TY - JOUR
T1 - Lamotrigine use in pregnancy and risk of orofacial cleft and other congenital anomalies
AU - Dolk, Helen
AU - Wang, Hao
AU - Loane, Maria
AU - Morris, Joan
AU - Garne, Ester
AU - Addor, Marie-Claude
AU - Arriola, Larraitz
AU - Bakker, Marian
AU - Barisic, Ingeborg
AU - Doray, Berenice
AU - Gatt, Miriam
AU - Kallen, Karin
AU - Khoshnood, Babak
AU - Klungsoyr, Kari
AU - Lahesmaa-Korpinen, Anne-Marie
AU - Latos-Bielenska, Anna
AU - Mejnartowicz, Jan
AU - Nelen, Vera
AU - Neville, Amanda
AU - O'Mahony, Mary
AU - Pierini, Anna
AU - Rissmann, Anke
AU - Tucker, David
AU - Wellesley, Diana
AU - Wiesel, Awi
AU - de Jong-van den Berg, Lolkje
PY - 2016/5/3
Y1 - 2016/5/3
N2 - AbstractObjective: To test previous signals of a risk of orofacial cleft (OC) and clubfoot with exposure to the antiepileptic lamotrigine, and to investigate risk of other congenital anomalies (CA). Methods: Population-based case- malformed control study based on 21 EUROCAT CA registries covering 10.1 million births 1995-2011, including births to 2005 in which the clubfoot signal was generated and a subsequent independent study population of 6.3 million births. A total of 226,806 babies with CA included livebirths, stillbirths and terminations of pregnancy following prenatal diagnosis. First trimester lamotrigine monotherapy exposure in OC cases and clubfoot cases was compared to other non-chromosomal CA (controls). Odds Ratios (OR) were adjusted for registry. An exploratory analysis compared the proportion of each standard EUROCAT CA subgroup among all babies with non-chromosomal CA exposed to lamotrigine monotherapy with non-AED exposed pregnancies.Results: There were 147 lamotrigine monotherapy exposed babies with non-chromosomal CA. For all OC, ORadj was 1.31 (95%CI 0.73-2.33); isolated OC 1.45 (95%CI 0.80-2.63); isolated cleft palate 1.69 (95%CI 0.69-4.15). Overall ORadj for clubfoot was 1.83 (95%CI 1.01-3.31), and 1.43 (95%CI 0.66-3.08) in the independent study population. No other specific CA were significantly associated with lamotrigine monotherapy.Conclusions:The risk of OC was not significantly raised and we estimate the excess risk of OC to be less than one in every 550 exposed babies. We have not found strong independent evidence of a risk of clubfoot subsequent to our original signal. Our study cannot assess the general malformation risk among lamotrigine exposed pregnancies.
AB - AbstractObjective: To test previous signals of a risk of orofacial cleft (OC) and clubfoot with exposure to the antiepileptic lamotrigine, and to investigate risk of other congenital anomalies (CA). Methods: Population-based case- malformed control study based on 21 EUROCAT CA registries covering 10.1 million births 1995-2011, including births to 2005 in which the clubfoot signal was generated and a subsequent independent study population of 6.3 million births. A total of 226,806 babies with CA included livebirths, stillbirths and terminations of pregnancy following prenatal diagnosis. First trimester lamotrigine monotherapy exposure in OC cases and clubfoot cases was compared to other non-chromosomal CA (controls). Odds Ratios (OR) were adjusted for registry. An exploratory analysis compared the proportion of each standard EUROCAT CA subgroup among all babies with non-chromosomal CA exposed to lamotrigine monotherapy with non-AED exposed pregnancies.Results: There were 147 lamotrigine monotherapy exposed babies with non-chromosomal CA. For all OC, ORadj was 1.31 (95%CI 0.73-2.33); isolated OC 1.45 (95%CI 0.80-2.63); isolated cleft palate 1.69 (95%CI 0.69-4.15). Overall ORadj for clubfoot was 1.83 (95%CI 1.01-3.31), and 1.43 (95%CI 0.66-3.08) in the independent study population. No other specific CA were significantly associated with lamotrigine monotherapy.Conclusions:The risk of OC was not significantly raised and we estimate the excess risk of OC to be less than one in every 550 exposed babies. We have not found strong independent evidence of a risk of clubfoot subsequent to our original signal. Our study cannot assess the general malformation risk among lamotrigine exposed pregnancies.
KW - Lamotrigine
KW - Drug Safety
KW - Congenital Anomalies
UR - https://pure.ulster.ac.uk/en/publications/lamotrigine-use-in-pregnancy-and-risk-of-orofacial-cleft-and-othe-3
U2 - 10.1212/WNL.0000000000002540
DO - 10.1212/WNL.0000000000002540
M3 - Article
SN - 1526-632X
VL - 86
SP - 1716
EP - 1725
JO - Neurology
JF - Neurology
IS - 18
ER -
