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A mathematical model of maternal vascular growth and remodeling and changes in maternal hemodynamics in uncomplicated pregnancy

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Abstract

The maternal vasculature undergoes tremendous growth and remodeling (G&R) that enables a > 15-fold increase in blood flow through the uterine vasculature from conception to term. Hemodynamic metrics (e.g., uterine artery pulsatility index, UA-PI) are useful for the prognosis of pregnancy complications; however, improved characterization of the maternal hemodynamics is necessary to improve prognosis. The goal of this paper is to develop a mathematical framework to characterize maternal vascular G&R and hemodynamics in uncomplicated human pregnancies. A validated 1D model of the human vascular tree from the literature was adapted and inlet blood flow waveforms at the ascending aorta at 4 week increments from 0 to 40 weeks of gestation were prescribed. Peripheral resistances of each terminal vessel were adjusted to achieve target flow rates and mean arterial pressure at each gestational age. Vessel growth was governed by wall shear stress (and axial lengthening in uterine vessels), and changes in vessel distensibility were related to vessel growth. Uterine artery velocity waveforms generated from this model closely resembled ultrasound results from the literature. The literature UA-PI values changed significantly across gestation, increasing in the first month of gestation, then dramatically decreasing from 4 to 20 weeks. Our results captured well the time-course of vessel geometry, material properties, and UA-PI. This 1D fluid-G&R model captured the salient hemodynamic features across a broad range of clinical reports and across gestation for uncomplicated human pregnancy. While results capture available data well, this study highlights significant gaps in available data required to better understand vascular remodeling in pregnancy.

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References

  • Abdel Moety GAF, Almohamady M, Sherif NA, Raslana AN, Mohamed TF, El Moneam HMA et al (2016) Could first-trimester assessment of placental functions predict preeclampsia and intrauterine growth restriction? A prospective cohort study. J Matern Fetal Neonatal Med 29(3):413–417

    Article  Google Scholar 

  • Abduljalil K, Furness P, Johnson TN, Rostami-Hodjegan A, Soltani H (2012) Anatomical, physiological and metabolic changes with gestational age during normal pregnancy: a database for parameters required in physiologically based pharmacokinetic modelling. Clin Pharmacokinet 51(6):365–396

    Article  Google Scholar 

  • Adekanmi AJ, Roberts A, Akinmoladun JA, Adeyinka AO (2019) Uterine and umbilical artery doppler in women with pre-eclampsia and their pregnancy outcomes. Niger Postgrad Med J 26(2):106–112

    Article  Google Scholar 

  • Anastasakis E, Paraskevas KI, Papantoniou N, Daskalakis G, Mesogitis S, Mikhailidis DP et al (2008) Association between abnormal uterine artery Doppler flow velocimetry, risk of preeclampsia, and indices of arterial structure and function: a pilot study. Angiology 59(4):493–499

    Article  Google Scholar 

  • Arcangeli T, Giorgetta F, Farina A, De Musso F, Bellussi F, Salsi G et al (2013) Significance of uteroplacental Doppler at midtrimester in patients with favourable obstetric history. J Matern Fetal Neonatal Med 26(3):299–302

    Article  Google Scholar 

  • Audibert F, Boucoiran I, An N, Aleksandrov N, Delvin E, Bujold E et al (2010) Screening for preeclampsia using first-trimester serum markers and uterine artery Doppler in nulliparous women. Am J Obstet Gynecol. 203(4):383.e1-383.e8

    Article  Google Scholar 

  • Bahlmann F, Fittschen M, Reinhard I, Wellek S, Steiner E (2012) Reference values for blood flow velocity in the uterine artery in normal pregnancies from 18 weeks to 42 weeks of gestation calculated by automatic Doppler waveform analysis. Ultraschall in der Medizin (Stuttgart, Germany: 1980) 33(3):258–64

    Article  Google Scholar 

  • Bamfo JEAK, Kametas NA, Chambers JB, Nicolaides KH (2007a) Maternal cardiac function in fetal growth-restricted and non-growth-restricted small-for-gestational age pregnancies. Ultrasound Obstet Gynecol 29(1):51–57

    Article  Google Scholar 

  • Bamfo JEAK, Kametas NA, Nicolaides KH, Chambers JB (2007b) Maternal left ventricular diastolic and systolic long-axis function during normal pregnancy. Eur J Echocardiogr 8(5):360–368

    Article  Google Scholar 

  • Boileau E, Nithiarasu P, Blanco PJ, Müller LO, Fossan FE, Hellevik LR et al (2015) A benchmark study of numerical schemes for one-dimensional arterial blood flow modelling. Int J Numer Methods Biomed Eng 31(10):e02732

    Article  MathSciNet  Google Scholar 

  • Borghi C, Esposti DD, Immordino V, Cassani A, Boschi S, Bovicelli L et al (2000) Relationship of systemic hemodynamics, left ventricular structure and function, and plasma natriuretic peptide concentrations during pregnancy complicated by preeclampsia. Am J Obstet Gynecol 183(1):140–147

    Article  Google Scholar 

  • Borna S, Rahmani Z (2015) A Study of Doppler ultrasound indices of spiral placental and umbilical arteries in pregnant women with singlet on pregnancy suffering type-1 diabetes mellitus, gestational diabetes and normal pregnant women. J Appl Environ Biol Sci 5(10S):436–440

    Google Scholar 

  • Bosio PM, McKenna PJ, Conroy R, O’Herlihy C (1999) Maternal central hemodynamics in hypertensive disorders of pregnancy. Obstet Gynecol 94(6):978

    Google Scholar 

  • Brosens I (1964) A study of the spiral arteries of the decidua Basalis in normotensive and hypertensive pregnancies. BJOG Int J Obstet Gynaecol 71(2):222–230

    Article  Google Scholar 

  • Brosens I, Dixon HG (1966) The anatomy of the maternal side of the placenta. J Obstet Gynaecol Br Commonw 73(3):357–363

    Article  Google Scholar 

  • Brosens I, Robertson WB, Dixon HG (1967) The physiological response of the vessels of the placental bed to normal pregnancy. J Pathol Bacteriol 93(2):569–579

    Article  Google Scholar 

  • Brosens JJ, Pijnenborg R, Brosens IA (2002) The myometrial junctional zone spiral arteries in normal and abnormal pregnancies: a review of the literature. Am J Obstet Gynecol 187(5):1416–1423

    Article  Google Scholar 

  • Brosens I, Pijnenborg R, Vercruysse L, Romero R (2011) The “Great Obstetrical Syndromes” are associated with disorders of deep placentation. Am J Obstet Gynecol 204(3):193–201

    Article  Google Scholar 

  • Browne VA, Toledo-Jaldin L, Davila RD, Lopez LP, Yamashiro H, Cioffi-Ragan D et al (2011) High-end arteriolar resistance limits uterine artery blood flow and restricts fetal growth in preeclampsia and gestational hypertension at high altitude. Am J Physiol Regul Integr Comp Physiol 300(5):R1221–R1229

    Article  Google Scholar 

  • Burton GJ, Woods AW, Jauniaux E, Kingdom JCP (2009) Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta 30(6):473–482

    Article  Google Scholar 

  • Carson J, Warrander L, Johnstone E, van Loon R (2019) Personalising cardiovascular network models in pregnancy: a two-tiered parameter estimation approach. Int J Numer Method Biomed Eng. 37:e3267

    Google Scholar 

  • Carter EB, Goetzinger K, Tuuli MG, Odibo L, Cahill AG, Macones GA et al (2015) Evaluating the optimal definition of abnormal first-trimester uterine artery doppler parameters to predict adverse pregnancy outcomes. J Ultrasound Med Off J Am Inst Ultrasound Med 34(7):1265–1269

    Google Scholar 

  • Cavoretto P, Farina A, Gaeta G, Sigismondi C, Spinillo S, Casiero D, et al. Longitudinal cohort study of uterine artery Doppler in singleton pregnancies obtained by IVF/ICSI with fresh or frozen blastocyst transfers in relation to pregnancy outcomes. Ultrasound Obstet Gynecol. 2020:21969.

  • Chapman AB, Abraham WT, Zamudio S, Coffin C, Merouani A, Young D et al (1998) Temporal relationships between hormonal and hemodynamic changes in early human pregnancy. Kidney Int 54(6):2056–2063

    Article  Google Scholar 

  • Chen C, Huang R, Liu P, Ouyang Z, Guo H, Tang L et al (2010) Construction and clinical significance of normal uterine arterial vascular network models. Gynecol Obstet Invest 69(1):14–19

    Article  Google Scholar 

  • Cheng F, Li T, Wang Q-L, Zhou H-L, Duan L, Cai X (2015) Effects of hydrosalpinx on ultrasonographic parameters for endometrial receptivity during the window of implantation measured by power color Doppler ultrasound. Int J Clin Exp Med 8(4):6103–6108

    Google Scholar 

  • Clapp MJF III, Capeless MDE (1997) Cardiovascular function before, during, and after the first and subsequent pregnancies. Am J Cardiol 80(11):1469–1473

    Article  Google Scholar 

  • Clark SL, Cotton DB, Lee W, Bishop C, Hill T, Southwick J et al (1989) Central hemodynamic assessment of normal term pregnancy. Am J Obstet Gynecol 161(6 Pt 1):1439–1442

    Article  Google Scholar 

  • Clark AR, James JL, Stevenson GN, Collins SL (2018) Understanding abnormal uterine artery Doppler waveforms: A novel computational model to explore potential causes within the utero-placental vasculature. Placenta 66:74–81

    Article  Google Scholar 

  • Coppens M, Loquet P, Kollen M, DeNeubourg F, Buytaert P (1996) Longitudinal evaluation of uteroplacental and umbilical blood flow changes in normal early pregnancy. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 7(2):114–121

    Article  Google Scholar 

  • Corsini C, Cervi E, Migliavacca F, Schievano S, Hsia T-Y, Pennati G (2017) Mathematical modelling of the maternal cardiovascular system in the three stages of pregnancy. Med Eng Phys 47:55–63

    Article  Google Scholar 

  • Crovetto F, Figueras F, Triunfo S, Crispi F, Rodriguez-Sureda V, Dominguez C et al (2015) First trimester screening for early and late preeclampsia based on maternal characteristics, biophysical parameters, and angiogenic factors. Prenat Diagn 35(2):183–191

    Article  Google Scholar 

  • D’Antonio F, Rizzo G, Gustapane S, Buca D, Flacco ME, Martellucci C et al (2020) Diagnostic accuracy of Doppler ultrasound in predicting perinatal outcome in pregnancies at term: a prospective longitudinal study. Acta Obstet Gynecol Scand 99(1):42–47

    Article  Google Scholar 

  • D’Silva LA, Davies RE, Emery SJ, Lewis MJ (2013) Influence of somatic state on cardiovascular measurements in pregnancy. Physiol Meas 35(1):15–29

    Article  Google Scholar 

  • De Paco C, Ventura W, Oliva R, Miguel M, Arteaga A, Nieto A et al (2014) Umbilical artery Doppler at 19 to 22 weeks of gestation in the prediction of adverse pregnancy outcomes. Prenat Diagn 34(7):711–715

    Article  Google Scholar 

  • Del Bene R, Barletta G, Mello G, Lazzeri C, Mecacci F, Parretti E et al (2001) Cardiovascular function in pregnancy: effects of posture. BJOG Int J Obstet Gynaecol. 108(4):344–52

    Article  Google Scholar 

  • Dennis AT, Castro J, Carr C, Simmons S, Permezel M, Royse C (2012) Haemodynamics in women with untreated pre-eclampsia*. Anaesthesia 67(10):1105–1118

    Article  Google Scholar 

  • Desai DK, Moodley J, Naidoo DP (2004) Echocardiographic assessment of cardiovascular hemodynamics in normal pregnancy. Obstet Gynecol 104(1):20–29

    Article  Google Scholar 

  • Deurloo KL, Bolte AC, Twisk JWR, van Vugt JMG (2009) Longitudinal Doppler measurements of spiral artery blood flow in relation to uterine artery blood flow. J Ultrasound Med Off J Am Inst Ultrasound Med 28(12):1623–1628

    Google Scholar 

  • Deutinger J, Rudelstorfer R, Bernaschek G (1988) Vaginosonographic velocimetry of both main uterine arteries by visual vessel recognition and pulsed Doppler method during pregnancy. Am J Obstet Gynecol 159(5):1072–1076

    Article  Google Scholar 

  • Dickey RP (1995) Effect of ovulation induction on uterine blood flow and oestradiol and progesterone concentrations in early pregnancy. Human Reprod (Oxf, Engl) 10(11):2875–2879

    Article  Google Scholar 

  • Dickey RP (1997) Doppler ultrasound investigation of uterine and ovarian blood flow in infertility and early pregnancy. Hum Reprod Update 3(5):467–503

    Article  Google Scholar 

  • Dickey RP, Hower JF (1995) Ultrasonographic features of uterine blood flow during the first 16 weeks of pregnancy. Hum Reprod (Oxf, Engl) 10(9):2448–2452

    Article  Google Scholar 

  • Dickey RP, Hower JF, Matulich EM, Brown GT (1994) Effect of standing on non-pregnant uterine blood flow. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 4(6):480–487

    Article  Google Scholar 

  • Dickey RP, Gasser RF, Hower JF, Matulich EM, Brown GT (1995) Relationship of uterine blood-flow to chorionic sac and embryo growth-rates. Hum Reprod (Oxf, Engl) 10(10):2676–2679

    Article  Google Scholar 

  • Duvekot JJ, Cheriex EC, Pieters FAA, Peeters LLH (1995) Severely impaired fetal growth is preceded by maternal hemodynamic maladaptation in very early pregnancy. Acta Obstet Gynecol Scand 74(9):693–697

    Article  Google Scholar 

  • Easterling TR, Benedetti TJ, Schmucker BC, Millard SP (1990) Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal study. Obstet Gynecol 76(6):1061–1069

    Google Scholar 

  • Edgar JC. The practice of obstetrics: designed for the use of students and practitioners of medicine 1910

  • Ergin RN, Yayla M (2015) Uterine artery pulsatility index and diastolic notch laterality according to the placental location. Clin Exp Obstet Gynecol 42(5):640–643

    Article  Google Scholar 

  • Eser A, Zulfıkaroglu E, Eserdag S, Kılıc S, Danısman N (2011) Predictive value of middle cerebral artery to uterine artery pulsatility index ratio in preeclampsia. Arch Gynecol Obstet 284(2):307–311

    Article  Google Scholar 

  • Estensen M-E, Grindheim G, Remme EW, Swillens A, Smiseth OA, Segers P et al (2012) Systemic arterial response and ventriculo–arterial interaction during normal pregnancy. Am J Hypertens 25(6):672–677

    Article  Google Scholar 

  • Everett TR, Mahendru AA, McEniery CM, Wilkinson IB, Lees CC (2012) Raised uterine artery impedance is associated with increased maternal arterial stiffness in the late second trimester. Placenta 33(7):572–577

    Article  Google Scholar 

  • Farina A, Rapacchia G, Freni Sterrantino A, Pula G, Morano D, Rizzo N (2011) Prospective evaluation of ultrasound and biochemical-based multivariable models for the prediction of late pre-eclampsia. Prenat Diagn 31(12):1147–1152

    Article  Google Scholar 

  • Fernstrom I (1955) Arteriography of the uterine artery: its value in the diagnosis of uterine fibromyoma, tubal pregnancy, adnexal tumour, and placental site localization in cases of intra-uterine pregnancy. Acta Radiol Suppl 122:1–128

    Google Scholar 

  • Flo K, Wilsgaard T, Vårtun A, Acharya G (2010) A longitudinal study of the relationship between maternal cardiac output measured by impedance cardiography and uterine artery blood flow in the second half of pregnancy. BJOG Int J Obstet Gynaecol. 117(7):837–44

    Article  Google Scholar 

  • Fugino Y, Ito F, Matuoka I, Kojima T, Koh B, Ogita S (1993) Pulsatility index of uterine artery in pregnant and non-pregnant women. Human Reproduction (oxford, England) 8(7):1126–1128

    Article  Google Scholar 

  • García B, Llurba E, Valle L, Gómez-Roig MD, Juan M, Pérez-Matos C et al (2016) Do knowledge of uterine artery resistance in the second trimester and targeted surveillance improve maternal and perinatal outcome? Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 47(6):680–689

    Article  Google Scholar 

  • Geva T, Mauer MB, Striker L, Kirshon B, Pivarnik JM (1997) Effects of physiologic load of pregnancy on left ventricular contractility and remodeling. Am Heart J 133(1):53–59

    Article  Google Scholar 

  • Gilson G, Samaan S, Crawford M, Quails C, Curet L (1997) Changes in hemodynamics, ventricular remodeling, and ventricular contractility during normal pregnancy: a longitudinal study. Obstet Gynecol 89(6):957–962

    Article  Google Scholar 

  • Gleason RL, Taber LA, Humphrey JD (2004) A 2-D model of flow-induced alterations in the geometry, structure, and properties of carotid arteries. J Biomech Eng 126(3):371–381

    Article  Google Scholar 

  • Gómez O, Martínez JM, Figueras F, Del Río M, Borobio V, Puerto B et al (2005) Uterine artery Doppler at 11–14 weeks of gestation to screen for hypertensive disorders and associated complications in an unselected population. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 26(5):490–494

    Article  Google Scholar 

  • Gómez O, Figueras F, Fernández S, Bennasar M, Martínez JM, Puerto B et al (2008) Reference ranges for uterine artery mean pulsatility index at 11–41 weeks of gestation. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 32(2):128–132

    Article  Google Scholar 

  • Guanes PP, Remohí J, Gallardo E, Valbuena D, Simón C, Pellicer A (1996) Age does not affect uterine resistance to vascular flow in patients undergoing oocyte donation. Fertil Steril 66(2):265–270

    Article  Google Scholar 

  • Guedes-Martins L, Cunha A, Saraiva J, Gaio R, Macedo F, Almeida H (2014) Internal iliac and uterine arteries Doppler ultrasound in the assessment of normotensive and chronic hypertensive pregnant women. Sci Rep 4(1):3785–3788

    Article  Google Scholar 

  • Hale SA, Schonberg A, Badger GJ, Bernstein IM (2009) Relationship between prepregnancy and early pregnancy uterine blood flow and resistance index. Reprod Sci (Thousand Oaks, Calif) 16(11):1091–1096

    Article  Google Scholar 

  • Hennessy TG, MacDonald D, Hennessy MS, Maguire M, Blake S, McCann HA et al (1996) Serial changes in cardiac output during normal pregnancy: a Doppler ultrasound study. Eur J Obstet Gynecol Reprod Biol 70(2):117–122

    Article  Google Scholar 

  • Jamal A, Abbasalizadeh F, Vafaei H, Marsoosi V, Eslamian L (2013) Multicenter screening for adverse pregnancy outcomes by uterine artery Doppler in the second and third trimester of pregnancy. Med Ultrason 15(2):95–100

    Article  Google Scholar 

  • James JL, Chamley LW, Clark AR (2017) Feeding your baby in utero: How the uteroplacental circulation impacts pregnancy. Physiology (bethesda) 32(3):234–245

    Google Scholar 

  • Jauniaux E, Jurkovic D, Campbell S (1991) In vivo investigations of the anatomy and the physiology of early human placental circulations. Ultrasound Obstet Gynecol 1(6):435–445

    Article  Google Scholar 

  • Jeffreys RM, Stepanchak W, Lopez B, Hardis J, Clapp JF (2006) Uterine blood flow during supine rest and exercise after 28 weeks of gestation. BJOG Int J Obstet Gynaecol. 113(11):1239–47

    Article  Google Scholar 

  • Jones TB, Price RR, Gibbs SJ (1981) Volumetric determination of placental and uterine growth relationships from B-mode ultrasound by serial area-volume determinations. Invest Radiol 16(2):101–106

    Article  Google Scholar 

  • Jurkovic D, Jauniaux E, Kurjak A, Hustin J, Campbell S, Nicolaides KH (1991) Transvaginal color Doppler assessment of the uteroplacental circulation in early pregnancy. Obstet Gynecol 77(3):365–369

    Google Scholar 

  • Kaihura C, Savvidou MD, Anderson JM, McEniery CM, Nicolaides KH (2009) Maternal arterial stiffness in pregnancies affected by preeclampsia. Am J Physiol: Heart Circ Physiol 297(2):H759–H764

    Google Scholar 

  • Kaminopetros P, Higueras MT, Nicolaides KH (1991) Doppler study of uterine artery blood flow: comparison of findings in the first and second trimesters of pregnancy. Fetal Diagn Ther 6(1–2):58–64

    Article  Google Scholar 

  • Kamiya A, Togawa T (1980) Adaptive regulation of wall shear stress to flow change in the canine carotid artery. Am J Physiol: Heart Circ Physiol 239:H14-21

    Google Scholar 

  • Khalil A, Morales-Roselló J, Townsend R, Morlando M, Papageorghiou A, Bhide A et al (2016) Value of third-trimester cerebroplacental ratio and uterine artery Doppler indices as predictors of stillbirth and perinatal loss. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 47(1):74–80

    Article  Google Scholar 

  • Kienast C, Moya W, Rodriguez O, Jijón A, Geipel A (2016) Predictive value of angiogenic factors, clinical risk factors and uterine artery Doppler for pre-eclampsia and fetal growth restriction in second and third trimester pregnancies in an Ecuadorian population. J Matern Fetal Neonatal Med 29(4):537–543

    Article  Google Scholar 

  • Konje JC, Kaufmann P, Bell SC, Taylor DJ (2001) A longitudinal study of quantitative uterine blood flow with the use of color power angiography in appropriate for gestational age pregnancies. Am J Obstet Gynecol 185(3):608–613

    Article  Google Scholar 

  • Kroon W, Huberts W, Bosboom M, van de Vosse F (2012) A numerical method of reduced complexity for simulating vascular hemodynamics using coupled 0D lumped and 1D wave propagation models. Comput Math Methods Med 2012(6):156094–156110

    MathSciNet  MATH  Google Scholar 

  • Kuleva M, Youssef A, Maroni E, Contro E, Pilu G, Rizzo N et al (2011) Maternal cardiac function in normal twin pregnancy: a longitudinal study. Ultrasound Obstet Gynecol 38(5):575–580

    Article  Google Scholar 

  • Kumar M, Gupta U, Bhattacharjee J, Singh R, Singh S, Goel M et al (2016) Early prediction of hypertension during pregnancy in a low-resource setting. Int J Gynaecol Obstet Off Organ Int Fed Gynaecol Obstet 132(2):159–164

    Article  Google Scholar 

  • Lai J, Poon LCY, Pinas A, Bakalis S, Nicolaides KH (2013) Uterine Artery Doppler at 30–33 weeks’ gestation in the prediction of preeclampsia. Fetal Diagn Ther 33(3):156–163

    Article  Google Scholar 

  • Lakatta EG (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises. Circulation 107(3):490–497

    Article  Google Scholar 

  • Laurent S, Boutouyrie P, Cunha PG, Lacolley P, Nilsson PM (2019) Concept of extremes in vascular aging. Hypertension 74(2):218–228

    Article  Google Scholar 

  • Leite JF, Lobo GAR, Nowak PM, Antunes IR, Araujo Júnior E (2019) Pares DBS Prediction of preeclampsia in the first trimester of pregnancy using maternal characteristics, mean arterial pressure, and uterine artery Doppler data in a Brazilian population. Obstet Gynecol Sci. 62(6):391–396

    Article  Google Scholar 

  • Lof M, Olausson H, Bostrom K, Janerot-Sjöberg B, Sohlstrom A, Forsum E (2005) Changes in basal metabolic rate during pregnancy in relation to changes in body weight and composition, cardiac output, insulin-like growth factor I, and thyroid hormones and in relation to fetal growth. Am J Clin Nutr 81(3):678–685

    Article  Google Scholar 

  • Mabie WC, DiSessa TG, Crocker LG, Sibai BM, Arheart KL (1994) A longitudinal study of cardiac output in normal human pregnancy. Am J Obstet Gynecol 170(3):849–856

    Article  Google Scholar 

  • Mahendru AA, Everett TR, Wilkinson IB, Lees CC, McEniery CM (2014) A longitudinal study of maternal cardiovascular function from preconception to the postpartum period. J Hypertens 32(4):849–856

    Article  Google Scholar 

  • Mahendru AA, Foo FL, McEniery CM, Everett TR, Wilkinson IB, Lees CC (2017) Change in maternal cardiac output from preconception to mid-pregnancy is associated with birth weight in healthy pregnancies. Ultrasound Obstet Gynecol 49(1):78–84

    Article  Google Scholar 

  • Mäkikallio K, Tekay A, Jouppila P (2004) Uteroplacental hemodynamics during early human pregnancy: a longitudinal study. Gynecol Obstet Invest 58(1):49–54

    Article  Google Scholar 

  • Meah VL, Cockcroft JR, Backx K, Shave R, Stöhr EJ (2016) Cardiac output and related haemodynamics during pregnancy: a series of meta-analyses. Heart 102(7):518

    Article  Google Scholar 

  • Mesa A, Jessurun C, Hernandez A, Adam K, Brown D, Vaughn WK et al (1999) Left ventricular diastolic function in normal human pregnancy. Circulation 99(4):511–517

    Article  Google Scholar 

  • Mo LYL, Bascom PAJ, Ritchie K, McCowan LME (1988) A Transmission-Line Modeling Approach to the Interpretation of Uterine Doppler Waveforms. Ultrasound Med Biol 14(5):365–376

    Article  Google Scholar 

  • Moertl MG, Schlembach D, Papousek I, Hinghofer-Szalkay H, Weiss EM, Lang U et al (2012) Hemodynamic evaluation in pregnancy: limitations of impedance cardiography. Physiol Meas 33(6):1015–1026

    Article  Google Scholar 

  • Mone SM, Sanders SP, Colan SD (1996) Control Mechanisms for physiological hypertrophy of pregnancy. Circulation 94(4):667–672

    Article  Google Scholar 

  • Nevo O, Soustiel JF, Thaler I (2010) Maternal cerebral blood flow during normal pregnancy: a cross-sectional study. Am J Obstet Gynecol 203(5):475.e1-475.e6

    Article  Google Scholar 

  • Nii M, Ishida M, Dohi K, Tanaka H, Kondo E, Ito M et al (2018) Myocardial tissue characterization and strain analysis in healthy pregnant women using cardiovascular magnetic resonance native T1 mapping and feature tracking technique. J Cardiov Magn Reson 20(1):52

    Article  Google Scholar 

  • Novelli GP, Vasapollo B, Gagliardi G, Tiralongo GM, Pisani I, Manfellotto D et al (2012) Left ventricular midwall mechanics at 24 weeks’ gestation in high-risk normotensive pregnant women: relationship to placenta-related complications of pregnancy. Ultrasound Obstet Gynecol 39(4):430–437

    Article  Google Scholar 

  • Odibo AO, Zhong Y, Goetzinger KR, Odibo L, Bick JL, Bower CR et al (2011) First-trimester placental protein 13, PAPP-A, uterine artery Doppler and maternal characteristics in the prediction of pre-eclampsia. Placenta 32(8):598–602

    Article  Google Scholar 

  • Ogueh O, Brookes C, Johnson MR (2009) A Longitudinal study of the maternal cardiovascular adaptation to spontaneous and assisted conception pregnancies. Hypertens Pregnancy 28(3):273–289

    Article  Google Scholar 

  • Oliveira N, Magder LS, Blitzer MG, Baschat AA (2014) First-trimester prediction of pre-eclampsia: external validity of algorithms in a prospectively enrolled cohort. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 44(3):279–285

    Article  Google Scholar 

  • Olofsson P, Laurini RN, Marsál K (1993) A high uterine artery pulsatility index reflects a defective development of placental bed spiral arteries in pregnancies complicated by hypertension and fetal growth retardation. Eur J Obstet Gynecol Reprod Biol 49(3):161–168

    Article  Google Scholar 

  • Osol G, Mandala M (2009) Maternal uterine vascular remodeling during pregnancy. Physiology (bethesda) 24(1):58–71

    Google Scholar 

  • Osol G, Moore LG (2014) Maternal uterine vascular remodeling during pregnancy. Microcirculation (New York, NY: 1994) 21(1):38–47

    Article  Google Scholar 

  • Oyama-Kato M, Ohmichi M, Takahashi K, Suzuki S, Henmi N, Yokoyama Y et al (2006) Change in pulse wave velocity throughout normal pregnancy and its value in predicting pregnancy-induced hypertension: a longitudinal study. Am J Obstet Gynecol 195(2):464–469

    Article  Google Scholar 

  • Özkaya Ü, Özkan S, Özeren S, Çorakçı A (2007) Doppler examination of uteroplacental circulation in early pregnancy: Can it predict adverse outcome? J Clin Ultrasound 35(7):382–386

    Article  Google Scholar 

  • Palmer SK, Zamudio S, Coffin C, Parker S, Stamm E, Moore LG (1992) Quantitative estimation of human uterine artery blood flow and pelvic blood flow redistribution in pregnancy. Obstet Gynecol 80(6):1000–1006

    Google Scholar 

  • Perry H, Lehmann H, Mantovani E, Thilaganathan B, Khalil A (2020) Are maternal hemodynamic indices markers of fetal growth restriction in pregnancies with a small-for-gestational-age fetus? Ultrasound Obstet Gynecol 55(2):210–216

    Article  Google Scholar 

  • Pilalis A, Souka AP, Antsaklis P, Daskalakis G, Papantoniou N, Mesogitis S et al (2007) Screening for pre-eclampsia and fetal growth restriction by uterine artery Doppler and PAPP-A at 11–14 weeks' gestation. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 29(2):135–140

    Article  Google Scholar 

  • Plasencia W, González-Dávila E, Lorenzo AG, Armas-González M, Padrón E, González-González NL (2015) First trimester placental volume and vascular indices in pregnancies complicated by preeclampsia. Prenat Diagn 35(12):1247–1254

    Article  Google Scholar 

  • Ponmozhi G, Keepanasseril A, Mathaiyan J, Manikandan K (2019) Nitric oxide in the prevention of pre-eclampsia (NOPE): A double-blind randomized placebo-controlled trial assessing the efficacy of isosorbide mononitrate in the prevention of pre-eclampsia in high-risk women. J Obstet Gynaecol India 69(Suppl 2):103–110

    Article  Google Scholar 

  • Poon LCY, Kametas NA, Maiz N, Akolekar R, Nicolaides KH (2009a) First-trimester prediction of hypertensive disorders in pregnancy. Hypertension 53(5):812–818

    Article  Google Scholar 

  • Poon LCY, Karagiannis G, Leal A, Romero XC, Nicolaides KH (2009b) Hypertensive disorders in pregnancy: screening by uterine artery Doppler imaging and blood pressure at 11–13 weeks. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 34(5):497–502

    Article  Google Scholar 

  • Poppas A, Shroff SG, Korcarz CE, Hibbard JU, Berger DS, Lindheimer MD et al (1997) Serial assessment of the cardiovascular system in normal pregnancy: role of arterial compliance and pulsatile arterial load. Circulation 95(10):2407–2415

    Article  Google Scholar 

  • Prajapati SR, Maitra N (2013) Prediction of pre-eclampsia by a combination of maternal history, uterine artery Doppler, and mean arterial pressure (a prospective study of 200 cases). J Obstet Gynaecol India 63(1):32–36

    Article  Google Scholar 

  • Prodan N, Wagner P, Sonek J, Hoopmann M, Mutz A, Brucker S et al (2019) First trimester uterine artery pulsatility index levels in euploid and aneuploid pregnancies. Arch Gynecol Obstet 300(6):1559–1564

    Article  Google Scholar 

  • Rang S, Lapiedra BP, Montfrans GA, Bouma BJ, Wesseling KH, Wolf H (2007) Modelflow: a new method for noninvasive assessment of cardiac output in pregnant women. Am J Obstet Gynecol. 196(3):235.e1-235.e8

    Article  Google Scholar 

  • Rang S, Montfrans GA, Wolf H (2008) Serial hemodynamic measurement in normal pregnancy, preeclampsia, and intrauterine growth restriction. Am J Obstet Gynecol. 198(5):519.e1-519.e9

    Article  Google Scholar 

  • Reymond P, Merenda F, Perren F, Rüfenacht D, Stergiopulos N (2009) Validation of a one-dimensional model of the systemic arterial tree. Am J Physiol: Heart Circ Physiol 297(1):H208–H222

    Google Scholar 

  • Rigano S, Ferrazzi E, Boito S, Pennati G, Padoan A, Galan H (2010) Blood flow volume of uterine arteries in human pregnancies determined using 3D and bi-dimensional imaging, angio-Doppler, and fluid-dynamic modeling. Placenta 31(1):37–43

    Article  Google Scholar 

  • Robb AO, Mills NL, Din JN, Smith IBJ, Paterson F, Newby DE et al (2009) Influence of the menstrual cycle, pregnancy, and preeclampsia on arterial stiffness. Hypertension 53(6):952–958

    Article  Google Scholar 

  • Robertson WB (1976) Uteroplacental vasculature. J Clin Pathol Suppl (r Coll Pathol) 10:9–17

    Article  Google Scholar 

  • Robson SC, Hunter S, Boys RJ, Dunlop W (1989) Serial study of factors influencing changes in cardiac output during human pregnancy. Am J Physiol 256(4 Pt 2):H1060–H1065

    Google Scholar 

  • Sagol S, Özkinay E, Öztekin K, Özdemir N (1999) The Comparison of uterine artery Doppler velocimetry with the Histopathology of the Placental Bed. Aust N Z J Obstet Gynaecol 39(3):324–329

    Article  Google Scholar 

  • Savu O, Jurcuţ R, Giuşcă S, van Mieghem T, Gussi I, Popescu BA et al (2012) Morphological and functional adaptation of the maternal heart during pregnancy. Circ Cardiovasc Imaging 5(3):289–297

    Article  Google Scholar 

  • Savvidou MD, Kaihura C, Anderson JM, Nicolaides KH (2011) Maternal arterial stiffness in women who subsequently develop pre-eclampsia. PloS ONE 6(5):e18703

    Article  Google Scholar 

  • Scazzocchio E, Figueras F, Crispi F, Meler E, Masoller N, Mula R et al (2013) Performance of a first-trimester screening of preeclampsia in a routine care low-risk setting. Am J Obstet Gynecol. 208(3):203.e1-203.e10

    Article  Google Scholar 

  • Schannwell CM, Zimmermann T, Schneppenheim M, Plehn G, Marx R, Strauer BE (2002) Left ventricular hypertrophy and diastolic dysfunction in healthy pregnant women. Cardiology 97(2):73–78

    Article  Google Scholar 

  • Sciscione AC, Hayes EJ, Medicine SM-F (2009) Uterine artery Doppler flow studies in obstetric practice. Am J Obstet Gynecol 201(2):121–6

    Article  Google Scholar 

  • Sengupta SP, Bansal M, Hofstra L, Sengupta PP, Narula J (2017) Gestational changes in left ventricular myocardial contractile function: new insights from two-dimensional speckle tracking echocardiography. Int J Cardiovasc Imaging 33(1):69–82

    Article  Google Scholar 

  • Simmons LA, Gillin AG, Jeremy RW (2002) Structural and functional changes in left ventricle during normotensive and preeclamptic pregnancy. Am J Physiol Heart C 283(4):H1627–H1633

    Article  Google Scholar 

  • Stergiopulos N, Young DF, Rogge TR (1992) Computer simulation of arterial flow with applications to arterial and aortic stenoses. J Biomech 25(12):1477–1488

    Article  Google Scholar 

  • Tekay A, Martikainen H, Jouppila P (1996) Comparison of uterine blood flow characteristics between spontaneous and stimulated cycles before embryo transfer. Hum Reprod (Oxf, Engl) 11(2):364–368

    Article  Google Scholar 

  • Tezcan ME, Temizkan O, Ozderya A, Melikoglu M, Aydin K, Sargin M et al (2015) Color Doppler analysis of female reproductive vasculature in Behçet’s disease. Reumatismo 67(3):103–108

    Article  Google Scholar 

  • Thaler I, Manor D, Itskovitz J, Rottem S, Levit N, Timor-Tritsch I et al (1990) Changes in uterine blood flow during human pregnancy. Am J Obstet Gynecol 162(1):121–125

    Article  Google Scholar 

  • Valensise H, Novelli GP, Vasapollo B, Borzi M, Arduini D, Galante A et al (2000) Maternal cardiac systolic and diastolic function: relationship with uteroplacental resistances. A Doppler and echocardiographic longitudinal study. Ultrasound Obstet Gynecol 15(6):487–97

    Article  Google Scholar 

  • Valensise H, Novelli GP, Vasapollo B, Ruzza GD, Romanini ME, Marchei M et al (2001) Maternal diastolic dysfunction and left ventricular geometry in gestational hypertension. Hypertension 37(5):1209–1215

    Article  Google Scholar 

  • Valensise H, Vasapollo B, Novelli GP, Pasqualetti P, Galante A, Arduini D (2006) Maternal total vascular resistance and concentric geometry: a key to identify uncomplicated gestational hypertension. BJOG Int J Obstet Gynaecol. 113(9):1044–52

    Article  Google Scholar 

  • Valensise H, Vasapollo B, Gagliardi G, Novelli GP (2008) Early and late preeclampsia. Hypertension 52(5):873–880

    Article  Google Scholar 

  • Valentin L, Sladkevicius P, Laurini R, Söderberg H, Marsál K (1996) Uteroplacental and luteal circulation in normal first-trimester pregnancies: Doppler ultrasonographic and morphologic study. Am J Obstet Gynecol 174(2):768–775

    Article  Google Scholar 

  • van den Boom T, Stevens R, Delhaas T, van de Vosse F, Huberts W (2018) Zero-dimensional lumped approach to incorporate the dynamic part of the pressure at vessel junctions in a 1D wave propagation model. Int J Numer Methods Biomed Eng 34(9):e3116

    Article  MathSciNet  Google Scholar 

  • van der Graaf A, Cuffie-Jackson C, Vissers MN, Trip MD, Gagné C, Shi G et al (2008) Efficacy and safety of coadministration of Ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia. J Am Coll Cardiol 52(17):1421–1429

    Article  Google Scholar 

  • Vårtun Å, Flo K, Acharya G (2014) Effect of passive leg raising on systemic hemodynamics of pregnant women: a dynamic assessment of maternal cardiovascular function at 22–24 weeks of gestation. PLoS ONE. 9(4):e94629

    Article  Google Scholar 

  • Vasapollo B, Novelli GP, Valensise H (2008) Total vascular resistance and left ventricular morphology as screening tools for complications in pregnancy. Hypertension 51(4):1020–1026

    Article  Google Scholar 

  • Vinayagam D, Thilaganathan B, Stirrup O, Mantovani E, Khalil A (2018) Maternal hemodynamics in normal pregnancy: reference ranges and role of maternal characteristics. Ultrasound Obstet Gynecol 51(5):665–671

    Article  Google Scholar 

  • Vlahović-Stipac A, Stankić V, Popović ZB, Putniković B, Nešković AN (2010) Left ventricular function in gestational hypertension: serial echocardiographic study. Am J Hypertens 23(1):85–91

    Article  Google Scholar 

  • Wan W, Gleason RL (2013) Dysfunction in elastic fiber formation in fibulin-5 null mice abrogates the evolution in mechanical response of carotid arteries during maturation. Am J Physiol Heart Circ Physiol 304(5):H674–H686

    Article  Google Scholar 

  • Wang L, Qiao J, Li R, Zhen X, Liu Z (2010) Role of endometrial blood flow assessment with color Doppler energy in predicting pregnancy outcome of IVF-ET cycles. Reprod Biol Endocrinol 8(1):122–127

    Article  Google Scholar 

  • Willeit P, Tschiderer L, Allara E, Reuber K, Seekircher L, Gao L et al (2020) Carotid intima-media thickness progression as surrogate marker for cardiovascular risk: meta-analysis of 119 clinical trials involving 100 667 patients. Circulation 142(7):621–642

    Article  Google Scholar 

  • Wilson MJ, Lopez M, Vargas M, Julian C, Tellez W, Rodriguez A et al (2007) Greater uterine artery blood flow during pregnancy in multigenerational (Andean) than shorter-term (European) high-altitude residents. Am J Physiol Regul Integr Comp Physiol 293(3):R1313–R1324

    Article  Google Scholar 

  • Woessner JF, Brewer TH (1963) Formation and breakdown of collagen and elastin in the human uterus during pregnancy and post-partum involution. Biochem J 89(1):75–82

    Article  Google Scholar 

  • Wolfe LA, Preston RJ, Burggraf GW, McGrath MJ (1999) Effects of pregnancy and chronic exercise on maternal cardiac structure and function. Can J Physiol Pharmacol 77(11):909–917

    Article  Google Scholar 

  • Yalti S, Gürbüz B, Ficicioglu C, Canova H (2003) Doppler evaluation of the uterine, intraovarian, stromal and spiral arteries on the day of human chorionic gonadotrophin administration in controlled ovarian hyperstimulation. J Obstet Gynaecol J Inst Obst Gynaecol 23(4):402–406

    Article  Google Scholar 

  • Yu CKH, Khouri O, Onwudiwe N, Spiliopoulos Y, Nicolaides KH, Group FMFS-TS (2008) Prediction of pre-eclampsia by uterine artery Doppler imaging: relationship to gestational age at delivery and small-for-gestational age. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol 31(3):310–3

    Article  Google Scholar 

  • Zamudio S, Palmer SK, Droma T, Stamm E, Coffin C, Moore LG (1995) Effect of altitude on uterine artery blood flow during normal pregnancy. J Appl Physiol (Bethesda, MD: 1985) 79(1):7–14

    Article  Google Scholar 

  • Zebitay AG, Tutumlu M, Verit FF, Ilhan GK, Gungor ES, Cetin O et al (2016) A comparative analysis of arterial blood flow in unexplained infertility, tubal infertility and fertile groups. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol 32(6):442–445

    Article  Google Scholar 

  • Zieman SJ, Melenovsky V, Kass DA (2005) Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol 25(5):932–943

    Article  Google Scholar 

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We gratefully acknowledge the support from the US National Science Foundation (CMMI 1727573).

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Gleason, R.L., Sedaghati, F. A mathematical model of maternal vascular growth and remodeling and changes in maternal hemodynamics in uncomplicated pregnancy. Biomech Model Mechanobiol 21, 647–669 (2022). https://doi.org/10.1007/s10237-021-01555-0

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