Is there a reduction of congenital abnormalities in the offspring of diabetic pregnant women after folic acid supplementation? A population-based case-control study

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

Efficacy of medical care of epileptic pregnant women based on the rate of congenital abnormalities in their offspring

The objective of the present study was to check the efficacy of progress in the medical care of epileptic pregnant women on the basis of the reduction of different congenital abnormalities (CAs) in their offspring. First, the prevalence of medically recorded epilepsy was compared in 95 pregnant women who later had offspring with different CAs (case group) and 90 pregnant women who later delivered newborn infants without CA (control group) and matched to cases in the Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980-1996. Second, the rate of different CAs was compared in the offspring of epileptic pregnant women between 1980 and 1989 and 1990-1996. Cleft lip with or without cleft palate, cleft palate, cardiovascular CAs, oesophageal atresia/stenosis, hypospadias and multiple CAs showed a higher risk in the offspring of pregnant women with epilepsy treated with different antiepileptic drugs, explained mainly by polytherapy. There was no higher risk for total CAs after monotherapy. There was no significantly lower rate of total CAs in the offspring of epileptic pregnant women during the second period of the study. The efficacy of special medical care of epileptic pregnant women was not shown on the basis of decrease in the rate of CAs in the offspring of epileptic pregnant women

Oral Clefts with Associated Anomalies: Findings in the Hungarian Congenital Abnormality Registry

BACKGROUND: Over the years, great efforts have been made to record the frequency of orofacial clefts in different populations. However, very few studies were able to account for the etiological and phenotypic heterogeneity of these conditions. Thus, data of cases with syndromic orofacial clefts from large population-based studies are infrequent. METHODS: Clinically recognized and notified syndromes and associations including cleft lip with or without cleft palate and other congenital anomalies were selected from the Hungarian Congenital Abnormality Registry (HCAR) between 1973 and 1982 and prevalence rates were calculated. RESULTS: Of 3,110 cases reported as having orofacial clefts, 653 had multiple congenital abnormalities. Of these, 60 (9.2%) had a known etiology (monogenic: 25 or 3.8%, chromosomal: 31 or 4.7%, teratogenic: 4 or 0.6%). Seventy-three subjects (11.2%) had schisis in addition to the oral cleft. Skeletal anomalies were the most common malformations among cases with cleft lip with/without cleft palate (CL/P) and cleft palate (CP). Disorders of the central nervous system and cardiovascular malformations were also frequently associated. CONCLUSION: Surveillance systems, such as the HCAR, provide useful information about prevalence rates of congenital anomalies in a population. However, in a field where new syndromes are being discovered and classifications regularly updated, these rates should only be accepted as provisional.Massachusetts Center for Birth Defects Research and Prevention of the Massachusetts Department of Public Health; Peer Foundation/Cleft Palate Foundation Etiology Gran

A study of the risk of mental retardation among children of pregnant women who have attempted suicide by means of a drug overdose

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 (Χ21=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

Attempted suicide and pregnancy

BACKGROUND: The aim of the Budapest Monitoring System of Self-Poisoning Pregnant Women was to evaluate the potential congenital abnormality inducing effect of extremely large doses of drugs among pregnant women who attempted suicide. This system was appropriate to describe the characteristics of these pregnant women as a secondary finding from this model. METHODS: All self-poisoned patients were cared for at a toxicological inpatient clinic in Budapest, between 1960 and 1993. Of a total of 1,044 pregnant women identified from the three different periods of the project, only 19 (1.8%) died. Women who survived were visited at home to reveal birth outcomes, and their exposed children were examined medically to identify congenital abnormalities and tested to estimate their cognitive-behavioral status. The previous or subsequent children of these pregnant women were used as controls with a similar examination protocol. RESULTS: In general, self-poisoned pregnant women were young (peak age was between 18 and 20 years), 62% had their first pregnancy, 55% were unmarried, they had lower socioeconomic status, 46% were smokers and 22.5% drinkers, but depression/panic disorder occurred only among 17 pregnant women. Suicide attempts with drugs were most frequent in the fourth post-conceptional week and second month of pregnancy. In general they used smaller doses of drugs for suicide than non-pregnant age-matched women. Of 1,044 self-poisoned pregnant women, 926 had known pregnancy outcomes and 411 (44.4%) delivered live-born babies. CONCLUSIONS: The self-poisoning model appears to have several benefits (e.g., dose-response estimation of drugs) in comparison with other methods when evaluating teratogenic/fetotoxic effect of drugs. It is suggested that an international monitoring system of self-poisoned pregnant women should be established to provide a larger data base

Association of drug treatments in pregnant women with the risk of external ear congenital abnormalities in their offspring: a population-based case-control study

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