International experience with trisomy 21 infants placed on extracorporeal membrane oxygenation.

OBJECTIVE: To characterize the international experience concerning neonates with trisomy 21 (T21) managed with extracorporeal membrane oxygenation (ECMO), and to compare and contrast this group of patients to the neonatal ECMO population as a whole. METHODS: Data from the Extracorporeal Life Support Organization for newborn infants placed on ECMO between January 1984 and June 1999 were analyzed. Infants with T21 were compared with the group of infants without T21. RESULTS: Fifteen thousand nine hundred forty-six infants, including 91 (n = 91) with the diagnosis of T21, were placed on ECMO for neonatal respiratory failure during the 14.5-year period. T21 infants were overrepresented in the ECMO population by several-fold when compared with the incidence of T21 in the general population. Eighty-seven of the 91 T21 infants were placed on ECMO after 1989. The distribution of primary diagnoses leading to ECMO differed between the groups (T21 vs non-T21): primary persistent pulmonary hypertension, 47.3% versus 13%; meconium aspiration syndrome, 23.1% versus 32.9%; sepsis, 7.7% versus 13.2%; congenital diaphragmatic hernia, 7.7% versus 19.9%; and respiratory distress syndrome, 3.3% versus 7.9%. Although survival to discontinuation of ECMO was similar in the 2 groups, likelihood of survival to discharge was decreased for T21 infants (65.9% vs 75.6%) because of increased post-ECMO mortality. CONCLUSIONS: Extracorporeal Life Support Organization registry data suggests that T21 infants are at a significantly higher risk of being placed on ECMO for neonatal respiratory failure than the general population, perhaps as a result of delayed extrauterine pulmonary vascular adaptation, as manifested in the high rate of primary persistent pulmonary hypertension as the primary diagnosis. There may have been a shift in attitude regarding the use of ECMO in the T21 patient after 1989. Although most T21 patients placed on ECMO will survive, the prognosis is more guarded in this population when compared with all infants so managed. The long-term neurodevelopmental outcome of this group of T21 ECMO survivors is currently unknown.

Persistent pulmonary hypertension in a neonate with cystic adenomatoid malformation of the lung following lobectomy: survival with prolonged extracorporeal membrane oxygenation therapy.

A full-term neonate is reported with congenital cystic adenomatoid malformation of the lung treated by lobectomy with development of pulmonary hypertension. The infant was successfully treated with extracorporeal membrane oxygenation (ECMO) for persistent pulmonary hypertension, which developed postoperatively. An 18-day course of venovenous ECMO was necessary to effectively reverse the severe pulmonary hypertension. This was probably a result of significant pulmonary hypoplasia of the compressed lung. Although not all congenital cystic adenomatoid malformations of the lung are associated with pulmonary hypoplasia and persistent pulmonary hypertension, this is one case where severe pulmonary hypertension developed secondary to a mass effect by a large lesion in the chest.

Maternal use of alcohol during pregnancy is a risky lifestyle.

Alcohol is a well known teratogen. Its role in causing fetal alcohol syndrome/fetal alcohol effects is well documented. A vast amount of study over the past several decades has finally provided insight into many aspects of its effect. The only effective treatment is complete abstinence from the drug during pregnancy.

Bacterial and fungal infection in neonates undergoing venoarterial extracorporeal membrane oxygenation: an analysis of the registry data of the extracorporeal life support organization.

A review and analysis of 5,001 neonatal venoarterial (VA) extracorporeal membrane oxygenation (ECMO) cases showed that bacterial and fungal infection occurred in 147 (2.9%) and 26 (0.6%) patients, respectively, with an overall incidence of 3.5%. Bivariate analysis was used to compare infected infants with controls, bacterial versus fungal groups, and bacterial subgroups with respect to patient demographics, primary diagnosis, mechanical complications, patient complications, duration of the ECMO course, and hospital mortality. Logistic regression models were constructed using variables that were statistically significant from the bivariate comparisons. Variables that remained significant after multivariate analysis included primary diagnosis of pneumonia/sepsis, mechanical complications of oxygenator failure, rupture of raceway or tubing, clots, and patient complications of hypertension and hyperbilirubinemia. The infection group had significantly longer mean total hours on bypass and higher hospital mortality. Infants with fungal infection had a significantly higher hospital mortality rate compared with those with bacterial infection. We conclude that infection during ECMO, especially fungal infection, carries an increased risk of hospital mortality and that mechanical complications are associated with an increased risk of infection, Key Words: Extracorporeal membrane oxygenation-Nosocomial-Bacterial infection-Fungal infection-Extracorporeal membrane oxygenation outcome.

Hanford miniature swine model for extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is now an accepted therapy for neonatal respiratory failure due to reversible lung disease. There is a continued need to train ECMO team members using animal models. Hanford miniature swine are an appropriate model for this purpose because of the availability and size as well as anatomic and physiologic similarities to humans. This article describes training ECMO team members in venoarterial and venovenous bypass utilizing Hanford miniature swine.

28-day survival rates of 6676 neonates with birth weights of 1250 grams or less.

Survival rates specific for birth weight, gestational age, sex, and race are described for 6676 inborn neonates who weighed less than 1251 g at birth and were born during 1986 through 1987. Overall 28-day survival increased with gestational age and birth weight, from 36.5% at 24 weeks' gestation to 89.9% at 29 weeks' gestation, or from 30.0% for neonates of 500 through 599 g birth weight to 91.3% for neonates of 1200 through 1250 g. The expected birth weight-specific survival advantage for female neonates and black neonates diminished when the data were controlled for gestational age, showing that certain previously reported survival advantages are based on lower birth weight for a given gestational age. Multivariate analysis showed that all tested variables were significant predictors for survival, in order of descending significance: gestational age and birth weight, sex, race, single birth, and small-for-gestational-age status. The powerful effect of gestational age on survival highlights the need for an accurate neonatal tool to assess the gestational age of very low birth weight neonates after birth.

Neonatal renal failure: a complication of maternal antihypertensive therapy.

Persistent anuria was diagnosed in a neonate born to a mother whose pregnancy was complicated by severe hypertension and systemic lupus erythematosus. Severe maternal hypertension necessitated the use of a battery of antihypertensive medications that included enalapril, an angiotensin converting enzyme inhibitor. The role of enalapril in neonatal renal failure is discussed.

Drug-induced paralysis (muscle relaxant) therapy in the mechanically ventilated neonate.

Drug-induced paralysis in the mechanically ventilated neonate is prescribed primarily to control breathing and, secondarily, to favorably affect underlying pulmonary disease and associated complications. Although the control of breathing can be achieved, it is controversial when pulmonary disease is favorably influenced by paralysis. However, such therapy may lessen the severity, and the incidence of the complications in specific subgroups of infants. In view of significant adverse effects, muscle paralysis should be used judiciously in neonates.

Studies on LHRH and physiological fluid amino acids in human colostrum and milk.

Various physiological fluid amino acids including essential, nonessential and neuroinhibitory as well as excitatory entities in human milk, colostrum, and infant formula were determined on a microcolumn ion-exchange analyzer equipped with ninhydrin detection system and integrator. The levels of 6 essential and 6 nonessential amino acids were significantly lower in infant formula than those in milk and colostrum. The neurotransmitter amino acids were also high in milk except taurine. Peptide hormones like LHRH were undetectable in infant formula, but were found in appreciable quantities in milk and colostrum by high pressure liquid chromatography. LHRH levels in milk were 6 to 7 fold higher than the corresponding plasma values as measured by radioimmunoassay. These and other several unique ingredients in human breast milk play a very prominent role in the development of the neonate. The presence of such complex components makes it impossible to humanize cow's milk or any other alternate formulation and to serve as a substitute for human milk. Further extensive work in defining the role of such essential components in milk on the development of the infant is indicated.

Perinatal events and necrotizing enterocolitis in premature infants.

Among 2123 premature infants monitored during a large multicenter study of patent ductus arteriosus, necrotizing enterocolitis (NEC) was diagnosed in 121 (5.7%) of these infants. Rates ranged from 13.5% among infants with a birth-weight (BW) of 500 to 749 g to 2.9% among infants whose BW was between 1500 and 1750 g. The presence of a hemodynamically significant patent ductus arteriosus did not alter the incidence of NEC. Of a large number of perinatal events and conditions considered, only BW and maternal toxemia were found to be associated with the rate of NEC, both relating inversely. Thus, these data do not support a relationship between NEC and a variety of perinatal factors previously postulated as potential determinants of the disorder.

Umbilical versus peripheral tobramycin administration.

This study evaluated the disposition of tobramycin (T) after umbilical artery catheter (UAC), intravenous (i.v.), and intramuscular administration to a group of 12 premature neonates. Patients varied in gestational age (31-42 weeks) and weight (1.76-3.98 kg). Each neonate received a 2 mg/kg dose of T at 12-h intervals for 2-15 days. Multiple blood samples after the first and last doses of T, as well as daily measurements, were made during the course of therapy. Analysis of drug concentration data revealed a biphasic distribution of T, which required a two-compartment model for description. Mean values for the alpha and beta elimination phases, t1/2 beta, Vc, and Vdss after the first dose of T were 7.604 h-1, 0.087 h-1, 11.18 h, 0.214 L/kg, and 0.645 L/kg, respectively. Average drug clearance (ClT) increased during therapy from 71 to 103 ml/min, associated with an increase in the renal function of patients. Serum concentrations of T were out of the therapeutic range in 50% of study patients. The variability of drug clearance in the neonate requires the measurement of T concentration in order to ensure safe and effective therapy.

Risk factors for retrolental fibroplasia: experience with 3,025 premature infants. National Collaborative Study on Patent Ductus Arteriosus in Premature Infants.

The rate of retrolental fibroplasia in relation to prenatal and neonatal characteristics was explored on the basis of a cohort of 3,025 neonates with birth weight less than 1,750 g. The overall rate of retrolental fibroplasia of any degree at hospital discharge was 11%, varying from 43% for those with birth weight between 500 and 749 g to 3% for those in the 1,500- to 1,750-g category. Among the potential determinants, the main interest was in nonhyperoxic characteristics, conditional on measures of prematurity and oxygen supplementation. Maternal diabetes and antihistamine use during the last 2 weeks of pregnancy were associated with significantly higher rates of retrolental fibroplasia, whereas toxemia was associated with lower rates. Frequent apneic spells, bronchopulmonary dysplasia, and sepsis in the neonate were also associated with significantly higher rates. On the other hand, the data indicate no independent role of low Apgar score, intraventricular hemorrhage, exchange transfusion, patent ductus arteriosus, or certain other characteristics previously postulated as risk factors.

Renal failure and other serious sequelae of epinephrine toxicity in neonates.

Epinephrine has numerous potent pharmacologic actions with protean manifestations. We have described a patient in whom inadvertent intra-aortic administration of a large dose of racemic epinephrine produced serious adverse effects, including hypertension, acidemia, tachycardia, and protracted but reversible renal failure. In view of the ubiquitous use of epinephrine in neonatal intensive care, we hope that this report heightens awareness of its more serious and potentially fatal toxic effects.

Bronchial laceration in a newborn with persistent posterior pneumomediastinum.

A large posterior pneumomediastinum that compromised the respiratory status and reaccumulated promptly after needle aspiration, aroused the suspicion of airway laceration. Tracheogram was consistent with laceration of the right bronchus. Evacuation of air with chest tube resulted in complete resolution of pneumomediastinum and healing of bronchial tear with no recurrence following removal of chest tube after seven days.

Primary renal candidiasis in two preterm neonates. Report of cases and review of literature on renal candidiasis in infancy.

Primary renal candidiasis and hydronephrosis were diagnosed in two premature neonates in whom systemic hypertension developed. The clinical course in these patients and in 16 patients with renal candidiasis described in the literature indicated that prematurity, use of broad-spectrum antibiotics, and use of intravenous (IV) catheters are predisposing factors. Anuria and flank mass were the initial manifestations in the reviewed cases. Only four of the 16 patients survived following either antifungal therapy or nephrectomy. Both of our patients survived after antifungal therapy with amphotericin B and flucytosine for systemic effect as well as topical instillation of amphotericin B solution via a nephrostomy. We believe that a high index of suspicion in infants at risk and early institution of antifungal therapy for systemic as well as topical effect can improve the outcome in infants with renal candidiasis.

Surgical closure of patent ductus arteriosus in 268 preterm infants.

Over a 2 year period ending in April, 1981, 268 premature infants with birth weight below 1,750 gm underwent operation for a "hemodynamically significant" patent ductus arteriosus. Operations were performed in 13 centers participating in a collaborative study, which was primarily designed to evaluate the role of indomethacin in the management of patent ductus arteriosus. No patient died during the operations, which were done at a median age of 10 days. Eight infants (3%) died within 36 hours after operation. In only one was the death directly attributable to the operative procedure. Hospital mortality (23%) and postoperative morbidity, which included bronchopulmonary dysplasia, pneumothorax, and sepsis, were unrelated to birth weight, age at operation, and degree of preexisting pulmonary disease or preoperative treatment of the infant with indomethacin. Results indicate that surgical ligation is a safe and effective procedure for treating patent ductus arteriosus with large left-to-right shunting in small premature infants.