The Oxytocin Product Correlates with Total Oxytocin Received during Labor: A Research Methods Study

Abstract

Objective Total dose of oxytocin received during labor is an important variable in studies of human labor but is difficult to calculate. We sought to identify a surrogate measure for total dose of oxytocin received.

Study Design For each subject receiving oxytocin during labor, the oxytocin total dose received in labor was calculated as the area under the curve. Maximal oxytocin infusion rate, total duration of oxytocin infusion, and the product of both, defined as the oxytocin product, were then each correlated with the total dose of oxytocin received using the Pearson's correlation coefficient.

Results Oxytocin dosing data were available from 402 women at Duke and 6,907 women from Pithagore6. The two variables alone, or combined as the oxytocin product, demonstrated a high correlation with the oxytocin total dose (r > 0.7), with the oxytocin product demonstrating the highest (r > 0.9). This was true whether labor was induced or augmented and whether delivery was vaginal or cesarean.

Conclusion The oxytocin product, composed of two easily obtained variables, demonstrated a very high correlation with total oxytocin dose received in labor and represents a simple and accurate surrogate for total dose of oxytocin received during labor. The oxytocin product can be used in clinical studies in which oxytocin dose is an important variable.

Keywords

area under the curve - augmentation of labor - labor - labor induction - oxytocin - pregnancy

Note

This work was presented in part at the 35th Annual Meeting of the Society for Maternal-Fetal Medicine, San Diego, CA, February 2015.

Funding

This work was supported by NIH grant K08-HD070872 to CAG. The Pithagore6 project was funded by the French Ministry of Health under its Clinical Research Hospital Program (contract number 27–35) and the Caisse Nationale d'Assurance Maladie (CNAMTS).

• References

• 1 Leake RD, Weitzman RE, Glatz TH, Fisher DA. Plasma oxytocin concentrations in men, nonpregnant women, and pregnant women before and during spontaneous labor. J Clin Endocrinol Metab 1981; 53 (04) 730-733
• 2 ACOG Committee on Practice Bulletins – Obstetrics. ACOG Practice Bulletin No. 107: induction of labor. Obstet Gynecol 2009; 114 (2 Pt 1): 386-397
• 3 Leake RD, Weitzman RE, Fisher DA. Oxytocin concentrations during the neonatal period. Biol Neonate 1981; 39 (3-4): 127-131
• 4 Seitchik J, Amico J, Robinson AG, Castillo M. Oxytocin augmentation of dysfunctional labor. IV. Oxytocin pharmacokinetics. Am J Obstet Gynecol 1984; 150 (03) 225-228
• 5 Grotegut CA, Feng L, Mao L, Heine RP, Murtha AP, Rockman HA. β-Arrestin mediates oxytocin receptor signaling, which regulates uterine contractility and cellular migration. Am J Physiol Endocrinol Metab 2011; 300 (03) E468-E477
• 6 Crall HD, Mattison DR. Oxytocin pharmacodynamics: effect of long infusions on uterine activity. Gynecol Obstet Invest 1991; 31 (01) 17-22
• 7 Balki M, Cristian AL, Kingdom J, Carvalho JC. Oxytocin pretreatment of pregnant rat myometrium reduces the efficacy of oxytocin but not of ergonovine maleate or prostaglandin F 2 alpha. Reprod Sci 2010; 17 (03) 269-277
• 8 Magalhaes JK, Carvalho JC, Parkes RK, Kingdom J, Li Y, Balki M. Oxytocin pretreatment decreases oxytocin-induced myometrial contractions in pregnant rats in a concentration-dependent but not time-dependent manner. Reprod Sci 2009; 16 (05) 501-508
• 9 Grotegut CA, Paglia MJ, Johnson LN, Thames B, James AH. Oxytocin exposure during labor among women with postpartum hemorrhage secondary to uterine atony. Am J Obstet Gynecol 2011; 204 (01) 56.e1-56.e6
• 10 Belghiti J, Kayem G, Dupont C, Rudigoz RC, Bouvier-Colle MH, Deneux-Tharaux C. Oxytocin during labour and risk of severe postpartum haemorrhage: a population-based, cohort-nested case-control study. BMJ Open 2011; 1 (02) e000514
• 11 Kjaergaard H, Olsen J, Ottesen B, Dykes AK. Incidence and outcomes of dystocia in the active phase of labor in term nulliparous women with spontaneous labor onset. Acta Obstet Gynecol Scand 2009; 88 (04) 402-407
• 12 Oakley RH, Laporte SA, Holt JA, Barak LS, Caron MG. Molecular determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin complexes after receptor endocytosis*. J Biol Chem 2001; 276 (22) 19452-19460
• 13 Grotegut CA, Mao L, Pierce SL, Swamy GK, Heine RP, Murtha AP. Enhanced uterine contractility and stillbirth in mice lacking G protein-coupled receptor kinase 6 (GRK6): implications for oxytocin receptor desensitization. Mol Endocrinol 2016; 30 (04) 455-468
• 14 Deneux-Tharaux C, Dupont C, Colin C. , et al. Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the PITHAGORE6 cluster-randomised controlled trial. BJOG 2010; 117 (10) 1278-1287