Chari Otis

Effect of sustained pharmacologic vitamin E levels on incidence and severity of retinopathy of prematurity: A controlled clinical trial

The incidence and severity of retinopathy of prematurity (ROP) as affected by vitamin E prophylaxis at pharmacologic serum levels (5 mg/dl) were evaluated in a double-masked clinical trial of infants with a birth weight less than or equal to 2000 gm or a gestational age less than or equal to 36 weeks. The infants were enrolled by age 5 days and randomly assigned to receive parenterally administered, and later orally administered, free alpha-tocopherol (vitamin E) or its placebo. Study medication was continued until retinal vascularization was complete or active ROP had subsided, except in infants with a diagnosis of severe disease, in whom vitamin E was substituted for study medication. Acute ROP data were collected on 755 infants. Logistic regression analysis, with control for immaturity, oxygen exposure, and other illness risk factors, showed a decrease in incidence of ROP in vitamin E-treated infants (p = 0.003, all infants; p = 0.035, infants weighing less than or equal to 1500 gm at birth). Among the 424 infants weighing less than or equal to 1500 gm at birth, the age at enrollment influenced treatment effect (age day 0 to 1, p = 0.006 (n = 288) vs age day 2 to 5, p greater than 0.1 (n = 136]. Overall, 77.6% of infants with ROP had mild disease. Moderate to severe ROP was confined to infants weighing greater than or equal to 1500 gm at birth (25 given placebo, 25 given vitamin E), with progression to severe disease in nine placebo-treated versus three vitamin E-treated infants (p = 0.048). The incidence of severe ROP per se was not significantly decreased (all birth weights, p = 0.086; less than or equal to 1500 gm birth weight, p = 0.080); the sample size was too small, however, to assess this end point adequately. An increased incidence of sepsis and late-onset necrotizing enterocolitis was found among vitamin E-treated infants weighing less than or equal to 1500 gm at birth who received study medication for greater than or equal to 8 days (p = 0.006). Because most ROP is mild in degree and regresses completely, the risk/benefit ratio of pharmacologic prophylaxis for ROP is unfavorable. Treatment of moderate and severe ROP with vitamin E above physiologic serum levels (greater than 3 mg/dl) appears promising and should be further investigated. The interpretation of cicatricial outcome was confounded by the small number of patients involved and by subsequent treatment of severe ROP in placebo-treated infants with vitamin E.

VITAMIN E SUPPLEMENTATION AND THE RETINOPATHY OF PREMATURITY

The effect of high-dosage E treatment (Rx) initiated at the stage of 3-plus active disease (target serum E levels, 5-6 mg/dl) was evaluated by a standardized scoring system of visual morbidity at the one to two year eye exam among infants cared for in the University of Pennsylvania Neonatal Complex (1976-1978). The incidence of legal blindness in both eyes or worse was decreased from 71 to 40% in E Rx (n = 10) as compared to non-E Rx (n = 14) infants, and the number of infants with minimal visual morbidity was increased. Pilot studies (1972-76; target serum E level, 1.5 and 3.0 mg/dl) of the prophylactic effect of E Rx from birth on showed a decrease in mean severity of acute stage disease and a decrease in sequelae at one to two years. A strikingly difference in visual morbidity following resolved low-grade ROP was seen when prestudy infants (1968-72) who were fed early iron supplements and given formulas with low E:PUFA ratios were compared to non-E Rx as well as to E Rx 1972-76 infants. Vitamin E seems to exert a beneficial effect at all stages of ROP, perhaps because of its broadly based regulatory role.

1421 DOES BREAST MILK-TAURINE PROTECT AGAINST RETINOPATHY OF PREMATURITY (ROP)

Taurine (T) is essential to normal retinal function. It is present in high concentrations in human milk but virtually absent in infant formulas and parenteral feedings. Its concentration in the retina increases until about 2 months post a term birth. Deficiency results in retinal abnormalities. T appears to regulate membrane excitability, promote homeostasis and protect membranes against oxidant damage along with Zn and vitamin E. We therefore reviewed the records of 385 infants (216≤1500g BW, 169>1500<2000g BW, 1979-1981) to see if partial breast feeding (versus no breast feeding) influenced ROP. Mean serum E±SD during retinal vascular immaturity and mean ml blood received per kg BW (a marker for degree of illness) were similar between groups.Incidence of ROP was significantly decreased in infants who received breast milk (p<0.05, BW≤1500g; p<0.05, BW>1500g). The data suggest a protective effect of breast milk in ROP which may be related to improved taurine nutrition. Controlled clinical trials would appear to be in order.

BIRTHWEIGHT|[sol]|GESTATIONAL AGE PROFILES FOR METROPOLITAN PHILADELPHIA

Birthweight (BW) as a function of gestational age (GA) was evaluated for a broad spectrum of both urban and suburban population, in Philadelphia and the Delaware Valley, who delivered at Penna. Hosp. A total of 13467 live-births occurred at this institution during the years 1977 to 1981. The racial spectrum was 62% Black (49.7% females); 30% White (47.8% females); and 8% Hispanics, Orientals, Asians, etc. GA was calculated on the mothers dates, obstetrical evaluation and then, the clinical estimation of GA. The data was analyzed by a UNIVAC computer programmed to calculate the percentiles of BW for each week of GA (26 to 42 weeks) for the total population and ethnic subcategories. BW curves were developed for all data. Total population BW exhibited different values of central tendency and were statistically different from known curves (Fig 1). Statistically different curves were also developed on the basis of race and sex. Differences in geographic location, altitude and composition of ethnic populations probably account for these observations. These data emphasize the need to utilize local regional standards classification of neonates according to their GA, and thus predict the risk of their morbidity and mortality.

977 CORRELATION OF FETAL OUTCOME WITH ANTENATAL TESTING IN ISOIMMUNIZED PATIENTS

Sixty-seven pregnant women at risk for fetal isoimmunization were followed prospectively from 6/78–6/84 and scored by nonstress testing (NST) (reactive =2, nonreactive =0), amniotic fluid Δ 450 (slope: increasing =2, stable =1, decreasing =0), and fetal ultrasound (U/S) (erythroblastosis fetalis: none =2, minimal-moderate =1, moderate-severe =0). Postnatally, the 67 infants (GA 36.6±3.1 wks, mean±SD, BW 2850±656 grams) were independently scored without knowledge of the maternal score (living =2, dead =0; treatment: none =2, phototherapy =1, exchange transfusion =0; problems of prematurity: none =2, mild =1, moderate-severe =0). The mothers and infants were each assigned a rank from 1–10 according to their scores. A sign test (non-parametric) between the maternal and infant scores revealed no significant difference indicating agreement between rankings. The chi square goodness of fit for the distribution of scores when grouped as 1/2/3, 4/5/6/7, and 8/9/10 also indicated no significant differences in rankings. The correlation coefficient for infants rank against maternal rank was .76 at p<.001. No single antenatal test has thus far been shown to be predictive of neonatal outcome. We have shown prospectively that, in combination, NST, Δ450 and U/S can reliably predict severity of isoimmunization. The composite score can therefore be used to optimize timing of delivery with respect to the risks of prematurity and erythroblastosis fetalis.

606 LACK OF CORRELATION BETWEEN SERUM VITAMIN E AND TOTAL LIPID LEVELS IN PRETERM INFANTS

In adults and children there is a significant correlation between serum concentration of vitamin E (E) and total lipid (TL). Therefore use of the serum ratio of E to TL (E/TL) as a measure of E nutrition, rather than E alone, has been recommended. This ratio may not be useful in infants because of the higher proportion of polyunsaturated fats in their diets. In order to evaluate this relationship in neonates, 70 infants XBW 2085gm±502 SD, XGA 34.8wks±2.1 SD were studied. Serum E and TL were measured during the following time periods: (I) within a few hours of birth; (II) 1 week of age, NPO, on hyperalimentation (HAL) and Intralipid (IL); (III) after 1-2 weeks of combined enteral feeds. HAL, IL; (IV) 1–2 weeks after full enteral feeds.Multiple measurements within each group showed a significant correlation between E and TL (r=.43, p<.01) only in period I and if all babies were considered. The r value however was only 0.43, which reflects a relatively poor correlation. After exogenous nutrition was started (periods II-IV), there was no correlation between E and TL (r=.02-.34) in any birthweight group. Serial measurements of serum vitamin E levels appear to be the only practical means of monitoring E nutrition in the preterm neonate.

INCIDENCE OF INTRAVENTRICULAR HEMORRHAGE BY DELIVERY METHOD

The optimal method for delivery of the infant less than 1500 grams is still under debate. In order to assess this situation we examined the records of all infants born between June,1981 and Dec., 1982. During that 18 month period, 226 infants were delivered between 500 and 1500 gms. A total of 91 infants were born vaginally and 135 by C/section. All infants were inborn. The overall survival rate was 85%. For this study only non-asphyxiated infants (5 minute Apgar ≥ 7) were included, for a total of 155 infants. There were 60 infants born vaginally and 95 born by C/section. The mean birth weights were 1161±255 gms and 1153±231 gms respectively. All infants had a routine cranial ultrasound during the first 72 hours of life, and then weekly thereafter as indicated. The overall incidence of intraventricular hemorrhage (IVH) was 12%. The results by delivery were as follows:The incidence of IVH, diagnosed after the fifth day of life was 8% in both groups. This would indicate neonatal rather than perinatal factors being more contributory. Although the numbers ultimately were small and there was no difference in survival noted, delivery tended to favor C/section.

1402 THE RELATIONSHIP OF ANTENATAL STEROIDS AND PROLONGED RUPTURE OF MEMBRANES (PROM) TO DEVELOPMENT OF HYALINE MEMBRANE DISEASE (HMD)

There are conflicting data about the effect of PROM on the development of HMD. We performed a retrospective analysis of 95 neonates with PROM. 41% received antenatal glucocorticoids and 59% were managed expectantly. Labor was induced for signs of chorioamnionitis. The charts were analyzed for presence of HMD, birth weight (BW), Apgar score, length of PROM, sex, gestational age (GA) and route of delivery. The data were analyzed by step wise multiple regression and chi square with all factors weighed against HMD for each group (I: PROM with steroid; II: PROM alone).BW was the only factor correlating with HMD. BW and GA were the only correlating variables. There was no difference in the incidence of HMD in the presence or absence of steroids in this PROM population.