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

Abstract

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.

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

“…These possible triggering factors such as maternal diseases (e.g. diabetes mellitus) and drugs (antiepileptic medicines) were detected in the origin of IMA in our previous studies [2,3]. Table 3 The objective of the study was to test the multifactorial etiology of cases with IMA based on the comparison of observed and expected numbers of affected first degree relatives with IMA, and there was no significant difference between expected and observed total numbers of first degree relatives with IMA (p = 0.47).…”

“…congenital abnormalities (CAs) of external ears. Previously the possible environmental factors such as maternal socio-demographic features [1], diseases [2] and related drug treatments [3] were evaluated in these cases. The objective of this study is the analysis of the possible genetic origin of isolated microtia/anotia on the basis of their familial cluster.…”

Pregnancy as a valuable period for preventing hypoxia‐ischemia brain damage

“…Working with the hypothesis that phenytoin could be effective by limiting deleterious effects of intrapartum asphyxia, Lampley et al (1995) pre‐treatment of guinea pigs dams with phenytoin before hypoxia (7% O 2 , for 60 min) exposure and observed that the injury decreased Na + , K + ‐ATPase activity and increased lipoperoxidation; reversed by phenytoin pretreatment (Lampley et al, 1995). Although interesting for its capability in preventing early events of HI cascade in preclinical settings, we did not find additional reports using phenytoin in HI context, possibly due to its side effects such as hypotension, coagulation problems (Baxter et al, 2004) and increased risk for fetal abnormalities observed in the clinic (Paput et al, 2011).…”

Risk factors and demographics for microtia in South America: A case–control analysis

“…Although several published reports have attempted to identify risk factors for microtia, only four of these have been case–control studies (Table ) (Castilla and Orioli, ; Mastroiacovo et al, ; Paput et al, ; Van Bennekom et al, ). While they also recruited controls through population and hospital birth cohorts, these ranged in size from 172 to 411 cases, and control participation rates were reported for only one study (Van Bennekom et al, ) retaining the possibility that bias may have accounted for some of the associations which were reported.…”