Maternal drug histories and congenital malformations: limb reduction defects and oral clefts.

Abstract

SUMMARY In a case control study, prescription data were examined for the three months before the last menstrual period and for the first trimester ofpregnancy in (a) 115 mothers ofchildren with limb reduction defects, (b) 676 mothers of children with oral cleft, and (c) an equal number of control mothers ofnormal babies from the same doctor's practice for each case. In the limb reduction study, the study mothers were prescribed more drugs generally although this did not reach statistical significance, nor were there significant differences between study and control mothers for individual groups of drugs. In the oral cleft study, significantly more drugs were prescribed to study mothers in the three months before the last menstrual period, and a similar trend, which did not reach statistical significance, was observed in the first trimester. Anticonvulsant drugs were prescribed significantly more frequently to study mothers during the whole period of the study. A significant association was also demonstrated between oral contraceptives taken in the three months before the last menstrual period and oral cleft, but doubt must remain concerning this relationship; the risk is not well understood and is likely to be nonspecific. A number of other significant associations were identified, although their importance in practice is uncertain in view ofthe confounding factors that may affect a study of this kind.

Chemical exposure during pregnancy and oral clefts in newborns

“…The investigation estimated relative risks, controlling for potential confounders, on the order of 1.2 (95% CI: 0.5-3.2) for cleft lip with or without cleft palate and 2.0 for cleft palate only (95% CI: 0.6-6.5), neither statistically significant. Hill et al (1988) observed an increased use of medication ranging from pre-conception through the first trimester of pregnancy among mothers of children with orofacial clefts, although not statistically significant. The most frequent report was the use of anti-convulsive drugs during the pre-gestational period.…”

“…Evaluating four methods for selection of controls, Lieff et al (1999) found that the best option is the use of controls with malformations other than the one under study. On the other hand, the use of such control groups in association studies can produce questionable results, according to Hill et al (1988) and Prieto & Martínez-Frías (1999). The use of unhealthy controls could be useful to measure the specificity of the association between exposure and a particular defect, but it would not allow to estimate a risk ratio per se (Prieto & Martínez-Frías, 1999).…”

“…With regard to orofacial clefts (Table 3), the most extensively identified association was between the use of anticonvulsivant drugs and cleft lip with or without cleft palate, especially with the use of diphenylhydantoin, phenobarbital, and multi-drug therapy (Castilla et al, 1996). Various authors observed a two-fold risk of birth defects among children of epileptic mothers undergoing this form of prolonged treatment during pregnancy (Hill et al, 1988;Wyszynski et al, 1996 In the 1970s, Saxén (1974) reported increased occurrence of cleft palate among children of mothers using benzodiazepines, particularly diazepam. Likewise, Safra & Oakley (1975) reported an increased association between the diazepam group and oral clefts as compared to other malformations.…”

Fendas orofaciais no recém-nascido e o uso de medicamentos e condições de saúde materna: estudo caso-controle na cidade do Rio de Janeiro, Brasil

“…14 Particularmente no caso de FL ± P, a condição materna mais freqüentemente associada é a epilepsia, embora vários autores tenham observado que a elevação do risco ocorre somente entre as crianças cujas mães tenham sido submetidas à terapia com drogas antiepiléticas, particularmente a politerapia. 1,4,10 Neste estudo, foram detectados 21 relatos de epilepsia/convulsões, sendo que das nove mães com relato de uso freqüente de terapia antiepilética (especialmente fenobarbital) 100% tiveram conceptos portadores da malformação em questão. De 12 casos de uso eventual/isolado, sete apresentavam FL ± P.…”

“…Algumas malformações congênitas estão comprovadamente associadas ao uso de medicamentos em um período gestacional precoce, como é o caso da redução de membros (dentre outros defeitos) causados pelo uso da talidomida e a associação das fendas orofaciais e o uso de drogas anticonvulsivantes. 1,2 Contudo, a ação teratogênica de outras drogas mais comumente usadas é controversa. Estatísticas norte-americanas estimam que cerca de metade das gestações não são planejadas 3 e, portanto, muitas mulheres expõem inadvertidamente seus fetos a ação de medicamentos.…”