The Risk of Specific Congenital Anomalies in Relation to Newer Antiepileptic Drugs:A Literature Review

BACKGROUND: More information is needed about possible associations between the newer anti-epileptic drugs (AEDs) in the first trimester of pregnancy and specific congenital anomalies of the fetus. OBJECTIVES: We performed a literature review to find signals for potential associations between newer AEDs (lamotrigine, topiramate, levetiracetam, gabapentin, oxcarbazepine, eslicarbazepine, felbamate, lacosamide, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, vigabatrin, and zonisamide) and specific congenital anomalies. METHODS: We searched PubMed and EMBASE to find observational studies with pregnancies exposed to newer AEDs and detailed information on congenital anomalies. The congenital anomalies in the studies were classified according to the congenital anomaly subgroups of European Surveillance of Congenital Anomalies (EUROCAT). We compared the prevalence of specific congenital anomalies in fetuses exposed to individual AEDs in the combined studies with that of the general population in a reference database. A significantly higher prevalence based on three or more fetuses with anomalies was considered a signal. RESULTS: Topiramate showed a higher rate of congenital anomalies than the other newer AEDs. Four signals were found. The signals for associations between topiramate and cleft lip with/without cleft palate and hypospadias were considered strong. Associations between lamotrigine and anencephaly and transposition of great vessels were found within one study and were not supported by other studies. No signals were found for the other newer AEDs, or the information was too limited to provide such a signal. CONCLUSION: In terms of associations between monotherapy with a newer AED in the first trimester of pregnancy and a specific congenital anomaly, the signals for topiramate and cleft lip with/without cleft palate and hypospadias should be investigated further

Antibiotic drug use of children in the Netherlands from 1999 till 2005

Objective Antibiotics are the most commonly prescribed drugs used by children. Excessive and irrational use of antibiotic drugs is a world-wide concern. We performed a drug utilization study describing the patterns of antibiotic use in children aged 0-19 years between 1999 and 2005 in the Netherlands. Methods We used IADB.nl, a database with pharmacy drug dispensing data covering a population of 500,000 people and investigated all prescriptions of oral antibiotic drugs (ATC J01) for children Results The total number of antibiotic prescriptions per 1000 children per year ranged from 282 in 2004 to 307 in 2001 and did not change between years during the study period in a clinically relevant way. The prevalence of receiving at least one prescription varied between 17.8% in 2004 and 19.3% in 2001. Amoxicillin was the most frequently prescribed drug (46.4% of all antibiotic prescriptions in 1999 and 43.2% in 2005). Between 1999 and 2005 there was a shift from the small-spectrum phenethicillin, a penicillin preparation [ratio 2005/1999 0.76; 95% confidence interval (CI) 0.72-0.81], to amoxicillin/clavulanic acid (ratio 2005/1999 1.70; 95% CI 1.61-1.79) and from the old macrolide erythromycin (ratio 2005/1999 0.35; 95% CI 0.32-0.39) to the new macrolide antibiotic azithromycin (ratio 2005/1999 1.78; 95% CI 1.65-1.92). Conclusion The use of antibiotic drugs in treating children in the Netherlands is comparable to that in other northern European countries. Broad-spectrum antibiotics were prescribed more frequently than recommended by the guidelines and increased during our study period. Initiatives to improve guideline-directed antibiotic prescribing are strongly recommended