Determination of cholesterol absorption in man by intestinal perfusion

Gel filtration was used to measure drug interaction with protein-bound bilirubin in 0.5 ml samples of Gunn rat serum, human serum and fraction V human serum albumin. Using sulfadimethoxine as a prototype differences in displacement were found in all 3 sera. The differences between human and rat serum were related to the binding characteristics of sulfadimethoxine whereas the differences between human serum and fraction V human serum albumin were attributed to displacement of bilirubin from albumin to other proteins in serum. Gel filtration permitted the use of small samples with bilirubin-albumin ratios less than 1.0 and provided data that were used for analysis of drug displacement of bilirubin using principles of drug-receptor theory. Ten of 14 drugs found to alter serum bilirubin concentrations in icteric Gunn rats had measurable effects on protein binding of bilirubin.     

Group cognitive-behavioral treatment of binge eating disorder: a comparison of therapist-led versus self-help formats

A new enzymatic assay for selectively measuring conjugated bilirubin concentration in serum with use of bilirubin oxidase (BOD) has been developed. At pH 5.5 BOD can oxidize only conjugated bilirubin in the presence of reagents such as sodium fluoride and N-acetylcysteine which can decrease BOD reactivity to unconjugated bilirubin and bilirubin covalently bound to albumin (delta bilirubin). The resulting decrease in absorbance at 450 nm is linearly related to the concentration of conjugated bilirubin in serum. The BOD in this new assay was confirmed to oxidize conjugated bilirubin, and neither unconjugated nor delta bilirubin, based on both its reactivity to unconjugated bilirubin and HPLC results. This assay was found to give satisfactory results, such as in terms of the range of measurement, the reproducibility of the results, the lack of interference with coexisting substances in serum and the stability of the reagent solutions, in practical applications. The serum conjugated bilirubin concentrations determined using this assay correlate well with those determined by the HPLC analysis. This assay can be used for accurate monitoring of changes in the conjugated bilirubin concentration in patient sera. These findings suggest that the conjugated bilirubin assay is useful for fractional determination of bilirubin in icteric sera.     

Microdetermination of unbound bilirubin in icteric newborn sera: an enzymatic method employing peroxidase and glucose oxidase

An enzymatic assay method for the microdetermination of unbound bilirubin in newborn icteric sera is described. Unbound bilirubin is oxidized to colorless compounds by peroxidase in the presence of hydrogen peroxide derived from glucose by the mediation of glucose oxidase. In this method, the bilirubin is not significantly degraded before the addition of peroxidase, in contrast to the method using hydrogen peroxide. The oxidation rate is determined by spectrophotometry and chloroform extraction is eliminated. The unbound bilirubin concentration can be determined from the initial oxidation velocity of total bilirubin. The Michaelis constant, KM, was approximately 20 micrometer. The coefficient of variation for icteric serum determination was 4.4--6.5%. The concentration of unbound bilirubin was reduced after five days of storage at -20 degrees C. The bilirubin-albumin affinity was studied with purified albumin and adult serum. The dissociation constants were 2 x 10(-8) M and 5 x 10(-9) M, respectively, at bilirubin/albuminor molar ratios below 1.0. Clinically, serum samples from 75 icteric newborn infants were analysed, and the sera of premature infants were found to have remarkably high levels of unbound bilirubin compared to those of fullterm infants. The sera of a Rhesus immunization infant and an ABO incompatibility infant were remarkably higher than that of the nonhemolytic icteric sera. The unbound bilirubin concentration was also affected, in an in vitro study, by the addition of hemolysate.     

Plasma concentrations of phenobarbital in mother and child after combined prenatal and postnatal administration for prophylaxis of hyperbilirubinemia

Phenobarbital is known to reduce serum bilirubin concentration in the newborn infant, but optimal dosage is unknown. Ten pregnant women and their infants were given a standard regimen including prenatal maternal administration and postnatal administration to the infant during the first week of life. The plasma levels of phenobarbital in the infants were found to increase during the period of administration, and to remain high for many days beyond the period of hyperbilirubinemia. Optimal dose schedules for phenobarbital should be based both upon pharmacologic effects (including those other than bilirubin disposition) and upon the pharmacokinetic profile of the drug in the newborn infant.     

Trimethoprim-sulfamethoxazole for the prevention of methicillin-resistant Staphylococcus aureus pneumonia in severely burned patients

This study sought to examine the association between cigarette smoking and serum bilirubin antioxidant concentrations in 715 middle-aged men undergoing coronary angiography. The study involved 153 current smokers, 251 who quit smoking and 311 who never smoked. Serum bilirubin concentrations were divided into the following quartiles; 0.20-0.57, 0.58-0.73, 0.74-0.95 and 0.96-3.26 mg/dl. The percentage of individuals within each quartile were as follows; current smokers (42, 22, 24, 12), former smokers (22, 27, 23, 28), nonsmokers (16, 28, 27, 29). A total of 42% of the current smokers had bilirubin concentrations in the lowest quartile compared to 16% of the nonsmokers. Also, 12% of the current smokers had bilirubin concentrations in the highest quartile compared to 29% in the nonsmoking group. The Mantel-Haenszel chi-square test for association between ordered categorical variables was 30.6 (P < 0.0001). Subdividing the subjects according to maximum percent stenosis on angiography (< 10, 10-49, 50-100%) revealed a significant inverse association between smoking and bilirubin (< 0.01) within each subset. The data shows that smoking is associated with decreased serum bilirubin concentrations. In addition, it supports the hypothesis that cigarette smoking may increase the risk of coronary artery disease by lowering antioxidant concentrations and raising oxidized lipid and lipoprotein concentrations.     

The association between fasting hyperbilirubinaemia and serum non-esterified fatty acids in man

1. The concentrations of plasma total and unconjugated bilirubin and of serum nonesterified fatty acids (NEFA) have been measured in two healthy subjects during fasts of up to 21 h. 2. Fasting was either continuous or interrupted by various procedures that altered the concentrations of NEFA and total bilirubin. 3. When NEFA concentrations were increased by the administration of noradrenaline, heparin or caffeine, bilirubin concentrations also rose. 4. When NEFA concentrations were lowered by insulin, bilirubin concentrations fell. 5. Meals of 3-138 kJ and more, taken during the fasting period, lowered total bilirubin and NEFA concentrations in both subjects, whereas the effects of smaller meals were less consistent. 6. These studies demonstrate a statistically significant correlation between total bilirubin and NEFA during uninterrupted fasting and an association between these variables under other experimental conditions. They suggest that the control of bilirubin concentrations in the blood is linked to lipid metabolism.     

Common foot deformities in infancy and childhood

An enzymatic-fluorimetric method using a highly purified 3alpha-hydroxysteroid dehydrogenase (Sterognost-3alpha, Nyco) was used to determine fasting serum bile acid concentrations on 49 occasions in 43 patients with various liver diseases. A two-hour postprandial bile acid determination was carried out on 29 occasions in 27 of the patients. Fasting bile acid concentration correlated significantly both in cholestatic hepatobiliary and in parenchymatous liver disease to serum bilirubin and aspartate aminotransferase (ASAT) but not to alanine aminotransferase (ALAT), alkaline phosphatase, or albumin. The two-hour postprandial bile acid concentration was above normal in all patients with biochemical and/or histological signs of hepatobiliary disease, also when fasting concentration was within normal limits. In parenchymatous liver disease correlations existed between the two-hour postprandial bile acid concentration and bilirubin, ASAT, and ALAT. The sensitivity of serum bile acid estimation was compared to other liver function tests. Both the fasting and the postprandial serum bile acid concentrations tended to be more sensitive tests of hepatobiliary disease than bilirubin, ASAT and ALAT.     

Inhibition of thyroxine transport into cultured rat hepatocytes by serum of nonuremic critically ill patients: effects of bilirubin and nonesterified fatty acids

We investigated bilirubin and oleic acid as causes of low plasma T3 in nonuremic critically ill patients with gross changes in serum thyroid hormone levels (T4, < or = 60; T3, < or = 1.1; rT3, > or = 0.45 nmol/L) and elevated bilirubin concentrations (> or = 33 mumol/L). Iodide production from [125I]T4 was inhibited by 42% when rat hepatocytes in primary cultures were incubated with 10% serum from these patients. The mean serum concentration of albumin was reduced by 41%, while the concentrations of bilirubin and nonesterified fatty acids (NEFA) were increased by 2022% and 115%, respectively, in the patients. The molar ratios of bilirubin/albumin and NEFA/albumin in the patients were 0.42 and 3.18, respectively. Addition of oleic acid (50-400 mumol/L) and bilirubin (3-130 mumol/L) to 10% normal human serum (albumin, 70 mumol/L; NEFA, 54 mumol/L; bilirubin, 1.1 mumol/L) progressively inhibited the production of iodide by rat hepatocytes. The decreased iodide production was presumed to be caused by inhibition of T4 transport into hepatocytes. The deiodination of rT3 by rat liver microsomes was unaltered by free bilirubin and free oleic acid concentrations up to 0.1 mumol/L. These free concentrations are at least 1 order of magnitude higher than that attained in nonthyroidal illness. The inhibition of iodide production by the sera of critically ill patients (n = 12) was significantly correlated with the molar ratios of bilirubin/albumin (r = 0.72; P < 0.01) and NEFA/albumin (r = 0.58; P < 0.05). Extensive dialysis or treatment of the sera with charcoal did not completely remove the inhibitory activity on iodide production. Serum concentrations of indoxyl sulfate, 3-carboxy-4-methyl-5-propyl-2-furan propanoic acid, and hippuric acid in the critically ill patients (other known T4 transport inhibitors into hepatocytes) were similar to those in the normal subjects. This study together with the well known effects of carbohydrate on T3 neogenesis suggest that elevated bilirubin and NEFA and the low albumin level in non-uremic critical illness may be at least partly responsible for the T4 transport inhibition in T3-producing tissues (e.g. the liver) and, thus, the low plasma T3 levels in these critically ill patients. The question of whether inhibitors of T4 transport into the hepatocytes are also present in other patients with nonthyroidal illness who show only mild changes in thyroid hormone levels and have low concentrations of bilirubin and NEFA remains to be determined.     

Effects of AT-I on murine cytokins productions and NK cell activity in vivo

The objective of this prospective study was to assess the prognostic value of dynamic and static liver function tests and clinical symptoms in pediatric patients with chronic end-stage liver disease in a serial examination including three evaluations at 3-month intervals. Of the 24 patients entering the study, six were given transplants within the observation period of 10 months. Of the remaining 18 patients who were considered in the final evaluation, five died before transplantation was possible. The variables included in the analysis were monoethylglycinexylidide (MEGX) formation from lidocaine, bilirubin, albumin, and creatinine serum concentrations, catalytic serum concentration of cholinesterase (CHE), prothrombin time (PT), factors II and V, serum amino acids, body weight, and presence of ascites. In nonsurvivors (n = 5), MEGX serum concentrations 30 min after intravenous administration of lidocaine (1 mg/kg body weight) were < 10 micrograms/L at the first examination. Statistically significant differences between nonsurvivors and survivors were observed for initial MEGX test results (p = 0.0089) and serum bilirubin concentrations (p = 0.009), as well as for the last available MEGX and bilirubin data from each patient (p = 0.017 and 0.016, respectively). At a diagnostic sensitivity of 100%, the corresponding diagnostic specificities for MEGX and bilirubin from the first examination were 77 and 62%, respectively. These data show that consistently low MEGX test results < 10 micrograms/L, obtained 30 min after intravenous administration of lidocaine (1 mg/kg body weight), are a prognostically unfavorable sign in pediatric transplant candidates.     

A CCG repeat polymorphism adjacent to the CAG repeat in the Huntington disease gene: implications for diagnostic accuracy and predictive testing

STUDY HYPOTHESIS: Concentrated aqueous solutions of hydroxocobalamin (OHCob) are given intravenously for the treatment of cyanide poisoning. Because OHCob solutions are intensely red and have peak light absorptions at 352 nm and 525 nm, we investigated whether the presence of OHCob in serum would interfere with various automated, colorimetric chemistry measurements. DESIGN: Selected serum chemistry colorimetric measurements were compared in seven patients, using their own serum as control, with serum containing OHCob at the following concentrations: 100 mg/L, 500 mg/L, and 1,000 mg/L. These concentrations are in the range achieved with therapeutic doses of OHCob when given for cyanide poisoning. MEASUREMENTS AND MAIN RESULTS: Statistically significant alterations in serum values for aspartate aminotransferase, total bilirubin, creatinine, magnesium, and iron were seen in the presence of OHCob. CONCLUSION: The presence of OHCob in serum interferes with several chemistry methodologies, and such interference should be anticipated when this antidote is used.     

Association between the gamma-aminobutyric acid A3 receptor gene and multiple sclerosis

OBJECTIVE: Non-tumour causes of hyperprolactinaemia, including prolactin-elevating drugs, must be excluded. There is a general view that such drugs are unlikely to raise serum PRL above 3000 mU/I, but the literature is confusing. We report 8 patients receiving treatment with neuroleptic drugs, whose serum PRL concentrations were grossly elevated. METHODS: Prolactin was measured using a 2-site immunofluorometric assay (Abbott Laboratories; reference range < 500 mU/l). Seven of the eight women (age range 24-49 years) were symptomatic (galactorrhoea, oligo- or amenorrhoea). RESULTS: Prolactin concentrations ranged from 3600 mU/l to 7300 mU/l. All patients had a normal pituitary CT scan. Five patients were treated with bromocriptine without detriment to their mental state. CONCLUSION: Prolactin can rise to concentrations associated with prolactinomas in patients on neuroleptic drugs. As it is rarely possible to stop the drugs to see if the PRL concentration will decline to normal, neuroradiology is required in these patients to exclude a vision-threatening macroprolactinoma before deciding on medical treatment.     

Effects of serotonin reuptake inhibitors on hemostasis

OBJECTIVE: To examine the hematologic safety profile of the selective serotonin reuptake inhibitors (SSRIs), with particular emphasis on the effects of these drugs on platelet aggregation. METHODS: Platelet aggregation studies were undertaken at baseline, and repeated 2 and 4 weeks after the initiation of treatment with an SSRI. Other investigations undertaken included analysis of serum electrolyte and liver enzyme concentrations, complete blood count, and coagulation studies. Patients were also assessed for clinical signs of bleeding. Eight patients (7 treated with fluoxetine, 1 with paroxetine) completed the study protocol. RESULTS: Repeated ANOVA revealed no abnormalities in platelet aggregation, hematopoiesis, or coagulation profile. No patient developed clinical signs of abnormal hemostasis during the study period. A statistically significant elevation in the mean serum bilirubin concentration was detected, but this was not of clinical significance. CONCLUSIONS: Although the SSRIs may cause abnormal hemostasis, this effect is probably rare. Another possibility is that abnormal hemostasis is more likely to occur when high doses of SSRIs are administered.     

Hepatic lipidosis in anorectic, lactating holstein cattle: a retrospective study of serum biochemical abnormalities

The association between hepatic lipidosis (HL) and disease in 59 anorectic, ketotic, lactating Holstein heifers and cows was investigated. Severe HL, as determined by histologic evaluation of liver tissue, was present in 46 animals; only half of these animals required intensive treatment for ketosis, and only half had serum biochemical evidence of liver disease, as determined by the presence of a last value of 2-fold or greater than the upper limit of the reference ranges for at least 2 of the 4 serum tests: gamma-glutamyl transferase, aspartate aminotransferase, and sorbitol dehydrogenase activities and bile acid concentrations. Most cattle with biochemical evidence of liver disease and severe HL had been lactating for 14 or more days. Cows that required intensive treatment inconsistently had serum biochemical evidence of liver disease. Although cattle with severe HL had significantly higher serum bilirubin concentrations and aspartate aminotransferase and sorbitol dehydrogenase activities than cattle with less severe lipidosis, the specificity of abnormally high serum sorbitol dehydrogenase activity or bilirubin concentration for severe lipidosis was only 8%. Abnormally high serum aspartate aminotransferase activity was 83% sensitive and 62% specific for severe lipidosis. Serum glucose and total carbon dioxide concentrations were significantly lower in cattle with severe lipidosis than in those with mild or moderate lipidosis, and low serum glucose or total carbon dioxide concentrations were rare in cattle without severe lipidosis. From these data, we conclude that the use of a single biochemical or histopathologic criterion to define severity of disease or degree of liver compromise in anorectic, ketotic cows results in the misidentification of many animals.     

Evidence for a major gene elevating serum bilirubin concentration in Utah pedigrees

In case-control studies, lower serum bilirubin levels have been associated with increased risk of developing coronary heart disease (CHD). We have also previously shown that serum bilirubin has a significant polygenic component. The purpose of the present investigation was to determine whether there was statistical evidence for a major gene explaining a significant portion of individual variation in serum total bilirubin levels and whether this gene might alter the risk of CHD. Serum bilirubin measurements were obtained from 1240 adults in 84 Utah pedigrees screened twice: from 1980 to 1983 and again from 1983 to 1986. Bivariate maximum-likelihood segregation analysis of serum bilirubin levels obtained from the two clinic visits indicated that a major gene was responsible for elevated levels in 11.5% of the persons in these pedigrees. Phenotypic variations in visit 1 bilirubin arising from polygenes were highly correlated with the phenotypic variation due to polygenes in visit 2 bilirubin, indicating a stable genetic contribution to bilirubin over 2.5 years of follow-up. The major gene explained 27% and 28% of the variance in bilirubin levels at visit 1 and visit 2, respectively. There were no correlations of unmeasured environmental factors influencing bilirubin between the two clinic visits. At both visits, persons with early CHD had lower levels of bilirubin than unaffected persons (P < .01). The odds ratio for the risk of CHD in the high-homozygote group was 0.31, P = .09. We conclude that there is a major gene modestly raising serum bilirubin levels. Since cross-sectional data indicate that low serum bilirubin levels increase the risk of CHD, this major gene may be protective against CHD for about 12% of the persons in this study.     

The influence of various aminoglycoside preparations on bilirubin/albumin binding

The effect of antibiotics of aminoglycoside structure on the albumin binding of bilirubin has been tested in homozygous (jaundiced) Gunn rats aged 3-5 days. The following drugs were investigated: different preparations of gentamycin, kanamycin, tobramycin and sisomicin. The animals received 50-75% of the LD50 of heterozygous (non-jaundiced) Gunn rats. Mortality, weight gain and changes in the plasma bilirubin concentration were recorded. It was found that the displacement of bilirubin from albumin is caused by the different stabilizers used and not by the antibiotic itself. With the exception of lyophilized preparations of gentamycin for intrathecal application all vials contain different amounts of these preservatives. Special preparations used during the newborn period contain relatively more of these stabilizers. The toxicity of the additives has already a negative influence on the LD50 for heterozygous Gunn rats when the low dosed Refobacin and Sulmicin vials are given. For Refobacin (production 1973/74) the tolerance is reduced by nearly 50%. The toxicity caused by the stabilizer alone is even more marked when given to homozygous (jaundiced) Gunn rats. It becomes evident that benzylalcohol is the substance responsible for the displacement of bilirubin from albumin. The serum concentration of bilirubin decreases for 3-24 hrs depending on the doses given to the animal. This offers the opportunity to measure the competitive displacement of bilirubin easily and exactly. The free unbound, unconjugated bilirubin tends to diffuse into the lipid of the brain with resultant kernicterus. This was shown in histochemical preparations of the cerebellum of young homozygous Gunn rats. Using enzyme reactions for lactic acid dehydrogenase and NADH2-tetrazolium reductase the cytotoxic effect of bilirubin on PURKINJE cells could be demonstrated. The effect of the stabilizers used in the other antibiotic drugs tested can be neglected under clinical conditions. Finally the steepness and duration of the decrease of plasma bilirubin after injection of the dangerous stabilizers was studied in animals of different age (3-5 days; 3-4 weeks). Different results observed can be explained by the more rapid metabolism of benzoates in older animals. However, it remains an open question at what age Gunn rats reflect most precisely the human situation in premature and newborn babies.     

Evidence for a luteinizing hormone surge center in the hypothalamus of the pig

Lipoprotein-X (Lp-X) is an abnormal low-density lipoprotein frequently found in liver disease. It is regarded as the most sensitive and specific biochemical parameter for the diagnosis of intra- and extrahepatic cholestasis. Moreover, Lp-X is supposed to contribute to the development of hypercholesterolemia in cholestatic liver disease, because it fails to inhibit de novo cholesterol synthesis. This investigation will focus on the relationship between the presence of Lp-X and serum lipid concentrations in cirrhosis. The significance of Lp-X in the diagnosis of cholestasis, compared with alkaline phosphatase (AP), gamma-glutamyl transferase (GGT), and bilirubin levels, will be assessed as well. The present cross-sectional study includes 212 patients with histopathologically proven cirrhosis. The detection of Lp-X and the quantification of -, beta-, and pre-beta-cholesterol was based on agar gel electrophoresis and polyanion precipitation. For the characterization of liver function, the concentrations of albumin and bilirubin, the activities of liver enzymes, and coagulation times were assessed. In a subgroup of 40 individuals, liver biopsies were re-evaluated to confirm or exclude intrahepatic cholestasis. As a result, there was no association between the appearance of Lp-X and total cholesterol concentrations. While all patients with Lp-X showed intrahepatic cholestasis (predictive value of the positive test = 1), only 16 of 28 patients with cholestasis formed Lp-X (sensitivity = 0.57). The activities of AP and of GGT, as well as the concentrations of bilirubin, were strongly elevated in most patients, with and without cholestasis. The predictive values of AP, GGT, and bilirubin were 0.77, 0.69, and 0.74 for the positive test and 0.5, 0, and 0.6 for the negative test, respectively. We conclude that Lp-X is not related to hypercholesterolemia in cirrhosis. The positive, but not the negative, Lp-X test has high predictive value for the diagnosis of cholestasis in cirrhosis. The biochemical parameters traditionally used for the assessment of extrahepatic cholestasis, AP, GGT, and bilirubin, do not support the diagnosis of intrahepatic cholestasis caused by cirrhosis.     

Comparison of the bilirubin concentration and the bilirubin/albumin ration with the bilirubin-binding ability in neonatal serum

The bilirubin-binding ability of neonatal serum was measured and compared with the serum bilirubin concentration and the serum bilirubin/albumin ratio. The bilirubin/albumin ratio correlated no better with the bilirubin-binding ability than the bilirubin concentration alone.     

Inhibitory effects by a submandibular gland extract on luteinizing hormone-stimulated testosterone production by testicular cells

In order to develop an animal model for in vivo testing of the displacing action of various drugs and for study of the bilirubin deposition in the brain, some molecular properties of the serum albumin from different species i.e. pig, cat, human, dog, sheep, guinea pig and rat were investigated. These albumins were found to have differences in molecular weight, Stokes radius and electrophoretic mobility. They also showed different bilirubin binding characteristics when studied by spectroscopy and fluorescence quenching. It is therefore, necessary to consider the species differences when results of animal experimentation are used as a basis for the investigation of human kernicterus.     

The maternal and fetal levels of human chorionic gonadotropin, human placental lactogen and prolactin during the perinatal period (author's transl)

The levels of human chorionic gonadotropin (HCG), human placental lactogen (human choriosomatomamotropin HCS) and prolactin (PRL) were determined in the serum of 72 maternity patients and the serum of the newborn infants. The determinations were done with radioimmunologic tests (RIA). These three protein hormones were also determined in the amniotic fluid and in the maternal serum from 4-6 days prior to the delivery of the infant. The concentration of HCG or HCS in the serum of the newborn infants was a mean 0.43 or 0.37% of the level in the maternal serum. The concentration of PRL in the serum of the newborn was 118% and slightly higher than in the serum of the mothers. The concentration in the amniotic fluid was 1.5% for HCG, 5.8% for HCS, and 252% for PRL, compared to the corresponding levels in the maternal serum. The fact that the hormone concentrations in the amniotic fluid are significantly higher than in the serum of the newborn suggests excretion of the hormones from the fetal circulation via the fetal liver and the fetal kidney. The high levels of PRL in the maternal and the newborn serum may be caused by the high concentrations of estrogen or progesterone. Increased during the course of the pregnancy there was a significant sex linked difference in the level of HCG in the maternal serum correlated to the sex of the newborn infant.     

A prospective study of drugs and pregnancy. 4. Miscellaneous drugs

The results are presented of a prospective study on drug use during pregnancy involving antibiotics, analgesic drugs and iron and vitamin preparations. The study was conducted in Malm? between 1963 and 1965. No unfavourable effect of the use of antibiotics, mainly penicillin and sulphonamides, could be demonstrated. Among 15 women who had an infant with hypospadias, three had used penicillin during the first trimester, but this may well be coincidental. Analgesic drug use shows a variability which resembles that previously described for psychopharmaca. No effect on the malformation rate or infant survival could be found. A possible lengthening of the mean duration of pregnancy occurred after the use of analgesic drugs during the 2nd or 3rd trimesters. Women who are going to have a dead or malformed infant use iron and/or vitamin preparations less often during late pregnancy than women who prove to have a normal infant. When such drugs were used, the percentage of pregnancies ending in birth before the 38th week is reduced, and the birth weight among term babies is higher. The associations between pregnancy outcome and the use of iron and vitamin preparations is probably indirect, due to social factors associated with drug use.