Biochemical markers of renal function and maternal hypothyroidism in early pregnancy

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.

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.

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%.

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.