A quality improvement strategy to reduce unintended extubation in the very low birth weight infant: A case report.

BACKGROUND: Unintended extubations remain a common complication across neonatal intensive care units, with very low birthweight infants being the most vulnerable of them all. Ongoing efforts across different institutions exist with the goal of reducing the rate of unintended extubations to keep a median rate of <2 events per 100 ventilator days as defined by the Vermont Oxford Network. Our objective was to reduce unintended extubations in the very low birthweight infant in a large delivery hospital to ≤2/100 ventilator days. METHODS: A collaborative group was formed between two academic health institutions targeting training and implementation of the Children's National unintended extubation system, focusing on endotracheal tube securement methods and surveillance protocols. RESULTS: The unintended extubation rate decreased from 3.23 to 0.64 per 100 ventilator days. Changes were implemented from 2018-2020 with a sustained reduction in the unintended extubation rate of 1.54 per 100 ventilator days. Most events occurred between 12 : 00 pm -4 : 00 pm and the commonest cause was spontaneous (25%) followed by dislodgment during repositioning (19%). CONCLUSION: Very low birth weight infants present a challenge to endotracheal tube maintenance due to their developmental and anatomical changes during their neonatal intensive care unit stay. Successful reduction of unintended extubations in the very low birthweight infant can be achieved by adaptation of successful protocols for older infants.

Rationale for the administration of acellular pertussis vaccine to parents of infants in the neonatal intensive care unit.

Pertussis infections in the United States are increasing as a consequence of waning immunity and increased surveillance. Those most at-risk of mortality include infants less than 6 months of age and premature infants. The 2006 immunization schedule emphasizes an adolescent pertussis booster at 12 years of age. However, of concern is the current generation of parents and grandparents who will still be un-immunized and therefore, available vectors of pertussis to vulnerable neonates. Given the proximity of parents to medical care in the Neonatal Intensive Care Unit (NICU), and the potential for severe disease in their children, NICU personnel should consider administration of acellular pertussis vaccine to parents of hospitalized infants.

Inhaled nitric oxide-induced rebound pulmonary hypertension: role for endothelin-1.

Clinically significant increases in pulmonary vascular resistance have been noted on acute withdrawal of inhaled nitric oxide (NO). Endothelin (ET)-1 is a vasoactive peptide produced by the vascular endothelium that may participate in the pathophysiology of pulmonary hypertension. The objectives of this study were to determine the effects of inhaled NO on endogenous ET-1 production in vivo in the intact lamb and to determine the potential role of ET-1 in the rebound pulmonary hypertension associated with the withdrawal of inhaled NO. Seven 1-mo-old vehicle-treated control lambs and six PD-156707 (an ET(A) receptor antagonist)-treated lambs were mechanically ventilated. Inhaled NO (40 parts per million) was administered for 24 h and then acutely withdrawn. After 24 h of inhaled NO, plasma ET-1 levels increased by 119.5 +/- 42.2% (P < 0.05). Western blot analysis revealed that protein levels of preproET-1, endothelin-converting enzyme-1alpha, and ET(A) and ET(B) receptors were unchanged. On acute withdrawal of NO, pulmonary vascular resistance (PVR) increased by 77.8% (P < 0.05) in control lambs but was unchanged (-5.5%) in PD-156707-treated lambs. Inhaled NO increased plasma ET-1 concentrations but not gene expression in the intact lamb, and ET(A) receptor blockade prevented the increase in PVR after NO withdrawal. These data suggest a role for ET-1 in the rebound pulmonary hypertension noted on acute withdrawal of inhaled NO.

Human endometrial endothelial cells: isolation, characterization, and inflammatory-mediated expression of tissue factor and type 1 plasminogen activator inhibitor.

Binding of Ulex europaeus lectin to microvessels was used to isolate endothelial cells from cycling human endometrium. Cultured human endometrial endothelial cells (HEECs) exhibited endothelial cell-specific characteristics such as tube formation on a basement membrane matrix and sequestration of acetylated low-density lipoprotein. Markers for potentially contaminating epithelial, stromal, smooth muscle, and bone marrow-derived cells were not detected in the HEEC cultures. Basal and proinflammatory-stimulated immunostaining profiles for endothelial cell-specific adhesion markers, as exemplified by Von Willebrand's factor and E-selectin, were similar for cultured HEECs and human umbilical venous cord endothelial cells (HUVECs). However, HUVECs expressed several extracellular matrix proteins that were absent from cultured HEECs. In the latter, the protein kinase C agonist phorbol myristate acetate transiently enhanced tissue factor (TF) mRNA levels and elicited a more prolonged elevation in TF protein levels, but did not affect plasminogen activator inhibitor-1 (PAI-1) mRNA and protein levels. Inappropriate expression of TF, which initiates hemostasis by generating thrombin, and of PAI-1, which regulates hemostasis by acting as the primary inhibitor of fibrinolysis, can each lead to thrombosis. The differential regulation of TF and PAI-1 expression revealed in the current study emphasizes the importance of using HEECs to evaluate mechanisms regulating the hemostatic/thrombotic balance in human endometrium.

Retinopathy of prematurity: lack of association with prenatal care.

OBJECTIVES: The overall goal of this study was to prospectively assess risk factors for retinopathy of prematurity (ROP) in infants of birth weight <1250 g in an urban population at Bellevue Hospital Center, New York, New York. The hypothesis tested was that lack of prenatal care increases the incidence of ROP. METHODS: A consecutive sample of patients admitted to Bellevue Hospital Center's neonatal intensive care unit/special care nursery who weighed <1250 g at birth and survived until their ophthalmology screening examinations were included in the study. The main outcome measures were presence or absence of ROP and prenatal care. Additional relevant clinical information was collected on the patients. RESULTS: Ninety infants were evaluated. Sixty-one (68%) had ROP; 29 (32%) had no ROP. No differences in incidence or severity of ROP were detected with regard to prenatal care when the 2 groups were compared. In this population <1250 g, there were no differences in birth weight or gestational age with respect to prenatal care or lack of prenatal care. CONCLUSIONS: Lack of prenatal care was not associated with an increased risk for ROP in infants with birth weight <1250 g in this urban population.

Endothelin receptor blockade prevents the rise in pulmonary vascular resistance after cardiopulmonary bypass in lambs with increased pulmonary blood flow.

BACKGROUND: Children with increased pulmonary blood flow may experience morbidity as the result of increased pulmonary vascular resistance after operations in which cardiopulmonary bypass is used. Plasma levels of endothelin-1, a potent vasoactive substance implicated in pulmonary hypertension, are increased after cardiopulmonary bypass. OBJECTIVES: In a lamb model of increased pulmonary blood flow after in utero placement of an aortopulmonary shunt, we characterized the changes in pulmonary vascular resistance induced by hypothermic cardiopulmonary bypass and investigated the role of endothelin-1 and endothelin-A receptor activation in postbypass pulmonary hypertension. METHODS: In eleven 1-month-old lambs, the shunt was closed, and vascular pressures and blood flows were monitored. An infusion of a selective endothelin-A receptor blocker (PD 156707; 1.0 mg/kg/h) or drug vehicle (saline solution) was then begun 30 minutes before cardiopulmonary bypass and continued for 4 hours after bypass. The hemodynamic variables were monitored, and plasma endothelin-1 concentrations were determined before, during, and for 6 hours after cardiopulmonary bypass. RESULTS: After 90 minutes of hypothermic cardiopulmonary bypass, both pulmonary arterial pressure and pulmonary vascular resistance increased significantly in saline-treated lambs during the 6-hour study period (P <.05). In lambs pretreated with PD 156707, pulmonary arterial pressure and pulmonary vascular resistance decreased (P <. 05). After bypass, plasma endothelin-1 concentrations increased in all lambs; there was a positive correlation between postbypass pulmonary vascular resistance and plasma endothelin-1 concentrations (P <.05). CONCLUSIONS: This study suggests that endothelin-A receptor-induced pulmonary vasoconstriction mediates, in part, the rise in pulmonary vascular resistance after cardiopulmonary bypass. Endothelin-A receptor antagonists may decrease morbidity in children at risk for postbypass pulmonary hypertension. This potential therapy warrants further investigation.

Role of the endothelium in placental dysfunction after fetal cardiac bypass.

BACKGROUND: Fetal cardiac bypass causes placental dysfunction, characterized by increased placental vascular resistance, decreased placental blood flow, hypoxia, and acidosis. Vasoactive factors produced by the vascular endothelium, such as nitric oxide and endothelin 1, are important regulators of placental vascular tone and may contribute to this placental dysfunction. METHODS: To investigate the role of the vascular endothelium in placental dysfunction related to fetal cardiac bypass, we studied 3 groups of fetal sheep. In the first group (n = 7) we determined placental hemodynamic responses before and after bypass to an endothelium-dependent vasodilator (acetylcholine), an endothelium-independent vasodilator (nitroprusside), and endothelin 1. In the second group (n = 8) a nonspecific endothelin receptor blocker (PD 145065) was administered and placental hemodynamic values were measured before and after bypass. In the third group (n = 5) endothelin 1 levels were measured before and after bypass. RESULTS: Before fetal cardiac bypass exogenous endothelin 1 decreased placental blood flow by 9% and increased placental resistance by 9%. After bypass endothelin 1 decreased placental flow by 47% and increased resistance by 106%. There was also a significant attenuation of the placental vascular relaxation response to acetylcholine after bypass, whereas the response to nitroprusside was not significantly altered. In fetuses that received the PD 145065, placental vascular resistance increased significantly less than in control fetuses (28% versus 62%). Similarly, placental blood flow decreased significantly more (from 6. 3 +/- 3.1 to 28.3 +/- 10.4 pg/mL; P =.01) in control fetuses than in fetuses receiving PD 145065 (33% versus 20%). Umbilical venous endothelin 1 levels increased significantly in fetuses exposed to fetal bypass but did not change in control fetuses. CONCLUSIONS: The basal endothelial regulatory mechanisms of placental vascular tone were deranged after fetal cardiac bypass. Endothelin receptor blockade, which substantially reduced postbypass placental dysfunction, and other interventions aimed at preserving endothelial function may be effective means of optimizing fetal outcome after cardiac bypass.

Hyperoxia stimulates endothelin-1 secretion from endothelial cells; modulation by captopril and nifedipine.

PURPOSE: Retinopathy of prematurity (ROP) is a vasoproliferative condition that can result in severe visual impairment and blindness in preterm babies. Two conditions seen very early in radioimmunoassay (ROP) are vasoconstriction and vaso-obliteration. A potent vasoconstrictor secreted by endothelial cells is endothelin-1 (ET-1). Premature birth results in a relative systemic hyperoxia, compared to the in utero oxygen milieu. We tested the hypothesis that hyperoxia increases ET-1 expression as a possible mechanism for vasoconstriction in the retinal vasculature. METHODS: Bovine retinal endothelial cells and adrenal capillary endothelial cells were isolated and maintained in culture. Cells were exposed to control or hyperoxic culture conditions for 24 h, with and without addition of captopril and nifedipine. Media was collected and assayed for ET-1 by ROP. In addition, cell counts and secreted LDH assays were performed. RESULTS: Conditioned media from cultured bovine retinal and adrenal endothelial cells exposed to hyperoxic culture conditions for 24 h were found to have higher levels of ET-1 than conditioned media from normoxic control cells. Captopril (10(-6) M and 10(-4) M) and nifedipine (10(-6) M and 10(-4) M) inhibited ET-1 release from hyperoxia-exposed endothelial cells. Under normoxic conditions, ET-1 release was inhibited by 10(-4) M captopril or 10(-4) M nifedipine. CONCLUSIONS: These results demonstrate that (1) hyperoxia stimulates in vitro ET-1 secretion in bovine retinal and adrenal capillary endothelial cells, and (2) captopril and nifedipine downregulate ET-1 secretion under normoxic and hyperoxic culture conditions, in a dose-dependent fashion. We speculate that ET-1 may be involved in retinal vessel vasoconstriction seen early in the development of ROP. Further, ACE inhibitors and calcium-channel blocking agents, such as captopril and nifedipine, may provide an avenue for blocking vasoconstriction in ROP.

Antenatal dexamethasone and decreased severity of retinopathy of prematurity.

OBJECTIVE: To assess risk factors associated with the development of retinopathy of prematurity (ROP) in an urban population. DESIGN: Observational cohort study. SETTING: Bellevue Hospital Center, a regional perinatal referral center in New York City. PATIENTS: Surviving inborn infants with birth weight less than 1250 g undergoing an ophthalmologic screening examination. MAIN OUTCOME MEASURES: Screening examination results for ROP were obtained. Additional data included birth weight, gestational age, maternal factors, and common neonatal diagnoses and exposures. RESULTS: Sixty-three infants were included in the analysis. Mean +/- SD birth weight was 981+/-179 g and mean gestational age was 27.8+/-2.4 weeks. Infants whose mothers received antenatal dexamethasone developed significantly less ROP that was stage 2 or higher than infants without a history of antenatal dexamethasone exposure--8.7% (2/23) vs 35% (14/40), respectively (P=.04). Birth weight, gestational age, respiratory distress syndrome, bronchopulmonary dysplasia, and patent ductus arteriosus were also significantly associated with the development of ROP that was stage 2 or higher. After controlling for these confounders by multiple logistic regression analysis, antenatal dexamethasone administration was associated with a significantly decreased risk of development of ROP stage 2 or higher (adjusted odds ratio [OR], 0.14; 95% confidence interval [CI], 0.02-0.93). The association was stronger when the analysis was restricted to the 36 infants who were 24 to 28 weeks of gestational age (adjusted OR, 0.02; 95% CI, 0.00-0.76). CONCLUSION: Antenatal dexamethasone administration appears to be associated with a decreased incidence of development of ROP of stage 2 or higher in this urban population.

Rapid estimation of insertional length of endotracheal intubation in newborn infants.

OBJECTIVE: To create a simple and accurate method of predicting the correct insertional length of endotracheal intubation during resuscitation of neonates. STUDY DESIGN: Phase I of the study enrolled infants that required either orotracheal or nasotracheal intubations. The endotracheal tube position was confirmed by auscultation and radiographic images. Three regression equations were then created using nasal-tragus length, sternal length, and birth weight on insertional length. In phase II of the study, the modified regression equations of nasotracheal and sternal length were used to predict endotracheal tube insertional length in 50 infants (40 orotracheal and 10 nasotracheal). RESULTS: Nasal-tragus length and sternal length are good parameters to estimate insertional length for endotracheal intubation (p < 0.005 for both the parameters). The modified prediction equation for insertional length of the endotracheal tube for the orotracheal route is NTL or STL + 1. For the nasotracheal route the equation is NTL or STL + 2. CONCLUSION: During resuscitation of the neonate when vital parameters are difficult to obtain, the insertional length of endotracheal intubation can be quickly and accurately predicted by nasal-tragus length or sternal length.

Post-cardiopulmonary bypass pulmonary hypertension in lambs with increased pulmonary blood flow. A role for endothelin 1.

BACKGROUND: After cardiopulmonary bypass (CPB), pulmonary hypertension and its associated increased vascular reactivity are a major source of morbidity, particularly for children with increased pulmonary blood flow. Although post-CPB pulmonary hypertension is well described, its mechanisms remain incompletely understood. Plasma levels of endothelin 1. a potent vasoactive substance implicated in pulmonary hypertension, are increased after CPB. The purpose of the present study was threefold: to characterize the changes in pulmonary vascular resistance and vascular reactivity induced by hypothermic CPB; to investigate the effects of preexisting increased pulmonary blood flow on these changes; and to better define the role of endothelin 1 in the pathogenesis of post-CPB pulmonary hypertension. METHODS AND RESULTS: Vascular pressures and blood flows were monitored in 14 1-month-old lambs with increased pulmonary blood flow (after in utero placement of an aortopulmonary shunt) and 6 age-matched control lambs. During the 2-hour study period after 105.3 +/- 20.6 minutes of hypothermic CPB the increase in pulmonary vascular resistance was significantly augmented in lambs with increased pulmonary blood flow compared with control lambs (P < .05). Pretreatment with PD 145065 (a nonselective endothelin receptor blocker; 50 micrograms.kg-1.min-1) completely blocked this increase in pulmonary vascular resistance and blocked the increase in pulmonary vascular resistance in response to acute alveolar hypoxia after CPB (96.3 +/- 88.5% versus -9.7 +/- 16.4%; P < .05). Plasma endothelin 1 levels increased after CPB in all lambs. CONCLUSIONS: Preexisting increased pulmonary blood flow alters the response of the pulmonary circulation to hypothermic CPB; the increase in pulmonary vascular resistance induced by CPB is augmented in lambs with increased pulmonary blood flow. Pretreatment with endothelin 1 receptor blockers eliminated the increase in pulmonary vascular resistance and the pulmonary vasoconstricting response to alveolar hypoxia, suggesting a role for endothelin 1 in post-CPB pulmonary hypertension. Endothelin 1 receptor blockers may decrease morbidity in children at risk for pulmonary hypertension after surgical repair with CPB and warrants further study.

Cocaine-stimulated endothelin-1 release is decreased by angiotensin-converting enzyme inhibitors in cultured endothelial cells.

OBJECTIVE: The primary aim was to determine the action of pathophysiologically relevant cocaine concentrations (10(-7)-10(-5) M) on endothelin-1 (ET-1) release from cultured endothelial cells under various cellular conditions. Further aims were to evaluate the effect of angiotensin-converting enzyme inhibitors on cocaine-treated endothelial cells, to assess their potential for inhibition of ET-1-stimulated release. METHODS: Endothelin-1 release into the media was evaluated by radioimmunoassay under basal conditions and after 24 h treatment of endothelial cells with cocaine hydrochloride (HCl), or cocaine HCl and ACE inhibitors, captopril and lisinopril. The effect of serum and plasma under these conditions was also investigated. RESULTS: Cocaine HCl stimulated ET-1 release in a dose response fashion that was independent of plasma or serum factors. Furthermore, cocaine-stimulated ET-1 release was inhibited by administration of angiotensin-converting enzyme inhibitors captopril and lisinopril. CONCLUSIONS: These findings suggest that cocaine can directly stimulate endothelial cells to release ET-1 and that the observed increase is independent of serum or plasma factors. Furthermore, cocaine-stimulated endothelin-1 release appears to be mediated at least in part by the angiotensin system. These observations provide a framework for understanding the cellular mechanisms involved in cocaine-induced vasoconstriction.

Endothelin-1 vasoactive responses in lambs with pulmonary hypertension and increased pulmonary blood flow.

Increased concentrations of endothelin-1 (ET-1) are found in children with congenital heart diseases that produce increased pulmonary blood flow and pulmonary hypertension, but the role of ET-1 in the pathophysiology of pulmonary hypertension is unclear. Therefore, we investigated ET-1-induced vasoactive responses and ET-1 concentrations in an animal model of pulmonary hypertension and increased pulmonary blood flow. Vascular shunts were placed between the ascending aorta and main pulmonary artery in seven late-gestation fetal sheep. Four weeks after spontaneous delivery, ET-1 increased pulmonary vascular resistance by 29.7 +/- 34.4% (P < 0.05), the ETb-receptor agonist [Ala1,3,11,15]ET-1 (4AlaET-1) had no effect, and the ETa-receptor antagonist cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp) (BQ-123) decreased pulmonary vascular resistance by -16.0 +/- 5.6% (P < 0.05). In contrast, in six control lambs with a similar degree of pulmonary hypertension induced by U-46619, ET-1 and 4AlaET-1 decreased pulmonary vascular resistance by 24.8 +/- 17.6, and 20.0 +/- 13.8%, respectively (P < 0.05). In addition, systemic arterial concentrations of immunoreactive ET-1 were elevated in lambs with pulmonary hypertension (29.2 +/- 9.6 vs. 15.2 +/- 10.7 pg/ml, P < 0.05). Pulmonary hypertension and increased pulmonary blood flow alters the response of ET-1 from pulmonary vasodilation to vasoconstriction. These altered responses suggest a role for ET-1 and its receptors in the pathogenesis of pulmonary hypertension secondary to increased pulmonary blood flow.

Profile and stability of sensorineural hearing loss in persistent pulmonary hypertension of the newborn.

The purpose of this study was to examine the incidence, profile, and stability of sensorineural hearing loss (SNHL) in infants diagnosed with persistent pulmonary hypertension of the newborn (PPHN). Over a five-year period, 19 of 51 infants (37%) with PPHN were diagnosed with SNHL: 16 with bilateral and 3 with unilateral impairment. This incidence of SNHL is approximately 25 times greater than observed in graduates of our intensive care nursery. The profile of SNHL in the group of 19 children was typically downward sloping. However, there was considerable variation with respect to degree of loss. In addition, progressive SNHL was identified in 5 children whose hearing worsened an average of 55 dB at 2 to 4 kHz. On retrospective analysis, the perinatal variables associated with PPHN were comparable between hearing-impaired and normal-hearing infants. In contrast, the two groups were significantly different when treatment variables, such as the duration of mechanical ventilation or amikacin, were compared. Children with SNHL were treated for longer durations as compared to normal-hearing infants. Children with SNHL were subdivided into two groups, mild and severe, based on degree of loss and treatment variables, and compared again to the normal-hearing group. Two findings emerged from this analysis. First, the duration of hyperventilation was now the only variable significantly different between children with mild SNHL and children with normal hearing. Second, comparison of the mild with the severe SNHL groups showed that the duration of hyperventilation was similar. The pathophysiology and underlying mechanisms resulting in SNHL in PPHN survivors are discussed.

The role of the lumbar puncture in the admission sepsis evaluation of the premature infant.

Premature infants with respiratory distress commonly receive evaluation for sepsis, including a lumbar puncture, within a short time after admission to a neonatal intensive care unit. We questioned the use of the lumbar puncture during the early sepsis evaluation, and since 1979, have omitted this procedure as part of the initial evaluation for sepsis (within 6 hours of birth) of premature infants. We monitored this policy to detect any change in the incidence of meningitis, and now report results accumulated over a 7-year period. From 1979 to 1986, 1390 inborn premature infants of 34 weeks' gestation or less were evaluated for early sepsis within 6 hours of birth. Thirty-two infants (2.3%) were diagnosed with sepsis. Fifteen of these infants died in the first 24 hours of life. Meningitis was not demonstrated by autopsy evaluation. The surviving 17 infants diagnosed with sepsis did not have meningitis. One hundred twenty-three infants whose initial blood cultures were negative developed infection later in their hospital course. Eleven of these 123 infants had infections with perinatally acquired organisms; two had group B streptococcus (GBS) meningitis. Their cases were not compatible with missed meningitis. The remaining 112 infants developed nosocomial infections of which 38.3% developed meningitis without associated bacteremia. These results suggest that the omission of the lumbar puncture in the early sepsis evaluation of the premature infant did not result in any missed meningitis and spared many infants the procedure shortly after birth. The lumbar puncture, however, continues to be vital in the assessment of late infections of the neonate.

The effects of indomethacin on renal function and intracranial hemorrhage in infants with patent ductus arteriosus.

The effects of indomethacin on patent ductus arteriosus (PDA) were retrospectively studied by evaluating 1,600 consecutive infants less than 36 weeks gestation from 1983 to 1986. Two hundred thirteen infants were diagnosed with a PDA, and 102 infants received indomethacin. Indomethacin was associated with successful PDA closure in 81 infants (79%), with 59 infants (58%) closing after a single dose. No cases of renal failure were observed after indomethacin. Nine infants were treated despite a creatinine (Cr) value greater than or equal to 1.5 mg/dl. Cr improved in all these infants after therapy. Blood urea nitrogen values were greater than or equal to 30 mg/dl in 22 infants at the time of treatment; 18 infants (82%) improved. An intracranial hemorrhage (ICH) was detected in 23 infants (22%) by cranial ultrasound prior to indomethacin; there was no progression after treatment. Data suggest that indomethacin is highly associated with closure of a PDA, and therapy did not result in prolonged renal dysfunction or worsening ICH.

Membrane phospholipid methylation is associated with surfactant secretion in rabbit type II alveolar epithelial cells.

We investigated the involvement of membrane phospholipid methylation in receptor-mediated secretion of surfactant in adult rabbit type II alveolar epithelial cells (type II pneumocyte). Phospholipid methyltransferase activity was found in type II pneumocyte microsomes. Cell cultures of adult rabbit type II pneumocytes were then used to assay methyltransferase activity in the presence of the beta-adrenergic agonist, terbutaline, and the methyltransferase inhibitor, 3-deazaadenosine. Terbutaline predictably stimulated adenylate cyclase activity and surfactant secretion. It was also found to stimulate incorporation of methyl groups into phosphatidylcholine and to increase beta-adrenergic receptor availability as assayed by binding of dihydroalprenolol (DHA). Surfactant secretion, as well as adenylate cyclase activity, were stimulated by terbutaline and were inhibited by 3-deazaadenosine. 3-Deazaadenosine did not inhibit DHA binding. These results suggest that phospholipid methylation plays a role in stimulus-secretion coupling in adult rabbit type II pneumocytes.

Surfactant replacement therapy at birth: final analysis of a clinical trial and comparisons with similar trials.

A randomized trial of surfactant replacement therapy at birth was conducted at the University of Rochester between June 1983 and November 1985. Thirty-four premature infants, 25 to 29 weeks' gestational age, received a preventilatory dose of a calf lung surfactant extract in saline prepared at the University of Rochester. A control group of 31 infants received a preventilatory dose of saline alone. The major finding of this trial is that a single preventilatory dose of calf lung surfactant extract reduces the severity of the respiratory distress syndrome during the first 24 hours of life. The beneficial effects, however, are not sustained in many infants and diminish after 24 hours of life. The survival rate was 71% in both the control and surfactant-treated groups. There was a lower incidence of pneumothorax in the surfactant-treated group. There were no differences in the incidence of bronchopulmonary dysplasia, patent ductus arteriosus, and intraventricular hemorrhage. No adverse effects of surfactant replacement therapy were identified. Results of this study suggest that multiple postventilatory doses of surfactant will be required for optimal therapy.

Spontaneous focal gastrointestinal perforation in very low birth weight infants.

Spontaneous, focal gastrointestinal perforation occurred in six very low birth weight infants. The first recognized clinical sign of perforation in five of the six infants was striking blue-black discoloration of the abdominal wall. In all cases the clinical and radiographic presentations, as well as the histologic findings, were distinct from those associated with necrotizing enterocolitis. All 4 infants who underwent exploratory laparotomy and repair had excellent surgical outcomes.

Hearing loss in infants with persistent fetal circulation.

Infants with the diagnosis of persistent fetal circulation were evaluated for hearing loss. From Jan 1, 1982, to Jan 1, 1984, 28 infants with this diagnosis were retrospectively identified, and 18 were evaluated by formal audiologic testing. Additionally, 22 infants were prospectively followed by serial auditory evaluation from Jan 1, 1984, to Jan 1, 1986. Of the 40 infants evaluated, 21 were identified as having hearing impairment (52.5%), 14 of whom required hearing aids. For 82% of those retrospectively identified hearing-impaired infants who required hearing aids, parental concern was expressed for their lack of hearing acuity. This factor could have aided in the earlier recognition of these infants' impairment. Among those infants followed prospectively, formal audiologic testing, in some cases serially, was needed to diagnose a progressive hearing loss that was expressed at 6 to 8 months after discharge from the neonatal intensive care unit. Perinatal factors associated with the development and management of persistent fetal circulation were identified and compared in infants with confirmed hearing loss and those with normal hearing. Variables related to those infants with hearing loss were as follows: degree of alkalosis, duration of ventilation, and possibly use of furosemide. We concluded from these results that infants with persistent fetal circulation have an extremely high incidence of sensorineural hearing loss and suggest serial formal audiologic evaluations to aid in detection of hearing-impaired infants.