Editing Intrauterine growth restriction

{{Infobox medical condition
| name            = Intrauterine growth restriction
| synonyms        = Fetal growth restriction (FGR),<ref>{{Cite web | url=https://www.uptodate.com/contents/infants-with-fetal-intrauterine-growth-restriction | title=UpToDate}}</ref><ref>{{Cite web | url=https://patient.info/doctor/intrauterine-growth-restriction | title=Intrauterine Growth Restriction. IUGR information}}</ref> intrauterine growth retardation,<ref>{{cite journal|last1=Vandenbosche|first1=Robert C.|first2=Jeffrey T.|last2=Kirchner|date=15 October 1998|title=Intrauterine Growth Retardation|journal=[[American Family Physician]]|volume=56|issue=6|pages=1384–1390|pmid=9803202|quote=Intrauterine growth retardation (IUGR), which is defined as less than 10 percent of predicted fetal weight for gestational age, may result in significant fetal morbidity and mortality if not properly diagnosed. The condition is most commonly caused by inadequate maternal-fetal circulation, with a resultant decrease in fetal growth.|url=http://www.aafp.org/afp/1998/1015/p1384.html|access-date=20 February 2016|language=en}}</ref><ref>{{cite web|url=https://www.nlm.nih.gov/medlineplus/ency/article/001500.htm|title=Intrauterine growth restriction|last=White|first=Cynthia D.|date=16 November 2014|publisher=MedlinePlus Medical Encyclopedia|language=en|access-date=21 February 2016|quote=Alternative Names: Intrauterine growth retardation; IUGR}}</ref>
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'''Intrauterine growth restriction''' ('''IUGR'''), or '''fetal growth restriction''', is the poor [[prenatal development|growth]] of a [[fetus]] while in the [[womb]] during [[pregnancy]]. IUGR is defined by clinical features of [[malnutrition]] and evidence of reduced growth regardless of an infant's [[birth weight]] percentile.<ref name=":4">{{Cite journal|date=2019-04-01|title=Intrauterine Growth Restriction: Postnatal Monitoring and Outcomes|url=https://www.sciencedirect.com/science/article/abs/pii/S0031395518301962|journal=Pediatric Clinics of North America|language=en|volume=66|issue=2|pages=403–423|doi=10.1016/j.pcl.2018.12.009|pmid=30819345|issn=0031-3955|last1=Kesavan|first1=K.|last2=Devaskar|first2=S. U.|s2cid=73488004}}</ref> The causes of IUGR are broad and may involve maternal, fetal, or placental complications.<ref name="journals.lww.com">{{Cite journal|date=February 2021|title=Fetal Growth Restriction: ACOG Practice Bulletin, Number 227|url=https://dx.doi.org/10.1097/AOG.0000000000004251|journal=Obstetrics & Gynecology|language=en|volume=137|issue=2|pages=e16–e28|doi=10.1097/AOG.0000000000004251|pmid=33481528|s2cid=231680750|issn=0029-7844}}</ref>

At least 60% of the 4 million [[neonatal deaths]] that occur worldwide every year are associated with [[low birth weight]], caused by intrauterine growth restriction (IUGR), preterm delivery, and [[chromosome abnormality|genetic abnormalities]],<ref>{{cite journal |vauthors=Lawn JE, Cousens S, Zupan J | year = 2005 | title = 4 million neonatal deaths: when? Where? Why? | journal = The Lancet | volume = 365 | issue = 9462| pages = 891–900 | doi=10.1016/s0140-6736(05)71048-5 | pmid=15752534| s2cid = 20891663 }}</ref> demonstrating that under-nutrition is already a leading health problem at [[childbirth|birth]].

Intrauterine growth restriction can result in a baby being [[small for gestational age]] (SGA), which is most commonly defined as a weight below the 10th [[percentile]] for the [[Gestational age (obstetrics)|gestational age]].<ref>[https://www.nlm.nih.gov/medlineplus/ency/article/002302.htm Small for gestational age (SGA)] at [[MedlinePlus]]. Update Date: 8/4/2009. Updated by: Linda J. Vorvick. Also reviewed by David Zieve.</ref> At the end of pregnancy, it can result in a low birth weight.

==Types==
There are two major categories of IUGR: pseudo IUGR and true IUGR{{citation needed|date=December 2020}}

With pseudo IUGR, the fetus has a birth weight below the tenth percentile for the corresponding gestational age but has a normal ponderal index, subcutaneous fat deposition, and body proportion. Pseudo IUGR occurs due to uneventful intrauterine course and can be rectified by proper postnatal care and nutrition. Such babies are also called small for gestational age.{{citation needed|date=December 2020}}

True IUGR occurs due to pathological conditions which may be either fetal or maternal in origin. In addition to low body weight they have abnormal ponderal  index, body disproportion, and low subcutaneous fat deposition. There are two types-symmetrical and asymmetrical.<ref name="titleIntrauterine Growth Restriction">{{cite web |url=http://www.obgyn.ufl.edu/ultrasound/MedinfoVersion/sec7/7_3.html |title=Intrauterine Growth Restriction |access-date=2007-11-28 |archive-url=https://web.archive.org/web/20070609035143/http://www.obgyn.ufl.edu/ultrasound/MedinfoVersion/sec7/7_3.html <!-- Bot retrieved archive --> |archive-date=2007-06-09}}</ref><ref name="titleIntrauterine Growth Restriction: Identification and Management - August 1998 - American Academy of Family Physicians">{{cite journal |url=http://www.aafp.org/afp/980800ap/peleg.html |title=Intrauterine Growth Restriction: Identification and Management - August 1998 - American Academy of Family Physicians |journal=American Family Physician |volume=58 |issue=2 |pages=453–60, 466–7 |access-date=2007-11-28 |date=August 1998 |last1=Hunter |first1=Stephen K. |last2=Kennedy |first2=Colleen M. |last3=Peleg |first3=David |pmid=9713399 |archive-date=2011-06-06 |archive-url=https://web.archive.org/web/20110606040232/http://www.aafp.org/afp/980800ap/peleg.html |url-status=dead }}</ref> Some conditions are associated with both symmetrical and asymmetrical growth restriction.{{cn|date=September 2024}}

===Asymmetrical===
Asymmetrical IUGR accounts for 70-80% of all IUGR cases.<ref name=":5" /> In asymmetrical IUGR, there is decreased oxygen or nutrient supply to the fetus during the third trimester of pregnancy due to [[placental insufficiency]].<ref>{{Cite journal|last=Wollmann|first=null|date=1998|title=Intrauterine growth restriction: definition and etiology|url=https://pubmed.ncbi.nlm.nih.gov/9716819|journal=Hormone Research|volume=49|issue=# Suppl 2|pages=1–6|doi=10.1159/000053079|issn=1423-0046|pmid=9716819|s2cid=37436666}}</ref> This type of IUGR is sometimes called "head sparing" because brain growth is typically less affected, resulting in a relatively normal head circumference in these children.<ref name=":6">{{cite journal|last1=Sharma|first1=Deepak|last2=Shastri|first2=Sweta|last3=Farahbakhsh|first3=Nazanin|last4=Sharma|first4=Pradeep|date=December 2016|title=Intrauterine growth restriction - part 1|url=https://pubmed.ncbi.nlm.nih.gov/26856409|journal=The Journal of Maternal-Fetal & Neonatal Medicine|volume=29|issue=24|pages=3977–3987|doi=10.3109/14767058.2016.1152249|issn=1476-4954|pmid=26856409|s2cid=29439634}}</ref> Because of decreased oxygen supply to the fetus, blood is diverted to the vital organs, such as the brain and heart. As a result, blood flow to other organs - including liver, muscle, and fat - is decreased. This causes abdominal circumference in these children to be decreased.<ref name=":6" />

A lack of [[subcutis|subcutaneous fat]] leads to a thin and small body out of proportion with the liver. Normally at birth the brain of the fetus is 3 times the weight of its liver. In IUGR, it becomes 5-6 times. In these cases, the [[embryo]]/fetus has grown normally for the first two [[Pregnancy#Physiology|trimesters]] but encounters difficulties in the third, sometimes secondary to complications such as pre-eclampsia.     Other symptoms than the disproportion include dry, peeling skin and an overly-thin [[umbilical cord]]. The baby is at increased risk of [[Hypoxia (medical)|hypoxia]] and [[hypoglycemia]]. This type of IUGR is most commonly caused by [[extrinsic]] factors that affect the fetus at later gestational ages. Specific causes include:{{citation needed|date=December 2020}}
* Chronic [[high blood pressure]]
* Severe [[malnutrition]]
* Genetic [[mutations]], [[Ehlers–Danlos syndrome]]

===Symmetrical===
Symmetrical IUGR is commonly known as '''global growth restriction''', and indicates that the [[fetus]] has developed slowly throughout the duration of the pregnancy and was thus affected from a very early stage. The head circumference of such a newborn is in proportion to the rest of the body. Since most [[neurons]] are developed by the 18th week of gestation, the fetus with symmetrical IUGR is more likely to have permanent neurological [[sequelae]]. Common causes include:{{citation needed|date=December 2020}}
* Early [[uterus|intrauterine]] infections, such as [[cytomegalovirus]], [[rubella]] or [[toxoplasmosis]]
* [[Chromosome|Chromosomal]] abnormalities
* [[Anemia]]
* Maternal [[Substance abuse|substance use]] (prenatal alcohol use can result in [[Fetal alcohol syndrome]])

==Causes==
IUGR is caused by a variety of factors; these can be fetal, maternal, placental or genetic factors.<ref name=":5">{{cite journal|last1=Sharma|first1=Deepak|last2=Shastri|first2=Sweta|last3=Sharma|first3=Pradeep|date=2016|title=Intrauterine Growth Restriction: Antenatal and Postnatal Aspects|journal=Clinical Medicine Insights. Pediatrics|volume=10|pages=67–83|doi=10.4137/CMPed.S40070|issn=1179-5565|pmc=4946587|pmid=27441006}}</ref>

===Maternal===
* Pre-pregnancy weight and nutritional status
* Poor weight gain during pregnancy
* [[Malnutrition]]
* [[Anemia]]
* Substance use: smoking, alcohol, drugs including marijuana or cocaine
* Medication: warfarin, steroids, anticonvulsants
* Inter-pregnancy interval of less than 6 months
* [[Assisted reproductive technology|Assisted reproductive technologies]]
* [[diabetes mellitus|Pre-gestational diabetes]]
* [[Gestational diabetes]]
* Pulmonary disease
* Cardiovascular disease
* Kidney disease
* [[Hypertension]]
* [[Celiac disease]] increases the risk of intrauterine growth restriction by an [[odds ratio]] of approximately 2.48<ref name=SacconeBerghella2015>{{cite journal|vauthors=Saccone G, Berghella V, Sarno L, Maruotti GM, Cetin I, Greco L, Khashan AS, McCarthy F, Martinelli D, Fortunato F, Martinelli P|title=Celiac disease and obstetric complications: a systematic review and meta-analysis |journal=Am J Obstet Gynecol |volume=214|issue= 2|pages= 225–34|date= October 9, 2015 |pmid=26432464|doi=10.1016/j.ajog.2015.09.080|hdl=11369/330101|hdl-access=free}}</ref>
* Subclinical hypothyroidism<ref>{{Cite journal|last1=Tong|first1=Zhao|last2=Xiaowen|first2=Zhang|last3=Baomin|first3=Chen|last4=Aihua|first4=Liu|last5=Yingying|first5=Zhou|last6=Weiping|first6=Teng|last7=Zhongyan|first7=Shan|date=2016-05-01|title=The Effect of Subclinical Maternal Thyroid Dysfunction and Autoimmunity on Intrauterine Growth Restriction: A Systematic Review and Meta-Analysis|journal=Medicine|volume=95|issue=19|pages=e3677|doi=10.1097/MD.0000000000003677|issn=1536-5964|pmc=4902545|pmid=27175703}}</ref>
* [[Thrombophilia|Blood clotting disorder/disease]] (e.g., [[Factor V Leiden]])

===Uteroplacental===
* [[Preeclampsia]]
* [[Multiple birth|Multiple gestation]]
* [[uterus|Uterine]] malformations
* [[Placental insufficiency]]

===Fetal===
* [[Chromosome|Chromosomal abnormalities]]
* [[Vertically transmitted infection]]s: TORCH, [[Malaria]], congenital HIV infection, [[Syphilis]]
* [[Erythroblastosis fetalis]]
* [[Congenital abnormalities]]

=== Genetic ===
* Placental genes
* Maternal genes: Endothelin-1 over-expression, Leptin under-expression
* Fetal genes

==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}}

==Management==
Mothers whose fetus is diagnosed with intrauterine growth restriction can be managed with several monitoring and delivery methods. It is currently recommended that any fetus that has growth restriction and additional structural abnormalities should be evaluated with [[genetic testing]].<ref name="journals.lww.com" /> In addition to evaluating the fetal [[Growth chart|growth velocity]], the fetus should primarily be monitored by [[Ultrasound|ultrasonography]] every 3–4 weeks.<ref name="journals.lww.com"/> An additional monitoring technique is an [[Doppler fetal monitor|Doppler velocimetry]]. Doppler velocimetry is useful in monitoring blood flow through the uterine and umbilical arteries, and may indicate signs of [[Placental insufficiency|uteroplacental insufficiency]].<ref name=":1">{{Cite journal|last1=Lees|first1=C. C.|last2=Stampalija|first2=T.|last3=Baschat|first3=A. A.|last4=Silva Costa|first4=F.|last5=Ferrazzi|first5=E.|last6=Figueras|first6=F.|last7=Hecher|first7=K.|last8=Kingdom|first8=J.|last9=Poon|first9=L. C.|last10=Salomon|first10=L. J.|last11=Unterscheider|first11=J.|date=August 2020|title=ISUOG Practice Guidelines: diagnosis and management of small‐for‐gestational‐age fetus and fetal growth restriction|url=https://onlinelibrary.wiley.com/doi/10.1002/uog.22134|journal=Ultrasound in Obstetrics & Gynecology|language=en|volume=56|issue=2|pages=298–312|doi=10.1002/uog.22134|pmid=32738107|issn=0960-7692|hdl=11343/276085|s2cid=220909268|hdl-access=free}}</ref> This method may also detect blood vessels, specifically the [[ductus venosus]] and [[Middle cerebral artery|middle cerebral arteries]], which are not developing properly or may not adapt well after birth.<ref name=":1"/> Monitoring via Doppler velocimetry has been shown to decrease the risk of morbidity and mortality before and after parturition among IUGR patients.<ref name="Sharma, D. 2016">{{cite journal | vauthors = Sharma D, Shastri S, Sharma P | title = Intrauterine Growth Restriction: Antenatal and Postnatal Aspects | journal = Clinical Medicine Insights. Pediatrics | volume = 10 | pages = 67–83 | date = 2016 | pmid = 27441006 | pmc = 4946587 | doi = 10.4137/CMPed.S40070 }}</ref> Standard fetal surveillance via nonstress tests and/or biophysical profile scoring is also recommended.<ref name=":1" /><ref name="journals.lww.com"/> [[Bed rest]] has not been found to improve outcomes and is not typically recommended.<ref>{{cite journal|last1=McCall|first1=CA|last2=Grimes|first2=DA|last3=Lyerly|first3=AD|date=June 2013|title="Therapeutic" bed rest in pregnancy: unethical and unsupported by data.|journal=Obstetrics and Gynecology|volume=121|issue=6|pages=1305–8|doi=10.1097/AOG.0b013e318293f12f|pmid=23812466|s2cid=9069311}}</ref> There is currently a lack of evidence supporting any dietary or supplemental changes that may prevent the development of IUGR.<ref name="journals.lww.com"/>

The optimal timing of delivery for a fetus with IUGR is unknown. However, the timing of  delivery is currently based on the cause of IUGR<ref name="journals.lww.com"/> and parameters collected from the umbilical artery doppler. Some of these include: pulsatility index, resistance index, and end-diastolic velocities, which are measurements of the fetal circulation.<ref name="Sharma, D. 2016"/> Fetuses with an anticipated delivery before 34 weeks gestation are recommended to receive corticosteroids to facilitate fetal maturation.<ref name="journals.lww.com"/><ref>{{Cite journal|date=March 2009|title=Antenatal Corticosteroid Therapy for Fetal Maturation|url=http://dx.doi.org/10.1097/01.aoa.0000344672.12959.0d|journal=Obstetric Anesthesia Digest|volume=29|issue=1|pages=11|doi=10.1097/01.aoa.0000344672.12959.0d|issn=0275-665X}}</ref> Anticipated births before 32 weeks should receive magnesium sulfate to protect development of the fetal brain.<ref>{{Cite journal|date=December 2007|title=Magnesium Sulphate Given Before Very-Preterm Birth to Protect Infant Brain: The Randomised Controlled PREMAG Trial|url=http://dx.doi.org/10.1097/01.aoa.0000302277.08830.d0|journal=Obstetric Anesthesia Digest|volume=27|issue=4|pages=175–176|doi=10.1097/01.aoa.0000302277.08830.d0|issn=0275-665X}}</ref>

==Outcomes==

=== Postnatal complications ===

After correcting for several factors such as low gestational parental weight, it is estimated that only around 3% of pregnancies are affected by true IUGR. 20% of [[stillbirth|stillborn]] infants exhibit IUGR. Perinatal [[mortality rate]]s are 4-8 times higher for infants with IUGR, and [[morbidity]] is present in 50% of surviving infants.<ref>{{Cite book|last=Carlo L. Acerini|url=https://www.worldcat.org/oclc/1223311499|title=Oxford Handbook of Paediatrics|date=2013|others=Robert J. McClure, Robert C. Tasker|publisher=OUP Oxford |isbn=9780191015885|oclc=1223311499}}</ref> Common causes of mortality in fetuses/infants with IUGR include: [[Placental insufficiency|severe placental insufficiency]] and chronic hypoxia, [[congenital malformations]], [[congenital infection]]s, [[placental abruption]], cord accidents, [[Umbilical cord prolapse|cord prolapse]], [[Placental infarction|placental infarcts]], and [[Postpartum depression|severe perinatal depression]].<ref name=":4" />

IUGR is more common in preterm infants than in full term (37–40 weeks gestation) infants, and its frequency decreases with increasing gestational age. Relative to premature infants who do not exhibit IUGR, premature infants with IUGR are more likely to have adverse neonatal outcomes, including [[Infant respiratory distress syndrome|respiratory distress syndrome]], [[intraventricular hemorrhage]], and [[necrotizing enterocolitis]]. This association with prematurity suggests utility of screening for IUGR as a potential risk factor for preterm labor.<ref>{{Cite journal|last1=Gilbert|first1=William M.|last2=Danielsen|first2=Beate|date=2003|title=Pregnancy outcomes associated with intrauterine growth restriction|url=https://linkinghub.elsevier.com/retrieve/pii/S0002937803003387|journal=American Journal of Obstetrics and Gynecology|volume=188|issue=6|pages=1596–1601|doi=10.1067/mob.2003.384|pmid=12824998|issn=0002-9378}}</ref>

Feeding intolerance, [[hypothermia]], [[hypoglycemia]], and [[hyperglycemia]] are all common in infants in the postnatal period, indicating the need to closely manage these patients' temperature and nutrition.<ref>{{Cite journal|last1=Hoe|first1=Francis M.|last2=Thornton|first2=Paul S.|last3=Wanner|first3=Laura A.|last4=Steinkrauss|first4=Linda|last5=Simmons|first5=Rebecca A.|last6=Stanley|first6=Charles A.|date=February 2006|title=Clinical features and insulin regulation in infants with a syndrome of prolonged neonatal hyperinsulinism|url=https://linkinghub.elsevier.com/retrieve/pii/S0022347605009832|journal=The Journal of Pediatrics|language=en|volume=148|issue=2|pages=207–212|doi=10.1016/j.jpeds.2005.10.002|pmid=16492430}}</ref> Furthermore, rapid metabolic and physiologic changes in the first few days after birth can yield susceptibility to [[hypocalcemia]], [[polycythemia]], immunologic compromise, and [[renal dysfunction]].<ref>{{Cite journal|last1=Hyman|first1=Sharon J.|last2=Novoa|first2=Yeray|last3=Holzman|first3=Ian|date=October 2011|title=Perinatal Endocrinology: Common Endocrine Disorders in the Sick and Premature Newborn|url=https://linkinghub.elsevier.com/retrieve/pii/S0031395511000897|journal=Pediatric Clinics of North America|language=en|volume=58|issue=5|pages=1083–1098|doi=10.1016/j.pcl.2011.07.003|pmid=21981950}}</ref><ref>{{Cite journal|last1=Mukhopadhyay|first1=Dhriti|last2=Weaver|first2=Laura|last3=Tobin|first3=Richard|last4=Henderson|first4=Stephanie|last5=Beeram|first5=Madhava|last6=Newell-Rogers|first6=M. Karen|last7=Perger|first7=Lena|date=May 2014|title=Intrauterine growth restriction and prematurity influence regulatory T cell development in newborns|url=https://doi.org/10.1016/j.jpedsurg.2014.02.055|journal=Journal of Pediatric Surgery|volume=49|issue=5|pages=727–732|doi=10.1016/j.jpedsurg.2014.02.055|pmid=24851757|issn=0022-3468}}</ref>

=== Long-term consequences ===
According to the theory of [[thrifty phenotype]], intrauterine growth restriction triggers [[epigenetic]] responses in the fetus that are otherwise activated in times of chronic food shortage. If the offspring actually develops in an environment where food is readily accessible, 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=Barker, D. J. P.|location=London}}</ref>

Infants with IUGR may continue to show signs of abnormal growth throughout childhood. Infants with asymmetric IUGR (head-sparing) typically have more robust [[Compensatory growth (organism)|catch-up postnatal growth]], as compared with infants with symmetric IUGR, who may remain small throughout life. The majority of [[catch-up growth]] occurs in the first 6 months of life, but can continue throughout the first two years. Approximately 10% of infants who are small for gestational age due to IUGR will still have short stature in late childhood.<ref>{{Cite journal|last1=Karlberg|first1=J.|last2=Albertsson-Wikland|first2=K.|date=1995|title=Growth in Full- Term Small-for-Gestational-Age Infants: From Birth to Final Height|journal=Pediatric Research|language=en|volume=38|issue=5|pages=733–739|doi=10.1203/00006450-199511000-00017|pmid=8552442|issn=1530-0447|doi-access=free}}</ref>

Infants with IUGR are also at elevated risk for neurodevelopmental abnormalities, including motor delay and [[cognitive impairments]]. Low [[IQ]] in adulthood may occur in up to one third of infants born small for gestational age due to IUGR. Infants who fail to display adequate catch-up growth in the first few years of life may exhibit worse outcomes.<ref>{{Cite journal|last1=Løhaugen|first1=Gro C.C.|last2=Østgård|first2=Heidi Furre|last3=Andreassen|first3=Silje|last4=Jacobsen|first4=Geir W.|last5=Vik|first5=Torstein|last6=Brubakk|first6=Ann-Mari|last7=Skranes|first7=Jon|last8=Martinussen|first8=Marit|date=2013|title=Small for Gestational Age and Intrauterine Growth Restriction Decreases Cognitive Function in Young Adults|url=https://doi.org/10.1016/j.jpeds.2013.01.060|journal=The Journal of Pediatrics|volume=163|issue=2|pages=447–453.e1|doi=10.1016/j.jpeds.2013.01.060|pmid=23453550|issn=0022-3476}}</ref><ref>{{Cite journal|last1=Lundgren|first1=Ester Maria|last2=Cnattingius|first2=Sven|last3=Jonsson|first3=Björn|last4=Tuvemo|first4=Torsten|date=2001|title=Intellectual and Psychological Performance in Males Born Small for Gestational Age With and Without Catch-Up Growth|journal=Pediatric Research|language=en|volume=50|issue=1|pages=91–96|doi=10.1203/00006450-200107000-00017|pmid=11420424|issn=1530-0447|doi-access=free}}</ref>

Catch-up growth can alter fat distribution in children diagnosed with IUGR as infants and increase risk of [[metabolic syndrome]].<ref>{{Cite journal|last1=McMillen|first1=I. C.|last2=Muhlhausler|first2=B. S.|last3=Duffield|first3=J. A.|last4=Yuen|first4=B. S. J.|date=2004|title=Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth|url=https://www.cambridge.org/core/product/identifier/S0029665104000552/type/journal_article|journal=Proceedings of the Nutrition Society|language=en|volume=63|issue=3|pages=405–412|doi=10.1079/PNS2004370|pmid=15373950|issn=0029-6651|hdl=2440/3152|s2cid=29901966|hdl-access=free}}</ref> Infants with IUGR may be susceptible to long-term dysfunction of several endocrine processes, including [[Growth hormone|growth hormone signaling]], the [[Hypothalamic–pituitary–adrenal axis|hypothalamic-pituitary-adrenal axis]], and [[puberty]].<ref>{{Cite journal|author1-link=Simon Langley-Evans|last1=Langley-Evans|first1=Simon C.|last2=Gardner|first2=David S.|last3=Jackson|first3=Alan A.|date=1996-06-01|title=Maternal Protein Restriction Influences the Programming of the Rat Hypothalamic-Pituitary-Adrenal Axis|journal=The Journal of Nutrition|volume=126|issue=6|pages=1578–1585|doi=10.1093/jn/126.6.1578|pmid=8648431|issn=0022-3166|doi-access=free}}</ref> [[Renal dysfunction]], disrupted lung development, and [[Bone metabolism|impaired bone metabolism]] are also associated with IUGR.<ref>{{Cite journal|last1=Bacchetta|first1=Justine|last2=Harambat|first2=Jérôme|last3=Dubourg|first3=Laurence|last4=Guy|first4=Brigitte|last5=Liutkus|first5=Aurélia|last6=Canterino|first6=Isabelle|last7=Kassaï|first7=Behrouz|last8=Putet|first8=Guy|last9=Cochat|first9=Pierre|date=2009|title=Both extrauterine and intrauterine growth restriction impair renal function in children born very preterm|journal=Kidney International|volume=76|issue=4|pages=445–452|doi=10.1038/ki.2009.201|pmid=19516242|issn=0085-2538|doi-access=free}}</ref>

==Animals==
In sheep, intrauterine growth restriction can be caused by heat stress in early to mid pregnancy.  The effect is attributed to reduced placental development causing reduced fetal growth.<ref name=Vatnick1991>{{cite journal | vauthors = Vatnick I, Ignotz G, McBride BW, Bell AW | title = Effect of heat stress on ovine placental growth in early pregnancy | journal = Journal of Developmental Physiology | volume = 16 | issue = 3 | pages = 163–6 | date = September 1991 | pmid = 1797923 }}</ref><ref name=Bell1989>{{cite journal |author1=Bell A. W. |title=Chronic Heat Stress and Prenatal Development in Sheep: I. Conceptus Growth and Maternal Plasma Hormones and Metabolites |journal=Journal of Animal Science |author2=McBride B. W. |author3=Slepetis R. |author4=Early R. J. |author5=Currie W. B. | year = 1989 | volume = 67 | issue = 12| pages = 3289–3299 | doi=10.2527/jas1989.67123289x|pmid=2613577 |s2cid=9440955 }}</ref><ref name=Regnault1999>{{cite journal | vauthors = Regnault TR, Orbus RJ, Battaglia FC, Wilkening RB, Anthony RV | title = Altered arterial concentrations of placental hormones during maximal placental growth in a model of placental insufficiency | journal = The Journal of Endocrinology | volume = 162 | issue = 3 | pages = 433–42 | date = September 1999 | pmid = 10467235 | doi = 10.1677/joe.0.1620433 | doi-access = free }}</ref>  Hormonal effects appear implicated in the reduced placental development.<ref name=Regnault1999/> Although early reduction of placental development is not accompanied by concurrent reduction of fetal growth;<ref name=Vatnick1991/> it tends to limit fetal growth later in gestation.  Normally, ovine placental mass increases until about day 70 of gestation,<ref name="pmid8710803">{{cite journal | vauthors = Ehrhardt RA, Bell AW | title = Growth and metabolism of the ovine placenta during mid-gestation | journal = Placenta | volume = 16 | issue = 8 | pages = 727–41 | date = December 1995 | pmid = 8710803 | doi = 10.1016/0143-4004(95)90016-0| doi-access = free }}</ref>  but high demand on the placenta for fetal growth occurs later.  (For example, research results suggest that a normal average singleton Suffolk x Targhee sheep fetus has a mass of about 0.15&nbsp;kg at day 70, and growth rates of about 31 g/day at day 80, 129 g/day at day 120 and 199 g/day at day 140 of gestation, reaching a mass of about 6.21&nbsp;kg at day 140, a few days before parturition.<ref name="pmid4819552">{{cite journal | vauthors = Rattray PV, Garrett WN, East NE, Hinman N | title = Growth, development and composition of the ovine conceptus and mammary gland during pregnancy | journal = Journal of Animal Science | volume = 38 | issue = 3 | pages = 613–26 | date = March 1974 | pmid = 4819552 | doi = 10.2527/jas1974.383613x | doi-access = free }}</ref>)

In adolescent ewes (i.e. ewe hoggets), overfeeding during pregnancy can also cause intrauterine growth restriction, by altering nutrient partitioning between dam and conceptus.<ref>{{cite journal | author = Wallace J. M. | year = 2000 | title = Nutrient partitioning during pregnancy: adverse gestational outcome in overnourished adolescent dams | journal = Proc. Nutr. Soc. | volume = 59 | issue = 1| pages = 107–117 | doi=10.1017/s0029665100000136| pmid = 10828180 | doi-access = free }}</ref><ref name=Wallace2005>{{cite journal |author1=Wallace J. M. |author2=Regnault T. R. H. |author3=Limesand S. W. |author4=Hay Jr. |author5=Anthony R. V. | year = 2005 | title = Investigating the causes of low birth weights in contrasting ovine paradigms | journal = J. Physiol. | volume = 565 | issue = Pt 1| pages = 19–26 | doi=10.1113/jphysiol.2004.082032|pmid=15774527 |pmc=1464509 }}</ref>  Fetal growth restriction in adolescent ewes overnourished during early to mid pregnancy is not avoided by switching to lower nutrient intake after day 90 of gestation; whereas such switching at day 50 does result in greater placental growth and enhanced pregnancy outcome.<ref name=Wallace2005/>  Practical implications include the importance of estimating a threshold for "overnutrition" in management of pregnant ewe hoggets.  In a study of Romney and Coopworth ewe hoggets bred to Perendale rams, feeding to approximate a conceptus-free live mass gain of 0.15&nbsp;kg/day (i.e. in addition to conceptus mass), commencing 13 days after the midpoint of a synchronized breeding period, yielded no reduction in lamb birth mass, where compared with feeding treatments yielding conceptus-free live mass gains of about 0 and 0.075&nbsp;kg/day.<ref name="MorrisKenyon2010">{{cite journal|vauthors =Morris ST, Kenyon PR, West DM |title=Effect of hogget nutrition in pregnancy on lamb birthweight and survival to weaning|journal=New Zealand Journal of Agricultural Research|volume=48|issue=2|year=2010|pages=165–175|issn=0028-8233|doi=10.1080/00288233.2005.9513647|doi-access=free}}</ref>
In both of the above models of IUGR in sheep, the absolute magnitude of uterine blood flow is reduced.<ref name=Wallace2005/>  Evidence of substantial reduction of placental glucose transport capacity has been observed in pregnant ewes that had been heat-stressed during placental development.<ref name="pmid3559063">{{cite journal | vauthors = Bell AW, Wilkening RB, Meschia G | title = Some aspects of placental function in chronically heat-stressed ewes | journal = Journal of Developmental Physiology | volume = 9 | issue = 1 | pages = 17–29 | date = February 1987 | pmid = 3559063}}</ref><ref name="pmid1415644">{{cite journal | vauthors = Thureen PJ, Trembler KA, Meschia G, Makowski EL, Wilkening RB | title = Placental glucose transport in heat-induced fetal growth retardation | journal = The American Journal of Physiology | volume = 263 | issue = 3 Pt 2 | pages = R578–85 | date = September 1992 | pmid = 1415644 | doi = 10.1152/ajpregu.1992.263.3.R578 }}</ref>

==See also==
* [[Runt]]
* [[Interspecific pregnancy]] can cause this in animals

==References==
{{Reflist}}

== External links ==
{{Medical resources
|  DiseasesDB     = 6895
|  ICD10          = {{ICD10|P|05|9|p|05}}
|  ICD9           = {{ICD9|764.9}}
|  ICDO           =
|  OMIM           =
|  MedlinePlus    = 001500
|  eMedicineSubj  = article
|  eMedicineTopic = 261226
|  MeshID         = D005317
}}
{{Certain conditions originating in the perinatal period}}
{{Authority control}}

[[Category:Disorders related to length of gestation and fetal growth]]
[[Category:Human pregnancy]]
[[Category:Embryology]]