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

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

Self-poisoning during pregnancy as a model for teratogenic risk estimation of drugs.

The results of animal investigations cannot be directly extrapolated to pregnant women. Clinical and analytical epidemiological studies for human teratogenic risks have many inherent methodological problems and their predictions must be regarded with caution. Evaluation of the potential teratogenicity of extremely large doses of drugs in self-poisoned pregnant women who attempted suicide offers a unique model for finding associations between congenital abnormalities and different drugs. All self-poisoned patients were cared for at a toxicological inpatient clinic in Budapest, between 1960 and 1993. Out of 1044 pregnant women identified from three different periods of the project, 19 died. Women who survived were visited at home to reveal birth outcomes, and their children were evaluated medically to identify congenital abnormalities and to estimate cognitive-behavioral status. The previous or subsequent children of these pregnant women were used as controls. In general, self-poisoned pregnant women were young (peak age was 18 to 20 years) and primiparous; 55% were unmarried and of lower socioeconomic status. Suicide attempts with drugs were most frequent in the fourth postconceptional week and second pregnancy month. Of 1044 self-poisoned pregnant women, 411 delivered live-born babies, of which 367 children (89.3%) were evaluated. The self-poisoning model appears to have several benefits (e.g., dose-response estimation) in comparison with other methods. It is suggested that an international monitoring system of self-poisoned pregnant women should be established to provide a larger database.

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

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

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

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

Smoking and alcohol drinking during pregnancy. The reliability of retrospective maternal self-reported information.

BACKGROUND: The reliability of retrospective maternal self-reported information regarding smoking and alcohol drinking during pregnancy seemed necessary to be checked. METHODS: Two groups of congenital abnormalities were selected for the study from the population based Hungarian Congenital Abnormality Registry. The prevalence of smoking and drinking during the study pregnancy was measured in the mothers of 81 cases affected with isolated orofacial cleft and 537 cases with congenital limb deficiencies, and in their matched control pairs without any defect by maternal self-reported retrospective information through a mailed structured questionnaire. In the second step the latter data were checked by an independent personal interview of fathers and other family members at the home visit or in our department using the same structured questionnaire. RESULTS: The family consensus indicated the low reliability of retrospective maternal self-reported information concerning smoking in the mothers of cases but not in mothers of controls. However, the comparison of retrospective maternal self-reported data and information of close relatives indicated a reported bias concerning the drinking of alcohol beverages during pregnancy in both controls and cases. CONCLUSIONS: Since retrospective maternal self-reported data had low reliability, therefore, data of smoking and alcohol drinking were not collected for the data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996.

Validation studies of drug exposures in pregnant women.

The aim of these studies was to check the quality of data collection concerning drug use during pregnancy in the Hungarian Case-Control Surveillance of Congenital Abnormalities from four different aspects. (a) The parents of non-respondent cases were visited at home to collect data, but the Ethics Committee did not allow collection of comparable data from non-respondent control women. Thus only 200 selected non-respondent controls were visited at home and questioned about drug use as part of a validation study. There was no difference in the distribution and occurrence of frequently used drugs between the respondent and non-respondent control groups. (b) Data collection was compared between the usual method of the Case-Control Surveillance and personal interview in case with congenital limb deficiencies. In general, the two methods produced similar results with respect to drug use, but the personal interview revealed a higher use of unintended contraceptive pills while the use of antenatal care logbooks in the Case-Control Surveillance showed a higher use of drugs to prevent threatened abortion and preterm delivery. (c) A check of source and completeness of drug exposure showed that about one-quarter of the drugs used during pregnancy were not recorded in the Case-Control Surveillance, and the proportion of lack of recall was about 23%. A small group of women (2.4%) did not use prescribed drugs due to the suspected teratogenic risk. (d) The teratogenic labelling of drugs deters pregnant patients from the use of prescribed drugs, or at least shortens the duration of drug intake. Thus the evaluation of drug use on the basis of medically recorded prescribed drugs and/or usual recommendations produces a bias thus it is necessary to complete it with information from the patients.

[Successful outcome of an intrauterine twin pregnancy combined with ectopic pregnancy]. / Méhen kívüli terhességgel szövödött, sikeresen kiviselt méhen belüli ikerterhesség esete.

Authors present a case of twin intrauterine pregnancy combined with ectopic pregnancy. The simultaneous pregnancies occurred after the use of clomiphene citrate. In this case viable intrauterine twin gestation was observed by vaginal ultrasound examination, the simultaneous ectopic pregnancy was observed by laparotomy. Right salpingectomy was performed. The intrauterine twin pregnancy continued normally to the 35th week of pregnancy, finished with normal vaginal delivery. The healthy twin boys weighed 2650 g and 2070 g left the hospital in a good general condition on the 5th past delivery day. Authors discuss the etiology, the mode of diagnosis and the therapy of this rare condition.