A study of the effects of large doses of medazepam used for self-poisoning in 10 pregnant women on fetal development

Abstract

The purpose of this article is to report an evaluation of the teratogenic and fetotoxic potential of medezepam in humans based on pregnant women who used very large doses of medazepam for a suicide attempt. All self-poisoned patients were cared for at the Department of Toxicology Internal Medicine, Koranyi Hospital, a toxicological inpatients clinic in Budapest, Hungary, between 1960 and 1993. Pregnant women were identified from self-poisoned subjects admitted from a population base of three million people of Budapest and the surrounding region. The rates of congenital abnormalities (CAs), intrauterine fetal development, cognitive and behavioral status in children born to mothers who attempted suicide with medazepam alone or in combination with other drugs during pregnancy was compared in their sib controls. Between 1980 and 1993, 835 pregnant women in our study attempted suicide during pregnancy with drugs. Of these, 314 delivered live-born infants and 283 were examined and/or evaluated. Thirty-two (3.8%) of these 835 pregnant women used medazepam with or without other drugs for self-poisoning; 10 of these women delivered live-born babies. The dose of medazepam used for the suicide attempt ranged between 60 and 500 mg, with a mean of 276 mg. Eight of the 32 suicide attempts involving medazepam occurred between the 4th and 12th postconceptional weeks. Of the 10 live-born exposed children, one was affected with congenital inguinal hernia; one of the 13 sib controls had a lethal hydronephrosis. No adverse effects were observed on intrauterine growth, cognitive status, or behavioral deviations in the 10 children born to mothers who attempted suicide with medazepam during pregnancy. Very large doses of medazepam were used for self-poisoning during pregnancy. These doses did not increase the rate of CAs even though eight mothers attempted suicide during the most critical period for production of CAs. No fetotoxic, including neurotoxic, effects of exposure of live-born children to a very large dose of medazepam were observed. Our experiences show the feasibility and benefits of use of the self-poisoning model in estimating human teratogenic and fetotoxic risks of drugs.

Suicidal ideation in pregnancy: an epidemiologic review

“…The majority of studies that have assessed the impact of suicidal ideation during pregnancy on fetal development have done so in the context of self-poisoning. A series of 15 articles were published from the Budapest Monitoring System of Self-Poisoning Pregnant Women that evaluated the potential effects of large doses of drugs on fetal development among pregnant women who attempted suicide (Czeizel et al, 1997, Czeizel et al, 1999, Timmermann et al, 2009, Gidai et al, 2008c, Gidai et al, 2008a, Gidai et al, 2008d, Gidai et al, 2008b, Gidai et al, 2010, Petik et al, 2008a, Petik et al, 2008b, Petik et al, 2012, Timmermann et al, 2008b, Timmermann et al, 2008a, Timmermann et al, 2008c). With regards to congenital anomalies, the primary outcomes of these studies, no statistically significant associations were reported with self-poisoning (Czeizel et al, 1997, Czeizel et al, 1999, Timmermann et al, 2009, Gidai et al, 2008c, Gidai et al, 2008a, Gidai et al, 2008d, Gidai et al, 2008b, Gidai et al, 2010, Petik et al, 2008a, Petik et al, 2008b, Petik et al, 2012, Timmermann et al, 2008b, Timmermann et al, 2008a, Timmermann et al, 2008c).…”

Association of prenatal exposure to benzodiazepines and child internalizing problems: A sibling-controlled cohort study

“…Withdrawal syndrome and floppy infant syndrome have been reported in babies after maternal use of BZDs towards the end of pregnancy [12–15]. Results of previous studies on mental health outcomes in the offspring following prenatal exposure to BZDs or z-hypnotic drugs have been conflicting [16–18]. A sibling-matched study found no association with behavioral deviation in children at age 8–12 months after prenatal exposure to medazepam [16].…”

“…Results of previous studies on mental health outcomes in the offspring following prenatal exposure to BZDs or z-hypnotic drugs have been conflicting [16–18]. A sibling-matched study found no association with behavioral deviation in children at age 8–12 months after prenatal exposure to medazepam [16]. In contrast, a study on 1.5-year-old children showed reduced personal-social behavior abilities in children exposed to BZDs [17].…”

Association of prenatal exposure to benzodiazepines and child internalizing problems: A sibling-controlled cohort study

“…Results of previous studies on mental health outcomes in the offspring following prenatal exposure to BZDs or z-hypnotic drugs have been conflicting [16][17][18]. A sibling-matched study found no association with behavioral deviation in children at age 8-12 months after prenatal exposure to medazepam [16]. In contrast, a study on 1.5-year-old children showed reduced personal-social behavior abilities in children exposed to BZDs [17].…”

“…Withdrawal syndrome and floppy infant syndrome have been reported in babies after maternal use of BZDs towards the end of pregnancy [12][13][14][15]. Results of previous studies on mental health outcomes in the offspring following prenatal exposure to BZDs or z-hypnotic drugs have been conflicting [16][17][18]. A sibling-matched study found no association with behavioral deviation in children at age 8-12 months after prenatal exposure to medazepam [16].…”