Register-based studies of delivery outcome after maternal use of some common drugs

Abstract: This thesis aimed to study neonatal outcome including the presence of congenital malformations and to describe maternal characteristics for women using some common drugs during pregnancy. Drugs used in one benign condition (nausea and vomiting) and one chronic disease (hypothyroidism) and the CNS-active drugs benzodiazepines and hypnotic benzodiazepine receptor agonists were selected. The studies were based on the Swedish Medical Birth Register (MBR). The main advantages with MBR are that relatively large numbers of exposed women and their infants can be identified (coverage 98- 99% of deliveries in Sweden). Drug exposure as well as information about putative confounders are based on information retrieved early in pregnancy, before the birth of the child, and are therefore prospective. The information on the outcome is based on medical documents and is basically not affected by the exposure. Some weaknesses in MBR are that interview data will probably understate drug use, drugs may be taken but not reported/recorded, the indication for drug use is often not known and the information of exact duration and dosage is often incomplete. Further, the studies are based on born infants, aborted foetuses are not included. Pregnant women exposed to antiemetic drugs, a surrogate marker for nausea and vomiting during pregnancy, showed an overall better neonatal outcome including prevalence at birth of malformations in the infants. For some antiemetic drugs the number of exposures was low. Young maternal age, non-smoking, low education, parity >=2, were characteristics of women exposed to antiemetic drugs. There was an excess of girls and twins among born infants. Women using benzodiazepines or hypnotic benzodiazepine receptor agonists during pregnancy differ in many aspects from non-users. These differences may act as confounders in the analysis of pregnancy outcome, and were adjusted for. An increased risk for preterm birth, low birth weight and when exposed late during pregnancy also an increased risk for respiratory problems was seen in neonates. The teratogenic potential does not appear to be strong, but a higher than expected number of infants with pylorostenosis or alimentary tract atresia (especially small gut) was found. No increased risk for orofacial clefts was found. Women substituted with thyroid hormones during pregnancy had diabetes co-morbidity more often than expected as well as co-medication with, e.g., cardiovascular drugs, systemic corticosteroids and psychiatric drugs. Subfertility, previous miscarriage, pre-eclampsia, caesarean section and induction of labour were more common than in non-users. Neonates were only slightly affected, although a marginal increased risk for premature birth, increased rates of neonatal thyroid disease and a slightly increased rate of malformations was found. In conclusion, the Swedish Medical Birth Register has advantages and disadvantages but is a powerful tool for surveillance and assessment of teratogenic risks. However, possible associations found are hypothesis generating and need to be confirmed or rejected in new studies.