic ages and in those born at later gestational ages. Serum creatinine and postconceptional age (PCA) were the best overall predictors of meropenem elimination: CL (L/h/kg) = 0.041 + 0.040/SCr + 0.003 x (PCA-35). MCS demonstrated that in infants during the first 2 weeks of life, a dosage of 20 mg/kg/dose every 8 hours achieved the desired PD target in 95% of preterm neonates and 91% of term neonates against Pseudomonas aeruginosa isolated from patients managed in adult and pediatric intensive care units in the United States. CONCLUSIONS: MCS based on PPK determinations demonstrated that a meropenem dose of 20 mg/kg every 8 hours should provide adequate therapy for most nosocomial Gram-negative pathogens.

A cluster-randomized trial of benchmarking and multimodal quality improvement to improve rates of survival free of bronchopulmonary dysplasia for infants with birth weights of less than 1250 grams.

OBJECTIVE: We tested whether NICU teams trained in benchmarking and quality improvement would change practices and improve rates of survival without bronchopulmonary dysplasia in inborn neonates with birth weights of <1250 g. METHODS: A cluster-randomized trial enrolled 4093 inborn neonates with birth weights of <1250 g at 17 centers of the National Institute of Child Health and Human Development Neonatal Research Network. Three centers were selected as best performers, and the remaining 14 centers were randomized to intervention or control. Changes in rates of survival free of bronchopulmonary dysplasia were compared between study year 1 and year 3. RESULTS: Intervention centers implemented potentially better practices successfully; changes included reduced oxygen saturation targets and reduced exposure to mechanical ventilation. Five of 7 intervention centers and 2 of 7 control centers implemented use of high-saturation alarms to reduce oxygen exposure. Lower oxygen saturation targets reduced oxygen levels in the first week of life. Despite these changes, rates of survival free of bronchopulmonary dysplasia were all similar between intervention and control groups and remained significantly less than the rate achieved in the best-performing centers (73.3%). CONCLUSIONS: In this cluster-randomized trial, benchmarking and multimodal quality improvement changed practices but did not reduce bronchopulmonary dysplasia rates.

Oxygen delivery through nasal cannulae to preterm infants: can practice be improved?

OBJECTIVE: Oxygen delivery through nasal cannulae to convalescent preterm infants is a common but largely unstudied practice. To learn more about current nasal cannula oxygen delivery practices, we examined the variations in oxygen delivery through nasal cannulae among the centers of the Neonatal Research Network, the frequency of prescription of low levels of oxygen, and the success of weaning to room air. We hypothesized that some infants treated with oxygen through nasal cannulae were receiving oxygen levels equivalent to those of room air. METHODS: This was a descriptive, nested, cohort study of nasal cannula oxygen prescription among 187 infants with birth weights of <1250 g. All infants were studied at a postmenstrual age of 36 weeks, with a timed oxygen reduction challenge to establish their ability to be weaned to room air. The results of this challenge were compared with the fraction of inspired oxygen (FIO2) delivered, calculated as effective FIO2. Infants who maintained oxygen saturation values of > or =90% during oxygen weaning and during a 30-minute period in room air were defined as passing the challenge. RESULTS: Fifty-two infants (27.8%) were receiving oxygen concentrations and flow rates through nasal cannulae that delivered an effective FIO2 of <0.23, of whom 16 were receiving oxygen concentrations and flow rates that delivered an effective FIO2 of 0.21. In addition, 22 infants (11.8%) were prescribed room air through nasal cannulae intentionally. Seventy-two percent of those prescribed an effective FIO2 of <0.23 passed the room air challenge. CONCLUSIONS: Prescription of oxygen with combinations of flow rates and oxygen concentrations that delivered a low effective FIO2 was common. We speculate that some of this, including the inadvertent prescription of an effective FIO2 equivalent to that of room air, is related to lack of knowledge of the effective FIO2. Routine calculation of effective FIO2 values may prompt earlier trials of room air and thus reduce unnecessary days of oxygen therapy.

Population pharmacokinetics of cefepime in the neonate.

Newborn infants cared for in neonatal intensive care units may develop nosocomial infections. Cefepime, a "fourth-generation" cephalosporin (i.e., with activity against virtually all of the chromosomal-beta-lactamase-producing and many extended-spectrum-beta-lactamase-producing organisms), provides excellent activity against many gram-negative pathogens resistant to expanded-spectrum cephalosporins currently used to treat neonatal infections. The purpose of this study was to determine the pharmacokinetics of cefepime in this population to optimize dosing and minimize potential adverse events. Premature and term infants <4 months of age hospitalized in two neonatal intensive care units were studied. Limited pharmacokinetic (PK) sampling occurred following a dose of cefepime at 50 mg/kg of body weight infused over 30 min. Population pharmacokinetic parameters were determined using the program NONMEM. Fifty-five infants were enrolled. Their average (+/- standard deviation) gestational age at birth was 30.5 +/- 5.3 weeks, and their average postnatal age at PK evaluation was 14.5 +/- 14.7 days. In the final PK model, cefepime clearance (CL) was strongly associated with serum creatinine (SCr) (CL [ml/min/kg] = 0.26 + 0.59/SCr). The volume of distribution for infants with a postconceptional age of <30 weeks was larger than that for infants with a postconceptional age of >30 weeks (0.51 versus 0.39 liter/kg, respectively). The Bayesian analysis-predicted cefepime trough concentration at a dose of 50 mg/kg every 12 h for infants < or = 14 days of age was 29.9 +/- 16.6 microg/ml. Cefepime, dosed at 30 mg/kg/dose every 12 h for infants less than 14 days of age, regardless of gestational age, should provide antibiotic exposure equivalent to or greater than 50 mg/kg every 8 h in older infants and children.

A randomized, multicenter masked comparison trial of poractant alfa (Curosurf) versus beractant (Survanta) in the treatment of respiratory distress syndrome in preterm infants.

We compared the onset of clinical response and safety of two surfactants, poractant alfa (Curosurf, Chiesi Pharmaceuticals, Parma, Italy) and beractant (Survanta, Ross Laboratories, Columbus, OH), for treatment of respiratory distress syndrome (RDS) in preterm infants weighing 750 to 1750 g at birth and <35 weeks gestation. The study was performed as a 20-center prospective, randomized, masked comparison trial. Preterm infants (n = 293) with RDS were randomized to receive an initial dose of either 100 (n = 96) or 200 (n = 99) mg/kg of poractant alfa or 100 ( n = 98) mg/kg of beractant. All repeat dosing was given at 100 mg/kg. The onset of clinical response after the first dose was studied by comparing changes in the fraction of inspired oxygen (F IO(2)) between 0 and 6 hours measured using the area under the curve (F IO(2) AUC (0-6)); other outcomes were assessed for the entire cohort at 28 days and for infants born at < or = 32 weeks gestation at 36 weeks postconceptional age. We found that the mean F IO(2) AUC (0-6) values for the 100 and 200 mg/kg poractant alfa groups were both significantly lower than the mean F IO(2) AUC (0-6) values for the beractant group ( p < 0.005) but were not different from each other. Other outcomes were not different among the three groups for the entire cohort, but in infants born at < or = 32 weeks gestation, mortality up to 36 weeks postconceptional age was significantly less in the 200 mg/kg poractant alfa group than in either the beractant group (3% versus 11%; p = 0.034) or in the 100 mg/kg poractant alfa group (3% versus 11%; p = 0.046). Need for more than one dose of surfactant was significantly lower in infants treated with an initial dose of 200 mg/kg poractant alfa in comparison to the beractant-treated group ( p < 0.002). Treatment with poractant alfa (200 mg/kg initial dose) resulted in rapid reduction in supplemental oxygen with fewer additional doses of surfactant versus treatment with beractant in infants <35 weeks gestation with RDS, and significantly reduced mortality ( p <0.05) than either beractant or poractant alfa (100 mg/kg dosing) in infants < or =32 weeks gestation with RDS.