Congenital and perinatal tuberculosis: discussion of difficult issues in diagnosis and management.

Tuberculosis (TB) has become more prevalent in women of childbearing age and, as well, more frequent in their children. This has occurred for a number of reasons, including: (1) women and children who have immigrated to this country from areas where TB is endemic, such as Mexico and Southeast Asia; (2) the development of multidrug-resistant organisms; (3) the increase seen in patients who live in congregate areas who are at higher risk for acquisition of TB; (4) more difficult access to adequate medical care; and (5) increases in adults and children who have become infected with human immunodeficiency virus. The focus of this review is on congenital and perinatally acquired TB including discussion of epidemiology, the stages of TB, the effects of TB infection and disease during pregnancy on the fetus and mother, congenital and perinatal TB, the potential role of the use of BCG vaccine in infants, and the emergence of multidrug-resistant TB on therapy of the pregnant mother and her fetus and the mother and her infant after delivery.

Neonatal cardiopulmonary resuscitation: the good news and the bad.

Many health care professionals all over the world have been taught neonatal cardiopulmonary resuscitation (CPR) using the neonatal CPR course based upon the work of Bloom and Cropley. The purpose of this article is to provide a retrospective review of the development of some of the neonatal CPR techniques, to discuss current techniques and to complement the dedication of this issue to Dr. Ronald Brown and Catherine Copley, MN, RN.

Caring for the graduate from the neonatal intensive care unit. At home, in the office, and in the community.

This article focuses on recent progress in the understanding of optimal care for the neonatal intensive care unit (NICU) graduate in three domains that have relevance to primary care pediatricians: the concept of developmentally supportive care for the immature central nervous system of fragile premature infants; an understanding of the function and systems of community-based early intervention available for medically complex, developmentally challenged and at-risk infants; and the management of technology-dependent children at home.

An introduction to the structure and function of inflammatory mediators for clinicians.

As is apparent from a brief overview of some of the more important mediators involved in perinatal physiology and disease states, basic science research has provided many clinically relevant observations that, as discussed in other articles in this issue, have resulted in the discovery and development of clinically effective medications used daily in the care of the gravid mother and her fetus or neonate. In addition, an excellent base for the understanding of the mechanisms of the physiology of the maternal-fetal-placental unit has been established via extensive general and more focused research involving mediators.

Cardiopulmonary resuscitation of the newborn. An update.

The abrupt transition from intrauterine to extrauterine life represents a series of profound physiologic changes. This process puts the baby at risk for asphyxia. At birth, the newborn is, therefore, more frequently in need of resuscitation than at any other age. This article reviews the rationale for the sequence and process of neonatal resuscitation, emphasizing recent changes in recommendations.

Tuberculosis in infancy in the 1990s.

In 1990, 25,701 cases of tuberculosis (TB) were reported in the United States, the largest annual increase since 1953. Children younger than 15 years of age accounted for 1596 new cases. The resurgence of TB can largely be contributed to the HIV epidemic. The clinical course, diagnosis, therapy, and prevention of TB in the perinatal period and in infancy are discussed in view of the epidemics of HIV and TB in the adult population.

Evaluation of a prostacyclin analog in prevention of pulmonary oxygen toxicity.

Prolonged exposure to high concentrations of oxygen can result in significant lung injury, although newborn animals are tolerant relative to adults. We previously reported that relative O2 tolerance in the rabbit is lost by 10 days of age, and is coincident with a decline in lung prostacyclin. In the current study we administered iloprost, a stable prostacyclin analog, by continuous infusion to maturing rabbits exposed to greater than 95% oxygen. Compared to vehicle-treated controls, iloprost-treated rabbits had significantly lower protein in bronchoalveolar lavage fluid at 84 h, a smaller percentage of neutrophils at 65 and 84 h, and lower mortality at 96 h. The partial protection against pulmonary oxygen toxicity afforded by iloprost is likely due to its membrane stabilizing effect, and its inhibitory actions on neutrophil migration, activation, production of oxygen radicals and proteolytic enzymes.

Education of personnel involved in the transport program.

Inclusive in the demand for transport services is the need for an ongoing formal educational curriculum to ensure that a high standard of care is consistently provided to patients. Those who provide transport services must ensure that the staff has an adequate baseline level of training and licensure, an ongoing system of educational review, and the frequency of activity necessary to maintain skills. Team members should have an acceptable level of cognitive and technical skills to transport patients and perform needed procedures safely. Such skills may be acquired and maintained by participation in nontransport activities, through a didactic curriculum and a system of ongoing case review, through team members providing training to referring hospitals, and through a "buddy" system of supervised transport activities. While an ongoing educational curriculum and its structure remain constant, the content can and should be tailored to the type of patients transported, from the very low birth weight infant and pregnant mother to pediatric and adult patients.

Evaluation of a leukotriene receptor antagonist in prevention of hyperoxic lung injury in newborn rabbits.

Prolonged exposure to hyperoxia can result in significant lung injury and has been associated with the development of bronchopulmonary dysplasia. Leukotrienes (LT) recruit polymorphonuclear leukocytes (PMN) to the lung, increase vascular permeability, and have therefore been postulated to play a role in the pathogenesis of hyperoxic lung injury. This study investigates ICI 198,615 (ICI), an LTD4 and LTE4 receptor antagonist in preventing hyperoxic lung injury in newborn rabbits. Matched littermates of 7-day-old rabbits received ICI (0.1 or 1.0 microM/kg/h) or vehicle alone, were exposed to greater than 95% O2, and sacrificed after 48, 72, 84 and 96 h of exposure. Bronchoalveolar alveolar lavage fluid (BAL) of the left lung was analyzed for white cell count, differential, absolute number of PMNs, total protein, and cyclooxygenase products 6-keto-PGF1 alpha, and thromboxane B2. Lung water was quantified utilizing the right lung. Results demonstrated no significant differences between the ICI groups or between the ICI groups and controls. In conclusion, the administration of the LTD4 and LTE4 receptor antagonist ICI 198,615 was insufficient to reduce the formation of pulmonary edema, reduce mortality or attenuate hyperoxic lung injury. These experiments suggest that a number of other mediators may be involved in the hyperoxic lung injury process and that the functional inhibition of a portion of the arachidonic acid cascade was not sufficient to either prevent or attenuate hyperoxic lung injury in newborn rabbits.

Anticardiolipin antibody-positive serum enhances endothelial cell platelet-activating factor production.

Circulating antiphospholipids have been linked to recurrent pregnancy loss by a mechanism involving placental and decidual thrombosis. We hypothesized that platelet-activating factor, an autacoid synthesized by vascular endothelium, might mediate this phenomenon through its ability to promote platelet aggregation and fibrin deposition. Alternatively, antiphospholipid antibodies might exert a procoagulant effect by inhibiting the synthesis of prostacyclin. To evaluate these theories, endothelial cells (harvested from human umbilical veins) were grown to confluence and incubated for 48 hours with 20% concentrations of anticardiolipin antibody-positive and -negative human sera as well as fetal bovine serum. After incubation culture wells were stimulated with 10 mumol/ml calcium ionophore A23187 (an agonist of platelet-activating factor and prostacyclin synthesis). Intracellular platelet-activating factor was measured by tritiated acetate incorporation, phospholipid extraction, thin-layer chromatography, and scintillation spectrophotometry. Enhanced platelet-activating factor synthesis was identified in cultures incubated with anticardiolipin antibody-positive serum (25,544 +/- 2604 disintegrations per minute, mean +/- SD) when compared with anticardiolipin antibody-negative serum (18,600 +/- 3316 dpm) or fetal bovine serum (19,014 +/- 4233 dpm; analysis of variance, p = 0.033). In similar experiments, prostacyclin synthesis was determined by measuring its primary metabolite, 6-keto-prostaglandin F1 alpha, in culture supernatants. No differences between anticardiolipin antibody-positive and control cultures were observed (analysis of variance, p = 0.90). We conclude that in this endothelial cell model, anticardiolipin antibody-positive serum enhances ionophore-mediated platelet-activating factor synthesis but has no apparent effect on the production of prostacyclin. These findings suggest a potential role for platelet-activating factor in anticardiolipin antibody-mediated vascular thrombosis.

Circulating plasma platelet activating factor in persistent pulmonary hypertension of the newborn.

Platelet activating factor (PAF) is an endogenous phospholipid mediator that causes pulmonary hypertension and thrombocytopenia in experimental animal models. To investigate circulating PAF in persistent pulmonary hypertension of the newborn (PPHN), we studied PAF and its degradative enzyme, acetylhydrolase. Thirteen neonates with PPHN, diagnosed by routine clinical methods including echocardiography, were compared to six age-matched control patients with respiratory distress. Overall, plasma PAF levels were elevated in patients with PPHN compared to control patients (20.1 +/- 3.9 versus 1.6 +/- 0.7 ng/ml, p less than 0.01). In addition, plasma PAF concentrations in patients with PPHN correlated with the severity of disease as defined by the delta AaPO2 (r = 0.65, p = 0.015). In three patients with elevated PAF levels, as the clinical status improved, the plasma PAF values decreased. Acetylhydrolase activity was similar in both groups (3.96 +/- 0.90 versus 3.78 +/- 1.44 nmol/ml/min, p = NS). We conclude that PAF production is increased in PPHN and that abnormal production of PAF may be associated with pulmonary hypertension.

National survey of diagnosis and management of persistent pulmonary hypertension of the newborn.

The diagnosis and management of persistent pulmonary hypertension of the newborn remains controversial. A national survey was performed to analyze recent trends in the incidence, diagnosis, management, and survival of patients with persistent pulmonary hypertension of the neonate. Sixty-six institutions from all geographical regions responded. The overall admission incidence was 3.9% +/- 2.6%. Secondary persistent pulmonary hypertension of the neonate was more common than primary. Unexplained hypoxemia, ductal level right-to-left shunting, echocardiography, and a positive response to hyperventilation were all used frequently (in at least 79% of institutions) to diagnose persistent pulmonary hypertension of the neonate. The majority of institutions considered a positive response to hyperventilation to be determined by an increase of PaO2 by 30 mm Hg with a concomitant decrease in PaCO2 to 25 mm Hg. Approximately 70% of institutions use varying ventilator techniques (ie, with or without hyperventilation), but the majority use hyperventilation predominantly. Almost all (greater than 90%) institutions used muscle paralytic agents and pulmonary vasodilators. Tolazoline was the first choice of pulmonary vasodilator therapy. The overall survival rate of persistent pulmonary hypertension of the newborn was 77.4% +/- 13.4%. Survival rate did not differ between different geographic areas of the country. There was a trend noted for improved survival with less use of muscle paralyzing agents. Yet despite varying treatment protocols, survival rates are improving.

Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis.

Because previous investigations have suggested that platelet activating factor and tumor necrosis factor-alpha (TNF-alpha) are important mediators of experimental necrotizing enterocolitis in the rat, we measured platelet activating factor, acetylhydrolase (the platelet activating factor breakdown enzyme), and TNF-alpha in the plasma of 12 human neonates with necrotizing enterocolitis and eight age-matched control subjects with similar gestational ages, postnatal ages, and weights. Almost all patients with necrotizing enterocolitis had elevated plasma platelet activating factor values (18.1 +/- 3.6 ng/ml vs. 3.1 +/- 0.9 ng/ml in control subjects, p less than 0.01). Plasma acetylhydrolase activity was lower in patients than in control subjects (10.6 +/- 0.7 nmol/ml/min vs 23.0 +/- 1.4 nmol/ml/min, p less than 0.01). Plasma TNF-alpha concentration was significantly elevated in patients with necrotizing enterocolitis (136 +/- 75 U/ml vs 1.5 +/- 0.8 U/ml, p less than 0.05), although the individual variation was high. There was no correlation between individual TNF-alpha and platelet activating factor levels. We conclude that platelet activating factor and TNF-alpha are elevated in patients with necrotizing enterocolitis and that suppressed platelet activating factor degradation contributes to the increased platelet activating factor levels; platelet activating factor and TNF-alpha may contribute to the pathophysiology of necrotizing enterocolitis.

Perinatal management of meconium staining of the amniotic fluid.

The pathogenesis of meconium passage and the pathophysiology of meconium aspiration are reviewed. Intrapartum and neonatal strategies for the prevention of meconium aspiration syndrome are presented in historical perspective, and newer interventions are appraised.