Extremely Preterm Infants Research Articles

Quality and stability studies of red blood cell concentrates from umbilical cord blood compared to their adult counterparts.

Prematurity is a significant health issue due to its incidence and associated complications. Anemia is common in extremely preterm infants (EPI) and often requires transfusions. Red blood cells (RBC) from adult blood (AB) donors have been linked to oxygen-related complications in EPI, leading to the exploration of cord blood (CB) as an alternative source. However, standardization of CB-RBC manufacturing and comparison with AB-RBC characteristics are necessary before clinical studies can be conducted. This study investigated the quality and characteristics of leukoreduced, gamma-irradiated CB-RBC obtained using a commercial closed system from CB donations not meeting hematopoietic transplantation criteria. CB-RBC units were compared with AB-RBC units, both stored in saline-adenine-glucose-mannitol (SAGM). Various parameters, including hematological and biochemical characteristics, pH, 2,3-DPG levels, blood gases and potential toxicants, were evaluated during storage. CB-RBC units had acceptable initial quality parameters and a hematocrit (55±2%) comparable to AB-RBC. The main finding during storage was a faster rise in hemolysis compared to AB-RBC. Potassium (K+) significantly increased during storage in both sources. As expected, glucose levels decreased, and conversely, lactate levels increased, indicating similar patterns of anaerobic glycolysis during storage. pH decreased, affecting the oxygen dissociation curve due to reduced 2,3-DPG levels. After irradiation at 14 days of storage, CB-RBC were less stable as hemolysis and K+ significantly increased compared to AB-RBC at 24 hours. Phthalate concentrations, indicative of plasticizers, increased during storage, but significantly less in CB compared to AB-RBC. Most metals measured were within acceptable ranges. The quality of CB-RBC during storage is primarily influenced by levels of hemolysis and extracellular K+ content. Based on the analyzed parameters, we suggest that the expiration date for CB-RBC stored with SAGM should be set at 14 days, with transfusion occurring within <24 hours after irradiation.

A Necrotic Ulcer in an Extremely Premature Infant.

A Necrotic Ulcer in an Extremely Premature Infant.

Plasma Proteome Profiles Associated with Early Development of Lung Injury in Extremely Preterm Infants.

The biological mediators which initiate lung injury in extremely preterm infants during early postnatal life remain largely unidentified, limiting opportunities for early treatment and diagnosis. This exploratory study used SWATH-mass spectrometry to identify bronchopulmonary dysplasia (BPD)-specific changes in protein abundance in plasma samples obtained in the first 72 hours of life from extremely preterm infants and bioinformatic analysis to identify BPD-related biological categories and pathways. Lasty, binary logistic regression analysis was used to test the BPD predictive potential of a base model alone (gestational age, birth weight, sex) and with the protein biomarker added, with bootstrap resampling used to internally validate protein predictors and adjust for overoptimism. We observed disturbance of key processes including coagulation, complement activation, development and extracellular matrix organisation in the first days of life in extremely preterm infants who were later diagnosed with BPD. In the BPD prediction analysis, 49 plasma proteins were identified which when each singularly was combined with birth characteristics had a C-index of 0.65-0.84 (optimism-adjusted C-index) suggesting predictive potential for BPD outcomes. Taken together, this study demonstrates that alterations in plasma proteins can be detected from 4 hours of age in extremely preterm infants who later develop BPD and that protein biomarkers when combined with three birth characteristics have the potential to predict BPD development within the first 72 hours of life.

The evolution of nutritional care in preterm infants with a focus on the extreme preterm infant.

The evolution of nutritional care in preterm infants, particularly those classified as extremely preterm, has undergone significant advancements in recent years. These infants, born at less than 28 weeks of gestation, face unique challenges related to their elevated nutrient requirements, underdeveloped organ systems and minimal reserves, posing a need for timely and specialised nutritional strategies. Historically, the nutritional management of preterm infants focussed on short-term goals to promote survival. In recent years, the focus has shifted to the quality of nutrient provision to optimise neurodevelopment and longer-term health outcomes. This review highlights the shift from a generalised nutritional approach to a robust, evidence-based approach for preterm infants, acknowledging the intricate interplay between nutrition, holistic care and developmental outcomes. As neonatal care continues to evolve, ongoing research will refine nutritional interventions, optimise growth and enhance the long-term health outcomes of these vulnerable infants.

Two risk assessment models for predicting white matter injury in extremely preterm infants.

Extremely preterm infants (EPIs) are at high-risk of white matter injury (WMI), leading to long-term neurodevelopmental impairments. We aimed to develop nomograms for WMI. The study included patients from 31 provinces, spanning ten years. 6074 patients before 2018 were randomly divided into a training and internal validation group (7:3). The external validation group comprised 1492 patients from 2019. Predictors were identified using the least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression and nomograms were constructed. Models' performance was evaluated using receiver operating characteristic (ROC), decision curve analysis (DCA) and calibration curves. The prenatal nomogram included multiple gestation, premature rupture of membranes (PROM), chorioamnionitis, prenatal glucocorticoids, hypertensive disorder complicating pregnancy (HDCP) and Apgar 1 min, with area under the curve (AUC) of 0.805, 0.816 and 0.799 in the training, internal validation and external validation group, respectively. Days of mechanical ventilation (MV), shock, patent ductus arteriosus (PDA) ligation, intraventricular hemorrhage (IVH) grade III-IV, septicemia, hypothermia and necrotizing enterocolitis (NEC) stage II-III were identified as postpartum predictors. The AUCs were 0.791, 0.813 and 0.823 in the three groups, respectively. DCA and calibration curves showed good clinical utility and consistency. The two nomograms provide clinicians with precise and efficient tools for prediction of WMI. This study is a large-sample multicenter study, spanning 10 years. The two nomograms are convenient for identifying high-risk infants early, allowing for reducing poor prognosis.

The Effect of Plastic Wrap Use to Prevent Hypothermia on Neonatal Mortality and Morbidity in Extreme Preterm Infants

Background: Hypothermia immediately afterbirth is common, especially in preterm (PT) infants because of their skin immaturity. If it is prolonged, it can lead to mortality and morbidity. Although plastic wrap (PW) can improve neonatal hypothermia by decreasing evaporative heat loss, its effect on mortality and morbidity is uncertain. Aim: The aim of the study was to detect if PW can decrease mortality and morbidity in PT infants from 240 to 296 weeks’ gestation. Design: The study design was a retrospective study. Setting: The study was conducted at two neonatal intensive care units (NICUs). Materials and Methods: NICUs medical records from 2021 to 2023. Statistical Analysis: The data were analyzed using logistic regression analysis. Results: A total of 187 PT infants from 240 to 296-week gestation were admitted to both NICUs during that period, 148 PT infants were included in the study. Mean gestational age (GA) was 27.2 ± 2.7 weeks and mean birth weight was 865 ± 375 g; 75 PT infants (51%) were male, and 30 PT infants (20.2%) were hypothermic on admission. After adjusting for risk factors that potentially increased the mortality, admission temperature did not affect the mortality significantly (odds ratio [OR]: 0.8, confidence interval [CI]: 0.6–1.1). The only factor that increased the mortality significantly was GA (OR: 1.1, CI: 1.05–1.4). The other model that tested the effect of admission temperature on the morbidity showed that none of the morbidities were significantly decreased after adjusting for risk factors, necrotizing enterocolitis (OR: 1.05, CI: 0.8–1.3), intraventricular hemorrhage (OR: 0.8, CI: 0.6–1.09), bronchopulmonary dysplasia (OR: 1.1, CI: 0.8–1.3), retinopathy of prematurity (OR: 1.2, CI: 0.9–1.4), and late-onset sepsis (OR: 1.1, CI: 0.9–1.4). Conclusion: PW applied immediately after birth seemed to improve admission temperature in PT infants from 240 to 296-week gestation, but it did not improve neonatal mortality or morbidity.

Treatment of Severe Hyperglycemia in Extremely Preterm Infants Using Continuous Subcutaneous Insulin Therapy.

Hyperglycemia in preterm infants is usually treated with adjustment of glucose intake and, if persistent, with continuous insulin infusion. However, hypoglycemia is a well-known complication of iv insulin treatment. The aim of our study was to evaluate the feasibility of continuous subcutaneous insulin infusion (CSII) in extremely preterm infants. Clinical data from 15 extemely premature infants (< 28 weeks of gestation) undergoing CSII treatment for severe hyperglycemia at the NICU were included. Blood glucose levels during CSII as well as the nutritional intake and insulin intake were sampled. Data were analyzed and compared to a control group of very preterm infants receiving iv insulin therapy. Normoglycemia rates were best in the iv insulin-cohort (50.3%; 15.6%). Hypoglycemia was very rare in both groups (0.4%; 0.0%). CSII therapy might require higher insulin doses compared to continuous iv therapy. Subcutaneous Insulin therapy in extremely preterm infants is feasible, regarding the prevention of hypoglycemia. However, dose control needs to be improved. The results justify further model validation and clinical trial research to explore a model-based protocol and the use of CSII.

PDA management strategies and pulmonary hypertension in extreme preterm infants with bronchopulmonary dysplasia.

Premature infants are at risk for developing pulmonary hypertension (PH) in the context of bronchopulmonary dysplasia (BPD). Studies suggest a potential link between prolonged patent ductus arteriosus (PDA) exposure and BPD-PH, though management strategies remain controversial. Retrospective echocardiographic evaluation of newborns <29 weeks gestational age with BPD at two distinct centers. Primary objective was to evaluate the relationship between center-specific PDA management strategies (interventional or conservative) and the prevalence of BPD-PH. BPD was defined as oxygen or respiratory support at 36 weeks post-menstrual age (PMA). The presence of PH was defined as either an estimated sPAP of ≥40 mmHg or sEI ≥1.3. Center A has a conservative PDA policy. Center B has a targeted interventional policy. PH rates were similar between sites (21% vs 17%), while rates of PDA treatment was different (7% vs 81). Adjusted models did not demonstrate an association for center or PDA treatment exposure for PH and EI, although infants from Center A had echocardiography evidence of higher systolic eccentricity index (EI; 1.12 ± 0.19 vs 1.06 ± 0.15, p = 0.04). Markers of RV function (TAPSE and RV-FAC) were similar between groups. In preterm infants <29 weeks with BPD, conservative PDA treatment policy was not associated with higher rate of pulmonary hypertension diagnosis. The association between PDA-management approaches and the occurrence of BPD-associated pulmonary vascular disease in premature infants has sparsely been described. We found that a conservative policy, regarding the PDA, was not associated with an increase in pulmonary hypertension diagnosis. We identified that, in patients with BPD, echocardiographic metrics of LV performance were lower.

Sensorineural hearing impairment among preterm children: a Norwegian population-based study

ObjectiveTo investigate the risk for sensorineural hearing impairment (SNHI) in preterm infants, and to what extent the risk is attributed to perinatal morbidities and therapies.DesignPopulation-based cohort study using data from...

Assessment of extremely premature lambs supported by the Extrauterine Environment for Neonatal Development (EXTEND).

Our team has previously reported physiologic support by the EXTra-uterine Environment for Neonatal Development (EXTEND) of 105 to 117 days gestational age (GA) lambs for up to 28 days with normal organ maturation. However, the fetal lamb brain matures more rapidly, requiring the study of 90-105 day GA fetal lambs to assess more neurodevelopmentally equivalent lambs to the 23-25 week GA extreme premature infant. Extremely preterm lambs (90-95 days of GA) were delivered by C-section and supported by EXTEND. Estimated circuit flows were maintained at around 325 ml/kg/min. After support on EXTEND, MRI and histopathologic analysis were performed and compared to 105-112 days GA control lambs. The extremely preterm group includes 10 animals with a mean GA of 91.6 days, a mean weight at cannulation of 0.98 kg and a mean length of stay on EXTEND of 13.5 days (10-21 days). Hemodynamics and oxygenation showed stable parameters. Animals showed growth and physiologic cardiac function. MRI volumetric and diffusion analysis was comparable to controls. Histologic brain analysis revealed no difference between study groups. EXTEND appears to support brain and cardiac development in an earlier gestation, less mature, lamb model. Prolonged (up to 21 days) physiological support of extremely preterm lambs of closer neurodevelopmental equivalence to the 24-28 gestational week human was achieved using the EXTEND system. EXTEND treatment supported brain growth and development in extremely preterm fetal lambs and was not associated with intraventricular hemorrhage or white matter injury. Daily echocardiography demonstrated physiologic heart function, absence of cardiac afterload, and normal developmental increase in cardiac chamber dimensions. This study demonstrates hemodynamic and metabolic support by the EXTEND system in the extremely preterm ovine model.

Neonatal morbidity in the 2011 JAKIDS Jamaican birth cohort

ABSTRACT This study reports the spectrum of discharge diagnoses in a national cohort of newborns admitted during a 3-month period to hospitals across Jamaica. The data were analyzed using measures of central tendency and risk assessed using odds ratio. Data on 1607 admissions were used to describe the spectrum of morbidity in hospitalized infants. Eight hundred and seven (50%) male and 754 (48%) female neonates were admitted. There was a 15% (240) readmission rate during the neonatal period. Infants of diabetic mothers were almost three times as likely to be admitted as infants whose mothers were not diabetic OR 2.89 (CI 1.96 − 4.13). Infants of women who were hypertensive were 1.5 times more likely to be admitted than infants of non-hypertensive women OR 1.56 (CI 1.56–1.9). The odds ratio for admission of an infant born to a woman delivered by caesarean section was 2.1 (CI: 1.67–2.38). Premature infants constituted 50% of admissions. The most prevalent discharge diagnosis included presumed sepsis, respiratory distress and neonatal jaundice in both preterm and term neonates. In the extreme preterm infant respiratory distress syndrome was the most predominant discharge diagnosis. Multiple gestation was a significant risk for admission OR 2.7 (CI 1.8 to 3.9). Prematurity, multiple gestation, macrosomia, maternal diabetes, maternal hypertension and low 5 minute Apgar score < 7 were all found to be independent predictors of neonatal admission in a logistic regression model (p < 0.001). The recognition of the discharge morbidity is useful for future health planning for the most vulnerable in our population.

Association of different doses of antenatal corticosteroids exposure with early major outcomes and early weight loss percentage in extremely preterm infants or extremely low birthweight infants: a multicentre cohort study

ObjectivesTo determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage (EWLP) in hospital among extremely preterm infants (EPI)...

Ventilatory Assistance Before Umbilical Cord Clamping in Extremely Preterm Infants

Providing assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants. To determine whether assisted ventilation in extremely preterm infants (23 0/7 to 28 6/7 weeks' gestational age [GA]) followed by cord clamping reduces intraventricular hemorrhage (IVH) or early death. This phase 3, 1:1, parallel-stratified randomized clinical trial conducted at 12 perinatal centers across the US and Canada from September 2, 2016, through February 21, 2023, assessed IVH and early death outcomes of extremely preterm infants randomized to receive 120 seconds of assisted ventilation followed by cord clamping vs delayed cord clamping for 30 to 60 seconds with ventilatory assistance afterward. Two analysis cohorts, not breathing well and breathing well, were specified a priori based on assessment of breathing 30 seconds after birth. After birth, all infants received stimulation and suctioning if needed. From 30 to 120 seconds, infants randomized to the intervention received continuous positive airway pressure if breathing well or positive-pressure ventilation if not, with cord clamping at 120 seconds. Control infants received 30 to 60 seconds of delayed cord clamping followed by standard resuscitation. The primary outcome was any grade IVH on head ultrasonography or death before day 7. Interpretation by site radiologists was confirmed by independent radiologists, all masked to study group. To estimate the association between study group and outcome, data were analyzed using the stratified Cochran-Mantel-Haenszel test for relative risk (RR), with associations summarized by point estimates and 95% CIs. Of 1110 women who consented to participate, 548 were randomized and delivered infants at GA less than 29 weeks. A total of 570 eligible infants were enrolled (median [IQR] GA, 26.6 [24.9-27.7] weeks; 297 male [52.1%]). Intraventricular hemorrhage or death occurred in 34.9% (97 of 278) of infants in the intervention group and 32.5% (95 of 292) in the control group (adjusted RR, 1.02; 95% CI, 0.81-1.27). In the prespecified not-breathing-well cohort (47.5% [271 of 570]; median [IQR] GA, 26.0 [24.7-27.4] weeks; 152 male [56.1%]), IVH or death occurred in 38.7% (58 of 150) of infants in the intervention group and 43.0% (52 of 121) in the control group (RR, 0.91; 95% CI, 0.68-1.21). There was no evidence of differences in death, severe brain injury, or major morbidities between the intervention and control groups in either breathing cohort. This study did not show that providing assisted ventilation before cord clamping in extremely preterm infants reduces IVH or early death. Additional study around the feasibility, safety, and efficacy of assisted ventilation before cord clamping may provide additional insight. ClinicalTrials.gov Identifier: NCT02742454.

Impact of Nutrient Intake on Body Composition in Very Low-Birth Weight Infants Following Early Progressive Enteral Feeding.

Preterm infants have increased body adiposity at term-equivalent age and risk of adverse metabolic outcomes. The aim of the study was to define how nutrient intake may impact body composition (BC) of very low-birth weight infants fed with early progressive enteral feeding and standard fortification. Eighty-six infants with <1500 g birth weight were included in the BC study and stratified into extremely preterm (EP) and very preterm (VP) groups. Nutrient intake was calculated during the first 28 days and BC assessed by dual X-ray absorptiometry at discharge and by skinfold thickness at 12 months of corrected age (CA). Total nutrient intake did not differ between the groups. EP infants had a higher fat mass percentage at discharge than VP infants (24.8% vs. 19.4%, p < 0.001); lean mass did not differ. None of the nutrients had any impact on BC of EP infants. Protein intake did not result in a higher lean mass in either group; fat intake was a significant predictor of increased fat mass percentage in VP infants at discharge (p = 0.007) and body adiposity at 12 months of CA (p = 0.021). Nutritional needs may depend on gestational age and routine fortification should be used with caution in more mature infants.

Long-term impact of late pulmonary hypertension requiring medication in extremely preterm infants with severe bronchopulmonary dysplasia

This study investigated whether late pulmonary hypertension (LPH) independently increases the risk of long-term mortality or neurodevelopmental delay (NDD) in extremely preterm infants (EPIs) with severe bronchopulmonary dysplasia (BPD). Using prospectively collected data from the Korean Neonatal Network, we included EPIs with severe BPD born at 22–27 weeks’ gestation between 2013 and 2021. EPIs having severe BPD with LPH (LPH, n = 124) were matched 1:3 with those without pulmonary hypertension (PH) as controls (CON, n = 372), via propensity score matching. LPH was defined as PH with the initiation of medication after 36 weeks’ corrected age (CA). Long-term mortality after 36 weeks’ CA or NDD at 18–24 months’ CA was analyzed. NDD was assessed using composite scores based on various neurodevelopmental assessment modalities. LPH had significantly higher long-term mortality or NDD (45.2% vs. 23.1%, P < 0.001), mortality (24.2% vs. 4.84%, P < 0.001), and NDD (68.4% vs. 37.8%, P = 0.001), respectively than CON, even after adjusting for different demographic factors. Multivariable regression demonstrated that LPH independently increased the risk of mortality or NDD (adjusted odds ratio, 1.95; 95% confidence intervals, 1.17–3.25). When LPH occurs in EPIs with severe BPD, special monitoring and meticulous care for long-term survival and neurodevelopment are continuously needed.

Metabolomic Analysis Reveals the Association of Severe Bronchopulmonary Dysplasia with Gut Microbiota and Oxidative Response in Extremely Preterm Infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease mainly affecting premature infants needing ventilation or oxygen for respiratory distress. This study aimed to evaluate the molecular linkages for BPD in very and extremely preterm infants using a metabolomics-based approach. A case-control study of enrolling preterm infants born before 32 weeks gestational age (GA) was prospectively performed. These preterm infants were subsequently stratified into the following two groups for further analysis: no or mild BPD, and moderate or severe BPD based on the 2019 NICHD criteria. Urinary metabolomic profiling was performed using 1H-Nuclear magnetic resonance (NMR) spectroscopy coupled with partial least squares discriminant analysis (PLS-DA) at a corrected age of 6 months. Metabolites significantly differentially related to GA and BPD severity were performed between groups, and their roles in functional metabolic pathways were also assessed. A total of 89 preterm infants born before 32 weeks gestation and 50 infants born at term age (above 37 completed weeks' gestation) served as controls and were enrolled into the study. There were 21 and 24 urinary metabolites identified to be significantly associated with GA and BPD severity, respectively (p < 0.05). Among them, N-phenylacetylglycine, hippurate, acetylsalicylate, gluconate, and indoxyl sulfate were five metabolites that were significantly higher, with the highest importance in both infants with GA < 28 weeks and those with moderate to severe BPD, whereas betaine and N,N-dimethylglycine were significantly lower (p < 0.05). Furthermore, ribose and a gluconate related pentose phosphate pathway were strongly associated with these infants (p < 0.01). In conclusion, urinary metabolomic analysis highlights the crucial role of gut microbiota dysbiosis in the pathogenesis of BPD in preterm infants, accompanied by metabolites related to diminished antioxidative capacity, prompting an aggressive antioxidation response in extremely preterm infants with severe BPD.

Comparison of singleton and twin birth weight reference percentile curves by gestational age and sex in extremely preterm infants: a population-based study

BackgroundWith the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth...

Risk Prediction of Severe Bronchopulmonary Dysplasia (BPD) Using the Respiratory Severity Score (RSS) in Extremely Preterm Infants: A Retrospective Study From Saudi Arabia.

Background Bronchopulmonary dysplasia (BPD) is a significant complication in extremely preterm infants. Therefore, early diagnosis of BPD is important for planning treatment strategies. In this study, we aimed to assess the predictive efficacy of the Respiratory Severity Score (RSS) in determining severe BPD or death outcomes in very preterm infants. Methodology This retrospective study included preterm infants born with a gestational age of ≤30 weeks. The inclusion criteria comprised individuals who were mechanically ventilated (<1 week) during the first four weeks of life. Any patients who died during the first seven days of life were excluded. RSS values were recorded on days 3, 14, 21, and 28 of life. Multivariate logistic regression was used to identify a correlation between RSS and patient outcomes. Results A total of 154 infants were included in the analysis, of whom 82 (53.24%) developed severe BPD and 38 (24.67%) died. RSS was higher in patients who either died or developed severe BPD compared to those who survived. The multivariate logistic regression analysis revealed that RSSs at postnatal day 14 (odds ratio (OR) = 3.970; 95% confidence interval (CI) = 1.114-14.147; p < 0.05), day 21 (OR = 6.201; 95% CI = 1.937-19.851; p < 0.05), and day 28 (OR = 8.925; 95% CI = 3.331-28.383; p < 0.05) was significantly associated with a higher risk of death or severe BPD. Conclusions The findings of the present study revealed that RSS can help predict the risk of severe BPD in very preterm infants.

Disrupted TGF-β signaling: a link between bronchopulmonary dysplasia and alveolar type 1 cells.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease common in extreme preterm infants and is characterized by alveolar simplification. Current BPD research mainly focuses on alveolar type 2 (AT2) cells, myofibroblasts, and the endothelium. However, a notable gap exists in the involvement of AT1 cells, which constitute a majority of the alveolar surface area. In this issue of the JCI, Callaway and colleagues explored the role of TGF-β signaling in AT1 cells for managing the AT1-to-AT2 transition and its involvement in the integration of mechanical forces with the pulmonary matrisome during development. The findings implicate AT1 cells in the pathogenesis of BPD.

Prophylactic early low-dose hydrocortisone and survival without bronchopulmonary dysplasia among extremely preterm infants born at 22-27 weeks' gestation.

To compare survival without BPD among extremely preterm infants (EPI) who received prophylactic early low-dose hydrocortisone (PEH) with those who did not (non-PEH). This single-center retrospective study compared risk-adjusted rates of survival without BPD, BPD, bowel perforation, and late-onset sepsis among infants (22-27 weeks' gestation at birth) who received PEH (n = 82) and who did not (n = 205). Infants in the PEH group were of lower gestational age, lower birthweight, and higher day-1 risk of death/BPD. After adjusting for risk of death/BPD, PEH-treated infants demonstrated increased survival without BPD (aOR 2.04, 95%CI 1.1-3.7), and lower BPD rates (aOR 0.46, 95%CI 0.25-0.87). Importantly, bowel perforation or sepsis rate were similar among both groups. After risk adjustment, PEH-treated infants demonstrated improved survival without BPD and did not increase rates of bowel perforation or sepsis. In our cohort of infants, PEH was safe and effective among the sickest preterm neonates.