Correlation of drug dose estimated from national prescription registers with mean blood level of antiseizure medication in pregnancy

• Published in: Pharmacoepidemiology and drug safety Vol. 33; no. 6; pp. e5811 - n/a
• Main Authors: Christensen, Jakob, Trabjerg, Betina, Dreier, Julie Werenberg
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Inc 01.06.2024; Wiley Subscription Services, Inc
• Subjects: Adult; Anticonvulsants - administration & dosage; Anticonvulsants - blood; antiepileptic drugs; antiseizure medication; Blood levels; Carbamazepine; Carbamazepine - administration & dosage; Denmark; Drug dosages; Drug Prescriptions - statistics & numerical data; Epilepsy - drug therapy; Etiracetam; Female; fetal risk; Humans; Lamotrigine; Lamotrigine - administration & dosage; Levetiracetam - administration & dosage; Pregnancy; Pregnancy Complications - blood; Pregnancy Complications - drug therapy; prescription registers; Registries; Topiramate; Topiramate - administration & dosage; Valproic acid; Valproic Acid - administration & dosage; Valproic Acid - blood; Young Adult; Denmark; antiepileptic drugs; antiseizure medication; fetal risk; prescription registers; pregnancy
• ISSN: 1053-8569; 1099-1557; 1099-1557
• DOI: 10.1002/pds.5811

Purpose The purpose was to examine the correlation of antiseizure medication drug dose estimated from prescription fill records from prescription registers with blood levels during pregnancy. Methods We conducted a Nation‐wide study of mothers who gave birth in Denmark between 1 January 2014 and 31 December 2018 using data from Danish Prescription and Laboratory Registers. We identified mothers with blood level measurements of antiseizure medication. The main exposure was estimated antiseizure medication dosage estimated from pregnancy‐filled prescriptions in the Danish Prescription Register. The main outcome was the correlation of estimated dose with mean blood level of antiseizure medication in pregnancy. For privacy reasons, the number of blood level measurement and prescription fills were rounded to nearest 10, but proportions reported as exact values. Results Among 298 560 pregnancies, we identified pregnancies with recorded prescription fill from the prescription register for valproate (N = 90), lamotrigine (N = 1360), levetiracetam (N = 340), topiramate (N = 100), and carbamazepine (N = 60). In these pregnancies, blood level measurements were available in 50 (53%) pregnancies for valproate, 850 (62%) pregnancies for lamotrigine, 320 (93%) pregnancies for levetiracetam, 50 (68%) pregnancies for carbamazepine, and 40 (35%) pregnancies for topiramate. Pearsons's correlation coefficients for the correlation of estimated antiseizure medication dose with mean blood levels were 0.67 (p < 0.0001) for valproate, 0.63 (p < 0.0001) for lamotrigine, 0.63 (p < 0.0001) for levetiracetam, 0.76 (<0.0001) for carbamazepine and 0.89 (<0.0001) for topiramate. Conclusions Dose of antiseizure medication estimated from prescription fills was a good proxy for blood levels and thus for biological exposure in pregnancy, suggesting that administrative prescription fill records may be a valuable resource for estimating exposure to antiseizure medication in pregnancy.