Berry R J, Kihlberg R, Devine O
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.
BMJ. 2005 Apr 9;330(7495):815. doi: 10.1136/bmj.38369.437789.82. Epub 2005 Feb 18.
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.
Modelling with population based data.
Swedish vital records for 1995-9.
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.
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.
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.
确定未能对瑞典一项研究中报告的体外受精（IVF）使用情况40%的错误分类进行充分校正，是否会导致得出叶酸会增加双卵双胎这一错误结论。
基于人群数据进行建模。
1995 - 1999年瑞典的生命记录。
根据女性是否使用IVF怀孕计算双胎率。通过使用IVF估计叶酸使用与双胎之间关联的未校正和校正优势比。
1995 - 1999年，使用IVF的瑞典女性怀双胞胎的几率几乎是未使用IVF女性的20倍（率比19.7，95%置信区间18.7至20.6）。在叶酸不存在真正影响的情况下，使用一个40%错误分类的替代变量来校正IVF的使用，会导致得出错误结论，即叶酸与双胎率增加两倍以上有关联。
IVF的使用是一个很强的混杂因素，因为它与叶酸使用和双胎都有关联。即使将IVF的错误分类降低到5%，这种偏倚在调整后的模型中仍然存在。如瑞典研究中所报告的，使用一个40%错误分类的替代变量来校正IVF，可能导致得出叶酸增加双卵双胎这一错误结论。
