Editing Intrauterine growth restriction (section)

==Pathophysiology==
If the cause of IUGR is [[extrinsic]] to the fetus (parental or uteroplacental), transfer of [[oxygen]] and nutrients to the fetus is decreased.  This causes a reduction in the fetus' stores of [[glycogen]] and [[lipids]].  This often leads to [[hypoglycemia]] at birth.  [[Polycythemia]] can occur secondary to increased [[erythropoietin]] production caused by the chronic [[hypoxemia]].  [[Hypothermia]], [[thrombocytopenia]], [[leukopenia]], [[hypocalcemia]], and [[hemorrhage|bleeding]] [[pulmonary|in the lungs]] are often results of IUGR.<ref name=":4"/>

Infants with IUGR are at increased risk of [[perinatal asphyxia]] due to [[Hypoxia (medical)|chronic hypoxia]], usually associated with [[placental insufficiency]], [[placental abruption]], or a umbilical cord accident.<ref name=":2">{{Cite journal|date=2013-12-01|title=Devenir précoce et prise en charge néonatale du nouveau-né petit pour l'âge gestationnel|url=https://www.sciencedirect.com/science/article/abs/pii/S0368231513002664|journal=Journal de Gynécologie Obstétrique et Biologie de la Reproduction|language=en|volume=42|issue=8|pages=985–995|doi=10.1016/j.jgyn.2013.09.020|issn=0368-2315|last1=Flamant|first1=C.|last2=Gascoin|first2=G.|pmid=24210715}}</ref> This chronic hypoxia also places IUGR infants at elevated risk of [[persistent pulmonary hypertension of the newborn]], which can impair an infant's [[blood oxygenation]] and [[Fetal circulation|transition to postnatal circulation]].<ref name=":3">{{Cite journal|last1=Steurer|first1=Martina A.|last2=Jelliffe-Pawlowski|first2=Laura L.|last3=Baer|first3=Rebecca J.|last4=Partridge|first4=J. Colin|last5=Rogers|first5=Elizabeth E.|last6=Keller|first6=Roberta L.|date=2017-01-01|title=Persistent Pulmonary Hypertension of the Newborn in Late Preterm and Term Infants in California|url=https://pediatrics.aappublications.org/content/139/1/e20161165|journal=Pediatrics|language=en|volume=139|issue=1|pages=e20161165|doi=10.1542/peds.2016-1165|issn=0031-4005|pmid=27940508|doi-access=free}}</ref>

If the cause of IUGR is [[Intrinsic and extrinsic properties|intrinsic]] to the fetus, growth is restricted due to genetic factors or as a sequela of infection. IUGR is associated with a wide range of short- and long-term [[neurodevelopmental disorders]].{{citation needed|date=December 2020}}

=== Cardiovascular ===
In IUGR, there is an increase in [[vascular resistance]] in the placental circulation, causing an increase in cardiac [[afterload]]. There is also increased [[vasoconstriction]] of the arteries in the periphery, which occurs in response to chronic [[Hypoxia (medical)|hypoxia]] in order to preserve adequate blood flow to the fetus' vital organs.<ref>{{Cite journal|last1=Cohen|first1=Emily|last2=Wong|first2=Flora Y.|last3=Horne|first3=Rosemary S. C.|last4=Yiallourou|first4=Stephanie R.|date=June 2016|title=Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy|journal=Pediatric Research|volume=79|issue=6|pages=821–830|doi=10.1038/pr.2016.24|issn=1530-0447|pmid=26866903|doi-access=free}}</ref> This prolonged vasoconstriction leads to remodeling and stiffening of the arteries, which also contributes to the increase in cardiac afterload. Therefore, the fetal heart must work harder to contract during each heartbeat, which leads to an increase in wall stress and cardiac [[Ventricular hypertrophy|hypertrophy]].<ref name=":0">{{Cite journal|last1=Malhotra|first1=Atul|last2=Allison|first2=Beth J.|last3=Castillo-Melendez|first3=Margie|last4=Jenkin|first4=Graham|last5=Polglase|first5=Graeme R.|last6=Miller|first6=Suzanne L.|date=2019|title=Neonatal Morbidities of Fetal Growth Restriction: Pathophysiology and Impact|journal=Frontiers in Endocrinology|volume=10|pages=55|doi=10.3389/fendo.2019.00055|issn=1664-2392|pmc=6374308|pmid=30792696|doi-access=free}}</ref> These changes in the fetal heart lead to increased long-term risk of [[hypertension]], [[atherosclerosis]], cardiovascular disease, and [[stroke]].<ref name=":0" />

=== Pulmonary ===
Normal lung development is interrupted in fetuses with IUGR, which increases their risk for [[respiratory compromise]] and impaired lung function later in life. Preterm infants with IUGR are more likely to have [[bronchopulmonary dysplasia]] (BPD), a chronic lung disease that is thought to be associated with prolonged use of mechanical ventilation.<ref name=":0" />

===Neurological===
IUGR is associated with long-term motor deficits and cognitive impairment.<ref name=":0" /> In order to adapt to the chronic hypoxia associated with placental insufficiency, blood flow is redirected to the brain to try to preserve brain growth and development as much as possible. Even though this is thought to be protective, fetuses with IUGR who have undergone this brain-sparing adaptation have worse neurological outcomes compared with those who have not undergone this adaptation.<ref>{{Cite journal|last1=Colella|first1=Marina|last2=Frérot|first2=Alice|last3=Novais|first3=Aline Rideau Batista|last4=Baud|first4=Olivier|date=2018|title=Neonatal and Long-Term Consequences of Fetal Growth Restriction|journal=Current Pediatric Reviews|volume=14|issue=4|pages=212–218|doi=10.2174/1573396314666180712114531|issn=1875-6336|pmc=6416241|pmid=29998808}}</ref>

[[Magnetic resonance imaging of the brain|Magnetic resonance imaging]] (MRI) can detect changes in volume and structural development of infants with IUGR compared with those whose growth is [[appropriate for gestational age]] (AGA). But MRI is not easily accessible for all patients.<ref name=":0" />

[[White matter]] effects – In postpartum studies of infants, it was shown that there was a decrease of the [[fractal dimension]] of the white matter in IUGR infants at one year corrected age. This was compared to at term and preterm infants at one year adjusted corrected age.{{citation needed|date=December 2020}}

[[Grey matter]] effects – Grey matter was also shown to be decreased in infants with IUGR at one year corrected age.<ref>{{Cite journal|last1=Keunen|first1=K.|last2=Kersbergen|first2=K. J.|last3=Groenendaal|first3=F.|last4=Isgum|first4=I.|last5=de Vries|first5=L. S.|last6=Benders|first6=M. J. N. L.|date=March 2012|title=Brain tissue volumes in preterm infants: prematurity, perinatal risk factors and neurodevelopmental outcome: a systematic review|url=https://pubmed.ncbi.nlm.nih.gov/22348253|journal=The Journal of Maternal-Fetal & Neonatal Medicine|volume=25|issue=Suppl 1 |pages=89–100|doi=10.3109/14767058.2012.664343|issn=1476-4954|pmid=22348253|s2cid=12698320}}</ref>

Children with IUGR are often found to exhibit brain reorganization including neural circuitry.<ref>{{cite journal |vauthors=Batalle D, Eixarch E, Figueras F, Muñoz-Moreno E, Bargallo N, Illa M, Acosta-Rojas R, Amat-Roldan I, Gratacos E | year = 2012 | title = Altered small-world topology of structural brain networks in infants with intrauterine growth restriction and its association with later neurodevelopmental outcome | journal = NeuroImage | volume = 60 | issue = 2| pages = 1352–66 | doi=10.1016/j.neuroimage.2012.01.059 | pmid=22281673| s2cid = 1242147 | url = https://kclpure.kcl.ac.uk/portal/en/publications/altered-smallworld-topology-of-structural-brain-networks-in-infants-with-intrauterine-growth-restriction-and-its-association-with-later-neurodevelopmental-outcome(4ed0ab74-33c5-4703-80af-ca17d3f43f4e).html }}</ref> Reorganization has been linked to learning and memory differences between children born at term and those born with IUGR.<ref>{{cite journal |vauthors=Geva R, Eshel R, Leitner Y, Valevski AF, Harel S | year = 2006 | title = Neuropsychological Outcome of Children With Intrauterine Growth Restriction: A 9-Year Prospective Study | journal = Pediatrics | volume = 118 | issue = 1| pages = 91–100 | doi=10.1542/peds.2005-2343 | pmid=16818553| s2cid = 11394000 }}</ref>

Studies have shown that children born with IUGR had lower [[intelligence quotient|IQ]]. They also exhibit other deficits that point to [[frontal lobe]] dysfunction.<ref>{{Cite journal |last=Pharoah |first=Peter O. D. |date=November 2007 |title=Prevalence and pathogenesis of congenital anomalies in cerebral palsy |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC2675398/ |journal=Archives of Disease in Childhood. Fetal and Neonatal Edition |volume=92 |issue=6 |pages=F489–493 |doi=10.1136/adc.2006.107375 |issn=1468-2052 |pmc=2675398 |pmid=17428819}}</ref>

IUGR infants with brain-sparing show accelerated maturation of the [[hippocampus]] which is responsible for memory.<ref name="pmid15498545">{{cite journal | vauthors = Black LS, deRegnier RA, Long J, Georgieff MK, Nelson CA | title = Electrographic imaging of recognition memory in 34-38 week gestation intrauterine growth restricted newborns | journal = Experimental Neurology | volume = 190 | pages = S72–83 | date = November 2004 | issue = Suppl 1 | pmid = 15498545 | doi = 10.1016/j.expneurol.2004.05.031| s2cid = 7742685 }}</ref> This accelerated maturation can often lead to uncharacteristic development that may compromise other networks and lead to memory and learning deficiencies.{{citation needed|date=December 2020}}