Serum Melatonin as a Biomarker for Assessment of Late-term and Postterm Pregnancies in Women without Spontaneous Onset of Labor

Abstract

We conducted a prospective study to assess serum melatonin as a biomarker to predict the development of late-term and postterm pregnancies and spontaneous beginning of labor in women with term pregnancies. Population of this prospective study included pregnant women with late-term and postterm pregnancies and term pregnancies as controls. In these study groups, serum melatonin concentrations were measured in women with or without labor and their perinatal data were collected. In the postterm pregnancies without labor, the lowest median melatonin concentrations were measured (p<0.05). In the late-term and postterm pregnancies with and without labor, the median serum melatonin concentrations were significantly lower than term ones (p<0.05). In the term pregnancies with labor, the highest median melatonin concentration was measured (p<0.05). A serum melatonin concentration≤34 pg/mL as a cut-off value determines late-term and postterm pregnancy with a sensitivity of 80.4% and a specificity of 81.4%. A serum melatonin concentration>29.35 pg/mL as a cut-off value determines presence of labor with a sensitivity of 82.1% and a specificity of 55.0%. In women with term pregnancies, with the measurement of serum melatonin, it is possible to predict the development of late-term and postterm pregnancies and whether these pregnancies undergo spontaneous labor. With further studies, these findings need to be supported before their routine clinical use.

Key words

Melatonin - postterm pregnancy - late term pregnancy - spontaneous labor

Publication History

Received: 18 October 2020

Accepted after revision: 29 March 2021

Article published online:
31 May 2021

• References

• 1 Nakamura Y, Tamura H, Kashida S. et al. Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy. Pineal Res 2001; 30: 29-33
• 2 Tamura H, Takasaki A, Taketani T. et al. Melatonin and female reproduction. J Obstet Gynaecol Res 2014; 40: 1-11
• 3 Olcese J, Lozier S, Paradise C. Melatonin and the circadian timing of human parturition. Reprod Sci 2013; 20: 168-174
• 4 Schlabritz-Loutsevitch N, Hellner N, Middendorf R. et al. The human myometrium as a target for melatonin. J Clin Endocrinol Metab 2003; 88: 908-913
• 5 Sharkey J, Olcese J. Transcriptional inhibition of oxytocin receptor expression in human myometrial cells by melatonin involves protein kinase C signaling. J Clin Endocrinol Metab 2007; 92: 4015-4019
• 6 McCarthy R, Jungheim ES, Fay JC. et al. Riding the rhythm of melatonin through pregnancy to deliver on time. Front Endocrinol (Lausanne) 2019; 10: 616
• 7 Bates K, Herzog ED. Maternal-fetal circadian communication during pregnancy. Front Endocrinol (Lausanne) 2020; 11: 198
• 8 American College of Obstetricians and Gynecologists. Practice bulletin no. 146: Management of late-term and postterm pregnancies. Obstet Gynecol 2014; 124 (2 Pt 1) 390-396
• 9 Vitale SG, Marilli I, Rapisarda AM. et al. Diagnosis, antenatal surveillance, and management of prolonged pregnancy: current perspectives. Minerva Ginecol 2015; 67: 365-373
• 10 Norwitz ER. Postterm pregnancy. In: Post TW. UpToDate. Waltham: MA; 2020
• 11 Martin JA, Hamilton BE, Osterman MJK. et al. Births: final data for 2017. Natl Vital Stat Rep 2018; 67: 1-50
• 12 Zeitlin J, Blondel B, Alexander S. et al. Variation in rates of postterm birth in Europe: reality or artefact?. BJOG 2007; 114: 1097-1103
• 13 Torricelli M, Novembri R, Voltolini C. et al. Biochemical and biophysical predictors of the response to the induction of labor in nulliparous postterm pregnancy. Am J Obstet Gynecol 2011; 204: 1-6
• 14 Anderka M, Declercq ER, Smith W. A time to be born. Am J Public Health 2000; 90: 124-126
• 15 Timofeev J. Postterm pregnancy. Postgraduate Obstet Gynecol 2011; 31: 8
• 16 American College of Obstetricians and Gynecologists. Practice bulletin Management of postterm pregnancy. Obstet Gynecol 2004; 104: 639-646
• 17 Kadam P, Bhalerao S. Sample size calculation. Int J Ayurveda Res 2010; 1: 55-57
• 18 Wennerholm UB, Saltvedt S, Wessberg A. et al. Induction of labour at 41 weeks versus expectant management and induction of labour at 42 weeks. BMJ 2019; 367: l6131
• 19 Aylamazyan EK, Evsyukova II, Kvetnoy IM. Melatonin: pregnancy and labor. Journal of obstetrics and women's diseases 2014; 63: 67-77
• 20 Galal M, Symonds I, Murray H. et al. Postterm pregnancy. Facts Views Vis Obgyn 2012; 4: 175-187
• 21 Caughey AB. Postterm Pregnancy. 2016 https://emedicine.medscape.com/article/261369-overview
• 22 Masana MI, Dubocovich ML. Melatonin receptor signaling: finding the path through the dark. Sci STKE 2001; 107: 39
• 23 Martensson LG, Andersson RG, Berg G. Melatonin together with noradrenaline augments contractions of human myometrium. Eur J Pharmacol 1996; 316: 273-275
• 24 Olcese J, Beesley S. Clinical significance of melatonin receptors in the human myometrium. Fertil Steril 2014; 102: 329-335
• 25 Karpovitch AE, Inna E, Moiseevich KI. In Melatonin: pregnancy and childbirth. MOJ Curr Res & Rev 2018; 1: 206-210
• 26 Carlomagno G, Minini M, Tilotta M, Unfer V. From implantation to birth: insight into molecular melatonin functions. Int J Mol Sci 2018; 19: 2802
• 27 Casper RF, Gladanac B. Introduction: circadian rhythm and its disruption: impact on reproductive function. Fertil Steril 2014; 102: 319-320
• 28 Rahman SA, Bibbo C, Olcese J. et al. Relationship between endogenous melatonin concentrations and uterine contractions in late third trimester of human pregnancy. J Pineal Res 2019; 66: 12566
• 29 Kosinska-Kaczynska K, Bomba-Opon D, Bobrowska K. et al. Phosphorylated IGFBP-1 in predicting successful vaginal delivery in post-term pregnancy. Arch Gynecol Obstet 2015; 292: 45-52
• 30 Vallikkannu N, Lam WK, Omar SZ. et al. Insulin-like growth factor binding protein 1, Bishop score, and sonographic cervical length: tolerability and prediction of vaginal birth and vaginal birth within 24 hours following labour induction in nulliparous women. BJOG 2017; 124: 1274-1283