Abstract Objectives: The objectives of the study were to assess the prevalence of anxiolytic use in pregnancy, the rate of congenital malformations in neonates at in utero exposure to these agents, and the possible association of congenital malformations with the use of these drugs in pregnancy. Method: The study was conducted as cross-sectional study. The study was performed at university departments of gynecology and obstetrics in four Zagreb hospitals and included 893 pregnant women. Main outcome measures were pathological defects and congenital malformations. Results: The main anatomic group N drugs (nervous system) was predominated by the use of the benzodiaze- pine anxiolytic diazepam (FDA group D), which increased with gestational age. Diazepam was used by 74 (8.3%), 127 (14.2%) and 212 (23.7%) women in the first, second and third trimester, respectively. Diazepam ranked second among twenty most frequently prescribed drugs in pregnancy. It was taken by 303 (33.9%) pregnant women, while congenital cardiovascular malformations were recorded in three children and genitourinary malfor- mations in three children too. Conclusions: The high utilization of diazepam in pregnancy that is not supported by professional guidelines is an issue of serious concern. In spite of some study limitations, its results pointed to inappropriate and even potentially harmful use of drugs in pregnant women from Zagreb, thus calling for upgrading the quality of therapy in this vulnerable period of life. In our opinion, other measures appear to be a more appropriate therapeutic modality than medicamentous therapy in many cases. Key words: anxiolytics, pregnancy, diazepam, benzo- diazepines Introduction Pregnancy is a period in which attention should be paid to the use of medication in particular because drugs can exert dual adverse effects in pregnant women. Drugs can threaten maternal health and influence the course of pregnancy, and may also exert adverse effects on the fetus by reaching it via placental route and influencing its growth and development. As a great proportion of pregnancies have not been planned, maternal exposure to the adverse effects of medication may occur while still being unaware of pregnancy (1, 2). Every child as a unique person is characterized by his/her own response and sensitivity to the drug used by the mother. The cause of variable fetal response remains unknown. Different pregnant women may take the same drug at the same dosage and over the same period of time, while their fetuses/infants will differ in their response to it (3, 4). The use of drugs in pregnancy has come into focus of interest after thalidomide tragedy that upset the public worldwide in the 1960s. Thalidomide, a sedative and hypnotic, largely advertised as being safe for use in pregnancy, resulted in the birth of some 10,000 neonates with phocomelia, i.e. absence of the proximal portion of limbs (5-9). Drugs prescribed to pregnant women should primarily treat maternal disease. Pregnancy is associated with some specific pharmacokinetic features because the drug that is not intended for the fetus reaches fetus via placental route. During pregnancy, major changes occur at the level of drug distribution and elimination. Controlled studies of drug use in pregnancy cannot be performed for ethical reasons; therefore data can only be obtained from animal experiments, general databases, profes- sional literature, and individual reports on sporadic use of drugs in pregnancy (10). Many data are cate- gorized as ‘probable’ for being based on epidemio- logical retrospective studies. Animal experiments provide data on structural teratogenicity, yet limited by the fact that none of the animal species resembles humans to such an extent that the results can be Acta Neurol. Belg., 2010, 110, 163-167 The effects of benzodiazepines in pregnancy Marcel LEPPÉE PhD 1 , Josip CULIG PhD 1,2 , Mirela ERIC MSc 3 , Sinisa SIJANOVIC PhD 4 1 Department od Pharmacoepidemiology, Andrija Stampar Institute of Public Health, 10000 Zagreb, Croatia; 2 Department of Pharmacology, School of Medicine, Josip Juraj Strossmayer University, 31000 Osijek, Croatia; 3 Department of Anatomy, School of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia; 4 Department of Obstetrics and Gynecology, Clinical Hospital Osijek, 31000 Osijek, Croatia ————