placental insufficiency


Summary: Failure of the PLACENTA to deliver an adequate supply of nutrients and OXYGEN to the FETUS.

Top Publications

  1. Lane R, Ramirez R, Tsirka A, Kloesz J, McLaughlin M, Gruetzmacher E, et al. Uteroplacental insufficiency lowers the threshold towards hypoxia-induced cerebral apoptosis in growth-retarded fetal rats. Brain Res. 2001;895:186-93 pubmed
    ..We speculate that the decrease in Bcl-2 gene expression increases the vulnerability towards cerebral apoptosis in fetal rats exposed initially to uteroplacental insufficiency and subsequent hypoxic stress. ..
  2. Rees S, Harding R, Walker D. An adverse intrauterine environment: implications for injury and altered development of the brain. Int J Dev Neurosci. 2008;26:3-11 pubmed
    ..These effects are more profound at mid than late gestation. Chronic mild placental insufficiency can result in fetal growth restriction and deficits in neural connectivity and myelination...
  3. Alexander B. Placental insufficiency leads to development of hypertension in growth-restricted offspring. Hypertension. 2003;41:457-62 pubmed
    ..present study was to determine whether a model of intrauterine growth restriction produced in response to placental insufficiency in the pregnant rat was associated with marked elevations in blood pressure...
  4. Leos R, Anderson M, Chen X, Pugmire J, Anderson K, Limesand S. Chronic exposure to elevated norepinephrine suppresses insulin secretion in fetal sheep with placental insufficiency and intrauterine growth restriction. Am J Physiol Endocrinol Metab. 2010;298:E770-8 pubmed publisher
    In this study, we examined chronic norepinephrine suppression of insulin secretion in sheep fetuses with placental insufficiency-induced intrauterine growth restriction (IUGR)...
  5. Barry J, Rozance P, Anthony R. An animal model of placental insufficiency-induced intrauterine growth restriction. Semin Perinatol. 2008;32:225-30 pubmed publisher
    Intrauterine growth restriction (IUGR), often associated with functional placental insufficiency, results in increased perinatal mortality and morbidity...
  6. Siebel A, Mibus A, De Blasio M, Westcott K, Morris M, Prior L, et al. Improved lactational nutrition and postnatal growth ameliorates impairment of glucose tolerance by uteroplacental insufficiency in male rat offspring. Endocrinology. 2008;149:3067-76 pubmed publisher
    ..This study identifies early life as a target for intervention to prevent later diabetes after prenatal restraint. ..
  7. Baserga M, Hale M, Wang Z, Yu X, Callaway C, McKnight R, et al. Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension. Am J Physiol Regul Integr Comp Physiol. 2007;292:R1943-55 pubmed
    ..We conclude that in our animal model, UPI decreases fetal COX-2 expression during a period of active nephrogenesis in the IUGR rat, which is also characterized by decreased nephron number and adult-onset hypertension. ..
  8. Loeliger M, Duncan J, Louey S, Cock M, Harding R, Rees S. Fetal growth restriction induced by chronic placental insufficiency has long-term effects on the retina but not the optic nerve. Invest Ophthalmol Vis Sci. 2005;46:3300-8 pubmed
    ..05) between groups. Chronic placental insufficiency in late gestation results in long-lasting effects on specific retinal components, including photoreceptor ..
  9. Goyal R, Yellon S, Longo L, Mata Greenwood E. Placental gene expression in a rat 'model' of placental insufficiency. Placenta. 2010;31:568-75 pubmed publisher
    b>Placental insufficiency is a major factor associated with pregnancy complications such as miscarriages, intrauterine growth restriction and pre-eclampsia...

More Information


  1. Rozance P, Limesand S, Barry J, Brown L, Hay W. Glucose replacement to euglycemia causes hypoxia, acidosis, and decreased insulin secretion in fetal sheep with intrauterine growth restriction. Pediatr Res. 2009;65:72-8 pubmed publisher
    ..275 +/- 0.071 Glu vs. 7.354 +/- 0.003 Sal, p < 0.01) in the Glu group. We conclude that correction of fetal hypoglycemia is not well tolerated and fails to increase insulin concentrations or beta-cell mass in IUGR fetuses. ..
  2. Murthi P, Said J, Doherty V, Donath S, Nowell C, Brennecke S, et al. Homeobox gene DLX4 expression is increased in idiopathic human fetal growth restriction. Mol Hum Reprod. 2006;12:763-9 pubmed
    Idiopathic fetal growth restriction (FGR) is often associated with placental insufficiency. Previously, we isolated and characterized homeobox gene DLX4 from the placenta and provided evidence that DLX4 may regulate placental development...
  3. Baserga M, Bertolotto C, Maclennan N, Hsu J, Pham T, Laksana G, et al. Uteroplacental insufficiency decreases small intestine growth and alters apoptotic homeostasis in term intrauterine growth retarded rats. Early Hum Dev. 2004;79:93-105 pubmed
    ..We speculate that the morphological change and associated altered apoptotic homeostasis contribute to the increased morbidity of infants affected by uteroplacental insufficiency. ..
  4. Chaddha V, Viero S, Huppertz B, Kingdom J. Developmental biology of the placenta and the origins of placental insufficiency. Semin Fetal Neonatal Med. 2004;9:357-69 pubmed
  5. Thorn S, Regnault T, Brown L, Rozance P, Keng J, Roper M, et al. Intrauterine growth restriction increases fetal hepatic gluconeogenic capacity and reduces messenger ribonucleic acid translation initiation and nutrient sensing in fetal liver and skeletal muscle. Endocrinology. 2009;150:3021-30 pubmed publisher
    ..metabolism in liver and skeletal muscle were investigated in a late-gestation fetal sheep model of placental insufficiency intrauterine growth restriction (PI-IUGR)...
  6. Limesand S, Jensen J, Hutton J, Hay W. Diminished beta-cell replication contributes to reduced beta-cell mass in fetal sheep with intrauterine growth restriction. Am J Physiol Regul Integr Comp Physiol. 2005;288:R1297-305 pubmed publisher
    ..Diminished beta-cell mass in IUGR infants at birth, if not adequately compensated for after birth, may contribute to insufficient insulin production in later life and, thus, a predisposition to noninsulin-dependent diabetes...
  7. Bonel H, Stolz B, Diedrichsen L, Frei K, Saar B, Tutschek B, et al. Diffusion-weighted MR imaging of the placenta in fetuses with placental insufficiency. Radiology. 2010;257:810-9 pubmed publisher fetuses with and fetuses without intrauterine growth restriction (IUGR) who were suspected of having placental insufficiency. The study was approved by the local ethics committee, and written informed consent was obtained...
  8. Loeliger M, Louey S, Cock M, Harding R, Rees S. Chronic placental insufficiency and foetal growth restriction lead to long-term effects on postnatal retinal structure. Clin Exp Ophthalmol. 2003;31:250-3 pubmed
  9. Sitras V, Paulssen R, Leirvik J, Vårtun A, Acharya G. Placental gene expression profile in intrauterine growth restriction due to placental insufficiency. Reprod Sci. 2009;16:701-11 pubmed publisher
    ..Placental samples were collected from IUGR pregnancies due to placental insufficiency ascertained by hemodynamic studies. Four IUGR pregnancies were associated with preeclampsia...
  10. Chen X, Fahy A, Green A, Anderson M, Rhoads R, Limesand S. ?2-Adrenergic receptor desensitization in perirenal adipose tissue in fetuses and lambs with placental insufficiency-induced intrauterine growth restriction. J Physiol. 2010;588:3539-49 pubmed publisher
    b>Placental insufficiency-induced intrauterine growth restriction (IUGR) fetuses have chronic hypoxaemia and elevated plasma catecholamine concentrations...
  11. Greer L, Ziadie M, Casey B, Rogers B, McIntire D, Leveno K. An immunologic basis for placental insufficiency in fetal growth restriction. Am J Perinatol. 2012;29:533-8 pubmed publisher
    ..05). Chronic villitis was associated with anatomic and functional placental insufficiency manifested as placental hypoplasia, growth restriction, increased risk of cesarean for nonreassuring ..
  12. Regnault T, Galan H, Parker T, Anthony R. Placental development in normal and compromised pregnancies-- a review. Placenta. 2002;23 Suppl A:S119-29 pubmed
    ..However, it has been difficult to fully assess their role during the development of placental insufficiency (PI) in the human, underscoring the need for animal models...
  13. Herrmann W, Hübner U, Koch I, Obeid R, Retzke U, Geisel J. Alteration of homocysteine catabolism in pre-eclampsia, HELLP syndrome and placental insufficiency. Clin Chem Lab Med. 2004;42:1109-16 pubmed
    ..such as pre-eclampsia, 'hemolysis, elevated liver enzymes, low platelet' (HELLP)-syndrome and placental insufficiency. The aim of our study was to investigate the alterations of homocysteine catabolism in these patients in ..
  14. Joss Moore L, Wang Y, Campbell M, Moore B, Yu X, Callaway C, et al. Uteroplacental insufficiency increases visceral adiposity and visceral adipose PPARgamma2 expression in male rat offspring prior to the onset of obesity. Early Hum Dev. 2010;86:179-85 pubmed publisher
    ..We speculate that the increase in visceral adiposity may contribute to the metabolic morbidities experienced by this population. ..
  15. Ke X, McKnight R, Wang Z, Yu X, Wang L, Callaway C, et al. Nonresponsiveness of cerebral p53-MDM2 functional circuit in newborn rat pups rendered IUGR via uteroplacental insufficiency. Am J Physiol Regul Integr Comp Physiol. 2005;288:R1038-45 pubmed
  16. Miller J, Turan S, Baschat A. Fetal growth restriction. Semin Perinatol. 2008;32:274-80 pubmed publisher
    ..Choosing appropriate monitoring intervals based on anticipated disease acceleration and intervention when fetal risks exceed neonatal risks are the prevailing current management approaches. ..
  17. Hagen A, Orbus R, Wilkening R, Regnault T, Anthony R. Placental expression of angiopoietin-1, angiopoietin-2 and tie-2 during placental development in an ovine model of placental insufficiency-fetal growth restriction. Pediatr Res. 2005;58:1228-32 pubmed publisher
    ..FGR) is associated with increased perinatal morbidity and mortality, and often results from functional placental insufficiency. Placentation requires extensive vasculogenesis and subsequent angiogenesis, in both maternal and fetal ..
  18. Damodaram M, Story L, Eixarch E, Patel A, McGuinness A, Allsop J, et al. Placental MRI in intrauterine fetal growth restriction. Placenta. 2010;31:491-8 pubmed publisher
    ..singleton growth restricted fetuses with increasing severity of fetal growth restriction secondary to placental insufficiency. 20 growth restricted fetuses and 28 normal fetuses were scanned once during pregnancy at varying ..
  19. Regnault T, Orbus R, de Vrijer B, Davidsen M, Galan H, Wilkening R, et al. Placental expression of VEGF, PlGF and their receptors in a model of placental insufficiency-intrauterine growth restriction (PI-IUGR). Placenta. 2002;23:132-44 pubmed
    ..two maturational time points (55 and 90 days post coitus, dpc) in a hyperthermic-induced ovine model of placental insufficiency-intrauterine growth restriction (PI-IUGR)...
  20. Hromadnikova I, Kotlabova K, Doucha J, Dlouha K, Krofta L. Absolute and relative quantification of placenta-specific micrornas in maternal circulation with placental insufficiency-related complications. J Mol Diagn. 2012;14:160-7 pubmed publisher
    b>Placental insufficiency-related complications are one of the leading causes of maternal and perinatal morbidity and mortality...
  21. Loeliger M, Briscoe T, Lambert G, Caddy J, Rehn A, Dieni S, et al. Chronic placental insufficiency affects retinal development in the guinea pig. Invest Ophthalmol Vis Sci. 2004;45:2361-7 pubmed
    ..This study was conducted to determine whether chronic placental insufficiency (CPI), sufficient to cause growth restriction, results in neurochemical alterations to retinal ..
  22. Limesand S, Rozance P, Smith D, Hay W. Increased insulin sensitivity and maintenance of glucose utilization rates in fetal sheep with placental insufficiency and intrauterine growth restriction. Am J Physiol Endocrinol Metab. 2007;293:E1716-25 pubmed publisher
  23. Danielson L, McMillen I, Dyer J, Morrison J. Restriction of placental growth results in greater hypotensive response to alpha-adrenergic blockade in fetal sheep during late gestation. J Physiol. 2005;563:611-20 pubmed
    b>Placental insufficiency resulting in restriction of fetal substrate supply and fetal hypoxaemia is a major cause of restricted fetal growth and increased neonatal morbidity...
  24. Lane R, Kelley D, Gruetzmacher E, Devaskar S. Uteroplacental insufficiency alters hepatic fatty acid-metabolizing enzymes in juvenile and adult rats. Am J Physiol Regul Integr Comp Physiol. 2001;280:R183-90 pubmed
    ..These results suggest that uteroplacental insufficiency leads to altered hepatic fatty acid metabolism that may contribute to the adult dyslipidemia associated with low birth weight...
  25. Gallo L, Tran M, Moritz K, Mazzuca M, Parry L, Westcott K, et al. Cardio-renal and metabolic adaptations during pregnancy in female rats born small: implications for maternal health and second generation fetal growth. J Physiol. 2012;590:617-30 pubmed publisher
    ..Female rats born small exhibit mostly normal cardio-renal adaptations but altered glucose control during late pregnancy making them vulnerable to lifestyle challenges...
  26. Torrance H, Voorbij H, Wijnberger L, van Bel F, Visser G. Lung maturation in small for gestational age fetuses from pregnancies complicated by placental insufficiency or maternal hypertension. Early Hum Dev. 2008;84:465-9 pubmed publisher
    Clinical studies suggest that respiratory outcome of infants born preterm may be influenced by placental insufficiency and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome...
  27. Henriksen T, Clausen T. The fetal origins hypothesis: placental insufficiency and inheritance versus maternal malnutrition in well-nourished populations. Acta Obstet Gynecol Scand. 2002;81:112-4 pubmed
    ..Fetal malnutrition has two main causes, poor maternal nutrition and placental insufficiency. A distinction between these causes is important because it is likely that maternal nutrition has been ..
  28. Ke X, Lei Q, James S, Kelleher S, Melnyk S, Jernigan S, et al. Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats. Physiol Genomics. 2006;25:16-28 pubmed
    ..Despite these differences, caloric, fat, and protein content were similar in breast milk from Con and IUGR dams. We conclude that IUGR results in postnatal changes in cerebral chromatin structure and that these changes are sex specific. ..
  29. Louey S, Jonker S, Giraud G, Thornburg K. Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes. J Physiol. 2007;580:639-48 pubmed
    Umbilicoplacental embolization (UPE) in sheep has been used to investigate the effects of placental insufficiency on fetal development. However, its specific effects on the heart have been little studied...
  30. Jones H, Crombleholme T, Habli M. Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms. PLoS ONE. 2013;8:e74632 pubmed publisher
    ..GLUT3, localized to the mouse fetal endothelial cells, was reduced in placental insufficiency but maintained with Ad-I GF-1 treatment...
  31. Limesand S, Rozance P, Macko A, Anderson M, Kelly A, Hay W. Reductions in insulin concentrations and ?-cell mass precede growth restriction in sheep fetuses with placental insufficiency. Am J Physiol Endocrinol Metab. 2013;304:E516-23 pubmed publisher
    In pregnancy complicated by placental insufficiency (PI) and intrauterine growth restriction (IUGR), the fetus near term has reduced basal and glucose-stimulated insulin concentrations and reduced ?-cell mass...
  32. Barker D. Fetal origins of cardiovascular disease. Ann Med. 1999;31 Suppl 1:3-6 pubmed
    ..Prevention of the diseases may depend on prevention of imbalances in fetal growth or imbalances between prenatal and postnatal growth, or imbalances in nutrient supply to the fetus. ..
  33. Hromadnikova I, Zejskova L, Kotlabova K, Jancuskova T, Doucha J, Dlouha K, et al. Quantification of extracellular DNA using hypermethylated RASSF1A, SRY, and GLO sequences--evaluation of diagnostic possibilities for predicting placental insufficiency. DNA Cell Biol. 2010;29:295-301 pubmed publisher
    ..However, this is strongly individualized, and not a rule for all cases, and probably depends on the actual occurrence of excessive placental trophoblast apoptosis. ..
  34. Morrison J. Sheep models of intrauterine growth restriction: fetal adaptations and consequences. Clin Exp Pharmacol Physiol. 2008;35:730-43 pubmed publisher
    ..The extent and range of the fetal physiological adaptations to chronic placental insufficiency are determined by the duration of exposure and the degree of the severity of substrate supply restriction...
  35. Yinon Y, Kingdom J, Proctor L, Kelly E, Salle J, Wherrett D, et al. Hypospadias in males with intrauterine growth restriction due to placental insufficiency: the placental role in the embryogenesis of male external genitalia. Am J Med Genet A. 2010;152A:75-83 pubmed publisher
    Our aim was to define the association between early onset intra-uterine growth restriction (IUGR) due to placental insufficiency and hypospadias in males...
  36. Schober M, McKnight R, Yu X, Callaway C, Ke X, Lane R. Intrauterine growth restriction due to uteroplacental insufficiency decreased white matter and altered NMDAR subunit composition in juvenile rat hippocampi. Am J Physiol Regul Integr Comp Physiol. 2009;296:R681-92 pubmed publisher
    ..Our results suggest that apparent recovery in the IUGR hippocampus may be associated with synaptic hyperexcitability. We speculate that the NMDAR plays an important role in IUGR-associated cognitive impairment. ..
  37. Lee S, Park J, Choi Y, Cho S, Ahn J, Kwon D, et al. Comparative proteomic analysis associated with term placental insufficiency in cloned pig. Proteomics. 2007;7:1303-15 pubmed
    ..Taken together, our results suggest that placental insufficiency in scNT-derived placentas may be due to apoptosis, induced in part by the down-regulation of 14-3-3 ..
  38. Heazell A, Sumathi G, Bhatti N. What investigation is appropriate following maternal perception of reduced fetal movements?. J Obstet Gynaecol. 2005;25:648-50 pubmed
    It has been proposed that maternal perception of reduced fetal movements may be indicative of placental insufficiency, and that women who present with reduced fetal movements should be investigated for evidence of placental insufficiency...
  39. Pham T, Maclennan N, Chiu C, Laksana G, Hsu J, Lane R. Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full-term IUGR rat kidney. Am J Physiol Regul Integr Comp Physiol. 2003;285:R962-70 pubmed
    ..We speculate that these changes represent mechanisms that contribute to the fetal origins of adult disease. ..
  40. Ojeda N, Grigore D, Yanes L, Iliescu R, Robertson E, Zhang H, et al. Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring. Am J Physiol Regul Integr Comp Physiol. 2007;292:R758-63 pubmed
    Our laboratory uses a model of intrauterine growth restriction (IUGR) induced by placental insufficiency in the rat to examine the developmental origins of adult disease...
  41. Acharya G, Tronnes A, Rasanen J. Aortic isthmus and cardiac monitoring of the growth-restricted fetus. Clin Perinatol. 2011;38:113-25, vi-vii pubmed publisher
    ..This review evaluates the available scientific information and discusses the role of aortic isthmus in fetal circulation. ..
  42. Conroy A, Silver K, Zhong K, Rennie M, Ward P, Sarma J, et al. Complement activation and the resulting placental vascular insufficiency drives fetal growth restriction associated with placental malaria. Cell Host Microbe. 2013;13:215-26 pubmed publisher
    ..These data suggest that C5a drives fetal growth restriction in PM through dysregulation of angiogenic factors essential for placental vascular remodeling resulting in placental vascular insufficiency. ..
  43. Chalubinski K, Repa A, Stammler Safar M, Ott J. Impact of Doppler sonography on intrauterine management and neonatal outcome in preterm fetuses with intrauterine growth restriction. Ultrasound Obstet Gynecol. 2012;39:293-8 pubmed publisher
    ..This was a retrospective cohort study of 110 fetuses with an antenatal diagnosis of IUGR due to placental insufficiency which had a very low birth weight (< 1500 g), delivered at the Department of Fetomaternal Medicine of ..
  44. Wang K, Chen C, Chen Y. The effects of absent or reversed end-diastolic umbilical artery Doppler flow velocity. Taiwan J Obstet Gynecol. 2009;48:225-31 pubmed publisher
    ..flow with absent or reversed end-diastolic velocity (AREDV) during pregnancy is a strong indication of placental insufficiency. When AREDV occurs prenatally, a close follow-up or expeditious delivery should be contemplated...
  45. Le Guern V, Goffinet F. [Pregnancy and antiphospholipid antibodies]. Presse Med. 2008;37:1666-75 pubmed publisher
    ..Pregnancy in these women is associated with increased rates of preeclampsia, placental insufficiency, and preterm delivery...
  46. Sharygin S, Kulida L, Barinova M, Peretiatko L. [Morphological diagnosis of placental pathology in uterine contraction disorders]. Arkh Patol. 2005;67:25-7 pubmed
  47. Mari G, Hanif F. Fetal Doppler: umbilical artery, middle cerebral artery, and venous system. Semin Perinatol. 2008;32:253-7 pubmed publisher
  48. Barbosa M, Carvalho F, Araujo Júnior E, Nardozza L, Santana R, Torloni M, et al. Prediction of acidemia at birth by Doppler assessment of fetal cerebral transverse sinus in pregnancies with placental insufficiency. Ultrasound Obstet Gynecol. 2009;33:188-92 pubmed publisher
    ..and to determine the best parameter and cut-off values for its prediction in pregnancies complicated with placental insufficiency. This was a prospective cross-sectional study involving 69 pregnant women (26-40 weeks' gestation) with ..
  49. Mari G, Picconi J. Doppler vascular changes in intrauterine growth restriction. Semin Perinatol. 2008;32:182-9 pubmed publisher
    Intrauterine growth restriction (IUGR) secondary to placental insufficiency is a major cause of perinatal morbidity and mortality in the United States...
  50. Sebire N, Backos M, El Gaddal S, Goldin R, Regan L. Placental pathology, antiphospholipid antibodies, and pregnancy outcome in recurrent miscarriage patients. Obstet Gynecol. 2003;101:258-63 pubmed
    ..There are no specific histopathologic placental abnormalities characteristic of treated patients with antiphospholipid antibody syndrome and poor reproductive history, but complications of uteroplacental disease are more common. ..
  51. Kulida L, Panova I, Peretiatko L. [The role placental factors in formation of perinatal pathology in gestosis of different severity]. Arkh Patol. 2005;67:17-21 pubmed
    ..Hypoplasia of placentas, umbilical cord pathology and chronical placental hypertension in gestosis of a grave degree. ..
  52. Novak D. Nutrition in early life. How important is it?. Clin Perinatol. 2002;29:203-23 pubmed
    ..Prospective studies, though difficult because of the time involved, will play a key role in this process, as will more basic research on the mechanisms underlying both normal and pathologic fetal development. ..
  53. Intapad S, Dasinger J, Fahling J, Backstrom M, Alexander B. Testosterone is protective against impaired glucose metabolism in male intrauterine growth-restricted offspring. PLoS ONE. 2017;12:e0187843 pubmed publisher
    b>Placental insufficiency alters the intrauterine environment leading to increased risk for chronic disease including impaired glucose metabolism in low birth weight infants...