Advertisement

Abnormal endothelium-dependent microvascular dilator reactivity in pregnancies complicated by normotensive intrauterine growth restriction

Published:September 17, 2008DOI:https://doi.org/10.1016/j.ajog.2008.07.022

      Objective

      Normotensive intrauterine growth restriction and preeclampsia share a similar placenta pathophysiology, whereas maternal clinical manifestations differ. Clinical symptoms of preeclampsia are partly attributed to vascular endothelial dysfunction, but it is unclear whether this phenomenon plays a role in intrauterine growth restriction. Therefore, we investigated microvascular endothelial function in women with intrauterine growth restriction.

      Study Design

      Laser Doppler fluxmetry was used combined with iontophoresis of acetylcholine and sodium nitroprusside, namely, endothelium-dependent and endothelium-independent vasodilators. We studied 12 women with intrauterine growth restriction and 16 controls in the third trimester of pregnancy. All women had prepregnancy body mass indexes < 26.

      Results

      Acetylcholine-mediated vasodilatation was significantly increased in women with intrauterine growth restriction compared with controls (743% ± 120% vs 390% ± 67%, P = .01); sodium nitroprusside-mediated vasodilatation was not different (360% ± 55% vs 363% ± 65%, P > .99).

      Conclusion

      Nonobese women with normotensive intrauterine growth restriction show abnormal endothelium-dependent microvascular vasodilatation, suggesting endothelial dysfunction as in preeclampsia. Obviously, for the clinical manifestation of preeclampsia additional factors are required, and a role of metabolic syndrome and obesity has been suggested.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • McIntire D.D.
        • Bloom S.L.
        • Casey B.M.
        • Leveno K.J.
        Birth weight in relation to morbidity among newborn infants.
        N Engl J Med. 1999; 340: 1234-1238
        • Garite T.J.
        • Clark R.
        • Thorp J.A.
        Intrauterine growth restriction increases morbidity and mortality among premature neonates.
        Am J Obstet Gynecol. 2004; 191: 481-487
        • Lubchenco L.O.
        • Hansman C.
        • Boyd E.
        Intrauterine growth as estimated from live born birth-weight data at 24-42 weeks of gestation.
        Pediatrics. 1963; 32: 793-800
        • Resnik R.
        Intrauterine growth restriction.
        Obstet Gynecol. 2002; 99: 490-496
        • Wollmann H.A.
        Intrauterine growth restriction: definition and etiology.
        Horm Res. 1998; 49: 1-6
        • Aardema M.W.
        • Oosterhof H.
        • Timmer A.
        • van Rooy I.
        • Aarnoudse J.G.
        Uterine artery Doppler flow and uteroplacental vascular pathology in normal pregnancies and pregnancies complicated by preeclampsia and small for gestational age fetuses.
        Placenta. 2001; 22: 405-411
        • Ness R.B.
        • Sibai B.M.
        Shared and disparate components of the pathophysiologies of fetal growth restriction and preeclampsia.
        Am J Obstet Gynecol. 2006; 195: 40-49
        • Villar J.
        • Carroli G.
        • Wojdyla D.
        • et al.
        Preeclampsia, gestational hypertension and intrauterine growth restriction, related or independent conditions?.
        Am J Obstet Gynecol. 2006; 194: 921-931
        • Goswami D.
        • Tannetta D.S.
        • Magee L.A.
        • et al.
        Excess syncytiotrophoblast microparticle shedding is a feature of early-onset pre-eclampsia but not normotensive intrauterine growth restriction.
        Placenta. 2006; 27: 56-61
        • Mayhew T.M.
        • Ohadike C.
        • Baker P.N.
        • Crocker I.P.
        • Mitchell C.
        • Ong S.S.
        Stereological investigation of placental morphology in pregnancies complicated by pre-eclampsia with and without intrauterine growth restriction.
        Placenta. 2003; 24: 219-226
        • Khong T.Y.
        • de Wolf F.
        • Robertson W.B.
        • Brosens I.
        Inadequate maternal vascular response to placentation in pregnancies complicated by preeclampsia and by small-for gestational age infants.
        Br J Obstet Gynaecol. 1986; 93: 1049-1059
        • Sheppard B.L.
        • Bonnar J.
        An ultrastructural study of utero-placental spiral arteries in hypertensive and normotensive pregnancy and fetal growth retardation.
        Br J Obstet Gynaecol. 1981; 88: 695-705
        • Roberts J.M.
        • Cooper D.W.
        Pathogenesis and genetics of pre-eclampsia.
        Lancet. 2001; 357: 53-56
        • Sibai B.
        • Dekker G.
        • Kupferminc M.
        Pre-eclampsia.
        Lancet. 2005; 365: 785-799
        • Corretti M.C.
        • Anderson T.J.
        • Benjamin E.J.
        • et al.
        Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force.
        J Am Coll Cardiol. 2002; 39: 257-265
        • Raitakari O.T.
        • Celermajer D.S.
        Flow-mediated dilatation.
        Br J Clin Pharmacol. 2000; 50: 397-404
        • Savvidou M.D.
        • Hingorani A.D.
        • Tsikas D.
        • Frölich J.C.
        • Vallance P.
        • Nicolaides K.H.
        Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia.
        Lancet. 2003; 361: 1511-1517
        • Yoshida A.
        • Nakao S.
        • Kobayashi M.
        • Kobayashi H.
        Flow-mediated vasodilation and plasma fibronectin levels in preeclampsia.
        Hypertension. 2000; 36: 400-404
        • Chambers J.C.
        • Fusi L.
        • Malik I.S.
        • Haskard D.O.
        • de Swiet M.
        • Kooner J.S.
        Association of maternal endothelial dysfunction with preclampsia.
        JAMA. 2001; 285: 1607-1612
        • Khan F.
        • Belch J.J.
        • Macleod M.
        • Mires G.
        Changes in endothelial function precede the clinical disease in women in whom preeclampsia develops.
        Hypertension. 2005; 46: 1123-1128
        • Blaauw J.
        • Graaff R.
        • van Pampus M.G.
        • et al.
        Abnormal endothelium-dependent microvascular reactivity in recently preeclamptic women.
        Obstet Gynecol. 2005; 105: 626-632
        • Davis R.R.
        • Ponnampalam J.
        • Hayman R.
        • Baker P.N.
        • Arulkumaran S.
        • Donnelly R.
        Microvascular vasodilator response to acetylcholine is increased in women with pre-eclampsia.
        BJOG. 2001; 108: 610-614
        • Blaauw J.
        • van Pampus M.G.
        • Rakhorst G.
        • Aarnoudse J.G.
        Endothelium-dependent and -independent vasodilatation in preeclampsia and HELLP syndrome.
        Am J Obstet Gynecol. 2006; (Abstract 468)
        • Kloosterman G.J.
        On intrauterine growth.
        Int J Gynaecol Obstet. 1970; 8: 895-912
        • Snijders R.J.M.
        • Nicolaides K.H.
        Fetal biometry at 14-40 weeks' gestation.
        Ultrasound Obstet Gynecol. 1994; 4: 34-48
        • Achaya G.
        • Wilsgaard T.
        • Berntsen G.K.R.
        • Maltau J.M.
        • Kiserud T.
        Reference ranges for serial measurements of umbilical artery Doppler indices in the second half of pregnancy.
        Am J Obstet Gynecol. 2005; 192: 937-944
        • Morris S.J.
        • Shore A.C.
        • Tooke J.E.
        Responses of the skin microcirculation to acetylcholine and sodium nitroprusside in patients with NIDDM.
        Diabetologia. 1995; 38: 1337-1344
        • Serne E.H.
        • Stehouwer C.D.
        • ter Maaten J.C.
        • et al.
        Microvascular function relates to insulin sensitivity and blood pressure in normal subjects.
        Circulation. 1999; 99: 896-902
        • de Jongh R.T.
        • Serne E.H.
        • IJzerman R.G.
        • et al.
        Impaired microvascular function in obesity: implications for obesity-associated microangiopathy, hypertension, and insulin resistance.
        Circulation. 2004; 109: 2529-2535
        • Kernick D.P.
        • Tooke J.E.
        • Shore A.C.
        The biological zero signal in laser Doppler fluximetry: origins and practical implications.
        Pflugers Arch. 1999; 437: 624-631
        • Nienhuis H.L.
        • de Leeuw K.
        • Smit A.J.
        • et al.
        Enhanced endothelium-dependent microvascular responses in patients with Wegener's granulomatosis.
        J Rheumatol. 2007; 34: 1875-1881
        • Johnson M.R.
        • Anim-Nyame N.
        • Johnson P.
        • Sooranna S.R.
        • Steer P.J.
        Does endothelial cell activation occur with intrauterine growth restriction?.
        BJOG. 2002; 109: 836-839
        • Ramsay J.E.
        • Ferrell W.R.
        • Crawford L.
        • Wallace A.M.
        • Greer I.A.
        • Sattar N.
        Divergent metabolic and vascular phenotypes in pre-eclampsia and intrauterine growth restriction: relevance of adiposity.
        J Hypertens. 2004; 22: 2177-2183
        • Myers J.
        • Mires G.
        • Macleod M.
        • Baker P.
        In preeclampsia, the circulating factors capable of altering in vitro endothelial function precede clinical disease.
        Hypertension. 2005; 45: 258-263
        • Agewall S.
        • Henareh L.
        • Kublickiene K.
        Endothelial function in conduit and resistance artreries in men with coronary disease.
        Atherosclerosis. 2006; 184: 130-136
        • Clapp B.R.
        • Hirschfield G.M.
        • Storry C.
        Inflammation and endothelial function: direct vascular effects of human C-reactive protein on nitric oxide bioavailability.
        Circulation. 2005; 111: 1530-1536
        • Furchgott R.F.
        • Zawadzki J.V.
        The obligatory role of endothelial cell in the relaxation of arterial smooth muscle by acetylcholine.
        Nature. 1980; 288: 373-376
        • Luksha L.
        • Nisell H.
        • Kublickiene K.
        The mechanism of EDHF-mediated responses in subcutaneous small arteries from healthy pregnant women.
        Am J Physiol Reg Integr Comp Physiol. 2004; 286: R1102-R1109
        • Gori T.
        • Di Stolfo G.
        • Sicuro S.
        • et al.
        Correlation analysis between different parameters of conduit artery and microvascular vasodilation.
        Clin Hemorheol Microcirc. 2006; 35: 509-515
        • Houben A.J.
        • de Leeuw P.W.
        • Peeters L.L.
        Configuration of the microcirculation in pre-eclampsia: possible role of the venular system.
        J Hypertens. 2007; 25: 1665-1670
        • Vollebregt K.C.
        • Boer K.
        • Mathura K.R.
        • de Graaff J.C.
        • Ubbink D.T.
        • Ince C.
        Impaired vascular function in women with pre-eclampsia observed with orthogonal polarisation spectral imaging.
        BJOG. 2001; 108: 1148-1153
        • O'Brien T.E.
        • Ray J.G.
        • Chan W.S.
        Maternal body mass index and the risk of preeclampsia: a systematic review.
        Epidemiology. 2003; 14: 368-374