Association of unit size, resource utilization and occupancy with outcomes of preterm infants.

OBJECTIVE: Assess association of NICU size, and occupancy rate and resource utilization at admission with neonatal outcome. STUDY DESIGN: Retrospective cohort study of 9978 infants born at 23-32 weeks gestation and admitted to 23 tertiary-level Canadian NICUs during 2010-2012. Adjusted odds ratios (AOR) were estimated for a composite outcome of mortality/any major morbidity with respect to NICU size, occupancy rate and intensity of resource utilization at admission. RESULTS: A total of 2889 (29%) infants developed the composite outcome, the odds of which were higher for 16-29, 30-36 and >36-bed NICUs compared with <16-bed NICUs (AOR (95% CI): 1.47 (1.25-1.73); 1.49 (1.25-1.78); 1.55 (1.29-1.87), respectively) and for NICUs with higher resource utilization at admission (AOR: 1.30 (1.08-1.56), Q4 vs Q1) but not different according to NICU occupancy. CONCLUSION: Larger NICUs and more intense resource utilization at admission are associated with higher odds of a composite adverse outcome in very preterm infants.

Pulse oximetry advantages in infants with bronchopulmonary dysplasia.

We studied 12 infants with a clinical and radiologic diagnosis of bronchopulmonary dysplasia who were oxygen dependent and older than 30 days. Simultaneous readings of hemoglobin oxygen saturation (SaO2) determined by two pulse oximeters (Nellcor 100, BTI Biox III) and transcutaneous (tc) PO2 (Sensor Medics, Transend) were correlated with SaO2 (Radiometer, OSM 2 Hemoximeter) and PaO2 (Corning 178) measured on blood from an indwelling arterial catheter. For each infant, the fractional inspiratory oxygen (FiO2) was adjusted to obtain three to five sets of data in the range of 70% to 95% SaO2. Fifty-three data points were generated and pooled for analysis. The slope of the regression line generated for the Nellcor 100 was .86; for the BTI Biox III, it was .91; and for the Sensor Medics Transend, it was .55, resulting in average errors of +2.5%, +1.0%, and -29%, respectively, when comparing corresponding transcutaneous and arterial values. When SaO2 was equal to or less than 95%, no infants were hyperoxic. These data confirm reports by others that tcPO2 values do not accurately represent PaO2 values in older infants with bronchopulmonary dysplasia. Pulse oximeters do not require user calibration, and their sensor is unheated so they will not cause skin burns. We conclude that pulse oximetry offers major advantages over tcPO2 measurements in the management of infants with bronchopulmonary dysplasia.

Effects of high-frequency and conventional ventilation on the premature lamb lung.

Twelve sets of twin lambs were delivered prematurely by cesarean section at 133-136 days gestational age and ventilated for 3 h with either high-frequency oscillation (HFO) or conventional mechanical ventilation (CMV). Blood gases and pH values were monitored at 30-min intervals, and ventilator settings were adjusted to maintain CO2 partial pressure (PCO2) values within the normal range. There were no differences in the sequential blood gas or pH values between the HFO or CMV lambs. Mean airway pressures (MAP) between 8.0 and 20.4 cmH2O were required, indicating lung disease of variable severity in the lambs. The bidirectional protein leak from the vascular space to the airways and alveoli and vice versa was measured with radiolabeled albumins given by intravascular injection and with fetal lung fluid at birth. The albumin leaks in both directions increased as MAP required to normalize PCO2 increased, but the degree of leak was independent of type of ventilation. Pathological findings of epithelial necrosis and hyaline membranes occurred to a similar extent in lung sections from both groups of lambs. In the HFO animals less phosphatidylcholine in the alveolar wash and more of a tracer dose of radiolabeled natural surfactant that had been given at birth became tissue associated. These results indicate a decrease in the initial secretion of surfactant and/or a stimulation of reuptake in the HFO animals. HFO did not protect the immature lung from the development of large protein leaks or the pathological changes of the respiratory distress syndrome.

Development of the pulmonary airways in the fetal rat and its relation to the prenatal environment.

We studied the left lung using multi-focus microphotography in 378 rat fetuses, assessing airway branching from day 13 to day 19 of gestation, and lung growth variables from day 13 to day 21. Longitudinal growth, and monopodial and dichotomous branching brought about a consistent airway pattern with variations within each day of gestation and a small overlap between adjacent days. Amniotic fluid weight and pole to pole (PTP) distance of the lung increased quadratically with age, while fetal weight and the peripheral airway count (PAC) increased exponentially. The location of the fetus within the uterus had no effect on fetal variables, but correlations were found between maternal weight gain and both fetal weight and PTP. Fetal weight was the best predictor of PAC from gestational ages 15 to 19 days (P < 0.008). The method described allows for observations that are reproducible within the environmental variations present in normal gestation and can be used to study the effect of external factors on lung development.

Effect of triamcinolone acetonide on the development of the pulmonary airways in the fetal rat.

Triamcinolone acetonide (TAC) has a potent teratogenic effect on various mammalian fetal tissues as well as a steroid effect on the lung. Less well documented is the fact that it produces profound oligohydramnios. We wished to determine what effect TAC would have on branching morphogenesis and other aspects of lung development, using an in vivo model described previously. Thirty rats were randomized to receive 0.6 mg/kg of TAC or saline on days 12, 13, and 14 of gestation. At gestational days 15, 17, 18, and 21, the left lungs of 365 fetuses were studied by dissecting microscopy, histology, and morphometry. TAC produced profound pulmonary hypoplasia (dry Jung weight/body weight 0.025, compared with 0.06 in controls) on day 21. TAC decreased maternal weight gain, fetal weight, placental weight, aminiotic fluid, and pole to pole length (PTP), while it increased the peripheral airway count (PAC). The number of central and intermediate airway branches was reduced, and they were dilated. Growth of peripheral airways was enhanced. In treated fetuses epithelial cells lining these airspaces were histologically more mature and the mesenchyme thinner than in controls. These findings were confirmed by the morphometric measurements. We conclude that when TAC is administered in the early phase of fetal rat lung development, the lungs become hypoplastic, with hypoplasia of the intermediate airways, an increase in the number of peripheral airways, and increased differentiation. We speculate that these effects are primarily due to the steroid action of TAC and that the mechanisms of monopodial branching are different from those of dichotomous branching.

Chronic lung disease following neonatal ventilation. I. incidence in two geographically defined populations.

The objective of this study was to compare the incidence of chronic lung disease following neonatal ventilation in two geographically defined populations. Prospective data collection was carried out over a 1 year period from March 11, 1990 to February 28, 1991 in the Trent Health Region (England) and in British Columbia, Canada. All infants < or = 32 weeks gestation and/or < or = 1500 g birthweight born to mothers normally resident in either the Trent Health Region or British Columbia were included. The main outcome measures were mortality rate, presence of chronic lung disease, days of ventilation, and oxygen used by each infant. The proportion of shortened gestation, low birthweight babies was 1.5% in Trent and 1.2% in British Columbia (957 of 63,350 births in Trent and 526 of 45,333 births in British Columbia). There were no significant differences in mean birthweight or gestation between the two cohorts, but there was a trend towards lower mortality for infants 750-1500 g birthweight in British Columbia. The incidence of chronic lung disease (using either of two definitions) was significantly higher in British Columbia, with a corresponding greater amount of respiratory care required. This occurred despite higher use of antenatal steroids and surfactant therapy in the British Columbia group. We conclude that there are important clinical and resource implications resulting from the number of ventilator and oxygen days used by the preterm population in terms of planning of neonatal services. The role of individual treatment modalities in producing differences in the incidence of chronic lung disease warrants further study in the setting of a geographically defined population.

Waxing and waning hyperinflation in congenital cystic adenomatoid malformation of the lung.

This report describes a newborn with respiratory distress, waxing and waning left lung hyperinflation, and pulmonary hemorrhage. This atypical presentation of congenital cystic adenomatoid malformation of the lung has not been previously reported, posed a major diagnostic problem, and delayed potentially lifesaving surgery.

Impact of early surfactant and inhaled nitric oxide therapies on outcomes in term/late preterm neonates with moderate hypoxic respiratory failure.

OBJECTIVE: We conducted a post-hoc analysis of early inhaled nitric oxide (iNO)-randomized controlled trial data to identify associations pertinent to the management of moderate hypoxic respiratory failure in term/late preterm infants. STUDY DESIGN: Univariate and multivariate logistic regression analyses were used to determine risk factors for the progression of respiratory failure and extracorporeal membrane oxygenation (ECMO)/death. RESULT: Among the 299 enrolled infants, oxygenation index (OI) <20 at enrollment (odds ratio 0.52, confidence interval (CI) 0.27 to 0.97) and surfactant use before randomization (odds ratio 0.47, CI 0.24 to 0.91) were associated with decreased ECMO/death rates. Early surfactant use for respiratory distress syndrome, perinatal aspiration syndrome and pneumonia/sepsis was associated with lower risk of ECMO/death (P<0.001). Early iNO (OI 15 to 25) decreased the progression of respiratory failure to OI >30 (P=0.002) and to composite outcome of OI >30 or ECMO/death (P=0.02). CONCLUSION: This post-hoc analysis suggests that early use of surfactant and iNO in moderate respiratory failure is associated with improved outcomes.

Midfacial hypoplasia associated with long-term intubation for bronchopulmonary dysplasia.

Six preterm infants with bronchopulmonary dysplasia were nasotracheally intubated for 68 to 243 days. Gestational age at birth ranged from 24 to 35 weeks. Endotracheal tube size was changed to account for growth and varied from 2.5 to 4.0 mm. These infants developed features of midfacial hypoplasia, namely, depressed nasal bridge, small-tipped nose, long philtrum, underdeveloped malar areas, and carplike mouth. These features have not been associated with long-term intubation in premature infants. We suggest that features of prolonged nasotracheal intubation, such as direct compression by the tube and the method of tube fixation, decreased air flow through the developing nares and sinuses and reduced faciomuscular activity, resulting in the observed midfacial hypoplasia. The degree to which growth corrects these deformations is unknown.

Increased compliance in response to salbutamol in premature infants with developing bronchopulmonary dysplasia.

We compared the effect of salbutamol and placebo in a double-blind study of preterm infants with bronchopulmonary dysplasia, using a randomized, crossover design with several replicates per subject. Sixty-two tests were performed on 20 ventilator-dependent infants weighing less than 1500 gm. Patients were entered as early as the first week of life and studied for at least 4 weeks or until extubation. Each subject was his own control subject and was randomly assigned to a placebo-salbutamol or salbutamol-placebo sequence administered on 2 consecutive days of each week. Static compliance, expiratory resistance of the respiratory system, and changes in transcutaneous oxygen and carbon dioxide tension were measured. Static compliance improved by 0.240 ml/cm H2O/kg (35.3%) after salbutamol and by 0.010 ml/cm H2O/kg (2.8%) after placebo (p less than 0.0001). The presence of a predetermined decrease in carbon dioxide tension correlated with large changes in static compliance per kilogram and with the need for a high level of fractional inspired oxygen. The magnitude of the clinical and physiologic improvement observed, and the early response suggest that long-term bronchodilator therapy starting as early as the second week of life may be beneficial for very low birth weight infants with early bronchopulmonary dysplasia.

The measurement of knee-heel length in newborn infants using a simple vernier calipers.

OBJECTIVE: To assess the usefulness of a simple vernier calipers for measuring knee-heel length in neonates. SUBJECTS AND METHODS: Using a simple vernier calipers, knee-heel length was measured five times by 2 observers in 50 babies (29M, 21F; mean birthweight 1597 g; median gestational age at birth 29 weeks) at a median postnatal age of 11 days. A subgroup of 20 babies had knee-heel length measured similarly at weekly intervals for 3 weeks. Corrected gestational age and weight were simultaneously recorded. One observer was experienced in using the vernier calipers. The precision of the calipers was established using 4 steel gauge blocks of varying length (7.62-10.17 cm). RESULTS: The calipers were very precise when measuring steel gauge blocks. In babies, there was a downward trend across the first 2 measurements for both observers, the measurements stabilizing over the last three. Using the final three measurements per baby (n = 50), the experienced observer had a mean standard deviation of 0.023 cm and mean coefficient of variation 0.23% when measuring an average knee-heel length of 9.99 cm. The inexperienced observer had a mean standard deviation of 0.057 cm and a mean coefficient of variation of 0.56%, when measuring an average knee-heel length of 10.14 cm. The inter-observer reliability, measured by the intra-class correlation coefficient, was 0.99. The agreement between observers was such that one observer measured knee-heel length consistently less (0.15 cm, SD 0.18 cm) than the other. The reliability for knee-heel length velocity was lower (R = 0.85), but agreement between observers was high with an average difference of 0.016 cm/week. Knee-heel length was significantly correlated (p < 0.001) with corrected gestational age (r = 0.85) and with weight (r = 0.96). There was a weaker but significant correlation (r = 0.47, p < 0.001) between knee-heel length velocity and rate of weight gain (g/day), indicating that weight gain may not always be accompanied by an increase in linear growth. CONCLUSION: The measurement of knee-heel length by a simple vernier calipers is an accurate, reproducible and non-invasive method of assessing short-term linear growth in neonates. However, it is recommended that measurements of knee-heel length in a individual baby should be made by a single experienced observer.

Growth and growth factors in premature infants receiving dexamethasone for bronchopulmonary dysplasia.

Physical growth and the serum growth factors, insulin growth factor 1 (IGF1) and its binding protein (IGFBP3) were measured weekly during dexamethasone treatment and for 3 weeks after stopping therapy in 10 ventilated babies [median (range) birth weight 860 g (640-1210); median (range) gestational age 26 weeks (24-29)] with bronchopulmonary dysplasia (BPD). The mean (+/- SE) rates of change of all physical measures except crown-rump length (CRL) increased significantly after stopping dexamethasone: weight gain 13.2 (+/- 1.5) on versus 1.0 (+/- 1.9) g/day off treatment; occipital-frontal circumference 0.7 (+/- 0.1) cm/week; CRL 0.5 (+/- 0.1) versus 0.7 (+/- 0.1) (TBL) 0.7 (+/- 0.1) versus 1.1 (+/- 0.1) cm/week; CRL 0.5 (+/- 0.1) versus 0.7 (+/- 0.1) cm/week, and knee-ankle length (KAL) 0.13 (+/- 0.02) versus 0.36 (+/- 0.04) cm/week. Mean serum IGF-1 (1.57 +/- 0.13 versus 3.56 +/- 0.41 nmol/L) and IGFBP3 (0.94 +/- 0.03 versus 1.12 +/- 0.05 mg/L) levels also increased off treatment. The weekly dose of dexamethasone (mg/kg) was significantly negatively correlated with all physical growth measures (P < 0.01), but showed no correlation with growth factors. Protein intake (g/kg/day) was significantly correlated (P < 0.01) with weight gain (r = 0.28), changes (TBL) (r = 0.32), serum IGF1 levels (r = 0.60), and IGFBP3 levels (r = 0.37). All aspects of physical growth are compromised during dexamethasone treatment for BPD. Poor growth during steroid treatment is associated with lower IGF1 and IGFBP3 levels. Further study is needed to examine the effect of varying dexamethasone dosage regimes and nutritional intake on the growth process in BPD.

Prenatally diagnosed fetal neck teratoma. Case report and novel management options.

A case of fetal neck teratoma diagnosed at 32 weeks' gestation is reported. Planning before delivery included consultations with the neonatologist, the anesthesiologist, the otolaryngologist and the social worker. Delivery by cesarean section under epidural anesthesia was carried out at 34 weeks because of preterm labor. The head was delivered and the fetus was intubated within 4(1/2) min using a rigid bronchoscope. Magnesium sulfate and nitroglycerin provided uterine relaxation allowing fetal oxygenation via the uteroplacental circulation. Umbilical artery blood gases were satisfactory. The early neonatal course was complicated by hemorrhage from the teratoma externally as well as intratracheal bleeding and ventilatory problems. The baby died at 40 min of age in his mother's arms.

The new American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiac care: presented by the Emergency Cardiac Care Subcommittee of the Heart and Stroke Foundation of Canada.

CPR courses (both basic and advanced) continue to evolve. The recent CPR and ECC guidelines by the AHA consolidate the research and vast experience in one document. These guidelines are helpful to lay people and health care professionals who intervene in cases of cardiac arrest. They are also excellent resources for those involved in coordinating ECC systems in the community.

L-selectin expression on polymorphonuclear leukocytes and monocytes in premature infants: reduced expression after dexamethasone treatment for bronchopulmonary dysplasia.

We examined the effect of dexamethasone on the expression of the adhesion molecule L-selectin on circulating polymorphonuclear leukocytes (PMLs) and monocytes from premature infants with bronchopulmonary dysplasia (BPD). Nineteen infants who received dexamethasone (Dex group) and 28 who did not receive dexamethasone (no Dex group) were studied. L-selectin expression, measured as mean fluorescence intensity, was lower on circulating PMLs (5.7 +/- 0.6 vs 10.6 +/- 0.7, p < 0.001) and monocytes (7.9 +/- 0.9 vs 12.5 +/- 0.9, p < 0.02) isolated from those who had received dexamethasone. Because L-selectin is important for the recruitment of PMLs to inflammatory foci in the lungs, we speculate that one of the mechanisms by which dexamethasone reduces inflammation in BPD is by impairing the ability of leukocytes to migrate into the BPD lesions.

Randomized, double-blind, controlled trial of long-term diuretic therapy for bronchopulmonary dysplasia.

The effects of continuous therapy with hydrochlorothiazide and spironolactone on pulmonary function in 34 premature infants with severe bronchopulmonary dysplasia were assessed in a randomized double-blind controlled trial. Subjects were greater than or equal to 30 days old, were supported by mechanical ventilation in greater than or equal to 30% oxygen, and had radiographic evidence of bronchopulmonary dysplasia. The treatment group (n = 19) and the placebo group (n = 15) were similar in all respects except for distribution of gender. Anthropometrics, ventilatory measurements, and the results of pulmonary function tests were evaluated at study entry and at 1, 4, and 8 weeks into therapy. Poststudy chest radiographs were compared with those obtained before the study. The proportion of infants alive at discharge was significantly increased (84%) in the treatment group compared with the placebo group (47%) (p = 0.05). There were no statistically significant differences in total hospital days or in total ventilator days. Total respiratory system compliance at 4 weeks was higher in the treatment group (0.61 +/- 0.18) than in the placebo group (0.45 +/- 0.13) (p = 0.016). No difference in outcome was detected between male and female infants in the treatment group. These results suggest that long-term diuretic therapy improves outcome in infants with bronchopulmonary dysplasia.

Morphine pharmacokinetics and pain assessment in premature newborns.

OBJECTIVES: To determine morphine pharmacokinetics in premature neonates varying in postconceptional age (PCA) and evaluate behavioral pain response in relationship to serum morphine concentrations. METHODS: Premature neonates (n = 48), stratified by weeks of PCA (group 1 = 24-27 weeks, group 2 = 28-31 weeks, group 3 = 32-35 weeks, and group 4 = 36-39 weeks) received morphine infusions. Blood samples were drawn at 48, 60, and 72 hours and at discontinuation of morphine, followed by 3 samples obtained during the next 24 hours. Newborns were videotaped during heel lances and restful states, with morphine at steady-state concentrations and without morphine. Pain was assessed by using the Neonatal Facial Coding System (NFCS). Statistical analysis included regression between NFCS score changes from baseline to painful procedure with and without morphine. RESULTS: Morphine clearance for groups 1, 2, 3, and 4 was calculated as 2.27 +/- 1.07, 3.21 +/- 1.57, 4.51 +/- 1.97, and 7.80 +/- 2.67 mL/kg/min, respectively, and correlated with PCA (r = 0.63, P <.001). Pain measured by facial expression was diminished; however, it did not correlate with morphine concentrations. CONCLUSION: Morphine clearance in premature neonates is less than reported, increasing with PCA. Facial activity discloses morphine analgesia; however, it is unrelated to morphine concentrations.

Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants.

BACKGROUND: The prophylactic administration of indomethacin reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants (those with birth weights below 1500 g). Whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in renal, intestinal, and cerebral blood flow is not known. METHODS: Soon after they were born, we randomly assigned 1202 infants with birth weights of 500 to 999 g (extremely low birth weight) to receive either indomethacin (0.1 mg per kilogram of body weight) or placebo intravenously once daily for three days. The primary outcome was a composite of death, cerebral palsy, cognitive delay, deafness, and blindness at a corrected age of 18 months. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly within the same time frame. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrhage, chronic lung disease, ultrasonographic evidence of intracranial abnormalities, necrotizing enterocolitis, and retinopathy. RESULTS: Of the 574 infants with data on the primary outcome who were assigned to prophylaxis with indomethacin, 271 (47 percent) died or survived with impairments, as compared with 261 of the 569 infants (46 percent) assigned to placebo (odds ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4; P=0.61). Indomethacin reduced the incidence of patent ductus arteriosus (24 percent vs. 50 percent in the placebo group; odds ratio, 0.3; P<0.001) and of severe periventricular and intraventricular hemorrhage (9 percent vs. 13 percent in the placebo group; odds ratio, 0.6; P=0.02). No other outcomes were altered by the prophylactic administration of indomethacin. CONCLUSIONS: In extremely-low-birth-weight infants, prophylaxis with indomethacin does not improve the rate of survival without neurosensory impairment at 18 months, despite the fact that it reduces the frequency of patent ductus arteriosus and severe periventricular and intraventricular hemorrhage.