Table 1 Overview of the main characteristics of included studies
First author, year (+ overlap) | Setting / source of data | Nb of participants | Maternal age at pregnancy in years, mean (SD) | Maternal epilepsy type | Convulsive seizures during pregnancy | Outcome | Adjusted covariates |
|---|---|---|---|---|---|---|---|
Baker, 2015 [31] (overlap: Bromley, 2010 [32]) | 11 National Health Service hospitals within Merseyside and Greater Manchester (LMNDG group), UK | Exposed = 36 | 27.7 (6) | Idiopathic generalized epilepsy 23.3% Focal epilepsy 56.7% Unclassified 20.0% | 40.0% | - Language (based on continuous data) - Cognitive developmental delay (based on continuous data) | |
Unexposed WWE = 34 | 25.9 (5) | Idiopathic generalized epilepsy 32.0% Focal epilepsy 40.0% Unclassified 28.0% | 4.0% | None | |||
Unexposed disease free = 287 | 29.4 (5) | ||||||
Bjørk, 2018 [11] (overlap: Veiby, 2013 [38]) | Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway | Exposed = 104 | NA | NA | NA | - ASD | |
Unexposed WWE = 389 | NA | NA | NA | None | |||
Unexposed disease free = 104,222 | NA | ||||||
Bjørk, 2022 [3] | SCAN-ASD: Nordic register-based study of antiepileptic drugs in pregnancy | Exposed = 5073 | 30.1 (5.2)a | NA | NA | - Neuro-developmental disorders - ASD - Cognitive developmental delay | |
Unexposed WWE = 21,634 | 29.6 (5.4) | NA | NA | Maternal age, education and marital status, parity, child’s birth year, sex, and country of birth. All the models were run with separate strata for country and year. Maternal use of antidepressants or opioids, depression, anxiety, personality disorders, number of chronic somatic diseases, and number of hospitalizations the year before last menstrual period were sometimes added to the models. | |||
Unexposed NOS = 4,463,879 | 30.2 (5.2) | NA | NA | None | |||
Bromley, 2013 [39] (overlap: Baker, 2015 [31], Charlton 2017 [12], Bromley, 2010 [32], and Bromley, 2008 [40]) | 11 National Health Service hospitals within Merseyside and Greater Manchester (LMNDG group), UK | Exposed = 36 | 28 (NA) | Idiopathic generalized epilepsy 23.3% Focal 56.7% Unclassified 20.0% | 40.0% | - Neuro-developmental disorders - ASD - ADHD - Psychomotor | |
Unexposed WWE = 34 | 26 (NA) | Idiopathic generalized epilepsy 32.0% Focal 40.0% Unclassified 28.0% | 4.0% | None | |||
Unexposed disease free = 285 | 29 (NA) | Seizures during pregnancy, maternal IQ, maternal age, socio-economic status, alcohol or nicotine exposure, gender and gestational age at birth. However, the variables kept in the final regression model are not specified (data not shown). | |||||
Bromley, 2010 [32] | 11 National Health Service hospitals within Merseyside and Greater Manchester (LMNDG group), UK | Exposed = 34 | NA | NA | NA | - Cognitive developmental delay | |
Unexposed WWE = 27 | NA | NA | NA | None | |||
Unexposed disease free = 230 | NA | Matched for age, within a 5-year band, and for parity | |||||
Charlton, 2017 [12] | The United Kingdom Clinical Practice Research Datalink (CPRD) | Exposed = 122 | NA | NA | NA | - Neuro-developmental disorders | |
Unexposed WWE = 472 | NA | NA | NA | ||||
Unexposed disease free = 6048 | 28.9 | Matching on maternal age at pregnancy start, year of delivery, sex of the child, general practitioner practice/socioeconomic status of general practitioner practice, and adjustment for alcohol drinking status. | |||||
Cohen-Israel, 2018 [13] | The Beilinson Teratology Information Service, Israel | Exposed = 83 | NA | NA | NA | - Language - ASD - Psychomotor - Learning disorders - Cognitive developmental delay | |
Unexposed disease free = 83 | NA | Matched for gestational age and date of birth | |||||
Dean, 2007 [34] | Aberdeen Maternity Hospital, Scotland | Exposed = 4 | NA | NA | NA | - Neuro-developmental disorders | |
Unexposed WWE = 46 | NA | NA | NA | None | |||
Cummings, 2011 [33] | The UK epilepsy and pregnancy register | Exposed = 35 | Range: 16–39 | NA | NA | - Cognitive developmental delay | |
Unexposed disease free = 44 | Range: 20–49 | Confounding variables which persisted as significant adverse factors, were age, gender and socioeconomic status. | |||||
Elkjaer, 2018 [35] | Danish national registries (the Danish Medical Birth Registry…) | Exposed = 243 | NA | Focal 23.5% Generalized 22.2% Other 54.3% | NA | - Learning disorders (based on continuous data) | |
Unexposed WWE = 1909 | NA | NA | NA | Test year, child sex, and maternal education and household income at birth. | |||
Gopinath, 2015 [36] | The Kerala Registry of Epilepsy and Pregnancy (KREP), India | Exposed = 1 | NA | NA | NA | - Cognitive developmental delay | |
Unexposed WWE = 16 | NA | NA | NA | None | |||
Husebye, 2020 [14] | Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway | Exposed = 112 | 29.0 (24.0)a | NA | 12% | - Language | |
Unexposed WWE = 388 | 29.0 (25.0) | NA | 3% | None | |||
Unexposed disease free = 113,674 | 30.0 (39.0) | Maternal age, parental socioeconomic status, low household income, parity, maternal prepregnancy, BMI, maternal report of familial language delay (5y model), smoking and alcohol (8y model), maternal anxiety/depression, Apgar score at 5 min, gestational age, report of seldom/never helping child read letters and sounds during a typical week (5y model) or report of never reading to their child (8y model) | |||||
Kasradze, 2017 [15] | The Georgian branch of the International Registry of Antiepileptic Drugs and Pregnancy (EURAP) | Exposed = 3 | 30.5 (4.9)a | Focal 86% Generalized 14% | NA | - Language (based on continuous data) - Cognitive developmental delay (based on continuous data) | |
Unexposed disease free = 50 | 31.7 (5.2) | Age and gender-matched. | |||||
Meador, 2021 [16] | The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study, US | Exposed = 97 | 30.9 (5.2)a | Generalized 33.8% Focal 59.0% Unclassified/multiple 7.1% | mean (95% CI) 0.7 (0.4, 1.0) | - Language (based on continuous data) | |
Unexposed disease free = 106 | 29.8 (5.2) | Mother’s IQ, education level, post-birth average Beck Anxiety Inventory (BAI) score, child’s sex, ethnicity, and birthweight. | |||||
Rihtman, 2013 [37] | The Israeli Teratogen Information Service | Exposed = 42 | 33.56 (4.58) | Grand mal 53% Focal/temporal lobe 5.5% Petit mal 14% Other 22% Not reported 5.5% | NA | - Neuro-developmental disorders - ADHD (based on continuous data) - Psychomotor (based on continuous data) - Language (based on continuous data) - Cognitive developmental delay (based on continuous data) | |
Unexposed NOS = 52 | 33.00 (4.69) | NA | NA | None | |||
Veiby, 2013 [38] | Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway | Exposed = 104 | NA | NA | NA | - ADHD | |
Unexposed WWE = 393 | NA | NA | NA | None | |||
Unexposed disease free = 107,597 | NA | None | |||||
Videman, 2016 [17] | The Helsinki University Hospital, Finland | Exposed = 8 | NA | NA | NA | - Language (based on continuous data) - Psychomotor (based on continuous data) - Cognitive developmental delay (based on continuous data) | |
Unexposed disease free = 67 | NA | None | |||||
Wiggs, 2020 [18] | Swedish Medical Birth Register | Exposed = NA | NA | NA | NA | - ASD - ADHD | |
Unexposed WWE = 11,298 | NA | NA | NA | Maternal and paternal characteristics included age, highest education, cohabitation status, country of origin, neighborhood deprivation and averaged maternal and paternal disposable income, parental psychiatric and behavioral problems, inpatient diagnosis of seizures in the year before pregnancy, birth order, child sex, and maternal smoking during pregnancy and concurrent medication use. | |||
When result is expressed in a continuous manner in the publication so there is not a countable number of cases, thus indicated as NA in the table | |||||||
ASD Autism spectrum disorder, ADHD Attention deficit / hyperactivity disorder, NA Not available, IQ Intelligence quotient, BMI Body mass index, WWE Women With Epilepsy | |||||||
aWhen the mean maternal age is only available for all exposures assessed (not only lamotrigine-exposed women) | |||||||