Maternal thyroid function and biochemical markers of placental function in early pregnancy

Maja Lundgaard; Marianne Sinding; Anne Sorensen; Aase Handberg; Stig Andersen; Nanna Torp; Stine Andersen

doi:10.1530/endoabs.101.OP-08-05

Objective: A link between levels of maternal thyroid hormones in pregnancy and the biochemical markers of placental dysfunction, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), has been brought forward. Sparse evidence is available on the dynamics of sFlt-1 and PlGF in early pregnancy and the association with maternal thyroid function in early pregnant women specifically.

Methods: A retrospective cohort study within the North Denmark Region Pregnancy Cohort, 2011-2015, that contained maternal blood samples (n = 17,647) drawn in early pregnancy as part of prenatal screening for chromosomal anomalies. The samples were later used for assessment of thyroid-stimulating hormone (TSH) (ADVIA Centaur XPT, Siemens Healthineers). For the present study, a random sub-group of pregnant women (n = 858) were selected for measurement of sFlt-1 and PlGF as well as β-human chorionic gonadotropin (β-hCG) (Kryptor Compact, ThermoFisher Scientific). Regression analysis was used to evaluate the association between maternal TSH and β-hCG and pregnancy week-specific percentile levels of sFlt-1 and PlGF. Results were reported as geometric mean and adjusted beta coefficient (aβ) including potential confounders.

Results: Blood samples were drawn in median pregnancy week 10 (range 4-16). When evaluating the association between maternal TSH and categories of the placental biomarkers, higher percentile levels of sFlt-1 and PlGF associated with lower TSH in crude and adjusted analyses (Table). An opposite association between the placental biomarkers and β-hCG was found, with higher levels of β-hCG for increasing levels of sFlt-1 and PlGF (Table). Finally, high levels of β-hCG (> 75 percentile) associated with lower TSH (aβ 0.60 (95% CI: 0.48-0.75)).

Table 1
	n	Mean TSH (mIU/l)	aβ	95% CI	Mean β-hCG (IU/l)	aβ	95% CI
sFlt-1
< 25 percentile	235	1.18	Ref.		35.8	Ref.
25-75 percentile	415	0.86	0.76	0.65-0.88	55.1	1.56	1.38-1.76
> 75 percentile	208	0.75	0.66	0.55-0.81	82.6	2.34	2.05-2.67
PlGF
< 25 percentile	210	1.03	Ref.		46.4	Ref.
25-75 percentile	407	0.95	0.97	0.83-1.12	54.9	1.19	1.05-1.35
> 75 percentile	241	0.75	0.78	0.64-0.96	59.9	1.27	1.10-1.47

Conclusions: In a large cohort of Danish pregnant women, higher levels of sFlt-1 and PlGF associated with lower levels of TSH. In contrast, higher levels of the placental biomarkers associated with higher levels of β-hCG. Considering the physiological link between TSH and β-hCG in early pregnancy, an intermediate role of β-hCG in the association between maternal thyroid function and biochemical markers of placental function may be proposed in this early window of pregnancy.

Endocrine Abstracts

OP-08-05