Inflammation and Cardiovascular Risk in Women with Preterm Labor

Abstract

Background:

Women with a history of preterm delivery have about twice the normal risk of cardiovascular disease (CVD). Mechanisms underlying this association are not well understood. The aim of the present study was to evaluate the relationships between selected metabolic CVD risk factors and markers of both systemic inflammation and endothelial dysfunction in women with spontaneous preterm labor (sPL).

Methods:

This was a case-control study in a university tertiary referral center. Forty pregnant women with sPL were compared to 50 controls during gestation. Maternal serum triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, glycemia, insulinemia, homeostasis model assessment (HOMA), leptin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), selectin, and myeloperoxidase (MPO) were measured.

Results:

Gestational age at study was similar in both groups (31.56±3.14 weeks of gestation vs. 31.27±2.14 weeks of gestation, p=0.62, for the control and the sPL groups, respectively). Body mass index (BMI) (21.72±2.99 vs. 23.56±3.80, p=0.01), all cholesterol fractions (HDL-C 53.44±18.22 vs. 68.32±18.38, p=0.0003; LDL-C 125.71±35.56 vs. 142.15±36.07, p=0.03, and total cholesterol 219.55±32.29 vs. 240.38±40.01, p=0.009) and MPO (3.07±0.63 vs. 3.48±0.32, p=0.0009) were significantly lower in women with sPL. Serum levels of IL-6 (0.61±0.46 vs. 0.33±0.46, p=0.007) and the ratio of total cholesterol/HDL-C (4.52±1.48 vs. 3.77±1.37, p=0.01) were significantly increased and correlated each other (r=0.21, p=0.04). Logistic regression showed that the best predictive model for sPL (R ²=0.36, p=0.001) included BMI and total cholesterol.

Conclusions:

A combination of low maternal BMI, low cholesterol levels, and high total cholesterol/HDL-C ratio is present in women with sPL and is related to inflammation.

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References

Smith

GCS

, Pell

, Walsh

. Pregnancy complications and maternal risk of ischaemic heart disease: A retrospective cohort study of 129, 290 births. Lancet, 2001; 357:2002–2006.

Davey-Smith

, Whitley

, Gissler

, Hemminki

. Birth dimensions of offspring, premature birth, and the mortality of mother. Lancet, 2000; 356:2066–2067.

Catov

, Newman

, Roberts

et al. Preterm delivery and later maternal cardiovascular disease risk. Epidemiology, 2007; 18:733–739.

Freibert

, Mannino

, Bush

, Crofford

. The association of adverse pregnancy events and cardiovascular disease in women 50 years of age and older. J Womens Health, 2011; 20:287–293.

Guzick

, Winn

. The association of chorioamnionitis with preterm delivery. Obstet Gynecol, 1985; 65:11–16.

Polzin

, Brady

. The etiology of premature rupture of the membranes. Pitkin

, Scott

. Clinical obstetrics and gynecology. Philadelphia Lippincot Williams & Wilkins, 1998; 4:810–816.

Thomson

, Telfer

, Young

et al. Leukocytes infiltrate the myometrium during human parturition: Further evidence that labor is an inflammatory process. Hum Reprod, 1999; 14:229–236.

Ridker

, Hennekens

, Buring

, Rifai

. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med, 2000; 342:836–843.

Lorenzo

, Okoloise

, Williams

, Stern

, Haffner

. The metabolic syndrome as predictor of type 2 diabetes. The San Antonio Heart Study. Diabetes Care, 2003; 26:3153–3159.

10.

Catov

, Bodnar

, Kip

et al. Early pregnancy lipid concentrations and spontaneous preterm birth. Am J Obstet Gynecol, 2007; 197:610.

11.

vanLeeuwen

, Heezius

, Dallinga

et al. Lipoprotein metabolism in patients with severe sepsis. Crit Care Med, 2003; 31:1359–1366.

12.

Catov

, Bodnar

, Ness

, Barron

, Roberts

. Inflammation and dyslipidemia related to risk of spontaneous preterm birth. Am J Epidemiol, 2007; 166:1312–1319.

13.

Edison

, Berg

, Remaley

et al. Adverse birth outcome among mothers with low serum cholesterol. Pediatrics, 2007; 120:723–733.

14.

Khoury

, Henriksen

, Seljeflot

, Mørkrid

, Frøslie

, Tonstad

. Effects of an antiatherogenic diet during pregnancy on markers of maternal and fetal endothelial activation and inflammation: The CARRDIP study. Br J Obstet Gynaecol, 2007; 114:279–288.

15.

Khoury

, Henriksen

, Christophersen

, Tonstad

. Effect of a cholesterol-lowering diet on maternal, cord, and neonatal lipids, and pregnancy outcome: A randomized clinical trial. Am J Obstet Gynecol, 2005; 193:1292–1301.

16.

Catov

, Ness

, Wellons

, Jacobs

, Roberts

, Gunderson

. Prepregnancy lipids related to preterm birth risk: The Coronary Artery Risk Development in Young Adults study. J Clin Endocrinol Metab, 2010; 95:3711–3718.

17.

Romero

, Chaiworapongsa

, Espinoza

. Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome. J Nutr, 2003; 133,Suppl 2:1668S–1673S

18.

Gomez

, Romero

, Edwin

, David

. Pathogenesis of preterm labor and preterm premature rupture of membranes associated with intra-amniotic infection. Infect Dis Clin North Am, 1997; 11:135–176.

19.

Alvarez de la Rosa

, Rebollo

, Codoceo

, Gonzalez Gonzalez

. Maternal serum interleukin 1, 2, 6, 8 and interleukin-2 receptor levels in preterm labor and delivery. Eur J Obstet Gynecol Reprod Biol, 2000; 88:57–60.

20.

Škrablin

, Lovrić

, Banović

, Kralik

, Dijaković

, Kalafatić

. Maternal plasma interleukin-6, interleukin-1β and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery. J Matern Fetal Neonatal Med, 2007; 20:335–341.

21.

Bahar

, Ghalib

, Moosa

, Zaki

ZMS

, Thomas

, Nabri

. Maternal serum interleukin-6, interleukin-8, tumor necrosis factor-α and interferon-γ in preterm labor. Acta Obstet Gynecol Scand, 2003; 82:543–549.

22.

Curry

, Vogel

, Drews

et al. Mid-pregnancy maternal plasma levels of interleukin 2, 6, and 12, tumor necrosis factor-alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor and spontaneous preterm delivery. Acta Obstet Gynecol Scand, 2007; 86:1103–1110.

23.

Rein

, Saely

, Beer

, Vonbank

, Drexel

. Roles of the metabolic syndrome, HDL cholesterol, and coronary atherosclerosis in subclinical inflammation. Diabetes Care, 2010; 33:1853–1855.

24.

Rohrer

, Hersberger

, von Eckardstein

. High density lipoproteins in the intersection of diabetes mellitus, inflammation and cardiovascular disease. Curr Opin Lipidol, 2004; 15:269–278.

25.

Liuba

, Persson

, Luoma

et al. Acute infections in children are accompanied by oxidative modification of LDL and decrease of HDL cholesterol, and are followed by thickening of carotid intima-media. Eur Heart J, 2003; 24:515–521.

26.

Steinborn

, Sohn

, Scharf

, Geka

, Heger

, Kaufmann

. Serum intercellular adhesion molecule-1 levels and histologic chorioamnionitis. Obstet Gynecol, 2000; 95:671–676.

27.

Prokopenko

, Aleshina

, Frolova

, Anan'eva

, Kokriakov

, Arutiunian

. Myeloperoxidase in the human placenta at preterm labor. Vopr Med Khim, 2002; 48:378–380.

28.

Simhan

, Bodnar

. Prepregnancy body mass index, vaginal inflammation, and the racial disparity in preterm birth. Am J Epidemiol, 2006; 163:459–466.

29.

Ehrenberg

, Dierker

, Milluzzi

, Mercer

. Low maternal weight, failure to thrive in pregnancy, and adverse pregnancy outcomes. Am J Obstet Gynecol, 2003; 189:1726–1730.

30.

Meis

, Michielutte

, Peters

et al. Factors associated with preterm birth in Cardiff, Wales. II. Indicated and spontaneous preterm birth. Am J Obstet Gynecol, 1995; 173:597–602.

31.

Wise

, Palmer

, Heffner

, Rosenberg

. Prepregnancy body size, gestational weight gain, and risk of preterm birth in African-American women. Epidemiology, 2010; 21:243–252

32.

Bartha

, González-Bugatto

, Fernández-Macías

, González-González

, Comino-Delgado

, Hervías-Vivancos

. Metabolic syndrome in normal and complicated pregnancies. Eur J Obstet Gynecol Reprod Biol, 2008; 137:178–184.

33.

Catov

, Dodge

, Yamal

, Roberts

, Piller

, Ness

. Prior preterm or small-for-gestational-age birth related to maternal metabolic syndrome. Obstet Gynecol, 2011; 117:225–232.