Preparedness of pediatric residents for fellowship: a survey of US neonatal-perinatal fellowship program directors.

OBJECTIVE: To evaluate the preparedness of pediatric residents entering accredited neonatal-perinatal medicine (NPM) fellowships in the United States. STUDY DESIGN: A multi-domain, validated survey was distributed to Program Directors (PDs) of US NPM fellowship programs. The 47-item survey explored 5 domains: professionalism, independent practice, psychomotor ability, clinical evaluation, and academia. A systematic, qualitative analysis on free-text comments was also performed. RESULTS: Sixty-one PDs completed the survey, for a response rate of 62% (61/98). For entering fellows, PDs assessed performance in professionalism positively, including 76% as communicating effectively with parents and 90% treating residents/house-staff with respect. In contrast, most PDs rated performance in psychomotor abilities negatively, including 59% and 79% as deficient in bag-and-mask ventilation and neonatal endotracheal intubation, respectively. Although 62% of PDs assessed entering fellows positively for genuine interest in academic projects, fewer than 10% responded positively that entering fellows understood research protocol design, basic statistics, or were capable of writing a cohesive manuscript well. Thematic clustering of qualitative data revealed deficits in psychomotor ability and academia/scholarship. CONCLUSIONS: On the basis of the perspective of front line educators, graduating pediatric residents are underprepared for subspecialty fellowship training in NPM. To provide the best preparation for pediatric graduates who pursue advanced training, changes to residency education to address deficiencies in these important competencies are warranted.

Predicting death or extended length of stay in infants with congenital diaphragmatic hernia.

OBJECTIVE: To predict mortality or length of stay (LOS) >109 days (90th percentile) among infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We conducted a retrospective analysis using the Children's Hospital Neonatal Database during 2010 to 2014. Infants born >34 weeks gestation with CDH admitted at 22 participating regional neonatal intensive care units were included; patients who were repaired or were at home before admission were excluded. The primary outcome was death before discharge or LOS >109 days. Factors associated with this outcome were used to develop a multivariable equation using 80% of the cohort. Validation was performed in the remaining 20% of infants. RESULTS: The median gestation and age at referral in this cohort (n=677) were 38 weeks and 6 h, respectively. The primary outcome occurred in 242 (35.7%) infants, and was distributed between mortality (n=180, 27%) and LOS >109 days (n=66, 10%). Regression analyses showed that small for gestational age (odds ratio (OR) 2.5, P=0.008), presence of major birth anomalies (OR 5.9, P<0.0001), 5- min Apgar score ⩽3 (OR 7.0, P=0.0002), gradient of acidosis at the time of referral (P<0.001), the receipt of extracorporeal support (OR 8.4, P<0.0001) and bloodstream infections (OR 2.2, P=0.004) were independently associated with death or LOS >109 days. This model performed well in the validation cohort (area under curve (AUC)=0.856, goodness-of-fit (GF) χ(2), P=0.16) and acted similarly even after omitting extracorporeal support (AUC=0.82, GF χ(2), P=0.05). CONCLUSIONS: Six variables predicted death or LOS ⩾109 days in this large, contemporary cohort with CDH. These results can assist in risk adjustment for comparative benchmarking and for counseling affected families.

Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children's Hospitals Neonatal Consortium HIE focus group.

OBJECTIVE: To characterize infants affected with perinatal hypoxic ischemic encephalopathy (HIE) who were referred to regional neonatal intensive care units (NICUs) and their related short-term outcomes. STUDY DESIGN: This is a descriptive study evaluating the data collected prospectively in the Children's Hospital Neonatal Database, comprised of 27 regional NICUs within their associated children's hospitals. A consecutive sample of 945 referred infants born ⩾36 weeks' gestation with perinatal HIE in the first 3 days of life over approximately 3 years (2010-July 2013) were included. Maternal and infant characteristics are described. Short-term outcomes were evaluated including medical comorbidities, mortality and status of survivors at discharge. RESULT: High relative frequencies of maternal predisposing conditions, cesarean and operative vaginal deliveries were observed. Low Apgar scores, profound metabolic acidosis, extensive resuscitation in the delivery room, clinical and electroencephalographic (EEG) seizures, abnormal EEG background and brain imaging directly correlated with the severity of HIE. Therapeutic hypothermia was provided to 85% of infants, 15% of whom were classified as having mild HIE. Electrographic seizures were observed in 26% of the infants. Rates of complications and morbidities were similar to those reported in prior clinical trials and overall mortality was 15%. CONCLUSION: Within this large contemporary cohort of newborns with perinatal HIE, the application of therapeutic hypothermia and associated neurodiagnostic studies appear to have expanded relative to reported clinical trials. Although seizure incidence and mortality were lower compared with those reported in the trials, it is unclear whether this represented improved outcomes or therapeutic drift with the treatment of milder disease.

Short-term outcomes for preterm infants with surgical necrotizing enterocolitis.

OBJECTIVE: To characterize the population and short-term outcomes in preterm infants with surgical necrotizing enterocolitis (NEC). STUDY DESIGN: Preterm infants with surgical NEC were identified from 27 hospitals over 3 years using the Children's Hospitals Neonatal Database; infants with gastroschisis, volvulus, major congenital heart disease or surgical NEC that resolved prior to referral were excluded. Patient characteristics and pre-discharge morbidities were stratified by gestational age (<28 vs 28(0/7) to 36(6/7) weeks' gestation). RESULT: Of the 753 eligible infants, 60% were born at <28 weeks' gestation. The median age at referral was 14 days; only 2 infants were inborn. Male gender (61%) was overrepresented, whereas antenatal steroid exposure was low (46%). Although only 11% had NEC totalis, hospital mortality (<28 weeks' gestation: 41%; 28(0/7) to 36(6/7) weeks' gestation: 32%, P=0.02), short bowel syndrome (SBS)/intestinal failure (IF) (20% vs 26%, P=0.06) and the composite of mortality or SBS/IF (50% vs 49%, P=0.7) were prevalent. Also, white matter injury (11.7% vs 6.6%, P=0.02) and grade 3 to 4 intraventricular hemorrhages (23% vs 2.7%, P<0.01) were commonly diagnosed. After referral, the median length of hospitalization was longer for survivors (106 days; interquartile range (IQR) 79, 152) relative to non-survivors (2 days; IQR 1,17; P<0.001). These survivors were prescribed parenteral nutrition infrequently after hospital discharge (<28 weeks': 5.2%; 28(0/7) to 36(6/7) weeks': 9.9%, P=0.048). CONCLUSION: After referral for surgical NEC, the short-term outcomes are grave, particularly for infants born <28 weeks' gestation. Although analyses to predict outcomes are urgently needed, these data suggest that affected infants are at a high risk for lengthy hospitalizations and adverse medical and neuro-developmental abnormalities.

The Children's Hospitals Neonatal Database: an overview of patient complexity, outcomes and variation in care.

The Children's Hospitals Neonatal Consortium is a multicenter collaboration of leaders from 27 regional neonatal intensive care units (NICUs) who partnered with the Children's Hospital Association to develop the Children's Hospitals Neonatal Database (CHND), launched in 2010. The purpose of this report is to provide a first summary of the population of infants cared for in these NICUs, including representative diagnoses and short-term outcomes, as well as to characterize the participating NICUs and institutions. During the first 2 1/2 years of data collection, 40910 infants were eligible. Few were born inside these hospitals (2.8%) and the median gestational age at birth was 36 weeks. Surgical intervention (32%) was common; however, mortality (5.6%) was infrequent. Initial queries into diagnosis-specific inter-center variation in care practices and short-term outcomes, including length of stay, showed striking differences. The CHND provides a contemporary, national benchmark of short-term outcomes for infants with uncommon neonatal illnesses. These data will be valuable in counseling families and for conducting observational studies, clinical trials and collaborative quality improvement initiatives.

Predicting death or tracheostomy placement in infants with severe bronchopulmonary dysplasia.

OBJECTIVE: To estimate the risk of death or tracheostomy placement (D/T) in infants with severe bronchopulmonary dysplasia (sBPD) born < 32 weeks' gestation referred to regional neonatal intensive care units. STUDY DESIGN: We conducted a retrospective cohort study in infants born < 32 weeks' gestation with sBPD in 2010-2011, using the Children's Hospital Neonatal Database. sBPD was defined as the need for FiO2 ⩾ 0.3, nasal cannula support >2 l min(-1) or positive pressure at 36 weeks' post menstrual age. The primary outcome was D/T before discharge. Predictors associated with D/T in bivariable analyses (P < 0.2) were used to develop a multivariable logistic regression equation using 80% of the cohort. This equation was validated in the remaining 20% of infants. RESULT: Of 793 eligible patients, the mean gestational age was 26 weeks' and the median age at referral was 6.4 weeks. D/T occurred in 20% of infants. Multivariable analysis showed that later gestational age at birth, later age at referral along with pulmonary management as the primary reason for referral, mechanical ventilation at the time of referral, clinically diagnosed pulmonary hypertension, systemic corticosteroids after referral and occurrence of a bloodstream infection after referral were each associated with D/T. The model performed well with validation (area under curve 0.86, goodness-of-fit χ(2), P = 0.66). CONCLUSION: Seven clinical variables predicted D/T in this large, contemporary cohort with sBPD. These results can be used to inform clinicians who counsel families of affected infants and to assist in the design of future prospective trials.

Therapeutic interventions and short-term outcomes for infants with severe bronchopulmonary dysplasia born at <32 weeks' gestation.

OBJECTIVE: To characterize the treatments and short-term outcomes in infants with severe bronchopulmonary dysplasia (sBPD) referred to regional neonatal intensive care units. STUDY DESIGN: Infants born <32 weeks' gestation with sBPD were identified using the Children's Hospital Neonatal Database. Descriptive outcomes are reported. RESULT: A total of 867 patients were eligible. On average, infants were born at 26 weeks' gestation and referred 43 days after birth. Infants frequently experienced lung injury (pneumonia: 24.1%; air leak: 9%) and received systemic corticosteroids (61%) and mechanical ventilation (median duration 37 days). Although 91% survived to discharge, the mean post-menstrual age was 47 weeks. Ongoing care such as supplemental oxygen (66%) and tracheostomy (5%) were frequently needed. CONCLUSION: Referred infants with sBPD sustain multiple insults to lung function and development. Because affected infants have no proven, safe or efficacious therapy and endure an exceptional burden of care even after referral, urgent work is required to observe and improve their outcomes.

Effects of hyperoxia on postnatal intestinal development.

Fetuses develop in a marked hypoxic environment in utero. Premature infants often require high concentrations of oxygen to survive and develop in an environment that would be considered an oxygen stress for the fetus. Postnatal hyperoxia alters organ development, but there is minimal research regarding the role of hyperoxia in intestinal development. We attempted to determine whether postnatal hyperoxia exposure alters intestinal growth and function by using a reliable, objective and sensitive set of methods to study region-specific postnatal intestinal maturation. Rat pups born naturally were placed in continual exposure to room air (normoxia) or 85% oxygen (hyperoxia) immediately after birth. Pups were sacrificed at 1 and 2 weeks of age. Intestines were removed and fixed in formalin. Average mucosal, submucosal, and muscularis thicknesses were measured on hematoxylin and eosin stained sections. Immunohistochemistry was performed using antibodies against NOS II. The staining intensity was determined and quantified for site-specific regions of intestinal sections. No differences in mucosal thickness, submucosal thickness, or muscularis thickness were measured in the duodenum, jejunum or colon at any age. At two weeks of age, the thickness of the ileal mucosa was significantly greater in the group reared in 85% oxygen, and the group exposed to room air demonstrated significantly greater NOS II protein concentration than the hyperoxia group within the distal villus, proximal villus/crypts, submucosa, and muscularis in the distal small intestine.

Relationship between flow rate and NO production in postnatal mesenteric arteries.

We studied mesenteric arterial arcades from 3- and 35-day-old swine to determine the relationship between perfusate flow rate and release of nitric oxide (NO) into mesenteric effluent. Mesenteric arterial arcades were perfused under controlled-flow conditions with a peristaltic pump using warm oxygenated Krebs buffer. Basal rates of NO production were 43.6 +/- 4.2 vs. 12.1 +/- 2.5 nmol/min in 3- vs. 35-day-old mesentery during perfusion at in vivo flow rates (9 vs. 20 ml/min, respectively). Rate of NO production was directly related to flow rate over a wide range of flows (5-40 ml/min) in 3- but not 35-day-old mesentery. Both age groups demonstrated a brisk, albeit brief, increase in NO production in response to infusion of NO-dependent vasodilator substance P (10(-8) M/min). Tyrosine kinase inhibitor herbimycin A and L-arginine analog L-NMMA significantly attenuated flow-induced increase in NO production, and phosphatase inhibitor phenylarsine oxide increased magnitude of flow-induced increase in NO production in 3-day-olds. Removal of extracellular Ca(2+) and depletion of intracellular Ca(2+) stores (Ca(2+)-free Krebs with EGTA plus thapsigargin) had no effect on NO production in either group. Thus, basal rate of NO production is greater in mesenteric arterial arcades from 3- than from 35-day old swine, a direct relationship between flow rate and NO production rate is present in mesentery from 3- but not 35-day-olds, and phosphorylation events are necessary for this interaction to occur.

Age-dependent changes in the postnatal intestinal microcirculation.

Significant changes occur in intestinal hemodynamics during the transition from fetal to newborn life and then again during the first postnatal month. Most importantly, basal vascular resistance substantially decreases following birth. It then decreases further between postnatal days 1 and 3, plateaus, and then begins a slow, progressive increase between postnatal days 12 and 30. The basal rate of intestinal blood flow mirrors the changes in vascular resistance in an inverse manner. The postnatal changes in vascular resistance appear to be mediated, in large part, by an increase in the constitutive and stimulated production of nitric oxide. Most importantly, the diameter of terminal mesenteric arteries (150-300 microm diameter) in newborn (i.e., 1 day old) swine is determined by three intrinsic vascular control systems: endothelial production of nitric oxide and endothelin, and the inherent myogenic response of vascular smooth muscle. In contrast, these vessels in older subjects (i.e., 35 days old) are primarily passive in nature and fail to demonstrate significant diameter change in response to blockade of endogenous nitric oxide production or endothelin receptors, or applied perturbations of pressure or flow rate. The circulatory physiology of the perinatal and newborn intestine is exceptional when compared to the adult condition inasmuch as several hemodynamic variables change quite dramatically between fetal and neonatal life and during the first postnatal month. The unique hemodynamic conditions that characterize the perinatal and newborn intestine appear to be part of the overall physiological transition that occurs as the fetus, once born, replaces the placenta with his gastrointestinal tract to obtain nutrition. The goal of this review is to describe the circulatory physiology of the perinatal and newborn intestine, with a particular emphasis on those portions of the intestinal microcirculation that have thus far been studied. First, however, it is important to discuss the age-dependent changes that occur within the intestinal circulation during perinatal and early newborn life.

Pressure and flow characteristics of terminal mesenteric arteries in postnatal intestine.

The responses of buffer-perfused terminal mesenteric arteries from 3- and 35-day-old swine to manipulation of intravascular pressure and flow rate were determined. Under in vivo conditions, these vessels demonstrated age-dependent differences in resting diameter (182 vs. 301 microns in 3- vs. 35-day-old swine). A proximal-to-distal pressure gradient was present in vessels from both age groups (delta 13 vs. delta 16 mmHg in 3- vs. 35-day-old swine), suggesting their functional role as resistance vessels. Vessels were mounted within an in vitro perfusion apparatus that allowed independent regulation of inflow and outflow pressure. Vessels from both age groups demonstrated the development of active tone in response to an incremental rise in pressure, applied in the absence of flow. However, myogenic vasoconstriction was only observed in younger arterioles. Similarly, both groups demonstrated dilation in response to a flow stimulus generated in the absence of a net change in intravascular pressure, although the magnitude of this response was significantly greater in younger vessels (+27 vs. +7% in 3- vs. 35-day-old swine). The dilatory response to flow was eliminated by NG-monomethyl-L-arginine (10(-4)M) but restored by coadministration of L-arginine (10(-3)M). Myogenic vasoconstriction was overridden by flow-mediated dilation in terminal mesenteric arteries from 3- but not 35-day-old swine after concomitant application of pressure and flow stimuli. We conclude that the hemodynamic characteristics of terminal mesenteric arteries are age dependent in postnatal swine.