EpilepsyMONEADNCT01730170
Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD)
An observational study of Epilepsy and Pregnancy, run by Stanford University at 20 sites in United States.
Trial summary
Epilepsy is one of the most common neurological disorders affecting women of childbearing age. Poor pregnancy outcomes are increased in these women and their children. The proposed studies will increase our knowledge on multiple levels to improve care and reduce adverse outcomes in these mothers and children. Read more about this study
- Who is it for?
- Ages 14 to 45 years, women onlyHealthy volunteers can take part
- How many people
- 565 participants
- Where
- 20 sitesUnited States
- Study dates
- Jan 2013to 12 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 45 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Study population: Subjects will be recruited by the investigators from their clinic populations and advertisements.
Who may be able to join
- Pregnant women with epilepsy up to 20 weeks gestation, healthy pregnant women without epilepsy up to 20 weeks gestation, or non-pregnant women with epilepsy.
- Ability to maintain a daily medical diary.
- Language skills in English or Spanish adequate to perform the cognitive tests and questionnaires.
- Access to a telephone for phone contacts.
- Age 14-45 inclusive.
- Inclusion Criteria applicable for pregnant women only. -Ability for follow-up through 6 years after giving birth.
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- Criteria applicable for non-pregnant women with epilepsy only:
- Minimum of 9 months post live birth, miscarriage, or elective termination.
- Not currently breastfeeding.
- The Father must be the biological father of the child in the study.
- The Maternal Relative must be a full biological relative or half-sibling of the mother chosen by the following hierarchy:
- st choice: Sister of closest age to the mother in the trial
- nd Sister of next closest age
- rd Brother of closest age
- th Brother of next closest age
- th Mother
- th Father of pregnant mother in the study
- th Half-Sibling if NO Primary FULL relatives are available.
Who cannot join
- Women with an expected IQ<70.
- IV drug use in past year or any of the following since the beginning of pregnancy: Alcohol abuse, cocaine, or methamphetamine) or sequelae of drug/alcohol abuse.
- History of psychogenic non-epileptic spells.
- History of positive Syphilis test.
- History of HIV positive test.
- Progressive cerebral disease (e.g., multiple sclerosis, progressive brain tumor).
Show all 18Show fewer
- Presence of other major medical illness (e.g., diabetes, cancer).
- Any medical, psychiatric, or other condition that, in the judgment of the investigator, is a contraindication to protocol participation or impairs ability to give informed consent.
- Concurrent participation in an experimental drug trial.
- Exposure to known teratogens during pregnancy, excluding AEDs.
- Detection of fetal major congenital malformation prior to enrollment in current pregnancy.
- History of a known genetic disorder in herself or a primary relative (may contact MONEAD team with details for possible exception).
- Use of non-licensed midwife as primary source of natal care and/or planning home delivery or delivery at a stand-alone birth center, independent from a hospital.
- -Planned surgical intervention for epilepsy that would occur during the subject's participation in the project
- Exclusion criteria applicable for pregnant women with epilepsy only. -History of switching AEDs during pregnancy prior to enrollment. "Switching" AEDs includes changing from no AED therapy to therapy, discontinuing a current AED therapy, or changing to a different AED therapy.
- Diagnosed by a health care professional as perimenopausal or postmenopausal.
- History of switching AEDs within 90 days of enrollment. "Switching" AEDs includes changing from no AED therapy to therapy, discontinuing a current AED therapy, or changing to a different AED therapy.
- Any medical, psychiatric, or other condition that, in the judgment of the investigator, is a contraindication to protocol participation or impairs ability to give informed consent.
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
United States20 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
Medical College of Georgia at Georgia Regents University
Augusta, Georgia, 30912-0004
John Hopkins Bayview Medical Center
Baltimore, Maryland, 21224-2735
University of Alabama Birmingham Hospital- UAB
Birmingham, Alabama, 35294-0021
Brigham & Women's Hospital - Harvard
Boston, Massachusetts, 02115-6110
Northwestern Memorial Hospital-Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
University of Cincinnati UC Health University Hospital
Cincinnati, Ohio, 45267-0525
Geisinger Medical Center
Danville, Pennsylvania, 17822-9800
Henry Ford Hospital
Detroit, Michigan, 48202-2608
Keck Hospital of the University of Southern California
Los Angeles, California, 90089
North Shore Jewish Medical Center
Manhasset, New York, 11040-1402
University of Miami Hospital - University of Miami School of Medicine
Miami, Florida, 33136
New York University School of Medicine
New York, New York, 10016-6402
Columbia University Medical Center/NY Presbyterian Hospital
New York, New York, 10032-7133
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Minnesota Epilepsy Group
Roseville, Minnesota, 55113
University of Washington Medical Center
Seattle, Washington, 98104
Stanford University
Stanford, California, 94305
University of Arizona - University Medical Center
Tucson, Arizona, 85724-5023
Wake Forest Baptist Health-Wake Forest University School of Medicine
Winston-Salem, North Carolina, 27157
About this study
Official title: Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs
Epilepsy is one of the most common neurological disorders affecting women of childbearing age. Poor pregnancy outcomes are increased in these women and their children. The proposed studies will increase our knowledge on multiple levels to improve care and reduce adverse outcomes in these mothers and children. An overall goal of this study is to establish the relationship between antiepileptic drug exposure and outcomes in the mother and child as well as describe and explain the variability in antiepileptic drug exposure and response.
Read the detailed description
There is a compelling need for prospective, properly controlled studies in women with epilepsy (WWE) during pregnancy to improve maternal and child outcomes. The proposed investigations are pertinent to the National Institute of Neurological Disorders and Stroke Epilepsy Research Benchmarks and will address multiple gaps in our knowledge noted by the recent American Academy of Neurology guidelines. This multicenter investigation will employ a prospective, observational, parallel-group, cohort design with an established research team.
The specific aims are to:
- Determine if women with epilepsy have increased seizures during pregnancy and delineate the contributing factors;
- Determine if C-section rate is increased in women with epilepsy and delineate contributing factors;
- Determine if women with epilepsy have an increased risk for depression during pregnancy and post-partum period and characterize risks factors;
- Determine the long-term effects of in utero antiepileptic drug exposure on verbal intellectual abilities and other neurobehavioral outcomes in the children of women with epilepsy;
- Determine if small for gestation age and other adverse neonatal outcomes are increased in children of women with epilepsy;
- Determine if breastfeeding when taking antiepileptic drugs impairs the child's verbal intellectual and other cognitive abilities.
An overall goal of the proposed research is to establish the relationship between antiepileptic drug exposure and outcomes in the mother and child as well as describe and explain the variability in antiepileptic drug exposure and response.
Anticonvulsant blood levels (ABLs) and area-under-the-concentration-time-curves (AUCs) will be used as direct measures of drug exposure. The results will enable clinicians to prospectively calculate individual dosing regimens for the mother in order to optimize dosing and limit unnecessary drug exposure to the child. In addition, genetic samples will be collected, which will provide a valuable resource for future pharmacogenetics studies to further delineate individual variability across patients.
FACTORS ASSESSED IN MONEAD.
Maternal factors: IQ, age, education, employment, ethnic group, maternal and family medical history including prior pregnancies and psychiatric disorders, socioeconomic status, site, periconception and pregnancy folate, concomitant medications, alcohol use, tobacco use, or other drug use during pregnancy, unwanted pregnancy, pregnancy complications, medical diseases and serious adverse events, McMaster Family Assessment Device (FAD), Block Food Frequency, and for WWE: types and frequency of seizures or epilepsy, antiepileptic drug dosages \& blood levels, and compliance.
Depression during pregnancy and post-partum as determined by the screening instrument (Beck Depression Inventory-II; BDI-II), the EPDS (Edinburgh Postnatal Depression Scale) and confirmed by the Structured Clinical Interview for DSM-IV (SCID), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Index, and Perceived Stress Scale in mothers, Parental Stress Index, and Neurological Disorders Depression Inventory in Epilepsy (NDDI-E).
Maternal hormones (estradiol, progesterone) and Vit D will be drawn at Visit 1, 2, 3, 4, 5, 6 and 7. Maternal continine Levels will be collected via urine sample at Visit 3 on all non-smoking mothers. If the continine result is positive for tobacco smoke exposure, an LC/MS (liquid chromatography/mass spectrometry test.
Paternal \& relative factors: In fathers and a primary maternal relative, the following were collected: head circumference, IQ estimates, socioeconomic status, dob, race, ethnicity, family history, and medical history. For the father, marital status, total household income, employment status. weight, height, and handedness were also collected.
Adult IQ Assessments:
Peabody Picture Vocabulary Test (PPVT), Wechsler's Adult Intelligence Scale (WAIS).
Child factors: enrollment \& birth gestational ages, birthweight, breastfeeding, AED levels when breastfeeding, physical examinations, childhood medical diseases (including congenital malformations), head circumference, weight, serious adverse events, developmental delays, and special education. Also, obtained premature delivery, APGARs (1 \& 5 minutes), Neonatal Intensive Care Unit admissions and all admissions >12hrs, hypoglycemia (<45), need for resuscitation, and neonatal death. Child Hgb, Hct, PKU, TSH, and T4 at delivery from med records if collected.
Child Cognitive/Behavioral Assessments:
Denver II, Behavior Assessment System for Children - Parent (BASCP-2) and Teacher (BASCT-2), Behavior Rating Inventory of Executive Functioning Preschool (BRIEFP) and version 2 (BRIEF-2), Adaptive Behavior Assessment Scale 3 (ABAS-3), Modified Checklist for Autism in Toddlers (M-CHAT), Modified Edinburgh Handedness Inventory, Gilliam Autism Rating Scale 3 (GARS-3), Bayley Scales of Infant and Toddler Development-3 (BSID-III), Differential Abilities Scale-II (DAS-II), Preschool Language Scale-5 (PLS-5), Peabody Picture Vocabulary Test-4 (PPVT-4), Beery-Buktenica Developmental Test of Visual-Motor Integration-6 (VMI-6), Torrance Test of Creative Thinking- Figural (TTCT-F), NEuroPSYchological Assessment 2nd edition (NEPSY2), Expressive One Word Picture Vocabulary Test-4 (EOWPVT4), Wechsler's Intelligence Scale for Children 5 (WISC5) Coding subtest, Children's Memory Scale (CMS), Lafayette Grooved Pegboard (GPB), Wide Range Achievement Test 5th edition (WRAT5), and Social Responsiveness Scale 2
Verbal intellectual ability at age 6 years is the ultimate primary outcome. It is determined by Verbal Index which is average of Word Definitions and Verbal Similarities subtests from the Differential Ability Scales-2nd ed. (DAS-II),50 -School Age Level, Expressive One-Word Picture Vocabulary Test-4,51 the Phonological Processing, Comprehension of Instructions and Sentence Repetition subscales from the NEPSY-2 57 and the Peabody Picture Vocabulary Test-4th ed. (PPVT-4).52 Children will not reach age 6 in this initial grant period, so primary outcome at age 2 will be the Language Scale from the Bayley Scales of Infant \& Toddler Development-III.
Cerebral Lateralization will be assessed as verbal minus non-verbal difference scores and proportion of dextrals in PWWE vs. HPW and in their children as assessed by the Edinburgh Handedness Inventory.
- Keywords
- Epilepsy, Pregnancy
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Pregnant Women without Epilepsy | Women in their first trimester of pregnancy who are not diagnosed with epilepsy | |
| Nonpregnant Women with Epilepsy | Women diagnosed with epilepsy and not currently pregnant. | |
| Pregnant Women with Epilepsy | Women in their first trimester of pregnancy and diagnosed with epilepsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in seizure frequency over pregnancy vs. post-partum (comparable time periods for non-pregnant women with epilepsy).
Change in seizure frequency during pregnancy vs postpartum as measured by subject completed daily electronic seizure diaries
Measured: Pregnant women with epilepsy:1st Trimester through 9 months post-partum; Nonpregnant women with epilepsy: Study enrollment through 18 months participation
C-section Rate
rate of C-sections in pregnant women without epilepsy vs pregnant women with epilepsy
Measured: Pregnant women with epilepsy & Pregnant women without epilepsy at child's birth
Rate of Depression
Rate of depression during pregnancy in pregnant women with epilepsy vs pregnant women without epilepsy screened by the Beck Depression Inventory and confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual-IV.
Measured: Pregnant women: 1st Trimester through 9 months post partum, again when child is 2 and 3 Years of age. Nonpregnant women with epilepsy: Study enrollment through 6months participation, then 12 months until 18 months participation
Child Intellectual Ability (2YO)
Child intellectual ability as measured by the Language Scale of the Bayley Scales of Infant Development -III at visit 9 (2YO). All of the outcome measures for cognitive outcomes at the various ages are scale scores which are continuous with a mean of 100 and a standard deviation of 15.
Measured: When child is 2 Years of age
Child Intellectual Ability (4.5 YO)
Child intellectual ability as measured by the Torrence Test of Creative Thinking at visit 11 (4.5YO). All of the outcome measures for cognitive outcomes at the various ages are scale scores which are continuous with a mean of 100 and a standard deviation of 15.
Measured: When child is 4.5 Years of age
Child Intellectual Ability (3 and 6 YO)
Child intellectual ability as measured by the Verbal Index Score at visit 10 (3YO) and visit 12 (6YO). All of the outcome measures for cognitive outcomes at the various ages are scale scores which are continuous with a mean of 100 and a standard deviation of 15.
Measured: When child is 3 and 6 Years of age
Small for Gestational Age Rate
Rate of children considered small for gestational age (<10%tile)born to women with epilepsy vs women without epilepsy
Measured: Child's birth
Breastfeeding Effects on verbal intellectual ability in children
Measuring difference in verbal intellectual ability in breastfed children vs non-breastfed children born to women on aeds via the Bayley Scales of Infant Development III Language scale at 2 years of age and Differential Abilities Scale III at 3, 4.5 and 6 Years of age.
Measured: Birth until the child is 2 Years of age, although we anticipate not all children will breastfeed until 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2012 (estimated)
- Study startJan 2013
- Primary completion12 Dec 2022
- Study completion12 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 565 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- The Emmes Company, LLC, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Kimford Jay Meador, Stanford University
- Investigators
- Kimford J Meador, M.D., Principal investigator, Stanford UniversityPage B Pennell, M.D., Principal investigator, University of PittsburghAbigail Matthews, PhD, Principal investigator, The Emmes Company, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01730170
- Sponsor's protocol ID
- IRB00060793
- Other IDs
- 2U01NS038455-11A1
- Acronym
- MONEAD
- Status last verified
- Jul 2023
- First submitted
- 9 Nov 2012
- Last updated
- 13 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Pennell PB, Li D, Kerr WT, Pack AM, French J, Gerard E, Birnbaum AK, McFarlane KN, Meador KJ; MONEAD Study Group. Antiseizure Medication Dosing Strategy During Pregnancy and Early Postpartum in Women With Epilepsy in MONEAD. Neurology. 2026 Jan 27;106(2):e214483. doi: 10.1212/WNL.0000000000214483. Epub 2025 Dec 29.
PubMed 41461064Meador KJ, Cohen MJ, Loring DW, Matthews AG, Brown C, Robalino CP, Carmack A, Birnbaum AK, Voinescu PE, Gerard EE, Kalayjian LA, Gedzelman ER, Hanna J, Cavitt J, Sam M, Hwang S, Pack AM, French JA, Tsai JJ, Taylor C, Pennell PB; Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) Investigator Group. Neuropsychological Outcomes in 6-Year-Old Children of Women With Epilepsy: A Prospective Nonrandomized Clinical Trial. JAMA Neurol. 2025 Jan 1;82(1):30-39. doi: 10.1001/jamaneurol.2024.3982.
PubMed 39585668Meador KJ, Cohen MJ, Loring DW, Matthews AG, Brown CA, Robalino C, Carmack A, Sumners S, Birnbaum AK, Kalayjian LA, Gedzelman E, Voinescu PE, Gerard EE, Hanna J, Cavitt J, Sam M, Hwang ST, Pack AM, Tsai JJ, Pennell PB; Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Investigator Group. Association of Prenatal Exposure to Antiseizure Medications With Creative and Executive Function at Age 4.5 Years. Neurology. 2024 Jun 25;102(12):e209448. doi: 10.1212/WNL.0000000000209448. Epub 2024 May 29.
PubMed 38810172Gerard EE, Meador KJ, Robalino CP, Brown CA, Matthews AG, Voinescu PE, Kalayjian LA, Gedzelman E, Hanna J, Cavitt J, Sam M, French JA, Pack AM, Hwang ST, Tsai JJ, Taylor C, Pennell PB; MONEAD Investigator Study Group. Initiation and Duration of Breastfeeding in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Study. Neurology. 2023 Nov 27;101(22):e2266-e2276. doi: 10.1212/WNL.0000000000207812.
PubMed 37816636Meador KJ, Stowe ZN, Brown C, Robalino CP, Matthews AG, Kalayjian LA, Voinescu PE, Gerard EE, Penovich P, Gedzelman ER, Cavitt J, Pennell PB; MONEAD Investigator Group. Prospective Cohort Study of Depression During Pregnancy and the Postpartum Period in Women With Epilepsy vs Control Groups. Neurology. 2022 Oct 11;99(15):e1573-e1583. doi: 10.1212/WNL.0000000000200958. Epub 2022 Aug 17.
PubMed 35977832Toprani S, Meador KJ, Robalino CP, Brown CA, Matthews AG, Gerard EE, Penovich P, Gedzelman E, Cavitt J, Hwang ST, Kalayjian LA, Sam M, Pack A, Pennell PB; MONEAD. Effect of Epilepsy on Sleep Quality During Pregnancy and Postpartum. Neurology. 2022 Oct 10;99(15):e1584-e1597. doi: 10.1212/WNL.0000000000200959.
PubMed 35853745Meador KJ, Cohen MJ, Loring DW, May RC, Brown C, Robalino CP, Matthews AG, Kalayjian LA, Gerard EE, Gedzelman ER, Penovich PE, Cavitt J, Hwang S, Sam M, Pack AM, French J, Tsai JJ, Pennell PB; Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Investigator Group. Two-Year-Old Cognitive Outcomes in Children of Pregnant Women With Epilepsy in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Study. JAMA Neurol. 2021 Aug 1;78(8):927-936. doi: 10.1001/jamaneurol.2021.1583.
PubMed 34096986Pennell PB, French JA, May RC, Gerard E, Kalayjian L, Penovich P, Gedzelman E, Cavitt J, Hwang S, Pack AM, Sam M, Miller JW, Wilson SH, Brown C, Birnbaum AK, Meador KJ; MONEAD Study Group. Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy. N Engl J Med. 2020 Dec 24;383(26):2547-2556. doi: 10.1056/NEJMoa2008663.
PubMed 33369356
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs
- ClinicalTrials.gov ID
- NCT01730170
- Acronym / sponsor ID
- MONEAD / IRB00060793
- Keywords
- Epilepsy, Pregnancy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 565 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- The Emmes Company, LLC, National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Jan 2013 (actual)
- Primary completion
- 12 Dec 2022 (actual)
- Study completion
- 12 Dec 2022 (actual)
- First posted
- 21 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Epilepsy is one of the most common neurological disorders affecting women of childbearing age. Poor pregnancy outcomes are increased in these women and their children. The proposed studies will increase our knowledge on multiple levels to improve care and reduce adverse outcomes in these mothers and children. An overall goal of this study is to establish the relationship between antiepileptic drug exposure and outcomes in the mother and child as well as describe and explain the variability in antiepileptic drug exposure and response.
Detailed description
There is a compelling need for prospective, properly controlled studies in women with epilepsy (WWE) during pregnancy to improve maternal and child outcomes. The proposed investigations are pertinent to the National Institute of Neurological Disorders and Stroke Epilepsy Research Benchmarks and will address multiple gaps in our knowledge noted by the recent American Academy of Neurology guidelines. This multicenter investigation will employ a prospective, observational, parallel-group, cohort design with an established research team.
The specific aims are to:
- Determine if women with epilepsy have increased seizures during pregnancy and delineate the contributing factors;
- Determine if C-section rate is increased in women with epilepsy and delineate contributing factors;
- Determine if women with epilepsy have an increased risk for depression during pregnancy and post-partum period and characterize risks factors;
- Determine the long-term effects of in utero antiepileptic drug exposure on verbal intellectual abilities and other neurobehavioral outcomes in the children of women with epilepsy;
- Determine if small for gestation age and other adverse neonatal outcomes are increased in children of women with epilepsy;
- Determine if breastfeeding when taking antiepileptic drugs impairs the child's verbal intellectual and other cognitive abilities.
An overall goal of the proposed research is to establish the relationship between antiepileptic drug exposure and outcomes in the mother and child as well as describe and explain the variability in antiepileptic drug exposure and response.
Anticonvulsant blood levels (ABLs) and area-under-the-concentration-time-curves (AUCs) will be used as direct measures of drug exposure. The results will enable clinicians to prospectively calculate individual dosing regimens for the mother in order to optimize dosing and limit unnecessary drug exposure to the child. In addition, genetic samples will be collected, which will provide a valuable resource for future pharmacogenetics studies to further delineate individual variability across patients.
FACTORS ASSESSED IN MONEAD.
Maternal factors: IQ, age, education, employment, ethnic group, maternal and family medical history including prior pregnancies and psychiatric disorders, socioeconomic status, site, periconception and pregnancy folate, concomitant medications, alcohol use, tobacco use, or other drug use during pregnancy, unwanted pregnancy, pregnancy complications, medical diseases and serious adverse events, McMaster Family Assessment Device (FAD), Block Food Frequency, and for WWE: types and frequency of seizures or epilepsy, antiepileptic drug dosages \& blood levels, and compliance.
Depression during pregnancy and post-partum as determined by the screening instrument (Beck Depression Inventory-II; BDI-II), the EPDS (Edinburgh Postnatal Depression Scale) and confirmed by the Structured Clinical Interview for DSM-IV (SCID), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Index, and Perceived Stress Scale in mothers, Parental Stress Index, and Neurological Disorders Depression Inventory in Epilepsy (NDDI-E).
Maternal hormones (estradiol, progesterone) and Vit D will be drawn at Visit 1, 2, 3, 4, 5, 6 and 7. Maternal continine Levels will be collected via urine sample at Visit 3 on all non-smoking mothers. If the continine result is positive for tobacco smoke exposure, an LC/MS (liquid chromatography/mass spectrometry test.
Paternal \& relative factors: In fathers and a primary maternal relative, the following were collected: head circumference, IQ estimates, socioeconomic status, dob, race, ethnicity, family history, and medical history. For the father, marital status, total household income, employment status. weight, height, and handedness were also collected.
Adult IQ Assessments:
Peabody Picture Vocabulary Test (PPVT), Wechsler's Adult Intelligence Scale (WAIS).
Child factors: enrollment \& birth gestational ages, birthweight, breastfeeding, AED levels when breastfeeding, physical examinations, childhood medical diseases (including congenital malformations), head circumference, weight, serious adverse events, developmental delays, and special education. Also, obtained premature delivery, APGARs (1 \& 5 minutes), Neonatal Intensive Care Unit admissions and all admissions >12hrs, hypoglycemia (<45), need for resuscitation, and neonatal death. Child Hgb, Hct, PKU, TSH, and T4 at delivery from med records if collected.
Child Cognitive/Behavioral Assessments:
Denver II, Behavior Assessment System for Children - Parent (BASCP-2) and Teacher (BASCT-2), Behavior Rating Inventory of Executive Functioning Preschool (BRIEFP) and version 2 (BRIEF-2), Adaptive Behavior Assessment Scale 3 (ABAS-3), Modified Checklist for Autism in Toddlers (M-CHAT), Modified Edinburgh Handedness Inventory, Gilliam Autism Rating Scale 3 (GARS-3), Bayley Scales of Infant and Toddler Development-3 (BSID-III), Differential Abilities Scale-II (DAS-II), Preschool Language Scale-5 (PLS-5), Peabody Picture Vocabulary Test-4 (PPVT-4), Beery-Buktenica Developmental Test of Visual-Motor Integration-6 (VMI-6), Torrance Test of Creative Thinking- Figural (TTCT-F), NEuroPSYchological Assessment 2nd edition (NEPSY2), Expressive One Word Picture Vocabulary Test-4 (EOWPVT4), Wechsler's Intelligence Scale for Children 5 (WISC5) Coding subtest, Children's Memory Scale (CMS), Lafayette Grooved Pegboard (GPB), Wide Range Achievement Test 5th edition (WRAT5), and Social Responsiveness Scale 2
Verbal intellectual ability at age 6 years is the ultimate primary outcome. It is determined by Verbal Index which is average of Word Definitions and Verbal Similarities subtests from the Differential Ability Scales-2nd ed. (DAS-II),50 -School Age Level, Expressive One-Word Picture Vocabulary Test-4,51 the Phonological Processing, Comprehension of Instructions and Sentence Repetition subscales from the NEPSY-2 57 and the Peabody Picture Vocabulary Test-4th ed. (PPVT-4).52 Children will not reach age 6 in this initial grant period, so primary outcome at age 2 will be the Language Scale from the Bayley Scales of Infant \& Toddler Development-III.
Cerebral Lateralization will be assessed as verbal minus non-verbal difference scores and proportion of dextrals in PWWE vs. HPW and in their children as assessed by the Edinburgh Handedness Inventory.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pregnant Women without Epilepsy | – | –Women in their first trimester of pregnancy who are not diagnosed with epilepsy |
| Nonpregnant Women with Epilepsy | – | –Women diagnosed with epilepsy and not currently pregnant. |
| Pregnant Women with Epilepsy | – | –Women in their first trimester of pregnancy and diagnosed with epilepsy |
Who may qualify
- Ages
- 14 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Subjects will be recruited by the investigators from their clinic populations and advertisements.
Key inclusion criteria (18 listed)
- Pregnant women with epilepsy up to 20 weeks gestation, healthy pregnant women without epilepsy up to 20 weeks gestation, or non-pregnant women with epilepsy.
- Ability to maintain a daily medical diary.
- Language skills in English or Spanish adequate to perform the cognitive tests and questionnaires.
- Access to a telephone for phone contacts.
- Age 14-45 inclusive.
Key exclusion criteria (18 listed)
- Women with an expected IQ<70.
- IV drug use in past year or any of the following since the beginning of pregnancy: Alcohol abuse, cocaine, or methamphetamine) or sequelae of drug/alcohol abuse.
- History of psychogenic non-epileptic spells.
- History of positive Syphilis test.
- History of HIV positive test.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in seizure frequency over pregnancy vs. post-partum (comparable time periods for non-pregnant women with epilepsy).
Time frame: Pregnant women with epilepsy:1st Trimester through 9 months post-partum; Nonpregnant women with epilepsy: Study enrollment through 18 months participation
Change in seizure frequency during pregnancy vs postpartum as measured by subject completed daily electronic seizure diaries
C-section Rate
Time frame: Pregnant women with epilepsy & Pregnant women without epilepsy at child's birth
rate of C-sections in pregnant women without epilepsy vs pregnant women with epilepsy
Rate of Depression
Time frame: Pregnant women: 1st Trimester through 9 months post partum, again when child is 2 and 3 Years of age. Nonpregnant women with epilepsy: Study enrollment through 6months participation, then 12 months until 18 months participation
Rate of depression during pregnancy in pregnant women with epilepsy vs pregnant women without epilepsy screened by the Beck Depression Inventory and confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual-IV.
Child Intellectual Ability (2YO)
Time frame: When child is 2 Years of age
Child intellectual ability as measured by the Language Scale of the Bayley Scales of Infant Development -III at visit 9 (2YO). All of the outcome measures for cognitive outcomes at the various ages are scale scores which are continuous with a mean of 100 and a standard deviation of 15.
Child Intellectual Ability (4.5 YO)
Time frame: When child is 4.5 Years of age
Child intellectual ability as measured by the Torrence Test of Creative Thinking at visit 11 (4.5YO). All of the outcome measures for cognitive outcomes at the various ages are scale scores which are continuous with a mean of 100 and a standard deviation of 15.
Child Intellectual Ability (3 and 6 YO)
Time frame: When child is 3 and 6 Years of age
Child intellectual ability as measured by the Verbal Index Score at visit 10 (3YO) and visit 12 (6YO). All of the outcome measures for cognitive outcomes at the various ages are scale scores which are continuous with a mean of 100 and a standard deviation of 15.
Small for Gestational Age Rate
Time frame: Child's birth
Rate of children considered small for gestational age (<10%tile)born to women with epilepsy vs women without epilepsy
Breastfeeding Effects on verbal intellectual ability in children
Time frame: Birth until the child is 2 Years of age, although we anticipate not all children will breastfeed until 2 Years
Measuring difference in verbal intellectual ability in breastfed children vs non-breastfed children born to women on aeds via the Bayley Scales of Infant Development III Language scale at 2 years of age and Differential Abilities Scale III at 3, 4.5 and 6 Years of age.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2023.
- Derived from this study: PubMed 41461064Pennell PB, Li D, Kerr WT, Pack AM, French J, Gerard E, Birnbaum AK, McFarlane KN, Meador KJ; MONEAD Study Group. Antiseizure Medication Dosing Strategy During Pregnancy and Early Postpartum in Women With Epilepsy in MONEAD. Neurology. 2026 Jan 27;106(2):e214483. doi: 10.1212/WNL.0000000000214483. Epub 2025 Dec 29.
- Derived from this study: PubMed 39585668Meador KJ, Cohen MJ, Loring DW, Matthews AG, Brown C, Robalino CP, Carmack A, Birnbaum AK, Voinescu PE, Gerard EE, Kalayjian LA, Gedzelman ER, Hanna J, Cavitt J, Sam M, Hwang S, Pack AM, French JA, Tsai JJ, Taylor C, Pennell PB; Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) Investigator Group. Neuropsychological Outcomes in 6-Year-Old Children of Women With Epilepsy: A Prospective Nonrandomized Clinical Trial. JAMA Neurol. 2025 Jan 1;82(1):30-39. doi: 10.1001/jamaneurol.2024.3982.
- Derived from this study: PubMed 38810172Meador KJ, Cohen MJ, Loring DW, Matthews AG, Brown CA, Robalino C, Carmack A, Sumners S, Birnbaum AK, Kalayjian LA, Gedzelman E, Voinescu PE, Gerard EE, Hanna J, Cavitt J, Sam M, Hwang ST, Pack AM, Tsai JJ, Pennell PB; Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Investigator Group. Association of Prenatal Exposure to Antiseizure Medications With Creative and Executive Function at Age 4.5 Years. Neurology. 2024 Jun 25;102(12):e209448. doi: 10.1212/WNL.0000000000209448. Epub 2024 May 29.
- Derived from this study: PubMed 37816636Gerard EE, Meador KJ, Robalino CP, Brown CA, Matthews AG, Voinescu PE, Kalayjian LA, Gedzelman E, Hanna J, Cavitt J, Sam M, French JA, Pack AM, Hwang ST, Tsai JJ, Taylor C, Pennell PB; MONEAD Investigator Study Group. Initiation and Duration of Breastfeeding in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Study. Neurology. 2023 Nov 27;101(22):e2266-e2276. doi: 10.1212/WNL.0000000000207812.
- Derived from this study: PubMed 35977832Meador KJ, Stowe ZN, Brown C, Robalino CP, Matthews AG, Kalayjian LA, Voinescu PE, Gerard EE, Penovich P, Gedzelman ER, Cavitt J, Pennell PB; MONEAD Investigator Group. Prospective Cohort Study of Depression During Pregnancy and the Postpartum Period in Women With Epilepsy vs Control Groups. Neurology. 2022 Oct 11;99(15):e1573-e1583. doi: 10.1212/WNL.0000000000200958. Epub 2022 Aug 17.
- Derived from this study: PubMed 35853745Toprani S, Meador KJ, Robalino CP, Brown CA, Matthews AG, Gerard EE, Penovich P, Gedzelman E, Cavitt J, Hwang ST, Kalayjian LA, Sam M, Pack A, Pennell PB; MONEAD. Effect of Epilepsy on Sleep Quality During Pregnancy and Postpartum. Neurology. 2022 Oct 10;99(15):e1584-e1597. doi: 10.1212/WNL.0000000000200959.
- Derived from this study: PubMed 34096986Meador KJ, Cohen MJ, Loring DW, May RC, Brown C, Robalino CP, Matthews AG, Kalayjian LA, Gerard EE, Gedzelman ER, Penovich PE, Cavitt J, Hwang S, Sam M, Pack AM, French J, Tsai JJ, Pennell PB; Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Investigator Group. Two-Year-Old Cognitive Outcomes in Children of Pregnant Women With Epilepsy in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Study. JAMA Neurol. 2021 Aug 1;78(8):927-936. doi: 10.1001/jamaneurol.2021.1583.
- Derived from this study: PubMed 33369356Pennell PB, French JA, May RC, Gerard E, Kalayjian L, Penovich P, Gedzelman E, Cavitt J, Hwang S, Pack AM, Sam M, Miller JW, Wilson SH, Brown C, Birnbaum AK, Meador KJ; MONEAD Study Group. Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy. N Engl J Med. 2020 Dec 24;383(26):2547-2556. doi: 10.1056/NEJMoa2008663.
- MONEAD Study WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kimford J Meador, M.D. principal investigator
Stanford University
Page B Pennell, M.D. principal investigator
University of Pittsburgh
Abigail Matthews, PhD principal investigator
The Emmes Company, LLC
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Epilepsy and Pregnancy, run by Stanford University at 20 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in seizure frequency over pregnancy vs. post-partum (comparable time periods for non-pregnant women with epilepsy). (time frame: Pregnant women with epilepsy:1st Trimester through 9 months post-partum; Nonpregnant women with epilepsy: Study enrollment through 18 months participation). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01730170, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2023.