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Estimating Bias From Loss to Follow-up in the Danish National Birth Cohort

Greene, Naomia; Greenland, Sandera,b; Olsen, Jørna,c; Nohr, Ellen Aagaardd

doi: 10.1097/EDE.0b013e31822939fd

Loss to follow-up in cohort studies may result in biased association estimates. Of 61,895 women entering the Danish National Birth Cohort and completing the first data-collection phase, 37,178 (60%) opted to be in the 7-year follow-up. Using national registry data to obtain end point information on all members of the cohort, we estimated associations in the baseline and the 7-year follow-up participant populations for 5 exposure-outcome associations: (a) size at birth and childhood asthma, (b) assisted reproductive treatment and childhood hospitalizations, (c) prepregnancy body mass index and childhood infections, (d) alcohol drinking in early pregnancy and childhood developmental disorders, and (e) maternal smoking in pregnancy and childhood attention-deficit hyperactivity disorder (ADHD). We estimated follow-up bias in the odds or rate ratios by calculating relative ratios. For all but one of the above analyses, the bias appeared to be small, between −10% and +8%. For maternal smoking in pregnancy and childhood ADHD, we estimated a positive bias of approximately 33% (95% bootstrap limits of −30% and +152%). The presence and magnitude of bias due to loss to follow-up depended on the nature of the factors or outcomes examined, with the most pronounced contribution in this study coming from maternal smoking. Our methods and results may inform bias analyses in future pregnancy cohort studies.

From the aDepartment of Epidemiology, School of Public Health, University of California, Los Angeles, CA; bDepartment of Statistics, University of California, Los Angeles, CA; cDanish Epidemiology Science Centre, Department of Epidemiology, Aarhus, Denmark; and dDepartment of Epidemiology, Institute of Public Health, Aarhus University, Aarhus, Denmark.

Submitted 11 August 2010; accepted 3 June 2011; posted 14 September 2011.

The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the Danish National Birth Cohort. The cohort is furthermore a result of a major grant from this Foundation. Additional support for the Danish National Birth Cohort is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation, and the Health Foundation. The DNBC 7-year follow-up is supported by the Lundbeck Foundation (195/04) and the Danish Medical Research Council (SSVF 0646).

Correspondence: Naomi Greene, Department of Epidemiology, UCLA School of Public Health, Box 951772, Los Angeles, CA 90095. E-mail:

© 2011 Lippincott Williams & Wilkins, Inc.