The safety of newer medications to treat illnesses in pregnancy including the neurological condition, epilepsy, is uncertain. Women need to know more about medication safety when balancing benefits of treatment with risks to their unborn child. Studying medication safety in pregnancy is complicated by the need for large groups of women and their children, needing to capture rare events including functional anomalies in babies, that occur during pregnancy and the need to follow up children as they develop over time.
These are challenges that can be addressed by using data collected through routine healthcare appointments. By using this approach we can provide important evidence to women and healthcare professionals making challenging decisions about treatment. This study will include women with a medication prescribed to prevent seizures before or during pregnancy. Comparisons will be made between different treatment groups.
We will use information recorded about pregnancy management including medications prescribed and we will find out whether their pregnancy ended with a loss or a livebirth. We will link the records of the mothers and their children to allow us to collect information about development and diagnoses. Outcomes in children will be compared between mothers who used different medications during pregnancy. This work will improve the care of women in their childbearing years through providing information both women and their doctors need to make pregnancy as safe as possible for the mother and child.
Women with epilepsy or other chronic conditions may need to take antiseizure medications in pregnancy to prevent seizures or alleviate other symptoms. There is limited evidence about the safety of the newer antiseizure medications in pregnancy. This work aims to understand prescribing and safety of antiseizure medications in pregnancy to better inform patients and healthcare professionals in planning pregnancies.
This study will use anonymised data from CPRD AURUM. The study period will run from 01-Jan-2002 to 31-June-2021. Women with a prescription for an anti-seizure medication prescribed before or during pregnancy will be identified. Prescribing of antiseizure medications will be described by one month time periods in terms of mono and polytherapy; any switching or cessation of medications will be described. Comparisons will be made between pregnancies with a prescription for lamotrigine during pregnancy and pregnancies where a different antiseizure medication(s) was prescribed. Outcomes to be investigated include pregnancy loss, stillbirth, early neonatal death, maternal death and in the offspring, major congenital malformations, neurodevelopmental outcomes and childhood cancer.
Analyses will be grouped by indication for prescribing of antiseizure medications: women who have an epilepsy diagnosis before pregnancy; women who have an alternative or no indication for prescribing an antiseizure medication. Absolute risks of each outcome will be reported with 95% confidence intervals; conditional logistic regression will be used to evaluate major congenital malformations and survival analysis will be used to evaluate pregnancy loss, stillbirth, neurodevelopmental disorder outcomes and childhood cancer. Analyses will compare different antiseizure medications as mono and polytherapy and at different dosages; adjustments for confounders will be made and sensitivity analyses will test potential misclassification of exposure and outcomes.
Pregnancy loss; stillbirth; neonatal death; major congenital malformations; neurodevelopmental diagnoses; childhood cancer; maternal death.
Anita McGrogan - Chief Investigator - University of Bath
Rachel Charlton - Corresponding Applicant - University of Bath
Julia Snowball - Collaborator - University of Bath
Marte-Helene Bjork - Collaborator - Not from an Organisation
Rachel Charlton - Collaborator - University of Bath
Rebecca Bromley - Collaborator - University of Manchester
Patient Level Index of Multiple Deprivation;CPRD Aurum Mother-Baby Link;CPRD Aurum Pregnancy Register