Impact of misclassification of in vitro fertilisation in studies of folic acid and twinning: modelling using population based Swedish vital records.

OBJECTIVE To determine whether failure to adequately adjust for a reported 40% misclassification of use of in vitro fertilisation (IVF) as reported in a Swedish study could have led to a false finding that folic acid increases dizygotic twinning. DESIGN Modelling with population based data. SETTING Swedish vital records for 1995-9. MAIN OUTCOME MEASURES Rates of twinning calculated according to whether women used IVF to become pregnant. Estimated unadjusted and adjusted odds ratios of the association between use of folic acid and twinning by use of IVF. RESULTS In 1995-9, Swedish women who used IVF had an almost 20 times the chance of having twins than women who did not use IVF (rate ratio 19.7, 95% confidence interval 18.7 to 20.6). In the absence of a true effect of folic acid, the use of a 40% misclassified surrogate variable to adjust for use of IVF would have resulted in a false finding that folic acid was associated with a more than twofold increase in twinning. CONCLUSION Use of IVF is a strong confounder because it is associated with both use of folic acid and twinning. Even when misclassification of IVF was reduced to 5%, this bias persisted in the adjusted model. Using a 40% misclassified surrogate to adjust for IVF, as reported in the Swedish study, probably led to a false finding that folic acid increased dizygotic twinning.