Autonomic Dysfunction in Preeclampsia: A Systematic Review

Dalia Yousif, Ioannis Bellos, Ana Isabel Penzlin, Mido Max Hijazi, Ben Min-Woo Illigens, Alexandra Pinter, Timo Siepmann, Dalia Yousif, Ioannis Bellos, Ana Isabel Penzlin, Mido Max Hijazi, Ben Min-Woo Illigens, Alexandra Pinter, Timo Siepmann

Abstract

Background: Preeclampsia (PE) is a major obstetric complication that leads to severe maternal and fetal morbidity. Early detection of preeclampsia can reduce the severity of complications and improve clinical outcomes. It is believed that the autonomic nervous system (ANS) is involved in the pathogenesis of PE. We aimed to review the current literature on the prevalence and nature of ANS dysfunction in women with PE and the possible prognostic value of ANS testing in the early detection of PE. Methods: Literature search was performed using Medline (1966-2018), EMBase (1947-2018), Google Scholar (1970-2018), BIOSIS (1926-2018), Web of science (1900-2018); CINAHL (1937-2018); Cochrane Library, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL) and Cochrane Methodology Register (1999-2018). Additionally, the reference lists of articles included were screened. Results: A total of 26 studies were included in the present review presenting data of 1,854 pregnant women. Among these women, 453 were diagnosed with PE, 93.6% (424/453) of which displayed autonomic dysfunction. ANS function was assessed by cardiovascular reflex tests (n = 9), heart rate variability (n = 11), cardiac baroreflex gain (n = 5), muscle sympathetic nerve activity (MSNA) (n = 3), and biomarkers of sympathetic activity (n = 4). Overall, 21 studies (80.8%) reported at least one of the following abnormalities in ANS function in women diagnosed with PE compared to healthy pregnant control women: reduced parasympathetic activity (n = 16/21, 76%), increased sympathetic activity (n = 12/20, 60%), or reduced baroreflex gain (n = 4/5, 80%). Some of these studies indicated that pressor and orthostatic stress test may be useful in early pregnancy to help estimate the risk of developing PE. However, autonomic function tests seem not to be able to differentiate between mild and severe PE. Conclusions: Current evidence suggests that autonomic dysfunction is highly prevalent in pre-eclamptic women. Among autonomic functions, cardiovascular reflexes appear to be predominantly affected, seen as reduced cardiac parasympathetic activity and elevated cardiac sympathetic activity. The diagnostic value of autonomic testing in the prediction and monitoring of autonomic failure in pre-eclamptic women remains to be determined.

Keywords: autonomic nervous system modulation; baroreflex sensitivity; heart rate variability; muscle sympathetic nerve activity; parasympathetic activity; preeclampsia; sympathetic activity.

Figures

Figure 1
Figure 1
PRISMA diagram showing systematic search process, which started with 4,947 articles identified through searching Medline, EMBase, BIOSIS, Web of Science, CINAHL, and the entire Cochrane Library in addition to 136 articles retrieved from the references list of the selected studies. Duplicate articles were excluded. From 168 articles screened, 123 articles were excluded because they didn't meet the inclusion criteria (animal studies, letter to the editor, case reports). The number of full articles assessed for eligibility was 45, of which 19 articles were found not- eligible due to lacking a PE group, lacking a healthy control group or including non pregnant women with history of PE. Finally, 26 studies were found eligible for inclusion in our review.

References

    1. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. (2009) 33:130–7. 10.1053/j.semperi.2009.02.010
    1. ACOG practice bulletin No 202 summary. (2019). Obstet Gynecol. 133:211–4. 10.1097/aog.0000000000003019
    1. Tranquilli AL, Landi B, Giannubilo SR, Sibai BM. Preeclampsia: no longer solely a pregnancy disease. Pregnancy Hypertens. (2012) 2:350–7. 10.1016/j.preghy.2012.05.006
    1. O'Tierney-Ginn PF, Lash GE. Beyond pregnancy: modulation of trophoblast invasion and its consequences for fetal growth and long-term children's health. J Reproduct Immunol. (2014) 104–105:37–42. 10.1016/j.jri.2014.04.002
    1. Townsend R, O'Brien P, Khalil A. Current best practice in the management of hypertensive disorders in pregnancy. Integrat Blood Pressure Control. (2016) 9:79–94. 10.2147/IBPC.S77344
    1. Benyo DF, Miles TM, Conrad KP. Hypoxia stimulates cytokine production by villous explants from the human placenta. J Clin Endocrinol Metabol. (1997) 82:1582–8. 10.1210/jc.82.5.1582
    1. Veerbeek JH, Brouwers L, Koster MP, Koenen SV, van Vliet EO, Nikkels PG, et al. . Spiral artery remodeling and maternal cardiovascular risk. J Hypertens. (2016) 34:1570–7. 10.1097/HJH.0000000000000964
    1. Karumanchi SA, Granger JP. Preeclampsia and pregnancy-related hypertensive disorders. Hypertension. (2016) 67:238–42. 10.1161/HYPERTENSIONAHA.115.05024
    1. Heiskanen N, Saarelainen H, Valtonen P, Lyyra-Laitinen T, Laitinen T, Vanninen E, et al. . Blood pressure and heart rate variability analysis of orthostatic challenge in normal human pregnancies. Clin Physiol Funct Imag. (2008) 28:384–90. 10.1111/j.1475-097X.2008.00818.x
    1. Ekholm EM, Piha SJ, Erkkola RU, Antila KJ. Autonomic cardiovascular reflexes in pregnancy. a longitudinal study. Clin Autonom Res. (1994) 4:161–65. 10.1007/BF01826181
    1. Thayer JF, Yamamoto SS, Brosschot JF. The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors. Int J Cardiol. (2010) 141:122–31. 10.1016/j.ijcard.2009.09.543
    1. Robbe HW, Mulder LJ, Rüddel H, Langewitz WA, Veldman JB, Mulder G. Assessment of baroreceptor reflex sensitivity by means of spectral analysis. Hypertension. (1987) 10:538–43. 10.1161/01.HYP.10.5.538
    1. Ewing DJ, Martyn CN, Young RJ, Clarke BF. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care. (1985) 8:491–8. 10.2337/diacare.8.5.491
    1. Camm AJM, Malik JT, Bigger G, Breithardt S, Cerutti RJ, Cohen P, et al. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task force of the European society of cardiology and the north American society of pacing and electrophysiology. Circulation. (1996) 93:1043–65. 10.1161/01.CIR.93.5.1043
    1. Kingwell BA, Thompson JM, Kaye DM, McPherson GA, Jennings GL, Esler MD. Heart rate spectral analysis, cardiac norepinephrine spillover, and muscle sympathetic nerve activity during human sympathetic nervous activation and failure. Circulation. (1994) 90:234–40. 10.1161/01.CIR.90.1.234
    1. Shaffer F, Ginsberg JP. An overview of heart rate variability metrics and norms. Front Public Health. (2017) 5:258. 10.3389/fpubh.2017.00258
    1. Morris MJ, Russell AE, Kapoor V, Cain MD, Elliott JM, West MJ, et al. . Increases in plasma neuropeptide y concentrations during sympathetic activation in man. J Auton Nerv Syst. (1986) 17:143–9. 10.1016/0165-1838(86)90089-5
    1. Freeman R. Assessment of cardiovascular autonomic function. Clin Neurophysiol. (2006) 117:716–30. 10.1016/j.clinph.2005.09.027
    1. Grassi G, Esler M. How to assess sympathetic activity in humans. J Hypertens. (1999) 17:719–34. 10.1097/00004872-199917060-00001
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses : the PRISMA statement. Int J Surg. (2010) 8:336–41. 10.1016/j.ijsu.2010.02.007
    1. Egerman RS, Andersen RN, Manejwala FM, Baha M. Neuropeptide Y and nitrite levels in preeclamptic and normotensive gravid women. Am J Obstet Gynecol. (1999) 181:921–23. 10.1016/S0002-9378(99)70326-1
    1. Manyonda IT, Obstetrician C, Slater C. A role for noradrenaline in pre-eclampsia : towards a unifying hypothesis for the pathophysiology. Br J Obstet Gynaecol. (1998) 105:641–48. 10.1111/j.1471-0528.1998.tb10179.x
    1. Øian P, Kjeldsen SE, Eide I, Maltau JM. Increased arterial catecholamines in pre-eclampsia. Acta Obstet Gynecol Scand. (1986) 65:613–7. 10.3109/00016348609158398
    1. Beilin LJ, Deacon J, Michael CA, Vandongen R, Lalor CM, Barden AE, et al. . Diurnal rhythms of blood pressure, plasma renin activity, angiotensin ii and catecholamines in normotensive and hypertensive pregnancies. Clin Exp Hypertens. (1983) 2:271–93. 10.3109/10641958309006086
    1. Chaswal M, Kapoor R, Batra A, Verma S, Yadav BS. Heart rate variability and cardiovascular reflex tests for assessment of autonomic functions in preeclampsia. Int J Hypertens. (2018) 2018:8163824. 10.1155/2018/8163824
    1. Lakhno I. Autonomic imbalance captures maternal and fetal circulatory response to pre-eclampsia. Clini Hypertens. (2017) 23:5. 10.1186/s40885-016-0061-x
    1. Musa SM, Adam I, Lutfi MF. Heart rate variability and autonomic modulations in preeclampsia. PLoS ONE. (2016) 11:152704. 10.1371/journal.pone.0152704
    1. Flood P, McKinley P, Monk C, Muntner P, Colantonio LD, Goetzl L, et al. . Beat-to-beat heart rate and blood pressure variability and hypertensive disease in pregnancy. Am J Perinatol. (2015) 32:1050–8. 10.1055/s-0035-1548542
    1. Yokuşoglu M, Dede M, Uzun M, Baysan O, Köz C, Cemal Yenen M, et al. Cardiac autonomic balance is impaired in preeclampsia. Turkiye Klinikleri J Med Sci. (2009) 29:605–10.
    1. Swansburg ML, Brown CA, Hains SM, Smith GN, Kisilevsky BS. Maternal cardiac autonomic function and fetal heart rate in preeclamptic compared to normotensive pregnancies. Can J Cardiovasc Nurs. (2005) 15:42–52.
    1. Rang S, Wolf H, van Montfrans GA, Karemaker JM. Serial assessment of cardiovascular control shows early signs of developing pre-eclampsia. J Hypertens. (2004) 22:369–76. 10.1097/00004872-200402000-00022
    1. Miyake Y, Ohnishi M, Fujii TK, Yamamoto T, Yoneda C, Takahashi S, et al. . The effects of postural changes of Baroreflex gain in normal and hypertensive pregnancies. Clin Exp Hypertens. (2002) 24:23–31. 10.1081/CEH-100108712
    1. Woisetschläger C, Waldenhofer U, Bur A, Herkner H, Kiss H, Binder M, et al. . Increased blood pressure response to the cold pressor test in pregnant women developing pre-eclampsia. J Hypertens. (2000) 18:399–403. 10.1097/00004872-200018040-00007
    1. Yang CC, Chao TC, Kuo TB, Yin CS, Chen HI. Preeclamptic pregnancy is associated with increased sympathetic and decreased parasympathetic control of HR. Am J Physiol Heart Circ Physiol. (2000) 278:1269–73. 10.1152/ajpheart.2000.278.4.H1269
    1. Lewinsky RM, Riskin-Mashiah S. Autonomic imbalance in preeclampsia: evidence for increased sympathetic tone in response to the supine-pressor test. Obstetrics Gynecol. (1998) 91:935–9. 10.1097/00006250-199806000-00011
    1. Eneroth E, Storck N. Preeclampsia and maternal heart rate variability. Gynecol Obstetric Invest. (1998) 45:170–3. 10.1159/000009949
    1. Ahmad HR, Akhtar S, Khan MA, Khan KS, Qureshi AA, Romana H, et al. . Dynamic and steady state response of heart rate to orthostatic stress in normotensive and hypertensive pregnant women. Eur J Obstet Gynecol Reprod Biol. (1996) 66:31–7.
    1. Airaksinen KE, Kirkinen P, Takkunen JT. Autonomic nervous dysfunction in severe pre-eclampsia. Eur J Obstetr Gynecol Reproduct Biol. (1985) 19:269–76. 10.1016/0028-2243(85)90040-1
    1. Fischer T, Schobel HP, Frank H, Andreae M, Schneider KT, Heusser K. Pregnancy-induced sympathetic overactivity: a precursor of preeclampsia. Euro J Clin Invest. (2004) 34:443–8. 10.1111/j.1365-2362.2004.01350.x
    1. Greenwood JP, Scott EM, Walker JJ, Stoker JB, Mary DA. The magnitude of sympathetic hyperactivity in pregnancy-induced hypertension and preeclampsia. Am J Hypertens. (2003) 16:194–99. 10.1016/S0895-7061(02)03256-9
    1. Schobel HP, Fischer T, Heuszer K, Geiger H, Schmieder RE. Preeclampsia—a state of sympathetic overactivity. New Engl J Med. (1996) 335:1480–5. 10.1056/NEJM199611143352002
    1. Weber TM, Lackner HK, Roessler A, Papousek I, Kolovetsiou-Kreiner V., Lucovnik M, et al. . Heart rate variability and baroreceptor reflex sensitivity in early- versus late-onset preeclampsia. PLoS ONE. (2017) 12:e0186521. 10.1371/journal.pone.0186521
    1. Faber R, Baumert M, Stepan H, Wessel N, Voss A, Walther T. Baroreflex sensitivity, heart rate, and blood pressure variability in hypertensive pregnancy disorders. J Human Hypertens. (2004) 18:707–12. 10.1038/sj.jhh.1001730
    1. Silver HM, Tahvanainen KUO, Kuusela TA, Eckberg DL. Comparison of vagal baroreflex function in nonpregnant women and in women with normal pregnancy, preeclampsia, or gestational hypertension. Am J Obstet Gynecol. (2001) 184:1189–95. 10.1067/mob.2001.112871
    1. Molino P, Veglio F, Genova GC, Melchio R, Benedetto C, Chiarolini L, et al. . Baroreflex control of heart rate is impaired in pre-eclampsia. J Human Hypertens. (1999) 13:179–83. 10.1038/sj.jhh.1000789
    1. Seligman SA. Baroreceptor reflex function in pre-eclampsia. J Obstetr Gynaecol Br Commonwealth. (1971) 78:413–16. 10.1111/j.1471-0528.1971.tb00294.x
    1. Davey DA, MacGillivray I. The classification and definition of the hypertensive disorders of pregnancy. Am J Obstet Gynecol. (1988) 158:892–8. 10.1016/0002-9378(88)90090-7
    1. Report of the national high blood pressure education program working group on high blood pressure in pregnancy Am J Obstet Gynecol. (2000) 183:S1–22. 10.1067/mob.2000.107928
    1. Roberts JM, August PA, Bakris G, Barton JR, Bernstein IM, Druzin M, et al. (2013). Hypertension in pregnancy. Obstetr Gynecol. 122:1122–31. 10.1097/01.AOG.0000437382.03963.88
    1. Rang S, Wolf H, Montfrans GA, Karemaker JM. Non–invasive assessment of autonomic cardiovascular control in normal human pregnancy and pregnancy- associated hypertensive disorders. J Hypertens. (2002) 20:2111–9. 10.1097/00004872-200211000-00002
    1. Voss A, Baumert M, Baier V, Stepan H, Walther T, Faber R. Autonomic cardiovascular control in pregnancies with abnormal uterine perfusion. Am J Hypertens. (2006) 19:306–12. 10.1016/j.amjhyper.2005.08.008
    1. Schobel HP, Fischer T, Heuszer K, Geiger H, Schmieder RE. Preeclampsia—a state of sympathetic overactivity. Obstet Gynecol Survey. (1997) 52:211–2. 10.1097/00006254-199704000-00002
    1. Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al. (2004). The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analysis. Available online at: . (accessed February 26, 2018).
    1. McDonald SD, Malinowski A, Zhou Q, Yusuf S, Devereaux PJ. (2008). Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses. Am Heart J. 156:918–30. 10.1016/j.ahj.2008.06.042
    1. Lazdam M, Davis EF, Lewandowski AJ, Worton SA, Kenworthy Y, Kelly B, et al. . Prevention of vascular dysfunction after preeclampsia: a potential long-term outcome measure and an emerging goal for treatment. J Pregnancy. (2012) 2012:704146. 10.1155/2012/704146
    1. Siepmann T, Boardman H, Bilderbeck A, Griffanti L, Kenworthy Y, Zwager C, et al. . Long-term cerebral white and gray matter changes after preeclampsia. Neurology. (2017) 88:1256–64. 10.1212/WNL.0000000000003765
    1. Spradley FT. Sympathetic nervous system control of vascular function and blood pressure during pregnancy and preeclampsia. J Hypertens. (2018) 37:476–87. 10.1097/HJH.0000000000001901
    1. Rangaswami J, Naranjo M, McCullough PA. Preeclampsia as a form of type 5 cardiorenal syndrome: an underrecognized entity in women's cardiovascular health. Cardiorenal Med. (2018) 8:160–72. 10.1159/000487646
    1. Fu Q, Levine BD. Autonomic circulatory control during pregnancy in humans. Semin Reprod Med. (2009) 27:330–7. 10.1055/s-0029-1225261
    1. Ruprai R, Ghuge S. A comparative study of autonomic function tests (sympathetic and parasympathetic) in three trimesters of pregnancy. Int J Med Sci Public Health. (2017) 6:139–42. 10.5455/ijmsph.2017.08072016574
    1. Zhou SS, Zhou YM, Li D, Chen NN. Preeclampsia and future cardiovascular risk: a point of view from the clearance of plasma vasoactive amines. Hypertens Pregnancy. (2016) 35:1–14. 10.3109/10641955.2015.1115062
    1. Redman CW, Sargent IL. Placental stress and pre-eclampsia: a revised view. Placenta. (2009) 30:38–42. 10.1016/j.placenta.2008.11.021
    1. Rodie VA, Freeman DJ, Sattar N, Greer IA. Pre-eclampsia and cardiovascular disease: metabolic syndrome of pregnancy? Atherosclerosis. (2004) 175:189–202. 10.1016/j.atherosclerosis.2004.01.038
    1. Poston L. Endothelial dysfunction in pre-eclampsia. Pharmacol Rep. (2006) 58:69–74.
    1. Levine RJ, Lam C, Qian C, Yu KF, Maynard SE, Sachs BP, et al. . Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. (2006) 355:992–1005. 10.1056/NEJMoa055352
    1. Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. . Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. (2004) 350:672–83. 10.1056/NEJMoa031884
    1. Ahmad S, Ahmed A. Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia. Circulat Res. (2004) 95:884–91. 10.1161/01.RES.0000147365.86159.f5
    1. Jarvis SS, Shibata S, Bivens TB, Okada Y, Casey BM, Levine BD, et al. . Sympathetic activation during early pregnancy in humans. J Physiol. (2012) 590:3535–43. 10.1113/jphysiol.2012.228262
    1. Wang A, Rana S, Karumanchi SA. Preeclampsia: the role of angiogenic factors in its pathogenesis. Physiology. (2009) 24:147–58. 10.1152/physiol.00043.2008
    1. Greenwood JP, Scott EM, Stoker JB, Walker JJ, Mary DA. Sympathetic neural mechanisms in normal and hypertensive pregnancy in humans. Circulation. (2001) 104:2200–4. 10.1161/hc4301.098253
    1. Collén AC, Manhem K, Sverrisdóttir YB. Sympathetic nerve activity in women 40 years after a hypertensive pregnancy. J Hypertens. (2012) 30:1203–10. 10.1097/HJH.0b013e3283531ed2
    1. Bosio PM, McKenna PJ, Conroy R, O'Herlihy C. Maternal central hemodynamics in hypertensive disorders of pregnancy. Obstet Gynecol. (1999) 94:978–84. 10.1016/S0029-7844(99)00430-5
    1. Andreas M, Kuessel L, Kastl SP, Wirth S, Gruber K, Rhomberg F, et al. . Bioimpedance cardiography in pregnancy: a longitudinal cohort study on hemodynamic pattern and outcome. BMC Pregnancy Child. (2016) 16:128. 10.1186/s12884-016-0918-8
    1. Yoffe L, Gilam A, Yaron O, Polsky A, Farberov L, Syngelaki A, et al. . Early detection of preeclampsia using circulating small non-coding RNA. Sci Rep. (2018) 8:3401. 10.1038/s41598-018-21604-6
    1. Beckham AJ, Greene TB, Meltzer-Brody S. A pilot study of heart rate variability biofeedback therapy in the treatment of perinatal depression on a specialized perinatal psychiatry inpatient unit. Arch Womens Mental Health. (2013) 16:59–65. 10.1007/s00737-012-0318-7
    1. Pinter A, Szatmari S, Horvath T, Penzlin AI, Barlinn K, Siepmann M, et al. . Cardiac dysautonomia in depression – heart rate variability biofeedback as a potential add-on therapy. Neuropsychiatr Dis Treat. (2019) 15:1287–310. 10.2147/NDT.S200360

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する