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Objective: To determine whether failure to adequately adjust for a reported 40 %misclassification of use of in vitro fertilisation (IVF) as reported in a Swed ish study could have led to a false finding that folic acid increases dizygotic twinning. Design: Modelling with population based data. Setting: Swedish vital r ecords for 1995-9. Main outcome measures: Rates of twinning calculated accordin g to whether women used IVF to become pregnant. Estimated unadjusted and adjuste d odds ratios of the association between use of folic acid and twinning by use o f IVF. Results: In 1995-9, Swedish women who used IVF had almost 20 times the c hance of having twins than women who did not use IVF (rate ratio 19.7, 95%confi dence 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 ha ve resulted in a false finding that folic acid was associated with a more than t wo fold increase in twinning. Conclusion: Use of IVF is a strong confounder beca use it is associated with both use of folic acid and twinning. Even when misclas sification 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 Swedi sh study, probably led to a false finding that folic acid increased dizygotic tw inning.
Objective: To determine whether failure to adequately adjust for a reported 40% misclassification of use of in vitro fertilization (IVF) as reported in a Swed ish study could have led to a false finding that folic acid increases dizygotic twinning. Design: Modeling with population based data. Setting: Swedish vital r ecords for 1995-9. Main outcome measures: Rates of twinning calculated accordin g to whether women used IVF to become pregnant. Estimated unadjusted and adjuste d 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 almost 20 times the c hance of having twins than women who did not use IVF (rate ratio 19.7, 95% confi dence 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 ha ve resulted in a false finding that folic acid was associated with a more than t wo fold increase in twinning. Conclus ion: Use of IVF is a strong confounder beca use it is associated with both use of folic acid and twinning. Even when misclasification 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 Swedi sh study, probably led to a false finding that folic acid increased dizygotic tw inning.