Epilepsy is the most common serious neurological disorder. Antiepileptic drugs are used to treat epilepsy and are also used as mood stabilisers for some mental disorders such as bipolar disorder. While these drugs may prevent harm to the mother, they may harm the fetus. We will study the effects of taking these drugs, and the underlying conditions for which they are prescribed during pregnancy. Our study will answer four questions. First: what are the patterns of antiepileptic drug prescribing across the pregnancy period? Second: what are the risks of adverse maternal, pregnancy and child outcomes among women with epilepsy and other indications of antiepileptic prescribing? Third: does use of these drugs during pregnancy influence the risk of adverse maternal, child and pregnancy outcomes? Fourth: are our results robust to the various assumptions made by our analysis techniques. Our results will help doctors and patients make informed decisions about using these medicines.
Antiepileptic and mood stabiliser medications (collectively abbreviated as AEDs) refer to an overlapping group of drugs prescribed for a range of neuropsychiatric conditions including epilepsy and bipolar disorder. Their use in pregnancy is often necessary to reduce harms to the mother. There is little robust evidence for the maternal and fetal safety profile of many AEDs although some drugs such as sodium valproate are known to be teratogenic.
Aims: Using data from UK CPRD and Swedish registry data, we will i) describe trends across time in the usage of AEDs during pregnancy; ii) quantify the risk of maternal, pregnancy and child developmental outcomes related to prescribing of AEDs during pregnancy (complete list below), iii) quantify the risk of maternal, pregnancy and child developmental outcomes of epilepsy and other indications for which AEDs are prescribed, and iv) triangulate evidence from multiple methods to strengthen causal inference.
Design: Observational intergenerational cohort study.
Setting: Clinical Practice Research Datalink (CPRD) primary care records linked to Hospital Episodes Statistics (HES), Office of National Statistics (ONS) death records, pregnancy register and social deprivation data in the UK; Records from Swedish national and local registers.
Target population: Representative population-based sample in the UK and Sweden.
Inclusion Criteria: Women in the CPRD pregnancy register, who were registered with the same practice for at least 1 year before pregnancy and throughout the pregnancy period, with data linkage to their child .
Health technologies being assessed: AEDs during pregnancy vs no drug treatment during pregnancy; and continuing vs stopping use of AEDs during pregnancy. Exposures of interest also include indications for AED prescribing.
Outcomes: Maternal: Pregnancy outcomes and delivery outcomes in the mother. Child: diagnosis of autism, ADHD and intellectual disability(ID).
Statistical analyses: Our analysis will involve multivariable regression methods, appropriate for each outcome, while accounting for time at risk.
Maternal outcomes
1. Hospital admission for epilepsy/status epilepticus/psychiatric morbidities;
2. Outpatient care for epilepsy/status epilepticus/psychiatric morbidities;
3. Accident and Emergency department visits;
4. Self-harm and suicide attempts;
5. Prolonged hospitalisation during pregnancy or following delivery;
6. All cause and cause specific mortality;
Pregnancy outcomes:
7. Obstetric complications (including pre-eclampsia/eclampsia);
8. Pregnancy loss (miscarriage, termination of pregnancy, stillbirth);
9. Mode of delivery (including vaginal birth/C-section delivery);
10. Gestational age at birth (Preterm birth);
Outcomes in children:
11. Birth defects;
12. Diagnosis of autism spectrum disorder;
13. Diagnosis of attention deficit hyperactivity disorder;
14. Diagnosis of intellectual disability;
15. Diagnosis of epilepsy.
Dheeraj Rai - Chief Investigator - University of Bristol
Paul Madley-Dowd - Corresponding Applicant - University of Bristol
- Collaborator -
Caichen Zhong - Collaborator - Drexel University
Deepika Chauhan - Collaborator - University of Bristol
Florence Martin - Collaborator - University of Bristol
Harriet Forbes - Collaborator - University of Bristol
Jessica Rast - Collaborator - Drexel University
Kristen Lyall - Collaborator - Drexel University
Kritika Jain - Collaborator - University of Bristol
Neil Davies - Collaborator - University of Bristol
Deepika Chauhan - Collaborator - Drexel University
CPRD Mother-Baby Link;HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation;Pregnancy Register