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

Introduction Electronic healthcare data has 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.Objectives 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.Methods 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 01-01-2000 to 31-03-2007 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 a NDD diagnosis by 6 years were identified from Read 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 to the results of the prospective Liverpool and Manchester Neurodevelopmental Group study which completed assessment on 201 WWE and 214 without epilepsy at age 6 years.Results In the CPRD, 1,018 mother-child pairs to WWE and 6,048 without epilepsy were identified. The CPRD identified a lower prevalence of NDDs compared to the prospective study. In both studies, NDDs were more frequently reported in children of women with epilepsy than without epilepsy, although the CPRD risk estimate was lower (2.16% versus 0.96% p<0.001 and 7.46% versus 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 (ORadj2.02 CI950.52-7.86) observed in the prospective study (ORadj6.05 CI951.65-24.53).Conclusion 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.