Relationship between serum inositol concentration and development of retinopathy of prematurity: a prospective study.

PURPOSE: To examine the relationship between the intake of sugar inositol, serum inositol levels, and ROP in three groups of low birthweight infants receiving feedings containing various concentrations of inositol. METHODS: Infants with a birthweight <1500 g, with severe lung disease, were eligible for the study when they began enteral feedings. Infant formulas contained three different inositol concentrations: 2500, 710, and 242 micromol/L. Serum inositol concentrations were averaged over specific time intervals. A logistic regression model was used to investigate the confounding effect of duration of mechanical ventilation and oxygen therapy, birthweight, Apgar score, and serum inositol concentration on development of ROP. RESULTS: Infants receiving high inositol formula and with higher serum inositol concentrations at birth and after 30 days had a statistically significant lower incidence of severe ROP than those receiving the lower inositol formula and with lower serum concentrations (P<.05). The effective serum inositol concentration (EC90) associated with lesser disease was >215 micromol/L. By logistic regression, the odds of developing severe ROP were greater among infants with low serum inositol concentration (odds ratio=4.7, 95% confidence interval 0.90-24.8, P=.017). CONCLUSION: Inositol supplementation may help prevent the most severe form of ROP.

Survival and neutrophil kinetics in infants with severe group B streptococcal disease treated with gamma globulin.

To estimate the efficacy of intravenous gamma globulin adjunct therapy on the course of severe neonatal group B streptococcal (GBS) disease, the hospital records of 67 confirmed cases of early-onset GBS sepsis associated with neutropenia were reviewed. Among the 33 infants who had received antibiotic agents without gamma globulin, 13 (39%) died. Among the 34 who had received antibiotic agents plus gamma globulin, 6 (18%) died (p < 0.05). Among 52 low birth weight infants, 5 (20%) of the 25 given gamma globulin died compared with 13 (48%) of the 27 not given gamma globulin (p < 0.03). Neutrophil counts rose more rapidly among survivors who received gamma globulin than among those who did not. This retrospective study suggests that intravenous gamma globulin adjunct therapy for neonatal GBS disease associated with neutropenia promotes a more rapid increase in neutrophil count and improves survival.

Metabolism and disposition of indomethacin in preterm infants.

38 preterm infants with symptomatic patent ductus arteriosus received indomethacin intravenously. Plasma samples were collected at 2, 4, 6 or 8 and 12 h after each of 3 doses. Indomethacin, demethylindomethacin and p-chlorobenzoic acid were determined in plasma and urine along with acid-labile metabolites using HPLC. Fifty-eight percent of the infants demethylated indomethacin; half of the unchanged and demethylated drug was found as conjugates in urine; 14% deacylated the drug. Shorter elimination half-life, smaller area under the plasma concentration-time curves and increased plasma clearance were associated with demethylation. Postnatal age greater than 2 weeks correlated with both demethylation and failure of indomethacin to effect ductal closure.

Intravenous gamma globulin as adjunct therapy for severe group B streptococcal disease in the newborn.

Group B streptococcal (GBS) disease remains a significant cause of morbidity and mortality among newborns despite aggressive antibiotic and supportive therapy. Recent success with the prophylactic use of intravenous gamma globulin (IVIg) in newborns suggests that use of IVIg may be an additional therapy for infants with severe GBS disease. Eighty-four infants with GBS antigen in serum, urine, and in some cases spinal fluid were identified by a rapid latex agglutination assay. Twenty-four of these infants had both neutropenia and serum GBS antigen titers of 1:10 or greater and had the highest risk of dying from their infection. Before the availability of IVIg, seven of the first 12 of these infants identified with the highest risk factors died (58%). Twelve additional patients with these highest risk factors have been treated with IVIg. Two of these 12 died (17%), p less than 0.01 when compared with the previous highest risk group. In surviving patients in both IVIg-treated and non-IVIg-treated groups, the time for recovery from neutropenia was 2 to 4 days. Our study suggests a possible beneficial effect of IVIg as adjunct therapy in severe GBS disease.

Serum alpha-tocopherol concentrations in preterm infants receiving less than 25 mg/kg/day alpha-tocopherol acetate supplements.

Alpha-tocopherol (aT) concentrations were determined in 52 preterm infants receiving less than 25 mg/kg/day alpha-tocopherol acetate (aTA) supplements through intravenous hyperalimentation solutions, lipid, and oral aTA. One fourth of the study infants had aT concentrations greater than 3.5 mg/dl at least once, and an association between concentrations greater than 3.5 mg/dl and necrotizing enterocolitis was demonstrated. In contrast, another one fourth of the infants' concentrations remained less than 0.5 mg/dl through the first postnatal week. The highly variable serum tocopherol concentrations correlated with total serum lipid content but not with plasma aTA hydrolysis activity.

Rapid diagnosis of group B streptococcal infection utilizing a commercially available latex agglutination assay.

The Wellcogen Strep B latex assay rapidly identifies all cases of culture-positive sepsis and meningitis and may be more sensitive than standard culture techniques for identifying group B Streptococcus disease and assessing the degree of severity. The quantitation of antigen concentration combined with the peripheral WBC count proves helpful in predicting poor outcome.

Gentamicin disposition in asphyxiated newborns: relationship to mean arterial blood pressure and urine output.

The purpose of this study was to investigate the effects of changes in renal function on gentamicin disposition following perinatal asphyxia. Gentamicin pharmacokinetics, renal function, mean arterial pressure (MAP) and five-minute Apgar scores were determined in 80 preterm infants admitted to two neonatal intensive care units over an 18 month period. A 2.5 mg/kg dose of gentamicin was infused intravascularly over 20 to 30 minutes in a retrograde fashion. The gentamicin half-life and clearance were prolonged in asphyxiated infants. For the asphyxiated infants gentamicin half-life increased and urine output decreased with a significant correlation (r = -0.66, p less than 0.05). Gentamicin clearance and urine output in the asphyxia group correlated with MAP (r = +0.67, p = 0.07). In non-asphyxia infants no such correlation was seen. This study does not distinguish between asphyxia-induced or gentamicin-induced nephrotoxicity following gentamicin therapy. We suggest that gentamicin concentrations be closely monitored in asphyxiated newborns who demonstrate compromised renal function.

Indomethacin and the preterm infant with a patent ductus arteriosus: relationship between plasma concentration and ductus closure.

The relationship of indomethacin pharmacokinetics to clinical and echocardiographic evidence of closure of the patient ductus arteriosus (PDA) is described in 9 preterm infants. PDA closures occurred in 4 infants when peak indomethacin plasma concentrations were 0.71-1.10 micrograms/ml, mean 0.93 +/- 0.16 microgram/ml. With partial or no PDA response to oral treatment, the peak concentrations were 0.20-0.69 microgram/ml, mean 0.57 +/- 0.08 microgram/ml, p less than 0.01. The left atrial size in the study infants correlated inversely with the indomethacin peak concentrations, r = 0.75. The plasma apparent terminal half-life correlated with postnatal age, r = 0.75. All patients with peak concentrations greater than 0.50 microgram/ml had transient oliguria. This study suggests that a minimum indomethacin concentration may be needed to promote PDA constriction.

Effect of indomethacin on desoxycorticosterone acetate-sodium chloride-induced renal lesions in the pregnant rat and her offspring.

To explore the effects of inhibition of prostaglandin synthesis on renal lesions, 37 female rats were made hypertensive and of these, 22 were treated with indomethacin. The blood pressure (207 +/- 5 mm Hg) in the indomethacin group was significantly (p < 0.01) higher than the blood pressure (191 +/- 7 mm Hg) in the control group. Weight changes were not significantly different. Renal lesions of varying severity were noted in mothers and offspring of both groups. The lesions ranged from thickening of the basement membranes to glomerular congestion, some with nearly complete eradication of glomerular architecture. Although the lesions appeared to be more marked in the indomethacin-treated group, no specific pattern of lesion location nor significant differences in the severity of the lesions was demonstrated. These data suggest that the lesions noted were the result of the hypertension. However, exacerbation by indomethacin could not be excluded.

Problems with a walking donor transfusion program.

A walking donor transfusion program is outlined in detail. A total of 205 transfusions from 72 walking donors were given to 57 newborns in a Newborn Intensive Care Unit over a nine-month period. The average recipient weighed 1,762 g and the average transfusion was 15 ml of blood. Because a suitable walking donor was not always available when a transfusion was needed, 19 units of regular adult blood were also used to support the program. No immediate or delayed transfusion reactions were noted, but one fatal incident of serum hepatitis transmission occurred. Our experience suggests that a walking donor program carries an inherent significant risk of transmission of hepatitis and alternative methods with strict blood bank control are needed to assure maximum safety in neonatal transfusion.

Pedi-pack transfusion in a newborn intensive care unit.

Two hundred and ninety-one transfusions using 221 pediatric frozen red blood cell packs (Pedi-Packs) were given to 141 newborn babies and infants in the newborn intensive care unit. In 18 patients, 47 transfusions were studied for transfusion and clinical characteristics. Two possible hemolytic episodes are described in detail and remain unexplained. Blood loss for laboratory tests was found to average 3.1 ml/kg per day spent in the newborn intensive care unit. The rise in hematocrit was found to be excellent. Overall, the transfusion of thawed pediatric red blood cell packs was found to be convenient, safe and effective. Because of pretesting possibilities with the use of this source of red blood cells, one of the problems associated with a walking donor program is eliminated.