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.


METHODS
Modelling with population based data.


METHODS
Swedish vital records for 1995-9.


METHODS
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.


CONCLUSIONS
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.
Berry
R J
RJ
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. RJBerry@cdc.gov
Kihlberg
R
R
Devine
O
O
D003625:Data Collection / Q000592:standards*; D019587:Dietary Supplements; D005260:Female; D005307:Fertilization in Vitro / Q000706:statistics & numerical data; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D016017:Odds Ratio; D011247:Pregnancy; D011272:Pregnancy, Multiple / Q000706:statistics & numerical data*; D013548:Sweden; D014429:Twins, Dizygotic
D005492:Folic Acid
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