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

doi:10.1136/bmj.38369.437789.82

BMJ, doi: 10.1136/bmj.38369.437789.82, (Published 18 February 2005)

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

R J Berry ¹, R Kihlberg ², O Devine ¹

¹ National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Department of Health and Human Services, 1600 Clifton Road, MS E-86, Atlanta, GA 30333, USA
² Riddarvägen 37B, 184 51, Österskär, Stockholm, Sweden

Objective To determine whether failure to adequately adjustfor a reported 40% misclassification of use of in vitro fertilisation(IVF) as reported in a Swedish study could have led to a falsefinding that folic acid increases dizygotic twinning.

DesignModelling with population based data.

Setting Swedish vitalrecords for 1995-9.

Main outcome measures Rates of twinning calculatedaccording to whether women used IVF to become pregnant. Estimatedunadjusted and adjusted odds ratios of the association betweenuse of folic acid and twinning by use of IVF.

Results In 1995-9,Swedish women who used IVF had an almost 20 times the chanceof 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 trueeffect of folic acid, the use of a 40% misclassified surrogatevariable to adjust for use of IVF would have resulted in a falsefinding that folic acid was associated with a more than twofoldincrease in twinning.

Conclusion Use of IVF is a strong confounderbecause it is associated with both use of folic acid and twinning.Even when misclassification of IVF was reduced to 5%, this biaspersisted in the adjusted model. Using a 40% misclassified surrogateto adjust for IVF, as reported in the Swedish study, probablyled to a false finding that folic acid increased dizygotic twinning.

(Accepted 10 January 2005)

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