Until today the role of oxygen in the development of the fetus remains controversially discussed. It is still believed that lack of oxygen in utero might be responsible for some of the known congenital cardiovascular malformations. Over the last two decades detailed research has given us new insights and a better understanding of embryogenesis and fetal growth. But most importantly it has repeatedly demonstrated that oxygen only plays a minor role in the early intrauterine development. After organogenesis has taken place hypoxia becomes more important during the second and third trimester of pregnancy when fetal growth occurs. This review will briefly adress causes and mechanisms leading to intrauterine hypoxia and their impact on the fetal cardiovascular system. 1. Introduction Embryogenesis, fetal growth, and survival of the perinatal period all depend on optimal maternal health and normal placental development. Maternal exposure to a persistently hypoxic environment may lead to critical injury to vital organs. Failure of the normal placental function may have profound acute and chronic effects on the developing fetus and lead to intrauterine growth restriction (IUGR), asphyxia, multiorgan failure, premature delivery, and perinatal demise. In the United States, IUGR and prematurity complicate about 12% of the deliveries and represent the leading cause of perinatal mortality and morbidity to this day, accounting for up to 75% of perinatal deaths. Long-term disabilities such as cerebral palsy, hearing loss, retinopathies, and chronic lung disease are associated with a substantial emotional burden for affected families and health care costs to the society [1]. In this paper, we will briefly adress relevant aspects of the normal fetomaternal physiology and then focus our attention on the causes of chronic intrauterine hypoxia and how this affects the development and performance of the fetal heart. 2. Normal Pregnancy The process of placentation is initiated once the blastocyst makes contact with the epithelium of the uterus. An initial trophoblastic shell is penetrated by columns of proliferating extravillous cytotrophoblast that form the anchoring vili and provide specialized invasive cells that transform the decidual and proximal portions of the decidual spiral arteries [2]. During the initial phase of implantation and uterine wall invasion, the main role of extravillous trophoblast is to form plugs that occlude capillaries in the endometrial gland stroma; this prevents maternal hemorrhage form disrupting the conceptus and maternal blood from entering
References
[1]
C. V. Ananth and A. M. Vintzileos, “Epidemiology of preterm birth and its clinical subtypes,” Journal of Maternal-Fetal and Neonatal Medicine, vol. 19, no. 12, pp. 773–782, 2006.
[2]
J. A. Irving, J. J. Lysiak, C. H. Graham, S. Hearn, V. K. M. Han, and P. K. Lala, “Characteristics of trophoblast cells migrating from first trimester chorionic villus explants and propagated in culture,” Placenta, vol. 16, no. 5, pp. 413–433, 1995.
[3]
G. J. Burton, E. Jauniaux, and A. L. Watson, “Maternal arterial connections to the placental intervillous space during the first trimester of human pregnancy: the Boyd collection revisited,” American Journal of Obstetrics and Gynecology, vol. 181, no. 3, pp. 718–724, 1999.
[4]
E. Jauniaux, N. Greenwold, J. Hempstock, and G. J. Burton, “Comparison of ultrasonographic and Doppler mapping of the intervillous circulation in normal and abnormal early pregnancies,” Fertility and Sterility, vol. 79, no. 1, pp. 100–106, 2003.
[5]
E. Jauniaux, D. Jurkovic, S. Campbell, and J. Hustin, “Doppler ultrasonographic features of the developing placental circulation: correlation with anatomic findings,” American Journal of Obstetrics and Gynecology, vol. 166, no. 2, pp. 585–587, 1992.
[6]
F. Rodesch, P. Simon, C. Donner, and E. Jauniaux, “Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy,” Obstetrics and Gynecology, vol. 80, no. 2, pp. 283–285, 1992.
[7]
E. Jauniaux, A. L. Watson, J. Hempstock, Y.-P. Bao, J. N. Skepper, and G. J. Burton, “Onset of maternal arterial blood flow and placental oxidative stress: a possible factor in human early pregnancy failure,” American Journal of Pathology, vol. 157, no. 6, pp. 2111–2122, 2000.
[8]
A. L. Watson, J. N. Skepper, E. Jauniaux, and G. J. Burton, “Susceptibility of human placental syncytiotrophoblastic mitochondria to oxygen-mediated damage in relation to gestational age,” Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 5, pp. 1697–1705, 1998.
[9]
S. K. Palmer, S. Zamudio, C. Coffin, S. Parker, E. Stamm, and L. G. Moore, “Quantitative estimation of human uterine artery blood flow and pelvic blood flow redistribution in pregnancy,” Obstetrics and Gynecology, vol. 80, no. 6, pp. 1000–1006, 1992.
[10]
M. A. Cadnapaphornchai, M. Ohara, K. G. Morris Jr. et al., “Chronic NOS inhibition reverses systemic vasodilation and glomerular hyperfiltration in pregnancy,” American Journal of Physiology, vol. 280, no. 4, pp. F592–F598, 2001.
[11]
A. B. Chapman, W. T. Abraham, S. Zamudio et al., “Temporal relationships between hormonal and hemodynamic changes in early human pregnancy,” Kidney International, vol. 54, no. 6, pp. 2056–2063, 1998.
[12]
N. Furuhashi, H. Kimura, H. Nagae, and A. Yajima, “Maternal plasma endothelin levels and fetal status in normal and preecramptic pregnancies,” Gynecologic and Obstetric Investigation, vol. 39, no. 2, pp. 88–92, 1995.
[13]
R. R. Magness, “Maternal cardiovascular and other physiologic responses to the endocrinology of pregnancy,” in The Endocrinology of Pregnancy, F. W. Bazer, Ed., pp. 507–539, Humana Press, Totowas, NJ, USA, 1998.
[14]
A. E. Abbas, S. J. Lester, and H. Connolly, “Pregnancy and the cardiovascular system,” International Journal of Cardiology, vol. 98, no. 2, pp. 179–189, 2005.
[15]
R. D. Miller, Anesthesia, Churchill Livingston, Philadelphia, Pa, USA, 5th edition, 2000.
[16]
S. C. Siu and J. M. Colman, “Congenital heart disease: heart disease and pregnancy,” Heart, vol. 85, no. 6, pp. 710–715, 2001.
[17]
X.-Q. Hu, S. Yang, W. J. Pearce, L. D. Longo, and L. Zhang, “Effect of chronic hypoxia on alpha-1 adrenoceptor-mediated inositol 1,4,5-trisphosphate signaling in ovine uterine artery,” Journal of Pharmacology and Experimental Therapeutics, vol. 288, no. 3, pp. 977–983, 1999.
[18]
S. Mateev, A. H. Sillau, R. Mouser et al., “Chronic hypoxia opposes pregnancy-induced increase in uterine artery vasodilator response to flow,” American Journal of Physiology, vol. 284, no. 3, pp. H820–H829, 2003.
[19]
D. Xiao, X. Huang, S. Bae, C. A. Ducsay, and L. Zhang, “Cortisol-mediated potentiation of uterine artery contractility: effect of pregnancy,” American Journal of Physiology, vol. 283, no. 1, pp. H238–H246, 2002.
[20]
L. E. Keyes, L. G. Moore, S. J. Walchak, and E. C. Dempsey, “Pregnancy-stimulated growth of vascular smooth muscle cells: importance of protein kinase C-dependent synergy between estrogen and platelet-derived growth factor,” Journal of Cellular Physiology, vol. 166, no. 1, pp. 22–32, 1996.
[21]
M. J. Mulvany, G. L. Baumbach, C. Aalkjaer et al., “Vascular remodeling,” Hypertension, vol. 28, no. 3, pp. 505–506, 1996.
[22]
Y. Ni, V. May, K. Braas, and G. Osol, “Pregnancy augments uteroplacental vascular endothelial growth factor gene expression and vasodilator effects,” American Journal of Physiology, vol. 273, no. 2, pp. H938–H944, 1997.
[23]
J. M？nner, J. M. Pérez-Pomares, D. Macías, and R. Mu？oz-Chápuli, “The origin, formation and developmental significance of the epicardium: a review,” Cells Tissues Organs, vol. 169, no. 2, pp. 89–103, 2001.
[24]
J. M？nner, “Does the subepicardial mesenchyme contribute myocardioblasts to the myocardium of the chick embryo heart? A quail-chick chimera study tracing the fate of the epicardial primordium,” Anatomical Record, vol. 255, no. 2, pp. 212–226, 1999.
[25]
J. M？nner, “Cardiac looping in the chick embryo: a morphological review with special reference to terminological and biomechanical aspects of the looping process,” Anatomical Record, vol. 259, no. 3, pp. 248–262, 2000.
[26]
V. M. Christoffels, P. E. M. H. Habets, D. Franco et al., “Chamber formation and morphogenesis in the developing mammalian heart,” Developmental Biology, vol. 223, no. 2, pp. 266–278, 2000.
[27]
S. Webb, M. Kanani, R. H. Anderson, M. K. Richardson, and N. A. Brown, “Development of the human pulmonary vein and its incorporation in the morphologically left atrium,” Cardiology in the Young, vol. 11, no. 6, pp. 632–642, 2001.
[28]
A. Wessels, R. H. Anderson, R. R. Markwald et al., “Atrial development in the human heart: an immunohistochemical study with emphasis on the role of mesenchymal tissues,” Anatomical Record, vol. 259, no. 3, pp. 288–300, 2000.
[29]
J. C. P. Kingdom and P. Kaufmann, “Oxygen and placental villous development: origins of fetal hypoxia,” Placenta, vol. 18, no. 8, pp. 613–621, 1997.
[30]
G. M. Jensen and L. G. Moore, “The effect of high altitude and other risk factors on birthweight: independent or interactive effects?” American Journal of Public Health, vol. 87, no. 6, pp. 1003–1007, 1997.
[31]
D. A. Giussani, P. S. Phillips, S. Anstee, and D. J. P. Barker, “Effects of altitude versus economic status on birth weight and body shape at birth,” Pediatric Research, vol. 49, no. 4, pp. 490–494, 2001.
[32]
J. P. Mortola, P. B. Frappell, L. Aguero, and K. Armstrong, “Birth weight and altitude: a study in Peruvian communities,” Journal of Pediatrics, vol. 136, no. 3, pp. 324–329, 2000.
[33]
E. Krampl, C. Lees, J. M. Bland, J. E. Dorado, G. Moscoso, and S. Campbell, “Fetal biometry at 4300 m compared to sea level in Peru,” Ultrasound in Obstetrics and Gynecology, vol. 16, no. 1, pp. 9–18, 2000.
[34]
L. E. Keyes, J. F. Armaza, S. Niermeyer, E. Vargas, D. A. Young, and L. G. Moore, “Intrauterine growth restriction, preeclampsia, and intrauterine mortality at high altitude in Bolivia,” Pediatric Research, vol. 54, no. 1, pp. 20–25, 2003.
[35]
B. Sibai, G. Dekker, and M. Kupferminc, “Pre-eclampsia,” The Lancet, vol. 365, no. 9461, pp. 785–799, 2005.
[36]
S. K. Palmer, L. G. Moore, D. A. Young, B. Cregger, J. C. Berman, and S. Zamudio, “Altered blood pressure course during normal pregnancy and increased preeclampsia at high altitude (3100 meters) in Colorado,” American Journal of Obstetrics and Gynecology, vol. 180, no. 5, pp. 1161–1168, 1999.
[37]
L. G. Moore, D. W. Hershey, D. Jahnigen, and W. Bowes Jr., “The incidence of pregnancy-induced hypertension is increased among Colorado residents at high altitude,” American Journal of Obstetrics and Gynecology, vol. 144, no. 4, pp. 423–429, 1982.
[38]
X.-Q. Hu, L. D. Longo, R. D. Gilbert, and L. Zhang, “Effects of long-term high-altitude hypoxemia on α1-adrenergic receptors in the ovine uterine artery,” American Journal of Physiology, vol. 270, no. 3, pp. H1001–H1007, 1996.
[39]
S. N. Mateev, R. Mouser, D. A. Young, R. P. Mecham, and L. G. Moore, “Chronic hypoxia augments uterine artery distensibility and alters the circumferential wall stress-strain relationship during pregnancy,” Journal of Applied Physiology, vol. 100, no. 6, pp. 1842–1850, 2006.
[40]
L. Zhang, D. Xiao, and X. Hu, “Effect of cGMP on pharmacomechanical coupling in the uterine artery of near-term pregnant sheep,” Journal of Pharmacology and Experimental Therapeutics, vol. 327, no. 2, pp. 425–431, 2008.
[41]
J. L. James, P. R. Stone, and L. W. Chamley, “The regulation of trophoblast differentiation by oxygen in the first trimester of pregnancy,” Human Reproduction Update, vol. 12, no. 2, pp. 137–144, 2006.
[42]
T. Kitanaka, R. D. Gilbert, and L. D. Longo, “Maternal responses to long-term hypoxemia in sheep,” American Journal of Physiology, vol. 256, no. 6, part 2, pp. R1340–R1347, 1989.
[43]
N. A. Kametas, F. McAuliffe, E. Krampl, J. Chambers, and K. H. Nicolaides, “Maternal cardiac function during pregnancy at high altitude,” BJOG, vol. 111, no. 10, pp. 1051–1058, 2004.
[44]
S. Zamudio, S. K. Palmer, T. Droma, E. Stamm, C. Coffin, and L. G. Moore, “Effect of altitude on uterine artery blood flow during normal pregnancy,” Journal of Applied Physiology, vol. 79, no. 1, pp. 7–14, 1995.
[45]
L. G. Moore, D. Young, R. E. McCullough, T. Droma, and S. Zamudio, “Tibetan protection from intrauterine growth restriction (IUGR) and reproductive loss at high altitude,” American Journal of Human Biology, vol. 13, no. 5, pp. 635–644, 2001.
[46]
C. G. Julian, M. J. Wilson, M. Lopez et al., “Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth,” American Journal of Physiology, vol. 296, no. 5, pp. R1564–R1575, 2009.
[47]
S. C. Siu, J. M. Colman, S. Sorensen et al., “Adverse neonatal and cardiac outcomes are more common in pregnant women with cardiac disease,” Circulation, vol. 105, no. 18, pp. 2179–2184, 2002.
[48]
S. C. Siu, M. Sermer, J. M. Colman et al., “Prospective multicenter study of pregnancy outcomes in women with heart disease,” Circulation, vol. 104, no. 5, pp. 515–521, 2001.
[49]
A. Hameed, I. S. Karaalp, P. P. Tummala et al., “The effect of valvular heart disease on maternal and fetal outcome of pregnancy,” Journal of the American College of Cardiology, vol. 37, no. 3, pp. 893–899, 2001.
[50]
P. Presbitero, J. Somerville, S. Stone, E. Aruta, D. Spiegelhalter, and F. Rabajoli, “Pregnancy in cyanotic congenital heart disease: outcome of mother and fetus,” Circulation, vol. 89, no. 6, pp. 2673–2676, 1994.
[51]
J. S. Sellman and R. L. Holman, “Thromboembolism during pregnancy: risks, challenges, and recommendations,” Postgraduate Medicine, vol. 108, no. 4, pp. 71–84, 2000.
[52]
“ACOG technical bulletin. Pulmonary disease in pregnancy. Number 224—June 1996. American College of Obstetricians and Gynecologists,” International Journal of Gynaecology and Obstetrics, vol. 54, no. 2, pp. 187–196, 1996.
[53]
R. Kumar, “Prenatal factors and the development of asthma,” Current Opinion in Pediatrics, vol. 20, no. 6, pp. 682–687, 2008.
[54]
E. S. Guy, A. Kirumaki, and N. A. Hanania, “Acute asthma in pregnancy,” Critical Care Clinics, vol. 20, no. 4, pp. 731–745, 2004.
[55]
L. D. Inge and J. W. Wilson, “Update on the treatment of tuberculosis,” American Family Physician, vol. 78, no. 4, pp. 457–470, 2008.
[56]
S. M. Rowe, S. Miller, and E. J. Sorscher, “Cystic fibrosis,” The New England Journal of Medicine, vol. 352, no. 19, pp. 1992–2001, 2005.
[57]
E. Y. Cheng, C. H. Goss, E. F. McKone et al., “Aggressive prenatal care results in successful fetal outcomes in CF women,” Journal of Cystic Fibrosis, vol. 5, no. 2, pp. 85–91, 2006.
[58]
I. ？degaard, B. Stray-Pedersen, K. Hallberg, O. C. Haanaes, O. T. Storr？sten, and M. Johannesson, “Maternal and fetal morbidity in pregnancies of Norwegian and Swedish women with cystic fibrosis,” Acta Obstetricia et Gynecologica Scandinavica, vol. 81, no. 8, pp. 698–705, 2002.
[59]
A. Rosenberg, “The IUGR newborn,” Seminars in Perinatology, vol. 32, no. 3, pp. 219–224, 2008.
[60]
C. H. Goss, G. D. Rubenfeld, K. Otto, and M. L. Aitken, “The effect of pregnancy on survival in women with cystic fibrosis,” Chest, vol. 124, no. 4, pp. 1460–1468, 2003.
[61]
D. S. Hardin, J. Rice, R. C. Cohen, K. J. Ellis, and J. A. Nick, “The metabolic effects of pregnancy in cystic fibrosis,” Obstetrics and Gynecology, vol. 106, no. 2, pp. 367–375, 2005.
[62]
S. W. McColgin, L. Glee, and B. A. Brian, “Pulmonary disorders complicating pregnancy,” Obstetrics and Gynecology Clinics of North America, vol. 19, no. 4, pp. 697–717, 1992.
[63]
J. M. Shapiro, “Critical care of the obstetric patient,” Journal of Intensive Care Medicine, vol. 21, no. 5, pp. 278–286, 2006.
[64]
S. Mahajan, R. Aalinkeel, P. Shah, S. Singh, and N. Kochupillai, “Nutritional anaemia dysregulates endocrine control of fetal growth,” British Journal of Nutrition, vol. 100, no. 2, pp. 408–417, 2008.
[65]
P. N. Singla, M. Tyagi, A. Kumar, D. Dash, and R. Shankar, “Fetal growth in maternal anaemia,” Journal of Tropical Pediatrics, vol. 43, no. 2, pp. 89–92, 1997.
[66]
P. N. Baker, S. J. Wheeler, T. A. Sanders et al., “A prospective study of micronutrient status in adolescent pregnancy,” American Journal of Clinical Nutrition, vol. 89, no. 4, pp. 1114–1124, 2009.
[67]
L. H. Allen, “Pregnancy and iron deficiency: unresolved issues,” Nutrition Reviews, vol. 55, no. 4, pp. 91–101, 1997.
[68]
D. J. P. Barker, A. R. Bull, C. Osmond, and S. J. Simmonds, “Fetal and placental size and risk of hypertension in adult life,” British Medical Journal, vol. 301, no. 6746, pp. 259–262, 1990.
[69]
T. T. Lao and W. M. Wong, “Placental ratio—its relationship with mild maternal anaemia,” Placenta, vol. 18, no. 7, pp. 593–596, 1997.
[70]
L. A. Williams, S. F. Evans, and J. P. Newnham, “Prospective cohort study of factors influencing the relative weights of the placenta and the newborn infant,” British Medical Journal, vol. 314, no. 7098, pp. 1864–1868, 1997.
[71]
S. C. Davies, E. Cronin, M. Gill, P. Greengross, M. Hickman, and C. Normand, “Screening for sickle cell disease and thalassaemia: a systematic review with supplementary research,” Health Technology Assessment, vol. 4, no. 3, pp. 1–87, 2000.
[72]
A. G. Motulsky, “Frequency of sickling disorders in U.S. blacks,” The New England Journal of Medicine, vol. 288, no. 1, pp. 31–33, 1973.
[73]
“ACOG practice bulletin no. 78: hemoglobinopathies in pregnancy,” Obstetrics and Gynecology, vol. 109, no. 1, pp. 229–238, 2007.
[74]
P. M. Sun, W. Wilburn, B. D. Raynor, and D. Jamieson, “Sickle cell disease in pregnancy: twenty years of experience at Grady Memorial Hospital, Atlanta, Georgia,” American Journal of Obstetrics and Gynecology, vol. 184, no. 6, pp. 1127–1130, 2001.
[75]
M. Koshy, L. Burd, D. Wallace, A. Moawad, and J. Baron, “Prophylactic red-cell transfusions in pregnant patients with sickle cell disease. A randomized cooperative study,” The New England Journal of Medicine, vol. 319, no. 22, pp. 1447–1452, 1988.
[76]
H. H. Kazazian Jr., “The thalassemia syndromes: molecular basis and prenatal diagnosis in 1990,” Seminars in Hematology, vol. 27, no. 3, pp. 209–228, 1990.
[77]
A. Aessopos, F. Karabatsos, D. Farmakis et al., “Pregnancy in patients with well-treated β-thalassemia: outcome for mothers and newborn infants,” American Journal of Obstetrics and Gynecology, vol. 180, no. 2, part 1, pp. 360–365, 1999.
[78]
C. E. Jensen, S. M. Tuck, and B. Wonke, “Fertility in β thalassaemia major: a report of 16 pregnancies, preconceptual evaluation and a review of the literature,” British Journal of Obstetrics and Gynaecology, vol. 102, no. 8, pp. 625–629, 1995.
[79]
H. C. Ong, J. C. White, and T. A. Sinnathuray, “Haemoglobin H disease and pregnancy in a Malaysian woman,” Acta Haematologica, vol. 58, no. 4, pp. 229–233, 1977.
[80]
J. E. Ramsay, F. Stewart, I. A. Greer, and N. Sattar, “Microvascular dysfunction: a link between pre-eclampsia and maternal coronary heart disease,” BJOG, vol. 110, no. 11, pp. 1029–1031, 2003.
[81]
B. J. Wilson, M. S. Watson, G. J. Prescott et al., “Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study,” British Medical Journal, vol. 326, no. 7394, pp. 845–849, 2003.
[82]
L. Haukkamaa, M. Salminen, H. Laivuori, H. Leinonen, V. Hiilesmaa, and R. Kaaja, “Risk for subsequent coronary artery disease after preeclampsia,” American Journal of Cardiology, vol. 93, no. 6, pp. 805–808, 2004.
[83]
D. J. P. Barker, “Growth in utero and coronary heart disease,” Nutrition Reviews, vol. 54, no. 2, pp. S1–S7, 1996.
[84]
D. J. P. Barker, C. Osmond, J. Golding, D. Kuh, and M. E. J. Wadsworth, “Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease,” British Medical Journal, vol. 298, no. 6673, pp. 564–567, 1989.
[85]
D. J. P. Barker, A. W. Shiell, M. E. Barker, and C. M. Law, “Growth in utero and blood pressure levels in the next generation,” Journal of Hypertension, vol. 18, no. 7, pp. 843–846, 2000.
[86]
E. A. Herrera, V. M. Pulgar, R. A. Riquelme et al., “High-altitude chronic hypoxia during gestation and after birth modifies cardiovascular responses in newborn sheep,” American Journal of Physiology, vol. 292, no. 6, pp. R2234–R2240, 2007.
[87]
C. N. Martyn, D. J. P. Barker, S. Jespersen, S. Greenwald, C. Osmond, and C. Berry, “Growth in utero, adult blood pressure, and arterial compliance,” British Heart Journal, vol. 73, no. 2, pp. 116–121, 1995.
[88]
C. Sartori, Y. Allemann, L. Trueb, A. Delabays, P. Nicod, and U. Scherrer, “Augmented vasoreactivity in adult life associated with perinatal vascular insult,” The Lancet, vol. 353, no. 9171, pp. 2205–2207, 1999.
[89]
R. B. Ness and B. M. Sibai, “Shared and disparate components of the pathophysiologies of fetal growth restriction and preeclampsia,” American Journal of Obstetrics and Gynecology, vol. 195, no. 1, pp. 40–49, 2006.
[90]
J. G. Ray, M. J. Vermeulen, M. J. Schull, and D. A. Redelmeier, “Cardiovascular health after maternal placental syndromes (CHAMPS): population-based retrospective cohort study,” The Lancet, vol. 366, no. 9499, pp. 1797–1803, 2005.
[91]
A. Y. Lausman, J. C. Kingdom, T. J. Bradley, C. Slorach, and J. G. Ray, “Subclinical atherosclerosis in association with elevated placental vascular resistance in early pregnancy,” Atherosclerosis, vol. 206, no. 1, pp. 33–35, 2009.
[92]
E. J. Roccella, “Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy,” American Journal of Obstetrics and Gynecology, vol. 183, no. 1, pp. S1–S22, 2000.
[93]
B. M. Sibai, “Diagnosis and management of gestational hypertension and preeclampsia,” Obstetrics and Gynecology, vol. 102, no. 1, pp. 181–192, 2003.
[94]
K. A. Douglas and C. W. G. Redman, “Eclampsia in the United Kingdom,” British Medical Journal, vol. 309, no. 6966, pp. 1395–1400, 1994.
[95]
B. M. Sibai, “Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count,” Obstetrics and Gynecology, vol. 103, no. 5, part 1, pp. 981–991, 2004.
[96]
C. W. G. Redman, “Platelets and the beginnings of preeclampsia,” The New England Journal of Medicine, vol. 323, no. 7, pp. 478–480, 1990.
[97]
J. C. Hauth, M. G. Ewell, R. J. Levine et al., “Pregnancy outcomes in healthy nulliparas who developed hypertension,” Obstetrics and Gynecology, vol. 95, no. 1, pp. 24–28, 2000.
[98]
M. D. Hnat, B. M. Sibai, S. Caritis et al., “Perinatal outcome in women with recurrent preeclampsia compared with women who develop preeclampsia as nulliparas,” American Journal of Obstetrics and Gynecology, vol. 186, no. 3, pp. 422–426, 2002.
[99]
A. Buchbinder, B. M. Sibai, S. Caritis et al., “Adverse perinatal outcomes are significantly higher in severe gestational hypertension than in mild preeclampsia,” American Journal of Obstetrics and Gynecology, vol. 186, no. 1, pp. 66–71, 2002.
[100]
J. Zhang, S. Meikle, and A. Trumble, “Severe maternal morbidity associated with hypertensive disorders in pregnancy in the United States,” Hypertension in Pregnancy, vol. 22, no. 2, pp. 203–212, 2003.
[101]
P.-Y. Jayet, S. F. Rimoldi, T. Stuber et al., “Pulmonary and systemic vascular dysfunction in young offspring of mothers with preeclampsia,” Circulation, vol. 122, no. 5, pp. 488–494, 2010.
[102]
R. N. Pollack and M. Y. Divon, “Intrauterine growth retardation: definition, classification, and etiology,” Clinical Obstetrics and Gynecology, vol. 35, no. 1, pp. 99–107, 1992.
[103]
K. Meyer and L. Zhang, “Fetal programming of cardiac function and disease,” Reproductive Sciences, vol. 14, no. 3, pp. 209–216, 2007.
[104]
W. S. Webster and D. Abela, “The effect of hypoxia in development,” Birth Defects Research Part C, vol. 81, no. 3, pp. 215–228, 2007.
[105]
L. Zhang, “Prenatal hypoxia and cardiac programming,” Journal of the Society for Gynecologic Investigation, vol. 12, no. 1, pp. 2–13, 2005.
[106]
W. Al-Ghazali, S. K. Chita, M. G. Chapman, and L. D. Allan, “Evidence of redistribution of cardiac output in asymmetrical growth retardation,” British Journal of Obstetrics and Gynaecology, vol. 96, no. 6, pp. 697–704, 1989.
[107]
G. Rizzo, D. Arduini, and C. Romanini, “Doppler echocardiographic assessment of fetal cardiac function,” Ultrasound in Obstetrics and Gynecology, vol. 2, no. 6, pp. 434–445, 1992.
[108]
J.-C. Fouron, A. Skoll, S.-E. Sonesson, M. Pfizenmaier, E. Jaeggi, and M. Lessard, “Relationship between flow through the fetal aortic isthmus and cerebral oxygenation during acute placental circulatory insufficiency in ovine fetuses,” American Journal of Obstetrics and Gynecology, vol. 181, no. 5, pp. 1102–1107, 1999.
[109]
J. W. Wladimiroff, H. M. Tonge, and P. A. Stewart, “Doppler ultrasound assessment of cerebral blood flow in the human fetus,” British Journal of Obstetrics and Gynaecology, vol. 93, no. 5, pp. 471–475, 1986.
[110]
J.-C. Fouron, G. Teyssier, E. Maroto, M. Lessard, and G. Marquette, “Diastolic circulatory dynamics in the presence of elevated placental resistance and retrograde diastolic flow in the umbilical artery: a Doppler echographic study in lambs,” American Journal of Obstetrics and Gynecology, vol. 164, no. 1, pp. 195–203, 1991.
[111]
G. Rizzo and D. Arduini, “Fetal cardiac function in intrauterine growth retardation,” American Journal of Obstetrics and Gynecology, vol. 165, no. 4, pp. 876–882, 1991.
[112]
S. Gudmundsson, G. Tulzer, J. C. Huhta, and K. Marsal, “Venous Doppler in the fetus with absent end-diastolic flow in the umbilical artery,” Ultrasound in Obstetrics and Gynecology, vol. 7, no. 4, pp. 262–267, 1996.
[113]
V. A. Browne, V. M. Stiffel, W. J. Pearce, L. D. Longo, and R. D. Gilbert, “Cardiac β-adrenergic receptor function in fetal sheep exposed to long-term high-altitude hypoxemia,” American Journal of Physiology, vol. 273, no. 6, pp. R2022–R2031, 1997.
[114]
V. A. Browne, V. M. Stiffel, W. J. Pearce, L. D. Longo, and R. D. Gilbert, “Activator calcium and myocardial contractility in fetal sheep exposed to long-term high-altitude hypoxia,” American Journal of Physiology, vol. 272, no. 3, part 2, pp. H1196–H1204, 1997.
[115]
F. C. Garcia, V. M. Stiffel, W. J. Pearce, L. Zhang, and R. D. Gilbert, “ sensitivity of fetal coronary arteries exposed to long-term, high-altitude hypoxia,” Journal of the Society for Gynecologic Investigation, vol. 7, no. 3, pp. 161–166, 2000.
[116]
M. Kamitomo, J. G. Alonso, T. Okai, L. D. Longo, and R. D. Gilbert, “Effects of long-term, high-altitude hypoxemia on ovine fetal cardiac output and blood flow distribution,” American Journal of Obstetrics and Gynecology, vol. 169, no. 3, pp. 701–707, 1993.
[117]
L. P. Thompson, “Effects of chronic hypoxia on fetal coronary responses,” High Altitude Medicine and Biology, vol. 4, no. 2, pp. 215–224, 2003.
[118]
D. J. P. Barker, “The fetal origins of adult hypertension,” Journal of Hypertension, vol. 10, no. 7, pp. S39–S44, 1992.
[119]
D. J. P. Barker, “Fetal nutrition and cardiovascular disease in later life,” British Medical Bulletin, vol. 53, no. 1, pp. 96–108, 1997.
[120]
D. J. P. Barker, P. D. Gluckman, K. M. Godfrey, J. E. Harding, J. A. Owens, and J. S. Robinson, “Fetal nutrition and cardiovascular disease in adult life,” The Lancet, vol. 341, no. 8850, pp. 938–941, 1993.
[121]
D. J. Barker, “The fetal origins of coronary heart disease,” European Heart Journal, vol. 18, no. 6, pp. 883–884, 1997.
[122]
D. J. P. Barker, “In utero programming of chronic disease,” Clinical Science, vol. 95, no. 2, pp. 115–128, 1998.
[123]
D. J. P. Barker, “In utero programming of cardiovascular disease,” Theriogenology, vol. 53, no. 2, pp. 555–574, 2000.
[124]
D. J. P. Barker, S. P. Bagby, and M. A. Hanson, “Mechanisms of disease: in utero programming in the pathogenesis of hypertension,” Nature Clinical Practice Nephrology, vol. 2, no. 12, pp. 700–707, 2006.
[125]
D. A. Leon, H. O. Lithell, D. V？ger？ et al., “Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915–1929,” British Medical Journal, vol. 317, no. 7153, pp. 241–245, 1998.
[126]
A.-K. E. Bonamy, A. Bendito, H. Martin, E. Andolf, G. Sedin, and M. Norman, “Preterm birth contributes to increased vascular resistance and higher blood pressure in adolescent girls,” Pediatric Research, vol. 58, no. 5, pp. 845–849, 2005.
[127]
S. Johansson, A. Iliadou, N. Bergvall, T. Tuvemo, M. Norman, and S. Cnattingius, “Risk of high blood pressure among young men increases with the degree of immaturity at birth,” Circulation, vol. 112, no. 22, pp. 3430–3436, 2005.
[128]
H. Martin, J. Hu, G. Gennser, and M. Norman, “Impaired endothelial function and increased carotid stiffness in 9-year-old children with low birthweight,” Circulation, vol. 102, no. 22, pp. 2739–2744, 2000.
[129]
S. Lewington, R. Clarke, N. Qizilbash, R. Peto, and R. Collins, “Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies,” The Lancet, vol. 360, no. 9349, pp. 1903–1913, 2002.
[130]
L. Blais and M.-F. Beauchesne, “Use of inhaled corticosteroids following discharge from an emergency department for an acute exacerbation of asthma,” Thorax, vol. 59, no. 11, pp. 943–947, 2004.
[131]
S. Bae, Y. Xiao, G. Li, C. A. Casiano, and L. Zhang, “Effect of maternal chronic hypoxic exposure during gestation on apoptosis in fetal rat heart,” American Journal of Physiology, vol. 285, no. 3, pp. H983–H990, 2003.
[132]
L. H. E. H. Snoeckx, R. N. Cornelussen, F. A. van Nieuwenhoven, R. S. Reneman, and G. J. van der Vusse, “Heat shock proteins and cardiovascular pathophysiology,” Physiological Reviews, vol. 81, no. 4, pp. 1461–1497, 2001.
[133]
L. Xi, D. Tekin, P. Bhargava, and R. C. Kukreja, “Whole body hyperthermia and preconditioning of the heart: basic concepts, complexity, and potential mechanisms,” International Journal of Hyperthermia, vol. 17, no. 5, pp. 439–455, 2001.
[134]
D. M. Yellon, E. Pasini, A. Cargnoni, M. S. Marber, D. S. Latchman, and R. Ferrari, “The protective role of heat stress in the ischaemic and reperfused rabbit myocardium,” Journal of Molecular and Cellular Cardiology, vol. 24, no. 8, pp. 895–907, 1992.
[135]
H. M. Beere and D. R. Green, “Stress management—heat shock protein-70 and the regulation of apoptosis,” Trends in Cell Biology, vol. 11, no. 1, pp. 6–10, 2001.
[136]
J. J. Hutter, R. Mestril, E. K. W. Tam, R. E. Sievers, W. H. Dillmann, and C. L. Wolfe, “Overexpression of heat shock protein 72 in transgenic mice decreases infarct size in vivo,” Circulation, vol. 94, no. 6, pp. 1408–1411, 1996.
[137]
J. Jayakumar, K. Suzuki, I. A. Sammut et al., “Heat shock protein 70 gene transfection protects mitochondrial and ventricular function against ischemia-reperfusion injury,” Circulation, vol. 104, no. 12, supplement 1, pp. i303–i307, 2001.
[138]
G. Li, Y. Xiao, J. L. Estrella, C. A. Ducsay, R. D. Gilbert, and L. Zhang, “Effect of fetal hypoxia on heart susceptibility to ischemia and reperfusion injury in the adult rat,” Journal of the Society for Gynecologic Investigation, vol. 10, no. 5, pp. 265–274, 2003.
[139]
L. P. Thompson and Y. Dong, “Chronic hypoxia decreases endothelial nitric oxide synthase protein expression in fetal guinea pig hearts,” Journal of the Society for Gynecologic Investigation, vol. 12, no. 6, pp. 388–395, 2005.
[140]
R.-P. Xiao, “Cell logic for dual coupling of a single class of receptors to and proteins,” Circulation Research, vol. 87, no. 8, pp. 635–637, 2000.
[141]
A. Chesley, M. S. Lundberg, T. Asai et al., “The β2-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through -dependent coupling to phosphatidylinositol -kinase,” Circulation Research, vol. 87, no. 12, pp. 1172–1179, 2000.
