High expression of leptin by human bone marrow adipocytes in primary culture

Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10-80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was significantly reduced in either preterm neonates (51+/-21 vs 23+/-17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45+/-20 vs 20+/-17, P < .0001), 'idiopathic' PPHN (39+/-14 vs 14+/-9, P < .0001), and sepsis (55+/-25 vs 26+/-20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less significant and sustained (OI=41+/-16 vs 28+/-18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI=58+/-25 vs 46+/-32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age > or =34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants.     

Early response to inhaled nitric oxide and its relationship to outcome in children with severe hypoxemic respiratory failure

OBJECTIVE: To examine whether the early response to inhaled nitric oxide (iNO) is a measure of reversibility of lung injury and patient outcome in children with acute hypoxemic respiratory failure (AHRF). DESIGN: Retrospective review study. SETTING: Pediatric ICUs. PATIENTS: Thirty infants and children, aged 1 month to 13 years (median, 7 months) with severe AHRF (mean alveolar arterial oxygen gradient of 568+/-9.3 mm Hg, PaO2/fraction of inspired oxygen of 56+/-2.3, oxygenation index [OI] of 41+/-3.8, and acute lung injury score of 2.8+/-0.1). Eighteen patients had ARDS. INTERVENTIONS: The magnitude of the early response to iNO was quantified as the percentage change in OI occurring within 60 min of initiating 20 ppm iNO therapy. This response was compared to patient outcome data. MEASUREMENTS AND RESULTS: There was a significant association between early response to iNO and patient outcome (Kendall tau B r=0.43, p < 0.02). All six patients who showed < 15% improvement in OI died; 4 of the 11 patients (36%) who had a 15 to 30% improvement in OI survived, while 8 of 13 (61%) who had a > 30% improvement in OI survived. Overall, 12 patients (40%) survived, 9 with ongoing conventional treatment including iNO, and 3 with extracorporeal support. CONCLUSIONS: In AHRF in children, greater early response to iNO appears to be associated with improved outcome. This may reflect reversibility of pulmonary pathophysiologic condition and serve as a bedside marker of disease stage.     

Congenital diaphragmatic hernia: experience with preoperative stabilization and delayed surgery without ECMO and inhaled nitric oxide

Despite many advances in the management of congenital diaphragmatic hernia (CDH), the condition carries a mortality rate of 40-50% usually consequent to pulmonary hypoplasia and/or persistent pulmonary hypertension. Several centers have reported improved survival with preoperative stabilization and delayed surgery, which is now an accepted method of management. This is a retrospective analysis of all neonates with respiratory distress at birth due to CDH who were treated at our institution with neither extracorporeal membrane oxygenation nor nitric oxide being used. The medical records of all neonates with CDH and respiratory distress at birth who were treated at this institution from August 1, 1992 through March 1, 1997 were reviewed. There were 21 patients, 11 male and 10 female. There were 17 full-term and 4 premature infants; two premature infants at 30 and 34 weeks' gestation were not resuscitated because of severe associated congenital anomalies. Surgery was performed from 5 to 144 hr (mean 45 hr) in 18 infants. One infant died during preoperative stabilization from severe pulmonary hypoplasia and pulmonary hypertension and one infant died postoperatively from the same conditions. Seventeen of 19 infants (89.5%) survived and were discharged home. Three infants (17.6%) who failed to thrive due to severe gastroesophageal reflux (GER) required fundoplication. Eleven infants (64.7%) who had sepsis proven by blood culture responded satisfactorily to appropriate antibiotics. Preoperative stabilization and delayed surgery has been a satisfactory form of management in our series. The significant complication was sepsis, which must be addressed.     

Plasma immunoreactive endothelin-1 concentrations in infants with persistent pulmonary hypertension of the newborn

Plasma concentrations of endothelin-1 (ET-1) have been reported to be elevated in children and adults with pulmonary hypertension. We hypothesized that infants with persistent pulmonary hypertension of the newborn (PPHN) have elevated plasma concentrations of ET-1. Plasma concentrations of immunoreactive-endothelin-1 (ir-ET-1) were measured using a radioimmunoassay in 20 infants with PPHN and 20 normal term infants. Mean birthweight and gestational age of the infants were comparable in the two groups. The mean plasma ir-ET-1 concentrations were significantly elevated in neonates with PPHN compared to those of normal term infants (2.04 +/- 0.30 versus 1.04 +/- 0.29 pg/mL, p = 0.02). A linear regression analysis demonstrated a significant relationship between ir-ET-1 concentrations and alveolar-arterial oxygen gradient (r = 0.49, p = 0.02) and mean airway pressure (r = 0.49, p = 0.02). There was also a significant correlation between ir-ET-1 concentrations and duration of extracorporeal membrane oxygenation among infants with PPHN (r = 0.44, p = 0.05). We conclude that plasma ir-ET-1 concentrations are elevated in infants with PPHN. The presence of elevated ir-ET-1 concentrations and their positive correlation with disease severity suggests that ET-1 may serve as a marker of the disease severity in these infants. However, further studies are needed to elucidate the role of ET-1 in the pathophysiology of PPHN.     

Audit of early experience with inhaled nitric oxide in New Zealand neonatal intensive care units

AIMS: To audit the use of inhaled nitric oxide for the treatment of persistent pulmonary hypertension of the newborn in New Zealand neonatal intensive care units. METHODS: Prospective data collection on all infants treated with inhaled nitric oxide in neonatal intensive care units in the 20-month period from first use to December 1995. Data included perinatal factors, principal diagnosis, echocardiogram results, ventilation details and response to nitric oxide, adverse reactions and outcome. RESULTS: Twenty-eight infants received nitric oxide in three centres, all bar one being 36 weeks or more gestation. Overall survival was 68%. Thirteen infants (46%) responded to nitric oxide treatment, 12 (92%) surviving. Seven (47%) of non-responders survived. Infants with primary pulmonary hypertension or meconium aspiration syndrome had 90% survival and more often responded to nitric oxide than infants with congenital diaphragmatic hernia (40% survival) or pulmonary hypoplasia (no survivors). No serious complications of treatment were recorded. CONCLUSIONS: Inhalational nitric oxide was not universally successful treatment for pulmonary hypertension of the newborn but was likely to have been life-saving in a proportion of cases. Future studies may allow better case selection. Ongoing audit of this new treatment is warranted.     

Inhaled nitric oxide in congenital hypoplasia of the lungs due to diaphragmatic hernia or oligohydramnios

OBJECTIVE: We determined whether inhaled nitric oxide (NO) could improve systemic oxygenation in human neonates with hypoplastic lungs. METHODS: A multicenter nonrandomized investigation was performed to study the efficacy of short-term NO inhalation. Inhaled NO was administered at 80 ppm to nine neonates without evidence of structural cardiac disease by echocardiography. Lung hypoplasia was due to congenital diaphragmatic hernia (CDH) in eight patients and to oligohydramnios in one patient. A total of 15 trials of NO inhalation were performed in these nine patients. Eight trials in seven patients were performed before extracorporeal membrane oxygenation ((ECMO); one patient had two trials) and seven trials were performed in five patients after decannulation from ECMO (two patients had two trials each). RESULTS: NO inhalation before ECMO did not change postductal PaO2 (42 +/- 3 mmHg vs 42 +/- 4 mmHg), oxygen saturation (SpO2; 89% vs 88%) or oxygenation index (31 +/- 4 cm H2O/torr vs 31 +/- 4 cm H2O/torr) for the group. All patients required ECMO support, which lasted from 5 to 17 days (mean 9). After decannulation from ECMO, NO inhalation increased postductal PaO2 from a median of 56 mm Hg (range 41 to 94) to a median of 113 mm Hg (range 77 to 326), P < .05. It decreased the oxygenation index from a median of 23 cm H2O/torr (range 11 to 7) to a median of 11 cm H2O/torr (range 4 to 21), P < .05. It increased SpO2 from 91% to 96% (P < .05) and pH from 7.48 +/- .03 to 7.50 +/- .03. CONCLUSION: In our patients with hypoplastic lungs, inhaled NO was effective only after ECMO. This could be due to maturational changes such as activating the endogenous surfactant system. Inhaled NO may be effective in neonates with hypoplastic lungs who have recurrent episodes of pulmonary hypertension after ECMO, even if they were previously unresponsive.     

Benign intracranial hypertension in chronic myeloid leukemia

Persistent pulmonary hypertension of the newborn (PPHN) is a challenge for the neonatologist and a common indication for treatment with extracorporeal membrane oxygenation (ECMO) when medical management fails. We observed 132 neonates born between January 1985 and December 1988 with the diagnosis of persistent pulmonary hypertension of the newborn: 73 (55%) met the Bartlett criteria for treatment with ECMO with 80% predicted mortality; 21 (29%) deteriorated despite conventional medical treatment, were thought to be dying, and were sent for ECMO. Among the 52 patients who were medically treated 40 (77%) survived, a marked difference compared with a predicted 20% survival. All ECMO-treated neonates survived. Although conventionally treated infants showed a trend toward less dependence on supplemental oxygen at > 28 days of life, this study failed to detect a significant difference between those two groups. We conclude that mortality was lower for ECMO-treated infants than for those who were medically treated (0 of 21 vs 12 of 52, p < 0.05); mortality for infants with persistent pulmonary hypertension of the newborn who met Bartlett's criteria and were medically treated was lower than published data; and there was no significant difference in oxygen dependence at > 28 days between the survivors who received ECMO and those who received medical therapy.     

Response to inhaled nitric oxide in acute lung injury depends on distribution of pulmonary blood flow prior to its administration

Responses to inhaled nitric oxide (iNO) in acute lung injury (ALI), as evidenced by improvements in oxygenation, are variable. We hypothesized that the effect of iNO may be related to the pre-iNO distribution of pulmonary blood flow (PBF). In the present study we evaluated the effect of iNO on PBF in normal healthy dogs and in a canine model of ALI induced by oleic acid (OA). In Group "OA only" (n = 5), ALI was induced by central venous injection of 0.08 ml/kg OA. In Group "E+OA" (n = 5), hypoxic pulmonary vasoconstriction after ALI was blocked with low-dose endotoxin (15 microg/kg of Escherichia coli endotoxin) administered 30 min before giving the same dose of OA. Measurements of regional PBF and lung water concentration (LWC) using positron emission tomography (PET) and H215O were performed before and after OA or placebo, and then again at concentrations of 10, 40, and 0 ppm iNO. One hundred twenty minutes after OA injury, PaO2/FIO2 fell significantly in Group OA only, from 567 +/- 32 to 437 +/- 67 mm Hg. In these animals, PBF redistributed from the dorsal edematous regions of the lungs to the nondependent zones, thus partially preserving normal ventilation/ perfusion relationships. As in the normal animals, in Group OA only, iNO did not significantly change either PBF or oxygenation. In Group E+OA, the administration of low-dose endotoxin eliminated perfusion redistribution from the dorsal edematous lung regions. As a result, PaO2/FIO2 fell from 558 +/- 70 to 119 +/- 53 mm Hg, a decrease that was significantly greater than that in Group OA only. In Group E+OA, administration of iNO restored perfusion redistribution to a similar level as in Group OA only, which was associated with a significant improvement in PaO2/FIO2, from 119 +/- 53 to 251 +/- 159 (10 ppm iNO), and 259 +/- 165 mm Hg (40 ppm iNO). We conclude that the effect of iNO on oxygenation after ALI depends on the pre-iNO perfusion pattern, which may help explain the variable response to iNO often observed in patients with acute respiratory distress syndrome.     

Delayed closed reduction of rotatory atlantoaxial dislocation: case report and literature review

The effect of inhaled nitric oxide (iNO) on bleeding time and platelet aggregation was studied in nine newborn infants with resolving pulmonary hypertension. Infants treated with iNO at 40 ppm for 30 minutes had bleeding times that were nearly twofold longer than those obtained 24 hours after iNO was discontinued. iNO had no effect on in vitro platelet aggregation studies.     

Range of echocardiographic findings in term neonates with high oxygen requirements

AIMS: To examine the hypothesis that right to left shunting occurs mainly in the lungs rather than through the fetal channels in neonates. METHODS: Thirty two term babies requiring over 70% oxygen had daily colour Doppler echocardiograms until recovery. Measurements included left ventricular fractional shortening, right and left ventricular outputs, colour and pulsed Doppler ductal and atrial shunting and systolic pulmonary artery pressure (SPAP) derived from ductal shunt or tricuspid incompetence velocities. RESULTS: The babies were retrospectively classified into a respiratory group (n = 19) and a persistent pulmonary hypertension (PPHN) group (n = 13) on the basis of clinical history and radiology. At the initial echocardiogram, just 50% of babies had suprasystemic SPAP. Despite better oxygenation, more of the PPHN group had suprasystemic PAP (85% vs 26%). A correlation between SPAP and Oxygen index (OI) was present only in the respiratory group (r = 0.7). Low ventricular outputs (< 150 ml/kg/min) were common in both groups (53% and 79%). The respiratory group had more closed ducts (47% vs 0%) and those ducts which were patient were more constricted (1.75 mm vs 2.6 mm). Pure right to left ductal shunts were seen in just 15% and pure right to left atrial shunts in just 6% of all babies. The serial echocardiograms showed that SPAP fell and ducts closed well before oxygenation improved. Ventricular outputs increased with age in both groups. CONCLUSIONS: Apart from early on in the sickest babies with a primarily respiratory diagnosis and the babies with primary PPHN, most right to left shunting occurred at an intrapulmonary level.     

Sudden cardiac death in hypertrophic cardiomyopathy: risk evaluation

The pathophysiology of the lamb model of congenital diaphragmatic hernia (CDH) involves pulmonary hypoplasia, pulmonary hypertension, and surfactant deficiency. Inhaled nitric oxide (NO) is a highly selective pulmonary vasodilator. The aim of this study was to determine the effects of inhaled NO on pulmonary gas exchange, acid-base balance, and pulmonary pressures in a lamb model of CDH with or without exogenous surfactant therapy. At the gestational age of 78 days (full term, 145 days) 11 lamb fetuses had a diaphragmatic hernia created via a left thoracotomy and then were allowed to continue development in utero. After cesarean section, performed at term, six lambs received exogenous surfactant therapy (50 mg/kg, Infasurf) and five served as controls. All animals were pressure-ventilated for 30 minutes and then received 80 ppm of inhaled NO at an F1O2 of .9 for a 10-minute interval. Compared with the control lambs, the lambs with exogenous surfactant therapy had higher pH (7.17 +/- .06 v 6.96 +/- .07; P < .05), lower PCO2 (73 +/- 8 v 122 +/- 20, p < .05), and higher PO2 (153 +/- 38 v 50 +/- 23; P < .05). In control CDH lambs (without surfactant), inhaled NO did not improve pH, PCO2, or PO2, or decrease pulmonary artery pressure. In CDH lambs given exogenous surfactant, NO decreased pulmonary artery pressures (42 +/- 4 v 53 +/- 5; P < .005) and further improved PCO2 and PO2. NO also made the difference between pulmonary and systemic artery pressures more negative in the surfactant-treated lambs (-15 +/- 4 v -2.3 +/- 2.4; P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Surfactant treatment in the neonate with severe respiratory distress syndrome

Eighteen preterm infants severely ill with respiratory distress syndrome who required assisted ventilaton were given modified natural surfactant (Survanta) endotracheally. They had a mean +/- SEM gestational age of 31.2 +/- 0.4 weeks (range 28-34) and a mean +/- SEM birthweight of 1562 +/- 71 g (range 1160-2010). Average time of initial surfactant administration was 15 +/- 1.7 hour (range 5-24). No significant side effects were found during surfactant instillation. Post surfactant, the air entry was improved, oxygenation and arterial/alveolar gradients increased, and the levels of inspired oxygen could be reduced. Some of the radiological abnormalities were resolved. In 13 infants, patent ductus arteriosus became clinically evident, seven of whom received Indomethacin. There were 4 cases of pulmonary air leak, 5 cases of pulmonary hemorrhage and 8 cases of bronchopulmonary dysplasia. Four infants expired, two were due to severe asphyxia/shock and two died of unrelated causes. Among the 14 survivors who came for follow-up, two cases of retinopathy of prematurity had gradually regressed, one had cerebral palsy and delayed development. Surfactant rescue therapy is a supplemental beneficial treatment for severe respiratory distress syndrome while newborn intensive care concept is necessary for efficient diagnosis and treatment of RDS.     

Feasibility for evaluation of the efficacy of conventional ventilatory support in very low birth weight infants

Morbidity and mortality analysis in prematurely born low birth weight (LBW) neonates, very low birth weight (VLBW) neonates and extremely low birth weight (ELBW) neonates forms the cornerstone in current pediatric decision-making from both medical and socioeconomic point of view. The successful introduction of artificial ventilation for neonatal respiratory failure treatment has changed tremendously the prognosis of many diseases with a fatal outcome. This retrospective observational longitudinal study was designed to evaluate the changes in the following main indices: mean airway pressure (MAP), oxygenation index (OI), arterial-to-alveolar oxygen tension ratio (a/A PO2), alveolar-arterial oxygen gradient (A-a)DO2, ventilation index and VEI in VLBW infants treated with conventional ventilatory support (CV), assess the information yield of these indices as indicators of gas exchange at each and every one moment of CV, and to analyze their feasibility, accuracy and real-time convenience as indicators of the adequacy of inhalation therapy and their role as an indispensable tool in constructing the optimal treatment regimen in VLBW infants. Forty-seven VLBW infants requiring ventilatory support within 24 hours of birth were enrolled in the study. Four of the infants survived and the remaining 43 died. The data collected were entered into a high-yield Neonatal Intensive Computer File and the indices were followed up sequentially and thoroughly analyzed as the primary outcome measures of the study. Our results show that: 1. The combination of indices we propose is a useful high-yield discriminating method for evaluating the efficacy of neonatal ventilatory support, arterial blood gas exchange and clinical status. 2. These indices allow early diagnosis of the changes in pulmonary mechanics, hemodynamics and blood saturation. 3. Using the combination of indices improves the diagnostic reliability and information yield of each one of them. 4. The twofold pattern of change of the indices in VLBW infants is well-recognized:--whereas a/A and OI change rapidly in the group of non-survivors reflecting the delicate balance in optimal gas-exchange using conventional methods in the survivors group there is a sustained tendency towards an increase in a/A values with a concomitant decrease in OI values. The airway pressure is constant in the presence of great fluctuations in OI values reflecting the breakdown in oxygenation at the high price paid for its sustenance in the nonsurvivors group whereas the mean airway pressure showed a gradual decrease in the survivors group and allowed early weaning from mechanical ventilation. (A-a)DO2 remained high in the non-survivors group thus reflecting a high-degree, practically constant shunting whereas the same index showed a tendency towards decrease in the survivors group. 5. These indices allow optimal management of neonatal ventilation and oxygenation and timely correction or a change of the ventilatory or/and oxygenation strategy. 6. This information forms the basis for prognostic conclusions regarding the current status or the survival of the neonates.     

High frequency ventilation in neonatal surgery

High frequency oscillatory ventilation (HFOV) is one of the artificial ventilation techniques used for the treatment of severe respiratory distress in the neonatal period. We studied (between 1987 and 1992) 57 newborn infants ventilated by HFOV during surgery. The aim was to facilitate the surgical procedure without having any deleterious effects on the gas exchange or the hemodynamic state of the infant. Three groups were studied. Group I (thoracic procedures: oesophageal atresia and pulmonary malformations, n = 25), group II (diaphragmatic hernia, n = 22), group III (abdominal procedures, n = 10). In the thoracic surgery group, no deleterious effect related to the HFOV was reported. The hyperventilation noticed after anaesthetic induction was rapidly corrected by placing the patient in a lateral position. In the three groups, no intraoperative complications related to the HFOV were observed. The diaphragmatic hernia group was divided into two subgroups according to the timing of surgery (emergency surgery, surgery after stabilization). In the latter subgroup, surgery was performed when the ventilation and gas exchange conditions had significantly improved. This subgroup showed the highest survival rate. This technique of peroperative ventilation is specifically used in the thoracic and diaphragmatic procedures of term and preterm newborn infants. It achieves a more stable operative field with less pulmonary expansions and diaphragmatic movements. In spite of the fact that HFOV is seldom used during anaesthesia, this study confirms its safety as well as the simplicity of its monitoring.     

Congenital diaphragmatic hernia and intrathoracic intestinal volvulus

The main symptom of the congenital diaphragmatic hernia (CDH) is the respiratory distress due to the pulmonary hypoplasia and the persistence of foetal pulmonary circulation. Sometimes the CDH appears outside of the neonatal period with respiratory symptoms, abdominal pain and seldom with intestinal obstruction. A case of CDH presenting with intrathoracic volvulus is reported. This case shows that tendency of delayed repair until the newborn has been recovered, require more attention because the good condition of the patient can be changed not only by the pulmonary hypoplasia and the persistence of the foetal pulmonary circulation but also by the symptoms of the intrathoracic gut complications.     

Inhaled nitric oxide in patients with cystic fibrosis during preoperative evaluation and during anaesthesia for lung transplantation

INTRODUCTION: Inhaled nitric oxide (iNO) has been recently used as pulmonary vasodilator without any systemic effects because of a rapid inactivation by haemoglobin. We studied haemodynamic and oxygenation effects during iNO administration in cystic fibrotic patients during preoperative evaluation and during anaesthesia for lung transplantation. METHODS: From March 1996 to November 1997, 35 patients received iNO (40 ppm) during preoperative evaluation in spontaneously breathing. 13 patients, who underwent double lung transplantation, received iNO (40 ppm) during the surgical procedures, after pulmonary artery clamping. RESULTS: In the preoperative evaluation a significant decrease of mean pulmonary artery pressure, pulmonary vascular resistance index and intrapulmonary shunt, with an increase of PaO2/FiO2, were observed during iNO administration, compared to baseline in 100% O2. During lung transplantation a significant decrease in intrapulmonary shunt was noted. All the transplants were successfully performed without cardio-pulmonary bypass. In all procedures, after iNO administration, we observed no modification of systemic haemodynamics. In conclusion, our study confirms the pulmonary effects of iNO without any systemic effects in patients affected by cystic fibrosis during preoperative evaluation and during anaesthesia for lung transplantation.     

Differential expression of HSU17714 gene in colorectal cancer and normal colonic mucosa

We describe an infant with severe eventration of the right diaphragm and pulmonary hypoplasia who presented like a newborn with congenital diaphragmatic hernia complicated by persistent pulmonary hypertension. Surgical correction while on extracorporeal life support was unsuccessful due to attachments of the liver which prevented reduction into the abdominal cavity and our inability to distinguish the true defect from complete agencies of the right hemidiaphragm. At autopsy the pulmonary remnant and the fibrous membrane separating it from the liver were identified.     

The next challenge for newborn intensive care in Alaska: improving the survival of the larger neonate

Using information from our database, a review of mortality for the Newborn Intensive Care Unit at Providence Alaska Medical Center was conducted for 1987-1996. There has been a significant decline in mortality over the last decade (p = 0.003). An analysis of mortality by birthweight and gestational age groups demonstrated a decline in mortality (p = 0.005) for infants with birthweight < 2 kg and infants < or = 34 weeks gestation, but no change for infants > or = 2 kg and > or = 35 weeks gestation. As a result, larger and more mature babies now account for an increasing proportion of NICU deaths. For 1995 and 1996 the major contributors to mortality for the smaller neonates were respiratory distress syndrome and congenital and nosocomial sepsis/pneumonia. The major contributors to mortality for larger neonates were persistent pulmonary hypertension of the newborn, congenital heart disease, congenital diaphragmatic hernia, and primary birth asphyxia. A majority of deaths in the larger neonates were due to non-lethal causes. We contend that improved survival in the larger neonate is an important and achievable goal. The introduction of ECMO (Extracorporeal Membrane Oxygenation) for the NICU and a focused review of the neonatal cardiac program offers the best possible potential for achieving this goal.