Changes in Circulating Kisspeptin Levels During Each Trimester in Women With Antenatal Complications

Abstract

Context Antenatal complications such as hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR), gestational diabetes (GDM), and preterm birth (PTB) are associated with placental dysfunction. Kisspeptin has emerged as a putative marker of placental function, but limited data exist describing circulating kisspeptin levels across all three trimesters in women with antenatal complications. Objective To assess whether kisspeptin levels are altered in women with antenatal complications. Design Women with antenatal complications (n=105) and those with uncomplicated pregnancies (n=265) underwent serial ultrasound scans and blood-sampling at least once during each trimester (March 2014 to March 2017). Setting Early Pregnancy Assessment Unit at Hammersmith Hospital, UK. Participants Women with antenatal complications: HDP (n=32), FGR (n=17), GDM (n=35) and PTB (n=11), and 10 women with multiple complications, provided 373 blood samples, and a further 265 controls provided 930 samples. Main outcome Differences in circulating kisspeptin levels. Results Third trimester kisspeptin levels were higher than controls in HDP but lower in FGR. The odds of HDP adjusted for gestational age, maternal age, ethnicity, BMI, smoking and parity were increased by 30% (95%CI 16-47%; p<0.0001), and of FGR were reduced by 28% (95%CI 4-46%; p=0.025), for every 1 nmol/L increase in plasma kisspeptin. Multiple of gestation-specific median values of kisspeptin were higher in pregnancies affected by PTB (p=0.014), and lower in those affected by GDM (p=0.020), but not significantly on multivariable analysis. Conclusion We delineate changes in circulating kisspeptin levels at different trimesters and evaluate the potential of kisspeptin as a biomarker for antenatal complications.

The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review

“…Moreover, no differences between metastin concentrations in umbilical arterial and venous blood have been observed [ 49 ]. These results are consistent with those obtained by Abbara et al, who have shown that gestational age was positively associated with the plasma level of kisspeptin ( p < 0.0001, 95% CI: 0.115–0.163, coefficient: 0.154), and its concentration increased as the pregnancy progressed [ 11 ].…”

“…The available data that analyzed changes in kisspeptin levels in patients with GDM compared to healthy pregnant women are limited to only a few clinical studies [ 10 , 11 , 64 , 67 , 68 , 69 ]. It has been reported that women with GDM had significantly lower plasma kisspeptin levels compared to healthy ones [ 64 ].…”

“…A different research methodology could partially explain distinctions among the obtained results. Kisspeptin concentrations were evaluated in serum, not in plasma, as in other authors’ studies [ 11 , 64 , 68 ].…”

“…Despite the considerable advances in their prevention, diagnostics, and monitoring, there are still many ambiguities about their pathogenesis. Many of these gestational complications have been previously reported to be associated with the family of kisspeptin and its receptor [ 9 , 10 , 11 ].…”

“…In Vitro experimental studies have shown decreased expression of kisspeptin/GPR54 in women with recurrent spontaneous abortion, thus suggesting that kisspeptin is engaged in the embryo implantation process [ 29 ]. Furthermore, the role of kisspeptin in developing diseases from the spectrum of impaired placentation, including PE and FGR, has been widely studied [ 11 ].…”