Dynamics and Predictors of Serum TSH and fT4 Reference Limits in Early Pregnancy: A Study Within the Danish National Birth Cohort

Context: Thyroid hormones are important developmental factors and levels should be adequate both in the pregnant woman and in the fetus. However, there is no consensus on maternal thyroid test reference limits in early pregnancy. Objective: Estimation of week-to-week changes in and predictors of TSH and free T-4 (fT(4)) reference limits in the first trimester of pregnancy. Design: Measurement of TSH and fT(4) in biobank sera collected in pregnancy weeks 5-19 from a random sample of the Danish National Birth Cohort that enrolled 101 032 pregnant in 1996-2002. Setting: National cohort of pregnant women. Participants: Healthy participants (n = 6671) were identified and individual characteristics retrieved using interview data and data from Danish national health registers. Intervention(s): None. Main Outcome Measure(s): Reference limits for TSH and fT(4) in each first trimester pregnancy week and predictors of these reference limits. Results: TSH reference limits were very variable. Up to and including week 6, nonpregnancy reference limits could be used. In weeks 9-12, TSH upper reference limit was approximately 0.4 mU/L lower than the nonpregnancy upper limit. The TSH lower reference limit was approximately 0.1 mU/L. fT(4) variations were reverse to those of TSH, but changes were small with approximately 4% higher reference limits during the weeks 9-12. TSH upper reference limit was lower in multiparous women and women with lower iodine intake but higher in obese women. fT(4) was lower in smokers. Conclusions: TSH reference limits differ widely in the first trimester of pregnancy. The use of a uniform set of reference limits is an inordinate simplification that will lead to frequent misclassification and possibly to incorrect choice of therapy.