Reduced Levels of Plasma Kisspeptin During the Antenatal Booking Visit Are Associated With Increased Risk of Miscarriage

Abstract

Context:Kisspeptin is a recently identified hormone encoded by the KISS1 gene, playing a critical role in human reproduction. Plasma kisspeptin levels rise dramatically during normal pregnancy due to placental synthesis, which implicates it as a potential tool for assessing risks of pregnancy complications. No previous prospective study has investigated the association between plasma kisspeptin and risk of miscarriage.Objective:The objective of the study was to determine whether a single plasma kisspeptin or serum human chorionic gonadotropin (hCG) measurement in asymptomatic women attending their booking antenatal visit is associated with miscarriage.Design:This was a prospective cohort study.Setting:The study was conducted at a tertiary obstetric center.Participants:A total of 993 asymptomatic pregnant women with a gestation of 6 weeks or longer attending routine antenatal booking visit were recruited between January 2010 and December 2012.Main Outcome Measures:Plasma kisspeptin and serum hCG were measured during the antenatal booking visit. Pregnancy outcome was recorded prospectively.Results:Plasma kisspeptin correlated with gestation (r2 = 0.57; P < .0001). Gestational age-corrected (multiples of median) plasma kisspeptin was 60.4% lower (P < .001), and multiples of median-hCG was 36.1% lower (P < .001) in women later diagnosed with miscarriage compared with women without miscarriage. Increased plasma kisspeptin was associated with reduced miscarriage risk, even after adjusting for age, body mass index, gestational age, smoking, and blood pressure [odds ratio 0.13 (95% confidence interval 0.08–0.22), P = .0001]. Kisspeptin had a higher diagnostic performance for miscarriage than hCG (receiver-operator characteristic-area under the curve 0.899 ± 0.025 plasma kisspeptin; 0.775 ± 0.040, serum hCG, P < .01 vs plasma kisspeptin).Conclusion:Our data suggest for the first time that a single plasma kisspeptin measurement taken during the antenatal booking visit provides a potential novel marker for identifying asymptomatic pregnant women at a gestation of 6 weeks or greater at increased risk of miscarriage.

Kisspeptin/GPR54 System: What Do We Know About Its Role in Human Reproduction?

“…Kisspeptin levels below 1630 pmol/L during the first trimester were considered a miscarriage biomarker, since women who suffer miscarriages show kisspeptin levels 60% lower than unaffected pregnancies [81].…”

Kisspeptin: new biomarker of pregnancy

“…14 In humans, the plasma concentration of kisspeptin increases dramatically in the pregnancy, with a 900-fold increase in the first trimester and further increases to over 7000-fold in the third trimester compared to the non-pregnant women. 15 It is most likely that the increase in the total number of trophoblast cells throughout the course of gestation is responsible for the dramatic increase in serum kisspeptin levels. 16 Kisspeptin are mainly derived from placenta, the levels of plasma or serum kisspeptin can probably act as a biomarker for the function of the placenta and therefore viability of pregnancy.…”

“…12,13 Plasma or serum kisspeptin levels are significantly increased in early pregnancy compared to non-pregnant controls. [13][14][15]…”

Kisspeptin across the human lifespan:evidence from animal studies and beyond

“…Jayasena and coworkers showed that circulating kisspeptin at antenatal booking correlated with risk of miscarriage (Jayasena et al 2014a), with gestation-corrected kisspeptin being 60% lower in women with a singleton pregnancy compared with unaffected singleton pregnancies (gestation-corrected multiple of median kisspeptin 1.06 ± 0.42 singleton no miscarriage vs 0.42 ± 0.39 singleton miscarriage, P < 0.001 with values representing mean ± s.d.). The relationship of kisspeptin with miscarriage was also demonstrated in twin pregnancies, where death of one foetus was associated with a lower kisspeptin level than those without complications.…”