Arnold J. Rudolph

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).

Colobomatous microphthalmia, heart disease, hearing loss, and mental retardation--a syndrome.

A syndrome consisting of colobomatous microphthalmia, heart disease, abnormalities of the external ear with associated hearing loss, and mental retardation is described. Nine children and one adult were evaluated. There is not race or sex predilection. The syndrome can be heritable, as shown by a mother and daughter who were among the patients. In addition to the four major components enumerated, multiple other anomalies may be associated. In some cases, the syndrome may occur incompletely. Whenever two or more of the four components are recognized, the other systems usually affected should be investigated.

Congenital rubella encephalitis: Course and early sequelae†

Neurological abnormalities were noted at some time between birth and 18 months of age in 81 of 100 patients with congenital rubella infection. These included lethargy, full fontanel, irritability, and increased concentration of protein and persistence of virus in the cerebrospinal fluid. Of the 64 survivors 44 had a wide range of neurological abnormalities at 18 months of age including motor paresis, restlessness, motor mannerisms, and developmental delay. Retardation in growth, particularly of the head, was still manifest at 18 months. Pathological changes in central nervous system structures included leptomeningitis, vasculitis, and multifocal areas of parenchymal necrosis and perivascular calcification.

Transient hypertrophic subaortic stenosis in infants of diabetic mothers

Three newborn infants with congestive heart failure had hemodynamic, angiographic, and echocardiographic features of hypertrophic subaortic stenosis (hypertrophic obstructive cardiomyopathy). Treatment with digitalis and diuretic drugs was ineffective, but improvement occurred when these agents were withheld in one patient, and when treatment with propranolol was begun in two patients. Echocardiography was helpful in establishing the diagnosis in two patients and showed resolution of the condition during the first six months of life. Serial cardiac catheterizations confirmed resolution of the outflow obstruction in the third patient. Family studies revealed no evidence of familial cardiomyopathy, but the mothers of two infants had insulin-dependent diabetes mellitus and the mother of the third was presumed to be prediabetic.

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.

Idiopathic respiratory distress syndrome of the newborn

AN I N F O R M A L discussion of hyaline membrane disease or the respiratory distress syndrome was held on July 2I, I959, at the IX International Congress of Pediatrics in Montreal. The following were the participants: Dr. E. K. Ahvenainen, Jyvaskyla, Finland Dr . Dr. Dr. Dr. Dr. Dr Dr Dr. Dr. Dr Dr. Dr Dr Virginia Apgar, New York Peter Auld, Boston and Montreal Mary Ellen Avery, Baltimore Heinrich Baar, Pownal, Maine Kurt Benirschke, Boston Eric Burnard, New York Albert Claireaux, London Stewart Clifford, Boston Myron Cohen, Baltimore Charles Cook, Boston Beryl Corner, Bristol John Craig, Pittsburgh V. Mary Crosse, Birmingham

Fulminant neonatal sepsis and necrotizing enterocolitis associated with a “nonenteropathogenic” strain of Escherichia coli+

During 1973 a nonendemic mucoid strain of Escherichia coli entered the nursery of a hospital in Houston. This organism caused septicemia and was associated with a high incidence of necrotizing enterocolitis. The illness was fulminant and characterized by apnea, abdominal distension, and shock. Diarrhea was not a feature of the symptom complex. The epidemic organism was nontypable. Assays for invasiveness, enterotoxin production, and Kl antigen were negative. Surveillance revealed a colonization rate of 14%, an attack rate in colonized infants of 19.5%, and a mortality rate of 87.5%. These data suggest that in certain instances the specific bowel flora may increase the incidence and severity of NEC.

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.

Gentamicin disposition and effect on development of renal function in the very low birth weight infant

The steady-state pharmacokinetics, renal function and quantitative beta 2-microglobulin (beta 2-M) excretion were prospectively evaluated in 22 very low birth weight (VLBW) infants (700-1,470 g birth weight and 25-33 weeks gestational age) receiving 2.4 mg/kg gentamicin at randomly assigned 12- or 18-hour dosing intervals. Gentamicin trough concentrations were significantly lower in only those infants greater than 1,000 g birth weight on the 18-hour schedule (p less than 0.05). ESTRIP analysis of gentamicin disposition at steady state revealed a biexponential function with half-life (mean +/- SEM), 9.78 +/- 0.86 h, plasma clearance 0.64 +/- 0.06 ml/kg/min and volume of distribution 0.50 +/- 0.03 liter/kg. Serum creatinine at steady state correlated with half-life (p less than 0.01), plasma clearance (p less than 0.01), and trough levels (p less than 0.001). Despite the frequent occurrence of gentamicin trough levels persistently greater than 2.0 micrograms/ml, renal function matured normally as serum creatinine progressively decreased (p less than 0.001) and creatinine clearance progressively increased (p less than 0.001) with advancing conceptional age. Urinary excretion of beta 2-M, thought to be a marker of proximal tubular damage from gentamicin, did not correlate with elevated trough levels, and was in fact lower in those infants with the highest measured trough levels (p less than 0.001). Nephrotoxicity was suspected in only 2 infants both of whom had additional renal insult during the first few days of life. Despite the frequent occurrence of elevated gentamicin trough levels and prolonged elimination half-life in these VLBW infants, their renal function matured normally throughout therapy and nephrotoxicity from gentamicin, as evidenced by beta 2-microglobulinuria, did not occur.

Suppression of severe retinopathy of prematurity with vitamin E supplementation. Ultrastructural mechanism of clinical efficacy

Three clinical trials enrolling 418 infants (less than or equal to 1500 g birth weight) and an ultrastructural data base of 71 pairs of whole eye donations have elucidated the efficacy of vitamin E in suppressing the development of severe retrolental fibroplasia (ROP). Only continuous vitamin E supplementation to adult physiologic levels from the first hours of life suppresses the development of severe ROP. Supplementation does not increase the incidence of necrotizing enterocolitis, sepsis, intraventricular hemorrhage, or mortality. Only multivariate analysis, which considers all risk factors simultaneously, is appropriate when appraising the efficacy of supplementation since all the clinical risk factors uniquely impinge on the oxygen dynamics of the developing retina. Mesenchymal spindle cells are the cellular mediators of the induction of ROP by oxygen in which increased oxygen tension triggers extensive gap junction formation between adjacent spindle cells. This cellular event, which occurs as early as four days of life, halts the normal vasoformative process and triggers neovascularization, which becomes clinically evident some 8 to 12 weeks later.