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The etiology of the severe hepatic dysfunction associated with total parenteral nutrition (TPN) remains unknown, but recent studies suggest that taurine deficiency may be associated with the development of cholestasis in experimental animals. That taurine deficiency might also play a role in the development of the severe hepatic dysfunction in human infants receiving TPN as their sole nutritional intake is the subject of the present report. Serial plasma aminograms were obtained from three children with severe hepatic dysfunction associated with TPN, in whom progressive disease led to death after 20, 13, and 14 months. All three children underwent massive intestinal resection for necrotizing enterocolitis, leaving 30, 44, and 17 cm of viable small bowel, respectively. Balanced TPN was given as 20 to 25 g/kg/d dextrose, 1.5 to 2.5 g/kg/d crystalline amino acids, and 2 to 3 g/kg/d fat emulsion; enteral feedings were attempted but were poorly tolerated. Mild cholestasis progressed to severe hepatic dysfunction manifested by hyperbilirubinemia, increased serum transaminases, hypoproteinemia, and abnormal coagulation profiles. Liver histology revealed extensive fibrosis, fatty replacement, and coarse cholestasis, necrosis not being prominent. Serial plasma aminograms revealed markedly elevated plasma levels of methionine (1353, 1168, and 113 nm/ml), low levels of 1/2 cystine (68.4, trace, and 17 nm/dL), and undetectable levels of taurine; plasma levels of branchedchain amino acids were normal. These results suggest that a block in the transsulfuration pathway, the end product of which is taurine, may be present in severe hepatic dysfunction associated with TPN which is not present in other forms of liver disease in infants; and further, that such a block may occur early in the pathway, resulting in a relative excess of methionine but a relative deficiency of cysteine and taurine. Given that taurine is the major bile acid conjugating amino acid in man, these data support the hypothesis that impaired bile acid conjugation due to taurine deficiency, by producing cholestasis, may play a role in the development of the severe hepatic dysfunction associated with TPN.

To determine whether serum prealbumin would be useful in identifying adequacy of protein and calorie intake in premature infants, 17 infants between 26 and 33 weeks gestational age were studied throughout hospitalization. Serial anthropometric measurements, nutritional intake, and serum prealbumin concentrations were correlated. When mean intake of calories and protein was lower than 100 kcal/kg/day and less than 2 gm/kg/day, respectively, there was a significant difference in mean prealbumin values, compared with those in infants with a higher intake (P much less than 0.001). For infants with birth weights of 1000 gm or less, prealbumin correlated with protein intake (r = 0.66) and calorie intake (r = 0.64). In these infants, when protein intake exceeded 2 gm/kg/day, prealbumin concentrations increased to values reported for full-term infants in the first months of life. There was no significant correlation between intake of calories or protein and prealbumin values for infants born weighing greater than 1000 gm. Anthropometric measurements did not correlate with protein or calorie intake. We conclude that prealbumin is a sensitive measure of protein and calorie intake in premature infants, and that the definition of adequate nutrition may be different for premature infants of different birth weights and at various postconceptional ages.

961 EFFECTS OF INTRALIPID INFUSIONS OF ARTERIAL BLOOD GASES AND PULMONARY FUNCTION IN SMALL PREMATURE NEONATES

Head growth velocity was assessed weekly during the neonatal period and at 3 month intervals up to one year of corrected age (CA) in 47 premature infants whose clinical data is shown below (mean ± SEM)

The effect of caloric intake, 24 hour heart rate and infant temperament (Carey Scale) on adipose tissue deposition was studied in two groups of healthy 18 month old infants: Group I (N=10) had weight by length (W/L) and triceps skinfold thickness (TSF) above the 75%ile and Group II (N=11) had W/L and TSF between 25-75%ile of the growth chart. The caloric intake in infants in group I and II was comparable (mean ± SEM 102.3 ± 7.8 vs. 121.5 ± 10.7 kcal/kg/day). No significant differences in heart rate during awake and asleep periods were seen between the two gorups. The number of infants in Group I and II classified into four temperament categories varying from easy, intermediate low, intermediate high, and difficult were respectively 1 vs 3, 4 vs 3, 2 vs 5 and 2 vs 0. Multiple linear regression analysis applied to this data showed that an increse in scores for difficult temperament in infants in Group II correlated positively with caloric intake (r2 = 0.41), and heart rate awake (r2 = 0.54), and negatively with five skinfold thickness (r2 = -0.71). Conversely, an increase in scores for difficult temperament in infants in Group I correlated negatively with caloric intake (r2 = 0.66), positively with five skinfold thickness (r2 = 0.94) and it was unrelated to changes in heart rate. This study shows that: 1) increased adiposity in infants studied was not explained by differences in caloric intake; 2) decreased adiposity observed in infants with difficult temperament was associated with elevations in heart rate suggesting either increased metabolic and/or physical activity of those infants; 3) the findings of increased adiposity in infants with difficult temperament warrant further investigation.

Heroin addiction was considered a high risk factor for hearing loss for a mother and her developing fetus due to well-known ototoxic effects of quinine, a common additive to heroin sold to addicts. 21 infants and their heroin addicted mothers were evaluated for auditory impairment from March 1974 through June 1976. Characteristics of the study population were: age of infants: 5 days to 34 months (mean 7.2 ± SD 10.2 mo); age of mothers: 21 to 29 years (mean 24.3 yr ± SD 3.4 yr); maternal length of addiction 1 to 12 years (mean 3.2 ± SD 3.43 yr); and dally habit cost: $5 to $150 (mean $40 ± SD $43). All mothers studied who were on methadone replacement programs (13) admitted to the infrequent but constant use of heroin throughout the pregnancy. A control group of infants and their non-addicted mothers were matched by age to the study infants. Evaluation in all subjects consisted of case history information, otological examination and standard audiological techniques. According to their ages, infants were tested by a neonatal screening test or by a soundfield audiometry or by play audiometry. The study showed no evidence of hearing impairment in either the addicted mothers or their infants. Although they were considered normal, responses of 6 addicted neonates were depressed as compared to their matched control possibly due to their use of phenobarbltal. Maternal heroin addiction did not seem to represent a high risk factor for hearing loss in this population possibly because quinine exposure had not reached toxic levels.

• Two hundred sixty-seven neonates who received parenteral nutrition were monitored for signs of liver dysfunction. Cholestatic jaundice occurred in 23 infants, with a higher incidence in the more immature infants. There was an inverse correlation between severity of jaundice and the degree of prematurity. Infants with cholestasis remained without gastrointestinal feedings and received parenteral nutrition for periods of time significantly higher than infants without cholestasis. The incidence of this complication did not seem to correlate with the amount of protein infusate (amino acid solution). A higher incidence of sepsis was noted in infants who were affected by cholestasis. Close monitoring for signs of liver dysfunction in all neonates receiving parenteral nutrition is strongly recommended. (Am J Dis Child1981;135:842-845)

We have previously described the association between maternal Li therapy during pregnancy and fetal macrosomia (Ped Res 17(4):304A, 1983). This study reviews the records of 241 infants reported to the Register of Lithium Babies between 1962-1978. All infants were included in calculating mortality statistics. Gestational age (GA), birthweight (BW), sex, Li dose and duration of therapy were analyzed in 180 infants. Premature delivery occurred in 39% of the pregnancies. Mothers of premature infants were treated with higher daily Li doses during the 1st and 2nd trimester than mothers of term infants (1.2 ± .6 gm vs. .9 ± .5 gm (1st trim.), p 90th %tile for GA) was identified in 36% of the infants with a higher frequency in infants born prematurely than in those born at term (59% vs. 26%). The degree of macrosomia was significantly more pronounced in premature infants than in full term infants (129 ± 23 vs. 106 ± 18, % mean BW for GA, p

To determine the effect of postnatal age on serum clearing of intravenous fat, 17 preterm, AGA infants with gestation age of 29 ± 0.4 SEM wks. and birthweight of 1.2 ± 0.07 SEM kg. and less than 3 wks. of age received 1 gm/kg of Intralipid over a 4 hour infusion. Plasma levels of triglyceride (TG), free fatty acids (FFA) and beta-hydroxibutyrate (BOB) were determined at 0, 4, and 8 hours after the infusion was started. Basal levels of TG, FFA, and BOB were similar in the 2 groups. Infants of less than 1 wk. old had higher peak TG levels at the end of the infusion (4 hr.), than infants 2-3 wks. old (p

A thyroid hormone binding inhibitor (THBI) which affects the ability of thyroxin binding globulin (TBG) to bind T4 was first described by Chopra et al as a possible explanation for the low T4 levels observed in some adults patients with non-thyroidal illness. Because low T4 levels are likewise a common clinical feature of prematurity, we examined THBI activity in 30 neonates (GA 26-43 weeks, BW 930-4360 grams) using a competitive ligand binding assay in order to determine whether increased THBI levels might be responsible for the hypothyroxinemia of prematurity. Serum concentrations of T4 and TBG were measured by RIA and the free T4 index calculated. THBI activity was expressed as the % CPM T4 1125 displaced from serum binding protein in the absence of THBI. A THBI index was then calculated, normalizing patients' samples relative to a baseline (control value of 1.0). Significant positive correlations between THBI activity and birthweight (r=0.76, p< 0.0001) and gestational age (r=0.74, p< 0.0002) were noted in infants born between 26 and 39 weeks of gestation, but not in more mature infants. No significant correlations were observed between THBI activity and TBG, T4 and free T4 index in these infants. The results of this study indicate that: 1) increased THBI activity is not a likely etiology for the hypothyroxinemia of prematurity; 2) the activity of THBI increases with fetal maturation until term gestation, and then it appears to decline; 3) the relationship between THBI activity, birthweight, gestational age, and systemic illness needs to be further investigated.

The age of introduction of solid foods and its effect on energy intake, growth and adiposity during the first 3 years of life were studied in 92 healthy male infants from the Greater Philadelphia area. The first solid foods introduced to infant diets were cereals (70%), fruits (4%), and a combination of cereals and fruits (26%). Solids were started by 2 months of age in 48% of infants, by 4 months in 89% and by 6 months in 99%. The age of introduction to solids was decided with basis on physicians' recommendation (39%), mothers' decision (38%), relatives' advice (11%), and other factors (12%). Infants introduced to solids by 2 months of age as compared to others introduced to solid foods after 2 months had: 1) higher but not statistically significant energy intake at 6, 12 and 18 months of age; 2) higher energy intake at 36 months (mean ± SEM 1585 ± 93 vs. 1375 ± 95 Kcal/day, p < 0.1); 3) greater triceps (8.2 ± 0.4 vs. 7.4 ± 1.1, p

A prognostic scoring system for infants with RDS was developed in an effort to better predict the need for the type of therapy that would be required. The differences of the means of 5 variables occurring in 100 infants treated from July 1974 to June 1975 were compared by the Student's “t” test for 3 treatment outcomes: 1) oxygen by hood (OBH); 2) continuous positive airway pressure (CPAP); 3) mechanical ventilation (MV). These 5 variables, 1) birthweight, 2) clinical RDS score, 3) FiO2, 4)pCO2, 5) pH were formated into a multivariate scoring system with a score ranging from a value of zero for mild disease to a value of ten for the severest condition. This was applied to 159 infants treated for RDS from July 1975 to June 1976. The mean scores were significantly different when therapy by OBH or CPAP were compared to MV. There was less striking difference when OBH was compared with CPAP When the various score levels were distributed according to the 3 therapeutic modalities it was seen that most of the patients with scores in the range of 0-2 did well with OBH or CPAP and only 8% required mechanical ventilation. On the other hand, of those infants scoring in the range of 7 or greater, 83% required MV and only 5% were treated with OBH only.

MAC/HC has been a useful anthropometric measure of malnutrition in older infants. Since standards have not been established for term or preterm neonates, we measured MAC/HC on day 3 of life in 104 term and 100 preterm infants (EGA 37.5-43 and 26-37 wks). A strong correlation between increasing gestational age and MAC/HC was found defining a standard curve y=.0056x + .066 (r=.85;p

Breast milk has been recommended for feeding high risk neonates due to the psychological, nutritional and immunological advantages of breastfeeding (BF). In order to assess the influence of maternal counselling, we studied the BF pattern of 503 mothers of infants admitted to the neonatal ICU for 2 periods of 6 months prior to and following initiation of counselling. A special group of certified counsellors, who successfully breastfed their own sick neonates, were available by phone to all mothers. With counselling there was a significant increase in the number of mothers who engaged in BF (32/242=13.2% to 92/261=34.8%, p

Cimetidine, a potent H2receptor antagonist, recently introduced for the treatment of peptic ulcer and other related disorders, has gained widespread use. Most of the current knowledge of its use and effects is based on adult clinical trials. There is a lack of data on its effects in children and infants and virtually none on the human fetus. Animal studies using radioactive labeled cimetidine at doses of 100 mg/kg indicate that this drug crosses the placental barrier and has thus the potential of producing a systemic effect in utero. Elevated transaminase levels have been reported in adults,1.2and cholestatic jaundice has been observed in children.3This report concerns the finding of liver impairment in an infant born to a mother receiving cimetidine in the last trimester of her pregnancy. Report of a Case.—This male patient was born to a 39-year-old, gravida 4, para 2, still-birth 1 whose

THE EFFECT OF SLOW LIPID INFUSION AND DOSAGE ON BILIRUBIN BINDING TO ALBUMIN IN THE PREMATURE INFANT

The use of pacifiers(NNS) during gavage(NG) feeding may be important for the feeding of small premature infants. Thus, transition to total nipple(po) feeding, caloric intake, intestinal motility and wt.gain/wk. were studied in 20 stable, gavage fed AGA infants (birth wt.