Exposure
The exposed group consisted of pregnant women exposed to BDZs and/or
hypnotic benzodiazepine receptor agonists (BDZs), BDZs exposure was
defined as using chronic BDZs any time from the first day of the last
menstrual period (LMP) until the end of the pregnancy. The LMP was
estimated from the gestational age reported in the patient file.
Exclusion criteria for both groups were a stillbirth delivery
(> 24 weeks of gestation) and multiple births. Also,
pregnancies with exposure to teratogenic drugs according to the
Teratology Information Centre (TIS) were excluded. However, we included
lithium because of its indication in bipolar disorders. Mother-child
couples were excluded in the case of paternal or maternal congenital
malformations according to ICD-10 codes class XVII (Q00-Q99) or in the
case of an actual maternal diagnosis of epilepsy (ICD-10 G40-G41),
because of the possibility of using teratogenic anti-epileptic drugs.
Further, mother-child couples with missing primary or secondary outcomes
were also excluded. Women with short-term use of BDZs only used during
hospital admission were excluded as these might bias the results because
it’s not related to psychiatric disease. In the presence of more than
one pregnancy concerning the same mother, we randomly selected one
pregnancy in our dataset. For statistical reasons, we included a double
number of pregnancies in the reference group at random compared to the
exposed group.