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PAPERS:
R J Berry, R Kihlberg, and O Devine
Impact of misclassification of in vitro fertilisation in studies of folic acid and twinning: modelling using population based Swedish vital records
BMJ 2005; 330: 815 [Abstract] [Full text]
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[Read Rapid Response] Folate supplementation and twinning
Kenneth Campbell   (8 April 2005)

Folate supplementation and twinning 8 April 2005
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Kenneth Campbell,
Clinical Information Officer (posted in private capacity)
Leukaemia Research Fund, WC1N 3JJ

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Re: Folate supplementation and twinning

Dear Sirs,

Swedish researcher have reported that folate supplementation in early pregnancy increases the risk of twin births. (e.g. Ericson et.al.(1)). Berry et.al. (2) suggest that this is wholly or largely a false result based on misclassification of in vitro fertilisation, itself a known risk factor for twinning. In assessing the credibility of the original Swedish reports it is useful to consider whether there is a plausible mechanism by which dietary supplementation might increase twinning rates.

The answer may lie in the "vanishing twin" phenomenon; Landy et.al. (3) in their 1986 review suggest that as many as 21% of twin pregnancies lead to early (first trimester) death of one twin with subsequent resorption. If folate and/or multivitamin supplementation reduces the rate of early twin loss it would lead to an increase in the number of twin deliveries without any effect on the rate of twin pregnancy. If this is correct it raises the dilemma that the benefits of folate supplementation (reduced rates of neural tube defect and, evidence suggests, childhood leukaemia) are not likely to be separable from increases in full-term twinning rates.

Yours sincerely,
Ken Campbell

(1) Ericson, A., Kallen, B., & Aberg, A. 2001, "Use of multivitamins and folic acid in early pregnancy and multiple births in Sweden", Twin.Res., vol. 4, no. 2, pp. 63-66.

(2) Impact of misclassification of in vitro fertilisation in studies of folic acid and twinning: modelling using population based Swedish vital records R J Berry, R Kihlberg, and O Devine BMJ 2005 330: 815.

(3) Landy, H. J., Weiner, S., Corson, S. L., Batzer, F. R., & Bolognese, R. J. 1986, "The "vanishing twin": ultrasonographic assessment of fetal disappearance in the first trimester", Am.J Obstet.Gynecol., vol. 155, no. 1, pp. 14-19.

Competing interests: None declared