A study of the teratogenic and fetotoxic effects of large doses of barbital, hexobarbital and butobarbital used for suicide attempts by pregnant women

Abstract

The teratogenic potential of barbiturates is debated. The objective of this study was to evaluate the effects of very large doses of different barbiturates, except phenobarbital and amobarbital, on fetal development in pregnant women who attempted suicide. These self-poisoned pregnant women were identified among the patients of the Department of Toxicology Internal Medicine, Korányi Hospital, Budapest. The prevalence at birth of congenital abnormalities and intrauterine fetal growth, based on pregnancy age at delivery and birth weight, as well as cognitive-behavioral status in exposed children born to mothers who attempted suicide with barbiturates alone or in combination with other drugs, during pregnancy, were compared with their sibs as controls. Of 1044 women with self-poisoning during pregnancy between 1960 and 1993, 411 delivered live-born babies; of these, 367 (89.3%) exposed children were evaluated. Of the 367 exposed children, 6, 5, 4 and 4 were born to mothers who attempted suicide with very large doses of Barbamid (butobarbital and aminophenazone), hexobarbital, butobarbital and Belloid (butobarbital, hyoscyamine and secalis cornuti alkaloida) tablets, respectively. Of 19 exposed children, two children with a congenital inguinal hernia were born to mothers who attempted suicide with 30 tablets of Belloid (900 mg butobarbital) in the 20th postconceptional week or with 20 tablets of Belloid in combination with chlordiazepoxide (100 mg) and nitrazepam (100 mg) in 12th postconceptional week. However, the critical period for production of congenital inguinal hernia is in the last months of pregnancy. None of the exposed children born to the other 12 pregnant women who attempted suicide with these barbiturates between the third and 12th postconceptional week, i.e., during the critical period for production of most major congenital abnormalities, had a congenital abnormality. Congenital abnormalities did not occur among 16 sib controls. Intrauterine fetal growth was similar between sibs and exposed children; cognitive status and behavioral scale also did not indicate any neurotoxic effects from large doses of these barbiturates. The very large doses of barbital, hexobarbital and/or butobarbital used for self-poisoning during pregnancy were not teratogenic to the children, although it must be recognized that the number of exposed children was limited.

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).…”

Suicidal mothers

“…69 Moreover, despite the use of barbiturates being progressively decreased in both neurological and psychiatric practice, such medications are still used by suicidal pregnant women. 70 The period of pregnancy at highest risk of suicide attempts seems to be the second trimester. 71 …”

Associations of antepartum suicidal behaviour with adverse infant and obstetric outcomes

“…Others have published studies on adverse outcomes associated with suicidal behaviour during pregnancy. [6][7][8][9][10][11]13 However, there has been little focus on infant outcomes besides congenital abnormalities, and the results have been mixed. 7,9,10 In our study, after taking into account a comprehensive list of potential confounders including psychiatric disorders, we found that women with suicidal behaviour had 1.3-fold to 1.4-fold increased odds of experiencing adverse infant outcomes.…”

“…3,4 Knowledge about the epidemiology of suicidal behaviour during pregnancy, including the causes and consequences of suicidal behaviour, is critical to inform suicide prevention strategies for pregnant women, and ultimately to reduce maternal mortality. 5 Although suicidal behaviour in pregnancy has been studied for decades, very few studies [6][7][8][9][10][11][12][13] have provided information on the associations of antepartum suicidal behaviour with infant and obstetric outcomes. 10,12 The majority of past studies have focused on suicide attempt by drug overdose.…”

“…10,12 The majority of past studies have focused on suicide attempt by drug overdose. [6][7][8][9]11,13 To date, only two studies have included suicidal behaviour 10,12 other than suicide attempt by overdose, and only one study 12 has evaluated the associations of suicidal ideation with pregnancy outcomes even though suicidal ideation is more frequent than suicide attempt during pregnancy. 14 In addition, the identification of suicidal behaviour in these two studies 10,12 relied solely on billing data, the International Classification of Diseases (ICD) codes, which may be subject to under-coding, miscoding, and incomplete diagnoses.…”