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.

Lactobezoars: a patient series and literature review.

Lactobezoar is a compact mass of undigested milk concretions located within the gastrointestinal tract. Most often found in infants, they can precipitate gastric outlet obstruction, mimicking a variety of medical and surgical conditions. A common etiology and method of cure have yet to be elucidated. A review of the literature provides some insight into causes, clinical presentations, diagnosis, and management. Data from the Medical University of South Carolina further help dispel the belief that lactobezoars are isolated to pre-term infants on caloric-dense formulas. Findings suggest bezoar formation may be more common than previously thought and a high index of suspicion could help avoid costly evaluations for obstructive symptoms.

Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group.

BACKGROUND: Inhaled nitric oxide improves gas exchange in neonates, but the efficacy of low-dose inhaled nitric oxide in reducing the need for extracorporeal membrane oxygenation has not been established. METHODS: We conducted a clinical trial to determine whether low-dose inhaled nitric oxide would reduce the use of extracorporeal membrane oxygenation in neonates with pulmonary hypertension who were born after 34 weeks' gestation, were 4 days old or younger, required assisted ventilation, and had hypoxemic respiratory failure as defined by an oxygenation index of 25 or higher. The neonates who received nitric oxide were treated with 20 ppm for a maximum of 24 hours, followed by 5 ppm for no more than 96 hours. The primary end point of the study was the use of extracorporeal membrane oxygenation. RESULTS: Of 248 neonates enrolled, 126 were randomly assigned to the nitric oxide group and 122 to the control group. Extracorporeal membrane oxygenation was used in 78 neonates in the control group (64 percent) and in 48 neonates in the nitric oxide group (38 percent) (P=0.001). The 30-day mortality rate in the two groups was similar (8 percent in the control group and 7 percent in the nitric oxide group). Chronic lung disease developed less often in neonates treated with nitric oxide than in those in the control group (7 percent vs. 20 percent, P=0.02). The efficacy of nitric oxide was independent of the base-line oxygenation index and the primary pulmonary diagnosis. CONCLUSIONS: Inhaled nitric oxide reduces the extent to which extracorporeal membrane oxygenation is needed in neonates with hypoxemic respiratory failure and pulmonary hypertension.

Mosaic trisomy 8: a cautionary note regarding missed antenatal diagnosis.

Chromosomal analysis of fetal cells is a commonly used, safe, and highly accurate procedure. The rate of false-negative results is unknown. Recent experience at four centers suggests that there may be a particular likelihood for mosaic trisomy 8 to be missed with routine antenatal diagnostic procedures. This report reviews these cases, the characteristic findings of mosaic trisomy 8, and the tissue-specific differential yield of chromosomal analysis that may contribute to the increased risk of missed antenatal diagnosis in patients with this disorder.

Comparative neonatal morbidity of abdominal and vaginal deliveries after uncomplicated pregnancies.

OBJECTIVE: To determine whether the risk of cesarean section following uncomplicated pregnancies has been reduced by current obstetric practices by comparing the neonatal risk of vaginal deliveries with the risk incurred following abdominal delivery in otherwise uncomplicated pregnancies. DESIGN: Observational, cohort study. A subpopulation of 11,702 women without complications of pregnancy was identified from a perinatal database, classified by subsequent mode of delivery, and compared for neonatal morbidity. This analysis was repeated after the cesarean section group was further narrowed to include only "repeated elective" deliveries. SETTING: Low-risk inborn setting. Tertiary care (level III nursery) referral center and a community (level II nursery) hospital. INTERVENTION: Cesarean section performed electively, for cephalopelvic disproportion, or for failure to progress. OUTCOME VARIABLES: Chosen prior to data analysis: neonatal mortality and morbidity. RESULTS: Groups differed with regard to ethnicity and sex. Infants who were delivered by cesarean section were more likely to have 1-minute Apgar scores less than 4, require intermediate or intensive nursery care at admission (6.3% vs 1.3% [P < .001]), and require greater respiratory support (mechanical ventilation, 1.6% vs 0.3%; oxygen therapy, 4.9% vs 1.4%; or room air, 93.5% vs 98.4% [P < .001]) than infants who were delivered vaginally. Similar results were found when patients who were delivered vaginally and by repeated elective cesarean section were compared. CONCLUSION: Although reports have recently emerged suggesting otherwise, abdominal delivery following an uncomplicated pregnancy remains a risk factor for adverse neonatal outcome despite current obstetric practices.

Aerosolized pharmacotherapy in the neonate.

The use of aerosolized pharmacotherapy (inhalation therapy) in the intensive care nursery has been expanding since the first reports in the early 1980s. The potential benefits of this route of therapy include delivery of high concentrations of medicines directly to the respiratory system, avoiding the side effects of systemic administration. However, the anatomy and physiology of the newborn infant provide obstacles to inhalation therapy not encountered in older children and adults. A review of the literature reveals only limited data supporting the use of medications delivered by aerosolization in the neonate. A need for continued basic and clinical research in this area is apparent.

Management of salt poisoning in an extremely low birth weight infant.

We present the first reported case of severe salt poisoning in an extremely low birth weight neonate. The salt poisoning was managed with the careful use of intravenous fluids, insulin to manage the severe hyperglycemia, and furosemide to induce a saline diuresis. The hypertonicity was normalized slowly over 3 days by following the corrected serum sodium (Na) (serum Na + 2.7 mEq for every 100 mg/dl of glucose over 100). No neurological damage was seen in our patient during the development of the hypertonicity or its correction. This suggests that the premature brain can develop osmoprotective molecules if hypertonicity develops slowly over 2-3 days. Slow correction is therefore recommended to avoid the development of water intoxication during correction. Despite the development of mild reversible renal failure, a large saline diuresis was induced with furosemide, thereby avoiding the need for dialysis in our patient. The only complication was the development of necrotizing enterocolitis, which has not been previously reported in association with salt poisoning.

Ontogeny of epithelial modulation of airway smooth muscle function in the guinea pig.

The purpose of this study was to investigate the ontogeny of guinea pig airway smooth muscle (ASM) responses and the epithelial modulation of these responses. Paired tracheal rings from fetal, newborn, and adult guinea pigs were studied. One of each pair was denuded of airway epithelium (AE) by gentle rubbing. Isometric tension was measured in rings mounted in organ baths filled with Krebs' solution. Cumulative dose-response curves were generated by adding either acetylcholine (ACh) or histamine over a concentration range of 10(-8)-10(-4) M. Significant agent-specific, age-related differences in maximal contraction were seen for both ACh and histamine in intact tissues (Ach: for fetus 66.7 +/- 6.2 x 10(-2) g/mg wet wt, for newborn 51.4 +/- 6.2, for adult 29.3 +/- 2.6; histamine: for fetus 46.1 +/- 5.1, for newborn 72.9 +/- 6.0, for adult 25.3 +/- 3.2). Similar differences in sensitivity to both agents were observed (EC50 with ACh: for fetus 0.80 +/- 0.11 x 10(-6) M; for newborn 0.85 +/- 0.26 x 10(-6) M; for adult 1.7 +/- 0.20 x 10(-6) M; EC50 with histamine; for fetus 1.88 +/- 0.50 x 10(-6) M; for newborn 1.34 +/- 0.16 x 10(-6) M; for adult 3.78 +/- 0.75 x 10(-6) M). Removal of AE caused a significant decrease in maximal responses to ACh in fetal tissue, a smaller, insignificant one for newborn and a nonsignificant alteration for adult tissues. Age-related sensitivity difference was abolished with removal of AE to ACh but not to histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Furosemide differentially relaxes airway and vascular smooth muscle in fetal, newborn, and adult guinea pigs.

Furosemide, an inhibitor of Cl-dependent Na+,K+ cotransport, is the most frequently used diuretic in newborns. Recently, furosemide was also demonstrated to decrease bronchial hyper-responsiveness in adults, although little is known about the direct effect of furosemide on smooth muscle of immature animals. This in vitro study was designed to determine the action of furosemide on airway and vascular smooth muscle during ontogeny. Extrathoracic trachea (ET), main stem bronchi, main pulmonary artery, and thoracic aorta ring segments from fetal, newborn, and adult Hartley albino guinea pigs were suspended in HEPES solution for measurement of isometric tension. Furosemide (30 or 300 microM) was administered after preconstriction with an ED35-70 concentration of histamine or acetylcholine for airway and ED40-100 concentration of norepinephrine for vessels. Furosemide (30 microM) caused significant relaxation of airway smooth muscle at all ages. After histamine-induced preconstriction, fetal airway segments exhibited greatest relaxation (183 +/- 28%), with newborn airway demonstrating 123 +/- 15% relaxation and modest relaxation seen in adults (40 +/- 4%). This pattern was similar for both ET and bronchus and appeared greater for histamine compared with ACh preconstriction. Epithelial removal slightly enhanced relaxation. Furosemide also relaxed pulmonary artery segments, but at a 10-fold higher concentration. In striking contrast to the pattern seen in airway, adult pulmonary artery relaxed more than newborn and newborn, more than fetus. Cyclooxygenase blockade and endothelium removal did not change pulmonary artery relaxation. Furosemide did not significantly relax aorta after NE preconstriction. Taken together, these results suggest that furosemide may be more effective in relaxing airway compared with vascular smooth muscle, and the ontogeny of these responses indicates a greater efficacy and selectivity in airways of immature animals.

Congenital chyloperitoneum as a cause of isolated fetal ascites.

Isolated fetal ascites is an unusual prenatal finding and must be differentiated from immune and nonimmune hydrops. This entity is most commonly associated with gastrointestinal and genitourinary anomalies. Fetal chyloperitoneum, however, should be considered as a possible cause. Pulmonary hypoplasia and abdominal dystocia during attempted vaginal delivery are potential complications. We present a case of isolated fetal ascites due to congenital chyloperitoneum.

Need for and impact on neonatal mortality of extracorporeal membrane oxygenation in infants of greater than 2500-gram birth weight.

The use of extracorporeal membrane oxygenation (ECMO) has increased significantly during the last 4 years, with more than 2400 infants now having been treated with the technique. In spite of an ill-defined role for ECMO as well as the potential for neurologic sequelae for these patients, additional centers continue to be established across the United States. To provide information regarding the number of babies who could be expected to require ECMO, the early neonatal deaths for the state of Georgia were reviewed for the 2-year period 1983-1984. By means of both linked birth and death certificate analysis and chart review of infants with a birth weight of 2500 g or more, identification was made of 36 infants whom we classified as potential ECMO candidates. These infants were thought to represent 80% of all infants who would have received ECMO during the 2 years, resulting in an estimate of 1 patient receiving ECMO per 3717 live births for the state. With a predicted survival rate of 80% for this group, the state neonatal mortality rate would have declined by 0.13 per 1000 live births, a decrease of 1.4%.

Pharmacokinetics of gentamicin in neonates on extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) has been used in more than 1,000 infants in 50 centers in the United States. The extracorporeal circuit contains approximately 400 ml of blood, an amount exceeding the blood volume of most full-term neonates. The effect of this additional blood volume on drug disposition is unknown. In this study, we determined the pharmacokinetic parameters of gentamicin in 10 infants on ECMO. Gentamicin concentrations were determined by a fluorescence polarization immunoassay. Pharmacokinetic parameters were determined from these concentrations by using a two-compartment model. Our study demonstrated a mean steady-state volume of distribution of 0.51 +/- 0.11 liters/kg, a figure similar to that in previous studies of full-term infants. The elimination half-life was found to be prolonged (mean, 573 +/- 263 min). The creatinine level in the plasma of the infants was found to be a statistically significant predictor of elimination half-life. Recommendations regarding initial dosing levels of gentamicin in infants on ECMO are made.