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  • Cited by 1
  • Print publication year: 2010
  • Online publication date: February 2011

10 - Clinical causes and aspects of placental insufficiency


This chapter uses new epidemiological data to examine the role of materno-placental interactions in initiating chronic disease in the offspring. The size, weight and shape of the placenta are all subject to wide variations. Its size reflects its ability to transfer nutrients. In humans, placental growth responds to maternal influences. Maternal anemia and high maternal body mass index are associated with a high placental weight to birth weight ratio. The observations on hypertension established that the relation between placental size/shape and fetal programming depend on the mother. There are similar materno-placental interactions in the programming of coronary heart disease. Growth of the placental surface is polarized from the time of implantation. The human fetus may attempt to compensate for undernutrition by expansion of the placental surface along its minor axis. The maternal/ placental programming of chronic disease differs in boys and girls.


1. CetinI, SparksJW. Determinants of intrauterine growth. In: Hay WW, Thureen P, eds. Neonatal Nutrition and Metabolism 2nd edn. Cambridge: Cambridge University Press, 2005.
2. BaschatAA. Fetal responses to placental insufficiency: an update. Br J Obstet Gynaecol 2004; 111: 1031–41.
3. AlexanderGR, KoganM, BaderDet al. US birth weight/gestational age-specific neonatal mortality: 1995–1997 rates for whites, hispanics, and blacks. Pediatrics 2003; 111: e61–6.
4. BaschatAA, CosmiE, BilardoCMet al. Predictors of neonatal outcome in early-onset placental dysfunction. Obstet Gynecol 2007; 109: 253–61.
5. PrysakM, LorenzRP, KislyA. Pregnancy outcome in nulliparous women 35 years and older. Obstet Gynecol 1995; 85(1): 65–70.
6. VisserGH, SadovskyG, NicolaidesKH. Antepartum heart rate patterns in small for gestational age third-trimester fetuses: correlations with blood gas values obtained at cordocentesis. Am J Obstet Gynecol 1990; 162: 698–703.
7. BerkowitzGS, SkovronML, LapinskiRH, BerkowitzRL. Delayed childbearing and the outcome of pregnancy. N Engl J Med 1990; 322 (10): 693–4.
8. BernsteinIM, HorbarJD, BadgerGJ, OhlssonA, Golan. A Morbidity and mortality among very-low-birth weight neonates with intrauterine growth restriction. Am J Obstet Gynecol 2000; 182: 198–206.
9. GortnerL, WauerRR, StockGJet al. Neonatal outcome in small for gestational age infants: do they really better?J Perinat Med 1999; 27: 484–9.
10. PardiG, CetinI. Human fetal growth and organ development: fifty years of discoveries. Am J Obstet Gynecol 2006; 194: 1088–99.
11. ParazziniF, CortinovisI, BotulusR, FedeleL. Standard di peso alla nascita in Italia. Ann Ost Gin Med Perinatol CXII 1991; 203–46.
12. CetinI, BoitoS, RadaelliT. Evaluation of fetal growth and fetal well-being. Semin Ultrasound CT MRI 2008; 29: 136–46.
13. EnziG, ZanardoV, CarettaF, InelmenEM, RubaltelliF. Intrauterine growth and adipose tissue development. Am J Clin Nutr 1981; 34: 1785–90.
14. MolteniRA, StysSJ, BattagliaFC. Relationship of fetal and placental weight in human beings: fetal/placental weight ratios at various gestational ages and birth weight distributions. J Reprod Med 1978; 21: 327–34.
15. SibleyCP, TurnerMA, CetinIet al. Placental phenotypes of intrauterine growth. Pediatr Res 2005; 58: 827–32.
16. SaemundssonY, SvantessonH, GudmundssonS. Abnormal uterine artery Doppler in pregnancies suspected of a SGA fetus is related to increased risk of recurrence during next pregnancy. Acta Obstet Gynecol Scand 2009; 88(7): 814–17.
17. BerghellaV. Prevention of reccurent fetal growth restriction. Obstet Gynecol 2007; 110: 904–12.
18. KupfermincMJ, EldorA, SteinmanNet al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 1999; 340: 9–13.
19. Infante-RivardC, RivardGE, YotovWVet al. Absence of association of thrombophilia polymorphism with intrauterine growth restriction. N Engl J Med 2002; 347: 19–25.
20. FranchiF, CetinI, TodrosTet al. Intrauterine growth restriction and genetic predisposition to thrombophilia. Haematologica 2004; 89: 444–9.
21. RodgerM, PaidasM, McLintockCet al. Inherited thrombophilia and pregnancy complications revisited. Obstet Gynecol 2008; 112: 320–4.
22. RobertsCT. Review: complicated interactions between genes and the environment in placentation, pregnancy outcome and long term health. Placenta 2010; 31: S47–S53.
23. DiplasAI, LambertiniL, LeeMJet al. Differential expression of imprinted genes in normal and IUGR human placentas. Epigenetics 2009; 4: 235–40.
24. GratiFR, MiozzoM, CassaniBet al. Fetal and placental chromosomal mosaicism revealed by QF-PCR in severe IUGR pregnancies. Placenta 2005; 26: 10–18.
25. BattagliaFC, MeschiaG. An Introduction to Fetal Physiology. London: Academic Press, 1986.
26. BellAW, WilkeningRB, MeschiaG. Some aspects of placental function in chronically heat-stressed ewes. J Dev Physiol 1987; 9: 17–29.
27. HeinonenS, TaipaleP, SaarikoskiS. Weights of placentae from small-for-gestational age infants revisited. Placenta 2001; 22: 399–404.
28. BarkerDJP, BullAR, OsmondCet al. Fetal and placental size and risk of hypertension in adult life. Br Med J 1990; 301: 259–62.
29. PardiG, MarconiAM, CetinI. Placental-fetal interrelationship in IUGR fetuses – a review. Trophoblast Res 2002; 23, S136–41.
30. MarconiAM, PaoliniCL, ZerbeG, BattagliaFC. Lactacidemia in intrauterine growth restricted (IUGR) pregnancies: relationship to clinical severity, oxygenation and placental weight. Pediatr Res 2006; 59: 570–4.
31. SalafiaCM, CharlesAK, MaasEM. Placenta and fetal growth restriction. Clin Obstet Gynecol 2006; 49: 236–56.
32. BiswasS, GhoshSK, ChhabraS. Surface area of chorionic villi of placentas: an index of intrauterine growth restriction of fetuses. J Obstet Gynaecol Res 2008; 34: 487–93.
33. BarkerDJP, ThornburgKL, OsmondC, KajanteE, Eriksson. The surface area of the placenta and hypertension in the offspring in later life. Int. J. Dev. Biol 2010; 54: 525–30.
34. LumeyLH. Decreased birth weights in infants after maternal in utero exposure to the Dutch famine of 1944–1945. Paediatr Perinatol Epidemiol 1992; 6(2): 240–53.
35. JanssonT, PowellTL. IFPA 2005 Award in Placentology Lecture. Human placental transport in altered fetal growth: does the placenta function as a nutrient sensor? a review. Placenta 2006; 27 Suppl A: S91–7.
36. BrosensI, RobertsonWB, Dixon. The physiological response to vessels of the placental bed to normal pregnancy. J Pathol Bacteriol 1967; 93, 569–79.
37. MeekinsJW, PijnenborgR, HanssensM, McFadyenIR, VanAssheA. A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br J Obstet Gynaecol 1994; 101: 669–74.
38. PijnenborgR, BlandJM, RobertsonWB, BrosensI. Uteroplacental arterial changes related to interstitial trophoblast migration in early human pregnancy. Placenta 1983; 4: 397–413.
39. BurtonGJ, WoodsAW, JauniauxE, KingdomJC. Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta 2009; 30: 473–82.
40. FowdenAL, ForheadAJ, CoanPM, BurtonGJ. The placenta and intrauterine programming. J Neuroendocrinol 2008; 20: 439–50.
41. LattuadaD, ColleoniF, MartinelliAet al. Higher mitochondrial DNA content in human IUGR placenta. Placenta 2008; 29: 1029–33.
42. RadaelliT, BoitoS, CozziVet al. Fetal oxygen consumption in term normal pregnancies. Society for Gynecologic Investigations, Los Angeles, CA, USA, March 23–26, 2005. J Soc Gynecol Invest 2005; Abstract 175, 12.
43. AcharyaG, SitrasV. Oxygen uptake of the human fetus at term. Acta Obstet Gynecol Scand 2009; 88: 104–9.
44. RadaelliT, BoitoS, TariccoEet al. Evalutation of Oxygen Uptake in IUGR Fetuses. Abstract #211 of the 55th Annual Meeting of the Society for Gynecologic Investigation, San Diego, CA, 2008.
45. TariccoE, RadaelliT, RossiGet al. Effects of gestational diabetes on fetal oxygen and glucose levels in vivo. Br J Obstet Gynaecol 2009; 116(13): 1729–35.
46. MarconiAM, PaoliniC, BuscagliaMet al. The impact of gestational age and fetal growth on the maternal-fetal glucose concentration difference. Obstet Gynecol 1996; 87: 937–42.
47. MarconiAM, CetinI, DavoliEet al. An evaluation of fetal glucogenesis in intrauterine growth-retarded pregnancies. Metabolism 1993; 42: 860–4.
48. CetinI. Amino acid interconversions in the fetal-placental unit: the animal model and human studies in vivo. Pediatr Res 2001; 49: 148–54.
49. CetinI, MarconiAM, BaggianiAMet al. In vivo placental transport of glycine and leucine in human pregnancies. Pediatr Res 1995; 37: 571–5.
50. PaoliniCL, MarconiAM, RonzoniSet al. Placental transport of leucine, phenylalanine, glycine, and proline in intrauterine growth-restricted pregnancies. J Clin Endocrinol Metab 2001; 86: 5427–32.
51. CetinI, Nobile De SantisMS, TariccoEet al. Maternal and fetal amino acid concentrations in normal pregnancies and in pregnancies with gestational diabetes mellitus. Am J Obstet Gynecol 2005; 192: 610–17.
52. ClealJK, BrownbillP, GodfreyKMet al. Modification of fetal plasma amino acid composition by placental amino acid exchangers in vitro. J Physiol 2007; 582: 871–82.
53. CetinI, RonzoniS, MarconiAMet al. Maternal concentrations and fetal-maternal concentration differences of plasma amino acids in normal and intrauterine growth-restricted pregnancies. Am J Obstet Gynecol 1996; 174(5): 1575–83.
54. MarconiAM, PaoliniCL, StramareLet al. Steady state maternal-fetal leucine enrichments in normal and intrauterine growth-restricted pregnancies. Pediatr Res 1999; 46(1): 114–19.
55. CetinI, KoletzkoB. Long-chain ω-3 fatty acid supply in pregnancy and lactation. Curr Opin Clin Nutr Metab Care 2008; 11: 297–302.
56. HaggartyP. Placental regulation of fatty acid delivery and its effect on fetal growth–a review. Placenta 2002; 23 Suppl A: S28–38.
57. TobinKA, JohnsenGM, StaffAC, DuttaroyAK. Long-chain polyunsaturated fatty acid transport across human placentachoriocarcinoma (BeWo) cells. Placenta 2009; 30: 41–7.
58. StefuljJ, PanzenboeckU, BeckerTet al. Human endothelial cells of the placental barrier efficiently deliver cholesterol to the fetal circulation via ABCA1 and ABCG1. Circ Res 2009; 104(5): 600–8.
59. CetinI, GiovanniniN, AlvinoGet al. Intrauterine growth restriction is associated with changes in polyunsaturated fatty acid fetal-maternal relationships. Pediatr Res 2002; 52: 750–5.
60. MagnussonAL, WatermanIJ, WennergrenM, JanssonT, PowellTL. Triglyceride hydrolase activities and expression of fatty acid binding proteins in the human placenta in pregnancies complicated by intrauterine growth restriction and diabetes. J Clin Endocrinol Metab 2004; 89: 4607–14.
61. TabanoS, AlvinoG, AntonazzoPet al. Placental LPL gene expression is increased in severe intrauterine growth restricted pregnancies. Pediatr Res 2006; 59: 250–3.
62. WadsackC, TabanoS, MaierAet al. Intrauterine growth restriction (IUGR) is associated with alterations in placental lipoprotein receptors and maternal lipoprotein composition. Am J Physiol Endocrinol Metab 2007; 292: 476–84.
63. GausterM, HidenU, BlaschitzAet al. Dysregulation of placental endothelial lipase and lipoprotein lipase in intrauterine growth-restricted pregnancies. J Clin Endocrinol Metab 2007; 92: 2256–63.
64. PardiG, CetinI, MarconiAMet al. Diagnostic value of blood sampling in fetuses with growth retardation. N Engl J Med 1993; 11; 328(10): 728–9.
65. ThorntonJG, HornbuckleJ, VailA, SpiegelhalterDJ, LeveneM; GRIT Study Group. Infant wellbeing at 2 years of age in the Growth Restriction Intervention Trial (GRIT): multicentred randomised controlled trial. Lancet 2004; 364: 513–20.
66. CetinI, BoitoS, RadaelliT. Evaluation of fetal growth and fetal well-being. Semin Ultrasound CT MRI 2008; 29(2): 136–46.
67. FerrazziE, BozzoM, RiganoSet al. Temporal sequence of abnormal Doppler changes in the peripheral and central circulatory systems of the severely growth-restricted fetus. Ultrasound Obstet Gynecol 2002; 19: 140–6.
68. Cruz-MartinezR, FiguerasF, OrosDet al. Cerebral blood perfusion and neurobehavioral performance in full-term small-for-gestational-age fetuses. Am J Obstet Gynecol 2009; 201(5): 474. e1–7.
69. BhattAB, TankPD, BarmadeKB, DamaniaKR. Abnormal Doppler flow velocimetry in the growth restricted foetus as a predictor for necrotising enterocolitis. J Postgrad Med 2002; 48(3): 182–5.