Background: Placentation (invasion of the placenta into the maternal endometrium) is hypothesised to be critical for healthy placental function and is abnormal in two thirds of miscarriages. Kisspeptin has emerged as a putative regulator of physiological placentation; it is highly expressed in placental syncytiotrophoblasts and could play an important paracrine role in the regulation of placentation. Circulating kisspeptin levels are considerably raised during healthy pregnancy and reduced in women with miscarriage. We aimed to investigate the utility of circulating kisspeptin concentrations in the assessment of pregnancy complications.
Methods: This study was performed in collaboration with the Early Pregnancy Outcome Study (EPOS), which aims to identify novel pregnancy biomarkers. Women were invited to attend for blood-sampling, clinical and ultrasound assessment fortnightly during the first trimester and again during the second and third trimesters. Asymptomatic women with healthy pregnancy (n=265) provided 960 blood-samples. Women with pregnancy complications including miscarriage (n=95), pre-eclampsia (PET; n=24), pregnancy induced hypertension (PIH; n=14), gestational diabetes (GDM; n=41), preterm birth (PTB; n=14) and intrauterine growth restriction (IUGR; n=24) provided 569 blood-samples.
Results: Gestation-adjusted circulating kisspeptin and βhCG levels were 66% and 57% lower, respectively, in women with miscarriage compared to healthy pregnant controls (P<0.0001). Area under ROC curve for diagnosis of miscarriage was greater for the combination of both kisspeptin and βhCG together (0.92) than for either measure alone (βhCG 0.859, kisspeptin 0.874). An adjusted logistic regression model revealed that an 100 pmol/l increase in plasma kisspeptin reduced the odds of miscarriage by 42%. Gestation-adjusted kisspeptin levels were lower in women with GDM (P=0.002), or IUGR (P<0.0001), and higher in women with PTB (P=0.004). Kisspeptin increased with gestation greater in PET (P=0.008) and PIH (P<0.0001) than in healthy controls.
Conclusions: Plasma kisspeptin is a promising biomarker for pregnancy complications and provides additional diagnostic capability over that provided by βhCG.