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Dynamics and Predictors of Serum TSH and fT4 Reference Limits in Early Pregnancy: A Study Within the Danish National
Peter Laurberg1, Stine Linding Andersen1, Peter Hindersson1
1Department of Endocrinology (P.L., S.L.A.), Aalborg University Hospital, DK-9000 Aalborg, Denmark; Department of Clinical Medicine (P.L.), Aalborg University, DK-9100 Aalborg, Denmark; Department of Clinical Biochemistry (S.L.A.), Aalborg University Hospital, DK-9000 Aalborg, Denmark; Department of Clinical Biochemistry (P.H.), Regionshospital Nordjylland, DK-9800 Hjørring, Denmark; Research Unit for Gynecology and Obstetrics (E.A.N.), Institute of Clinical Research, University of Southern Denmark, DK-5000 Odense, Denmark; and Department of Clinical Epidemiology (J.O.), Aarhus University Hospital, DK-8200 Aarhus, Denmark.
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 T4 (fT4) reference limits in the first trimester of pregnancy.
Design:
Measurement of TSH and fT4 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 fT4 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. fT4 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. fT4 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.
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