Risks of Infectious Diseases in Newborns Exposed to Alternative Perinatal Practices.

The purpose of this report is to educate providers about the risk of infectious diseases associated with emerging alternative peripartum and neonatal practices. This report will provide information pediatricians may use to counsel families before birth and to appropriately evaluate and treat neonates who have been exposed to these practices.

Lower foetal haemoglobin levels at 31- and 34-weeks post menstrual age is associated with the development of retinopathy of prematurity : PacIFiHER Report No. 1 PacIFiHER Study Group (Preterm Infants and Fetal Haemoglobin in ROP).

BACKGROUND/OBJECTIVES: Previous studies have suggested that lower mean foetal haemoglobin (HbF) levels is associated with an increased risk for developing retinopathy of prematurity (ROP). Lower HbF levels may lead to high oxygen exposure to the developing retina thereby increasing the risk of acute ROP. In this study, we characterize the temporal relationship of HbF levels and the development of ROP. SUBJECTS/METHODS: This is a single institution prospective observational cohort study. Preterm infants (born <31 weeks gestational age or <1500 g) with HbF measured at birth (cord blood), 31-, 34-, and 37-weeks post menstrual age (PMA); and at least one ROP exam, were enrolled. RESULTS: A total of 60 preterm infants (28 females, 47%) were enrolled. At 31-, 34-, 37-weeks PMA, infants with ROP (mild = Type 2 or less severe and severe = Type 1 ROP) had statistically lower percentages of HbF than infants with no ROP (28.2 ± 15 and 9.7 ± 2.9 vs 67.1 ± 29.6; p < 0.0001; 23.3 ± 14.7 and 32.5 vs 60.1 ± 25; p < 0.005; 31.9 ± 15.8 and 41.6 vs 60.2 ± 20.0; p < 0.0019). Infants with HbF levels in the lowest tercile at 31-weeks PMA were 7.6 times more likely to develop mild and severe ROP (95% CI 2.1-24.0, p value = 0.0006) and this risk increased to 12.3 times (95% CI: 2.6-59.0, p value = 0.0017) at 34-weeks PMA. CONCLUSIONS: Low HbF levels at 31- and 34-weeks PMA are associated with significantly increased risk of developing ROP. The decrease in HbF precedes the development of ROP and may be important in its pathogenesis.

Prolonged Tracheal Intubation and the Association Between Patent Ductus Arteriosus and Bronchopulmonary Dysplasia: A Secondary Analysis of the PDA-TOLERATE trial.

In the PDA-TOLERATE trial, persistent (even for several weeks) moderate to large patent ductus arteriosus (PDA) was not associated with an increased risk of BPD when the infant required <10 days of intubation. However, in infants requiring intubation for ≥10 days, prolonged PDA exposure (≥11 days) was associated with an increased risk of moderate/severe BPD.

Intestinal Failure-Associated Liver Disease in Neonates.

Intestinal failure-associated liver disease (IFALD) is common in neonates who suffer from intestinal failure and rely on parenteral nutrition. The etiology is multifactorial, relating to the infant's underlying cause of intestinal failure and other infant factors such as prematurity. Management of the disease includes transitioning to enteral feedings as soon as is safe for the infant. In infants who continue to rely on parenteral nutrition, alternative lipid emulsions and other medications may be used. This article reviews the epidemiology and factors that contribute to IFALD in neonates, in addition to management strategies.

Effect of Treating Parents Colonized With Staphylococcus aureus on Transmission to Neonates in the Intensive Care Unit: A Randomized Clinical Trial.

Importance: Staphylococcus aureus is a leading cause of health care-associated infections in the neonatal intensive care unit (NICU). Parents may expose neonates to S aureus colonization, a well-established predisposing factor to invasive S aureus disease. Objective: To test whether treating parents with intranasal mupirocin and topical chlorhexidine compared with placebo would reduce transmission of S aureus from parents to neonates. Design, Setting, and Participants: Double-blinded randomized clinical trial in 2 tertiary NICUs in Baltimore, Maryland. Neonates (n = 236) with S aureus-colonized parent(s) were enrolled. The study period was November 7, 2014, through December 13, 2018. Interventions: Parents were assigned to intranasal mupirocin and 2% chlorhexidine-impregnated cloths (active treatment, n = 117) or petrolatum intranasal ointment and nonmedicated soap cloths (placebo, n = 119) for 5 days. Main Outcomes and Measures: The primary end point was concordant S aureus colonization by 90 days, defined as neonatal acquisition of an S aureus strain that was the same strain as a parental strain at time of screening. Secondary outcomes included neonatal acquisition of any S aureus strain and neonatal S aureus infections. Results: Among 236 randomized neonates, 208 were included in the analytic sample (55% male; 76% singleton births; mean birth weight, 1985 g [SD, 958 g]; 76% vaginal birth; mean parent age, 31 [SD, 7] years), of whom 18 were lost to follow-up. Among 190 neonates included in the analysis, 74 (38.9%) acquired S aureus colonization by 90 days, of which 42 (56.8%) had a strain concordant with a parental baseline strain. In the intervention and placebo groups, 13 of 89 neonates (14.6%) and 29 of 101 neonates (28.7%), respectively, acquired concordant S aureus colonization (risk difference, -14.1% [95% CI, -30.8% to -3.9%]; hazard ratio [HR], 0.43 [95.2% CI, 0.16 to 0.79]). A total of 28 of 89 neonates (31.4%) in the intervention group and 46 of 101 (45.5%) in the control group acquired any S aureus strain (HR, 0.57 [95% CI, 0.31 to 0.88]), and 1 neonate (1.1%) in the intervention group and 1 neonate (1.0%) in the control group developed an S aureus infection before colonization. Skin reactions in parents were common (4.8% intervention, 6.2% placebo). Conclusions and Relevance: In this preliminary trial of parents colonized with S aureus, treatment with intranasal mupirocin and chlorhexidine-impregnated cloths compared with placebo significantly reduced neonatal colonization with an S aureus strain concordant with a parental baseline strain. However, further research is needed to replicate these findings and to assess their generalizability. Trial Registration: ClinicalTrials.gov Identifier: NCT02223520.

A Kangaroo Care Pathway for NICU Staff and Families: The Proof Is in the Pouch.

BACKGROUND: Kangaroo care (KC) improves bonding and neonatal health outcomes worldwide. However, concerns for patient safety, interrupted workflow, and parent readiness continued to impede KC in a level IV neonatal intensive care unit (NICU). Its current policy did not recommend using more than 1 staff member during patient transfer. In addition, NICU staff and parents lacked skills training and education regarding the feasibility of routine KC. PURPOSE: A KC pathway was developed and integrated within a multifaceted, champion-based, simulated educational training program for NICU staff and families to promote earlier and more frequent KC by increasing their knowledge and comfort with this practice. METHODS: Patient data collected before and after the study determined the frequency, timing, and mode of respiratory support during KC. Pre- and posttest surveys evaluated nurses' knowledge and comfort level with KC. RESULTS: The frequency of KC occurred 2.4 times more after the intervention. The percentage of KC episodes for intubated patients nearly doubled. The posttest survey scores for nursing knowledge and comfort level also markedly improved. IMPLICATIONS FOR PRACTICE: The KC pathway ameliorated feelings of discomfort by depicting criteria and instructions for safe practice. Multidisciplinary champions were invaluable in assisting the nursing staff with patient transfer during KC. IMPLICATIONS FOR RESEARCH: More dose-response studies are needed to maximize the clinical benefits of KC in developed countries.

Lack of Equipoise in the PDA-TOLERATE Trial: A Comparison of Eligible Infants Enrolled in the Trial and Those Treated Outside the Trial.

The PDA: TO LEave it alone or Respond And Treat Early trial compared the effects of 2 strategies for treatment of patent ductus arteriosus (PDA) in infants <280/7 weeks of gestation; however 137 potentially eligible infants were not recruited and received treatment of their PDA outside the PDA-TOLERATE trial due to "lack-of-physician-equipoise" (LPE). Despite being less mature and needing more respiratory support, infants with LPE had lower rates of mortality than enrolled infants. Infants with LPE treated before day 6 had lower rates of late respiratory morbidity than infants with LPE treated ≥day 6. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.

Comparative effectiveness of drugs used to constrict the patent ductus arteriosus: a secondary analysis of the PDA-TOLERATE trial (NCT01958320).

OBJECTIVE: To evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns < 28 weeks. METHODS: We performed a secondary analysis of the multi-center PDA-TOLERATE trial (NCT01958320). Infants with moderate-to-large PDAs were randomized 1:1 at 8.1 ± 2.1 days to either Drug treatment (n = 104) or Conservative management (n = 98). Drug treatments were assigned by center rather than within center (acetaminophen: 5 centers, 27 infants; ibuprofen: 7 centers, 38 infants; indomethacin: 7 centers, 39 infants). RESULTS: Indomethacin produced the greatest constriction (compared with spontaneous constriction during Conservative management): RR (95% CI) = 3.21 (2.05-5.01)), followed by ibuprofen = 2.03 (1.05-3.91), and acetaminophen = 1.33 (0.55-3.24). The initial rate of acetaminophen-induced constriction was 27%. Infants with persistent moderate-to-large PDA after acetaminophen were treated with indomethacin. The final rate of constriction after acetaminophen ± indomethacin was 60% (similar to the rate in infants receiving indomethacin-alone (62%)). CONCLUSION: Indomethacin was more effective than acetaminophen in producing ductus constriction.

PDA-TOLERATE Trial: An Exploratory Randomized Controlled Trial of Treatment of Moderate-to-Large Patent Ductus Arteriosus at 1 Week of Age.

OBJECTIVE: To compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given. STUDY DESIGN: A total of 202 neonates of <28 weeks of gestation age (mean, 25.8 ± 1.1 weeks) with moderate-to-large PDA shunts were enrolled between age 6 and 14 days (mean, 8.1 ± 2.2 days) into an exploratory randomized controlled trial. RESULTS: At enrollment, 49% of the patients were intubated and 48% required nasal ventilation or continuous positive airway pressure. There were no differences between the groups in either our primary outcome of ligation or presence of a PDA at discharge (early routine treatment [ERT], 32%; conservative treatment [CT], 39%) or any of our prespecified secondary outcomes of necrotizing enterocolitis (ERT, 16%; CT, 19%), bronchopulmonary dysplasia (BPD) (ERT, 49%; CT, 53%), BPD/death (ERT, 58%; CT, 57%), death (ERT,19%; CT, 10%), and weekly need for respiratory support. Fewer infants in the ERT group met the rescue criteria (ERT, 31%; CT, 62%). In secondary exploratory analyses, infants receiving ERT had significantly less need for inotropic support (ERT, 13%; CT, 25%). However, among infants who were ≥26 weeks gestational age, those receiving ERT took significantly longer to achieve enteral feeding of 120 mL/kg/day (median: ERT, 14 days [range, 4.5-19 days]; CT, 6 days [range, 3-14 days]), and had significantly higher incidences of late-onset non-coagulase-negative Staphylococcus bacteremia (ERT, 24%; CT,6%) and death (ERT, 16%; CT, 2%). CONCLUSIONS: In preterm infants age <28 weeks with moderate-to-large PDAs who were receiving respiratory support after the first week, ERT did not reduce PDA ligations or the presence of a PDA at discharge and did not improve any of the prespecified secondary outcomes, but delayed full feeding and was associated with higher rates of late-onset sepsis and death in infants born at ≥26 weeks of gestation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.

The impact of chlorhexidine gluconate bathing on skin bacterial burden of neonates admitted to the Neonatal Intensive Care Unit.

OBJECTIVE: To assess the impact of chlorhexidine gluconate (CHG) bathing on skin bacterial burden in neonates. STUDY DESIGN: In this prospective observational study, arm and groin skin bacterial growth was measured in 40 CHG-exposed and nonexposed neonates admitted to the NICU. Exposed neonates received 2% CHG baths per protocol for central line-associated bloodstream infection (CLABSI) prevention or Staphylococcus aureus decolonization. RESULTS: Forty neonates were enrolled, 18 of whom were CHG-exposed. Mean baseline Gram-positive (GP) bacterial burden was 2.19 log CFU/ml on the arm and 1.81 log CFU/ml on the groin. Bacterial burden decreased after the first bath, but returned to baseline by 72 h. Residual skin CHG concentration declined over time, with a corresponding increase in GP bacterial burden. CONCLUSIONS: CHG bathing reduces skin bacterial burden, but burden returns to baseline after 72 h. Twice weekly CHG bathing may be inadequate to suppress skin bacterial growth in hospitalized neonates.

Postoperative Enteral Nutrition Guidelines Reduce the Risk of Intestinal Failure-Associated Liver Disease in Surgical Infants.

OBJECTIVE: To assess the effectiveness of postoperative feeding guidelines in reducing the incidence and severity of intestinal failure-associated liver disease (IFALD) among infants. STUDY DESIGN: Two cohorts of infants <6 months old undergoing intestinal surgery were compared: preguideline (retrospective data from 2007 to 2013; n = 83) and postguideline (prospective data from 2013 to 2016; n = 81). The guidelines included greater initial enteral nutrition volumes of 20 mL/kg/d and daily feeding advancement if tolerated. The primary outcomes were incidence of IFALD (peak direct bilirubin [DB] >2 mg/dL) and severity (DB >5 mg/dL for moderate-severe). Multiple logistic regression was used to determine the odds of developing IFALD. Other outcomes were time to reach 50% and 100% goal calories from enteral nutrition and the incidence of necrotizing enterocolitis after feeding. RESULTS: The incidence of IFALD decreased from 71% to 51% (P = .031), and median peak DB decreased from 5.7 to 2.4 mg/dL (P = .001). After adjusting for diagnosis and prematurity, the odds of developing IFALD of any severity were reduced by 60% (OR 0.40, 95% CI 0.20-0.85), and the odds of developing moderate-to-severe IFALD were reduced by 72% (OR 0.28, 95% CI 0.13-0.58) with guideline use. Time to reach 50% enteral nutrition decreased from a median of 10 to 6 days (P = .020) and time to reach 100% enteral nutrition decreased from 35 to 21 days (P = .035) with guideline use. The incidence of necrotizing enterocolitis after initiating enteral nutrition did not change (5% vs 9%, P = .346). CONCLUSIONS: Implementation of feeding guidelines reduced time to reach feeding goals, significantly reducing IFALD incidence and severity.

Lessons Learned From Newborn Screening for Critical Congenital Heart Defects.

Newborn screening for critical congenital heart defects (CCHD) was added to the US Recommended Uniform Screening Panel in 2011. Within 4 years, 46 states and the District of Columbia had adopted it into their newborn screening program, leading to CCHD screening being nearly universal in the United States. This rapid adoption occurred while there were still questions about the effectiveness of the recommended screening protocol and barriers to follow-up for infants with a positive screen. In response, the Centers for Disease Control and Prevention partnered with the American Academy of Pediatrics to convene an expert panel between January and September 2015 representing a broad array of primary care, neonatology, pediatric cardiology, nursing, midwifery, public health, and advocacy communities. The panel's goal was to review current practices in newborn screening for CCHD and to identify opportunities for improvement. In this article, we describe the experience of CCHD screening in the United States with regard to: (1) identifying the target lesions for CCHD screening; (2) optimizing the algorithm for screening; (3) determining state-level challenges to implementation and surveillance of CCHD; (4) educating all stakeholders; (5) performing screening using the proper equipment and in a cost-effective manner; and (6) implementing screening in special settings such as the NICU, out-of-hospital settings, and areas of high altitude.

Active Surveillance Cultures and Decolonization to Reduce Staphylococcus aureus Infections in the Neonatal Intensive Care Unit.

BACKGROUND: Staphylococcus aureus is a common cause of healthcare-associated infections in neonates. OBJECTIVE: To examine the impact of methicillin-susceptible S. aureus (MSSA) decolonization on the incidence of MSSA infection and to measure the prevalence of mupirocin resistance. METHODS: We retrospectively identified neonates admitted to a tertiary care neonatal intensive care unit (NICU) from April 1, 2011, through September 30, 2014. We compared rates of MSSA-positive cultures and infections before and after implementation of an active surveillance culture and decolonization intervention for MSSA-colonized neonates. We used 2 measurements to identify the primary outcome, NICU-attributable MSSA: (1) any culture sent during routine clinical care that grew MSSA and (2) any culture that grew MSSA and met criteria of the National Healthcare Safety Network's healthcare-associated infection surveillance definitions. S. aureus isolates were tested for mupirocin susceptibility. We estimated incidence rate ratios using interrupted time-series models. RESULTS: Before and after the intervention, 1,523 neonates (29,220 patient-days) and 1,195 neonates (22,045 patient-days) were admitted to the NICU, respectively. There was an immediate reduction in the mean quarterly incidence rate of NICU-attributable MSSA-positive clinical cultures of 64% (incidence rate ratio, 0.36 [95% CI, 0.19-0.70]) after implementation of the intervention, and MSSA-positive culture rates continued to decrease by 21% per quarter (incidence rate ratio, 0.79 [95% CI, 0.74-0.84]). MSSA infections also decreased by 73% immediately following the intervention implementation (incidence rate ratio, 0.27 [95% CI, 0.10-0.79]). No mupirocin resistance was detected. CONCLUSION: Active surveillance cultures and decolonization may be effective in decreasing S. aureus infections in NICUs.

Treating Parents to Reduce NICU Transmission of Staphylococcus aureus (TREAT PARENTS) trial: protocol of a multisite randomised, double-blind, placebo-controlled trial.

INTRODUCTION: More than 33,000 healthcare-associated infections occur in neonatal intensive care units (NICUs) each year in the USA. Parents, rather than healthcare workers, may be a reservoir from which neonates acquire Staphylococcus aureus (S. aureus) colonisation in the NICU. This study looks to measure the effect of treating parents with short course intranasal mupirocin and topical chlorhexidine antisepsis on acquisition of S. aureus colonisation and infection in neonates. METHODS AND ANALYSIS: The TREAT PARENTS trial (Treating Parents to Reduce Neonatal Transmission of S. aureus) is a multicentre randomised, masked, placebo-controlled trial. Shortly after a neonate is admitted to the NICU, parents will be tested for S. aureus colonisation. If either parent screens positive for S. aureus, then both parents as a pair will be enrolled and randomised to one of the two possible masked treatment arms. Arm 1 will include assignment to intranasal 2% mupirocin plus topical antisepsis with chlorhexidine gluconate impregnated cloths for 5 days. Arm 2 will include assignment to placebo ointment and placebo cloths for skin antisepsis for 5 days. The primary outcome will be neonatal acquisition of an S. aureus strain that is concordant to the parental baseline S. aureus strain as determined by periodic surveillance cultures or a culture collected during routine clinical care that grows S. aureus. Secondary outcomes will include neonatal acquisition of S. aureus, neonatal S. aureus infection, eradication of S. aureus colonisation in parents, natural history of S. aureus colonisation in parents receiving placebo, adverse reactions to treatment, feasibility of intervention, and attitudes and behaviour in consented parents. Four hundred neonate-parent pairs will be enrolled. ETHICS AND DISSEMINATION: The study was approved by Johns Hopkins University IRB in June 2014 (IRB number 00092982). Protocol V.7 was approved in November 2014. Findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02223520.

Methicillin-resistant Staphylococcus aureus transmission and infections in a neonatal intensive care unit despite active surveillance cultures and decolonization: challenges for infection prevention.

OBJECTIVE: To characterize the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) transmission and infections in a level IIIC neonatal intensive care unit (NICU) and identify barriers to MRSA control. SETTING AND DESIGN: Retrospective cohort study in a university-affiliated NICU with an MRSA control program including weekly nares cultures of all neonates and admission nares cultures for neonates transferred from other hospitals or admitted from home. METHODS: Medical records were reviewed to identify neonates with NICU-acquired MRSA colonization or infection between April 2007 and December 2011. Compliance with hand hygiene and an MRSA decolonization protocol were monitored. Relatedness of MRSA strains were assessed using pulsed-field gel electrophoresis (PFGE). RESULTS: Of 3,536 neonates, 74 (2.0%) had a culture grow MRSA, including 62 neonates with NICU-acquired MRSA. Nineteen of 74 neonates (26%) had an MRSA infection, including 8 who became infected before they were identified as MRSA colonized, and 11 of 66 colonized neonates (17%) developed a subsequent infection. Of the 37 neonates that underwent decolonization, 6 (16%) developed a subsequent infection, and 7 of 14 (50%) that remained in the NICU for 21 days or more became recolonized with MRSA. Using PFGE, there were 14 different strain types identified, with USA300 being the most common (31%). CONCLUSIONS: Current strategies to prevent infections-including active identification and decolonization of MRSA-colonized neonates-are inadequate because infants develop infections before being identified as colonized or after attempted decolonization. Future prevention efforts would benefit from improving detection of MRSA colonization, optimizing decolonization regimens, and identifying and interrupting reservoirs of transmission.

Chlorhexidine inhibits L1 cell adhesion molecule-mediated neurite outgrowth in vitro.

BACKGROUND: Chlorhexidine is a skin disinfectant that reduces skin and mucous membrane bacterial colonization and inhibits organism growth. Despite numerous studies assessing chlorhexidine safety in term infants, residual concerns have limited its use in hospitalized neonates, especially low-birth-weight preterm infants. The aim of this study was to assess the potential neurotoxicity of chlorhexidine on the developing central nervous system using a well-established in vitro model of neurite outgrowth that includes laminin and L1 cell adhesion molecule (L1) as neurite outgrowth-promoting substrates. METHODS: Cerebellar granule neurons are plated on poly L-lysine, L1, or laminin. Chlorhexidine, hexachlorophene, or their excipients are added to the media. Neurons are grown for 24 h, fixed, and neurite length is measured. RESULTS: Chlorhexidine significantly reduced the length of neurites grown on L1 but not on laminin. Chlorhexidine concentrations as low as 125 ng/ml statistically significantly reduced neurite length on L1. Hexachlorophene did not affect neurite length. CONCLUSION: Chlorhexidine at concentrations detected in the blood following topical applications in preterm infants specifically inhibited L1-mediated neurite outgrowth of cerebellar granule neurons. It is now vital to determine whether the blood-brain barrier is permeable to chlorhexidine in preterm infants.

Implementation of computerized provider order entry in a neonatal intensive care unit: Impact on admission workflow.

OBJECTIVE: The study objective was to determine if computerized provider order entry (CPOE) systems impaired or enhanced workflow in the neonatal intensive care unit (NICU) by comparing the timing of administration of the first dose of antibiotics before and after CPOE system implementation. METHODS: We conducted a pre-post intervention comparative study of the length of time between admission and administration of initial antibiotics in neonates before and after a CPOE system was implemented. Clinical information and timing of antibiotic administration were collected on all inborn infants, who were admitted to the NICU in the first 4h of life and treated with antibiotics, for one year prior to the implementation of computerized order entry and for one year after the implementation. RESULTS: Infants admitted to the NICU were similar in both periods (mean birth weight 2183 g vs. 2091 g, gestational age 33.3 weeks vs. 33.0 weeks). There was no significant difference in mean length of time from admission to antibiotic administration in the pre-CPOE group (131 min [CI 124-139]) compared to the post-CPOE group (125 min [CI 116-133]) (p=0.07). The mean time to pharmacy verification for a subset of patients was significantly shorter for patients in the post-CPOE group (61 ± 58 min) compared to the pre-CPOE group (88 ± 76 min) (p=<0.001). CONCLUSIONS: While the introduction of a CPOE system in the NICU did not significantly improve antibiotic administration times, the timeliness of an important aspect of the medication process, time to pharmacy verification, was improved. These findings imply other factors are impeding workflow. Further studies are needed to evaluate how CPOE systems combined with patient care activities affect workflow and overall patient care.

Bronchopulmonary Dysplasia: Development and Progression in the Neonatal Intensive Care Unit.

Advances in neonatology have led to increased survival at younger gestational ages. These advances have included the ability to provide and titrate oxygen, improved modalities of assisted ventilation, improved nutritional and environmental support, and surfactant therapy. As a result of increasing survival of these immature infants, bronchopulmonary dysplasia (BPD) has become a consistent outcome despite improvements in technology. Varying definitions of BPD have emerged in an effort to best identify infants at risk for long-term adverse outcome and those who might benefit most from preventive therapies. Underlying abnormal pulmonary development of extremely preterm infants in the face of exposure to oxygen, assisted ventilation and inflammation make this a complex, multifactorial disease. Recent focus has been directed at preventing and treating inflammation. Efforts to minimize the inflammatory process include avoiding hyperoxia, minimizing injury from assisted ventilation, and preventing and treating postnatal infections. Additional therapies to modulate inflammation, such as steroid therapy or inhaled nitric oxide, need further investigation of both short- and long-term outcomes before routine use can be recommended.