Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy

Kimford J. Meador; Page B. Pennell; Ryan C. May; Linda Van Marter; Thomas F. McElrath; Carrie Brown; Elizabeth Gerard; Laura Kalayjian; Evan Gedzelman; Patricia Penovich; Jennifer Cavitt; Jacqueline French; Sean Hwang; Alison M. Pack; Maria Sam; Angela K. Birnbaum; Richard Finnell

doi:10.1212/WNL.0000000000008687

Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy

Kimford J. Meador, Page B. Pennell, Ryan C. May, Linda Van Marter, Thomas F. McElrath, Carrie Brown, Elizabeth Gerard, Laura Kalayjian, Evan Gedzelman, Patricia Penovich, Jennifer Cavitt, Jacqueline French, Sean Hwang, Alison M. Pack, Maria Sam, Angela K. Birnbaum, Richard Finnell

Experimental and Clinical Pharmacology

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

ObjectiveTo examine occurrence of severe adverse fetal outcomes (SAO), including fetal loss and major congenital malformations (MCMs), in pregnant women with epilepsy (PWWE) vs healthy pregnant women (HPW).MethodsThe Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes for both mother and child, which enrolled women December 2012 through January 2016.ResultsThe 351 PWWE had 365 conceptions, and 105 HPW had 109 conceptions. SAOs occurred more often in PWWE (7.9%) vs HPW (1.9%) (p = 0.025) with odds ratio (OR) 4.45 (95% confidence intervals [CI] 1.04-19.01). There were no significant differences for fetal loss (2.8% vs 0%, p = 0.126) or MCMs (5.2% vs 1.9%, p = 0.185; OR 2.86, 95% CI 0.65-12.53) individually. No fetal losses in PWWE appeared to be related to acute seizures. Outcomes were not affected by periconceptional folate, unplanned/unwanted pregnancies, prior maternal pregnancy history, or antiepileptic drug (AED) blood levels, except for an AED level effect for fetal loss that appeared to be due to polytherapy. Combined maternal or paternal family history of MCM was marginally associated with increased SAOs (p = 0.046).ConclusionsThe findings provide additional information on risks of SAOs in PWWE, assessing effects of both AED levels and periconceptional folate. Group differences in average enrollment gestational age could have affected fetal loss results. Analyses are limited by small sample sizes as the MONEAD study was not powered for these secondary outcomes. The large majority of pregnancies in women with epilepsy do not have SOAs.

Original language	English (US)
Pages (from-to)	E1502-E1511
Journal	Neurology
Volume	94
Issue number	14
DOIs	https://doi.org/10.1212/WNL.0000000000008687
State	Published - Apr 7 2020

Bibliographical note

Funding Information:
This work was supported by NIH NINDS, NICHD U01-NS038455 (K.J.M., P.B.P.), U01-NS050659 (R.C.M.), and 2U01-NS038455 (K.J.M., P.B.P., R.C.M.). The funding source had no role in the analyses, writing the manuscript, or the decision to submit for publication.

Funding Information:
K. Meador has received research support from the NIH and Sunovion Pharmaceuticals and travel support from UCB Pharma. The Epilepsy Study Consortium pays Dr. Meador’s university for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB Pharma, and Vivus Pharmaceuticals. In addition, Dr. Meador is Coinvestigator and Director of Cognitive Core of the Human Epilepsy Project for the Epilepsy Study Consortium. P. Pennell has received research support from the NIH and the Epilepsy Foundation

Publisher Copyright:
© American Academy of Neurology.

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Meador, K. J., Pennell, P. B., May, R. C., Van Marter, L., McElrath, T. F., Brown, C., Gerard, E., Kalayjian, L., Gedzelman, E., Penovich, P., Cavitt, J., French, J., Hwang, S., Pack, A. M., Sam, M., Birnbaum, A. K., & Finnell, R. (2020). Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy. Neurology, 94(14), E1502-E1511. https://doi.org/10.1212/WNL.0000000000008687

Meador, KJ, Pennell, PB, May, RC, Van Marter, L, McElrath, TF, Brown, C, Gerard, E, Kalayjian, L, Gedzelman, E, Penovich, P, Cavitt, J, French, J, Hwang, S, Pack, AM, Sam, M, Birnbaum, AK & Finnell, R 2020, 'Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy', Neurology, vol. 94, no. 14, pp. E1502-E1511. https://doi.org/10.1212/WNL.0000000000008687

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title = "Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy",

abstract = "ObjectiveTo examine occurrence of severe adverse fetal outcomes (SAO), including fetal loss and major congenital malformations (MCMs), in pregnant women with epilepsy (PWWE) vs healthy pregnant women (HPW).MethodsThe Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes for both mother and child, which enrolled women December 2012 through January 2016.ResultsThe 351 PWWE had 365 conceptions, and 105 HPW had 109 conceptions. SAOs occurred more often in PWWE (7.9%) vs HPW (1.9%) (p = 0.025) with odds ratio (OR) 4.45 (95% confidence intervals [CI] 1.04-19.01). There were no significant differences for fetal loss (2.8% vs 0%, p = 0.126) or MCMs (5.2% vs 1.9%, p = 0.185; OR 2.86, 95% CI 0.65-12.53) individually. No fetal losses in PWWE appeared to be related to acute seizures. Outcomes were not affected by periconceptional folate, unplanned/unwanted pregnancies, prior maternal pregnancy history, or antiepileptic drug (AED) blood levels, except for an AED level effect for fetal loss that appeared to be due to polytherapy. Combined maternal or paternal family history of MCM was marginally associated with increased SAOs (p = 0.046).ConclusionsThe findings provide additional information on risks of SAOs in PWWE, assessing effects of both AED levels and periconceptional folate. Group differences in average enrollment gestational age could have affected fetal loss results. Analyses are limited by small sample sizes as the MONEAD study was not powered for these secondary outcomes. The large majority of pregnancies in women with epilepsy do not have SOAs.",

author = "Meador, {Kimford J.} and Pennell, {Page B.} and May, {Ryan C.} and {Van Marter}, Linda and McElrath, {Thomas F.} and Carrie Brown and Elizabeth Gerard and Laura Kalayjian and Evan Gedzelman and Patricia Penovich and Jennifer Cavitt and Jacqueline French and Sean Hwang and Pack, {Alison M.} and Maria Sam and Birnbaum, {Angela K.} and Richard Finnell",

note = "Funding Information: This work was supported by NIH NINDS, NICHD U01-NS038455 (K.J.M., P.B.P.), U01-NS050659 (R.C.M.), and 2U01-NS038455 (K.J.M., P.B.P., R.C.M.). The funding source had no role in the analyses, writing the manuscript, or the decision to submit for publication. Funding Information: K. Meador has received research support from the NIH and Sunovion Pharmaceuticals and travel support from UCB Pharma. The Epilepsy Study Consortium pays Dr. Meador{\textquoteright}s university for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB Pharma, and Vivus Pharmaceuticals. In addition, Dr. Meador is Coinvestigator and Director of Cognitive Core of the Human Epilepsy Project for the Epilepsy Study Consortium. P. Pennell has received research support from the NIH and the Epilepsy Foundation Publisher Copyright: {\textcopyright} American Academy of Neurology.",

year = "2020",

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doi = "10.1212/WNL.0000000000008687",

language = "English (US)",

volume = "94",

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TY - JOUR

T1 - Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy

AU - Meador, Kimford J.

AU - Pennell, Page B.

AU - May, Ryan C.

AU - Van Marter, Linda

AU - McElrath, Thomas F.

AU - Brown, Carrie

AU - Gerard, Elizabeth

AU - Kalayjian, Laura

AU - Gedzelman, Evan

AU - Penovich, Patricia

AU - Cavitt, Jennifer

AU - French, Jacqueline

AU - Hwang, Sean

AU - Pack, Alison M.

AU - Sam, Maria

AU - Birnbaum, Angela K.

AU - Finnell, Richard

N1 - Funding Information: This work was supported by NIH NINDS, NICHD U01-NS038455 (K.J.M., P.B.P.), U01-NS050659 (R.C.M.), and 2U01-NS038455 (K.J.M., P.B.P., R.C.M.). The funding source had no role in the analyses, writing the manuscript, or the decision to submit for publication. Funding Information: K. Meador has received research support from the NIH and Sunovion Pharmaceuticals and travel support from UCB Pharma. The Epilepsy Study Consortium pays Dr. Meador’s university for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, UCB Pharma, and Vivus Pharmaceuticals. In addition, Dr. Meador is Coinvestigator and Director of Cognitive Core of the Human Epilepsy Project for the Epilepsy Study Consortium. P. Pennell has received research support from the NIH and the Epilepsy Foundation Publisher Copyright: © American Academy of Neurology.

PY - 2020/4/7

Y1 - 2020/4/7

N2 - ObjectiveTo examine occurrence of severe adverse fetal outcomes (SAO), including fetal loss and major congenital malformations (MCMs), in pregnant women with epilepsy (PWWE) vs healthy pregnant women (HPW).MethodsThe Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes for both mother and child, which enrolled women December 2012 through January 2016.ResultsThe 351 PWWE had 365 conceptions, and 105 HPW had 109 conceptions. SAOs occurred more often in PWWE (7.9%) vs HPW (1.9%) (p = 0.025) with odds ratio (OR) 4.45 (95% confidence intervals [CI] 1.04-19.01). There were no significant differences for fetal loss (2.8% vs 0%, p = 0.126) or MCMs (5.2% vs 1.9%, p = 0.185; OR 2.86, 95% CI 0.65-12.53) individually. No fetal losses in PWWE appeared to be related to acute seizures. Outcomes were not affected by periconceptional folate, unplanned/unwanted pregnancies, prior maternal pregnancy history, or antiepileptic drug (AED) blood levels, except for an AED level effect for fetal loss that appeared to be due to polytherapy. Combined maternal or paternal family history of MCM was marginally associated with increased SAOs (p = 0.046).ConclusionsThe findings provide additional information on risks of SAOs in PWWE, assessing effects of both AED levels and periconceptional folate. Group differences in average enrollment gestational age could have affected fetal loss results. Analyses are limited by small sample sizes as the MONEAD study was not powered for these secondary outcomes. The large majority of pregnancies in women with epilepsy do not have SOAs.

AB - ObjectiveTo examine occurrence of severe adverse fetal outcomes (SAO), including fetal loss and major congenital malformations (MCMs), in pregnant women with epilepsy (PWWE) vs healthy pregnant women (HPW).MethodsThe Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes for both mother and child, which enrolled women December 2012 through January 2016.ResultsThe 351 PWWE had 365 conceptions, and 105 HPW had 109 conceptions. SAOs occurred more often in PWWE (7.9%) vs HPW (1.9%) (p = 0.025) with odds ratio (OR) 4.45 (95% confidence intervals [CI] 1.04-19.01). There were no significant differences for fetal loss (2.8% vs 0%, p = 0.126) or MCMs (5.2% vs 1.9%, p = 0.185; OR 2.86, 95% CI 0.65-12.53) individually. No fetal losses in PWWE appeared to be related to acute seizures. Outcomes were not affected by periconceptional folate, unplanned/unwanted pregnancies, prior maternal pregnancy history, or antiepileptic drug (AED) blood levels, except for an AED level effect for fetal loss that appeared to be due to polytherapy. Combined maternal or paternal family history of MCM was marginally associated with increased SAOs (p = 0.046).ConclusionsThe findings provide additional information on risks of SAOs in PWWE, assessing effects of both AED levels and periconceptional folate. Group differences in average enrollment gestational age could have affected fetal loss results. Analyses are limited by small sample sizes as the MONEAD study was not powered for these secondary outcomes. The large majority of pregnancies in women with epilepsy do not have SOAs.

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Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy

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