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Benzodiazepine use during pregnancy: a prospective study
European Journal and Reproductive
ELSEVIER
of Obstetrics & Gynecology Biology 61 (1995) 181-182
Letter to the editor
Benzodiazepine use during pregnancy: a prospective study Winnie Courtens* a, Esther Vamosa, Joseph Valsamisb, Tenter
6 March
1995; accepted
Recently, clinical and epidemiological human studies suggested that benzodiazepines (BZD) may act as human teratogens [l-7]. Data on BZD use during pregnancy are scarce. The only (retrospective) study of BZD use during pregnancy was in Gothenburg, Sweden, where maternal (- 12th week of pregnancy) serum samples were analyzed; positive results were found in 7% of the pregnant women (2160). These rates are much higher than the estimated incidence (from interviews and outpatient prescriptions) of l-3% [4]. Other studies about the incidence of BZD use during pregnancy are only based on the frequency of BZD prescriptions (81. We performed a prospective study on the incidence of BZD use in unselected pregnant women, attending the prenatal consultation in a Brussels public hospital (low to middle social class). Serum samples of 307 pregnant women (mean age 27.5 years, range 15.2-44.6 years) were screened for the presence of BZD. The samples were taken at an average of 17 weeks 6 days gestation, according to ultrasounds (range 15-25 weeks). A complete history (including intake of BZD and other medications) was systematically performed. Drug addicted women (hard and soft drugs, multiple medications) were not included in the study. The screening method for BZD was performed using a fluorescence polarization immunoassay technology (Abbott Laboratories, NC, USA). The sensitivity, detined as the lowest measurable concentration which can be distinguished from zero, was determinated to be 12 rig/ml. None of these 307 pregnant women had a history of
author,
Willemsb, Alain VokaerC
of Medical Genetics, University Hospital Brugmann, A. Van Gehuchtenplein 4, 1020 Brussels, Belgium bLuboratory of Clinical Chemistry, University Hospital Brugmann, Brussels, Belgium ‘Department of Gynecology and Obstetrics, University Hospital Brugmann. Brussels, Belgium Received
* Corresponding
Dominique
Tel.: +32 2 4772217; Fax: +32 2 4798197.
0301-2115/95/$09.50 0 1995 Elsevier Science Ireland SSDI 0301-2115(95)02140-N
19 April
1995
BZD intake and the screening for BZD was negative in all the blood samples. In conclusion, our results obtained in a large population of pregnant women suggest that BZD use is negligible in our normal pregnant population (toxicomania excluded). A careful history is probably efficient enough to exclude BZD use in pregnant women. We do not confirm the 7% incidence of BZD use reported in the Gothenburg survey [4]. Such findings could be explained by geographic and cultural differences in BZD use during pregnancy. In addition, their data may eventually be biassed by a rather small sample. Teratogenicity of BZD used as mono-treatment is difficult to prove since most patients using BZD take also other drugs. Acknowledgments
This work was supported by the Yvonne Bo&l Foundation. References
111 121 (31
141
Pl
Ltd. All rights reserved
Courtens W, Hainaut M, Vergauwen P, Vamos E. Moebius syndrome in an infant exposed in utero to benzodiazepines. J Pediatr 1992; 121: 833-834. Laegreid L, Olegard R, Walstrijm J, Conradi N. Abnormalities in children exposed to benzodiazepines in utero. Lancet 1987; 1: 108-109. Laegreid L, Olegard R, Walstrijm J, Conradi N. Teratogenic effects of benzodiazepine use during pregnancy. J Pediatr 1989; 114: 126-131. Laegreid L, Olegard R, Conradi N, Hagberg G, Walstrom J, Abrahamsson L. Congenital malformations and maternal consumption of benzodiazepines: a case-control study. Dev Med Child Neurol 1990, 32: 432-441. Laegreid L, Hagberg G, Lundberg A. The effect of benzodiaze-
182
[6]
[7]
Letter to the editor/European
Journal of Obstetrics & Gynecology and Reproductive Biology 61 (1995) 181-182
pines on the fetus and the newborn. Neuropediatrics 1992; 23: 18-23. Laegreid L, Hagberg G, Lundberg A. Neurodevelopment in late infancy after prenatal exposure to benzodiazepines: a prospective study. Neuropediatrics 1992; 23: 60-67. Viggedal G, Hagberg BS, Laegreid L, Aronsson
M. Mental de-
[8]
velopment in late infancy after prenatal exposure to benzodiazepines: a prospective study. J Child Psycho1 Psychiatr 1993; 34: 295-305. Bergman U, Rosa FW, Baum C, Wiholm BE, Faith GA. Effects of exposure to benzodiazepine during fetal life. Lancet 1992; 340: 694-696.
ELSEVIER
of Obstetrics & Gynecology Biology 61 (1995) 181-182
Letter to the editor
Benzodiazepine use during pregnancy: a prospective study Winnie Courtens* a, Esther Vamosa, Joseph Valsamisb, Tenter
6 March
1995; accepted
Recently, clinical and epidemiological human studies suggested that benzodiazepines (BZD) may act as human teratogens [l-7]. Data on BZD use during pregnancy are scarce. The only (retrospective) study of BZD use during pregnancy was in Gothenburg, Sweden, where maternal (- 12th week of pregnancy) serum samples were analyzed; positive results were found in 7% of the pregnant women (2160). These rates are much higher than the estimated incidence (from interviews and outpatient prescriptions) of l-3% [4]. Other studies about the incidence of BZD use during pregnancy are only based on the frequency of BZD prescriptions (81. We performed a prospective study on the incidence of BZD use in unselected pregnant women, attending the prenatal consultation in a Brussels public hospital (low to middle social class). Serum samples of 307 pregnant women (mean age 27.5 years, range 15.2-44.6 years) were screened for the presence of BZD. The samples were taken at an average of 17 weeks 6 days gestation, according to ultrasounds (range 15-25 weeks). A complete history (including intake of BZD and other medications) was systematically performed. Drug addicted women (hard and soft drugs, multiple medications) were not included in the study. The screening method for BZD was performed using a fluorescence polarization immunoassay technology (Abbott Laboratories, NC, USA). The sensitivity, detined as the lowest measurable concentration which can be distinguished from zero, was determinated to be 12 rig/ml. None of these 307 pregnant women had a history of
author,
Willemsb, Alain VokaerC
of Medical Genetics, University Hospital Brugmann, A. Van Gehuchtenplein 4, 1020 Brussels, Belgium bLuboratory of Clinical Chemistry, University Hospital Brugmann, Brussels, Belgium ‘Department of Gynecology and Obstetrics, University Hospital Brugmann. Brussels, Belgium Received
* Corresponding
Dominique
Tel.: +32 2 4772217; Fax: +32 2 4798197.
0301-2115/95/$09.50 0 1995 Elsevier Science Ireland SSDI 0301-2115(95)02140-N
19 April
1995
BZD intake and the screening for BZD was negative in all the blood samples. In conclusion, our results obtained in a large population of pregnant women suggest that BZD use is negligible in our normal pregnant population (toxicomania excluded). A careful history is probably efficient enough to exclude BZD use in pregnant women. We do not confirm the 7% incidence of BZD use reported in the Gothenburg survey [4]. Such findings could be explained by geographic and cultural differences in BZD use during pregnancy. In addition, their data may eventually be biassed by a rather small sample. Teratogenicity of BZD used as mono-treatment is difficult to prove since most patients using BZD take also other drugs. Acknowledgments
This work was supported by the Yvonne Bo&l Foundation. References
111 121 (31
141
Pl
Ltd. All rights reserved
Courtens W, Hainaut M, Vergauwen P, Vamos E. Moebius syndrome in an infant exposed in utero to benzodiazepines. J Pediatr 1992; 121: 833-834. Laegreid L, Olegard R, Walstrijm J, Conradi N. Abnormalities in children exposed to benzodiazepines in utero. Lancet 1987; 1: 108-109. Laegreid L, Olegard R, Walstrijm J, Conradi N. Teratogenic effects of benzodiazepine use during pregnancy. J Pediatr 1989; 114: 126-131. Laegreid L, Olegard R, Conradi N, Hagberg G, Walstrom J, Abrahamsson L. Congenital malformations and maternal consumption of benzodiazepines: a case-control study. Dev Med Child Neurol 1990, 32: 432-441. Laegreid L, Hagberg G, Lundberg A. The effect of benzodiaze-
182
[6]
[7]
Letter to the editor/European
Journal of Obstetrics & Gynecology and Reproductive Biology 61 (1995) 181-182
pines on the fetus and the newborn. Neuropediatrics 1992; 23: 18-23. Laegreid L, Hagberg G, Lundberg A. Neurodevelopment in late infancy after prenatal exposure to benzodiazepines: a prospective study. Neuropediatrics 1992; 23: 60-67. Viggedal G, Hagberg BS, Laegreid L, Aronsson
M. Mental de-
[8]
velopment in late infancy after prenatal exposure to benzodiazepines: a prospective study. J Child Psycho1 Psychiatr 1993; 34: 295-305. Bergman U, Rosa FW, Baum C, Wiholm BE, Faith GA. Effects of exposure to benzodiazepine during fetal life. Lancet 1992; 340: 694-696.