Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations.
BACKGROUND
Exposure to Benzodiazepines (BZD) during foetal life has been suggested to contribute to neonatal morbidity and some congenital malformations, for example, orofacial clefts. Here we aimed to study the neonatal outcome and congenital malformations in neonates whose mothers reported use of BZD and/or hypnotic benzodiazepine receptor agonists (HBRA) during pregnancy.


METHODS
In the Swedish Medical Birth Register we identified 1979 infants whose mothers (n = 1944) reported use of BZD and/or HBRA in early pregnancy. An additional 401 infants were studied, born to 390 mothers who were prescribed such drugs during late pregnancy. Neonatal outcome including congenital malformations after exposure was compared with that of all births (n = 873 879).


RESULTS
An increased risk for preterm birth and low birth weight was detected in the exposed population. The rate of relatively major congenital malformations was moderately increased among infants exposed in early pregnancy (adjusted OR = 1.24, 95%CI 1.00-1.55), not explained by known teratogenic maternal co-medication. A higher than expected number of infants with pylorostenosis or alimentary tract atresia (especially small gut) was found. This was, however, based on only seven infants for each group of malformation without association to any specific BZD or HBRA. The earlier proposed increased risk for orofacial clefts was not confirmed in our study.


CONCLUSIONS
Maternal use of BZD and/or HBRA may increase the risk for preterm birth and low birth weight and cause neonatal symptoms, but does not appear to have a strong teratogenic potential. The tentative association with pylorostenosis and alimentary tract atresia needs confirmation.
Wikner
Birgitta Norstedt
BN
Department of Medicine, Solna, Karolinska Institutet, Clinical Pharmacology Unit, Karolinska University Hospital, Stockholm, Sweden. birgitta.norstedt-wikner@karolinska.se
Stiller
Carl-Olav
CO
Bergman
Ulf
U
Asker
Charlotte
C
Källén
Bengt
B
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology / Q000209:etiology*; D001569:Benzodiazepines / Q000009:adverse effects*; D002971:Cleft Lip / Q000209:etiology; D002972:Cleft Palate / Q000209:etiology; D005260:Female; D058785:GABA-A Receptor Agonists; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007409:Intestinal Atresia / Q000209:etiology; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000139:chemically induced* / Q000453:epidemiology; D011707:Pyloric Stenosis / Q000209:etiology; D012042:Registries; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors
D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines