Biochemical markers of renal function and maternal hypothyroidism in early pregnancy.

Objective: The physiological adaptations during a normal pregnancy affect renal and thyroid function and levels of associated biochemical markers. An association between cystatin C (CysC), creatinine, and thyroid function has been considered in nonpregnant individuals but not in pregnant women specifically.

Methods: Cohort study within the North Denmark Region Pregnancy Cohort (2011-2015) with assessment of thyroid function and autoantibodies (ADVIA Centaur XPT, Siemens Healthineers) in serum residues from the early pregnancy. Consecutive samples (n = 1112) were selected for measurement of CysC and creatinine (Atellica CH 930, Siemens Healthineers), and results were linked to information in Danish nationwide registers for (i) establishment of pregnancy-specific reference intervals for CysC and creatinine and (ii) evaluation of the prevalence of maternal hypothyroidism in early pregnancy according to levels of CysC and creatinine.

Results: The established reference intervals (2.5-97.5 percentiles) differed by week of pregnancy (week 4-8, 9-11, 12-15) and were CysC: 0.58-0.92 mg/L; 0.54-0.91 mg/L; 0.52-0.86 mg/L; creatinine: 46.9-73.0 µmol/L; 42.0-68.4 µmol/L; 38.8-66.4 µmol/L. The prevalence of maternal autoimmune hypothyroidism in early pregnancy differed by the level of CysC and creatinine (<25th percentile; 25th-75th percentile; >75th percentile) and was for CysC 1.7%, 3.8%, 7.4% and for creatinine 2.5%, 4.1%, 7.1%.

Conclusions: Reference intervals for CysC and creatinine were dynamic in early pregnancy and decreased with increasing gestational age. Furthermore, higher levels of CysC and creatinine associated with a higher prevalence of maternal autoimmune hypothyroidism. Results encourage considerations on the underlying mechanisms for the association between markers of renal and thyroid function.