Preconceptional Folate Use and Risk of a Multiple Birth: Measurement Error, Confounding and Effect Modification by In Vitro Fertilization

• Activity Number: 213
• Type: Contributed
• Date/Time: Tuesday, August 5, 2003 : 8:30 AM to 10:20 AM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Stein Emil Vollset*+ and Hakon K. Gjessing and Anne Tandberg and Thorbjorn Ronning and Valborg Baste
• Companies: University of Bergen and University of Bergen and Haukeland University Hospital and University of Bergen and Medical Birth Registry of Norway
• Keywords: folate ; multiple birth ; measurement error ; confounding ; perinatal epidemiology

Abstract

Studies have suggested that preconceptional folate use increases the risk of twins. This is an important public health issue, as it enters the current debate of the level of folate fortification in the U.S., and the introduction of fortification in other countries. We used recent data from Norway based on 176,167 pregnancies, of which 3226 were multiple. The use of in vitro fertilization (IVF) is associated both with higher frequency of folate use (23.5% vs. 6.1%) and multiple pregnancies (27.6% vs. 1.5%). In an overall age-adjusted analysis, preconceptional folate use was associated with 65% increased risk of a multiple pregnancy (OR=1.65, 95% CI: 1.47-1.85). The estimated odds ratio in women without reported use of IVF was reduced to 1.21 (95% CI: 1.04-1.40). Not all IVF pregnancies are registered, particularly when the procedure was performed outside Norway. Based on inquiries to fertility clinics in Denmark, we assumed 20% underreporting of IVF. Using a standard measurement error model, the resulting odds ratio was 1.05 (95% CI: 0.88-1.26). Underreporting of folate use and modeling of zygosity using gender of twins will be incorporated in the final analysis.