Abstract
A case control study on the association between maternal epilepsy, anticonvulsants use during pregnancy and birth defects was carried out in the Italian Multicentric Registry of Birth Defects (IPIMC).
In the period 1980–1983, 7,607 malformed babies out of 439,717 total births (still+live) were registered. Fourtyone malformed babies with maternal epilepsy were identified (5.39×1,000). The overall relative risk of having a malformed baby among pregnant epileptic women was 1.87.
Spina Bifida, Congenital Heart Defects, Clefts, Diaphragmatic Hernia and Trisomy 18 were more frequent than expected among babies with maternal epilepsy.
The different therapeutic regimens were also tested to identify the possible independent teratogenic effect of anticonvulsants. A statistically significant association between Spina Bifida and Valproic Acid (odds ratio 22.7; Fisher p value = 0.0364) was observed: no other anticonvulsant tested showed any association with any type of malformation.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Anonymous (1981) : A communication from the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS). - Int. J. Epid. 10: 245–246.
Anonymous (1982): Valproate and Malformations.- Lancet, 2: 1313–1314.
BjerkedalT. and BahnaL. (1973): The course and outcome of pregnancy in women with epilepsy. -Acta Obstet. Gynecol. Scand., 52: 245–248.
BjerkedalT., CzeizelA., GoujardJ. et al. (1982): Valproic Acid and Spina Bifida. - Lancet, 2: 1096.
BossiL. (1983): Fetal effects of anticonvulsants. In: Antiepileptic drug therapy in Pediatric. MorselliP.L., PiffengerC.E. and PerryJ.K. Editors Raven Press. New York, pp. 37–64.
BrownN.A., KaoI. and FabroS. (1980): Teratogenic potential of Valproic Acid. - Lancet, 1: 660–661.
CornfieldJ. (1956): A statistical problem arising from retrospective studies. Proceedings of the 3rd Berkeley Symposium. - Berkeley: University of California Press, 4: 135–148.
ElshoveJ. and VanEckJ.H.M. (1971): Aageboren misvormingen, metname gesplaten lip met of zonder geslepten verhemeltes, by kindaren van moeders met epilepsie. - Med. Tijdschr. Geneeskd., 115: 1371–1375.
FisherR.A. (1956): Statistical methods and scientific inference. - Oliver and Boyd Press. London.
GomezM.R. (1981): Possible teratogenicity of Valproic Acid. - J. Pediatr., 98: 508–509.
GoujardJ., HuelG. and Rumean-RoquetteC. (1974): Antiepileptiques et malformations congenitales. -J. Gynaecol. Obstet. Biol. Reprod., 3: 831–842.
HiilesmaaV.K., TeramoK. and GranstromM.L. (1981): Fetal head growth retardation associated with maternal entiepileptic drugs. - Lancet, 2: 165–167.
International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS) (1984): Annaul Report 1982. Garnisonstryckeriet. Stockholm. Available from Sylvia Hay 4141 Twentieth Street-CA 94114 San Francisco.
Italian League against Epilepsy (1984): Personal communication.
JanzD. and FuchsU. (1964): Sind antiepileptische medikamente wahrend der schwangerschaft schadlich?- Dtsch. Med. Wochenschr., 89: 241–243.
JanzD. (1982): On major malformations and minor anomalies in the offspring of parents with epilepsy: review of literature. In: Epilepsy, pregnancy and the child. Janz D., Bossi L. and Schmidt D. Editors Raven Press, New York, pp. 211–222.
KoppeJ.G., BosmanW., OffersV.M. et al. (1973): Epilepsie en aangeboren afwijkingen. - Med. Tijdschr. Geeneskd., 117: 229–224.
KuenssbergE.V. and KnoxJ.D.E. (1973): Teratogenic effect of anticonvulsivants. - Lancet, 1: 198.
LoweC.R. (1983): Congenital malformations among infants born to epileptic women. - Lancet, 1: 9–10.
MacRaeK.D. (1982): Sodium Valproate and Neural Tube Defects. - Lancet, 2: 1282.
MastroiacovoP. (1984): The Italian Birth Defects Monitoring System: baseline rates based on 283,453 births and comparison with other Registries. In: Progress in Clinical and Biological Research, Volume 163B ≪Prevention of physical and mental congenital defects. Part. B: Epidemiology, early detection and therapy, and enviromental factors ≫. Maurice Marois, Editor. Bennet H.S., Brent R.L., Klingberg M.A., Lauder J. and Saxen L. Associate Editors. Alan R. Liss, Inc., New York.
MastroiacovoP., MusacchioP. and BertolliniR. (1982): L'Indagine Policentrica Italiana sulle Malformazioni Congenite (IPIMC). Un progetto collaborativo pilota finalizzato alla sprveglianza delle malformazioni congenite. - Prosp. in Pediatr., 45: 23–38.
MeadowS.R. (1968): Anticonvulsant drugs and congenital malformations. - Lancet, 2: 1296.
MillerH.G.C. and NevinN.C. (1973): Congenital malformations and anticonvulsiant drugs. - Lancet, 1: 328.
NiswanderJ.D. and WerteleckiW. (1973): Congenital malformations among offspring of epileptic women. - Lancet; 1: 1062.
PaulsonG.W. and PaulsonR.B. (1981): Teratogenic effects of anticonvulsants. - Arch. NeurOl., 38: 140–143.
RallT.W. and SchleiferL.S. (1980): Drugs effective in the therapy of the epilepsies. In: The pharmachological basis of therapeutics. Goodman Gilman A., Goodman L.S. and Gilman A., Editors. Mac Millan Publishing Co., Inc., New York, p. 464.
RobertE. and GuibaudP. (1982): Maternal Valproic Acid and congenital Neural Tube Defects. -Lancet, 2: 937.
RobertE. and RosaF. (1983): Valproate and Birth Defects. - Lancet, 2: 1142.
RobertE., LofkvistE. and MouguireF. (1984): Valproate and Spina Bifida. - Lancet, 2: 1392.
ShapiroS., SloneD., HartzS.C. et al. (1976): Anticonvulsants and parental epilepsy in the development of birth defects. - Lancet, 1: 272–275.
SouthJ. (1972): Teratogenic effect of anticonvulsants.- Lancet, 2: 1154.
StanelyO.H. and ChambersT.L. (1982): Sodium Valproate and Neural Tube Defects. - Lancet, 2: 1282.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bertollini, R., Mastroiacovo, P. & Segni, G. Maternal epilepsy and birth defects: A case-control study in the Italian Multicentric Registry of Birth Defects (IPIMC). Eur J Epidemiol 1, 67–72 (1985). https://doi.org/10.1007/BF00162315
Issue Date:
DOI: https://doi.org/10.1007/BF00162315