Joseph A. Garcia-Prats

Retrolental Fibroplasia: Efficacy of Vitamin E in a Double-Blind Clinical Study of Preterm Infants

We performed a double-blind study in 101 preterm infants who weighed less than or equal to 1500 g at birth, who had respiratory distress, and who survived for at least four weeks, to evaluate the efficacy of oral vitamin E in preventing the development of retrolental fibroplasia. Weekly indirect ophthalmologic examinations begun when the infants were three weeks old revealed a significant decrease in the incidence of retrolental fibroplasia greater than or equal to Grade III (P less than 0.03) and greater than or equal to Grade II (P less than 0.05) (McCormick classification) in the 50 infants given 100 mg of vitamin E per kilogram of body weight per day as compared with 51 given 5 mg per kilogram per day (controls). When multivariate analysis was applied to the controls, five risk factors were identified: gestational age, level and duration of administration oxygen, intraventricular hemorrhage, sepsis, and birth weight. When multivariate analysis was applied to both control and treatment groups, the severity of retrolental fibroplasia was found to be significantly reduced in infants given 100 mg of vitamin E (P = 0.012).

Influenza A virus outbreak in a neonatal intensive care unit.

BACKGROUND Nosocomial infections with influenza virus are rarely recognized in neonatal intensive care units (NICU). An outbreak of influenza A virus infection in the NICU of an urban county hospital during the 1997 to 1998 influenza season is reported. METHODS Clinical and virologic data were recorded in all symptomatic NICU patients after influenza A infection was diagnosed in one infant in October, 1997. RESULTS Influenza A/H3N2 was isolated from two of four symptomatic infants. The application of rapid diagnostic techniques for the characterization of influenza virus infection allowed the timely institution of basic infection control measures, limiting this outbreak. Resistance to amantadine was documented for the first time in this patient population by reverse transcription-PCR within 48 h of treatment in one case. CONCLUSIONS Prevention by immunization is a priority in those caring for high risk NICU patients.

Improved outcome at 28 days of age for very low birth weight infants treated with a single dose of a synthetic surfactant

Two identical double-blind, controlled, randomized trials were initiated to determine whether the administration of a single 5 ml/kg dose of a synthetic surfactant (Exosurf Neonatal), soon after the delivery of infants with birth weights 700 to 1350 gm, would improve rates of survival without bronchopulmonary dysplasia. Both trials were terminated before enrolling their planned sample sizes because of the availability of Exosurf under the provisions of a Treatment Investigational New Drug program. We report the combined results of these trials. Study infants were stratified according to birth weight and gender before random assignment to a treatment regimen. One hundred ninety-two infants received Exosurf and 193 received an air placebo. The study groups were similar when a variety of demographic features describing the mothers, their pregnancies, the circumstances of the births, and the infants were compared. Exosurf-treated infants required significantly less oxygen and respiratory support during the first 3 days of life in comparison with the air-treated infants. Fewer infants in the Exosurf group had pulmonary interstitial emphysema (26 vs 13; p = 0.028). In the Exosurf group, there was a significant reduction in the combined outcome, neonatal death or survival with bronchopulmonary dysplasia (57 vs 39; p = 0.042), and there was a significant increase in rates of survival without this disease (128 vs 137; p = 0.042). There were no differences between treatment groups in the incidences of a variety of complications of prematurity, including apnea, patent ductus arteriosus, intraventricular hemorrhage, and necrotizing enterocolitis. We conclude that improvements in respiratory physiology after a single prophylactic dose of Exosurf result in an increased likelihood of neonatal survival without bronchopulmonary dysplasia.

Rapid Detection of Microorganisms in Blood Cultures of Newborn Infants Utilizing an Automated Blood Culture System

Background. Neonatal sepsis is a low incidence, high-risk disease with many sepsis work-ups performed to detect a single case. Seventy-two hours of antibiotic therapy have been traditionally recommended pending negative culture results. Improved culture media and new technology integrated into blood culture systems could shorten incubation time required to detect positive culture results. This would then change the length of antibiotic therapy in the management of the newborn infant with suspected sepsis. In addition, previous data supporting the 72-hour recommendation were retrospectively acquired, utilized nonautomated systems, and reported in an era with a different population of microorganisms cultured in special care nurseries. Objective. Evaluate the time of incubation to detect positive blood cultures from newborn infants with suspected sepsis using a computer-assisted, automated blood culture system, ESP (Trek Diagnostic Systems, Inc, Westlake, OH). Design. Prospective, observational study. Patients and Setting. All positive blood culture results that were obtained from term and preterm newborn infants born from November 1993 through June 1997 at a publicly funded hospital with over 6000 live births per year. Methods. As positive blood culture results were identified, data were prospectively obtained from the patients medical record. The computer algorithm in the automated blood culture system determined the time to positivity. Time to positivity was determined for blood cultures obtained before the initiation antimicrobial therapy and compared with those cultures obtained after beginning therapy. Time to positivity was also evaluated for clinically important Gram-positive and Gram-negative bacteria and yeast. Results. Four hundred fifty-five positive blood culture results were obtained from 222 patients. Gram-positive organisms accounted for 80% (366/455) of the positive culture results, Gram-negative organisms accounted for 11% (48/455), and yeast for 9% (41/455). Virtually all cultures growing clinically significant Gram-positive and Gram-negative organisms were positive by 24 to 36 hours of incubation. Cultures growing Staphylococcus epidermidis were virtually all positive after 36 to 48 hours of incubation. Of cultures growing yeast, 88% (36/41) were positive by 48 hours of incubation. There was no difference in time to positivity in pretherapy or posttherpay obtained positive blood cultures. Prenatally administered antibiotics did not affect time to positivity in positive cultures drawn on the first day of life. In a selected group of microorganisms that are the frequent cause of bacteremia in term infants, 97% and 99% of cultures were positive by 24 to 36 hours of incubation when only pretherapy cultures are evaluated. Conclusions. The ESP blood culture system identified 77%, 89% and 94% of all microorganisms at 24, 36, and 48 hours of incubation in aerobic cultures obtained from both term and preterm infants. Introduction of antimicrobial therapy did not affect time to positivity. Reducing duration of antibiotic therapy to 24 to 36 hours should be considered in term, asymptomatic newborn infants undergoing evaluation for suspected sepsis for maternal indications. Confirmation of similar rapidity of detection using other blood culture systems should be undertaken.

An outbreak of M serotype 1 group A Streptococcus in a neonatal intensive care unit

OBJECTIVE To describe the investigation and control of an outbreak of M serotype 1, Streptococcus pyogenes (group A Streptococcus, GAS) infections in a neonatal intensive care unit (NICU). STUDY DESIGN The study was conducted in an NICU in a large urban university-affiliated hospital. Retrospective review was performed of all infants and health care workers in the NICU, especially those either colonized or infected with GAS during the outbreak and the prospective surveillance period (July through September 1994). Prospective epidemiologic investigation, including cultures of throat, umbilicus, and anorectum (infants), or throat and anus (NICU personnel), identified a possible common source of the disease in case infants. Antimicrobial susceptibility testing and serotyping of all GAS strains were performed; M serotype 1 isolates were examined by DNA analysis with restriction fragment length polymorphism. The M-1 GAS isolates were tested for streptococcal pyrogenic exotoxin (SPE) A and SPE B production. A retrospective chart review and analysis of infants with GAS infection or colonization was conducted. RESULTS During a 1-week period, two very low birth weight infants more than 3 weeks of age had GAS septicemia and focal infection. Two additional very low birth weight infants with asymptomatic throat colonization were identified during the first week of surveillance. Benzathine penicillin G was administered to all NICU infants, but failed to eradicate throat colonization in the four case subjects. Seven days after completing parenteral antibiotic therapy, the index patient had a recurrence of GAS septicemia that was fatal. Eradication of throat colonization in the remaining three infants was achieved with a 10-day course of intravenous clindamycin therapy. Among 103 NICU personnel, five (4.9%) had asymptomatic GAS colonization with strains that were uniformly susceptible to penicillin. Each colonized adult was successfully treated with oral clindamycin therapy. Serotyping revealed that five isolates of GAS from four infants and one NICU respiratory therapist were M-1 isolates; DNA analysis confirmed that these were the same strain. The five M-1 isolates produced both SPE A and SPE B. CONCLUSIONS The previously documented increase in prevalence of M-1 strains of GAS in the United States is likely to be associated with their introduction into closed populations including NICUs. Control of such outbreaks may be achieved by isolation, cohorting of case subjects and possible carriers, and successful eradication of colonization in case subjects and carriers. Although GAS organisms are uniformly susceptible to penicillin G, eradication may require agents other than penicillin.

Hyaline membrane disease and intraventricular haemorrhage in small for gestational age infants.

19 small for gestational age (SGA) infants with gestational ages less than or equal to 32 weeks were matched with 19 appropriate for gestational age (AGA) preterm neonates with similar risk factors for intraventricular haemorrhage and hyaline membrane disease. Gestational age, 1- and 5-minute Apgar scores, type of delivery, survival rate, use of corticosteroids before delivery, sex, twinning, presence of premature rupture of membranes, and birth date were comparable in the two groups. Gestational age of both groups was 30 (+/- 1.8) weeks, and birthweights were 919 (+/- 202) g (SGA group) and 1268 (+/- 212) g (AGA group). The incidences of hyaline membrane disease and intraventricular haemorrhage were different: 74 and 42% respectively for AGA neonates, 5 and 11% respectively for SGA infants. We suggest that a stressful environment in utero may enhance maturation and prevent hyaline membrane disease and intraventricular haemorrhage.

Phase 1/2 Double-Blind, Placebo-Controlled, Dose Escalation, Safety, and Pharmacokinetic Study of Pagibaximab (BSYX-A110), an Antistaphylococcal Monoclonal Antibody for the Prevention of Staphylococcal Bloodstream Infections, in Very-Low-Birth-Weight Neonates

ABSTRACT Staphylococcal sepsis is a major cause of morbidity and mortality in very-low-birth-weight (VLBW) infants. A human chimeric monoclonal antibody, pagibaximab, was developed against staphylococcal lipoteichoic acid. We evaluated the safety, tolerability, and pharmacokinetics of pagibaximab in VLBW neonates. A phase 1/2, randomized, double-blind, placebo-controlled, dose escalation study was conducted in VLBW infants (700 to 1,300 g) 3 to 7 days old. Patients received two doses 14 days apart of intravenous pagibaximab (10, 30, 60, or 90 mg/kg of body weight) or placebo in a 2:1 ratio. Blood and urine samples were obtained pre- and postinfusion for analysis of safety and pharmacokinetics, and data on adverse events were gathered. Staphylococcal organisms causing sepsis were collected and evaluated. Fifty-three patients received at least one dose of pagibaximab or placebo. The average gestational age was 27.6 weeks; the average birth weight was 1,003 g. All serious adverse events were deemed unrelated or probably not drug related. Morbidity and mortality were similar across treatment groups. No evidence of immunogenicity of pagibaximab was detected. Pagibaximab pharmacokinetics was linear. The mean clearance (CL), volume of distribution, and elimination half-life of pagibaximab were independent of dose. The serum half-life was 20.5 ± 6.8 days. Pagibaximab enhanced serum opsonophagocytic activity. All staphylococci causing sepsis were opsonizable by pagibaximab. Two infusions of pagibaximab, administered 2 weeks apart to high-risk neonates appeared safe and tolerable, and pharmacokinetics were linear. Evaluation of more frequent doses, at the highest doses tested, in neonates at high-risk of staphylococcal sepsis, is warranted.

Necrotizing enterocolitis: Incidence, operative care, and outcome

At Jefferson Davis Hospital, the incidence of necrotizing enterocolitis (NEC) was three per 1,000 live births, and 30 per 1,000 low birth weight births. The occurrence of NEC was sporadic and no epidemics occurred. NEC occurred most frequently in infants weighing between 750 and 1,500 g, and the smaller infant with NEC was more likely to require surgical intervention. As the survival of small birth weight infants improved over the 4 years of the study, the patient population developing NEC became smaller. The age at operation also increased in the period between 1982 and 1984. Those infants who developed NEC after 30 days of age typically had more extensive disease and a less favorable prognosis. In this series, 31% of infants with acute NEC required surgical intervention. An additional 11% of those infants treated nonoperatively eventually required surgical intervention for late sequelae of NEC. The overall survival of infants with NEC was 75%. While the survival of all infants operated for NEC was 68%, the survival for those with the acute syndrome was 63% and those operated on for late sequelae was 87%. Primary anastomosis in selected patients did not adversely affect mortality and simplified the postoperative care of these infants with severe complications. Indeed, enterostomy closure in an infant who had previously had NEC was an extensive procedure that carried significant risk. Our results indicated that the trained pediatric surgeon could predict at the operating table which infants could safely undergo resection and anastomosis and that, with experience, the percent undergoing primary anastomosis increased to approximately 50%.

Early neurodevelopmental outcome of low birth weight infants surviving neonatal intraventricular hemorrhage

Neonatal intraventricular hemorrhage has emerged äs one of the most important and frequently encountered lesions in the central nervous System of the prematurely born infant [1]. Intraventricular hemorrhage is known to contribute significantly to neonatal mortality and morbidity. However, information regarding its effects on the long-term outcome of survivors is limited. This report describes the early neurodevelopmental Status of twenty-eight low birth weight infants surviving symptomatic neonatal intraventricular hemorrhage documented by computerized tomography and relates outcome to gestational age and grade of hemorrhage based on severity and location [2].

AN ASSOCIATION BETWEEN RETINOPATHY OF PREMATURITY AND INTRAVENTRICULAR HEMORRHAGE IN VERY LOW BIRTH WEIGHT INFANTS

ABSTRACT Procianoy, R. S., Garcia‐Prats, J. A., Hittner, H. M., Adams, J. M. and Rudolph, A. J. (Department of Pediatrics, Baylor College of Medicine, Texas Childrens Hospital, Houston, Texas). An association between retinopathy of prematurity and intraventricular hemorrhage in very low birth weight infants. Acta Paediatr Scand, 70:473,.–An association between cicatricial retinopathy of prematurity and intraventricular hemorrhage in very low birth weight infants was investigated retrospectively. Newborns were studied who weighed ≤1500 g at birth, who were ≤32 weeks gestational age and appropriate by weight, and admitted in the first 24 hours of life to our Neonatal Intensive Care Unit. Diagnosis of retinopathy of prematurity was made by retinal examination at approximately 4 weeks of age. Diagnosis of intraventricular hemorrhage was made by computerized tomography and clinical findings. A total of 138 infants were studied and divided into two groups: (A) birth weight ≤1000 g (31); (B) birth weight 1 001–1 500 g (107). There was a statistically significant association between cicatricial retinopathy of prematurity and intraventricular hemorrhage in both groups. There were no statistical differences between birth weight, gestational age, duration of oxygen therapy, highest oxygen concentration received, Apgar scores, incidence of hyaline membrane disease and patent ductus arteriosus between cicatricial retinopathy of prematurity and no retinopathy of prematurity patients in either group. This association may be an important consideration in the pathogenesis of both vascular diseases.