Achievement of maturational milestones among very low birth weight infants.

BACKGROUND: Very low birth weight (VLBW) infants must achieve several maturational milestones to be discharged home from the NICU. OBJECTIVE: Describe the timing of maturational milestones in VLBW infants and the impact of clinical variables and milestone achievement on postmenstrual age (PMA) at discharge. METHODS: For VLBW infants without severe lung disease discharged home from a level IV NICU, we assessed PMA at the achievement of thermoregulation, cardiorespiratory stability, feeding, and discharge. RESULTS: In 400 infants (median GA 28.4 weeks), lower birth weight, white race, and having multiple comorbidities of prematurity predicted later discharge PMA. The most common milestone sequence was CPAP discontinuation, caffeine discontinuation, thermoregulation, apnea resolution, and full oral feeds. PMA at apnea resolution and full oral feeds correlated highly with discharge PMA. CONCLUSIONS: In a single-center VLBW cohort, comorbidities of prematurity impacted the timing of NICU discharge through delay in oral feeding and cardiorespiratory stability.

Predicting risk for bronchopulmonary dysplasia: selection criteria for clinical trials.

Early identification of neonates in whom bronchopulmonary dysplasia is most likely to develop permits appropriate enrollment into clinical trials testing early intervention therapies for the prevention or treatment of bronchopulmonary dysplasia. Analysis of 160 neonatal intensive care unit survivors to 28 days revealed that supplemental oxygen requirement at 28 days could be predicted by a logistic regression including (1) birth weight, gestational age, 5-minute Apgar score, and peak inspiratory pressure at 12 hours for 12-hour-old neonates and (2) birth weight, gestational age, peak inspiratory pressure at 12 hours, and mean airway pressure at 10 days for 10-day-old neonates. These two regression analyses were applied prospectively to three new data sets totaling 238 neonates to test their predictive ability. Neonates were classified into low-, moderate-, or high-risk groups on the basis of their predicted probability of requiring oxygen supplementation at 28 days; low = probability of less than 25%, moderate = probability of 25% to 75%, and high = probability greater than 75%. Although these populations were demographically distinct from the original group, the regression analyses performed well. The regression analysis for 12 hours of age classified 125 neonates at low risk of whom 9% required supplemental oxygen at 28 days, and the regression analysis for 10 days classified 141 neonates at low risk of whom 7% required supplemental oxygen. The 12-hour regression analysis classified 80 neonates at moderate risk of whom 33% required supplemental oxygen at 28 days and the 10-day regression analysis classified 49 neonates at moderate risk of whom 24% required supplemental oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-blind, randomized trial of a calf lung surfactant extract administered at birth to very premature infants for prevention of respiratory distress syndrome.

Organic solvent extraction of surfactant obtained by lavage of calf lungs yields a highly surface-active material. A double blind, randomized clinical trial to determine the effect of this material on respiratory distress syndrome in premature infants was initiated in the Neonatal Intensive Care Unit at the University of Rochester in December 1983. Infants 25 to 29 weeks gestational age were eligible for entry into the trial. At the time of this interim analysis 32 patients had been randomly selected and entered into the trial, 16 surfactant-treated patients and 16 in a control group who received only saline. At birth, intrapulmonary instillation of the calf lung surfactant extract dispersed in saline or saline alone occurred in the delivery room immediately after intubation and prior to ventilation; infants were then ventilated and treated as usual. At 6, 12, 24, 48, and 72 hours after birth, the severity of respiratory distress was categorized as either minimal, intermediate, or severe based on oxygen and mean airway pressure requirements. Differences observed at six hours after birth were of marginal significance, but at 12 and 24 hours the surfactant-treated group had significantly (P less than .01) less severe respiratory distress compared with the control group. Differences between treated and control infants were not statistically significant at 48 and 72 hours after birth. In four surfactant-treated infants the severity of respiratory distress worsened between 24 and 48 hours after birth, suggesting that one dose of surfactant at birth may not be sufficient for some infants.

Early dexamethasone-attempting to prevent chronic lung disease.

BACKGROUND: We previously demonstrated improved survival and early outcomes in a pilot trial of 2 doses of intravenous dexamethasone for infants with surfactant-treated respiratory distress syndrome. (1) A multicenter, randomized, double-blind trial was undertaken to confirm these results. METHODS: Infants <30 weeks' gestation were eligible if they had respiratory distress syndrome, required mechanical ventilation at 12 to 18 hours of age, and had received at least 1 dose of exogenous surfactant. Infants were excluded if sepsis or pneumonia was suspected or if congenital heart disease or chromosomal abnormalities were present. A total of 384 infants were enrolled-189 randomized to dexamethasone (.5mg/kg birth weight at 12-18 hours of age and a second dose 12 hours later) and 195 to an equal volume of saline placebo. RESULTS: No differences were found in the dexamethasone versus placebo groups, respectively, regarding the primary outcomes of survival (79% vs 83%), survival without oxygen at 36 weeks' corrected gestational age (CGA; both 59%), and survival without oxygen at 36 weeks' CGA and without late glucocorticoid therapy (46% vs 44%). No significant differences between the groups in estimates from Kaplan-Meier survival analyses were found for median days on oxygen (50 vs 56 days), ventilation (20 vs 27 days), days to regain birth weight (15.5 vs 14 days), or length of stay (LOS; 88 vs 89 days). Infants given early dexamethasone were less likely to receive later glucocorticoid therapy for bronchopulmonary dysplasia during their hospitalization (27% vs 35%). No clinically significant side effects were noted in the dexamethasone group, although there were transient elevations in blood glucose and blood pressure followed by a return to baseline by study day 10. Among infants who died (40 vs 33), there were no differences in the median days on oxygen, ventilation, nor LOS. However, in survivors (149 vs 162), the following were observed: median days on oxygen 37 versus 45 days, ventilation 14 versus 19 days, and LOS 79 versus 81 days, for the dexamethasone versus placebo groups, respectively. CONCLUSIONS: This dose of early intravenous dexamethasone did not reduce the requirement for oxygen at 36 weeks' CGA and survival was not improved. However, early dexamethasone reduced the use of later prolonged dexamethasone therapy, and among survivors, reduced the median days on oxygen and ventilation. We conclude that this course of early dexamethasone probably represents a near minimum dose for instituting a prophylactic regimen against bronchopulmonary dysplasia.

Respiratory syncytial virus and premature infants born at 32 weeks' gestation or earlier: hospitalization and economic implications of prophylaxis.

OBJECTIVES: To assess the risk of hospitalization associated with respiratory syncytial virus (RSV) and to estimate the economic impact of RSV prophylaxis with either RSV immune globulin (RSV-Ig) or RSV monoclonal antibody (palivizumab) on a cohort of preterm infants born at 32 weeks' gestation or earlier. DESIGN: Historical cohort study. SETTING: A 12-county neonatal network served by the regional center in Rochester, NY. PARTICIPANTS: One thousand twenty-nine infants born at 32 weeks' gestation or earlier followed up until 1 year of corrected age. MAIN OUTCOME MEASURES: Rate of hospitalization with an RSV-associated illness; cost per hospitalization prevented resulting from either form of RSV prophylaxis. RESULTS: The probability of hospitalization with an RSV-associated illness for infants born at 32 weeks' gestation or earlier was estimated at 11.2%. The incidence of RSV hospitalization increased with decreasing gestational age (13.9% vs 4.4% for infants born at < or =26 weeks' gestation vs those born at 30-32 weeks' gestation). Infants requiring respiratory support at 36 weeks of postconceptual age (PCA) or older had a higher hospitalization rate (16.8% vs 6.2%), longer hospital stays, and higher hospital charges than infants requiring respiratory support at less than 36 weeks of PCA. For infants requiring respiratory support at less than 36 weeks of PCA, the incidence of RSV hospitalization still increased with decreasing gestational age (10.2% vs 4.3% for infants < or =26 weeks' gestation vs those 30-32 weeks' gestation). Analysis indicated that both forms of RSV prophylaxis would increase the net cost of care for all groups. Palivizumab was more cost-effective than RSV-Ig for preventing RSV hospitalization among infants who required respiratory support at less than 36 weeks of PCA, especially those born at 26 weeks' gestation or earlier. Overall, RSV-Ig was more cost-effective than palivizumab for infants requiring respiratory support at 36 weeks of PCA or older. CONCLUSIONS: This analysis suggests that available forms of RSV prophylaxis would increase the net cost of care not only for the entire cohort but for each of the subgroups studied. However, the RSV hospitalization rate and the cost-effectiveness of prophylaxis varied markedly by subgroup.

Lipid intolerance in neonates receiving dexamethasone for bronchopulmonary dysplasia.

BACKGROUND: We hypothesized that dexamethasone induces hypertriglyceridemia (triglyceride levels >2.82 mmol/L [250 mg/dL]) and increases free fatty acid (FFA) levels and that steroid-induced hypertriglyceridemia is associated with hyperinsulinemia and elevated FFA levels. OBJECTIVE: To study the effect of dexamethasone sodium phosphate on lipid metabolism in neonates receiving intravenous lipids. DESIGN: A prospective cohort study with patients serving as their own controls. SETTING: Neonatal Intensive Care Unit, Children's Hospital at Strong, Rochester, NY. METHODS: All neonates younger than 29 weeks' gestational age at birth receiving 3 g/kg per day of intravenous lipids who were to start dexamethasone therapy for bronchopulmonary dysplasia were eligible. Exclusion criteria included neonates with active infection, prior hypertriglyceridemia, bleeding manifestations, recent surgery, thyroid medication, and human recombinant insulin intravenous infusion therapy. Ten neonates were studied. Blood was drawn for triglyceride, FFA, and insulin assays before initiating and at 1, 2, 3, and 5 days after starting dexamethasone therapy. On day 3, dexamethasone dosage was decreased as per protocol. Intravenous lipid intake was kept constant. Statistical analysis was done using a paired t test. RESULTS: Six of 10 neonates reached a state of hypertriglyceridemia (95% confidence interval, 26.2%-87.8%). The mean average increase in triglycerides, insulin, and FFA levels in neonates receiving 3 g/kg per day of intravenous lipids after initiation of dexamethasone therapy was 0.75 mmol/L (66.6 mg/dL) (P=.007), 127 pmol/L (P = .006), and 47.5 micromol/L (P = .65), respectively. Six neonates who developed hypertriglyceridemia had significantly elevated mean peak FFA levels (918.3 micromol/L) prior to developing hypertriglyceridemia compared with 4 neonates (mean peak FFA levels, 380.2 micromol/L) who had triglyceride levels lower than 2.82 mmol/L (250 mg/dL) (P = .002). CONCLUSION: We conclude that dexamethasone induces hypertriglyceridemia in the presence of hyperinsulinemia and increased FFA levels.

Congenital ichthyosis with restrictive dermopathy and Gaucher disease: a new syndrome with associated prenatal diagnostic and pathology findings.

BACKGROUND: Since 1988, three nonrelated fatal cases of congenital ichthyosis associated with Gaucher disease have been described in Australia. CASE: We present a case of Gaucher disease with congenital ichthyosis and restrictive dermopathy and describe the associated prenatal sonographic findings and pathology of this new syndrome. CONCLUSION: The unusual association of congenital ichthyosis with lipid storage disease may be suspected prenatally. A high index of suspicion may prove this condition to be more common than previously thought.

Unusual manifestation of a vein of Galen malformation: value of CT angiography.

We describe a neonate with aneurysmal dilatation of the vein of Galen with arteriovenous fistulous sites located at the superior vermian vein. Helical CT angiography was useful for evaluating the anomalous vessels.

The effect of surfactant replacement therapy on conditions associated with respiratory distress syndrome: patent ductus arteriosus, intraventricular hemorrhage, and bronchopulmonary dysplasia.

In assessing the current experience with SRT, both considering its effects on respiratory function and on associated problems, there are strong suggestions that this therapy has the potential to have a major impact on the morbidity and mortality of premature infants. The studies to date have not disclosed any serious adverse reactions, and there are strong trends toward improvements in short-term respiratory function and in long-term outcomes. In particular, SRT does not seem to adversely effect cardiopulmonary circulatory status and worsen the effects of the patent ductus arteriosus. There are no adverse effects on intraventricular hemorrhage and some possibility that it may lead to a reduction in hemorrhages. The use of SRT will likely have its biggest effect on reducing the incidence and severity of bronchopulmonary dysplasia.

Drug therapy for bronchopulmonary dysplasia.

With improved survival of critically ill premature infants, BPD has become an important sequela of neonatal intensive care. A variety of medications are used in the management of BPD. In this article we have attempted to summarize clinical efficacy, pharmacokinetics, and side effects of many of these medications. Longer-term studies on the efficacy of drug therapy are needed and may be facilitated by the development of accurate and reproducible computerized techniques for the measurement of pulmonary mechanics in neonates. Ultimately, new pharmacologic agents or other strategies that will prevent lung injury from hyperoxia and mechanical ventilation or accelerate tissue repair once injury occurs will play a major role in the prevention and treatment of infants with BPD.

Disseminated coagulopathy associated with transtorcular embolization of vein of Galen aneurysm in a neonate.

We describe in this report the development of disseminated intravascular coagulopathy in a neonate after transtorcular embolization of an unusual vein of Galen aneurysm. This rare but potentially fatal complication associated with transtorcular embolization should be considered in decision-making and prognostic evaluation processes, especially in neonates with severe heart failure.

New strategies for the prevention of bronchopulmonary dysplasia.

This article reviews the progress being made into the prevention or arrest of this complex respiratory disease. The key elements in the pathophysiology are reviewed; the current problems in defining, classifying, and predicting the development of this disorder are discussed and potentially useful interventions also are introduced.

Cellular and molecular responses to lung injury in relation to induction of tissue repair and fibrosis.

Those factors that determine whether tissue injury is followed by regeneration and repair or irreversible destruction and fibrosis are only now being elucidated. This article examines the lung's response to injury, the prominent role of polypeptide growth factors and cytokines in directing tissue responses, and the effects of injury on cell-specific expression of a number of genes.

Acute intrapartum twin-twin transfusion. A case report.

A rare case of acute intrapartum twin-twin transfusion occurred. The well-recognized criteria of long-standing chronic twin-twin transfusion were absent. Although a cesarean section was performed for obstetric reasons, the hyperperfused twin, A, died intrapartum. Twin B, the hypoperfused twin, although liveborn, died neonatally of renal failure attributed to renal cortical necrosis as a sequel to hypotension.

Abnormal heart rate characteristics are associated with abnormal neuroimaging and outcomes in extremely low birth weight infants.

OBJECTIVE: Brain injury in preterm infants may lead to an inflammatory response and central nervous system dysfunction reflected by abnormal heart rate characteristics (HRC). We hypothesized that a continuously monitored HRC index reflecting reduced HR variability and decelerations correlates with abnormal neuroimaging and outcomes in extremely low birth weight infants (ELBW). STUDY DESIGN: We analyzed the average HRC index within 28 days after birth (aHRC28) and head ultrasound (HUS) in 384 ELBW infants. In 50 infants with brain magnetic resonance imaging (MRI) and 70 infants with Bayley neurodevelopmental testing at 1 year of age, we analyzed the relationship between aHRC28, MRI abnormalities and low Bayley scores. RESULT: aHRC28 was higher in infants with severe HUS abnormalities (2.65±1.27 for Grade III-IV intraventricular hemorrhage (IVH) or cystic periventricular leukomalacia (cPVL) versus 1.72±0.95 for normal or Grade I-II IVH, P<0.001). Higher aHRC28 was also associated with white matter damage on MRI and death or Bayley motor or mental developmental index <70. Associations persisted after adjusting for gestational age, birth weight and septicemia. For every one point increase in aHRC28, the odds ratio of death or Bayley score <70 was 2.45 (95% CI 1.46, 4.05, P<0.001). CONCLUSION: A continuously monitored HRC index provides an objective, noninvasive measure associated with abnormal brain imaging and adverse neurologic outcomes in ELBW infants.

Differential cytokine mRNA expression by neonatal pulmonary cells.

The purpose of this study was to describe cytokine profiles of human neonatal pulmonary cells isolated by tracheal aspiration (TA) and by deep pulmonary lavage (DPL). We hypothesized that mRNA phenotyping, using the technique of reverse transcriptase polymerase chain reaction (RT-PCR), would reveal differences in cytokine expression patterns between cells from proximal and distal airway compartments. We reasoned that cells derived by DPL may reflect pathogenic pathways indicative for the development of bronchopulmonary dysplasia in the premature infant. Here we have described the detection of mRNA for IL-1 alpha, IL-1 beta, IL-6, IL-8, and tumor necrosis factor-alpha. Fourteen paired TA and DPL samples from six premature infants were collected at 1, 7, or 28 d of age. Two of 14 samples were negative for beta-actin (a ubiquitous mRNA) by RT-PCR and were excluded from further analysis. Each of the remaining 12 samples expressed IL-8. Furthermore, each cytokine could be expressed by TA or DPL cells. Cytokine mRNA phenotype profiles were found to differ between TA and DPL cells in four of five paired samples. Our results show that cells retrieved from these two pulmonary compartments are sources for these cytokines and suggest that RT-PCR of TA/DPL cells can be used to test hypothetical predictive markers for the development of bronchopulmonary dysplasia.

Cell-specific expression of fibronectin in adult and developing rabbit lung.

Fibronectin (FN), a glycoprotein component of the extracellular matrix, plays a role in tissue morphogenesis and tissue-specific differentiation through its effects on cell adhesion, cell shape, and cytoskeletal organization. Immunohistochemistry has been used to show that during lung development FN deposition changes, yet the cell-specific sites of pulmonary FN synthesis have not been determined. Because cellular FN synthesis is reflected by FN mRNA abundance, we performed in situ hybridizations to identify pulmonary tissue with the capacity to synthesize FN. Both in situ mRNA hybridization and immunohistochemical staining were performed on tissue sections from lungs of adults and late gestation fetal and neonatal rabbits. In adults, FN transcripts and immunostaining were clearly seen in endothelial cells, smooth muscle cells, and chondrocytes. During lung development, FN transcripts were virtually ubiquitous except in airway epithelium. There was a gradual decrease in FN mRNA abundance with advancing fetal age, but low levels of FN mRNA persisted in neonatal and adult lungs. In contrast, parenchymal immunostaining increased throughout fetal development and remained elevated in the newborn. FN immunostaining was lower in adult lung. In all tissues examined, airway epithelial cells contained no FN transcripts above background. However, immunostaining was detected in airway basement membrane zones and on luminal surfaces of some epithelial cells. The lack of FN transcripts in airway epithelial cells suggests that FN synthesis does not normally occur in this cell type and that its associated FN immunostaining is from another source. The colocalization of FN mRNA and protein in pulmonary endothelial cells, smooth muscle cells, and chondrocytes in adults strongly suggests that these cells are sites of FN synthesis.