Laboratory evaluation of jaundice in newborns: corrections.
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Biomedical subjects
Publications and source records attributed to D K Stevenson.
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The impact of birth weight on cognitive performance in late adolescence was assessed in a study of 20,567 male infants born in Jerusalem between 1964-1970. The 17-year follow-up was performed by matching computerized data base records. Stepwise multiple regression analysis was used to estimate the effect of birth weight on intelligence test scores, adjusting for the influence of ethnic origin, maternal and paternal education, social class (determined by area of residence), maternal age, and birth order. These confounders explained 22% of the variance in intelligence test scores. The adjusted differences in intelligence test scores were significantly lower for groups with birth weight less than 2000 g (-6.5 points), 2000-2499 g (-3.6 points), and 2500-2999 g (-1.6 points) compared with the group weighing 3000-3499 g. Most low birth weight infants achieved intellectual performance within the normal range. However, despite this reassuring finding, low weight at birth in male subjects was found to have a statistically significant independent association with inferior intelligence test achievements in late adolescence.
In intensive care nurseries it has become common practice to use microwave thawing of frozen human milk for more rapid accessibility. Twenty-two freshly frozen human milk samples were tested for lysozyme activity, total IgA, and specific secretory IgA to Escherichia coli serotypes 01, 04, and 06. The samples were heated by microwave for 30 seconds at a low- or high-power setting and then reanalyzed. One-mL aliquots of 10 additional human milk samples were microwaved at low (20 degrees C to 25 degrees C), medium (60 degrees C to 70 degrees C), and high (greater than or equal to 98 degrees C) setting before the addition to each of 1 mL of diluted E coli suspension. E coli growth was determined after 3 1/2 hours of incubation at 37 degrees C. Microwaving at high temperatures (72 degrees C to 98 degrees C) caused a marked decrease in activity of all the tested antiinfective factors. E coli growth at greater than or equal to 98 degrees C was 18 times that of control human milk. Microwaving at low temperatures (20 degrees C to 53 degrees C) had no significant effect on total IgA, specific IgA to E coli serotypes 01 and 04, but did significantly decrease lysozyme and specific IgA to E coli serotype 06. Even at 20 degrees C to 25 degrees C, E coli growth was five times that of control human milk. Microwaving appears to be contraindicated at high temperatures, and questions regarding its safety exist even at low temperatures.
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The long-term effects of vacuum and forceps deliveries are largely unknown. We determined the long-term outcome of instrumental deliveries in 52,282 infants born in Jerusalem between 1964 and 1972. For each individual, events at birth were related to results of an intelligence test and medical examination done at 17 years of age by the Israeli Defence Forces draft board. 1747 individuals were delivered by vacuum, 937 by forceps, 47,500 by spontaneous delivery, and 2098 by caesarean section. Crude data showed that mean intelligence scores at 17 were significantly higher (p less than 0.0001) in the vacuum and forceps deliveries groups than in the spontaneous-delivery group; however, after adjustment for confounding factors by stepwise multiple regression, these differences were no longer seen. Although the forceps-delivery group had functional impairment of feet, vision, and retina compared with the spontaneous-delivery group, and the vacuum-extraction group had impairment of the legs, differences were small. Our findings suggest that infants delivered by vacuum or forceps are not at risk of physical and cognitive impairment at 17 years of age.
Objective--To study the effect of birth weight and body weight on blood pressure in late adolescence. Design--Analysis of data on weight, height, and blood pressure at age 17 of subjects from the Jerusalem perinatal study, according to their birth weight. Data for men and women were analysed separately. Setting--Jerusalem, Israel. Subjects--32,580 subjects (19,734 men and 12,846 women) born in the three major hospitals in Jerusalem during 1964-71 and subsequently drafted in to the army. MAIN OUTCOME MEASURES--Correlations between birth weight and blood pressure at age 17 and weight and height at age 17 and blood pressure. Results--Diastolic and systolic blood pressures were associated with birth weight in both young men and young women, but the correlation coefficients were low. A high body weight at age 17 (greater than 66 kg for women, greater than 75 kg for men) rather than a low birth weight (less than 2500 g) was linked with higher systolic and diastolic blood pressures in both men and women (p less than 0.01). Conclusions--Intrauterine environment, as reflected by birth weight, has little effect on blood pressure in young men and women. Modification of factors which lead to excess weight during adolescence may have a major role in preventing hypertension in adults.
To investigate the usefulness of measuring direct bilirubin in jaundiced term newborns, we reviewed the outcome of 5255 such measurements on 2877 term (37 weeks' gestation) newborns in two hospitals. Direct bilirubin tests were ordered 15 times as often per infant at the University of California, San Francisco, as at Stanford (Calif) University, and the reported results were more than twice as high. In most of the 149 infants with high (greater than 95th percentile) direct bilirubin levels, the high levels remained unexplained (52% of cases) or were due to apparent laboratory errors (21% of cases). Forty infants (27%) had conditions sometimes associated with high direct bilirubin levels. Elevation of direct bilirubin levels contributed to the diagnosis in only four of these infants. All had minor laboratory abnormalities that resolved spontaneously. Because of their low yield and poor specificity, direct bilirubin tests are seldom helpful in evaluating jaundice in term newborns.
Phosphorus magnetic resonance spectroscopy (31P MRS) was used to obtain in vivo spectra from rat kidneys undergoing acute tubular necrosis induced by a nephrotoxic dose of cephaloridine (CLD). Spectra were obtained 0, 24, and 48 h after injection of CLD (experimental group, n = 6) or saline vehicle (control group, n = 6). The nephrotoxicity of CLD was demonstrated by severely increased serum creatinine levels and the development of extensive proximal tubular necrosis in the CLD-injected rats, and the lack of such changes in the controls. 31P MRS showed an increase in the inorganic phosphate region signal (Pi, p = 0.004) and a decrease in the phosphodiester region signal (PDE, p = 0.01) in the experimental group by 48 h, whereas these parameters did not vary significantly in the control group during the experiment. Significant correlations were found between serum creatinine and the same two 31P MRS parameters. In summary, rat kidneys which have developed severe CLD-induced proximal tubular necrosis exhibit changes in the 31P spectrum 48 h after administration of the drug. The causes of these changes were not determined.
The records of 32 neonates in an intensive care unit were examined retrospectively to determine if fetal hemoglobin concentrations could be predicted on the basis of gestational or postnatal age, or on the volume of red blood cell transfusions. In nontransfused neonates, the correlation between measured concentrations of fetal hemoglobin and post-natal age was r = 0.53 with a 17.2 standard error of prediction. In these same neonates, the correlation between measured fetal hemoglobin divided by birth weight and gestational age was r = 0.70, with a 9.6 standard error of prediction. A three-variable regression equation (the latter two variables plus calculated fetal hemoglobin) was found to have a high correlation with data for measured fetal hemoglobin (r = 0.97) and a relatively low 8.4 standard error of prediction. In transfused neonates, however, measured hemoglobin concentrations divided by birth weight correlated poorly with gestational age (r = 0.30 and a 12.4 standard error of prediction). In addition, the transfused neonates had low correlations when fetal hemoglobin concentrations alone were compared with the total volume of red blood cell transfusions (r = 0.35) and with postnatal age (r = 0.18) and the standard errors of prediction were all approximately 17. The correlations found between concentrations of fetal hemoglobin and age in transfused neonates were poorer than those reported in earlier nontransfused infant studies. Previous studies have also shown that neonatal blood containing fetal hemoglobin interferes with the spectrophotometric measurements of carboxyhemoglobin and oxyhemoglobin. Because of the imprecision in the predictions of fetal hemoglobin using age, weight, or the volume of transfusion, we conclude that fetal hemoglobin should be measured if accurate spectrophotometric determinations of carboxyhemoglobin and oxyhemoglobin are desired.
We studied the interaction of social status and high parity in 15,102 consecutive births in one inner-city hospital, of which 1874 (12.4%) occurred in mothers who had given birth to seven or more infants (Grand multiparae). Group 1 consisted of 1258 grand multiparae from a socioeconomically stable and homogeneous ultra-orthodox Jewish community in Jerusalem, and group 2, included all other grand multiparae of relatively greater age and lower socioeconomic status. A significantly higher rate of small for gestational age, low birth weight and preterm infants was found in group 2 compared with group 1. The results suggest that grand multiparity is not of itself a risk factor, but reflects the confounding effect of environmental conditions.
The absence of intraluminal nutrients during weaning in rats was shown to result in altered intestinal growth and maturation. In this study intestinal length, mucosal weight, DNA, protein, and total disaccharidase activities were significantly lower in animals sustained by intravenous nutrients over the normal weaning age than were normally weaned controls but were greater than preweaning values. Absorptive capacity for sucrose (assessed by hydrogen-gas production) was diminished, directly linking incomplete maturation of sucrase to diminished intestinal function. To determine whether these alterations were permanent, rats previously deprived of intraluminal nutrients over the weaning period were refed. Eight days after refeeding, all variables except total lactase had attained values found in normally weaned age-matched controls, including absorptive capacity for sucrose. Although intestinal growth and maturation is abnormal in the absence of intraluminal nutrients during weaning, the abnormalities are not permanent and are rapidly corrected upon refeeding.
The authors evaluated the in vitro and in vivo efficacy and photosensitizing effects of zinc deuteroporphyrin 2,4-bis glycol (ZnBG) as an inhibitor of adult Wistar rat tissue heme oxygenase (HO) activity and bilirubin production. Concentrations of 0.02-0.05 microM ZnBG inhibited the HO activity in postmitochondrial supernatants of liver, spleen, brain, and kidney by at least 50%. Administration of 4 mumole ZnBG/kg body weight to adult rats significantly reduced the total body carbon monoxide (CO) excretion, an index of bilirubin formation, from 1 to 6 hours posttreatment. At 6 hours posttreatment, the HO activity in postmitochondrial supernatants of the liver and spleen, but not of the brain, was significantly lowered. ZnBG also behaved as an in vitro photooxidizer by degrading, in the presence of cool white light, the reduced form of nicotinamide adenine dinucleotide phosphate and histidine to CO and other nonidentified products. ZnBG also enhanced the natural photodegradation of bilirubin. Furthermore, administration of ZnBG to 1-day-old neonatal rats caused mortality within 12 hours in light-exposed animals, with a lethal dose 50 of 23 microM/kg body weight.
OBJECTIVE: To investigate the influence of maternal pre-eclampsia on the blood pressure, physique and intelligence of the offspring at the age of 17 years. DESIGN: Data obtained at the age of 17 during assessment for drafting to the Israel Defence Forces and from the records of the mothers' pregnancies from the Jerusalem Perinatal Study. SUBJECTS: Study subjects were 145 girls and 283 boys whose mothers had had pre-eclampsia and controls were 12,701 girls and 20,416 boys whose mothers did not have pre-eclampsia. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure, weight, height and intelligence scores at the age of 17 were related to birthweight and the occurrence of pre-eclampsia during their mothers' pregnancies. RESULTS: Systolic blood pressure was greater than 140 mmHg in 6.9 and 11.0% of the study girls and boys, compared with 2.9 and 9.9% of the control girls and boys. The study boys but not the girls had a higher mean body mass index than the controls (P less than 0.001). There were no differences in the intelligence scores. Using multiple logistic regression to allow for the confounding effects of body mass index, weight and birthweight, the odds ratio for the risk of a systolic pressure greater than 140 mmHg was 2.30 (95% CI 1.80-4.46) for the study girls but was not significantly increased for the study boys. CONCLUSION: Maternal pre-eclampsia does not impair growth and cognitive performance in the children who reach late adolescence but may be associated with hypertension.
The effect of low birth weight on the incidence of asthma by 17 years of age was investigated by studying medical draft examination records of 20,312 male subjects born in Jerusalem between January 1967 and December 1971. Additional information on birth weight and other demographic factors was abstracted from the Jerusalem Perinatal Study computerised database. A stepwise multiple logistic regression was used to estimate the odds ratios for developing asthma by 17 years of age in 500 g birthweight categories from less than 2000 g to 4500 g. The odds ratios were adjusted for the confounding effects of ethnic origin, social class (determined by area of residence), paternal education, maternal age, and birth order. The group with low birth weights (less than 2500 g, n = 1004) had a significantly increased risk of developing asthma by 17 years of age, with an adjusted odds ratio of 1.44 (95% confidence interval (CI) 0.79 to 2.66) for birthweight group less than 2000 g and 1.49 (95% CI 1.05 to 2.12) for birthweight group 2000-2499 g compared with the reference group of 3000-3499 g. We conclude that infants with birth weights of less than 2500 g may have a higher risk of asthma during childhood and adolescence than infants who were heavier at birth.
Zinc deuteroporphyrin IX 2,4-bis-glycol (ZnBG) is a potent inhibitor of heme oxygenase and may be useful in the prevention of neonatal jaundice. Enteral administration could be advantageous clinically, but it has been only minimally effective with other metalloporphyrins in rats and humans. Thus, the absorption of ZnBG by the small intestine in vivo was examined. ZnBG was administered enterally at 40 mumol/kg to 2-week-old suckling rats via in situ catheterization of the small intestine. Within 15 min ZnBG was absorbed by the small intestine, as it was measured in portal and systemic venous plasma, intestine, kidney, liver, and spleen. Concentrations exceeding 5.0 microM were found in plasma within 30 min, and 9.4 microM was found in the liver after 30 min. A total of 4.6% of the administered ZnBG dose was measured in plasma and tissues.
Zinc deuteroporphyrin IX 2,4 bis glycol (ZnBG) has been shown to be a potent inhibitor of heme oxygenase (HO) in vitro. Oral administration, which has been minimally effective with other metalloporphyrins, could be clinically advantageous for prevention of neonatal hyperbilirubinemia. Therefore, we examined the effect of oral administration of ZnBG on tissue HO activity and tissue ZnBG concentrations. Suckling rats at 2 weeks of age received ZnBG at 40 mumol/kg BW via gastric gavage. Rats were killed with anesthetic over-dose after 60 min. ZnBG was detected in the portal and systemic circulation (n = 12), and the liver, kidney, spleen, and intestine (n = 8). ZnBG concentrations of 7.9 nmol/g liver and 1.7 nmol/g spleen corresponded to 67 and 72% inhibition of control HO activity (n = 9; p less than 0.0005) respectively.
Anthropometric measurements and total bilirubin formation (TBF) estimates were performed on infants born to normal and diabetic mothers. Although we do not exclude the theoretical possibility of a low-frequency occurrence of increased TBF in macrosomic infants of normal mothers, we can conclude that infants of mothers whose diabetes is well managed may have normal TBF.