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

Prevention of Neural-Tube Defects with Periconceptional Folic Acid, Methylfolate, or Multivitamins?

Background/Aims: To review the main results of intervention trials which showed the efficacy of periconceptional folic acid-containing multivitamin and folic acid supplementation in the prevention of neural-tube defects (NTD). Methods and Results: The main findings of 5 intervention trials are known: (i) the efficacy of a multivitamin containing 0.36 mg folic acid in a UK nonrandomized controlled trial resulted in an 83-91% reduction in NTD recurrence, while the results of the Hungarian (ii) randomized controlled trial and (iii) cohort-controlled trial using a multivitamin containing 0.8 mg folic acid showed 93 and 89% reductions in the first occurrence of NTD, respectively. On the other hand, (iv) another multicenter randomized controlled trial proved a 71% efficacy of 4 mg folic acid in the reduction of recurrent NTD, while (v) a public health-oriented Chinese-US trial showed a 41-79% reduction in the first occurrence of NTD depending on the incidence of NTD. Conclusions: Translational application of these findings could result in a breakthrough in the primary prevention of NTD, but so far this is not widely applied in practice. The benefits and drawbacks of 4 main possible uses of periconceptional folic acid/multivitamin supplementation, i.e. (i) dietary intake, (ii) periconceptional supplementation, (iii) flour fortification, and (iv) the recent attempt for the use of combination of oral contraceptives with 6S-5-methytetrahydrofolate (methylfolate), are discussed. Obviously, prevention of NTD is much better than the frequent elective termination of pregnancies after prenatal diagnosis of NTD fetuses

Possible multifactorial etiology of isolated microtia/anotia-A population-based study

Objective: To test the possible multifactorial-threshold model in the origin of isolated microtia/anotia (IMA). Method: The observed number of IMA in the first degree relatives of cases affected was compared with the expected number of affected first degree relatives based on the multifactorial-threshold model in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Results: Of 354 cases with IMA, 14 (4.0%) had the affected first degree relatives with IMA. There was a low and similar rate of familial occurrence of IMA in parents and siblings of cases. The observed numbers of affected first degree relatives of cases with IMA and their expected numbers did not show significant difference (p= 0.47). Some other findings (e.g. male excess and the interaction of triggering environmental factors with polygenic predisposition) confirmed this hypothesis. Conclusions: The familial pattern of cases with IMA does not reject the hypothesis that the multifactorial-threshold model, i.e. gene-environmental interaction, may be the explanation for the origin of this congenital abnormality group, although the number of familial cases was quite small in the study. © 2011 Elsevier Ireland Ltd

Az anotiát és microtiát kísérő többszörös fejlődési rendellenességek eloszlása [Distribution of multiple congenital abnormalities including anotia and microtia]

To evaluate cases with unclassified multiple congenital abnormalities including microtia and anotia as component congenital abnormalities in order to reveal the characteristic pattern of other associated component congenital abnormalities and to make an attempt to establish a registry diagnosis on the pattern of associated congenital abnormalities and to stimulate the establishment of an international registry of cases with unclassified multiple congenital abnormalities comprising of microtia and anotia. METHODS: The large population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. RESULTS: A total of 156 cases with unclassified multiple congenital abnormalities including microtia and anotia were analyzed according to the number of 2-9 component congenital abnormalities. The comparison of the distribution and frequency of component congenital abnormalities in these cases showed significant differences from the data of other unclassified multiple congenital abnormalities. Of the 156 cases, registry diagnosis was possible in 48 (30.8%) cases. CONCLUSIONS: The evaluation of available dataset of unclassified multiple anotia and microtia may help the delineation of new syndromes and associations with better prognosis and recurrence risk estimation, thus finally a better chance for their prevention