John A. Smyth

Prevention and 18-Month Outcomes of Serious Pulmonary Hemorrhage in Extremely Low Birth Weight Infants: Results From the Trial of Indomethacin Prophylaxis in Preterms

OBJECTIVES. A patent ductus arteriosus is a risk factor for pulmonary hemorrhage; however, despite halving the incidence of patent ductus arteriosus, indomethacin prophylaxis did not reduce the rate of pulmonary hemorrhage in the Trial of Indomethacin Prophylaxis in Preterms. Inclusion of mild bleeds after trauma to the upper airways may have masked a beneficial drug effect. Using the Trial of Indomethacin Prophylaxis in Preterms database, we studied the effect of prophylactic indomethacin on the prevention of serious hemorrhages in extremely low birth weight infants. We also compared the 18-month outcomes of infants with and without a serious pulmonary bleed. METHODS. Pulmonary hemorrhage was classified as serious when it was treated with increased ventilator support, a higher concentration of oxygen, or transfusion of blood products. The cumulative risk for serious pulmonary hemorrhage was estimated for the first week of life and for the entire NICU stay. Poor outcome at a corrected age of 18 months was death or survival with cerebral palsy, cognitive delay, blindness, and/or deafness. RESULTS. A total of 123 (10.2%) of 1202 infants developed a serious pulmonary hemorrhage. During week 1, prophylactic indomethacin reduced the risk for serious pulmonary hemorrhage by 35%; however, during the entire NICU stay, the risk for such hemorrhages was decreased by only 23%. A reduced risk for patent ductus arteriosus explained 80% of the beneficial effect of prophylactic indomethacin on serious pulmonary bleeds. The risks for death or for survival with neurosensory impairment were doubled after a serious pulmonary hemorrhage. CONCLUSIONS. Extremely low birth weight infants with serious pulmonary hemorrhage have an increased risk for poor long-term outcome. Prophylactic indomethacin reduces the rate of early serious pulmonary hemorrhage, mainly through its action on patent ductus arteriosus. Prophylactic indomethacin is less effective in preventing serious pulmonary hemorrhages that occur after the first week of life.

Increased compliance in response to salbutamol in premature infants with developing bronchopulmonary dysplasia

We compared the effect of salbutamol and placebo in a double-blind study of preterm infants with bronchopulmonary dysplasia, using a randomized, crossover design with several replicates per subject. Sixty-two tests were performed on 20 ventilator-dependent infants weighing less than 1500 gm. Patients were entered as early as the first week of life and studied for at least 4 weeks or until extubation. Each subject was his own control subject and was randomly assigned to a placebo-salbutamol or salbutamol-placebo sequence administered on 2 consecutive days of each week. Static compliance, expiratory resistance of the respiratory system, and changes in transcutaneous oxygen and carbon dioxide tension were measured. Static compliance improved by 0.240 ml/cm H2O/kg (35.3%) after salbutamol and by 0.010 ml/cm H2O/kg (2.8%) after placebo (p less than 0.0001). The presence of a predetermined decrease in carbon dioxide tension correlated with large changes in static compliance per kilogram and with the need for a high level of fractional inspired oxygen. The magnitude of the clinical and physiologic improvement observed, and the early response suggest that long-term bronchodilator therapy starting as early as the second week of life may be beneficial for very low birth weight infants with early bronchopulmonary dysplasia.

Randomized, double-blind, controlled trial of long-term diuretic therapy for bronchopulmonary dysplasia.

The effects of continuous therapy with hydrochlorothiazide and spironolactone on pulmonary function in 34 premature infants with severe bronchopulmonary dysplasia were assessed in a randomized double-blind controlled trial. Subjects were greater than or equal to 30 days old, were supported by mechanical ventilation in greater than or equal to 30% oxygen, and had radiographic evidence of bronchopulmonary dysplasia. The treatment group (n = 19) and the placebo group (n = 15) were similar in all respects except for distribution of gender. Anthropometrics, ventilatory measurements, and the results of pulmonary function tests were evaluated at study entry and at 1, 4, and 8 weeks into therapy. Poststudy chest radiographs were compared with those obtained before the study. The proportion of infants alive at discharge was significantly increased (84%) in the treatment group compared with the placebo group (47%) (p = 0.05). There were no statistically significant differences in total hospital days or in total ventilator days. Total respiratory system compliance at 4 weeks was higher in the treatment group (0.61 +/- 0.18) than in the placebo group (0.45 +/- 0.13) (p = 0.016). No difference in outcome was detected between male and female infants in the treatment group. These results suggest that long-term diuretic therapy improves outcome in infants with bronchopulmonary dysplasia.

Erythropoietin therapy in neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions

OBJECTIVES To determine whether treatment with recombinant human erythropoietin (r-HuEPO) reduces transfusion requirements in premature neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions. STUDY DESIGN A double-blind, randomized, controlled trial. SUBJECTS Fifty-five infants appropriate in weight for gestational age (less than 1250 gm birth weight) who, at 10 days of age, were predicted to have a greater than 75% probability of having bronchopulmonary dysplasia. This criterion had previously been shown to identify infants requiring multiple transfusions. Twenty-seven infants were randomly assigned to receive r-HuEPO therapy and 28 to a control group. r-HuEPO was administered in a dosage of 20 U/kg body weight, subcutaneously, three times a week for 6 weeks. Control infants received sham treatment. RESULTS Infants treated with r-HuEPO required significantly fewer transfusions than control infants during their entire hospital stay (mean 3.48 +/- 1.58 vs 5.68 +/- 2.30; p = 0.0001) and had a higher mean reticulocyte count (p < or = 0.0005) and a higher mean hemoglobin concentration (p < or = 0.005) during the treatment period. At follow-up, 4 months after term, there were no significant differences between the groups in mean reticulocyte count (p = 0.86) or mean hemoglobin concentration (p = 0.56). However, two infants in each group had low serum ferritin values indicative of depleted iron stores. CONCLUSIONS Treatment with r-HuEPO effectively stimulated erythropoiesis in premature infants at high risk of having bronchopulmonary dysplasia and requiring multiple transfusions; the result was a reduction in transfusion requirements. This treatment, together with other strategies to reduce the need for transfusions, is appropriate in this population. Unrelated to r-HuEPO treatment, these infants may be at risk of having iron deficiency later in infancy.

Passively acquired human immunodeficiency virus seropositivity in a neonate after hepatitis B immunoglobulin

Since the initial documentation of acquired immunodeficiency syndrome and AIDS-related complex in infants, there has been concern about underdiagnosis in the pediatric population, particularly in the neonate. The neonate acquires human immunodeficiency virus transplacentally from the mother, who may well not be aware that she is a carrier. Intravenous drug abuse and sexual promiscuity in parents are major risk factors in the transmission of AiDS to the newborn infant. Therefore, our hospital policy is to request HIV serologic studies in the presence Of this history: The following case illustrates a potential pitfall in the diagnosis of HIV infection. CASE REPORT

CONJOINED TWINS: THE ULTIMATE CLINICAL ETHICAL DILEMMA? 164

The birth of conjoined twins is extremely rare, and survival even rarer, but their neonatal management poses clinical and ethical issues of the greatest complexity for the patients, their surrogate decision makers, health care workers and society. The clinical issues are highly complex as the unique detailed anatomy has to be defined as an urgent priority for assessment of viability and planning future management including separation if possible at an appropriate time. As two individuals connected together who may be physiologically interdependent, the mode of separation raises burdensome conflicts for preserving the separate rights of the two individuals and their equal right to best treatment, and concerns for sanctity of life if one has to be ”sacrificed“ that the other may live. One may suffer treatment induced harms for the benefit of the other and risk becoming a ”means to an end“. In planning treatment the motivation to do good is confounded by the high risk of poor or unpredictable outcome and consequent difficulty in balancing harms and benefits for two interdependent individuals. When is further treatment merely prolonging the dying process?. There is an unclear boundary between clinical care and unlicensed human experimentation which is most acutely felt by the bedside nurses. Principal caregivers need to be certain they are not pursuing a path of aggressive treatment to satisfy a personal achievement goal; an unacceptable conflict of interest between themselves and the patients. Likewise the institution must ensure that there are not corporate reasons for involvement in such cases because of the positive media exposure they may bring. Media interest in conjoined twins knows almost no bounds. Yet in such an environment confidentiality must be carefully maintained and parents protected from the media if it is the familys wish that their most personal family catastrophe be kept completely confidential. Such a degree of confidentiality is a heavy burden for caregivers at all levels who require debriefing sessions to assist in coping with on-going stress. Appropriate care of these patients requires extreme clinical sensitivity and humanity, and repeated validation of ethical issues.

THE RETICULOCYTE COUNT AS A PREDICTOR OF TRENDS IN HEMOGLOBIN IN PREMATURE INFANTS. † 1732

THE RETICULOCYTE COUNT AS A PREDICTOR OF TRENDS IN HEMOGLOBIN IN PREMATURE INFANTS. † 1732

1528 TRANSCUTANEOUS PULSE OXYGEN SATURATION (tcSaO2) MONITORS ARE SUPERIOR TO tcPO2 MONITORS IN INFANTS WITH BRONCHOPULMONARY DYSPLASIA (BPD)

We studied 12 infants with a clinical and radiologic diagnosis of BPD who were oxygen dependant and older than 30 days; tcSaO2, measured by two monitors (Nell-cor 100, BTI Biox III) and tcPO2, (Transend) were correlated with arterial SaO2, (Radiometer OSM2 Hemoximeter) and PaO2 (Corning 178) measured on blood from an indwelling catheter. For each infant, the FiO2 was adjusted to obtain 3-5 sets of data in the range of 70-95% SaO2.Our data confirms reports by others that tcPO2 does not accurately represent PaO2 in older infants with BPD. Based on accuracy, self-calibration and an unheated sensor that will not cause skin burns, monitoring tcSaO2 has major advantages over tcPO2 in the management of BPD.