1. The Cornwall Anti-psychotic Pregnancy Register The background work: The UK Epilepsy & Pregnancy Register Pregnancy, Epilepsy & Safety
Dr Rohit Shankar
MBBS, DPM, MRCPsych, CCT, PGC Cl. Research, PGC Aspergers
Consultant in Adult Developmental Neuropsychiatry –Cornwall Partnership NHS Foundation Trust
Hon. Associate Professor – Exeter Medical School

2. Investigators Chief Investigator – Dr Rohit Shankar
Researcher – Mrs Zoe Doran
Co- Investigators –
Dr Richard Laugharne
Mrs Clare Dale
Dr John Craig
Professor Ian Jones
Dr Darren Mackintosh
Dr Adrian Flynn
Dr Mike Metcalfe

3. Presentation Focus
A case study to highlight how good evidence influences practice
A model for generating good evidence base

4. Case Scenario 30 year old female recent history of Bipolar Disorder
well managed on Sodium Valproate 1500 mgs/day
suffered side effects from Lithium in the past
seeks to get pregnant and wants advice on medication

5. management is about balance
Case & Risk Management
Safety of child –
1. Acute Harm – delivery and breast feeding
2. Long term effects - congenital
Safety of mum –
Relapse
2. Adverse effects
3. Harm
Evidenced Based Medicine
management is about balance

6. Evidence Based Medicine - Discussion
Was it right for her to be on Valproate?
What is the risk of Valproate – for mum and foetus?
What other non –antipsychotic ‘mood stabilizers’ would you consider?
What is the evidence and how strong is it?

7. The Evidence
The risk of birth defects with valproate is 2-5 times higher than other frequently used antiepileptic drugs
absolute rates of birth defects 6-11%
doses over 1000 mg/day associated with almost 2 times higher risk than doses less than 1000mg/day
Children born to mothers using valproate have significantly lower IQ scores (9 points)
rates of autism exposed before birth in the cohort studied were 8.9%
Does prescribing controlled release valproate versus multiple daily administrations in pregnancy reduce the risk for malformations?
Higher malformation rates observed with in utero exposure to valproate are more likely related to total daily dose, rather than peak serum levels.

8. How Strong is the Evidence?
Outcome data available from 1109 pregnancies exposed to valproate in monotherapy
FDA
Category D for Mania
Category D for Epilepsy
Category X – for Migraine
How did we get this Evidence?
A pregnancy Category D medicine may still be given to a pregnant woman if the healthcare provider believes that the benefits to the woman outweigh the possible risks to the unborn child
Pregnancy Category X means that the risks of taking the medication during pregnancy clearly outweigh the benefits.

9. The UK Epilepsy and Pregnancy Register 1996
The UK Epilepsy and Pregnancy Register is a prospective, observational and follow up study set up to determine the risks of major congenital malformations for infants exposed to antiepileptic drugs in utero
Captures roughly 1 of 3 deliveries on AEDs
Devised and led by Professor Morrow and Dr Craig (co-investigator in our study)

10. Morrow, Russell, Guthrie et al (2006) Malformation risks of anti-epileptic drugs in pregnancy: A prospective study from the UK Epilepsy and pregnancy register. JNNP January 2006
Hunt, Craig, Russell et al (2006) Levetiracetam in pregnancy: Preliminary results from the UK Epilepsy and pregnancy register. Neurology 67
Topiramate in pregnancy: Preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 2008
Folic acid use and major congenital malformations in offspring of women with epilepsy. A prospective study from the UK Epilepsy and Pregnancy Register. JNNP 2008 (80)5: ( )
Cummings, Stewart, et al (2011) Neurodevelopment of children exposed in utero to Lamotrigine, sodium valproate and Carbamazepine. Arch Dis Chid. March 17th 2011
Shallcross, Bromley, Irwin et al (2011) Childevelopment following in utero Exposure: Levetiracetam Vs Sodium Valproate. Neurology: 76: 383
Hoeritzauer, Mawhinney, (2012) Increased Levetiracetam clearance in pregnancy: Is seizure frequency affected?. Seizure 21(7);
Mawhinney et al (2012) Valproate and the risk for congenital malformations: Is formulation and dosage regime important. Seizure
Ellen Mawhinney, John Craig, Jim Morrow, et al. (2013) Levetiracetam in Pregnancy Results from the UK and Ireland epilepsy and pregnancy registers. Neurology 80(4):400-5
Campbell, E., Devenney, E., Morrow, J. et al (2013) Recurrence risk of congenital malformations in infants exposed to antiepileptic drugs in utero. Epilepsia. 54 (1)
Campbell, E., Hunt, S., Kinney, M. Et al (2013) The effect of socioeconomic status on treatment and pregnancy outcomes in women with epilepsy in Scotland. Epilepsy & Behaviour
Campbell, E., Kennedy. Russell, A. et al (2014) Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers. JNNP January 2014

11. Notable Points
A prospective Register allows longitudinal collection of data
Simple, not time consuming and focused on recruitment
Not dependent on ‘power’
Answer important questions on potential for harm
Cost effective
Can be started in different countries though it is important that the Registers can ‘speak’ to each other – i.e. the data collection tools are similar

12. THANK YOU!