Abstract
The human embryo is totally dependent on the mother. Anything that affects the mother might have a direct impact on the growing embryo. While intoxication due to maternal drug abuse in industrialized countries is rare, chronic or intermittent hypoxia due to various causes remains one of the highest risks during pregnancy for the unborn child. This chapter will focus on the different mechanisms for intrauterine hypoxia and their impact on the fetal cardiovascular system.
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References
Abbas AE, Lester SJ, Connolly H (2005) Pregnancy and the cardiovascular system. Int J Cardiol 98(2):179–189
ACOG Committee on Obstetrics (2007) ACOG Practice Bulletin No. 78: hemoglobinopathies in pregnancy. Obstet Gynecol 109(1):229–237
Aessopos A et al (1999) Pregnancy in patients with well-treated beta-thalassemia: outcome for mothers and newborn infants. Am J Obstet Gynecol 180(2 Pt 1):360–365
Allen LH (1997) Pregnancy and iron deficiency: unresolved issues. Nutr Rev 55(4):91–101
American College of Obstetricians and Gynecologists (1996) ACOG technical bulletin. Pulmonary disease in pregnancy. Number 224--June 1996. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 54(2):187–196
Ananth CV, Vintzileos AM (2006) Epidemiology of preterm birth and its clinical subtypes. J Matern Fetal Neonatal Med 19(12):773–782
Bae S et al (2003) Effect of maternal chronic hypoxic exposure during gestation on apoptosis in fetal rat heart. Am J Physiol Heart Circ Physiol 285(3):H983–H990
Baker PN et al (2009) A prospective study of micronutrient status in adolescent pregnancy. Am J Clin Nutr 89(4):1114–1124
Barker DJ (1992a) The fetal origins of adult hypertension. J Hypertens Suppl 10(7):S39-44
Barker DJ (1992b) The fetal origins of diseases of old age. Eur J Clin Nutr 46(Suppl 3):S3–S9
Barker DJ (1992c) Fetal growth and adult disease. Br J Obstet Gynaecol 99(4):275–276
Barker DJ (1996) Growth in utero and coronary heart disease. Nutr Rev 54(2 Pt 2):S1–S7
Barker DJ, Martyn CN (1992) The maternal and fetal origins of cardiovascular disease. J Epidemiol Community Health 46(1):8–11
Barker DJ et al (1989) Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 298(6673):564–567
Barker DJ et al (1990) Fetal and placental size and risk of hypertension in adult life. BMJ 301(6746):259–262
Barker DJ et al (2000) Growth in utero and blood pressure levels in the next generation. J Hypertens 18(7):843–846
Beere HM, Green DR (2001) Stress management - heat shock protein-70 and the regulation of apoptosis. Trends Cell Biol 11(1):6–10
Blais L, Beauchesne MF (2004) Use of inhaled corticosteroids following discharge from an emergency department for an acute exacerbation of asthma. Thorax 59(11):943–947
Bonamy AK et al (2005) Preterm birth contributes to increased vascular resistance and higher blood pressure in adolescent girls. Pediatr Res 58(5):845–849
Browne VA et al (1997a) Cardiac beta-adrenergic receptor function in fetal sheep exposed to long-term high-altitude hypoxemia. Am J Phys 273(6 Pt 2):R2022–R2031
Browne VA et al (1997b) Activator calcium and myocardial contractility in fetal sheep exposed to long-term high-altitude hypoxia. Am J Phys 272(3 Pt 2):H1196–H1204
Buchbinder A et al (2002) Adverse perinatal outcomes are significantly higher in severe gestational hypertension than in mild preeclampsia. Am J Obstet Gynecol 186(1):66–71
Burton GJ, Jauniaux E, Watson AL (1999) Maternal arterial connections to the placental intervillous space during the first trimester of human pregnancy: the Boyd collection revisited. Am J Obstet Gynecol 181(3):718–724
Cadnapaphornchai MA et al (2001) Chronic NOS inhibition reverses systemic vasodilation and glomerular hyperfiltration in pregnancy. Am J Physiol Renal Physiol 280(4):F592–F598
Caniggia I et al (2000a) Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFbeta(3). J Clin Invest 105(5):577–587
Caniggia I et al (2000b) Oxygen and placental development during the first trimester: implications for the pathophysiology of pre-eclampsia. Placenta 21(Suppl A):S25–S30
Chapman AB et al (1998) Temporal relationships between hormonal and hemodynamic changes in early human pregnancy. Kidney Int 54(6):2056–2063
Cheng EY et al (2006) Aggressive prenatal care results in successful fetal outcomes in CF women. J Cyst Fibros 5(2):85–91
Chesley A et al (2000) The beta(2)-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through G(i)-dependent coupling to phosphatidylinositol 3'-kinase. Circ Res 87(12):1172–1179
Cipolla M, Osol G (1994) Hypertrophic and hyperplastic effects of pregnancy on the rat uterine arterial wall. Am J Obstet Gynecol 171(3):805–811
Davies SC et al (2000) Screening for sickle cell disease and thalassaemia: a systematic review with supplementary research. Health Technol Assess 4(3):i–v. 1–99
Dekker G, Sibai B (2001) Primary, secondary, and tertiary prevention of pre-eclampsia. Lancet 357(9251):209–215
Douglas KA, Redman CW (1994) Eclampsia in the United Kingdom. BMJ 309(6966):1395–1400
Einarsson JI, Sangi-Haghpeykar H, Gardner MO (2003) Sperm exposure and development of preeclampsia. Am J Obstet Gynecol 188(5):1241–1243
Fouron JC et al (1991) Diastolic circulatory dynamics in the presence of elevated placental resistance and retrograde diastolic flow in the umbilical artery: a Doppler echographic study in lambs. Am J Obstet Gynecol 164(1 Pt 1):195–203
Fouron JC et al (1999) Relationship between flow through the fetal aortic isthmus and cerebral oxygenation during acute placental circulatory insufficiency in ovine fetuses. Am J Obstet Gynecol 181(5 Pt 1):1102–1107
Furuhashi N et al (1995) Maternal plasma endothelin levels and fetal status in normal and preeclamptic pregnancies. Gynecol Obstet Investig 39(2):88–92
Garcia FC et al (2000) Ca(2+) sensitivity of fetal coronary arteries exposed to long-term, high-altitude hypoxia. J Soc Gynecol Investig 7(3):161–166
Giussani DA et al (2001) Effects of altitude versus economic status on birth weight and body shape at birth. Pediatr Res 49(4):490–494
Goss CH et al (2003) The effect of pregnancy on survival in women with cystic fibrosis. Chest 124(4):1460–1468
Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281(5381):1309–1312
Gudmundsson S et al (1996) Venous Doppler in the fetus with absent end-diastolic flow in the umbilical artery. Ultrasound Obstet Gynecol 7(4):262–267
Guy ES, Kirumaki A, Hanania NA (2004) Acute asthma in pregnancy. Crit Care Clin 20(4):731–745. x
Hameed A et al (2001) The effect of valvular heart disease on maternal and fetal outcome of pregnancy. J Am Coll Cardiol 37(3):893–899
Hardin DS et al (2005) The metabolic effects of pregnancy in cystic fibrosis. Obstet Gynecol 106(2):367–375
Harrison GL, Moore LG (1990) Systemic vascular reactivity during high-altitude pregnancy. J Appl Physiol 69(1):201–206
Haukkamaa L et al (2004) Risk for subsequent coronary artery disease after preeclampsia. Am J Cardiol 93(6):805–808
Hauth JC et al (2000) Pregnancy outcomes in healthy nulliparas who developed hypertension. Calcium for Preeclampsia Prevention Study Group. Obstet Gynecol 95(1):24–28
Herrera EA et al (2007) High-altitude chronic hypoxia during gestation and after birth modifies cardiovascular responses in newborn sheep. Am J Physiol Regul Integr Comp Physiol 292(6):R2234–R2240
Hnat MD et al (2002) Perinatal outcome in women with recurrent preeclampsia compared with women who develop preeclampsia as nulliparas. Am J Obstet Gynecol 186(3):422–426
Hu XQ et al (1996) Effects of long-term high-altitude hypoxemia on alpha 1-adrenergic receptors in the ovine uterine artery. Am J Phys 270(3 Pt 2):H1001–H1007
Hu XQ et al (1999) Effect of chronic hypoxia on alpha-1 adrenoceptor-mediated inositol 1,4,5-trisphosphate signaling in ovine uterine artery. J Pharmacol Exp Ther 288(3):977–983
Hutter JJ et al (1996) Overexpression of heat shock protein 72 in transgenic mice decreases infarct size in vivo. Circulation 94(6):1408–1411
Inge LD, Wilson JW (2008) Update on the treatment of tuberculosis. Am Fam Physician 78(4):457–465
Irving JA et al (1995) Characteristics of trophoblast cells migrating from first trimester chorionic villus explants and propagated in culture. Placenta 16(5):413–433
James JL, Stone PR, Chamley LW (2006) The regulation of trophoblast differentiation by oxygen in the first trimester of pregnancy. Hum Reprod Update 12(2):137–144
Jauniaux E et al (1992) Doppler ultrasonographic features of the developing placental circulation: correlation with anatomic findings. Am J Obstet Gynecol 166(2):585–587
Jauniaux E et al (2000) Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure. Am J Pathol 157(6):2111–2122
Jauniaux E, Watson A, Burton G (2001) Evaluation of respiratory gases and acid-base gradients in human fetal fluids and uteroplacental tissue between 7 and 16 weeks’ gestation. Am J Obstet Gynecol 184(5):998–1003
Jauniaux E et al (2003) Comparison of ultrasonographic and Doppler mapping of the intervillous circulation in normal and abnormal early pregnancies. Fertil Steril 79(1):100–106
Jayakumar J et al (2001) Heat shock protein 70 gene transfection protects mitochondrial and ventricular function against ischemia-reperfusion injury. Circulation 104(12 Suppl 1):I303–I307
Jensen GM, Moore LG (1997) The effect of high altitude and other risk factors on birthweight: independent or interactive effects? Am J Public Health 87(6):1003–1007
Jensen CE, Tuck SM, Wonke B (1995) Fertility in beta thalassaemia major: a report of 16 pregnancies, preconceptual evaluation and a review of the literature. Br J Obstet Gynaecol 102(8):625–629
Johansson S et al (2005) Risk of high blood pressure among young men increases with the degree of immaturity at birth. Circulation 112(22):3430–3436
Julian CG et al (2009) Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth. Am J Physiol Regul Integr Comp Physiol 296(5):R1564–R1575
Kajstura J et al (1995) Programmed cell death and expression of the protooncogene bcl-2 in myocytes during postnatal maturation of the heart. Exp Cell Res 219(1):110–121
Kametas NA et al (2004) Maternal cardiac function during pregnancy at high altitude. BJOG 111(10):1051–1058
Kamitomo M et al (1993) Effects of long-term, high-altitude hypoxemia on ovine fetal cardiac output and blood flow distribution. Am J Obstet Gynecol 169(3):701–707
Kazazian HH Jr (1990) The thalassemia syndromes: molecular basis and prenatal diagnosis in 1990. Semin Hematol 27(3):209–228
Keyes LE et al (1996) Pregnancy-stimulated growth of vascular smooth muscle cells: importance of protein kinase C-dependent synergy between estrogen and platelet-derived growth factor. J Cell Physiol 166(1):22–32
Keyes LE et al (2003) Intrauterine growth restriction, preeclampsia, and intrauterine mortality at high altitude in Bolivia. Pediatr Res 54(1):20–25
Kingdom JC, Kaufmann P (1997) Oxygen and placental villous development: origins of fetal hypoxia. Placenta 18(8):613–621. discussion 623–6
Kingdom J et al (2000) Development of the placental villous tree and its consequences for fetal growth. Eur J Obstet Gynecol Reprod Biol 92(1):35–43
Kitanaka T, Gilbert RD, Longo LD (1989) Maternal responses to long-term hypoxemia in sheep. Am J Phys 256(6 Pt 2):R1340–R1347
Koshy M et al (1988) Prophylactic red-cell transfusions in pregnant patients with sickle cell disease. A randomized cooperative study. N Engl J Med 319(22):1447–1452
Krampl E et al (2000) Fetal biometry at 4300 m compared to sea level in Peru. Ultrasound Obstet Gynecol 16(1):9–18
Kumar R (2008) Prenatal factors and the development of asthma. Curr Opin Pediatr 20(6):682–687
Lao TT, Wong WM (1997) Placental ratio--its relationship with mild maternal anaemia. Placenta 18(7):593–596
Li G et al (2003) Effect of fetal hypoxia on heart susceptibility to ischemia and reperfusion injury in the adult rat. J Soc Gynecol Investig 10(5):265–274
Magness RR (1998) Maternal cardiovascular and other physiologic responses to the endocrinology of pregnancy. In: Bazer FW (ed) The endocrinology of pregnancy. Humana Press, Totowas, pp 507–539
Mahajan S et al (2008) Nutritional anaemia dysregulates endocrine control of fetal growth. Br J Nutr 100(2):408–417
Martin H et al (2000) Impaired endothelial function and increased carotid stiffness in 9-year-old children with low birthweight. Circulation 102(22):2739–2744
Martyn CN et al (1995) Growth in utero, adult blood pressure, and arterial compliance. Br Heart J 73(2):116–121
Mateev S et al (2003) Chronic hypoxia opposes pregnancy-induced increase in uterine artery vasodilator response to flow. Am J Physiol Heart Circ Physiol 284(3):H820–H829
Mateev SN et al (2006) Chronic hypoxia augments uterine artery distensibility and alters the circumferential wall stress-strain relationship during pregnancy. J Appl Physiol 100(6):1842–1850
McAuliffe F et al (2001) Blood gases in pregnancy at sea level and at high altitude. BJOG 108(9):980–985
McColgin SW, Glee L, Brian BA (1992) Pulmonary disorders complicating pregnancy. Obstet Gynecol Clin N Am 19(4):697–717
Meyer K, Lubo Z (2007) Fetal programming of cardiac function and disease. Reprod Sci 14(3):209–216
Miller MD (2000) Anesthesia, 5th edn. Churchill Livingston, Elsevier
Moore LG (2001) Small babies and big mountains: John Lichty solves a Colorado mystery in Leadville. In: Reeves JT, Grover FT (eds) Attitudes on altitude. University of Colorado Press, Boulder
Moore LG et al (1982) The incidence of pregnancy-induced hypertension is increased among Colorado residents at high altitude. Am J Obstet Gynecol 144(4):423–429
Moore LG et al (1986) Maternal hypoxic ventilatory response, ventilation, and infant birth weight at 4,300 m. J Appl Physiol 60(4):1401–1406
Moore LG et al (2001) Tibetan protection from intrauterine growth restriction (IUGR) and reproductive loss at high altitude. Am J Hum Biol 13(5):635–644
Mortola JP et al (2000) Birth weight and altitude: a study in Peruvian communities. J Pediatr 136(3):324–329
Motulsky AG (1973) Frequency of sickling disorders in U.S. blacks. N Engl J Med 288(1):31–33
Mulvany MJ et al (1996) Vascular remodeling. Hypertension 28(3):505–506
Murphy KM, Streips UN, Lock RB (2000) Bcl-2 inhibits a Fas-induced conformational change in the Bax N terminus and Bax mitochondrial translocation. J Biol Chem 275(23):17225–17228
National High Blood Pressure Education Program Working Group (2000) Report of the National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy. Am J Obstet Gynecol 183(1):S1–S22
Neale D et al (2003) Maternal serum of women with pre-eclampsia reduces trophoblast cell viability: evidence for an increased sensitivity to Fas-mediated apoptosis. J Matern Fetal Neonatal Med 13(1):39–44
Ness RB, Sibai BM (2006) Shared and disparate components of the pathophysiologies of fetal growth restriction and preeclampsia. Am J Obstet Gynecol 195(1):40–49
Ni Y et al (1997) Pregnancy augments uteroplacental vascular endothelial growth factor gene expression and vasodilator effects. Am J Phys 273(2 Pt 2):H938–H944
Odegaard I et al (2002) Maternal and fetal morbidity in pregnancies of Norwegian and Swedish women with cystic fibrosis. Acta Obstet Gynecol Scand 81(8):698–705
Ong HC, White JC, Sinnathuray TA (1977) Haemoglobin H disease and pregnancy in a Malaysian woman. Acta Haematol 58(4):229–233
Palmer SK et al (1992) Quantitative estimation of human uterine artery blood flow and pelvic blood flow redistribution in pregnancy. Obstet Gynecol 80(6):1000–1006
Palmer SK et al (1999) Altered blood pressure course during normal pregnancy and increased preeclampsia at high altitude (3100 meters) in Colorado. Am J Obstet Gynecol 180(5):1161–1168
Peters B et al (2004) Effect of heterosexual intercourse on mucosal alloimmunisation and resistance to HIV-1 infection. Lancet 363(9408):518–524
Pollack RN, Divon MY (1992) Intrauterine growth retardation: definition, classification, and etiology. Clin Obstet Gynecol 35(1):99–107
Presbitero P et al (1994) Pregnancy in cyanotic congenital heart disease. Outcome of mother and fetus. Circulation 89(6):2673–2676
Ramsay JE et al (2003) Microvascular dysfunction: a link between pre-eclampsia and maternal coronary heart disease. BJOG 110(11):1029–1031
Redman CW (1990) Platelets and the beginnings of preeclampsia. N Engl J Med 323(7):478–480
Robertson SA et al (2002) Transforming growth factor beta--a mediator of immune deviation in seminal plasma. J Reprod Immunol 57(1-2):109–128
Rodesch F et al (1992) Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy. Obstet Gynecol 80(2):283–285
Rosenberg A (2008) The IUGR newborn. Semin Perinatol 32(3):219–224
Rowe SM, Miller S, Sorscher EJ (2005) Cystic fibrosis. N Engl J Med 352(19):1992–2001
Saikumar P et al (1998) Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. Oncogene 17(26):3401–3415
Saito S, Sakai M (2003) Th1/Th2 balance in preeclampsia. J Reprod Immunol 59(2):161–173
Sartori C et al (1999) Augmented vasoreactivity in adult life associated with perinatal vascular insult. Lancet 353(9171):2205–2207
Sellman JS, Holman RL (2000) Thromboembolism during pregnancy. Risks, challenges, and recommendations. Postgrad Med 108(4):71–72. 77–8, 81–4
Shapiro JM (2006) Critical care of the obstetric patient. J Intensive Care Med 21(5):278–286
Sibai BM (2003) Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol 102(1):181–192
Sibai BM (2004) Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol 103(5 Pt 1):981–991
Sibai B, Dekker G, Kupferminc M (2005) Pre-eclampsia. Lancet 365(9461):785–799
Singla PN et al (1997) Fetal growth in maternal anaemia. J Trop Pediatr 43(2):89–92
Siu SC, Colman JM (2001) Heart disease and pregnancy. Heart 85(6):710–715
Siu SC et al (2001) Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 104(5):515–521
Siu SC et al (2002) Adverse neonatal and cardiac outcomes are more common in pregnant women with cardiac disease. Circulation 105(18):2179–2184
Snoeckx LH et al (2001) Heat shock proteins and cardiovascular pathophysiology. Physiol Rev 81(4):1461–1497
Sun PM et al (2001) Sickle cell disease in pregnancy: twenty years of experience at Grady Memorial Hospital, Atlanta, Georgia. Am J Obstet Gynecol 184(6):1127–1130
Tanaka M et al (1994) Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes. Circ Res 75(3):426–433
Thompson LP (2003) Effects of chronic hypoxia on fetal coronary responses. High Alt Med Biol 4(2):215–224
Thompson LP, Dong Y (2005) Chronic hypoxia decreases endothelial nitric oxide synthase protein expression in fetal guinea pig hearts. J Soc Gynecol Investig 12(6):388–395
Wang JX et al (2002) Surgically obtained sperm, and risk of gestational hypertension and pre-eclampsia. Lancet 359(9307):673–674
Watson AL et al (1998) Susceptibility of human placental syncytiotrophoblastic mitochondria to oxygen-mediated damage in relation to gestational age. J Clin Endocrinol Metab 83(5):1697–1705
Webster WS, Abela D (2007) The effect of hypoxia in development. Birth Defects Res C Embryo Today 81(3):215–228
Williams LA, Evans SF, Newnham J (1997) Prospective cohort study of factors influencing the relative weights of the placenta and the newborn infant. BMJ 314(7098):1864–1868
Wilson BJ et al (2003) Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study. BMJ 326(7394):845
Xi L et al (2001) Whole body hyperthermia and preconditioning of the heart: basic concepts, complexity, and potential mechanisms. Int J Hyperth 17(5):439–455
Xiao RP (2000) Cell logic for dual coupling of a single class of receptors to G(s) and G(i) proteins. Circ Res 87(8):635–637
Xiao D et al (2002) Cortisol-mediated potentiation of uterine artery contractility: effect of pregnancy. Am J Physiol Heart Circ Physiol 283(1):H238–H246
Xu Y et al (2006) Hypoxia or nutrient restriction during pregnancy in rats leads to progressive cardiac remodeling and impairs postischemic recovery in adult male offspring. FASEB J 20(8):1251–1253
Yaniv G et al (2002) Hypoxia predisposes neonatal rat ventricular myocytes to apoptosis induced by activation of the Fas (CD95/Apo-1) receptor: Fas activation and apoptosis in hypoxic myocytes. Cardiovasc Res 54(3):611–623
Yellon DM et al (1992) The protective role of heat stress in the ischaemic and reperfused rabbit myocardium. J Mol Cell Cardiol 24(8):895–907
Zamudio S et al (1995) Effect of altitude on uterine artery blood flow during normal pregnancy. J Appl Physiol 79(1):7–14
Zhang L (2005) Prenatal hypoxia and cardiac programming. J Soc Gynecol Investig 12(1):2–13
Zhang J, Meikle S, Trumble A (2003) Severe maternal morbidity associated with hypertensive disorders in pregnancy in the United States. Hypertens Pregnancy 22(2):203–212
Zhang L, Xiao D, Hu X (2008) Effect of cGMP on pharmacomechanical coupling in the uterine artery of near-term pregnant sheep. J Pharmacol Exp Ther 327(2):425–431
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Hutter, D. (2018). The Human Embryo and Its Environment: In Utero Challenges and Physiological Outcomes. In: Burggren, W., Dubansky, B. (eds) Development and Environment. Springer, Cham. https://doi.org/10.1007/978-3-319-75935-7_16
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