A Deep Intronic PKHD1 Variant Identified by SpliceAI in a Deceased Neonate With Autosomal Recessive Polycystic Kidney Disease.

The etiologies of newborn deaths in neonatal intensive care units usually remain unknown, even after genetic testing. Whole-genome sequencing, combined with artificial intelligence-based methods for predicting the effects of non-coding variants, provide an avenue for resolving these deaths. Using one such method, SpliceAI, we identified a maternally inherited deep intronic PKHD1 splice variant (chr6:52030169T>C), in trans with a pathogenic missense variant (p.Thr36Met), in a newborn who died of autosomal recessive polycystic kidney disease at age 2 days. We validated the deep intronic variant's impact in maternal urine-derived cells expressing PKHD1. Reverse transcription polymerase chain reaction followed by Sanger sequencing showed that the variant causes inclusion of 147bp of the canonical intron between exons 29 and 30 of PKHD1 into the mRNA, including a premature stop codon. Allele-specific expression analysis at a heterozygous site in the mother showed that the mutant allele completely suppresses canonical splicing. In an unrelated healthy control, there was no evidence of transcripts including the novel splice junction. We returned a diagnostic report to the parents, who underwent in vitro embryo selection.

Response to first dose of inhaled albuterol in mechanically ventilated preterm infants.

BACKGROUND: Bronchodilator responses among preterm infants are heterogeneous. Bedside measurements may identify responders. STUDY DESIGN: Respiratory measurements (Resistance, Compliance, FiO2) and pulse oximetry (SpO2) patterns were downloaded from infants <30 weeks gestational age during the first 2 months of life. Mechanically ventilated infants who received albuterol were included (n = 33). Measurements were compared before and after first albuterol. Secondary analyses assessed subsequent doses. RESULTS: Median gestation and birthweight were 25 3/7 weeks and 730 g, respectively. Mean Resistance decreased post-albuterol (p = 0.007). Sixty-eight percent of infants were responders based on decreased Resistance. Compliance and FiO2 did not significantly differ. Percent time in hypoxemia (SpO2 < 85%) decreased post albuterol (p < 0.02). In responders, Resistance changes diminished with subsequent administration (all p = 0.01). CONCLUSIONS: Ventilator resistance decreased in two-thirds of preterm infants, consistent with studies that utilized formal pulmonary function testing. Albuterol had a variable effect on delivered FiO2; however, hypoxemia may be useful in evaluating albuterol response.

A comparison of the nutritive sucking performance of full term and preterm neonates at hospital discharge: A prospective study.

BACKGROUND: Studies show that 40% to 70% of premature infants exhibit both immature and atypical feeding ability. To establish thresholds of performance and develop efficacious treatments for initiating and advancing oral feedings, we must first identify the nutritive sucking performance measures impacted by preterm birth. AIMS: To compare objective measures of neonatal nutritive sucking between full term and preterm infants at hospital discharge. STUDY DESIGN AND METHODS: This was a prospective observational study including full term (FT; N = 32) and preterm (PT; N = 44) infants. Nutritive sucking performance at discharge was assessed. The outcome measures of interest were means and coefficients of variability of nutritive sucking peak amplitude, frequency, duration, and smoothness, and feeding-related length of stay. RESULTS: There was a significant difference in sucking performance between groups; FT infants demonstrated significantly lower mean suck frequency, with longer suck duration and greater suck smoothness as compared to PT. PT infants had significantly less variability in suck amplitude and frequency as compared to FT, while FT infants had significantly less variability in suck smoothness as compared to PT. Post hoc regression analyses found suck frequency alone accounted for 28% of the variance in feeding length of stay for PT; suck smoothness alone accounted for 34% of the variance in feeding length of stay for FT. CONCLUSIONS: Suck frequency may be an important intervention target for PT infants having difficulty transitioning to oral feeding. Suck smoothness may be a sensitive marker for identifying infants at high risk for feeding challenges.

Plasma Brain-Derived Neurotrophic Factor Levels in Newborn Infants with Neonatal Abstinence Syndrome.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS). Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS. OBJECTIVE: To compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS. METHODS: This is a prospective cohort study with no intervention involved. Infants ≥35 weeks of gestation were enrolled. BDNF level was measured using enzyme-linked immunosorbent assay technique from blood samples drawn within 48 h of life. The severity of NAS was determined by the length of hospital stay, number of medications required to treat NAS. RESULTS: 67 infants were enrolled, 34 NAS and 33 non-NAS. Mean gestational age did not differ between the two groups. Mean birth weight of NAS infants was significantly lower than the non-NAS infants (3,070 ± 523 vs. 3,340 ± 459 g, p = 0.028). Mean BDNF level in NAS group was 252.2 ± 91.6 ng/ml, significantly higher than 211.3 ± 66.3 ng/ml in the non-NAS group (p = 0.04). There were no differences in BDNF levels between NAS infants that required one medication vs. more than one medication (254 ± 91 vs. 218 ± 106 ng/ml, p = 0.47). There was no correlation between the BDNF levels and length of hospital stay (p = 0.68) among NAS infants. Overall, there were no significant correlations between BDNF levels and NAS scores except at around 15 h after admission (correlation 0.35, p = 0.045). CONCLUSION: Plasma BDNF level was significantly increased in NAS infants during the first 48 h when compared to non-NAS infants. The correlations between plasma BDNF levels and the severity of NAS warrant further study. These results suggest that BDNF may play a neuromodulatory role during withdrawal after in utero opiate exposure.

Neurological consequences of systemic inflammation in the premature neonate.

Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.

Quantifying Neonatal Sucking Performance: Promise of New Methods.

Neonatal feeding has been traditionally understudied so guidelines and evidence-based support for common feeding practices are limited. A major contributing factor to the paucity of evidence-based practice in this area has been the lack of simple-to-use, low-cost tools for monitoring sucking performance. We describe new methods for quantifying neonatal sucking performance that hold significant clinical and research promise. We present early results from an ongoing study investigating neonatal sucking as a marker of risk for adverse neurodevelopmental outcomes. We include quantitative measures of sucking performance to better understand how movement variability evolves during skill acquisition. Results showed the coefficient of variation of suck duration was significantly different between preterm neonates at high risk for developmental concerns (HRPT) and preterm neonates at low risk for developmental concerns (LRPT). For HRPT, results indicated the coefficient of variation of suck smoothness increased from initial feeding to discharge and remained significantly greater than healthy full-term newborns (FT) at discharge. There was no significant difference in our measures between FT and LRPT at discharge. Our findings highlight the need to include neonatal sucking assessment as part of routine clinical care in order to capture the relative risk of adverse neurodevelopmental outcomes at discharge.

Relationship between perfusion index and patent ductus arteriosus in preterm infants.

BACKGROUND: Perfusion index (PI) is a noninvasive measure of perfusion. ΔPI (difference between pre- and postductal PI) may identify hemodynamically significant PDA. However, studies are limited to brief and intermittent ΔPI sampling. Our objective is to assess the value of continuous high resolution ΔPI monitoring in the diagnosis of PDA. METHODS: Continuous ΔPI monitoring in preterm infants was prospectively performed using two high-resolution pulse oximeters. Perfusion Index measures (ΔPI mean and variability, pre- and postductal PI) were analyzed over a 4-h period prior to echocardiography. A cardiologist blinded to the results evaluated for PDA on echocardiography. Linear mixed regression models were utilized for analyses. RESULTS: We obtained 31 echocardiography observations. Mean ΔPI (-0.23 vs. 0.16; P < 0.05), mean pre-PI (0.86 vs. 1.26; P < 0.05), and ΔPI variability (0.39 vs. 0.61; P = 0.05) were lower in infants with PDA compared to infants without PDA at the time of echocardiography. CONCLUSION: Mean ΔPI, ΔPI variability, and mean pre-PI measured 4 h prior to echocardiography detect PDA in preterm infants. PI is dynamic and should be assessed continuously. Perfusion index is a promising bedside measurement to identify PDA in preterm infants.

Renal injury in neonates: use of "omics" for developing precision medicine in neonatology.

Preterm birth is associated with increased risks of morbidity and mortality along with increased healthcare costs. Advances in medicine have enhanced survival for preterm infants but the overall incidence of major morbidities has changed very little. Abnormal renal development is an important consequence of premature birth. Acute kidney injury (AKI) in the neonatal period is multifactorial and may increase lifetime risk of chronic kidney disease.Traditional biomarkers in newborns suffer from considerable confounders, limiting their use for early identification of AKI. There is a need to develop novel biomarkers that can identify, in real time, the evolution of renal dysfunction in an early diagnostic, monitoring and prognostic fashion. Use of "omics", particularly metabolomics, may provide valuable information regarding functional pathways underlying AKI and prediction of clinical outcomes.The emerging knowledge generated by the application of "omics" (genomics, proteomics, metabolomics) in neonatology provides new insights that can help to identify markers of early diagnosis, disease progression, and identify new therapeutic targets. Additionally, omics will have major implications in the field of personalized healthcare in the future. Here, we will review the current knowledge of different omics technologies in neonatal-perinatal medicine including biomarker discovery, defining as yet unrecognized biologic therapeutic targets, and linking of omics to relevant standard indices and long-term outcomes.

Early urinary biomarkers of acute kidney injury in preterm infants.

BACKGROUND: Acute kidney injury (AKI) in the neonatal intensive care setting is multifactorial and is associated with significant morbidity and mortality. This study evaluates the utility of novel urinary biomarkers to predict the development and/or severity AKI in preterm infants. METHODS: We performed a case-control study on a prospective cohort of preterm infants (<32 wk), to compare seven urine biomarkers between 25 infants with AKI and 20 infants without AKI. RESULTS: Infants with AKI had significantly higher neutrophil gelatinase-associated lipocalin (NGAL) (median, control (CTRL) vs. AKI; 0.598 vs. 4.24 µg/ml; P < 0.0001). In contrast, urinary epidermal growth factor (EGF) levels were significantly lower in infants who developed AKI compared to controls (median, CTRL vs. AKI; 0.016 vs. 0.006 µg/ml; P < 0.001). The area under the curve (AUC) for NGAL for prediction of stage I AKI on the day prior to AKI diagnosis (day-1) was 0.91, and for the prediction of stage II/III, AKI was 0.92. Similarly, urine EGF was a predictor of renal injury on day -1 (AUC: 0.97 for stage I and 0.86 for stage II/III AKI). CONCLUSION: Urinary biomarkers may be useful to predict AKI development prior to changes in serum creatinine (SCr) in preterm infants.

The contrast sensitivity of the newborn human infant.

PURPOSE: To measure the binocular contrast sensitivity (CS) of newborn infants using a fixation-and-following card procedure. METHODS: The CS of 119 healthy newborn infants was measured using stimuli printed on cards under the descending method of limits (93 infants) and randomized/masked designs (26 infants). One experienced and one novice adult observer tested the infants using vertical square-wave gratings (0.06 and 0.10 cyc/deg; 20/10,000 and 20/6000 nominal Snellen equivalent); the experienced observer also tested using horizontal gratings (0.10 cyc/deg) and using the Method of Constant Stimuli while being kept unaware of the stimulus values. RESULTS: The CS of the newborn infant was 2.0 (contrast threshold = 0.497; 95% confidence interval: 0.475-0.524) for vertically oriented gratings and 1.74 (threshold = 0.575; 95% confidence interval: 0.523-0.633) for horizontally oriented gratings (P < 0.0006). The standard deviation of infant CS was comparable to that obtained by others on adults using the Pelli-Robson chart. The two observers showed similar practice effects. Randomization of stimulus order and masking of the adult observer had no effect on CS. CONCLUSIONS: The CS of individual newborn human infants can be measured using a fixation-and-following card procedure.

Early feeding and neonatal hypoglycemia in infants of diabetic mothers.

OBJECTIVES: To examine the effects of early formula feeding or breast-feeding on hypoglycemia in infants born to 303 A1-A2 and 88 Class B-RF diabetics. METHODS: Infants with hypoglycemia (blood glucose < 40 mg/dL) were breast-fed or formula-fed, and those with recurrences were given intravenous dextrose. RESULTS: Of 293 infants admitted to the well-baby nursery, 87 (30%) had hypoglycemia, corrected by early feeding in 75 (86%), while 12 (14%) required intravenous dextrose. In all, 98 infants were admitted to the newborn intensive care unit for respiratory distress (40%), prematurity (33%) or prevention of hypoglycemia (27%). Although all newborn intensive care unit patients received intravenous dextrose, 22 (22%) had hypoglycemia. Of 109 hypoglycemia episodes, 89 (82%) were single low occurrences. At discharge, 56% of well-baby nursery and 43% of newborn intensive care unit infants initiated breast-feeding. CONCLUSIONS: Hypoglycemia among infants of diabetic mothers can be corrected by early breast-feeding or formula feeding.

Pediatrics residents' preparedness for neonatal resuscitation assessed using high-fidelity simulation.

BACKGROUND: Pediatrics residents are expected to demonstrate preparedness for neonatal resuscitation, yet research has shown gaps in residents' readiness to perform this skill. OBJECTIVE: To evaluate procedural skills and team performance of pediatrics residents during neonatal resuscitation (NR) using a high-fidelity mannequin, and to assess residents' confidence in their NR skills before and after training. METHODS: Two teams of residents (all had completed NR program training) participated in 2 separate, 90-minute sessions (2 to 3 weeks apart) in an off-site delivery room during their neonatal intensive care rotation. Residents' confidence in assisting and leading NR was surveyed before each session. Teams participated in a scenario (adapted from the NR program), which required 5 skills (positive pressure ventilation, chest compressions, endotracheal intubation, umbilical vein catheterization, and epinephrine administration). Video recording was used for debriefing and scoring. Skills were scored for technique and timeliness, and team behaviors were scored for communication, management, and leadership. RESULTS: Twenty-six residents (11 teams) completed 2 paired sessions. Self-confidence scores increased between the 2 sessions but were not correlated with performance. Gaps in procedural skill performance were observed, and timeliness for most skills did not meet expectations. Significant improvement in team communication was noted. CONCLUSIONS: Important gaps in procedural skill performance, particularly timeliness, were detected by NR simulation training; residents' improvements in self-confidence did not reflect gains in actual performance. Their relative unpreparedness for NR (despite prior certification) highlights the need for deliberate practice and specific team training before and during neonatal intensive care delivery room rotations.

Breastfeeding in women with severe preeclampsia.

BACKGROUND: In the United States, breastfeeding initiation is reported for 75% of all live births; however, little information is available for mothers affected by severe preeclampsia (SP) who because of magnesium sulfate treatment are separated from their infants in the immediate postpartum period. This study examined feeding practices and factors associated with breastfeeding initiation in 281 women with SP and their 200 late-preterm and 81 term infants. SUBJECTS AND METHODS: SP was diagnosed according to established clinical and laboratory criteria. Infant feeding preference was ascertained on admission to labor and delivery. Variables known to influence breastfeeding initiation, including maternal age, smoking, obesity, and racial and educational characteristics, were assessed. RESULTS: All mothers received magnesium sulfate for 24 hours following delivery. Of 281 infants, 54% were admitted to the neonatal intensive care unit (NICU). All mothers and infants survived. On admission, 149 women intended to breastfeed, 73 intended to feed formula, and 59 were undecided. Four of 73 women who did not wish to breastfeed and 27 of 59 originally undecided later initiated breastfeeding. At discharge, 144 (51%) of all these mothers had successfully initiated breastfeeding. Factors associated with breastfeeding initiation failure included African American race, younger age, lower education, multiparity, smoking, and obesity. Of 149 women who intended to breastfeed, 76% were successful, and logistic regression analysis showed that intention to breastfeed was the most significant predictor of breastfeeding initiation. During the first 24 hours postpartum, 78% of infants receiving well-baby care, and 4% of those admitted to the NICU visited with their mother once. Among women who intended to breastfeed, successful breastfeeding initiation involved 85% of infants receiving routine well-baby care and 69% of those admitted to the NICU. CONCLUSIONS: In spite of the challenges created by SP, including early maternal separation, breastfeeding initiation is possible. The strongest predictor for breastfeeding success remains the intention to breastfeed, whereas race, lower level of education, and obesity are associated with breastfeeding initiation failure.

Cellular strain amplifies LPS-induced stress signaling in immature enterocytes: potential implications for preterm infant NCPAP.

BACKGROUND: Recent clinical observations of increased necrotizing enterocolitis (NEC) incidence in some nasal continuous positive airway pressure (NCPAP) patients raise concerns about whether the related abdominal distension is benign or contributes to NEC. We tested the hypothesis that mechanical strain causes an exaggerated enterocyte inflammatory response and decreased enterocyte growth and proliferation in the absence and presence of lipopolysaccharide (LPS). METHODS: First we used a confluent enterocyte (IEC-6) monolayer to investigate effects of strain on inflammatory cytokine production and Toll-like receptor 4 (TLR-4) gene expression. Then we used a low seeding density to measure cell growth and proliferation. Ten percent mechanical strain was applied. RESULTS: Significant increases in interleukin (IL)-8 and in IL-6 were observed after 8 and 24 h of cellular strain, respectively, and maintained throughout the study. TLR-4 expression was increased at 48 h. Mechanical strain led to slower proliferation and division whereas LPS alone had minimal effects. The responses of LPS and strain were supra-additive, suggesting synergistic cellular effects. CONCLUSION: We speculate intestinal distension associated with the use of NCPAP, especially in the presence of abnormal gut colonization, may result in increased inflammatory cytokine production and be a contributing factor to neonatal intestinal morbidities.

LPS-binding protein enables intestinal epithelial restitution despite LPS exposure.

OBJECTIVES: Intestinal epithelial restitution is the first part in the process of mucosal repair after injury in the intestine. Integrity of the intestinal mucosal barrier is important as a first line of defense against bacteria and endotoxin. Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in extremely-low-birth-weight infants, but its mechanisms are not well defined. Abnormal bacterial colonization, immature barrier function, innate immunity activation, and inflammation likely play a role. Lipopolysaccharide (LPS)-binding protein (LBP) is secreted by enterocytes in response to inflammatory stimuli and has concentration-dependent effects. At basal concentrations, LBP stimulates the inflammatory response by presenting LPS to its receptor; however, at high concentrations, LBP is able to neutralize LPS and prevent an exaggerated inflammatory response. We sought to determine how LBP would affect wound healing in an in vitro model of intestinal cell restitution and protect against intestinal injury in a rodent model of NEC. METHODS: Immature intestinal epithelial cells (IEC-6) were seeded in poly-L-lysine-coated 8-chamber slides and grown to confluence. A 500-µm wound was created using a cell scraper mounted on the microscope to achieve uniform wounding. Media was replaced with media containing LPS ± LBP. Slide wells were imaged after 0, 8, and 24 hours and then fixed. Cellular restitution was evaluated via digital images captured on an inverted microscope and wound closure was determined by automated analysis. Toll-like receptor 4 (TLR4) was determined by reverse transcriptase-polymerase chain reaction after RNA isolation from wounded cells 24 hours after treatment. RESULTS: LPS alone attenuated wound healing in immature intestinal epithelium. This attenuation is reversed by 24 hours with increasing concentrations of LBP so that wound healing is equivalent to control (P < 0.001). TLR4 was increased with LPS alone but levels returned to that of control after addition of LBP in the higher concentrations. LBP had no effect on the development of intestinal injury when given during our rodent model of NEC. Abnormal bacterial colonization and activation of innate immunity by LPS are likely involved in the pathogenesis of NEC.The attenuation of wound healing was reversed when LBP was added to LPS but only in the higher concentrations. At these same concentrations of LBP, TLR4 was decreased to that of control. CONCLUSIONS: These results indicate that LBP may be a novel therapeutic strategy to facilitate wound healing after the acute phase of NEC and other forms of intestinal injury.

Maternal preeclampsia and neonatal outcomes.

Preeclampsia is a multiorgan, heterogeneous disorder of pregnancy associated with significant maternal and neonatal morbidity and mortality. Optimal strategies in the care of the women with preeclampsia have not been fully elucidated, leaving physicians with incomplete data to guide their clinical decision making. Because preeclampsia is a progressive disorder, in some circumstances, delivery is needed to halt the progression to the benefit of the mother and fetus. However, the need for premature delivery has adverse effects on important neonatal outcomes not limited to the most premature infants. Late-preterm infants account for approximately two thirds of all preterm deliveries and are at significant risk for morbidity and mortality. Reviewed is the current literature in the diagnosis and obstetrical management of preeclampsia, the outcomes of late-preterm infants, and potential strategies to optimize fetal outcomes in pregnancies complicated by preeclampsia.

Poly(ADP-ribose) polymerase-1: a novel therapeutic target in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of infancy, afflicting 11% of infants born 22-28 wk GA. Both inflammation and oxidation may be involved in NEC pathogenesis through reactive nitrogen species production, protein oxidation, and DNA damage. Poly(ADP-ribose) polymerase-1 (PARP-1) is a critical enzyme activated to facilitate DNA repair using nicotinamide adenine dinucleotide (NAD+) as a substrate. However, in the presence of severe oxidative stress and DNA damage, PARP-1 overactivation may ensue, depleting cells of NAD+ and ATP, killing them by metabolic catastrophe. Here, we tested the hypothesis that NO dysregulation in intestinal epithelial cells during NEC leads to marked PARP-1 expression and that administration of a PARP-1 inhibitor (nicotinamide) attenuates intestinal injury in a newborn rat model of NEC. In this model, 56% of control pups developed NEC (any stage) versus 14% of pups receiving nicotinamide. Forty-four percent of control pups developed high-grade NEC (grades 3-4), whereas only 7% of pups receiving nicotinamide developed high-grade NEC. Nicotinamide treatment protects pups against intestinal injury incurred in the newborn rat NEC model. We speculate that PARP-1 overactivation in NEC may drive mucosal cell death in this disease and that PARP-1 may be a novel therapeutic target in NEC.

Probiotics and prebiotics for the prevention of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) continues to be a major cause of morbidity and mortality in premature infants. Although the pathogenesis of NEC remains unclear, abnormal bacterial colonization has been postulated as playing a central role. Various factors impact bacterial colonization following delivery. Compared to term infants, the bacterial colonization pattern in prematurely born infants is markedly different, with a greater predilection for colonization with pathogenic bacteria. Probiotic and prebiotic administration offers the opportunity to manipulate the intestinal bacterial environment, favoring the growth of commensal bacteria. Experimental data from animal studies and data from human trials suggest that probiotics decrease the incidence of NEC. These preliminary studies support the need for a large, randomized, controlled trial to further investigate the role of probiotics in the prevention of NEC.

Necrotizing enterocolitis in neonates undergoing the hybrid approach to complex congenital heart disease.

OBJECTIVE: To investigate the prevalence of necrotizing enterocolitis (NEC) in neonates undergoing the Stage I hybrid procedure for palliation of complex congenital heart disease (CHD). Neonates undergoing the Norwood surgery for hypoplastic left-heart syndrome have the highest risk for NEC of all CHD patients. The hybrid procedure is another palliative option for hypoplastic left-heart syndrome, but NEC in neonates undergoing this procedure has not been reported. DESIGN: Retrospective chart review of 73 neonates who underwent the hybrid procedure for palliation of complex CHD. Demographic, perinatal, perioperative, clinical, and procedural data were collected. NEC was defined as modified Bell's Stage II and above. SETTING: The cardiothoracic and neonatal intensive care units in a large free-standing children's hospital. PATIENTS: All neonates who underwent the hybrid Stage I procedure for the palliation of complex CHD from April 2002 through April 2008. MEASUREMENTS AND MAIN RESULTS: Seventy-three neonates were reviewed and 11.0% (eight of 73) developed NEC. Of the patients with NEC, 37.5% (three of eight) died and two patients required abdominal surgery. Earlier gestational age (< 37 wks), lower maximum dose of prostaglandin infusion, and unexpected readmission to the intensive care unit were statistically associated with NEC (p = .009, 0.02, and 0.04, respectively). No other demographic, perinatal, perioperative, clinical, or procedural variables were associated with the development of NEC in this patient population, including enteral feeding regimens, umbilical artery catheters, inotrope use, and average oxygen saturation and diastolic blood pressure. CONCLUSIONS: The prevalence of NEC in patients undergoing the hybrid procedure is comparable to that reported for neonates undergoing the Norwood procedure. Earlier gestational age is a significant risk factor for NEC in patients who undergo the hybrid Stage I procedure. Multidisciplinary approaches to better understand abdominal complications and to develop feeding regimens in neonates undergoing the hybrid approach to complex CHD are needed to improve outcomes and decrease morbidities.

Use of polyethylene bags in extremely low birth weight infant resuscitation for the prevention of hypothermia.

OBJECTIVE: To compare the clinical responses of extremely low birth weight (ELBW) infants resuscitated in polyethylene bags with ELBW infants who were resuscitated using traditional temperature control measures. STUDY DESIGN: Retrospective cohort investigation of 70 ELBW infants who were resuscitated using polyethylene bags (study) and 70 ELBW infants (control) resuscitated without polyethylene bags matched by birth weight, gestational age and gender. RESULTS: Infants in the study and control groups were comparable demographically and in obstetric risk factors. Study and control infants were similar in birth weight, gestational age and low 5-minute Apgar score. Axillary temperature on admission to the neonatal intensive care unit (NICU) and at 1 hour was greater in the study group as compared with controls. The incidence of grade III-IV intraventricular hemorrhage and periventricular leukomalacia (PVL) combined was decreased in the study group as compared with controls. Other neonatal comorbidities were not different. CONCLUSION: Resuscitation of ELBW infants in polyethylene bags led to higher skin temperature on admission to the NICU and at 1 hour of life. These infants were less likely to develop grade 3-4 PVL than infants resuscitated using traditional temperature control measures. No deleterious clinical effects were observed in infants resuscitated using polyethylene bags.