Robert J. Boyle

NIH consensus development conference statement: Inhaled nitric-oxide therapy for premature infants

Premature birth is a major public health problem in the United States and internationally. Infants born at or before 32 weeks gestation (2% of all births in the United States in 2007) are at extremely high risk for death in the neonatal period or for pulmonary, visual, and neurodevelopmental morbidities with lifelong consequences including bronchopulmonary dysplasia, retinopathy of prematurity, and brain injury. Risks for adverse outcomes increase with decreasing gestational age. The economic costs to care for these infants are also substantial (estimated at

Patterns of fungal colonization in preterm infants weighing less than 1000 grams at birth

26 billion in 2005 in the United States). It is clear that the need for strategies to improve outcomes for this high-risk population is great, and this need has prompted testing of new therapies with the potential to decrease pulmonary and other complications of prematurity. Inhaled nitric oxide (iNO) emerged as one such therapy. To provide health care professionals, families, and the general public with a responsible assessment of currently available data regarding the benefits and risks of iNO in premature infants, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Heart, Lung, and Blood Institute, and the Office of Medical Applications of Research of the National Institutes of Health convened a consensus-development conference. Findings from a substantial body of experimental work in developing animals and other model systems suggest that nitric oxide may enhance lung growth and reduce lung inflammation independently of its effects on blood vessel resistance. Although this work demonstrates biological plausibility and the results of randomized controlled trials in term and near-term infants were positive, combined evidence from the 14 randomized controlled trials of iNO treatment in premature infants of ≤34 weeks gestation shows equivocal effects on pulmonary outcomes, survival, and neurodevelopmental outcomes.

Fluconazole Prophylaxis in Extremely Low Birth Weight Infants and Neurodevelopmental Outcomes and Quality of Life at 8 to 10 Years of Age

Background: Colonization with Candida spp. is an important risk factor for systemic infection in very low birth weight (VLBW; <1500 g) and extremely low birth weight (ELBW, <1000 g) infants. ELBW infants are at a higher risk than VLBW infants for fungal sepsis and its associated mortality, but few studies have examined fungal colonization exclusively in ELBW infants. Methods: Fungal colonization data were analyzed retrospectively in 50 high risk ELBW infants. Weekly surveillance fungal cultures of the skin, gastrointestinal tract, respiratory tract and umbilicus had been performed from birth through the first 6 weeks of life. Colonization was analyzed for time of initial colonization, site, species and spread of Candida from one site to another. Results: Candida was isolated from surveillance cultures in 31 of 50 (62%) infants. Colonization was inversely proportional to gestational age. Initial week of both the fungal colonization of the skin [1 (0–6) week, median (range)] and gastrointestinal tract [2 (0–6)] preceded colonization of the respiratory tract [3 (1–6)] (P = 0.0001). Among infants colonized by only 1 of the species, colonization at 2 or more sites occurred similarly with Candida albicans (77%) and Candida parapsilosis (85%), whereas colonization at 3 or more sites occurred more frequently with C. albicans (69%) compared with C. parapsilosis (23%) (P = 0.047). Conclusions: Fungal colonization occurs on the skin and gastrointestinal tract before the respiratory tract. In addition, C. albicans is more likely than C. parapsilosis to colonize multiple sites.

Parental rights at the birth of a near-viable infant: Conflicting perspectives

OBJECTIVEnTo examine the long-term effects of fluconazole prophylaxis in extremely low birth weight infants.nnnSTUDY DESIGNnNeurodevelopmental status and quality of life of survivors from a randomized, placebo-controlled trial of fluconazole prophylaxis were evaluated at 8 to 10 years of life using the Vineland Adaptive Behavior Scales-II (VABS-II) and the Child Health Questionnaire Parent-Completed Form 28 (CHQ-PF28), respectively.nnnRESULTSnVABS-II Domain Scores for the fluconazole-treated (n = 21; 9.1 ± 0.7 years) compared with the placebo group (n = 17; 9.3 ± 0.8 years) were similar for communication [94.6 (±14.8) versus 92.6 (±12.6), P = .65], daily living skills [87.9 (±10.6) versus 87.4 (±9.3), P = .89], socialization [97.2 (±9.2) versus 94.4 (±7.9), P = .31], and motor skills [92.1 (±17.8) versus 95.1 (±14.6), P = .57]. Internalizing and externalizing behaviors and maladaptive behavior index were also similar. The CHQ-PF28 revealed no differences between the two groups regarding quality of life. Survivors were also happy or satisfied with school (90% versus 100%, P = .49), friendships (90% versus 88%, P = 1.00), and life (95% versus 100%, P = 1.00). Self esteem scores were 87.3 ± 15.7 versus 89.7 ± 10.4 (P = .59). There were also no differences between groups regarding emotional difficulties or behavior problems.nnnCONCLUSIONSnFluconazole prophylaxis for the prevention of invasive Candida infections is safe in extremely low birth weight infants and does not appear to be associated with any long-term adverse effects on neurodevelopment and quality of life at 8 to 10 years of life.

Thrombocytopenia as the presenting manifestation of human T-lymphotropic virus type III infection in infants

OBJECTIVEnOur purpose was to clarify the roles of parents and caregivers in making decisions for resuscitation of near-viable infants.nnnSTUDY DESIGNnWe present two cases and review ethical and legal issues involved in making decisions for near-viable infants.nnnRESULTSnMedical responsibility for the infant shifts at birth from obstetrics to neonatology. Neonatologists will opt for life when prognosis is uncertain. As surrogate decision makers, parents have rights to make decisions about initiation of resuscitation, but these parental rights are limited by the infants best interests. If caregivers believe parents are not acting in the infants best interests, they may persuade parents, challenge parental refusal by petitioning the courts, or treat without consent with possible legal risk.nnnCONCLUSIONSnEffective communication is essential to prevent misunderstanding and conflicts. In most instances parents are the best decision makers for a near-viable infant. Parental rights are limited by best interests of the infant.

Transfusion-acquired human immunodeficiency virus infection in twelve neonates: epidemiologic, clinical and immunologic features.

Three infants between 8 and 9 months of age developed thrombocytopenia resulting from immune-mediated platelet destruction, as evidenced by the presence of serum antibody to platelets and elevated platelet-associated immunoglobulin G in two patients, and abundant bone marrow megakaryocytes in all patients. The patients had a satisfactory response to corticosteroid therapy, and platelet counts have remained normal during observation after therapy. All patients had serum antibody to human T-lymphotropic virus type III, and HTLV-III was isolated from the peripheral blood lymphocytes in two patients. The HTLV-III infections were presumably acquired via blood transfusions in the neonatal period; none of the patients mothers belonged to a risk group for HTLV-III infection, and all were HTLV-III seronegative. Although thrombocytopenia was the major clinical manifestation, the patients had a number of immunologic abnormalities characteristic of HTLV-III infection; these included hyperimmunoglobulinemia, a decreased proportion of peripheral blood T cells, and a marked reduction in the proportion of peripheral blood T helper-inducer lymphocytes. We conclude that the patients had immune-mediated thrombocytopenia caused by HTLV-III infection.

TRANSFUSION-ACQUIRED HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION IN NEONATES

Twelve neonates in 3 cohorts received blood transfusions from two donors who were infected with human immunodeficiency virus (HIV). All 12 infants developed laboratory and/or clinical evidence of HIV infection, usually in the first year of life. Ten of 12 infants had serum antibody to HIV when tested between 9 and 42 months of age. The two seronegative infants were severely hypogammaglobulinemic when they were tested. Nine infants developed a variety of illnesses attributable to HIV infection, but only 2 fulfilled criteria for the diagnosis of acquired immunodeficiency syndrome. In follow-up ranging from 2 1/2 to 4 years 5 patients (42%) have died. Four patients had HIV-associated illnesses but recovered and now have few if any symptoms attributable to HIV infection. Three children have never had signs or symptoms attributable to HIV. Immunologic abnormalities were present in all patients; the most consistent finding was a decrease in the proportion of T helper cells. Three patients had severe panhypogammaglobulinemia. The hypogammaglobulinemic infants had significantly lower numbers and percentages of T helper cells compared to the remaining patients (P less than 0.01). We conclude that exposure to HIV via transfusion in the neonatal period results in an extremely high rate of infection with substantial mortality and morbidity, but clinical recovery occurs in some patients. Also hypogammaglobulinemia may be more common in infants with HIV infection than previously appreciated.

Fluconazole Prophylaxis against Fungal Colonization and Infection in Preterm Infants

Eleven neonates received blood from two HIV infected donors. All developed laboratory and/or clinical evidence of HIV infection, usually in the first year of life. Nine of 11 had serum antibody to HIV when tested between 9 and 16 months of age; two seronegative infants were severely hypogammaglobulinemic when tested. Nine patients developed a variety of illnesses characterized by hepatosplenomegaly, lymphadenopathy, chronic diarrhea, failure to thrive, and thrombocytopenia. Infections, including pneumonia, mucocutaneous candidiasis, and sepsis were a major source of morbidity and mortality. Two children have remained continuously asymptomatic. In follow-up ranging from two to four years, five patients have died, four others had HIV associated illnesses, but recovered and are now healthy. All patients had immunologie abnormalities; the most consistent finding was a decreased proportion of T-helper cells. Three patients had panhypogammaglobulinemia. These infants had significantly lower numbers of T-helper cells compared to patients with normal or increased serum immunoglobulin concentrations (P=0.012). We conclude that exposure to HIV via transfusion in the neonatal period results in an extremely high rate of infection with substantial mortality and morbidity, but clinical recovery occurs in some patients. Second, hypogammaglobulinemia may be more common in infants with HIV infection than previously appreciated.