The use of valproic acid monotherapy in the first trimester was associated with significantly increased risks of several congenital malformations, as compared with no use of antiepileptic drugs or with use of other antiepileptic drugs.

Objective To compare the prescription of drugs in women over a period from 2 years before until 3 months after pregnancy, regarding the type of drugs used and the fetal risk.Design A cohort study based on pharmacy records of women giving birth to a child between 1994 and 2003.Setting The study was performed with data from the InterAction database, containing prescription-drug-dispensing data from community pharmacies.Population The study population included 5412 women for whom complete pharmacy records were available.Methods Drugs were classified into three categories: (1) drugs for chronic conditions, (2) drugs for occasional use and (3) drugs for pregnancy-related symptoms and also classified according to the Australian classification system.Main outcome measures The prescription rate was calculated as the number of women per 100 women who received one or more prescriptions for a given drug within a specified time period.Results About 79.1% of the women received at least one prescription during pregnancy. The prescription rate for most drugs for chronic diseases and for occasional use decreased during pregnancy, whereas, as expected, the prescription rate for pregnancy-related drugs increased. During the first trimester of pregnancy, 1.7% of all drugs prescribed for chronic conditions and 2.3% of the occasional drugs were classified as harmful.Conclusions The increase in prescription rate during pregnancy is caused by an increase in prescription rate of drugs for pregnancyrelated symptoms. The prescription of harmful drugs is more commonly associated with drugs for occasional use rather than with drugs for chronic conditions. Therefore, a more cautious prescribing of drugs to healthy women in the fertile age is necessary.Keywords Drug utilisation, fetal risk classification, pregnancy, prescription rate, register based.Please cite this paper as: Bakker M, Jentink J, Vroom F, Van Den Berg P, De Walle H, De Jong-Van Den Berg L. Drug prescription patterns before, during and after pregnancy for chronic, occasional and pregnancy-related drugs in the Netherlands. BJOG 2006; 113:559-568. IntroductionSince the teratogenic risk of most drugs is still undetermined, it is important to monitor drug use regularly among pregnant women. Drug-utilisation studies reveal that most women use drugs during pregnancy, with estimations varying from 44 1 to 99%. 2 However, comparison is difficult because of differences in study design. Interviews or prescription databases may be used for collecting drug-use data, and the type of drugs studied may or may not include over-the-counter (OTC) drugs such as vitamins, iron and analgesics. Most studies found an increasing trend in drug use during pregnancy. [2][3][4][5][6][7] Drug use cannot be always avoided during pregnancy. For women with certain chronic medical conditions such as epilepsy, diabetes, inflammatory bowel disease and asthma, the use of drugs is essential, and benefits for mother and child may well outweigh the teratogenic risk of the drug. 8,9 Other nonchronic diseases relate...

Objective To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy. Design A review of all published cohort studies to identify key indications and a population based case-control study to test these indications. Setting Review of PubMed, Web of Science, and Embase for papers about carbamazepine exposure in the first trimester of pregnancy and specific malformations, and the EUROCAT Antiepileptic Study Database, including data from 19 European population based congenital anomaly registries, 1995-2005. Participants The literature review covered eight cohort studies of 2680 pregnancies with carbamazepine monotherapy exposure, and the EUROCAT dataset included 98 075 registrations of malformations covering over 3.8 million births. Main outcome measures Overall prevalence for a major congenital malformation after exposure to carbamazepine monotherapy in the first trimester. Odds ratios for malformations with exposure to carbamazepine among cases (five types of malformation identified in the literature review) compared with two groups of controls: other non-chromosomal registrations of malformations and chromosomal syndromes. Results The literature review yielded an overall prevalence for a major congenital malformation of 3.3% (95% confidence interval 2.7 to 4.2) after exposure to carbamazepine monotherapy in the first trimester. In 131 registrations of malformations, the fetus had been exposed to carbamazepine monotherapy. Spina bifida was the only specific major congenital malformation significantly associated with exposure to carbamazepine monotherapy (odds ratio 2.6 (95% confidence interval 1.2 to 5.3) compared with no antiepileptic drug), but the risk was smaller for carbamazepine than for valproic acid (0.2, 0

We find no evidence of a specific increased risk of isolated orofacial clefts relative to other malformations due to lamotrigine (LTG) monotherapy. Our study is not designed to assess whether there is a generalized increased risk of malformations with LTG exposure.