title: Sensitivity of the UK Clinical Practice Research Datalink to Detect Neurodevelopmental Effects of Medicine Exposure in Utero: Comparative Analysis of an Antiepileptic Drug-Exposed Cohort.
abstract: Electronic healthcare data have several advantages over prospective observational studies, but the sensitivity of data on neurodevelopmental outcomes and its comparability with data generated through other methodologies is unknown.
  
  
  
  The objectives of this study were to determine whether data from the UK Clinical Practice Research Datalink (CPRD) produces similar risk estimates to a prospective cohort study in relation to the risk of neurodevelopmental disorders (NDDs) following prenatal antiepileptic drug (AED) exposure.
  
  
  
  A cohort of mother-child pairs of women with epilepsy (WWE) was identified in the CPRD and matched to a cohort without epilepsy. The study period ran from 1 January 2000 to 31 March 2007 and children were required to be in the CPRD at age 6 years. AED exposure during pregnancy was determined from prescription data and children with an NDD diagnosis by 6 years were identified from Read clinical codes. The prevalence and risk of NDDs was calculated for mother-child pairs in WWE stratified by AED regimen and for those without epilepsy. Comparisons were made with the results of the prospective Liverpool and Manchester Neurodevelopment Group study which completed assessment on 201 WWE and 214 without epilepsy at age 6 years.
  
  
  
  In the CPRD, 1018 mother-child pairs to WWE and 6048 to women without epilepsy were identified. The CPRD identified a lower prevalence of NDDs than the prospective study. In both studies, NDDs were more frequently reported in children of WWE than women without epilepsy, although the CPRD risk estimate was lower (2.16 vs. 0.96%, p < 0.001 and 7.46 vs. 1.87%, p = 0.0128). NDD prevalence differed across AED regimens but the CPRD data did not replicate the significantly higher risk of NDDs following in utero monotherapy valproate exposure (adjusted odds ratio [ORadj] 2.02, 95% confidence interval [CI] 0.52-7.86) observed in the prospective study (ORadj6.05, 95% CI 1.65-24.53).
  
  
  
  It was possible to identify NDDs in the CPRD; however, the CPRD appears to under-record these outcomes. Larger studies are required to investigate further.
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK. r.a.charlton@bath.ac.uk.
authors.forename: R A
authors.initials: RA
authors.lastname: Charlton
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
authors.forename: A
authors.initials: A
authors.lastname: McGrogan
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
authors.forename: J
authors.initials: J
authors.lastname: Snowball
authors.affiliation: The UK Teratology Information Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.|Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle Upon Tyne, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Yates
authors.affiliation: School of Life and Health Sciences, Aston Brain Centre, Aston University, West Midlands, UK.
authors.forename: A
authors.initials: A
authors.lastname: Wood
authors.affiliation: Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.|Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Clayton-Smith
authors.affiliation: Department of General Practice, University College Cork, Cork, Ireland.
authors.forename: W H
authors.initials: WH
authors.lastname: Smithson
authors.affiliation: The UK Teratology Information Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Richardson
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
authors.forename: N
authors.initials: N
authors.lastname: McHugh
authors.affiliation: The UK Teratology Information Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.|Medical Toxicology Centre, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: S H L
authors.initials: SH
authors.lastname: Thomas
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
authors.forename: G A
authors.initials: GA
authors.lastname: Baker
authors.affiliation: Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.|Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: R
authors.initials: R
authors.lastname: Bromley
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D016208:Databases, Factual; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D065886:Neurodevelopmental Disorders / Q000139:chemically induced / Q000453:epidemiology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D015995:Prevalence; D011446:Prospective Studies; D012107:Research Design; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000927:Anticonvulsants