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Biomedical subjects

Andrew E Czeizel

Publications and source records attributed to Andrew E Czeizel.

At least 19 recordsLinked to original sources

Use of phenytoin, phenobarbital, or diazepam during pregnancy and risk of congenital abnormalities: a case-time-control study.

PURPOSE: Case-control studies are often used to examine putative teratogenic drug effects during organogenesis but these studies are subject to confounding by indication, recall, and participation bias. The case-time-control approach is less susceptible to these sources of bias. We studied congenital abnormalities following exposure to phenytoin, phenobarbital, and diazepam in early pregnancy, i.e., second and third month, compared to mid-pregnancy, i.e., fifth and sixth month of pregnancy. METHODS: We analyzed data from the Hungarian Case-Control Surveillance of Congenital Abnormalities (1980-1996) in a case-time-control study. RESULTS: The study included 22 843 children with congenital abnormalities (cases) and 38 151 children with no abnormalities (controls). Overall, odds ratio (OR) for congenital abnormalities after exposure to one of the three drugs in early pregnancy was 1.2 (95% confidence interval (CI): 1.0-1.4). Among children exposed to phenytoin OR for congenital abnormalities was 3.7 (95%CI: 0.3-49.6), for children exposed to phenobarbital the OR was 1.1 (95%CI 0.7-1.7), and for diazepam, OR for congenital abnormalities was 1.2 (95%CI: 1.0-1.4). CONCLUSIONS: The associations we found between the drugs examined and congenital abnormalities were either only borderline significant or not statistically significant. The case-time-control study provides an interesting way of using existing case-control data to study rare side effect of drugs taken during pregnancy.

Abnormalities, Drug-Induced↗

A population-based case-control teratologic study of oral dipyrone treatment during pregnancy.

OBJECTIVE: To study the possible human teratogenic effect of oral dipyrone, an antipyretic and analgesic drug treatment during pregnancy. DESIGN AND SETTING: The analysis of cases with different congenital abnormalities and their matched population controls without congenital abnormalities, in addition to a comparison between cases and malformation controls (Down's syndrome) in the population-based, large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. STUDY PARTICIPANTS: 22 843 neonates or fetuses with congenital abnormalities (cases), 38 151 matched newborns without congenital abnormalities (population controls) and 834 neonates or fetuses with Down's syndrome (malformation controls). MAIN OUTCOME MEASURES: 25 congenital abnormality groups. RESULTS: 1382 (6%) cases, 1911 (5%) population controls and 74 (8.9%) malformation controls were born to mothers treated with dipyrone during pregnancy. The case-matched population control analysis showed a higher rate of diaphragmatic defect (adjusted prevalence odds ratio [POR] 2.7; 95% CI 1.0, 6.8), cardiovascular malformations (POR 1.3; 95% CI 1.0, 1.7) and other isolated congenital abnormalities (POR 1.8; 95% CI 1.1, 2.9) after oral dipyrone treatment during the second and third months of gestation, i.e. in the critical period for most major congenital abnormalities. However, the evaluation of only medically recorded dipyrone use did not confirm these possible associations. The comparison of dipyrone treatment between 25 congenital abnormalities groups and malformation controls as the referent group also did not show any difference in the dipyrone use during the second and third months of gestation. CONCLUSIONS: The higher occurrence of dipyrone treatment in the case mothers compared with population control mothers can be explained by recall bias and/or chance. However, the higher rate of diaphragmatic congenital abnormalities can be considered as a signal and merits further investigation.

Abnormalities, Drug-Induced↗

No association between periconceptional multivitamin supplementation and risk of multiple congenital abnormalities: a population-based case-control study.

Two previous Hungarian intervention trials showed that periconceptional folic acid-containing multivitamin supplementation did not change the total (birth + fetal) prevalence of cases with multiple congenital abnormalities (MCAs). However, two US observational studies found an elevated risk for MCAs in the offspring of women who reported periconceptional use of multivitamins containing folic acid. These conflicting results stimulated us to evaluate the data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities and to check the possible association between the use of periconceptional multivitamin supplementations and the total prevalence of cases with MCAs. Of 1,349 cases with MCA, 69 (5.1%) had mothers who used multivitamins during the second and third month of pregnancy. Of 2,405 matched controls without any defect, 126 (5.2%) had mothers who used multivitamin supplementation in early pregnancy. Of 21,494 malformed controls with isolated congenital abnormalities, 1,052 (4.9%) mothers received supplementation with multivitamins during the critical period of CAs including MCAs. There was no difference in the use of multivitamins among the study groups either in the total data set or at the evaluation of only prospective medically recorded data. Medically recorded folic acid use without any multivitamins in the second and third gestational month showed some protective effect for MCAs. In conclusion, our observational case-control study did not detect a folic acid containing multivitamins during the early pregnancy as a risk factor for MCAs.

Abnormalities, Multiple↗

Pregnancy complications and delivery outcomes in pregnant women with severe migraine.

OBJECTIVE: The objective was to study the possible association among maternal migraine during pregnancy, pregnancy complications, and the delivery outcomes: sex ratio, gestational age/birth weight and preterm birth/low birth weight. STUDY DESIGN: The population-based large data set of newborn infants without any defects of the Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980-1996 was analyzed. RESULTS: Out of 38,151 newborn infants, 713 (1.9%) had mothers who had severe migraine during pregnancy; 68% were medically recorded. Pregnant women with severe migraine had a higher prevalence of preeclampsia and severe nausea/vomiting, but a lower occurrence of threatened abortion and preterm delivery. However, mean gestational age and birth weight, as well as the proportion of low birth weight and preterm births, were similar in newborn infants born to mothers with or without migraine. CONCLUSION: Severe maternal migraine and its related drug treatment may increase the occurrence of preeclampsia and severe nausea/vomiting during pregnancy, but is not associated with unfavorable delivery outcomes.

Birth Certificates↗

Maternal use of oral contraceptives and risk of hypospadias - a population-based case-control study.

The aim of this population-based case-control study was to examine the risk of isolated hypospadias in boys born to mothers who have used oral contraceptives in early pregnancy. The study was based on data from the Hungarian Case-Control Surveillance of Congenital Abnormalities from 1980 to 1996, and included 3,038 boys with hypospadias (cases), 24,799 boys without congenital abnormalities (CA-free controls), and 11,881 boys with abnormalities other than hypospadias. We used unconditional logistic regression to adjust for birth order, maternal age, maternal employment status, maternal diabetes, and pre-eclampsia. When comparing cases with CA-free controls the OR for maternal use of OC was 1.21 (95% CI: 0.67-2.17). When comparing cases with boys with other abnormalities, the OR for maternal use of OC was 0.83 (95% CI: 0.46-1.50). Our data showed that self-reported maternal use of oral contraceptives during pregnancy was not associated with an increased risk of hypospadias in the offspring.

Abnormalities, Drug-Induced↗

A population-based case-control study of isolated primary congenital glaucoma.

We studied the possible etiological factors of isolated primary congenital glaucoma (IPCG) using data from the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002. The study group consisted of 52 cases with IPCG compared to 52 matched control pairs without any defects, and 22,744 malformed controls with non-ocular defects and 37,837 population controls with no defect. Exposure data and family history were collected (i) prospectively by prenatal logbook and other medical records, (ii) retrospectively through a structured questionnaire completed by mothers, and (iii) from supplementary information obtained by regional nurses visiting the homes of non-respondent mothers. Autosomal recessive inheritance of IPCG was suspected on the basis of sib occurrence and parental consanguinity in 15% of cases. The shorter gestational age (with high proportion of preterm birth), higher birth order, large proportion of births among unmarried women, low socioeconomic status, and high rate of unemployment may be related to Gypsy origin of at least 54% of cases of IPCG. We conclude that the higher incidence of IPCG in the Hungarian Gypsy population is associated with their inbreeding and the possible founder effect of a gene mutation.

Adult↗

Inverse association between severe nausea and vomiting in pregnancy and some congenital abnormalities.

The objective of the study was to investigate the possible association between nausea and vomiting in early pregnancy and congenital abnormalities. The prevalence of medically-recorded severe nausea and vomiting in early pregnancy in cases with congenital abnormalities and their available matched population controls without any defect was compared in the population-based large data set of the Hungarian Case-Control Surveillance System of congenital abnormalities, 1980-1996. Of 22,843 cases with as 25 different congenital abnormality groups, 1,713 (7.5%) cases had mothers with medically recorded and treated severe nausea and vomiting during pregnancy. Of 38,151 matched population controls, 3,777 (9.9%) had mothers with severe nausea and vomiting (adjusted prevalence odds ratio (POR) with 95% CI: 0.74, 0.68-0.79). Five congenital abnormality groups: cleft lip with or without cleft palate (0.50, 0.37-0.70), posterior cleft palate (0.53, 0.32-0.89), renal a/dysgenesis (0.23, 0.06-0.96), obstructive defects of urinary tract (0.32, 0.18-0.58), and cardiovascular malformations (0.68, 0.57-0.81) had mothers with a lower prevalence of severe nausea and vomiting in pregnancy (adjusted PORs with 95% CI included in parentheses). Of 25 congenital abnormality groups, 22 had POR lower than 1. Thus in this study the mothers of cases with congenital abnormalities were 26% less likely to have had severe nausea and vomiting in early pregnancy than the mothers of population controls without congenital abnormalities.

Adult↗

Population-based case-control study of allergic rhinitis during pregnancy for birth outcomes.

OBJECTIVE: Allergic rhinitis is frequent in women of childbearing age including pregnancy. The present study aimed to estimate the effect of maternal allergic rhinitis on birth outcomes, in particular congenital abnormalities, preterm birth and low birthweight newborns. STUDY DESIGN: Analysis of the population-based data of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. RESULTS: The evaluation of data did not reveal any teratogenic potential of allergic rhinitis and indeed a lower prevalence of total congenital abnormalities was found. In addition, a protective effect could be observed for preterm birth due to longer gestational age (adjusted t=2.97, p=0.003). CONCLUSION: Allergic rhinitis is not risk factor for pregnant women.

Adult↗

Maternal panic disorder and congenital abnormalities: a population-based case-control study.

BACKGROUND: Maternal panic disorder in pregnancy is the most common manifestation of anxiety disorders in Hungary. The association between panic disorder during pregnancy and structural birth defects, i.e., congenital abnormalities, was studied. METHODS: The prevalence of maternal panic disorder in cases with different congenital abnormalities was compared to that of matched controls in the population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities. RESULTS: Of 22,843 cases with congenital abnormalities, 210 (0.9%) had mothers with panic disorder during pregnancy compared to 187 (0.5%) of 38,151 controls (adjusted prevalence odds ratio [POR] 1.6; 95% CI, 1.3-2.0). Specific groups of congenital abnormalities were also assessed versus controls. Cases with isolated cleft lip with or without cleft palate (CL/P) (adjusted POR, 3.4; 95% CI, 1.3-9.0) and multiple congenital abnormalities (adjusted POR, 3.0; 95% CI, 1.2-7.2) were more likely to have had mothers with panic disorder during the study pregnancy. Notably, among mothers with panic disorders, the associations were found only in offspring of untreated mothers. CONCLUSIONS: A higher rate of isolated CL/P and multiple congenital abnormalities may be caused by the direct biological effect of panic disorder or by the interaction of maternal panic disorder and lifestyle factors. Antipanic drug treatment seems to have a protective effect for isolated CL/P and multiple congenital abnormalities. Birth Defects Research (Part A), 2006.

Abnormalities, Multiple↗

Maternal severe migraine and risk of congenital limb deficiencies.

BACKGROUND: Migraines occurs frequently during pregnancy; however, there are no published data on their possible teratogenic potential in a controlled epidemiological study. Therefore, we examined the risk of congenital abnormalities in infants born to women who had migraines and other headaches during pregnancy. METHODS: Between 1980 and 1996, the Hungarian Case-Control Surveillance of Congenital Abnormalities evaluated 22,843 cases (newborns or fetuses) with congenital abnormalities, 38,151 control newborn infants without any abnormalities, and 834 malformed controls with Down syndrome. RESULTS: Migraines anytime during pregnancy occurred in 565 (2.5%) mothers of the case group compared with 713 (1.9%) mothers in the control group (crude prevalence odds ratio [POR], 1.3; 95% confidence interval [CI], 1.2-1.5) and 24 (2.9%) pregnant women in the malformed control group (crude POR, 0.9; 95% CI, 0.6-1.3) The mothers of 247 cases, 533 controls, and 21 malformed controls had severe migraines during the second and/or third months of pregnancy. There was only 1 congenital abnormality group: limb deficiencies, which had a higher rate of maternal migraines during the second and third months of pregnancy both at the comparison of cases and matched controls (adjusted POR, 2.5; 95% CI, 1.1-5.8) and of cases and malformed controls (adjusted POR, 1.7; 95% CI, 1.3-3.0). There was no association between other headaches and different congenital abnormalities at the comparison of cases and controls. CONCLUSIONS: Our data showed that maternal severe migraines during the second and/or third months of pregnancy were associated with an increased risk of congenital limb deficiencies. A similar association was not detected between congenital anomalies and other headaches during pregnancy. Our study was not based on a prior hypothesis; therefore, these data can be considered only as a signal that needs confirmation by independent data sets.

Adult↗

Population-based case-control study of the common cold during pregnancy and congenital abnormalities.

The common cold is the most frequent maternal disease during pregnancy. The possible association between different congenital abnormalities and the common cold in pregnant women was evaluated in the data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Of 22,843 cases with congenital abnormalities, 3,827 (16.8%) had mothers with the common cold, while of 38,151 population controls without congenital abnormalities, 5,475 (14.4%) (adjusted prevalence odds ratio: POR: 1.26 with 95% CI: 1.20-1.32). Of 834 malformed controls with Down syndrome, 114 (17.3%) had mothers with the common cold (POR: 0.96 with 95% CI: 0.80-1.16). Nearly half of mothers with the common cold had secondary complications with antifever therapy. The comparison of cases with 25 congenital abnormalities and population control mothers with medically recorded common cold during the second and third months of gestation showed that five congenital abnormality groups: congenital hydrocephaly (3.6, 1.3-9.7), cleft lip+/-palate (2.3, 1.5-3.6), posterior cleft palate (2.3, 1.2-4.1), limb deficiencies (2.2, 1.1-4.1) and multiple CAs (2.0, 1.4-2.9) had adjusted POR 2 or more. The comparison of cases with different congenital abnormalities and malformed controls (including offspring with Down syndrome) as referent, indicated a higher prevalence of the common cold during the second and third month of gestation only in the mothers of cases with cleft lip+/-palate (adjusted POR: 1.7 with 95% CI: 1.2-2.5), however, congenital hydrocephaly, neural-tube defects and multiple CAs had also mothers with a somewhat higher occurrence of the common cold. The possible association between the common cold during early pregnancy and the above mentioned congenital abnormalities may be connected mainly with the indirect effect of secondary complications of maternal common cold, particularly high fever because antifever drugs were able to prevent the possible teratogenic effect of the common cold.

Analgesics, Non-Narcotic↗

Maternal herpes labialis in pregnancy and neural tube defects.

According to previous case reports, some congenital abnormalities (CAs) of the brain, such as microcephaly, are a result of intrauterine herpes simplex virus infection. A population-based case-control study was conducted to determine the risk of neural tube defects (NTDs) after maternal herpes labialis infection during pregnancy. Data were taken from the Hungarian Case-Control Surveillance of Congenital Abnormalities from 1980 to 1996, which included 1202 children with NTDs and 21641 comparison children with CAs other than NTDs. The adjusted relative risks (odds ratio [OR]) for NTDs associated with maternal herpes labialis in the first trimester of pregnancy was OR 1.19 (95% confidence interval [CI] 0.68-2.06), and in the entire pregnancy was OR 0.94 (95% CI 0.61-1.44). Self-reported maternal herpes labialis during pregnancy was not associated with a substantially increased risk of NTDs in infants.

Adult↗

Birth characteristics of different ocular congenital abnormalities in hungary.

AIMS: The aim of the study was to estimate the prevalence at birth of different ocular congenital abnormalities and to describe their birth characteristics in Hungary. METHODS: Two data sets were evaluated: the national-based Hungarian Congenital Abnormality Registry and the Hungarian Case-Control Surveillance of Congenital Abnormalities which include cases with ocular abnormalities and patient controls with other (non-ocular) congenital abnormalities, and population controls without abnormalities from the National Birth Registry. RESULTS: Seven hundred twelve cases were found with ocular abnormalities in the data set of the Hungarian Congenital Abnormality Registry (2.62 per 10,000 live births), while that of the Hungarian Case-Control Surveillance of Congenital Abnormalities included 314 cases with ocular defects among 2.7 million live births in Hungary between 1980 and 2002. There was an obvious underascertainment and/or notification of cases with ocular defects because an extra effort to ascertain all cases with ocular abnormalities resulted in a birth prevalence of 6.31 per 10,000 live births in 1999. The main birth characteristics of cases were male excess, shorter mean gestational age and smaller mean birth weight with a larger proportion of preterm birth and low birthweight. CONCLUSIONS: Earlier diagnosis of ocular abnormalities is necessary with a more complete notification of these cases to the Hungarian Congenital Abnormality Registry. The birth characteristics of cases with ocular abnormalities may have some associations with the origin of ocular defects; therefore, these variables will require further studies in case-control approach.

Birth Weight↗

Pregnancy complications and delivery outcomes of pregnant women with influenza.

OBJECTIVES: In a previous study, we showed that maternal influenza in pregnancy gives rise to an increase in some congenital abnormality groups. The aim of this study was to ascertain the relationship between influenza during pregnancy and pregnancy complications, and in addition, delivery outcomes particularly preterm birth and low birth weight in newborns. METHODS: The population-based large control (without any defects) data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities, in which pregnancy complications, gestational age and birth weight are medically recorded, was evaluated. RESULTS: Of 38,151 newborn infants, 1838 (4.8%) had mothers with influenza during pregnancy. The prevalence of pregnancy complications showed no difference between mothers with or without influenza during the study pregnancy. Mothers with influenza in pregnancy had a somewhat higher gestational age (0.1 week) and a lower proportion of preterm births (8.0% vs. 9.2%). These findings were reflected in the mean birth weight (+37 g) and lower proportion of low birth weight newborns (4.7% vs. 5.1%); these differences were explained by confounders. CONCLUSION: Maternal influenza during pregnancy does not increase the prevalence of pregnancy complications and unsuccessful delivery outcomes.

Adult↗

Possible association between maternal recurrent orofacial herpes in pregnancy and a lower rate of preterm birth.

OBJECTIVE: To study the possible association between orofacial herpes during pregnancy and pregnancy complications including preterm birth and low birth weight, since the results of previous studies are inconsistent. METHOD: The population-based large data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities was used; pregnancies in mothers with and without recurrent orofacial herpes were compared. RESULTS. Of 38,151 newborn infants, 572 (1.5%) had mothers with recurrent orofacial herpes during pregnancy, while 37 577 had mothers with no orofacial herpes. Pregnant women with recurrent orofacial herpes had a higher prevalence of severe nausea and vomiting, threatened preterm delivery, and placental disorders but a lower prevalence of preeclampsia. Mothers with recurrent orofacial herpes during pregnancy also had a somewhat longer (0.4 weeks) gestation (adjusted t = 2.7; p = 0.006) and an obviously lower proportion of preterm births (3.5% vs. 9.3%; adjusted POR with 95% CI = 0.42, 0.27-0.65). However, there was no significant difference in the mean birth weight and rate of low birth weight infants between the two study groups. CONCLUSION: Recurrent orofacial herpes during pregnancy is associated with a smaller proportion of preterm births.

Adult↗

Population-based case-control study of oxoline acid use during pregnancy for birth outcomes.

The objective of the study was to check the effect of oxoline acid, a bactericidal drug for the treatment of urinary tract infection during pregnancy, on congenital abnormalities of informative offspring and fetal development. Human data of oxoline acid use during pregnancy have not been reported, but the use of this quinolone derivative is not recommended during pregnancy by the US Food and Drug Administration. The teratogenic and fetotoxic potential of oxoline acid was evaluated in the population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Observed and expected numbers of congenital abnormalities were compared in the newborn infants and fetus of case mothers with oxoline acid treatment. In addition, gestational age and birthweight were evaluated in control newborn infants born to mothers with or without oxoline acid treatment. Of 38,151 newborn infants without any congenital abnormalities (control group), 13 (0.03%) had mothers who were treated with oxoline acid, while of 22,843 cases with congenital abnormalities, five (0.02%) had mothers who were treated with oxoline acid during pregnancy (POR with 95% CI: 0.6, 0.2-1.8). The comparison of observed and expected number of different congenital abnormalities did not show the teratogenic potential of oxoline acid. There was a 0.9 weak shorter gestational age without a smaller birthweight in the newborn infants born to mothers with oxoline acid treatment. Our data did not indicate teratogenic and fetotoxic effect of oxoline acid, however, the number of cases and controls was limited.

Abnormalities, Drug-Induced↗

Acute respiratory infections during pregnancy and congenital abnormalities: a population-based case-control study.

Diseases of respiratory system caused by acute infections are among the most common maternal diseases during pregnancy. The objective of the study was to estimate the association between congenital abnormalities and acute respiratory infections during the first trimester of pregnancy. The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities including 22 843 cases with congenital abnormalities, 38 151 population controls without congenital abnormalities and 834 malformed controls with Down syndrome between 1980 and 1996 was evaluated. 2118 cases with congenital abnormalities (9.3%), 3455 population controls (9.1%) and 92 malformed controls with Down syndrome (11.0%) had mothers with acute respiratory infections. Of 25 different congenital abnormality groups, esophageal atresia/stenosis showed a high adjusted prevalence odds ratios (POR) with 95% confidence interval (CI) for acute respiratory infections during the first trimester of pregnancy in case mothers compared with population controls (3.6, 1.4-9.1) and malformed controls (1.9, 1.0-3.5), respectively. In addition there was an association between medically recorded acute respiratory infections during the first trimester of pregnancy and a higher risk for some other congenital abnormalities, such as posterior cleft palate and multiple congenital abnormalities. In conclusion a possible association between some congenital abnormalities, particularly esophageal atresia/stenosis and maternal acute respiratory infections cannot be excluded due to the interactions of the microbial agents, related drug treatments and last but not least the indirect effect of maternal diseases, such as fever-hyperthermia, hypoxia and dietary deficiency. However, periconceptional multivitamin/folic acid supplementation during the early pregnancy was able to reduce the acute respiratory infection related risk for congenital abnormalities.

Abnormalities, Multiple↗