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.

No abstract

The objective of the study was to estimate the possible association of maternal diseases with the risk of isolated ear congenital abnormalities (IECA) including mainly microtia and anotia in their children. Incidence of acute and prevalence of chronic maternal diseases in the mothers with IECA and in the mothers of their matched controls and all controls without any defects, in addition in the mothers of malformed controls with other isolated defects was compared in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities. Of 354 cases with IECA, 32 had mothers with high fever related influenza-common cold during the critical period of IECA and it resulted in a higher risk of IECA in their live-born infants (adjusted OR with 95% CI: 4.3, 1.9-7.4) compared with their matched controls. However, the early and effective antifever treatment in these pregnant women prevented them from the IECA. In addition there was an association of maternal otitis media with higher risk of complex defects of middle and external ears (OR with 95% CI: 5.2, 1.6-28.3), however, this association was based on 4 cases only. In conclusion high fever related influenza-common cold with secondary complications may play a role in the origin of IECA, but is preventable with the early and effective antifever treatment of these pregnant women.

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.

No abstract