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The aim of the study was to estimate the possible association of pregnant women with paroxysmal supraventricular tachycardia (PSVT) with the possible risk for adverse birth outcomes, particularly different congenital abnormalities (CAs) in their children. Prospectively and medically recorded PSVT was evaluated in 103 pregnant women who later had offspring with CA (case group) and 149 pregnant women who later delivered newborn infants without CA (control group) and matched to cases in the population-based data set of the Hungarian Case–Control Surveillance System of Congenital Abnormalities, 1980–1996. Of 252 pregnant women with PSVT, 115 (45.6%) had the onset of this condition before the study pregnancy, that is, their PSVT was a chronic condition, while the rest (N = 137) of PSVT was considered as new onset in the study pregnancy. The comparison of occurrence of PSVT in pregnant women who had offspring with different CA groups and in control mothers showed a higher risk for cardiovascular CAs (adjusted OR with 95% CI: 2.1, 1.1–3.8) explained mainly by secundum atrial septal defect. This association was confirmed in pregnant women with PSVT in the second and/or third gestational month, that is, critical period of cardiovascular CAs. In conclusion PSVT in pregnant women associates with a higher risk of secundum atrial septal defect in their children. © 2015 Wiley Periodicals, Inc.

Previously an unexpected association of maternal angina pectoris (MAP) during pregnancy with a higher risk of orofacial clefts in their children was found. There were three objectives of this study: (i) to evaluate the validity of MAP-diagnoses in the previous study and the recent history of mothers with MAP in a follow-up study; (ii) to estimate the prevalence of other congenital abnormalities in the offspring of mothers with MAP; and (iii) to analyze the possible effect of confounders for the risk of orofacial clefts. The large dataset of population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980–1996 was evaluated including 22 843 cases with congenital abnormalities and 38 151 controls without any defect. Twenty-two cases (0.10%) and 12 controls (0.03%) were born to mothers with medically recorded MAP (odds ratio [OR] with 95% confidence interval [CI]: 3.7, 1.8–7.3). Of 22 cases, six had isolated cleft lip ± palate (OR with 95% CI: 13.3, 4.9–35.9) and two were affected with isolated cleft palate (OR with 95% CI: 10.5, 2.3–47.6). The diagnosis of MAP was confirmed in seven women visited at home in 2009–2010, two had recent myocardial infarction and five were smokers. There was no higher risk for other congenital abnormalities. In conclusion the higher risk of orofacial clefts was confirmed in the children of mothers with MAP and smoking may trigger the genetic predisposition of both MAP and orofacial clefts. However, the number of cases was limited and therefore further studies are needed to confirm or reject this theoretically and practically important observation.

Objective. To evaluate the effect of hydroxyethylrutoside (HER) for fetal development because this flavonoid derivate drug is frequently used in pregnant women for the treatment of vascular diseases. Method. Comparative analysis of exposure (HER treatment) during pregnancy in the newborn infants without any defects born to mothers with or without HER treatment in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities. Main outcomes measures were gestational age at delivery, birth weight, pre- and post-term birth, low and large birth weight. Results: Of 38,151 newborn infants, 1,143 (3.0%) were born to mothers with oral HER treatment. The mean birth weight of newborn infants born to mothers with HER was 115 grams larger and is associated with a lower rate of low birth weight and a higher rate of large birth weight. Conclusions. Oral HER treatment during pregnancy associates with a fetal growth promotion effect.

Hydroxyethylrutoside (HER), a flavonoid derivate drug, used frequently in pregnant women for the treatment of vascular diseases. The aim of this case-control study was to evaluate the teratogenic potential of oral HER treatment in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities.Comparative analysis of exposure (HER treatment) during pregnancy in the mothers of cases with congenital abnormalities and matched control newborns without any defect in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities.Of the 22,843 cases with congenital abnormalities, 567 (2.5%) had mothers with HER treatment while of 38,151 matched controls, 1143 (3.0%) were born to mothers with HER treatment (OR with 95% CI: 0.8, 0.7-0.9). However, an association of HER treatment during the second and/or third month of pregnancy was found with the higher risk of unilateral ocular coloboma (OR with 95% CI: 5.4, 2.2-12.9) and a new congenital abnormality syndrome including anotia/microtia, poly/syndactyly and caudal (genital and anal) defects (OR with 95% CI: 3.0, 1.3-27.4).Oral HER treatment during early pregnancy associates with a higher risk for ocular coloboma and for a newly delineated congenital abnormality syndrome.

Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD) as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled) trials indicated that periconceptional folic acid (FA)-containing multivitamin supplementation prevented the major proportion (about 90%) of neural-tube defects (NTD) as well as a certain proportion (about 40%) of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional supplementation; and (iii) flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin’s statement: “An ounce of prevention is better than a pound of care”.

Objective To investigate the association of pre-eclampsia (PE) or PE with superimposed chronic hypertension (PE + SCH) in pregnant women with the risk of various structural birth defects (i.e. congenital abnormalities) in their offspring. Study design A population-based case–control study using the Hungarian Case–Control Surveillance of Congenital Abnormalities data set (1980–1996), including 22,843 cases with congenital abnormalities and 38,151 matched controls without any congenital abnormalities. The incidence of PE and PE + SCH was compared in women who had offspring with congenital abnormalities (cases) and women who had offspring without any congenital abnormalities (controls). Results The incidence of PE was examined in 585 cases and 1017 controls, and the incidence of PE + SCH was examined in 154 cases and 269 controls. None of the 25 studied types of congenital abnormality was found to be more likely among the offspring of women with PE. However, the risks of renal dysgenesis [odds ratio (OR) 4.7, 95% confidence interval (CI) 1.7–12.8], esophageal atresia/stenosis (OR 4.6, 95% CI 1.8–12.2) and rectal/anal stenosis (OR 3.7, 95% CI 1.6–8.5) were higher in the offspring of pregnant women with PE + SCH. Conclusions PE in pregnant women was not associated with a higher risk of any congenital abnormalities in their offspring, but PE + SCH was associated with a higher risk of renal dysgenesis, esophageal atresia/stenosis and rectal/anal stenosis. These findings need confirmation in other studies.

Vitamin E is frequently used for prevention/treatment of repeated or threatened abortion and threatened preterm delivery in Hungarian pregnant women, though, internationally this old-fashion method is not recommended.The rate of preterm birth of newborns in pregnant women with high dose (estimated daily dose 450 mg) vitamin E treatment or without this treatment was compared in the population-based large data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities.Of 38,151 newborns with any defect, 2,287 (6.0%) had mothers with vitamin E treatment. Pregnant women with vitamin E treatment had very high rate of threatened abortion (43.6% vs. 15.4%) and high rate of threatened preterm delivery (27.5% vs. 13.4%) compared to pregnant women without vitamin E treatment. Nevertheless, the gestational age at delivery was 0.2 week longer and rate of preterm births was lower in the newborns of pregnant women with vitamin E treatment (6.6% vs. 9.3%; adjusted OR with 95% CI: 0.71, 0.63-0.84). This preterm preventive effect of vitamin E treatment could not be explained by known confounders, though folic acid/multivitamins also reduced the rate of preterm birth.The study showed nearly 30% reduction in preterm births of pregnant women with vitamin E treatment.

Background: The aim of the study was to estimate the effect on the fetal development of high doses of prescription drugs taken as a suicide attempt during pregnancy. Methods: Pregnant women were identified among self-poisoned females in the toxicological inpatient clinic in Budapest between 1960 and 1993. Congenital abnormalities, intrauterine development based on birth weight and post-conceptional age, mental retardation, cognitive-behavioral status were compared in exposed children born to mothers who had attempted suicide by means of a drug overdose during pregnancy with their siblings, born either before or after the affected pregnancy, as sib controls. Results: Of a total of 1 044 pregnant women, 74 used the combination of amobarbital, glutethimide and promethazine (Tardyl®, one of the most popular drugs for treatment of insomnia in Hungary) for suicide attempt. Of these 74 women, 27 delivered live-born babies. The mean dose of Tardyl® used for suicide attempts was 24 times the usually prescribed clinical dose. The rate of congenital abnormalities and intrauterine retardation was not higher in exposed children than in their sib controls. However, of the 27 exposed children, eight (29.6%) were mentally retarded (Χ\documentclass[12pt]{minimal} \usepackage{wasysym} \usepackage[substack]{amsmath} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage[mathscr]{eucal} \usepackage{mathrsfs} \DeclareFontFamily{T1}{linotext}{} \DeclareFontShape{T1}{linotext}{m}{n} { linotext }{} \DeclareSymbolFont{linotext}{T1}{linotext}{m}{n} \DeclareSymbolFontAlphabet{\mathLINOTEXT}{linotext} \begin{document} $$ {\mathrm{_{{1}}^{{2}}}} $$ \end{document} )=79.7, p= Sig) while mental retardation did not occur among 46 sib controls. These exposed children were born to mothers who attempted suicide with Tardyl® between the 14th and 20th post-conceptional weeks. The components of Tardyl® used separately for a suicide attempt during pregnancy were not associated with a higher risk of mental retardation. Therefore the high doses of Tardyl® associated with the high risk for mental retardation may be due to the interaction of its three drug components. Conclusions: The findings of the study showed that the high doses of a drug containing three components may be associated with a significantly increased risk for mental retardation without any structural defects, whereas each of these three component drugs taken alone was not associated with this adverse effect.

Introduction The human papillomavirus infection is one of the most frequent sexually transmitted diseases. The presence of human papillomavirus is demonstrable in nearly all cases of cervical cancer. Cervical cancer is the second most frequent tumourous disease among women, not just in the world but in Hungary. Aim Our aim was to estimate women's knowledge of the human papillomavirus and cervical cancer. We searched connection between the frequent mortality, the low participation rate of screenings and the knowledge of cervical cancer. Methods The related questionnaire contained 18 questions and was filled in by 422 women in cities and villages. The lower age limit of the randomly canvassed people was 14 years, but we reached older women as well. The incoming data were processed with a computer program. The completed questionnaires were differentiated by age, place of residence, qualification, whether the subject had children and whether she got human papillomavirus vaccination. Results The resul...

Objectives. To study the efficacy of vitamin E supplementation for the reduction of preterm birth/low birth- weight newborns in pre-eclamptic pregnant women. Design. Comparison of the rate of preterm birth and low birthweight in pre-eclamptic pregnant women with or without vitamin E treatment. Setting. Hungarian Case-Control Surveillance Sys- tem of Congenital Abnormalities, 1980-1996. Population. Newborn infants in Hungarian population. Methods. Medically recorded pre-eclampsia and birth outcomes of pregnant women were evaluated. Main outcome measures. Preterm birth, low birthweight. Results. There was no lower incidence of pre-eclampsia after vitamin E treatment. Pregnant women with pre-eclampsia and without vitamin E treatment had a higher rate of preterm births (10.4% vs. 9.3%) and low birthweight newborns (7.8% vs. 5.6%) than the reference sample of 34,928 pregnant women without pre-eclampsia and without vita- min E treatment. The newborns of 936 pregnant women with pre-eclampsia and without vitamin E treatment had higher rate of preterm birth (10.4% vs. 8.6%; OR with 95% CI: 0.8, 0.7-0.9) than 81 pregnant women with pre-eclampsia but with vitamin E treatment. However, the rate of low birthweight newborns was somewhat but not significantly higher (8.6% vs. 7.8%; OR with 95 CI: 1.1, 0.8-1.4) in pregnant women with pre-eclampsia and with vitamin E treatment. There was very high rate of threatened abortion (45.7% vs. 15.3%) and threatened preterm delivery (27.2% vs. 13.5%) in 81 pre- eclamptic pregnant women with vitamin E treatment compared to the reference group. Conclusions. Vitamin E treatment reduced the rate of preterm birth in pregnant women with pre-eclampsia but not the rate of low birthweight newborns.

The objective of this study was to evaluate the possible association of drug treatments in pregnant women with a higher risk of congenital abnormalities of the external ear, particularly microtia/anotia, in their children. The frequency of drug treatments was compared in the mothers of cases with isolated or multiple (syndromic) ear abnormalities and in the mothers of three different controls: controls matched to cases, all controls (these controls had no defects) and malformed controls in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities. There was no significantly higher use of any drug in the mothers of 354 cases with isolated external ear abnormalities than in the mothers of different controls. However, of 156 cases with multiple ear abnormalities, 11 had mothers with hydroxyethylrutosidea treatment and a characteristic pattern of congenital abnormalities was found in these children. Four cases with multiple ear abnormalities were born to epileptic mothers treated with valproate, phenytoin and polytherapy in two cases. Drug treatments are not important in the origin of isolated ear abnormalities. However, a higher risk of multiple ear abnormalities was found in children born to mothers with treatment of hydroxyethylrutosidea or antiepileptic drugs during pregnancy.

Human chorionic gonadotropin (hCG) is used for treatment of pregnant women with threatened and re- peated miscarriages/spontaneous abortions in Hungary. Thus the objective of the study was to evaluate the possible asso- ciation of medically recorded hCG treatment during the second and/or third gestational month in pregnant women with the risk of different congenital abnormalities in their offspring on the basis of comparison to pregnant women who were also treated with hCG and delivered control newborns without any defect in the population-based Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Of 22,843 cases with congenital abnormalities, 83 (0.36%), while of 38,151 controls without any defect, 97 (0.25%) had mothers with hCG treatment (adjusted OR with 95% CI: 1.6, 1.2- 2.1), though there was no association between any congenital abnormality group and a higher rate of maternal hCG treat- ment. In conclusion the detectable slight general risk for congenital abnormalities in the offspring of mothers with hCG treatment during early pregnancy may be connected with other factors, particularly the causes of previous miscarriages.

Previous studies reported controversial results regarding the possible association of recurrent genital herpes during pregnancy with a higher risk of preterm birth/low birth weight in newborns. Thus, birth outcomes of mothers with prospective and medically recorded symptomatic recurrent genital herpes confirmed by serological examination and of mothers without genital herpes were compared in the population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities. Our results showed that of 38,151 newborn infants, 86 (0.23%) had mothers with symptomatic recurrent genital herpes confirmed by serological examination during pregnancy. The rate of preterm births (14.0% vs. 9.2%) was higher in babies born to mothers with symptomatic recurrent genital herpes (OR with 95% CI: 1.7, 1.0–3.1) and this increase showed a trimester dependence with the highest rate in the third trimester (23.5%; OR with 95% CI: 2.6, 1.5–4.5). In conclusion, clinically diagnosed recurrent genital herpes during the third trimester of pregnancy associated with high risk for preterm birth.

The objective of the study was to estimate the prevalence at birth and epidemiologic characteristics of patients/cases with both isolated and multiple “syndromic” external ear congenital abnormalities (CAs) in Hungary. The Hungarian Congenital Abnormality Registry, 1980–1996, included 649 cases with isolated external ear CAs, while the number of cases with unclassified multiple CA, including ear CAs, was 331. Thus the prevalence at birth of cases with isolated external ear CAs and unclassified multiple CAs was 0.30 and 0.15, respectively, for a total 0.46 per 1000 births. After reevaluation of reported 354 cases with isolated external ears CAs in the Hungarian Case-Control Surveillance of Congenital Abnormalities, 74 (20.9%) and 236 (66.7%) were affected with mild and severe microtia, while 24 (6.8%) had anotia. The fourth group included 20 cases with the combination of anotia/microtia and external/middle ear CAs. Isolated ear CAs showed a slight male excess (54.0%) and strong predominance of unilateral manifestation (93.4%). Multiple ear CAs showed a stronger male excess (65.4%) and less frequent unilateral affection (62.2%). In conclusion, ear CAs had a low diagnostic validity; thus it was necessary to reassess the data and to reclassify several cases.

The objective of the present study was to estimate the preventive effect of folic acid for structural birth defects (i.e. congenital abnormalities [CAs]) in the offspring of pregnant women with diabetes mellitus type 1 (DM-1). The occurrence of medically recorded DM-1 in pregnant women who had malformed fetuses/newborns (cases) and delivered healthy babies (controls) with or without folic acid supplementation was compared in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities. The case group included 22 843 offspring, and there were 79 (0.35%) pregnant women with DM-1, while the control group comprised of 38 151 newborns, and 88 (0.23%) had mothers with DM-1. Case mothers with DM-1 associated with a higher risk of total rate of CAs in their offspring (OR with 95% CI: 1.5, 1.1–2.0) compared to the total rate of CAs in the offspring of non-diabetic case mothers. This higher risk can be explained by four specific types/groups of CAs: isolated renal a/dysgenesis; obstructive CA of the urinary tract; cardiovascular CAs; and multiple CAs, namely caudal dysplasia sequence. However, there was no higher rate of total CAs in the children of pregnant women with DM-1 after folic acid supplementation; in addition, neural-tube defect and renal a/dysgenesis did not occur. However, this benefit cannot be explained by the CA reduction effect of folic acid during the critical period of major CAs. In conclusion, there was a certain reduction in maternal teratogenic effect of DM-1 after folic acid supplementation during pregnancy, but the explanation of this effect requires further study.

Objective: In Hungary, vitamin E is frequently used to prevent repeated or threatened abortion. A previous study showed a higher risk of cardiovascular malformations in the children of pregnant women who had a high vitamin E intake either in their diet or by taking supplements. The objective was to examine this association. Methods: The Hungarian Case–Control Surveillance System of Congenital Abnormalities, 1980–1996, is a large, population-based dataset including 22,843 cases with congenital abnormalities, 38,151 healthy controls matched to the cases, and 834 patient controls with Down syndrome. Vitamin E treatment was compared in the mothers of these children. Results: The mothers of 1418 cases with congenital abnormalities (6.2%), 2267 controls (6.0%) and 43 patient controls (5.2%) had vitamin E treatment during pregnancy. A preliminary comparison of cases and controls showed a higher risk for four congenital abnormality groups, including cardiovascular malformations. However, if only prospectively and medically recorded vitamin E treatments in the prenatal maternity logbook were evaluated during the critical period of different congenital abnormalities, the higher risk for these congenital abnormalities was not found. Conclusions: The results of this study were based on relatively high-dose vitamin E intake in pregnant women and were not able to confirm the previously reported teratogenic effect of vitamin E.

Background The possible association between otitis media in pregnancy (OMP) and structural birth defects, that is, congenital abnormalities (CAs), in their offspring has not been studied. Methods The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980 and 1996, was evaluated. Results There were 58 (0.25%) and 55 (0.14%) of 22 843 cases and 38 151 controls with mothers who had OMP, respectively. There was association of OMP and a higher risk of ear CA. Conclusions A possible explanation for the association of OMP with higher risk of ear CA may be some morphological deviation of the inner ear.

After the short summary of history of primary prevention of neural tube defects by folic acid or folic acid-containing multivitamin supplementation during the periconception period, the three main unsolved problems are highlighted.Both intervention trials and observational studies confirmed that this new primary preventive method is effective - beyond the prevention of neural-tube defects - in the reduction of the most common structural birth defects: congenital cardiovascular abnormalities. Nevertheless, this important progress in the field of congenital abnormalities is not appreciated appropriately. The periconception supplementation of both folic acid alone and folic acid-containing multivitamin is useful; however, the available data indicate the higher efficacy of multivitamins in the primary prevention of neural-tube defects and congenital cardiovascular abnormalities. The optimal dose of folic acid is not known though this knowledge would be necessary from both a scientific and practical aspect.Periconception folic acid or folic acid-containing multivitamin supplementation has resulted in a breakthrough in the primary prevention of neural-tube defects, cardiovascular abnormalities and probably some other defects; however, extra efforts are necessary to eliminate folic acid or folic acid-containing multivitamin preventable congenital abnormalities.

Peptic ulcer disease (PUD) is a common disease which can also occur in pregnant women. However, the possible association of PUD and related drug treatments in pregnant women with the risk of structural birth defects (i.e. congenital abnormalities [CA]) in their offspring has not been estimated in controlled population-based epidemiological studies. Thus, the prevalence of PUD in pregnant women who later delivered babies (cases) with different CA and in pregnant women who delivered newborns without CA (controls) was compared in the Hungarian Case-Control Surveillance of Congenital Abnormalities. Controls were matched to cases. Of 22,843 cases with congenital abnormalities, 182 (0.80%) had mothers with reported/recorded PUD, while of 38,151 controls, 261 (0.68%) were born to mothers with reported/recorded PUD. However, PUD(?) based on maternal information and/or unspecified diagnostic criteria, and PUD(!) based on endoscopic diagnosis showed different variables of mothers and newborn infants. Thus, finally, 20 case mothers and 58 control mothers with PUD(!) and related drugs were evaluated in detail. There was no higher risk for total CA group in the offspring of mothers with PUD during pregnancy (adjusted OR with 95% CI: 0.6, 0.3-0.9). Specific CA groups in cases were also assessed versus controls, but specified CA had no higher risk in the offspring of pregnant women with PUD and related drug treatments. In conclusion, a higher rate of CA was not found in the offspring of mothers with PUD.

Hungarian Preconceptional Care includes the preconceptional screening of sexually transmitted infections/disorders (STD) and vaginal candidosis of potential mothers and pyospermia of potential fathers. The aim of this study was to evaluate the effect of this screening and treatment for the rate of preterm births. Clinical and subclinical vaginal candidiasis (asymptomatic candida colonisation), combination of STD and vaginal candidiasis, STD without vaginal candidiasis, finally women without STD and vaginal candidiasis as references were evaluated in 4,672 pregnant women. The association of STD in pregnant women with higher risk of preterm birth was confirmed. However, an association was also found between clinically diagnosed vaginal candidiasis, asymptomatic candida colonisation, and a higher risk for preterm births. This risk was reduced with clotrimazole treatment. However, pregnant women without recognized STD and/or vaginal candidiasis had a higher risk for preterm birth than pregnant women with STD or vaginal candidiasis after appropriate treatment. Thus the conclusion of the study is that the preconceptional screening of STD and vaginal candidiasis followed by appropriate treatment is important to prevent a certain part of preterm birth but it is necessary to improve the efficacy of the previously used methods for this screening.

The prevalence of epilepsy is 0.3-0.6% in pregnant women and the higher rate of structural birth defects, i.e. congenital abnormalities (CAs) was recognized in their children. There are four aims of this review based on the popula- tion-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980-1996 with the good validity of CA-diagnoses. (I) Most studies on the teratogenic/fetotoxic effects of antiepileptic drugs (AED) had too small samples therefore underpowered, thus the evaluation the findings of different studies together are appropri- ate to draw significant conclusions, therefore the data of HCCSCA are presented here. Of 22,843 cases with CA, 95 (0.42%), while of 38,151 controls without CA, 90 (0.24 %) had mothers with medically recorded epilepsy (OR with 95% CI: 1.8, 1.3-2.4) and AED in the prenatal maternity logbook. (II) Hungary had different spectrum of AED as in Western countries, thus the teratogenic potential of some less-known AED (e.g. sultiame) can be evaluated. (III) The efficacy of recent special medical care of epileptic pregnant women introduced in 1990 is worth checking. There was no significant increase in the proportion of monotherapy but the rate of total CAs decreased by 20% in the 1990s compared to the 1980s. (IV) Folic acid may reduce the teratogenic potential of some AED, nevertheless this analysis revealed that folic acid was used less frequently by epileptic pregnant women than by non-epileptic pregnant women. Thus an international consensus statement is an urgent task in this topic.

Objective. To evaluate the rate of preterm birth and low birth weight in the newborns of pregnant women with early and late onset pre-eclampsia according to folic acid supplementation.Study design. Birth outcomes of newborns were evaluated in 1,017 (2.7%) pregnant women with medically recorded pre-eclampsia and 37,134 pregnant women without pre-eclampsia as reference in the Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980–1996, in addition these study groups were differentiated according to the supplementation of high dose of folic acid alone from early pregnancy.Results. Pregnant women with pre-eclampsia associated with a higher rate of preterm birth (10.2% versus 9.1%) and low birthweight (7.9% versus 5.6%). There was a lower risk of preterm birth (6.8%) of newborn infants born to pregnant women with early onset pre-eclampsia after folic acid supplementation from early pregnancy though the rate of low birthweight was not reduced significantly. There was no significant reduction in the rate of preterm birth and low birthweight in pregnant women with late onset pre-eclampsia after folic acid supplementation.Conclusion. The rate of preterm birth in pregnant women with early onset pre-eclampsia was reduced moderately by high doses of folic acid supplementation from early pregnancy.

On 21 June 2011, the DSM Science & Technology Awards recognized and rewarded outstanding innovative young scientists active in fundamental and applied research. As in previous years, an international judging committee honored creative and groundbreaking PhD research. Twelve finalists, the top candidates from Switzerland, Austria, France and southern Germany, were invited for the final competition followed by the award ceremony attended by numerous representatives of universities, non-governmental organizations, institutes of technology and industry.

Chronic hypertension (CH) is a common chronic disease and occurs frequently in pregnant women. The teratogenic/fetotoxic effect of certain antihypertensive drugs has been shown. The objective of this study was to investigate the association between pregnant women with CH and the possible risk of congenital abnormalities (CAs) among their offspring. The prevalence of medically recorded CH in the prenatal maternity logbook was compared between 1030 pregnant women who later had offspring with CA (case group) and 1579 pregnant women with CH who later delivered newborn infants without CA (control group). Control newborn infants were matched to cases in the population-based data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities during 1980-1996. Of 23 different CA groups with informative offspring, esophageal atresia/stenosis was a greater risk in pregnant women with CH (adjusted odds ratios with 95% confidence intervals: 3.1, 1.4-6.8). In conclusion, a higher risk of esophageal atresia/stenosis was found in the offspring of pregnant women with severe CH, which could not be explained by related drug treatments. This finding requires confirmation or lack thereof by future studies.

Hypotension is frequent in pregnant women; nevertheless, its association with pregnancy complications and birth outcomes has not been investigated. Thus, the aim of this study was to analyze the possible association of hypotension in pregnant women with pregnancy complications and with the risk for preterm birth, low birthweight and different congenital abnormalities (CAs) in the children of these mothers in the population-based data set of the Hungarian Case-Control Surveillance of CAs, 1980-1996. Prospectively and medically recorded hypotension was evaluated in 537 pregnant women who later had offspring with CAs (case group) and 1268 pregnant women with hypotension who later delivered newborn infants without CAs (control group); controls were matched to sex and birth week of cases (in the year when cases were born), in addition to residence of mothers. Over half of the pregnant women who had chronic hypotension were treated with pholedrine or ephedrine. Maternal hypotension is protective against preeclampsia; however, hypotensive pregnant women were at higher risk for severe nausea or vomiting, threatened abortion (hemorrhage in early pregnancy) and for anemia. There was no clinically important difference in the rate of preterm births and low birthweight newborns in pregnant women with or without hypotension. The comparison of the rate of maternal hypotension in cases with 23 different CAs and their matched controls did not show a higher risk for CAs (adjusted OR with 95% confidence intervals: 0.66, 0.49-0.84). In conclusion, a higher risk for CAs and other adverse birth outcomes was not found in the offspring of pregnant women with hypotension, but maternal hypotension was associated with a higher risk of some pregnancy complications.

Pregnancy-associated breast cancer (PABC) is defined as cancer of the breast diagnosed during pregnancy and up to 1 year postpartum. The crude incidence is 1/3000 pregnant women. As women delay childbearing the incidence of PABC increases with age. Young patients with PABC do not have worse prognosis compared with those with non-PABC; however, pregnancy can contribute to a delay in breast cancer diagnosis, evaluation, and treatment. Primary care physicians and gynecologists should be careful in the thorough workup of breast symptoms in the pregnant population to expedite diagnosis and allow multidisciplinary treatment as early as possible following the established diagnosis. Authors report a case of a 30-year-old pregnant woman, who detected inflammatory signs of her right breast and a palpable axillary mass at the 21st week of gestation. Her symptoms did not improve with administration of antibiotics. Therefore fine needle aspiration biopsy of the axillary lump was performed, with the result of unequivocal diagnosis of metastatic invasive carcinoma. The patient was referred to the multidisciplinary tumor board of our Department at the 27st week of gestation with the symptoms of inflammatory breast cancer, palpable right axillary and supraclavicular lymph nodes. Core biopsy showed an ER and PR negative, Her-2 positive, grade 3, infiltrating ductal carcinoma of the breast. After multidisciplinary team consultation the patient declined any kind of therapy during her pregnancy. On the 30th week of gestation caesarean section was performed. The premature baby girl was treated in the Neonatal Intensive Care Unit. Imaging modalities revealed no evidence of distant metastases short after the delivery. After 6 cycles of chemotherapy (docetaxel-doxorubicin-cycclophosphamid) the patient underwent right mastectomy and axillary lymph node dissection. Complete pathological response was diagnosed, since no residual tumor was found in the surgical resection specimen. After radiotherapy, trastuzumab medication was initiated. To date, there is no evidence of local recurrence or distant metastases during her 24 months follow-up. The newborn is on close neurohabilitation follow-up due to the evidence of generalized muscle dystonia. Had the patient accepted chemotherapy, the damage of the newborn baby would have been avoidable.

The teratogenic potential of some antithyroid drugs is known, but the aim of the study was to estimate the risk of congenital abnormalities (CAs) in the offspring of pregnant women with hyperthyroidism with or without antithyroid drug treatment.Comparison of the occurrence of medically recorded hyperthyroidism who had malformed fetuses/newborns (cases) and who delivered healthy babies (controls) in the population-based Hungarian Case-Control Surveillance System of CAs, 1980-1996. Of 22,843 cases with congenital abnormalities, 71 (0.31%) while of 38,151 controls, 116 (0.30%) had mothers with hyperthyroidism. The rate of hyperthyroidism in the mothers of cases with different CAs and in the mothers of matched controls was compared.Preeclampsia-eclampsia occurred more frequently in pregnant women with hyperthyroidism without antithyroid treatment. The analysis of specific groups of CAs showed an association between hyperthyroidism in pregnant women and obstructive defects of urinary tract in their children.The lack of appropriate treatment of pregnant women affected with hyperthyroidism seems to be the major problem, because it would be necessary to prevent the hyperthyroidism related risks of pregnancy complications and CAs which exceed the risk of antithyroid medication in these pregnant women.

The two far ends of the age at the diagnosis of breast cancer are the age of younger than 35, and that of older than 70. Most probably, these two groups of patients differ in many ways. The aim of our present study was to underline the fact that age at the diagnosis of breast cancer is indeed a prognostic factor. Between October 1995 and March 2009, 80 old and 51 young breast cancer patients were treated at the Department of Diagnostic Radiology and Oncotherapy, Semmelweis University, Budapest. The prognostic and predictive factors of the tumors were analysed together with the disease-free and overall survival data. There were statistically significant differences between the two groups concerning the menstrual and reproductive factors, histological characteristics and immunophenotype of the tumors. Tumor size, nodal status and the Nottingham Prognostic Index did not show statistically significant differences. A trend to a shorter disease-free survival, higher rate of distant metastases and disease-specific death was seen in the group of young patients, but it was not significant. Overall survival was significantly shorter in the group of young patients. Therefore, we can state that young patients have a more aggressive disease and worse outcome. There is an increased importance of self examination in these groups, since both age groups are beyond the age limits of the screening population in Hungary. The media and primary school education as well should be involved in educating women concerning this aspect. The individual follow-up of young patients with positive family history should also be established.

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.

SUMMARY Background: Maternal cervical incompetence in pregnancy (CIP) showed an association with a higher rate of preterm births. The objective of this study was to determine the prevalence of CIP in Hungarian pregnant women, to determine the rate of preterm birth, and to check the preventive efficacy of preterm births due to CIP by therapeutic cerclage or bed rest alone. Methods: Analysis of the population-based large data set of 38,151 newborns (without any defects) of the Hungarian Case-Control Surveillance System of Congenital Abnormalities (HCCSCA), born during 1980–1996, i.e. 1.8% of Hungarian newborns. Prospective cohort analysis based on medically recorded variables of CIP, birth weight and gestational age. Results: A total of 2,795 (7.33%) newborns born to mothers with CIP. The newborns of mothers with CIP had a shorter gestational age at delivery (39.0 wk) and higher rate of preterm birth (11.1%) than the Hungarian reference sample without CIP (39.4 wk and 9.0%). Of 2,795 pregnant women with CIP 1,112 were treated by cerclage, while 1,683 with bed rest alone. The mean gestational age was shorter both after therapeutic cerclage (39.2 wk) and particularly bed rest alone (38.9 wk). The rate of preterm births was 9.1% and 12.7% after therapeutic cerclage and bed rest alone. Conclusions: CIP is very frequent in Hungary probably due the extremely high number of previous induced abortion performed by dilatation and curettage method. CIP associates with an increased risk for preterm births; however, this increased risk was reduced by bed rest alone and mainly by therapeutic cerclage.

Pholedrine was a frequently used drug for the treatment of severe hypotension in some countries, including Hungary. The possible teratogenic effect of pholedrine was not checked; therefore; the birth outcomes, particularly congenital abnormalities (CAs), of infants born to women treated with pholedrine during pregnancy, and pregnancy complications were evaluated in the population-based large dataset of the Hungarian Case-Control Surveillance System of Congenital Abnormalities. Cases with CA and their matched controls without CA born to mothers with pholedrine use during pregnancy were compared. Of 22 843 cases and 38 151 controls, 768 (3.4%) and 1509 (4.0%) were born to mothers with pholedrine treatment, respectively (adjusted odds ratios [OR] with 95% CI: 0.9, 0.8-1.0). There was no higher risk for any CA group in the offspring of mothers who used pholedrine during the second and/or third month of pregnancy (i.e. the critical period of most major CA). The mean gestational week at delivery and birthweight was similar in newborns of women with or without pholedrine treatment during pregnancy. The pattern of pregnancy complications was characteristic (lower incidence of preeclampsia/eclampsia, while higher incidence of severe nausea/vomiting and anemia), explained mainly by the underlying maternal hypotension. In conclusion, pholedrine treatment in pregnant women was not associated with a higher risk for CA or other adverse birth outcomes, such as preterm birth or low birthweight. The knowledge of the teratogenic potential of pholedrine may contribute to the evaluation of other sympathomimetic drugs.

To estimate the risk of structural birth defects (i.e. congenital abnormalities [CA]) in the offspring of pregnant women with type 1 (DM-1), type 2 (DM-2) and gestational diabetes mellitus (GDM) and to check the efficacy of recent specific care of diabetic pregnant women in the reduction of DM-related CA. Comparison was made of the occurrence of medically recorded types of diabetes mellitus in pregnant women who had malformed fetuses/newborns (cases) and who delivered healthy babies (controls) in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980-1996. In the case group, which included 22 843 offspring, there were 79 (0.35%) pregnant women with DM-1, 77 (0.34%) pregnant women with DM-2 and 120 (0.53%) pregnant women with GDM. The control group comprised 38 151 newborns, and 88 (0.23%), 141 (0.37%) and 229 (0.60%) pregnant women with DM-1, DM-2 and GDM, respectively. The total rate of cases with CA was higher only in the DM-1 group (adjusted OR with 95% CI: 1.5, 1.1-2.0) and within four specific types/groups: isolated renal a/dysgenesis, obstructive CA of the urinary tract, cardiovascular CA and multiple CA; namely, caudal dysplasia sequence. The risk of total CA was lower in the present study compared to the risk in previous studies and the DM-1-related spectrum of CA was also different. There was no higher risk of total CA in the offspring of pregnant women with DM-2 and GDM. The certain part of maternal teratogenic effect of DM-1 is preventable with appropriate periconceptional and prenatal care of diabetic women.

The administration of folic acid (FA) or multivitamin (MV) supplements during preconception to prevent neural tube defects is well established. Most pregnant women in Hungary use high doses of FA early in pregnancy, but it is unclear whether continuing these supplements after the first trimester reduces the rate of preterm delivery and low birth weight. The results of 2 meta-analyses on supplementation were inconclusive as to the benefits of continuation and recommended further investigation. Some practitioners have suggested that increased birth weight resulting from supplementation may increase the risk of complications. To address this issue, this study compared the effects of administering vitamin supplements in the second and the third trimester on length of gestation and fetal growth. Birth outcomes were determined using a population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities. The participants included 3 groups of women who ingested daily supplements containing (1) FA alone (n = 6293), (2) FA plus MV (n = 311), or (3) MV without FA (n = 169). The controls were a reference group comprising 7319 pregnant women who did not take the supplements. There was special emphasis on the third trimester, during which the most intensive fetal growth occurs. Compared to the reference sample, the mean gestational age at delivery in the FA alone group was 0.3 week longer (39.5 vs. 39.2) and the mean birth weight 37 g higher (3253 vs. 3216 g). The continuation of FA was associated with a significant reduction (7.6%) in the rate of preterm births compared with the reference sample (11.8%), but there was no similar reduction in the rate of low birth weight newborns. In the third trimester, the use of FA was associated with a 0.6 week prolongation of gestation (FA alone: 39.8 vs. reference sample: 39.2 weeks) and a lower rate of preterm birth (4.8%). These findings show that high dose FA supplementation during pregnancy, especially during the third trimester, are associated with a decreased risk of preterm birth.

Objective Uterine leiomyoma is not a rare pathological condition in pregnant women; thus the aim of the study was to evaluate the recent progress in the treatment of these pregnant women on the basis of the association of leiomyoma in pregnancy (LP) with pregnancy complications and birth outcomes including structural birth defects, i.e. congenital abnormalities (CA) in the offspring. Design Cases with CA and matched controls without CA in the population-based Hungarian Case-Control Surveillan- ce System of Congenital Abnormalities (HCC SCA) were evaluated. Only women with prospectively and medically recorded LP in prenatal maternity logbook and medically recorded birth outcomes (gestational age, birth weight, CA) were included to the study. Setting the HCCSCA, 1980-1996 contained 22,843 cases with CA and 38,151 matched controls without CA. Population Hungarian pregnant women and their informative offspring: live births, stillbirths and prenatally diagnosed malformed fetuses. Methods Comparison of birth outcomes of ca- ses with matched controls and pregnancy com- plications of pregnant women with or without LP. Main outcome measures Pregnancy complications, mean gestational age at delivery and birth weight, rate of preterm birth, low birthweight, CA. Results A total of 34 (0.15%) cases had mothers with LP compared to 71 (0.19%) controls. There was a higher incidence of threatened abortion, placental disorders, mainly abruption placentae and anaemia in mothers with LP. There was no significantly higher rate of preterm birth in the newborns of women with LP but their mean birth weight was higher and it associated with a higher rate of large birthweight newborns. A higher risk of total CA was not found in cases born to mothers with LP (adjusted OR with 95% CI = 0.7, 0.5-1.1), the spe- cified groups of CAs were also assessed versus controls, but a higher occurrence of women with LP was not revealed in any CA group. Con- clusions Women with LP have a higher risk of threatened abortion, placental disorders and anaemia, but a higher rate of adverse birth outcomes including CAs was not found in their offspring.

Objective to study the possible association between erosion of cervix in pregnant women (ECP) and structural birth defects, i.e. congenital abnormalities (CA) in their offspring. Study design: Comparison of cases with CA and all matched controls without any CA born to wo- men with prospectively and medical record ECP in the population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA). Results: HCC- SCA contained 22,843 cases and 38,151 matched controls, the informative offspring of 40 (0.18%) case mothers and the newborns of 25 control mothers (0.07%) with ECP were compared and the higher risk for total CA (adjusted OR with 95% CI: 2.7, 1.6-4.4) was found explained by the higher risk of 9 cases with hypospadias (OR with 95% CI: 4.5, 2.1-9.7) and 10 cases with car-diovascular CAs (OR with 95% CI: 3.4, 1.6-7.1), particularly with conotruncal CAs. Conclusions: An unexpected possible association of ECP with higher risk for hypospadias and conotrun-cal cardiovascular CAs was found and these findings are considered as signals that need confirmation or rejection

The possible association between Salmonella gastroenteritis (SGE) and infectious diarrhoea in pregnancy (IDP) and structural birth defects, i.e. congenital abnormalities (CA) in the offspring, has not been studied. The dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996 was evaluated. There were 15 (0.07%) and 82 (0.36%) out of 22,843 cases and 23 (0.06%) and 70 (0.18%) out of 38,151 (0.34%) controls with mothers who had medically recorded SGE and IDP, respectively. There was no association of SGE and a higher risk of CA. However, a higher risk of cleft lip +/- palate, congenital limb deficiencies, multiple CAs and cardiovascular CAs was found in the offspring of mothers with IDP. A possible explanation for the association of IDP with higher risk for some specific CAs may be the high fever in IDP.

Possible Association of Maternal Haemorrhoid with Congenital Abnormalities in their Children - a Population-Based Case-Control StudyObjectives: To look for a possible association of maternal haemorrhoid during pregnancy with a risk of congenital abnormalities in their children.Methods: Comparison of the prevalence of medically-recorded haemorrhoid in pregnant women who had fetuses/newborns (cases) with congenital abnormalities and healthy babies (controls) in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities.Results: Of 22,843 cases with congenital abnormalities, 798 (3.49%), while of 38,151 controls, 1,624 (4.26%) had mothers with recorded and usually treated severe haemorrhoids. We found a higher risk for exomphalos (OR with 95% CI: 4.9, 1.7-7.9), and malposition-malrotation of gut (OR with 95% CI: 17.2, 2.1-142.0) which were present in 14 and 8 children of pregnant women with haemorrhoid, respectively. These associations could not be explained by teratogenic effect of maternal haemorrhoid or by drug treatments, so we hypothesized a possible common genetic background.Conclusions: The higher frequency of exomphalos and malposition-malrotation of gut found in the children of mothers with haemorrhoid during pregnancy requires further study.

OBJECTIVE: To evaluate the teratogenic effect of very large doses of nitrazepam in children born to pregnant women who attempted suicide and to check the feasibility of self-poisoning pregnant women model. DESIGN AND SETTING: Comparative analysis of exposed children and their unexposed sibs born to the same mothers who attempted suicide during the study pregnancy and admitted to the toxicological inpatients clinic, Budapest, 1960-1993. STUDY PARTICIPANTS: Of 1044 pregnant women who attempted suicide, 107 (10.3%) used large doses of nitrazepam alone or combination with other drugs, and 43 delivered live-born babies, these exposed children were evaluated. MAIN OUTCOMES MEASURES: Structural birth defects, i.e., congenital abnormalities (CAs), pregnancy age at delivery, and birth weight. RESULTS: The mean dose of nitrazepam used for suicide attempt was 204 mg. Of 43 exposed children, 13 (30.2%) were affected with CAs, while of their 29 sib controls, 3 (10.3%) (OR with 95%CI: 3.8, 1.0-14.6). Most CAs in exposed children were mild and belonged to the deformation type. The mean pregnancy age was shorter. CONCLUSIONS: The very large doses of nitrazepam used for suicide attempt during pregnancy resulted in a high rate of CAs which may be connected with the disruption of protein metabolism in fetal mesenchyma. The self-poisoning pregnant women model is feasible for the evaluation of teratogenic effect of drugs. Language: en

Objective To estimate the risk of congenital abnormalities in the offspring of pregnant women with symptomatic cholelithiasis and complicated cholecystitis. Study design Comparison of the occurrence of medically recorded symptomatic cholelithiasis and complicated cholecystitis occurred any time of pregnancy (particularly in the second and/or third gestational month) of pregnant women who had malformed foetuses/newborns (cases) and who delivered healthy babies (controls) in the population-based Hungarian Case–Control Surveillance System of Congenital Abnormalities. Results Of 22,843 cases with CA, 62 (0.27%) had mothers with symptomatic cholelithiasis, while 119 (0.31%) mothers of 38,151 controls were recorded with symptomatic cholelithiasis. In addition, the mothers of 109 cases (0.48%) were affected by complicated cholecystitis during pregnancy compared with 145 controls (0.38%). Regarding the frequency, these two biliary diseases did not show any significant differences in the maternal variables, therefore case mothers were combined. The analysis of specific groups of congenital abnormalities showed an association between symptomatic cholelithiasis-complicated cholecystitis in the second and/or third gestation months, and neural tube defects (adjusted OR with 95% CI: 4.1, 1.3–13.4). Conclusion A higher rate of neural tube defects was found in the offspring of mothers with severe diseases of the biliary system during pregnancy. This finding needs to be confirmed by further studies and/or explanations to determine whether it is causal or a chance event.

OBJECTIVE: To study the effect of large doses of phenobarbital used for a suicide attempt during pregnancy for fetuses to estimate the teratogenic potential of phenobarbital. DESIGN AND SETTING: Comparative analysis of exposed children and their unexposed sibs born to pregnant patients who attempted suicide during pregnancy and admitted to the toxicological inpatient clinic, Budapest, 1960-1993. STUDY PARTICIPANTS: Of 1044 self-poisoned pregnant women, 88 used phenobarbital for suicide attempt and delivered newborn babies. MAIN OUTCOME MEASURES: Structural birth detects, i.e., congenital abnormalities (CAs). RESULTS: Doses ranged between 400 and 3000 mg of phenobarbital in 88 pregnant women who attempted suicide with this drug during pregnancy and later delivered live-born babies. Twelve (13.6%) of 88 exposed children and eight (10.3%) of 78 sibs were affected with CAs (odds ratios (OR) with 95%CI: 1.4, 0.6-3.5). Of 88 exposed children, 34 were born to mothers who attempted suicide with phenobarbital between the 3rd and 12th postconceptional weeks, the critical period of most CAs; 3 had CAs (diaphragmatic defect, multiple CA, undescended testis), but only diaphragmatic defect might be associated with phenobarbital used for suicide attempt. CONCLUSIONS: The use of phenobarbital once but extremely large doses in non-epileptic pregnant women does not seem to pose a significant risk for CAs. Our experiences show the feasibility and benefits of the disaster epidemiological self-poisoning model for estimating human teratogenic risks of drug exposure. Language: en