Background: Miscarriage is the spontaneous loss of pregnancy occurring prior to 24 weeks of gestation, and can be devastating for affected couples. Abnormal placental development is observed in two-thirds of miscarriages. Recently, the circulating placental markers kisspeptin, prokineticin-1 (PK-1), soluble fms-like tyrosine kinase-1 (sFlt1), soluble endoglin (sEng) and placental growth factor (PlGF) have been identified and investigated for potential associations with miscarriage. However, no previous study has evaluated the predictive value of these markers in identifying pregnancies which later result in miscarriage.
Methods: We conducted a prospective cohort study including over 900 asymptomatic women attending their booking antenatal visit at a single obstetric centre. In each patient, a single measurement of plasma PK-1 and kisspeptin, and serum human chorionic gonadotropin (hCG), sEng, sFlt1 and PlGF was made, and pregnancy outcome was monitored prospectively.
Results: During singleton pregnancies, multiples of median (MoM) kisspeptin, hCG, sFlt-1, PlGF and sEng were 63, 43, 36, 30 and 11% lower in women later experiencing miscarriage when compared with unaffected pregnancies, respectively. MoM PK-1 was not significantly different in the miscarriage group when compared with unaffected pregnancies. Associations of kisspeptin, hCG, sFlt-1 and PlGF with miscarriage remained significant despite adjusting for subject age, gestation, smoking, blood pressure, and body mass index during logistic regression modelling.
Conclusions: Our data suggest that circulating levels of kisspeptin, hCG, sFlt-1 and PlGF but neither sEng nor PK-1 may be independently associated with miscarriage risk in asymptomatic women attending their antenatal booking visit. These data further our understanding of placental function, and have important potential implications for utilising novel hormonal markers to detect adverse clinical outcomes during pregnancy.