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{{Short description|Failure of the placenta to deliver sufficient nutrients to the fetus during pregnancy}}
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'''Placental insufficiency''' or '''utero-placental insufficiency''' is the failure of the [[placenta]] to deliver sufficient nutrients to the fetus during [[pregnancy]], and is often a result of insufficient blood flow to the placenta. The term is also sometimes used to designate late decelerations of fetal heart rate as measured by electronic monitoring, even if there is no other evidence of reduced blood flow to the placenta, normal uterine blood flow rate being 600mL/min.
'''Placental insufficiency''' or '''utero-placental insufficiency''' is the failure of the [[placenta]] to deliver sufficient nutrients to the fetus during [[pregnancy]], and is often a result of insufficient blood flow to the placenta. The term is also sometimes used to designate late decelerations of fetal heart rate as measured by [[cardiotocography]] or an [[Nonstress test|NST]], even if there is no other evidence of reduced blood flow to the placenta, normal uterine blood flow rate being 600mL/min.


==Causes==
==Causes==
[[File:Histopathology of placenta with increased syncytial knotting of chorionic villi, annotated.jpg|thumb|Histopathology of placenta with increased syncytial knotting of chorionic villi, with two knots pointed out.]]
Placental insufficiency can be induced experimentally by bilateral [[uterine artery]] [[Ligature (medicine)|ligation]] of the pregnant rat.
⚫
The following characteristics of placentas have been said to be associated with placental insufficiency, however all of them occur in normal healthy placentas and full term healthy births, so none of them can be used to accurately diagnose placental insufficiency:{{citation needed|date=July 2020}}

⚫
* Abnormally thin placenta (less than 1&nbsp;cm)<ref>{{Cite book |last=Brant |first=William E. |title=The core curriculum, ultrasound |publisher=Lippincott Williams & Wilkins |year=2001 |isbn=9780683307337 |location=Philadelphia |pages=265}}</ref>
⚫
The following characteristics of placentas have been said to be associated with placental insufficiency, however all of them occur in normal healthy placentas and full term healthy births, so none of them can be used to accurately diagnose placental insufficiency:

⚫
* Abnormally thin placenta (less than 1&nbsp;cm)<ref>{{cite book|last=Brant|first=William E.|title=The core curriculum, ultrasound|year=2001|publisher=Lippincott Williams & Wilkins|location=Philadelphia|isbn=9780683307337|pages=265}}</ref>
* [[Circumvallate placenta]] (1% of normal placentas)
* [[Circumvallate placenta]] (1% of normal placentas)
* Amnion cell metaplasia, ([[amnion nodosum]]) (present in 65% of normal placentas)
* Amnion cell metaplasia, ([[amnion nodosum]]) (present in 65% of normal placentas)
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* [[Chorionic villi|Villi]] capillaries occupying about 50% of the villi volume or when <40% of capillaries are on the villous periphery
* [[Chorionic villi|Villi]] capillaries occupying about 50% of the villi volume or when <40% of capillaries are on the villous periphery


Placental insufficiency should not be confused with complete placental abruption, in which the placenta separates off the uterine wall, which immediately results in no blood flow to the placenta, which leads to immediate fetal demise. In the case of a marginal, incomplete placental abruption of less than 50%, usually weeks of hospitalization precedes delivery and outcomes are not necessarily affected by the partial abruption.<ref>{{cite journal|last=McCormack|first=RA|author2=Doherty, DA |author3=Magann, EF |author4=Hutchinson, M |author5= Newnham, JP |title=Antepartum bleeding of unknown origin in the second half of pregnancy and pregnancy outcomes.|journal=BJOG : An International Journal of Obstetrics and Gynaecology|date=October 2008|volume=115|issue=11|pages=1451–7|pmid=18715242|doi=10.1111/j.1471-0528.2008.01856.x}}</ref>
Placental insufficiency should not be confused with complete placental abruption, in which the placenta separates off the uterine wall, which immediately results in no blood flow to the placenta, which leads to immediate fetal demise. In the case of a marginal, incomplete placental abruption of less than 50%, usually weeks of hospitalization precedes delivery and outcomes are not necessarily affected by the partial abruption.<ref>{{Cite journal |last=McCormack |first=RA |last2=Doherty, DA |last3=Magann, EF |last4=Hutchinson, M |last5=Newnham, JP |date=October 2008 |title=Antepartum bleeding of unknown origin in the second half of pregnancy and pregnancy outcomes. |journal=BJOG: An International Journal of Obstetrics and Gynaecology |volume=115 |issue=11 |pages=1451–7 |doi=10.1111/j.1471-0528.2008.01856.x |pmid=18715242}}</ref>


==Pathophysiology==
==Pathophysiology==


===Maternal effects===
===Maternal effects===
Several aspects of maternal adaptation to pregnancy are affected by dysfunction of placenta. Maternal arteries fail to transform into low-resistance vessels (expected by 22–24 weeks of [[gestation]]).<ref>{{cite journal|last=Brosens|first=I|author2=Dixon, HG |author3=Robertson, WB |title=Fetal growth retardation and the arteries of the placental bed.|journal=British Journal of Obstetrics and Gynaecology|date=September 1977|volume=84|issue=9|pages=656–63|pmid=911717|doi=10.1111/j.1471-0528.1977.tb12676.x}}</ref><ref>{{cite journal|last=Meekins|first=JW|author2=Pijnenborg, R |author3=Hanssens, M |author4=McFadyen, IR |author5= van Asshe, A |title=A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies.|journal=British Journal of Obstetrics and Gynaecology|date=August 1994|volume=101|issue=8|pages=669–74|pmid=7947500|doi=10.1111/j.1471-0528.1994.tb13182.x}}</ref> This increases vascular resistance in fetoplacental vascular bed eventually leading to reduction in metabolically active mass of placenta like a [[vicious cycle]].
Several aspects of maternal adaptation to pregnancy are affected by dysfunction of placenta. Maternal arteries fail to transform into low-resistance vessels (expected by 22–24 weeks of [[gestation]]).<ref>{{Cite journal |last=Brosens |first=I |last2=Dixon, HG |last3=Robertson, WB |date=September 1977 |title=Fetal growth retardation and the arteries of the placental bed. |journal=British Journal of Obstetrics and Gynaecology |volume=84 |issue=9 |pages=656–63 |doi=10.1111/j.1471-0528.1977.tb12676.x |pmid=911717 |s2cid=33620598}}</ref><ref>{{Cite journal |last=Meekins |first=JW |last2=Pijnenborg, R |last3=Hanssens, M |last4=McFadyen, IR |last5=van Asshe, A |date=August 1994 |title=A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. |journal=British Journal of Obstetrics and Gynaecology |volume=101 |issue=8 |pages=669–74 |doi=10.1111/j.1471-0528.1994.tb13182.x |pmid=7947500 |s2cid=22676459}}</ref> This increases vascular resistance in the fetoplacental vascular bed, eventually leading to reduction in metabolically active mass of placenta in a type of [[vicious cycle]].{{citation needed|date=December 2020}}


===Fetal effects===
===Fetal effects===
Placental insufficiency can affect the fetus, causing [[Fetal distress]]. Placental insufficiency may cause [[oligohydramnios]], [[preeclampsia]], [[miscarriage]] or [[stillbirth]]. Placental insufficiency is most frequent cause of [[Small for gestational age#Asymmetrical|asymmetric IUGR]].<ref>{{cite book|title=Medical Physiology, 2e|publisher=Elsevier Health Sciences|isbn=978-1455711819|date=2012-01-13}}</ref>
Placental insufficiency can affect the fetus, causing [[fetal distress]]. Placental insufficiency may cause [[oligohydramnios]], [[preeclampsia]], [[miscarriage]] or [[stillbirth]]. Placental insufficiency is most frequent cause of [[Small for gestational age#Asymmetrical|asymmetric IUGR]].<ref>{{Cite book |title=Medical Physiology, 2e |date=2012-01-13 |publisher=Elsevier Health Sciences |isbn=978-1455711819}}</ref>


====Fetal metabolic changes====
====Fetal metabolic changes====
Metabolic changes occurring in uteroplacental insufficiency:<ref>{{cite book|editor-first=Steven G. |editor-last=Gabbe|title=Obstetrics : normal and problem pregnancies|publisher=Elsevier/Saunders|location=Philadelphia|isbn=978-1-4377-1935-2|edition=6th|date=2012-01-01}}</ref>
Metabolic changes occurring in uteroplacental insufficiency:<ref>{{Cite book |title=Obstetrics : normal and problem pregnancies |date=2012-01-01 |publisher=Elsevier/Saunders |isbn=978-1-4377-1935-2 |editor-last=Gabbe |editor-first=Steven G. |edition=6th |location=Philadelphia}}</ref>
{| class="wikitable"
{| class="wikitable"
|-
|-
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| [[Glucose]]|| Decreases in proportion to degree of fetal [[hypoglycemia]]
| [[Glucose]]|| Decreases in proportion to degree of fetal [[hypoglycemia]]
|-
|-
| [[Amino acid]]s ||
| [[Amino acid]]s ||
* Decrease in branched chain amino acids ([[valine]], [[leucine]], [[isoleucine]]), [[serine]] and [[lysine]].
* Decrease in branched chain amino acids ([[valine]], [[leucine]], [[isoleucine]]), [[serine]] and [[lysine]].
* Increase in [[hydroxyproline]]
* Increase in [[hydroxyproline]]
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* Decrease in overall fatty acid transport via [[umbilical cord]]
* Decrease in overall fatty acid transport via [[umbilical cord]]
|-
|-
| [[Oxygen]] and [[Carbon dioxide]]||
| [[Oxygen]] and [[Carbon dioxide]]||
* Degree of hypoxemia is proportional to villous damage
* Degree of hypoxemia is proportional to villous damage
* [[Hypercapnia]], [[acidemia]], [[hypoxemia]] and [[hyperlacticemia]] in proportion to hypoxemia
* [[Hypercapnia]], [[acidemia]], [[hypoxemia]] and [[hyperlacticemia]] in proportion to hypoxemia
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====Fetal hormonal changes====
====Fetal hormonal changes====
Decrease in overall thyroid function is correlated with fetal hypoxemia.<ref>{{cite journal|last=Thorpe-Beeston|first=JG|author2=Nicolaides, KH |author3=McGregor, AM |title=Fetal thyroid function.|journal=[[Thyroid (journal)|Thyroid]]|date=Fall 1992|volume=2|issue=3|pages=207–17|pmid=1422233|doi=10.1089/thy.1992.2.207}}</ref><ref>{{cite journal|last=Thorpe-Beeston|first=JG|author2=Nicolaides, KH |author3=Snijders, RJ |author4=Felton, CV |author5=Vyas, S |author6= Campbell, S |title=Relations between the fetal circulation and pituitary-thyroid function.|journal=British Journal of Obstetrics and Gynaecology|date=November 1991|volume=98|issue=11|pages=1163–7|pmid=1760429|doi=10.1111/j.1471-0528.1991.tb15371.x}}</ref> Serum [[glucagon]], [[adrenaline]], [[noradrenaline]] levels increase, eventually causing peripheral glycogenolysis and mobilization of fetal hepatic glycogen stores.<ref>{{cite journal|last=Hubinont|first=C|author2=Nicolini, U |author3=Fisk, NM |author4=Tannirandorn, Y |author5= Rodeck, CH |title=Endocrine pancreatic function in growth-retarded fetuses.|journal=[[Obstetrics & Gynecology (journal)|Obstetrics & Gynecology]]|date=April 1991|volume=77|issue=4|pages=541–4|pmid=2002976}}</ref><ref>{{cite journal|last=Weiner|first=CP|author2=Robillard, JE |title=Atrial natriuretic factor, digoxin-like immunoreactive substance, norepinephrine, epinephrine, and plasma renin activity in human fetuses and their alteration by fetal disease.|journal=[[American Journal of Obstetrics and Gynecology]]|date=December 1988|volume=159|issue=6|pages=1353–60|pmid=2974684|doi=10.1016/0002-9378(88)90555-8}}</ref><ref>{{cite journal|last=Greenough|first=A|author2=Nicolaides, KH |author3=Lagercrantz, H |title=Human fetal sympathoadrenal responsiveness.|journal=[[Early Human Development]]|date=June 1990|volume=23|issue=1|pages=9–13|pmid=2120028|doi=10.1016/0378-3782(90)90124-2}}</ref><ref>{{cite journal|last=Ville|first=Y|author2=Proudler, A |author3=Kuhn, P |author4= Nicolaides, KH |title=Aldosterone concentration in normal, growth-retarded, anemic, and hydropic fetuses.|journal=Obstetrics and Gynecology|date=October 1994|volume=84|issue=4|pages=511–4|pmid=8090385}}</ref>
Decrease in overall thyroid function is correlated with fetal hypoxemia.<ref>{{Cite journal |last=Thorpe-Beeston |first=JG |last2=Nicolaides, KH |last3=McGregor, AM |date=Fall 1992 |title=Fetal thyroid function. |journal=[[Thyroid (journal)|Thyroid]] |volume=2 |issue=3 |pages=207–17 |doi=10.1089/thy.1992.2.207 |pmid=1422233}}</ref><ref>{{Cite journal |last=Thorpe-Beeston |first=JG |last2=Nicolaides, KH |last3=Snijders, RJ |last4=Felton, CV |last5=Vyas, S |last6=Campbell, S |date=November 1991 |title=Relations between the fetal circulation and pituitary-thyroid function. |journal=British Journal of Obstetrics and Gynaecology |volume=98 |issue=11 |pages=1163–7 |doi=10.1111/j.1471-0528.1991.tb15371.x |pmid=1760429 |s2cid=2838294}}</ref> Serum [[glucagon]], [[adrenaline]], [[noradrenaline]] levels increase, eventually causing peripheral glycogenolysis and mobilization of fetal hepatic glycogen stores.<ref>{{Cite journal |last=Hubinont |first=C |last2=Nicolini, U |last3=Fisk, NM |last4=Tannirandorn, Y |last5=Rodeck, CH |date=April 1991 |title=Endocrine pancreatic function in growth-retarded fetuses. |journal=[[Obstetrics & Gynecology (journal)|Obstetrics & Gynecology]] |volume=77 |issue=4 |pages=541–4 |pmid=2002976}}</ref><ref>{{Cite journal |last=Weiner |first=CP |last2=Robillard, JE |date=December 1988 |title=Atrial natriuretic factor, digoxin-like immunoreactive substance, norepinephrine, epinephrine, and plasma renin activity in human fetuses and their alteration by fetal disease. |journal=[[American Journal of Obstetrics and Gynecology]] |volume=159 |issue=6 |pages=1353–60 |doi=10.1016/0002-9378(88)90555-8 |pmid=2974684}}</ref><ref>{{Cite journal |last=Greenough |first=A |last2=Nicolaides, KH |last3=Lagercrantz, H |date=June 1990 |title=Human fetal sympathoadrenal responsiveness. |journal=[[Early Human Development]] |volume=23 |issue=1 |pages=9–13 |doi=10.1016/0378-3782(90)90124-2 |pmid=2120028}}</ref><ref>{{Cite journal |last=Ville |first=Y |last2=Proudler, A |last3=Kuhn, P |last4=Nicolaides, KH |date=October 1994 |title=Aldosterone concentration in normal, growth-retarded, anemic, and hydropic fetuses. |journal=Obstetrics and Gynecology |volume=84 |issue=4 |pages=511–4 |pmid=8090385}}</ref>


====Fetal hematologic changes====
====Fetal hematologic changes====
Fetal hypoxemia triggers [[erythropoietin]] release. This stimulates [[Red blood cell|RBC]] production from medullary and extramedullary sites and eventually results in [[polycythemia]].<ref>{{cite journal|last=Weiner|first=CP|author2=Williamson, RA |title=Evaluation of severe growth retardation using cordocentesis--hematologic and metabolic alterations by etiology.|journal=Obstetrics and Gynecology|date=February 1989|volume=73|issue=2|pages=225–9|pmid=2536145}}</ref><ref>{{cite journal|last=Thilaganathan|first=B|author2=Athanasiou, S |author3=Ozmen, S |author4=Creighton, S |author5=Watson, NR |author6= Nicolaides, KH |title=Umbilical cord blood erythroblast count as an index of intrauterine hypoxia.|journal=Archives of Disease in Childhood: Fetal and Neonatal Edition|date=May 1994|volume=70|issue=3|pages=F192–4|pmid=8198413|pmc=1061039|doi=10.1136/fn.70.3.f192}}</ref><ref>{{cite journal|last=Franz|first=AR|author2=Pohlandt, F |title=Red blood cell transfusions in very and extremely low birthweight infants under restrictive transfusion guidelines: is exogenous erythropoietin necessary?|journal=Archives of Disease in Childhood: Fetal and Neonatal Edition|date=March 2001|volume=84|issue=2|pages=F96–F100|pmid=11207224|pmc=1721217|doi=10.1136/fn.84.2.f96}}</ref><ref>{{cite journal|last=Snijders|first=RJ|author2=Abbas, A |author3=Melby, O |author4=Ireland, RM |author5= Nicolaides, KH |title=Fetal plasma erythropoietin concentration in severe growth retardation.|journal=American Journal of Obstetrics and Gynecology|date=February 1993|volume=168|issue=2|pages=615–9|pmid=8438939|doi=10.1016/0002-9378(93)90505-d}}</ref> Oxygen carrying capacity of blood is thus increased. Prolonged tissue hypoxemia may cause early release of [[erythrocyte]]s from maturation sites and thus count of nucleated RBCs in blood increases.<ref>{{cite journal|last=Thilaganathan|first=B.|author2=Nicolaides, K. H. |title=Erythroblastosis in birth asphyxia|journal=Ultrasound in Obstetrics and Gynecology|date=1 January 1992|volume=2|issue=1|pages=15–17|doi=10.1046/j.1469-0705.1992.02010015.x|pmid=12797000}}</ref><ref>{{cite journal|last=Bernstein|first=PS|author2=Minior, VK |author3=Divon, MY |title=Neonatal nucleated red blood cell counts in small-for-gestational age fetuses with abnormal umbilical artery Doppler studies.|journal=American Journal of Obstetrics and Gynecology|date=November 1997|volume=177|issue=5|pages=1079–84|pmid=9396897|doi=10.1016/s0002-9378(97)70018-8}}</ref><ref>{{cite journal|last=Baschat|first=AA|author2=Gembruch, U |author3=Reiss, I |author4=Gortner, L |author5=Harman, CR |author6= Weiner, CP |title=Neonatal nucleated red blood cell counts in growth-restricted fetuses: relationship to arterial and venous Doppler studies.|journal=American Journal of Obstetrics and Gynecology|date=July 1999|volume=181|issue=1|pages=190–5|pmid=10411818|doi=10.1016/s0002-9378(99)70458-8}}</ref><ref>{{cite journal|last=Baschat|first=AA|author2=Gembruch, U |author3=Reiss, I |author4=Gortner, L |author5= Harman, CR |title=Neonatal nucleated red blood cell count and postpartum complications in growth restricted fetuses.|journal=Journal of Perinatal Medicine|year=2003|volume=31|issue=4|pages=323–9|pmid=12951889|doi=10.1515/JPM.2003.046}}</ref> These factors, increase in blood viscosity, decrease in cell membrane fluidity and platelet aggregation are important precursors in accelerating placental vascular occlusion.
Fetal hypoxemia triggers [[erythropoietin]] release. This stimulates [[Red blood cell|RBC]] production from medullary and extramedullary sites and eventually results in [[polycythemia]].<ref>{{Cite journal |last=Weiner |first=CP |last2=Williamson, RA |date=February 1989 |title=Evaluation of severe growth retardation using cordocentesis--hematologic and metabolic alterations by etiology. |journal=Obstetrics and Gynecology |volume=73 |issue=2 |pages=225–9 |pmid=2536145}}</ref><ref>{{Cite journal |last=Thilaganathan |first=B |last2=Athanasiou, S |last3=Ozmen, S |last4=Creighton, S |last5=Watson, NR |last6=Nicolaides, KH |date=May 1994 |title=Umbilical cord blood erythroblast count as an index of intrauterine hypoxia. |journal=Archives of Disease in Childhood: Fetal and Neonatal Edition |volume=70 |issue=3 |pages=F192–4 |doi=10.1136/fn.70.3.f192 |pmc=1061039 |pmid=8198413}}</ref><ref>{{Cite journal |last=Franz |first=AR |last2=Pohlandt, F |date=March 2001 |title=Red blood cell transfusions in very and extremely low birthweight infants under restrictive transfusion guidelines: is exogenous erythropoietin necessary? |journal=Archives of Disease in Childhood: Fetal and Neonatal Edition |volume=84 |issue=2 |pages=F96–F100 |doi=10.1136/fn.84.2.f96 |pmc=1721217 |pmid=11207224}}</ref><ref>{{Cite journal |last=Snijders |first=RJ |last2=Abbas, A |last3=Melby, O |last4=Ireland, RM |last5=Nicolaides, KH |date=February 1993 |title=Fetal plasma erythropoietin concentration in severe growth retardation. |journal=American Journal of Obstetrics and Gynecology |volume=168 |issue=2 |pages=615–9 |doi=10.1016/0002-9378(93)90505-d |pmid=8438939}}</ref> Oxygen carrying capacity of blood is thus increased. Prolonged tissue hypoxemia may cause early release of [[erythrocyte]]s from maturation sites and thus count of nucleated RBCs in blood increases.<ref>{{Cite journal |last=Thilaganathan |first=B. |last2=Nicolaides, K. H. |date=1 January 1992 |title=Erythroblastosis in birth asphyxia |journal=Ultrasound in Obstetrics and Gynecology |volume=2 |issue=1 |pages=15–17 |doi=10.1046/j.1469-0705.1992.02010015.x |pmid=12797000 |s2cid=11457412}}</ref><ref>{{Cite journal |last=Bernstein |first=PS |last2=Minior, VK |last3=Divon, MY |date=November 1997 |title=Neonatal nucleated red blood cell counts in small-for-gestational age fetuses with abnormal umbilical artery Doppler studies. |journal=American Journal of Obstetrics and Gynecology |volume=177 |issue=5 |pages=1079–84 |doi=10.1016/s0002-9378(97)70018-8 |pmid=9396897}}</ref><ref>{{Cite journal |last=Baschat |first=AA |last2=Gembruch, U |last3=Reiss, I |last4=Gortner, L |last5=Harman, CR |last6=Weiner, CP |date=July 1999 |title=Neonatal nucleated red blood cell counts in growth-restricted fetuses: relationship to arterial and venous Doppler studies. |journal=American Journal of Obstetrics and Gynecology |volume=181 |issue=1 |pages=190–5 |doi=10.1016/s0002-9378(99)70458-8 |pmid=10411818}}</ref><ref>{{Cite journal |last=Baschat |first=AA |last2=Gembruch, U |last3=Reiss, I |last4=Gortner, L |last5=Harman, CR |year=2003 |title=Neonatal nucleated red blood cell count and postpartum complications in growth restricted fetuses. |journal=Journal of Perinatal Medicine |volume=31 |issue=4 |pages=323–9 |doi=10.1515/JPM.2003.046 |pmid=12951889 |s2cid=608538}}</ref> These factors, increase in blood viscosity, decrease in cell membrane fluidity and platelet aggregation are important precursors in accelerating placental vascular occlusion.{{citation needed|date=December 2020}}


====Fetal immunological changes====
====Fetal immunological changes====
There is decrease in immunoglobulin, absolute B-cell counts<ref>{{cite journal|last=Singh|first=M|author2=Manerikar, S |author3=Malaviya, AN |author4=Premawathi |author5=Gopalan, R |author6= Kumar, R |title=Immune status of low birth weight babies.|journal=Indian Pediatrics|date=July 1978|volume=15|issue=7|pages=563–7|pmid=569131}}</ref> and total [[White blood cell|WBC]] count.<ref>{{cite journal|last=Davies|first=N|author2=Snijders, R |author3=Nicolaides, KH |title=Intra-uterine starvation and fetal leucocyte count|journal=Fetal Diagnosis and Therapy|year=1991|volume=6|issue=3–4|pages=107–12|pmid=1789915|doi=10.1159/000263633}}</ref> T-helper and cytotoxic T-cells are suppressed<ref>{{cite journal|last=Thilaganathan|first=B|author2=Plachouras, N |author3=Makrydimas, G |author4= Nicolaides, KH |title=Fetal immunodeficiency: a consequence of placental insufficiency.|journal=British Journal of Obstetrics and Gynaecology|date=November 1993|volume=100|issue=11|pages=1000–4|pmid=8251449|doi=10.1111/j.1471-0528.1993.tb15141.x}}</ref> in proportion of degree of acidemia. These conditions lead to higher infection susceptibility of infant after delivery.
There is decrease in immunoglobulin, absolute B-cell counts<ref>{{Cite journal |last=Singh |first=M |last2=Manerikar, S |last3=Malaviya, AN |last4=Premawathi |last5=Gopalan, R |last6=Kumar, R |date=July 1978 |title=Immune status of low birth weight babies. |journal=Indian Pediatrics |volume=15 |issue=7 |pages=563–7 |pmid=569131}}</ref> and total [[White blood cell|WBC]] count.<ref>{{Cite journal |last=Davies |first=N |last2=Snijders, R |last3=Nicolaides, KH |year=1991 |title=Intra-uterine starvation and fetal leucocyte count |journal=Fetal Diagnosis and Therapy |volume=6 |issue=3–4 |pages=107–12 |doi=10.1159/000263633 |pmid=1789915}}</ref> T-helper and cytotoxic T-cells are suppressed<ref>{{Cite journal |last=Thilaganathan |first=B |last2=Plachouras, N |last3=Makrydimas, G |last4=Nicolaides, KH |date=November 1993 |title=Fetal immunodeficiency: a consequence of placental insufficiency. |journal=British Journal of Obstetrics and Gynaecology |volume=100 |issue=11 |pages=1000–4 |doi=10.1111/j.1471-0528.1993.tb15141.x |pmid=8251449 |s2cid=23159297}}</ref> in proportion of degree of acidemia. These conditions lead to higher infection susceptibility of infant after delivery.{{cn|date=November 2021}}


====Fetal cardiovascular changes====
====Fetal cardiovascular changes====
There is decrease in magnitude of umbilical venous volume flow.<ref>{{cite journal|last=Rigano|first=S|author2=Bozzo, M |author3=Ferrazzi, E |author4=Bellotti, M |author5=Battaglia, FC |author6= Galan, HL |title=Early and persistent reduction in umbilical vein blood flow in the growth-restricted fetus: a longitudinal study.|journal=American Journal of Obstetrics and Gynecology|date=October 2001|volume=185|issue=4|pages=834–8|pmid=11641661|doi=10.1067/mob.2001.117356}}</ref> In response to this, the proportion of umbilical venous blood diverted to fetal heart increases.<ref>{{cite journal|last=Bellotti|first=M|author2=Pennati, G; De Gasperi, C; Bozzo, M; Battaglia, FC; Ferrazzi, E|title=Simultaneous measurements of umbilical venous, fetal hepatic, and ductus venosus blood flow in growth-restricted human fetuses|journal=American Journal of Obstetrics and Gynecology|date=May 2004|volume=190|issue=5|pages=1347–58|pmid=15167841|doi=10.1016/j.ajog.2003.11.018}}</ref> This eventually leads to elevation of pulmonary [[vascular resistance]] and increased right ventricular [[afterload]].<ref>{{cite journal|last=Rizzo|first=G|author2=Capponi, A |author3=Chaoui, R |author4=Taddei, F |author5=Arduini, D |author6= Romanini, C |title=Blood flow velocity waveforms from peripheral pulmonary arteries in normally grown and growth-retarded fetuses.|journal=Ultrasound in Obstetrics & Gynecology|date=August 1996|volume=8|issue=2|pages=87–92|pmid=8883309|doi=10.1046/j.1469-0705.1996.08020087.x}}</ref><ref>{{cite journal|last=Griffin|first=D|author2=Bilardo, K |author3=Masini, L |author4=Diaz-Recasens, J |author5=Pearce, JM |author6=Willson, K |author7= Campbell, S |title=Doppler blood flow waveforms in the descending thoracic aorta of the human fetus.|journal=British Journal of Obstetrics and Gynaecology|date=October 1984|volume=91|issue=10|pages=997–1006|pmid=6386040|doi=10.1111/j.1471-0528.1984.tb03678.x}}</ref><ref>{{cite journal|last=Akalin-Sel|first=T|author2=Nicolaides, KH |author3=Peacock, J |author4= Campbell, S |title=Doppler dynamics and their complex interrelation with fetal oxygen pressure, carbon dioxide pressure, and pH in growth-retarded fetuses.|journal=Obstetrics and Gynecology|date=September 1994|volume=84|issue=3|pages=439–44|pmid=8058245}}</ref> This [[fetal cerebral redistribution]]
There is decrease in magnitude of umbilical venous volume flow.<ref>{{Cite journal |last=Rigano |first=S |last2=Bozzo, M |last3=Ferrazzi, E |last4=Bellotti, M |last5=Battaglia, FC |last6=Galan, HL |date=October 2001 |title=Early and persistent reduction in umbilical vein blood flow in the growth-restricted fetus: a longitudinal study. |journal=American Journal of Obstetrics and Gynecology |volume=185 |issue=4 |pages=834–8 |doi=10.1067/mob.2001.117356 |pmid=11641661}}</ref> In response to this, the proportion of umbilical venous blood diverted to fetal heart increases.<ref>{{Cite journal |last=Bellotti |first=M |last2=Pennati, G |last3=De Gasperi, C |last4=Bozzo, M |last5=Battaglia, FC |last6=Ferrazzi, E |date=May 2004 |title=Simultaneous measurements of umbilical venous, fetal hepatic, and ductus venosus blood flow in growth-restricted human fetuses |journal=American Journal of Obstetrics and Gynecology |volume=190 |issue=5 |pages=1347–58 |doi=10.1016/j.ajog.2003.11.018 |pmid=15167841}}</ref> This eventually leads to elevation of pulmonary [[vascular resistance]] and increased right ventricular [[afterload]].<ref>{{Cite journal |last=Rizzo |first=G |last2=Capponi, A |last3=Chaoui, R |last4=Taddei, F |last5=Arduini, D |last6=Romanini, C |date=August 1996 |title=Blood flow velocity waveforms from peripheral pulmonary arteries in normally grown and growth-retarded fetuses. |journal=Ultrasound in Obstetrics & Gynecology |volume=8 |issue=2 |pages=87–92 |doi=10.1046/j.1469-0705.1996.08020087.x |pmid=8883309 |s2cid=8545352}}</ref><ref>{{Cite journal |last=Griffin |first=D |last2=Bilardo, K |last3=Masini, L |last4=Diaz-Recasens, J |last5=Pearce, JM |last6=Willson, K |last7=Campbell, S |date=October 1984 |title=Doppler blood flow waveforms in the descending thoracic aorta of the human fetus. |journal=British Journal of Obstetrics and Gynaecology |volume=91 |issue=10 |pages=997–1006 |doi=10.1111/j.1471-0528.1984.tb03678.x |pmid=6386040 |s2cid=22642248}}</ref><ref>{{Cite journal |last=Akalin-Sel |first=T |last2=Nicolaides, KH |last3=Peacock, J |last4=Campbell, S |date=September 1994 |title=Doppler dynamics and their complex interrelation with fetal oxygen pressure, carbon dioxide pressure, and pH in growth-retarded fetuses. |journal=Obstetrics and Gynecology |volume=84 |issue=3 |pages=439–44 |pmid=8058245}}</ref> This [[fetal cerebral redistribution]]
of blood flow is an early response to placental insufficiency. Blood flow is selectively redirected to the myocardium, adrenal glands, and in particular to the brain in a ''brain-sparing effect''<ref>{{cite book|last=Reece|first=E. Albert|title=Clinical obstetrics : the fetus and mother.|year=2006|publisher=Blackwell Pub.|location=Malden, MA|isbn=978-1-4051-3216-9|pages=107|edition=3}}</ref>.
of blood flow is an early response to placental insufficiency. Blood flow is selectively redirected to the myocardium, adrenal glands, and in particular to the brain in a ''brain-sparing effect''.<ref>{{Cite book |last=Reece |first=E. Albert |title=Clinical obstetrics : the fetus and mother. |publisher=Blackwell Pub. |year=2006 |isbn=978-1-4051-3216-9 |edition=3rd |location=Malden, MA |pages=107}}</ref>


In late stage, the redistribution becomes ineffective, there is decrease in [[cardiac output]], ineffective preload handling and elevation of central venous pressure.<ref>{{cite journal|last=Mäkikallio|first=K|author2=Jouppila, P |author3=Räsänen, J |title=Retrograde net blood flow in the aortic isthmus in relation to human fetal arterial and venous circulations.|journal=Ultrasound in Obstetrics & Gynecology|date=February 2002|volume=19|issue=2|pages=147–52|pmid=11876806|doi=10.1046/j.0960-7692.2001.00626.x}}</ref><ref>{{cite journal|last=Rizzo|first=G|author2=Arduini, D |title=Fetal cardiac function in intrauterine growth retardation.|journal=American Journal of Obstetrics and Gynecology|date=October 1991|volume=165|issue=4 Pt 1|pages=876–82|pmid=1951546|doi=10.1016/0002-9378(91)90431-p}}</ref><ref>{{cite journal|last=Rizzo|first=G|author2=Capponi, A |author3=Rinaldo, D |author4=Arduini, D |author5= Romanini, C |title=Ventricular ejection force in growth-retarded fetuses.|journal=Ultrasound in Obstetrics & Gynecology|date=April 1995|volume=5|issue=4|pages=247–55|pmid=7600206|doi=10.1046/j.1469-0705.1995.05040247.x}}</ref><ref>{{cite journal|last=Gudmundsson|first=S|author2=Tulzer, G |author3=Huhta, JC |author4= Marsal, K |title=Venous Doppler in the fetus with absent end-diastolic flow in the umbilical artery.|journal=Ultrasound in Obstetrics & Gynecology|date=April 1996|volume=7|issue=4|pages=262–7|pmid=8726878|doi=10.1046/j.1469-0705.1996.07040262.x}}</ref> This deterioration in circulation may ultimately lead to [[tricuspid insufficiency]] and death of the fetus.<ref>{{cite journal|last=Hecher|first=K|author2=Campbell, S |author3=Doyle, P |author4=Harrington, K |author5= Nicolaides, K |title=Assessment of fetal compromise by Doppler ultrasound investigation of the fetal circulation. Arterial, intracardiac, and venous blood flow velocity studies.|journal=Circulation|date=Jan 1, 1995|volume=91|issue=1|pages=129–38|pmid=7805194|doi=10.1161/01.cir.91.1.129}}</ref><ref>{{cite journal|last=Rizzo|first=G|author2=Capponi, A |author3=Pietropolli, A |author4=Bufalino, LM |author5=Arduini, D |author6= Romanini, C |title=Fetal cardiac and extracardiac flows preceding intrauterine death.|journal=Ultrasound in Obstetrics & Gynecology|date=Mar 1, 1994|volume=4|issue=2|pages=139–42|pmid=12797208|doi=10.1046/j.1469-0705.1994.04020139.x}}</ref> Peripheral circulatory disturbances also accompany these central circulatory changes.
In late stage, the redistribution becomes ineffective, there is decrease in [[cardiac output]], ineffective preload handling and elevation of central venous pressure.<ref>{{Cite journal |last=Mäkikallio |first=K |last2=Jouppila, P |last3=Räsänen, J |date=February 2002 |title=Retrograde net blood flow in the aortic isthmus in relation to human fetal arterial and venous circulations. |journal=Ultrasound in Obstetrics & Gynecology |volume=19 |issue=2 |pages=147–52 |doi=10.1046/j.0960-7692.2001.00626.x |pmid=11876806}}</ref><ref>{{Cite journal |last=Rizzo |first=G |last2=Arduini, D |date=October 1991 |title=Fetal cardiac function in intrauterine growth retardation. |journal=American Journal of Obstetrics and Gynecology |volume=165 |issue=4 Pt 1 |pages=876–82 |doi=10.1016/0002-9378(91)90431-p |pmid=1951546}}</ref><ref>{{Cite journal |last=Rizzo |first=G |last2=Capponi, A |last3=Rinaldo, D |last4=Arduini, D |last5=Romanini, C |date=April 1995 |title=Ventricular ejection force in growth-retarded fetuses. |journal=Ultrasound in Obstetrics & Gynecology |volume=5 |issue=4 |pages=247–55 |doi=10.1046/j.1469-0705.1995.05040247.x |pmid=7600206 |doi-access=free}}</ref><ref>{{Cite journal |last=Gudmundsson |first=S |last2=Tulzer, G |last3=Huhta, JC |last4=Marsal, K |date=April 1996 |title=Venous Doppler in the fetus with absent end-diastolic flow in the umbilical artery. |journal=Ultrasound in Obstetrics & Gynecology |volume=7 |issue=4 |pages=262–7 |doi=10.1046/j.1469-0705.1996.07040262.x |pmid=8726878 |doi-access=free}}</ref> This deterioration in circulation may ultimately lead to [[tricuspid insufficiency]] and death of the fetus.<ref>{{Cite journal |last=Hecher |first=K |last2=Campbell, S |last3=Doyle, P |last4=Harrington, K |last5=Nicolaides, K |date=Jan 1, 1995 |title=Assessment of fetal compromise by Doppler ultrasound investigation of the fetal circulation. Arterial, intracardiac, and venous blood flow velocity studies. |journal=Circulation |volume=91 |issue=1 |pages=129–38 |doi=10.1161/01.cir.91.1.129 |pmid=7805194}}</ref><ref>{{Cite journal |last=Rizzo |first=G |last2=Capponi, A |last3=Pietropolli, A |last4=Bufalino, LM |last5=Arduini, D |last6=Romanini, C |date=Mar 1, 1994 |title=Fetal cardiac and extracardiac flows preceding intrauterine death. |journal=Ultrasound in Obstetrics & Gynecology |volume=4 |issue=2 |pages=139–42 |doi=10.1046/j.1469-0705.1994.04020139.x |pmid=12797208 |s2cid=22358224}}</ref> Peripheral circulatory disturbances also accompany these central circulatory changes.{{cn|date=September 2024}}


====Fetal behavioral changes====
====Fetal behavioral changes====
Chronic hypoxemia leads to delay in all aspects of CNS maturation.<ref>{{cite journal|last=Arduini|first=D|author2=Rizzo, G |author3=Romanini, C |author4= Mancuso, S |title=Computerized analysis of behavioural states in asymmetrical growth retarded fetuses.|journal=Journal of Perinatal Medicine|year=1988|volume=16|issue=4|pages=357–63|pmid=3221294|doi=10.1515/jpme.1988.16.4.357|url=http://edoc.hu-berlin.de/18452/10527}}</ref><ref>{{cite journal|last=Arduini|first=D|author2=Rizzo, G |author3=Caforio, L |author4=Boccolini, MR |author5=Romanini, C |author6= Mancuso, S |title=Behavioural state transitions in healthy and growth retarded fetuses.|journal=Early Human Development|date=June 1989|volume=19|issue=3|pages=155–65|pmid=2776681|doi=10.1016/0378-3782(89)90076-5}}</ref><ref>{{cite journal|last=Nijhuis|first=IJ|author2=ten Hof, J; Nijhuis, JG; Mulder, EJ; Narayan, H; Taylor, DJ; Visser, GH|title=Temporal organization of fetal behavior from 24-weeks gestation onwards in normal and complicated pregnancies|journal=Developmental Psychobiology|date=May 1999|volume=34|issue=4|pages=257–68|pmid=10331150|doi=10.1002/(sici)1098-2302(199905)34:2<257::aid-dev2>3.0.co;2-v}}</ref><ref>{{cite journal|last=Vindla|first=S|author2=James, D |author3=Sahota, D |title=Computerised analysis of unstimulated and stimulated behaviour in fetuses with intrauterine growth restriction.|journal=European Journal of Obstetrics, Gynecology, and Reproductive Biology|date=March 1999|volume=83|issue=1|pages=37–45|pmid=10221608|doi=10.1016/s0301-2115(98)00238-3}}</ref> With worsening fetal hypoxemia, there is decline in fetal activity.<ref>{{cite journal|last=Ribbert|first=LS|author2=Nicolaides, KH |author3=Visser, GH |title=Prediction of fetal acidaemia in intrauterine growth retardation: comparison of quantified fetal activity with biophysical profile score.|journal=British Journal of Obstetrics and Gynaecology|date=July 1993|volume=100|issue=7|pages=653–6|pmid=8369249|doi=10.1111/j.1471-0528.1993.tb14233.x}}</ref> With further hypoxemia, fetal breathing ceases. Gross body movements and tone decrease further.<ref>{{cite journal|last=Vintzileos|first=AM|author2=Fleming, AD |author3=Scorza, WE |author4=Wolf, EJ |author5=Balducci, J |author6=Campbell, WA |author7= Rodis, JF |title=Relationship between fetal biophysical activities and umbilical cord blood gas values.|journal=American Journal of Obstetrics and Gynecology|date=September 1991|volume=165|issue=3|pages=707–13|pmid=1822963|doi=10.1016/0002-9378(91)90314-h}}</ref><ref>{{cite journal|last=Manning|first=FA|author2=Snijders, R |author3=Harman, CR |author4=Nicolaides, K |author5=Menticoglou, S |author6= Morrison, I |title=Fetal biophysical profile score. VI. Correlation with antepartum umbilical venous fetal pH.|journal=American Journal of Obstetrics and Gynecology|date=October 1993|volume=169|issue=4|pages=755–63|pmid=8238129|doi=10.1016/0002-9378(93)90002-Z}}</ref> [[Fetal heart rate]] decreases due to spontaneous deceleration due to direct depression of cardiac contractility. This leads to intrauterine fetal death.
Chronic hypoxemia leads to delay in all aspects of CNS maturation.<ref>{{Cite journal |last=Arduini |first=D |last2=Rizzo, G |last3=Romanini, C |last4=Mancuso, S |year=1988 |title=Computerized analysis of behavioural states in asymmetrical growth retarded fetuses. |url=http://edoc.hu-berlin.de/18452/10527 |journal=Journal of Perinatal Medicine |volume=16 |issue=4 |pages=357–63 |doi=10.1515/jpme.1988.16.4.357 |pmid=3221294 |s2cid=21529722}}</ref><ref>{{Cite journal |last=Arduini |first=D |last2=Rizzo, G |last3=Caforio, L |last4=Boccolini, MR |last5=Romanini, C |last6=Mancuso, S |date=June 1989 |title=Behavioural state transitions in healthy and growth retarded fetuses. |journal=Early Human Development |volume=19 |issue=3 |pages=155–65 |doi=10.1016/0378-3782(89)90076-5 |pmid=2776681}}</ref><ref>{{Cite journal |last=Nijhuis |first=IJ |last2=ten Hof, J |last3=Nijhuis, JG |last4=Mulder, EJ |last5=Narayan, H |last6=Taylor, DJ |last7=Visser, GH |date=May 1999 |title=Temporal organization of fetal behavior from 24-weeks gestation onwards in normal and complicated pregnancies |journal=Developmental Psychobiology |volume=34 |issue=4 |pages=257–68 |doi=10.1002/(sici)1098-2302(199905)34:2<257::aid-dev2>3.0.co;2-v |pmid=10331150}}</ref><ref>{{Cite journal |last=Vindla |first=S |last2=James, D |last3=Sahota, D |date=March 1999 |title=Computerised analysis of unstimulated and stimulated behaviour in fetuses with intrauterine growth restriction. |journal=European Journal of Obstetrics, Gynecology, and Reproductive Biology |volume=83 |issue=1 |pages=37–45 |doi=10.1016/s0301-2115(98)00238-3 |pmid=10221608}}</ref> With worsening fetal hypoxemia, there is decline in fetal activity.<ref>{{Cite journal |last=Ribbert |first=LS |last2=Nicolaides, KH |last3=Visser, GH |date=July 1993 |title=Prediction of fetal acidaemia in intrauterine growth retardation: comparison of quantified fetal activity with biophysical profile score. |journal=British Journal of Obstetrics and Gynaecology |volume=100 |issue=7 |pages=653–6 |doi=10.1111/j.1471-0528.1993.tb14233.x |pmid=8369249 |s2cid=9439096}}</ref> With further hypoxemia, fetal breathing ceases. Gross body movements and tone decrease further.<ref>{{Cite journal |last=Vintzileos |first=AM |last2=Fleming, AD |last3=Scorza, WE |last4=Wolf, EJ |last5=Balducci, J |last6=Campbell, WA |last7=Rodis, JF |date=September 1991 |title=Relationship between fetal biophysical activities and umbilical cord blood gas values. |journal=American Journal of Obstetrics and Gynecology |volume=165 |issue=3 |pages=707–13 |doi=10.1016/0002-9378(91)90314-h |pmid=1822963}}</ref><ref>{{Cite journal |last=Manning |first=FA |last2=Snijders, R |last3=Harman, CR |last4=Nicolaides, K |last5=Menticoglou, S |last6=Morrison, I |date=October 1993 |title=Fetal biophysical profile score. VI. Correlation with antepartum umbilical venous fetal pH. |journal=American Journal of Obstetrics and Gynecology |volume=169 |issue=4 |pages=755–63 |doi=10.1016/0002-9378(93)90002-Z |pmid=8238129}}</ref> [[Fetal heart rate]] decreases due to spontaneous deceleration due to direct depression of cardiac contractility. This leads to intrauterine fetal death.{{citation needed|date=December 2020}}


====Risk of later metabolic disease====
====Risk of later metabolic disease====
According to the theory of [[thrifty phenotype]], placental insufficiency triggers [[epigenetic]] responses in the fetus that are otherwise activated in times of chronic food shortage. If the offspring actually develops in an environment rich in food it may be more prone to metabolic disorders, such as [[obesity]] and [[Diabetes mellitus type 2|type II diabetes]].<ref>{{cite book |editor=Barker, D. J. P. |title=Fetal and infant origins of adult disease |publisher=British Medical Journal |location=London |year=1992 |isbn=978-0-7279-0743-1 }}</ref>
According to the theory of [[thrifty phenotype]], placental insufficiency triggers [[epigenetic]] responses in the fetus that are otherwise activated in times of chronic food shortage. If the offspring actually develops in an environment rich in food it may be more prone to metabolic disorders, such as [[obesity]] and [[Diabetes mellitus type 2|type II diabetes]].<ref>{{Cite book |title=Fetal and infant origins of adult disease |publisher=British Medical Journal |year=1992 |isbn=978-0-7279-0743-1 |editor-last=Barker, D. J. P. |location=London}}</ref>


==Diagnosis==
==Diagnosis==
The following tests have been promoted as supposedly diagnosing placental insufficiency, but all have been unsuccessful at predicting stillbirth due to placental insufficiency:<ref>{{cite journal|last=Haws|first=Rachel A|author2=Yakoob, Mohammad |author3=Soomro, Tanya |author4=Menezes, Esme V |author5=Darmstadt, Gary L |author6= Bhutta, Zulfiqar A |title=Reducing stillbirths: screening and monitoring during pregnancy and labour|journal=BMC Pregnancy and Childbirth|date=1 January 2009|volume=9|issue=Suppl 1|pages=S5|doi=10.1186/1471-2393-9-S1-S5|pmid=19426468 |pmc=2679411}}</ref><ref>{{cite journal|last=Smith|first=GC|author2=Fretts, RC |title=Stillbirth.|journal=Lancet|date=Nov 17, 2007|volume=370|issue=9600|pages=1715–25|pmid=18022035|doi=10.1016/S0140-6736(07)61723-1}}</ref>
The following tests have been promoted as supposedly diagnosing placental insufficiency, but all have been unsuccessful at predicting stillbirth due to placental insufficiency:<ref>{{Cite journal |last=Haws |first=Rachel A |last2=Yakoob, Mohammad |last3=Soomro, Tanya |last4=Menezes, Esme V |last5=Darmstadt, Gary L |last6=Bhutta, Zulfiqar A |date=1 January 2009 |title=Reducing stillbirths: screening and monitoring during pregnancy and labour |journal=BMC Pregnancy and Childbirth |volume=9 |issue=Suppl 1 |pages=S5 |doi=10.1186/1471-2393-9-S1-S5 |pmc=2679411 |pmid=19426468 |doi-access=free}}</ref><ref>{{Cite journal |last=Smith |first=GC |last2=Fretts, RC |date=Nov 17, 2007 |title=Stillbirth. |journal=Lancet |volume=370 |issue=9600 |pages=1715–25 |doi=10.1016/S0140-6736(07)61723-1 |pmid=18022035 |s2cid=208788871}}</ref>
* Placental grading
* Placental grading
* [[Amniotic fluid index]]
* [[Amniotic fluid index]]
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==References==
==References==
{{Reflist}}
{{Reflist}}

== External links ==
== External links ==
{{Medical resources
{{Medical resources
| DiseasesDB = 10107
| DiseasesDB = 10107
| ICD10 = {{ICD10|P|02|2|p|00}}
| ICD10 = {{ICD10|P|02|2|p|00}}
| ICD9 = {{ICD9|762.2}}
| ICD9 = {{ICD9|762.2}}
| ICDO =
| ICDO =
| OMIM =
| OMIM =
| MedlinePlus = 001485
| MedlinePlus = 001485
| eMedicineSubj =
| eMedicineSubj =
| eMedicineTopic =
| eMedicineTopic =
| MeshID = D010927
| MeshID = D010927
| SNOMED CT = 237292005
| Orphanet = 439167
}}
}}
{{Certain conditions originating in the perinatal period}}
{{Certain conditions originating in the perinatal period}}
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[[Category:Haemorrhagic and haematological disorders of fetus and newborn]]
[[Category:Haemorrhagic and haematological disorders of fetus and newborn]]
[[Category:Health issues in pregnancy]]
[[Category:Health issues in pregnancy]]
[[Category:Placentation disorders]]

Latest revision as of 14:53, 6 September 2024

Placental insufficiency
Other namesUtero-placental insufficiency
SpecialtyNeonatology, obstetrics, maternal–fetal medicine Edit this on Wikidata

Placental insufficiency or utero-placental insufficiency is the failure of the placenta to deliver sufficient nutrients to the fetus during pregnancy, and is often a result of insufficient blood flow to the placenta. The term is also sometimes used to designate late decelerations of fetal heart rate as measured by cardiotocography or an NST, even if there is no other evidence of reduced blood flow to the placenta, normal uterine blood flow rate being 600mL/min.

Causes

[edit]
Histopathology of placenta with increased syncytial knotting of chorionic villi, with two knots pointed out.

The following characteristics of placentas have been said to be associated with placental insufficiency, however all of them occur in normal healthy placentas and full term healthy births, so none of them can be used to accurately diagnose placental insufficiency:[citation needed]

  • Abnormally thin placenta (less than 1 cm)[1]
  • Circumvallate placenta (1% of normal placentas)
  • Amnion cell metaplasia, (amnion nodosum) (present in 65% of normal placentas)
  • Increased syncytial knots
  • Calcifications
  • Infarcts due to focal or diffuse thickening of blood vessels
  • Villi capillaries occupying about 50% of the villi volume or when <40% of capillaries are on the villous periphery

Placental insufficiency should not be confused with complete placental abruption, in which the placenta separates off the uterine wall, which immediately results in no blood flow to the placenta, which leads to immediate fetal demise. In the case of a marginal, incomplete placental abruption of less than 50%, usually weeks of hospitalization precedes delivery and outcomes are not necessarily affected by the partial abruption.[2]

Pathophysiology

[edit]

Maternal effects

[edit]

Several aspects of maternal adaptation to pregnancy are affected by dysfunction of placenta. Maternal arteries fail to transform into low-resistance vessels (expected by 22–24 weeks of gestation).[3][4] This increases vascular resistance in the fetoplacental vascular bed, eventually leading to reduction in metabolically active mass of placenta in a type of vicious cycle.[citation needed]

Fetal effects

[edit]

Placental insufficiency can affect the fetus, causing fetal distress. Placental insufficiency may cause oligohydramnios, preeclampsia, miscarriage or stillbirth. Placental insufficiency is most frequent cause of asymmetric IUGR.[5]

Fetal metabolic changes

[edit]

Metabolic changes occurring in uteroplacental insufficiency:[6]

Substrate Change
Glucose Decreases in proportion to degree of fetal hypoglycemia
Amino acids
Fatty acids
Oxygen and Carbon dioxide

Fetal hormonal changes

[edit]

Decrease in overall thyroid function is correlated with fetal hypoxemia.[7][8] Serum glucagon, adrenaline, noradrenaline levels increase, eventually causing peripheral glycogenolysis and mobilization of fetal hepatic glycogen stores.[9][10][11][12]

Fetal hematologic changes

[edit]

Fetal hypoxemia triggers erythropoietin release. This stimulates RBC production from medullary and extramedullary sites and eventually results in polycythemia.[13][14][15][16] Oxygen carrying capacity of blood is thus increased. Prolonged tissue hypoxemia may cause early release of erythrocytes from maturation sites and thus count of nucleated RBCs in blood increases.[17][18][19][20] These factors, increase in blood viscosity, decrease in cell membrane fluidity and platelet aggregation are important precursors in accelerating placental vascular occlusion.[citation needed]

Fetal immunological changes

[edit]

There is decrease in immunoglobulin, absolute B-cell counts[21] and total WBC count.[22] T-helper and cytotoxic T-cells are suppressed[23] in proportion of degree of acidemia. These conditions lead to higher infection susceptibility of infant after delivery.[citation needed]

Fetal cardiovascular changes

[edit]

There is decrease in magnitude of umbilical venous volume flow.[24] In response to this, the proportion of umbilical venous blood diverted to fetal heart increases.[25] This eventually leads to elevation of pulmonary vascular resistance and increased right ventricular afterload.[26][27][28] This fetal cerebral redistribution of blood flow is an early response to placental insufficiency. Blood flow is selectively redirected to the myocardium, adrenal glands, and in particular to the brain in a brain-sparing effect.[29]

In late stage, the redistribution becomes ineffective, there is decrease in cardiac output, ineffective preload handling and elevation of central venous pressure.[30][31][32][33] This deterioration in circulation may ultimately lead to tricuspid insufficiency and death of the fetus.[34][35] Peripheral circulatory disturbances also accompany these central circulatory changes.[citation needed]

Fetal behavioral changes

[edit]

Chronic hypoxemia leads to delay in all aspects of CNS maturation.[36][37][38][39] With worsening fetal hypoxemia, there is decline in fetal activity.[40] With further hypoxemia, fetal breathing ceases. Gross body movements and tone decrease further.[41][42] Fetal heart rate decreases due to spontaneous deceleration due to direct depression of cardiac contractility. This leads to intrauterine fetal death.[citation needed]

Risk of later metabolic disease

[edit]

According to the theory of thrifty phenotype, placental insufficiency triggers epigenetic responses in the fetus that are otherwise activated in times of chronic food shortage. If the offspring actually develops in an environment rich in food it may be more prone to metabolic disorders, such as obesity and type II diabetes.[43]

Diagnosis

[edit]

The following tests have been promoted as supposedly diagnosing placental insufficiency, but all have been unsuccessful at predicting stillbirth due to placental insufficiency:[44][45]

See also

[edit]

References

[edit]
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