A case control study to examine the pharmacological factors underlying ventricular septal defects in the North of England

Background: Amphetamine exposure is associated with congenital cardiac abnormalities in animals. We previously reported an association between recreational use of 2,4-methylenedioxymethamphetamine (ecstasy, MDMA) and ventricular septal defect in babies born to users. We have carried out a case control study to investigate risks in the occurrence of ventricular septal defect in a cohort of babies born in the North East of England. Methods: Cases were identified from paediatric cardiology units in Newcastle upon Tyne and Leeds, and controls were recruited froth the mothers of babies born in the same hospital as the index case. Research nurses carried out interviews using a structured questionnaire. Results: A total of 296 case control pairs were studied. There was insufficient exposure to ecstasy to test the primary hypothesis. Increased risk of ventricular septal defect was found to be associated with consumption of cough and cold remedies [pre-conception OR 2.2, 95% CI 1.41, 3.51: pregnancy OR 5.1, 95% CI 2.56, 11.27; exposure in either OR 2.83, 95% Cl 1.85, 4.45; P < 0.005] and in the case of non-steroidals for exposures in pregnancy (OR 4.2, 95% CI 1.54, 14.26; P < 0.005). Conclusions: These findings suggest that ventricular septal defect is associated with consuming the medications identified. They are also compatible with the hypothesis that sympathotnimetics (pseudoephedrine, phenylephrine and phenylpropanolamine) present in cough mixtures cause the increased risk, and with our original hypothesis that sympathomimetics and amphetamines are potentially cardiotoxic in utero.