Human anti-60 kD heat shock protein autoantibodies are characterized by basic features of natural autoantibodies.

Anti-human Hsp60 autoantibodies--known risk factor of atherosclerosis--were investigated in a mouse model and in samples of healthy subjects: polyreactivity, presence in cord blood samples of healthy newborns and life-long stability were tested. In IgM hybridoma panel from mouse spleens, polyreactivity of anti-Hsp60 autoantibodies was studied. In healthy pregnant women, umbilical vein and maternal blood samples were collected after childbirth, anti-Hsp-60 and -65 IgM and IgG levels were measured. Life-long stability of anti-Hsp-60 levels was studied on healthy patients during 5 years. ELISA was used in all studies. Polyreactivity of IgM clones of newborn mice and lifelong stability of these autoantibodies in healthy adults were established. IgM anti-Hsp60 autoantibodies in cord blood of healthy human infants were present, however, there was no correlation between maternal and cord blood IgM anti-Hsp60 concentrations. It is proposed that presence of anti-Hsp60 autoantibodies--as part of the natural autoantibody repertoire--may be an inherited trait. Level of anti-Hsp60 autoantibodies may be an independent, innate risk factor of atherosclerosis for the adulthood.

Biomechanics and vasoreactivity of female intramural coronaries in angiotensin II induced hypertension.

Hypertension causes small vessel remodeling, vasomotor alterations. We investigated diameter, tone and mechanics of intramural small coronaries of female rats that received chronic angiotensin treatment to induce hypertension.Angiotensin II infusion (AII, 100 ng/bwkg/min, sc.) was used to establish hypertension in 10 female rats. Other 10 rats served as controls. Following 4 weeks of treatment, side branches of the left anterior descendant coronary (diameter approximately 200 microm) were isolated, cannulated and pressure-diameter curves were registered between 2-90 mmHg. Changes in vessel diameter were measured in Krebs solution, in the presence of thromboxane A2 receptor agonist (U46619, 10(-6) M), bradykinin (BK, 10(-6) M), and finally at complete relaxation (in Ca2+-free solution). Chronic AII treatment raised the mean arterial pressure (130+/-5 mmHg vs. 96+/-2 mmHg, average +/-SEM) significantly. Wall thickness of the AII group was significantly greater (40.2+/-4.2 microm vs. 31.4+/-2.7 microm at 50 mmHg in Ca2+ -free solution), but cross-section of the vessel wall did not differ. Tangentional wall stress and elastic modulus decreased significantly in hypertensive animals. Constrictions in the presence of U46619 were greater in the AII group (24.4+/- 5.6% vs. 14.5+/-3.3% at 50 mmHg). In hypertension, intramural small coronaries showed inward eutrophic remodeling, as a morphological adaptation following AII treatment enhanced thromboxane A2-induced tone.

Possible association of folic acid supplementation during pregnancy with reduction of preterm birth: a population-based study.

OBJECTIVE: Periconceptional folic acid or multivitamin supplementation is recommended for prospective pregnant women to prevent neural-tube defects. The question is whether it is worth continuing these supplementations after the first trimester of pregnancy or not. Thus the possible fetal growth promoting and/or preterm birth reducing effect of vitamin supplements in the second and mainly in the third trimester was studied. STUDY DESIGN: Comparison of birth outcomes of singletons born to primiparous pregnant women with prospectively and medically recorded vitamin supplement in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980-1996 contained 6293, 169, and 311 primiparae with folic acid alone, multivitamins and folic acid+multivitamin supplementation, respectively, and their data were compared to the data of 7319 pregnant women without folic acid and folic acid-containing multivitamin supplementation as reference. RESULTS: Mean gestational age was 0.3 week longer and mean birth weight was by 37 g higher in the group of folic acid alone, than in the reference group (39.2 weeks; 3216 g). The rate of preterm births (7.6%) was significantly lower compared with the reference sample (11.8%), but the rate of low birth weight newborns did not show significant reduction. Folic acid alone in the third trimester associated with 0.6 week longer gestational age and a more significant reduction in the rate of preterm births (4.8%). CONCLUSIONS: Minor increase in mean birth weight after high dose of folic acid supplementation during pregnancy would not be expected to result in too large babies; however, the significant reduction in the rate of preterm births may have great public health benefit.

No association found between use of very large doses of diazepam by 112 pregnant women for a suicide attempt and congenital abnormalities in their offspring.

The teratogenic potential of diazepam is debated. The objective of this study was to examine the effects of extremely high doses of diazepam used for attempted suicide during pregnancy on embryo-fetal development. Pregnant women were identified from the female patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest, who had been admitted as self-poisoned subjects from the three million people of Budapest and the surrounding region. This evaluation compares the incidences and types of congenital abnormalities observed in exposed children born to mothers who attempted suicide with diazepam alone or in combination with other drugs during pregnancy with their sib controls. The database consists of a total of 1044 women with self-poisoning during pregnancy between 1960 and 1993. Of these 1044 self-poisoned pregnant women, 229 (21.9%) used diazepam with or without other drugs for a suicide attempt; 112 of these women delivered live-born infants. Doses of diazepam taken ranged between 25 and 800 mg. Of 112 exposed children, 15 (13.4%) had congenital abnormalities, whereas of their 112 matched sibs, eight (7.1%) had congenital abnormalities (odds ratios with 95% confidence intervals: 2.0, 0.8-5.0). Of 37 pregnant women who attempted suicide between the 4th and 12th postconceptional weeks, five (13.5%) delivered live-born babies with a congenital abnormality (undescended testis in two exposed children; congenital dysplasia of the hip, talipes equinovarus deformation type, congenital inguinal hernia-each in one exposed child). The suicide attempts of the mothers of these children did not occur during the critical periods for induction of these defects, indicating that the observations were unrelated to diazepam. The very large doses of diazepam used for self-poisoning during pregnancy did not increase the rate of congenital abnormalities in the offspring.

An evaluation of data for 10 children born to mothers who attempted suicide by taking large doses of alprazolam during pregnancy.

FDA has identified alprazolam, a new type of benzodiazepine, as pregnancy category D. The objective of this study was to evaluate the effects on fetal development of very large doses of alprazolam that were used for suicide attempts during pregnancy. Pregnant women were identified among the patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest, who were admitted as self-poisoned subjects from a total population of the three million people of Budapest and its surrounding region. Rates of congenital abnormalities, intrauterine fetal development, and cognitive-behavioral status were compared between children born to mothers who attempted suicide during pregnancy using alprazolam alone or in combination with other drugs and in their sib controls. Between 1984 and 1993, 559 pregnant women attempted suicide during pregnancy with drugs: 30 of these women self-poisoned with alprazolam, 10 delivered live-born infants who were examined. Doses of alprazolam used were between 7.5 and 100 mg, with a mean of 30 mg. Six of the 10 exposed children were born to mothers who attempted suicide between the 6th and 12th postconceptional weeks. Of the 10 exposed children, two had congenital abnormalities. One had a multiple congenital abnormality that included atypical gastroschisis and minor anomalies; an association of this defect and the 30 mg alprazolam used for self-poisoning in the 14th postconceptional week cannot be excluded. Another exposed child had mild pectus excavatum, but the times of the suicide attempt and the critical period for producing this defect did not overlap. Of 12 sibs, one had a multiple congenital abnormality. Thus, the rate of congenital abnormalities did not significantly differ between exposed children and their sibs. Mean birth weight was higher for babies born to mothers who attempted suicide by alprazolam during pregnancy than in their sib controls. Cognitive status and behavioral scale of the exposed children did not indicate fetotoxic effects, including neurotoxic effects, of large doses of alprazolam. The large doses of alprazolam used for self-poisoning during pregnancy did not result in a significantly higher rate of congenital abnormalities; however, there were only 10 self-poisoned pregnant women, and an association of one multiple congenital abnormality with a large dose of alprazolam cannot be excluded. The findings in this study did not identify fetotoxicity, including neurotoxicity, of very large doses of alprazolam. Our study shows that the self-poisoning model is feasible and provides beneficial information for use in estimating human teratogenic and fetotoxic risks of drugs.

A study of the potential teratogenic effect of large doses of promethazine used for a suicide attempt by 32 pregnant women.

In Hungary, promethazine, a phenothiazine antihistamine, is the second most frequently used drug during pregnancy. The purpose of this study was to examine the effects of very large doses of promethazine that were used for a suicide attempt during pregnancy on embryo-fetal development. Self-poisoned pregnant women were identified from patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest, who were admitted from the three million people of Budapest and surrounding region. The rate of congenital abnormalities, intrauterine development (based on pregnancy age at delivery and birth weight), and cognitive-behavioral status of exposed children born to mothers who attempted suicide with promethazine alone or in combination with other drugs during pregnancy was compared with their sib controls. In all, 89 of the 1044 women with self-poisoning during pregnancy between 1960 and 1993 used promethazine for a suicide attempt. Of these 89 women, 32 delivered newborn babies. The dose of promethazine taken by these women for self-poisoning ranged between 125 mg and 1750 mg (mean of 544 mg, i.e., 21.8 tablets). Of the 32 promethazine-exposed children, nine (28.1 %) were affected with congenital abnormalities. However, of 11 pregnant women who attempted suicide with promethazine between the 3rd and 12th postconceptional week, that is, the critical period for production of most major congenital abnormalities, only three were affected with defects, and the critical periods for producing these defects did not overlap with the time of the suicide attempt during pregnancy. Of 34 unexposed sibs, five (14.7%) had congenital abnormalities; the difference in the total rate of congenital abnormalities between the exposed children and their sib controls was not significant. There also was no difference in pregnancy age-specific birth weight between exposed children and their sibs. Mean intelligence quotient was not reduced, and the incidence of behavioral deviation was not increased in the exposed children. The findings of this study did not indicate teratogenic or fetotoxic (including neurotoxic) effects of large doses of promethazine in children born to mothers who self-poisoned during pregnancy, although the total rate of congenital abnormalities was very high. Our experience shows the feasibility and benefits of using the self-poisoning model in estimating human teratogenic/fetotoxic risks of exposure to drugs.

A study of the teratogenic and fetotoxic effects of large doses of chlordiazepoxide used for self-poisoning by 35 pregnant women.

The human teratogenic potential of chlordiazepoxide is debated. To study the effects on the fetal development of very large doses of chlordiazepoxide that were used for a suicide attempt during pregnancy, self-poisoned pregnant women were identified from patients in a toxicological inpatient clinic in Budapest, Hungary. Comparisons were made between congenital abnormalities, intrauterine fetal development, and cognitive-behavioral status of the exposed children born to mothers who attempted suicide with chlordiazepoxide alone or in combination with other drugs during pregnancy and their sib controls. Of 1044 women with self-poisoning during pregnancy between 1960 and 1993, 88 (8.4%) used chlordiazepoxide with or without other drugs for suicide attempt; 35 of these women delivered live-born infants. Doses of chlordiazepoxide taken ranged between 20 and 300 mg, with a mean of 117 +/- 86 mg. Of 35 exposed children, six (17.1 %) were affected with congenital abnormalities compared with three (13.6%) of their 22 sibs (OR with 95% CI: 1.3 (0.3-4.4). Of 18 pregnant women who attempted suicide between the 4th and 12th postconceptional week, the period most sensitive to congenital malformation, four delivered live-born children affected with a congenital abnormality (atrial septal defect type II, complex defect of respiratory system, mild pyelectasis because of the stenosis of ureteropelvic junction, congenital inguinal hernia). Two other children had fetal alcohol syndrome and unrecognized multiple congenital abnormality including talipes equinovarus, deformation type, and four minor anomalies. The pregnancy age-specific mean birth weight indicated intrauterine fetal growth retardation, which was confirmed by a dose-response relationship and by the higher rate of low birth-weight newborns. Cognitive status and behavioral scale of exposed children did not indicate neurotoxic effects. Very large doses of chlordiazepoxide used for suicide attempts during pregnancy did not induce a higher rate of congenital abnormalities but were associated with dose-dependent intrauterine growth retardation.

A study of the effects of large doses of glutethimide that were used for self-poisoning during pregnancy on human fetuses.

Animal investigations showed some embryolethal and teratogenic effects of glutethimide, a piperidindion derivative non-barbital hypnotic drug. Thus, the objective of this study was to evaluate the effects of very large doses of glutethimide that were used for a suicide attempt during pregnancy on the embryo-fetal development of exposed children. Self-poisoned pregnant women were identified from the population of female patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest who had been admitted from the 3 million people of Budapest and its surrounding region. The rates of congenital abnormalities, intrauterine fetal development (based on birth weight and pregnancy age at delivery) and cognitive-behavioral status of exposed children born to mothers who attempted suicide with glutethimide alone or in combination with other drugs during pregnancy were compared with their sib controls. Of 1044 pregnant women with self-poisoning during pregnancy between 1960 and 1993, 33 used glutethimide for a suicide attempt sixteen of these women delivered live-born infants. The dose of glutethimide ranged between 1000 and 15,000 mg with a mean of 4234 mg. Of the 16 exposed children, five were male and 11 were female. Three exposed children were affected with congenital abnormalities (atrial septal defect type II, pectus carinatum, fetal alcohol syndrome). Of their 16 matched unexposed sib pairs, two had congenital abnormalities. The mean birth weight of the exposed children was somewhat larger due to somewhat longer pregnancy age at delivery. Cognitive status and behavioral scale of the exposed children did not indicate a fetotoxic (including neurotoxic) effect of large doses of glutethimide. Very large doses of glutethimide used for a suicide attempt by 16 pregnant women did not produce teratogenic or fetotoxic (including neurotoxic) effects in their children.

A study of the teratogenic and fetotoxic effects of large doses of amobarbital used for a suicide attempt by 14 pregnant women.

The teratogenic effect of barbitals is debated, and this study was performed to identify the effects of very large doses of amobarbital used for suicide attempts during pregnancy on embryo-fetal development. Self-poisoned pregnant women were identified from patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest, Hungary, who were admitted from the 3 million people of Budapest and its surrounding region. A comparison was made between outcomes of pregnancies of women who attempted suicide with amobarbital alone or in combination with other drugs during pregnancy with sib controls. Of 1044 women with self-poisoning during pregnancy between 1960 and 1993, 33 used amobarbital for a suicide attempt. Of these 33 women, 14 delivered live-born babies. The dose of amobarbital taken by these women ranged between 600 and 10,000 mg, with a mean of 3886 mg. Of the 14 amobarbital-exposed children, 9 had mothers who attempted suicide between the 3rd and 12th post-conceptional weeks. None of these children had a congenital abnormality, and there was no evidence of fetal growth retardation. The distribution of cognitive status and behavioral scale of the exposed children were comparable with those of their sibs although one exposed child had a very low (about 75) IQ, whereas another one was treated because of a very severe aggressive behavioral deviation. Exposure to very large doses of amobarbital that were used for self-poisoning during pregnancy did not produce teratogenic effects in this study.

A study of teratogenic and fetotoxic effects of large doses of meprobamate used for a suicide attempt by 42 pregnant women.

The human teratogenic effect of meprobamate is debated. Thus, the available data set regarding very large doses of meprobamate used for a suicide attempt during pregnancy was evaluated for effects on fetal development. Pregnant women were identified from self-poisoned subjects of a total population of approximately three million people (Budapest and surrounding region) who were admitted to the Department of Toxicology Internal Medicine, Koranyi Hospital, Budapest. Comparisons were made of congenital abnormalities, intrauterine fetal growth, and cognitive-behavioral status in exposed children born to mothers who attempted suicide with meprobamate alone or in combination with other drugs during pregnancy with their control sibs. Of 1044 women with self-poisoning during pregnancy between 1960 and 1993, 107 (10.3%) used meprobamate, with or without other drugs for a suicide attempt; 42 of these 107 women delivered live-born infants. The dose of meprobamate used for the suicide attempt ranged between 1000 and 26,000 mg, with a mean of 3690 mg. Of 42 exposed children, seven (16.7%) were affected with congenital abnormalities, however, of their 27 sib controls, four had a CA (14.8%) (OR with 95% CI: 1.7, 0.5-4.9) of 14 had a congenital abnormality. Of 14 mothers who attempted suicide during the 4-12th postconceptional week, two delivered live-born babies affected with mild isolated congenital abnormality: undescended testis and congenital dysplasia of the hip. However, the critical period for production of these two defects did not overlap with the time of the mother's suicide attempt. Mean birth weight and pregnancy age, cognitive status, and behavioral scale of the exposed children did not indicate fetotoxic, including neurotoxic, effects of large doses of meprobamate. Very large doses of meprobamate that were used for self-poisoning during pregnancy did not result in teratogenic or fetotoxic, including neurotoxic, effects on fetal development.

A study of the effects of large doses of medazepam used for self-poisoning in 10 pregnant women on fetal development.

The purpose of this article is to report an evaluation of the teratogenic and fetotoxic potential of medezepam in humans based on pregnant women who used very large doses of medazepam for a suicide attempt. All self-poisoned patients were cared for at the Department of Toxicology Internal Medicine, Koranyi Hospital, a toxicological inpatients clinic in Budapest, Hungary, between 1960 and 1993. Pregnant women were identified from self-poisoned subjects admitted from a population base of three million people of Budapest and the surrounding region. The rates of congenital abnormalities (CAs), intrauterine fetal development, cognitive and behavioral status in children born to mothers who attempted suicide with medazepam alone or in combination with other drugs during pregnancy was compared in their sib controls. Between 1980 and 1993, 835 pregnant women in our study attempted suicide during pregnancy with drugs. Of these, 314 delivered live-born infants and 283 were examined and/or evaluated. Thirty-two (3.8%) of these 835 pregnant women used medazepam with or without other drugs for self-poisoning; 10 of these women delivered live-born babies. The dose of medazepam used for the suicide attempt ranged between 60 and 500 mg, with a mean of 276 mg. Eight of the 32 suicide attempts involving medazepam occurred between the 4th and 12th postconceptional weeks. Of the 10 live-born exposed children, one was affected with congenital inguinal hernia; one of the 13 sib controls had a lethal hydronephrosis. No adverse effects were observed on intrauterine growth, cognitive status, or behavioral deviations in the 10 children born to mothers who attempted suicide with medazepam during pregnancy. Very large doses of medazepam were used for self-poisoning during pregnancy. These doses did not increase the rate of CAs even though eight mothers attempted suicide during the most critical period for production of CAs. No fetotoxic, including neurotoxic, effects of exposure of live-born children to a very large dose of medazepam were observed. Our experiences show the feasibility and benefits of use of the self-poisoning model in estimating human teratogenic and fetotoxic risks of drugs.

A study of the teratogenic and fetotoxic effects of large doses of barbital, hexobarbital and butobarbital used for suicide attempts by pregnant women.

The teratogenic potential of barbiturates is debated. The objective of this study was to evaluate the effects of very large doses of different barbiturates, except phenobarbital and amobarbital, on fetal development in pregnant women who attempted suicide. These self-poisoned pregnant women were identified among the patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest. The prevalence at birth of congenital abnormalities and intrauterine fetal growth, based on pregnancy age at delivery and birth weight, as well as cognitive-behavioral status in exposed children born to mothers who attempted suicide with barbiturates alone or in combination with other drugs, during pregnancy, were compared with their sibs as controls. Of 1044 women with self-poisoning during pregnancy between 1960 and 1993, 411 delivered live-born babies; of these, 367 (89.3%) exposed children were evaluated. Of the 367 exposed children, 6, 5, 4 and 4 were born to mothers who attempted suicide with very large doses of Barbamid (butobarbital and aminophenazone), hexobarbital, butobarbital and Belloid (butobarbital, hyoscyamine and secalis cornuti alkaloida) tablets, respectively. Of 19 exposed children, two children with a congenital inguinal hernia were born to mothers who attempted suicide with 30 tablets of Belloid (900 mg butobarbital) in the 20th postconceptional week or with 20 tablets of Belloid in combination with chlordiazepoxide (100 mg) and nitrazepam (100 mg) in 12th postconceptional week. However, the critical period for production of congenital inguinal hernia is in the last months of pregnancy. None of the exposed children born to the other 12 pregnant women who attempted suicide with these barbiturates between the third and 12th postconceptional week, i.e., during the critical period for production of most major congenital abnormalities, had a congenital abnormality. Congenital abnormalities did not occur among 16 sib controls. Intrauterine fetal growth was similar between sibs and exposed children; cognitive status and behavioral scale also did not indicate any neurotoxic effects from large doses of these barbiturates. The very large doses of barbital, hexobarbital and/or butobarbital used for self-poisoning during pregnancy were not teratogenic to the children, although it must be recognized that the number of exposed children was limited.

A study of the potential teratogenic effects of large doses of drugs rarely used for a suicide attempt during pregnancy.

The available data set regarding pregnant women who attempted suicide during pregnancy was evaluated to estimate the teratogenic effect of very large doses of drugs based on the rate and distribution of congenital abnormalities of exposed children. These pregnant women were identified from patients of central toxicological inpatients clinic, Budapest, Hungary, 1960-1993. Of 1044 women with self-poisoning during pregnancy, 411 delivered live-born babies; 367 of these children were examined in this study. Data for 12 frequently used (10 or more times) drugs were published previously; this paper presents 77 medicines (58 drugs and 19 medicinal products including multiple components) that were rarely used for a suicide attempt by 197 pregnant women. Although 23 (11.7%) exposed children had congenital abnormalities (CAs), in general, a causal relationship of the CA and the drug taken by the pregnant woman cannot be assumed. This is because the suicide attempt often did not occur during a critical period for producing the CA. Of 67 pregnant women who attempted suicide between the 3rd and 12th postconceptional week, that is, the critical period of most major CAs, 7 (10.5%) children were affected with CAs. This high rate of CAs in exposed children can be explained by the intensive medical examinations, including diagnosis of mild CAs and minor anomalies, or the low socioeconomic status and hazardous lifestyle of mothers. None of the rarely used drugs was identified as a potential human teratogen. Experience of the authors shows the feasibility and benefits of using the self-poisoning model in estimating human teratogenic/fetotoxic risks of exposure to drugs.

Phenolphthalein treatment in pregnant women and congenital abnormalities in their offspring: A population-based case-control study.

Phenolphthalein is frequently used laxative drug since 1930s, but the possible teratogenic effect of phenolphthalein was not checked in casecontrol eptedmiological study. In addition US Food and Drug Administration (FDA) declared the mutagenic and carcinogenic effect of phenolphthalein in 1999, thus we decided to evaluate the birth outcomes particularly congenital abnormalities (CAs) of newborn infants born to women treated with phenolphthalein during pregnancy. Cases with CA and their matched controls without CA born to mothers with phenolphthalein use during pregnancy were compared in the population-based large data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities. Of 22,843 cases with CA, 191 (0.83%) while of 38,151 controls, 247 (0.64%) were born to mothers with phenolphthalein treatment (adjusted OR with 95% CI: 1.3, 1.0-1.5). The mean gestational week at delivery was somewhat longer in both the case (0.3 week) and control (0.2 week) groups while the mean birth weight was somewhat larger in cases (46 g) and controls (12 g) born to mothers with phenolphthalein treatment during the study pregnancy compared with mothers without phenolphthalein treatment. These differences were in agreement with the lower rate of preterm births and low birth weight in controls born to mothers with phenolphthalein treatment during pregnancy. The detailed analysis of different CA groups showed an association between maternal phenolphthalein treatment during pregnancy and a higher risk for Hirschsprung's disease (p = 0.01) based on 4 cases in the so-called other isolated CA-group. In conclusion phenolphthalein treatment in pregnant women associates with a higher risk for Hirschsprung's disease in their children, but this finding is only a signal which needs confirmation or rejection in other studies.

Maternal kidney stones during pregnancy and adverse birth outcomes, particularly congenital abnormalities in the offspring.

OBJECTIVE: The possible adverse birth outcomes, particularly congenital abnormalities (CAs) in pregnant women with kidney stones (KS) previously have not been evaluated; therefore, we decided to study this possible association. METHODS: The population-based data set of the Hungarian Case-Control Surveillance of CAs, 1980-1996, was used for this analysis. RESULTS: Of 22,843 newborns or fetuses with CAs, 69 (0.30%) had mothers with KS during pregnancy. Of 38,151 matched control newborns without any abnormalities, 147 (0.39%) had KS during pregnancy. KS were associated with an adjusted prevalence odds ratio (POR) with 95% CI of 0.8, 0.6-1.0 for CAs. A higher prevalence of maternal KS during the first trimester of pregnancy was not found in any CA group. There was no higher rate of preterm birth and low birthweight in the newborns of pregnant women with KS. CONCLUSIONS: There is no higher risk for adverse birth outcomes particularly CAs in the offspring of mothers with KS and related drug treatments during pregnancy.

Maternal urinary tract infection and related drug treatments during pregnancy and risk of congenital abnormalities in the offspring.

OBJECTIVE: The association between urinary tract infection (UTI) of pregnant women and preterm birth/low birthweight is known, but the possible association between UTI and congenital abnormalities (CAs) was evaluated rarely. Only one study showed an association with atrial septal defect, thus we decided to check this possible association. DESIGN: The population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA); most maternal UTIs were based on medically recorded data. SETTING The HCCSCA, 1980-1996, contained 22 843 newborns or fetuses with CAs and 38 151 matched controls, i.e. newborn infants without any HCAs. POPULATION: Hungarian informative offspring: live births, stillbirths and prenatally diagnosed malformed fetuses. METHODS: Case-control pair analysis. MAIN OUTCOME MEASURES: Twenty-five CA groups. RESULTS: A total of 1542 (6.75%) mothers in the case group had UTI during entire pregnancy compared with 2188 (5.74%) mothers in the control group (adjusted prevalence odds ratios [POR] with 95% CI: 1.15, 1.06-1.24). We did not find a higher prevalence of UTI during the second and/or third months of pregnancy in total case group (adjusted POR with 95% CI: 1.1, 0.9-1.2) and in any group of CAs including atrial septal defect type II. CONCLUSIONS: No evidence for the teratogenic effect of maternal UTI and related drug treatments during early pregnancy.

ErbB-2/HER-2 protein expression, serum tumour necrosis factor-alpha (TFM-alpha) and soluble tumour necrosis factor receptor-2 (TNFR-2) concentrations in human carcinoma of the uterine cervix.

The expression of erbB-2 protein (by immunohistochemistry), serum TNF-alpha, soluble TNF-receptor 2 (sTNFR-2, ELISA) concentrations and mitogenic (LPS, ConA, PHA) induced TNF-alpha production of the peripheral blood mononuclear cells (PBMNC) were studied in 91 (UICC Stage 1: 39, Stage 2: 33, Stage 3: 14, Stage 4: 5) patients with carcinoma of the uterine cervix. During a follow-up period of seven years 30 patients died (Stage 4: 5, Stage 3: 12, Stage 2: 11, Stage 1: 2). ErbB-2 protein expression was significantly more frequent in patients with UICC Stages 3-4 (14/19), and in those with fatal outcomes (14/30, p < 0.0001, chi-square test). Serum TNF-alpha (2.70 +/- 0.69 pg/ml) and sTNFR-2 (3.85 +/- 1.05 ng/ml) concentrations were significantly lower in cancer patients (p < 0.0001, Mann-Whitney test) as compared to 64 age-matched control women (TNF-alpha: 4.32 +/- 0.36, TNFR-2: 4.85 +/- 0.82). The mitogenic induced TNF-alpha production of PBMNC was also significantly less with all the three mitogens applied (LPS: 35.24 +/- 8.84, ConA: 26.28 +/- 7.81, PHA: 20.48 +/- 7.04 pg/l million of cells/24 hours, p < 0.0001) as compared to the controls (LPS: 65.33 +/- 8.82, ConA: 51.00 +/- 8.87, PHA: 41.80 +/- 9.01). Serum TNF-alpha, sTNFR-2 concentrations and the mitogenic induced TNF-alpha production of PBMNC was significantly decreased in patients with erbB-2 positivity as compared to those with negativity. In conclusion the expression of the oncoprotein and the lower levels of the members of the TNF system seem to be poor prognostic parameters in patients with carcinoma of the uterine cervix.