Association between Maternal Serum Lipids and Intrapartum Oxytocin Requirements during Labor Induction and Augmentation

Abstract

Objective This study aimed to investigate the relationship between maternal serum lipid parameters and oxytocin requirements among women with term vaginal deliveries.

Study Design In this secondary analysis of a prospective cohort study, women who presented for delivery at ≥37 weeks' gestation and received oxytocin during their labor were included. Maternal serum was collected intrapartum. The cohort was stratified into two groups based on maximum oxytocin infusion dose during labor. Primary outcomes were maternal total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels. Generalized linear regression models were used to assess the association between lipid parameters and maximum oxytocin dose requirements while controlling for potential confounders. For secondary analyses, the cohort was stratified by HDL-C into two groups. Multivariable logistic regression was used to evaluate the relationship between low maternal HDL-C and additional intrapartum oxytocin parameters.

Results There were no differences in maternal total cholesterol, LDL-C, or triglyceride values between high and low maximum oxytocin groups. Median serum HDL-C was significantly lower among women in the high oxytocin group compared with those in the low oxytocin group (56 vs. 62 mg/dL, p < 0.01). For every 0.26 mg/dL lower HDL-C, women had 1 mU/min higher maximum oxytocin infusion dose during labor. Women with low serum HDL-C were also more likely to require maximum oxytocin doses above the 75th percentile (adjusted odds ratio [aOR]: 1.99, 95% confidence interval [CI]: 1.06–3.75) and above the 90th percentile (aOR: 2.47, 95% CI: 1.10–5.54). Among women undergoing induction of labor, low serum HDL-C was also associated with longer duration of oxytocin infusion (aOR: 2.07, 95% CI: 1.02–4.20).

Conclusion Low maternal HDL-C levels at term are associated with higher maximum oxytocin infusion doses among women undergoing labor induction or augmentation. Given the growing prevalence of metabolic syndrome in the United States and persistently high rates of cesarean delivery, HDL-C or its components may present a new target for predicting and improving labor outcomes.

Key Points

• Serum HDL-C at term is inversely correlated with oxytocin infusion doses at term.

• Low maternal serum HDL-C is associated with higher oxytocin requirements during labor induction or augmentation.

• No association between maternal serum total cholesterol, LDL-C, or triglyceride levels and oxytocin requirements in labor.

Keywords

labor - lipids - oxytocin - lipoprotein - uterine contractility

Publikationsverlauf

Eingereicht: 07. Februar 2022

Angenommen: 07. November 2022

Accepted Manuscript online:
16. November 2022

Artikel online veröffentlicht:
27. Dezember 2022

• References

• 1 Murphy SP, Abrams BF. Changes in energy intakes during pregnancy and lactation in a national sample of US women. Am J Public Health 1993; 83 (08) 1161-1163
• 2 Palacín M, Lasunción MA, Asunción M, Herrera E. Circulating metabolite utilization by periuterine adipose tissue in situ in the pregnant rat. Metabolism 1991; 40 (05) 534-539
• 3 Ramos MP, Crespo-Solans MD, del Campo S, Cacho J, Herrera E. Fat accumulation in the rat during early pregnancy is modulated by enhanced insulin responsiveness. Am J Physiol Endocrinol Metab 2003; 285 (02) E318-E328
• 4 Herrera E, Desoye G. Maternal and fetal lipid metabolism under normal and gestational diabetic conditions. Horm Mol Biol Clin Investig 2016; 26 (02) 109-127
• 5 Napoli C, D'Armiento FP, Mancini FP. et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest 1997; 100 (11) 2680-2690
• 6 Wang J, Moore D, Subramanian A. et al. Gestational dyslipidaemia and adverse birthweight outcomes: a systematic review and meta-analysis. Obes Rev 2018; 19 (09) 1256-1268
• 7 Jiang S, Jiang J, Xu H. et al. Maternal dyslipidemia during pregnancy may increase the risk of preterm birth: a meta-analysis. Taiwan J Obstet Gynecol 2017; 56 (01) 9-15
• 8 Klein U, Gimpl G, Fahrenholz F. Alteration of the myometrial plasma membrane cholesterol content with beta-cyclodextrin modulates the binding affinity of the oxytocin receptor. Biochemistry 1995; 34 (42) 13784-13793
• 9 Gimpl G, Burger K, Politowska E, Ciarkowski J, Fahrenholz F. Oxytocin receptors and cholesterol: interaction and regulation. Exp Physiol 2000; 85 (Spec No): 41S-49S
• 10 Gimpl G, Fahrenholz F. Human oxytocin receptors in cholesterol-rich vs. cholesterol-poor microdomains of the plasma membrane. Eur J Biochem 2000; 267 (09) 2483-2497
• 11 Zhang Jie, Kendrick A, Quenby S, Wray S. Contractility and calcium signaling of human myometrium are profoundly affected by cholesterol manipulation: implications for labor?. Reprod Sci 2007; 14 (05) 456-466
• 12 Smith RD, Babiychuk EB, Noble K, Draeger A, Wray S. Increased cholesterol decreases uterine activity: functional effects of cholesterol alteration in pregnant rat myometrium. Am J Physiol Cell Physiol 2005; 288 (05) C982-C988
• 13 Committee on Practice Bulletins—Obstetrics and the American Institute of Ultrasound in Medicine. Practice bulletin no. 175: ultrasound in pregnancy. Obstet Gynecol 2016; 128 (06) e241-e256
• 14 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18 (06) 499-502
• 15 Hosmer DW, Lemeshow S, Sturdivant R. Applied Logistic Regression. 3rd ed. New York, NY: Wiley; 2013
• 16 Hill M, Reed KL, Cohen WR. Oxytocin utilization for labor induction in obese and lean women. J Perinat Med 2015; 43 (06) 703-706
• 17 Roloff K, Peng S, Sanchez-Ramos L, Valenzuela GJ. Cumulative oxytocin dose during induction of labor according to maternal body mass index. Int J Gynaecol Obstet 2015; 131 (01) 54-58
• 18 Carlson NS, Corwin EJ, Lowe NK. Oxytocin augmentation in spontaneously laboring, nulliparous women: multilevel assessment of maternal BMI and oxytocin dose. Biol Res Nurs 2017; 19 (04) 382-392
• 19 Fyfe EM, Rivers KS, Thompson JM. et al; SCOPE consortium. Elevated maternal lipids in early pregnancy are not associated with risk of intrapartum caesarean in overweight and obese nulliparous women. BMC Pregnancy Childbirth 2013; 13: 143
• 20 Bever AM, Mumford SL, Schisterman EF. et al. Maternal preconception lipid profile and gestational lipid changes in relation to birthweight outcomes. Sci Rep 2020; 10 (01) 1374
• 21 Farias DR, Franco-Sena AB, Vilela A, Lepsch J, Mendes RH, Kac G. Lipid changes throughout pregnancy according to pre-pregnancy BMI: results from a prospective cohort. BJOG 2016; 123 (04) 570-578
• 22 Vahratian A, Misra VK, Trudeau S, Misra DP. Prepregnancy body mass index and gestational age-dependent changes in lipid levels during pregnancy. Obstet Gynecol 2010; 116 (01) 107-113
• 23 Roland MCP, Lekva T, Godang K, Bollerslev J, Henriksen T. Changes in maternal blood glucose and lipid concentrations during pregnancy differ by maternal body mass index and are related to birthweight: a prospective, longitudinal study of healthy pregnancies. PLoS One 2020; 15 (06) e0232749
• 24 Oaks BM, Stewart CP, Laugero KD. et al. Maternal plasma cholesterol and duration of pregnancy: a prospective cohort study in Ghana. Matern Child Nutr 2017; 13(04):
• 25 Delisle H, Ntandou G, Sodjinou R, Couillard C, Després JP. At-risk serum cholesterol profile at both ends of the nutrition spectrum in West African adults? The Benin study. Nutrients 2013; 5 (04) 1366-1383
• 26 Mishra M, De Geest B. High-density lipoprotein-targeted therapies for heart failure. Biomedicines 2020; 8 (12) E620
• 27 Coldewey SM, Benetti E, Collino M. et al. Elevation of serum sphingosine-1-phosphate attenuates impaired cardiac function in experimental sepsis. Sci Rep 2016; 6: 27594
• 28 Fuerst E, Foster HR, Ward JP, Corrigan CJ, Cousins DJ, Woszczek G. Sphingosine-1-phosphate induces pro-remodelling response in airway smooth muscle cells. Allergy 2014; 69 (11) 1531-1539
• 29 Rosenfeldt HM, Amrani Y, Watterson KR, Murthy KS, Panettieri Jr RA, Spiegel S. Sphingosine-1-phosphate stimulates contraction of human airway smooth muscle cells. FASEB J 2003; 17 (13) 1789-1799
• 30 Garcia-Verdugo I, Leiber D, Robin P, Billon-Denis E, Chaby R, Tanfin Z. Direct interaction of surfactant protein A with myometrial binding sites: signaling and modulation by bacterial lipopolysaccharide. Biol Reprod 2007; 76 (04) 681-691
• 31 Leiber D, Banno Y, Tanfin Z. Exogenous sphingosine 1-phosphate and sphingosine kinase activated by endothelin-1 induced myometrial contraction through differential mechanisms. Am J Physiol Cell Physiol 2007; 292 (01) C240-C250
• 32 Tanaka S, Couret D, Tran-Dinh A. et al. High-density lipoproteins during sepsis: from bench to bedside. Crit Care 2020; 24 (01) 134
• 33 Chernick D, Zhong R, Li L. The role of HDL and HDL mimetic peptides as potential therapeutics for Alzheimer's disease. Biomolecules 2020; 10 (09) E1276
• 34 Sirtori CR, Ruscica M, Calabresi L, Chiesa G, Giovannoni R, Badimon JJ. HDL therapy today: from atherosclerosis, to stent compatibility to heart failure. Ann Med 2019; 51 (7-8): 345-359
• 35 Carlson NS, Frediani JK, Corwin EJ, Dunlop A, Jones D. Metabolomic pathways predicting labor dystocia by maternal body mass index. AJP Rep 2020; 10 (01) e68-e77
• 36 Grundy SM, Stone NJ, Bailey AL. et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019; 139 (25) e1082-e1143
• 37 Teis A, Cediel G, Amigó N. et al. Particle size and cholesterol content of circulating HDL correlate with cardiovascular death in chronic heart failure. Sci Rep 2021; 11 (01) 3141
• 38 Silliman K, Tall AR, Kretchmer N, Forte TM. Unusual high-density lipoprotein subclass distribution during late pregnancy. Metabolism 1993; 42 (12) 1592-1599
• 39 Silliman K, Shore V, Forte TM. Hypertriglyceridemia during late pregnancy is associated with the formation of small dense low-density lipoproteins and the presence of large buoyant high-density lipoproteins. Metabolism 1994; 43 (08) 1035-1041