胎児発育遅延、胎児成長遅滞、胎児発育遅滞

関: intrauterine growth retardation、IUGR、small-for-gestational-age

WordNet

cultivate by growing, often involving improvements by means of agricultural techniques; "The Bordeaux region produces great red wines"; "They produce good ham in Parma"; "We grow wheat here"; "We raise hogs here" (同)raise, farm, produce
come to have or undergo a change of (physical features and attributes); "He grew a beard"; "The patient developed abdominal pains"; "I got funny spots all over my body"; "Well-developed breasts" (同)develop, produce, get, acquire
become attached by or as if by the process of growth; "The tree trunks had grown together"
become larger, greater, or bigger; expand or gain; "The problem grew too large for me"; "Her business grew fast"
cause to grow or develop; "He grows vegetables in his backyard"
increase in size by natural process; "Corn doesnt grow here"; "In these forests, mushrooms grow under the trees"; "her hair doesnt grow much anymore"
(biology) the process of an individual organism growing organically; a purely biological unfolding of events involved in an organism changing gradually from a simple to a more complex level; "he proposed an indicator of osseous development in children" (同)growing, maturation, development, ontogeny, ontogenesis
(pathology) an abnormal proliferation of tissue (as in a tumor)
a progression from simpler to more complex forms; "the growth of culture"
something grown or growing; "a growth of hair"
vegetation that has grown; "a growth of trees"; "the only growth was some salt grass"
the extent to which something is delayed or held back
lack of normal development of intellectual capacities (同)mental_retardation, backwardness, slowness, subnormality
of or relating to a fetus; "fetal development" (同)foetal

PrepTutorEJDIC

『成長する』,育つ,〈植物が〉生える,茂る / (類・量・程などにおいて)『増大する』,大きくなる / 『しだいになる』 / …‘を'成長させる,大きくする,育てる / …から生じる(起こる)
〈U〉(…の)『成長』,発育;『発達』,発展《+『of』+『名』》 / 〈U〉(数・量,重要性・力などの)『増加』,増大,拡張《+『of』+『名』》 / 〈U〉《修飾語[句]を伴って》栽培,生産,…産 / 〈C〉成育した物,(草,木,髪,ひげなどの)生えたもの / 〈C〉腫瘍(しゅよう)
〈U〉遅延,遅滞 / 〈C〉遅らせるもの;妨害物 / 〈U〉〈C〉知能(学業など)の遅れ

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/30 12:30:35」(JST)

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Intrauterine growth restriction (IUGR) refers to poor growth of a fetus while in the mother's womb during pregnancy. The causes can be many, but most often involve poor maternal nutrition or lack of adequate oxygen supply to the fetus.

At least 60% of the 4 million neonatal deaths that occur worldwide every year are associated with low birth weight (LBW), caused by intrauterine growth restriction (IUGR), preterm delivery, and genetic/chromosomal abnormalities,^[1] demonstrating that under-nutrition is already a leading health problem at birth.

Intrauterine growth restriction can result in baby being Small for Gestational Age (SGA), which is most commonly defined as a weight below the 10th percentile for the gestational age.^[2] At the end of pregnancy, it can result in a low birth weight.

Symmetrical vs. asymmetrical

There are 2 major categories of IUGR: symmetrical and asymmetrical.^[3]^[4] Some conditions are associated with both symmetrical and asymmetrical growth restriction.

Asymmetrical IUGR is more common (70%). In asymmetrical IUGR, there is restriction of weight followed by length. The head continues to grow at normal or near-normal rates (head sparing). A lack of subcutaneous fat leads to a thin and small body out of proportion with the head. This is a protective mechanism that may have evolved to promote brain development. In these cases, the embryo/fetus has grown normally for the first two 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 and hypoglycaemia. This type of IUGR is most commonly caused by extrinsic factors that affect the fetus at later gestational ages. Specific causes include:

Chronic high blood pressure
Severe malnutrition
Genetic mutations, Ehlers–Danlos syndrome

Symmetrical IUGR is less common (20-25%). It 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 sequela. Common causes include:

Early intrauterine infections, such as cytomegalovirus, rubella or toxoplasmosis
Chromosomal abnormalities
Anemia
Maternal substance abuse (prenatal alcohol use can result in Fetal alcohol syndrome)

Causes

Maternal

pre-pregnancy weight and nutritional status
poor weight gain during pregnancy
poor nutrition
anemia
alcohol and/or drug use
maternal smoking
recent pregnancy
pre-gestational diabetes
gestational diabetes
pulmonary disease
cardiovascular disease
renal disease
hypertension
Celiac disease increases the risk of intrauterine growth restriction by an odds ratio of approximately 1.5.^[5]

Uteroplacental

preeclampsia
multiple gestation
uterine malformations
Placental insufficiency

Fetal

chromosomal abnormalities
Vertically transmitted infections

Pathophysiology

If the cause of IUGR is extrinsic to the fetus (maternal 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 pulmonary hemorrhage are often results of IUGR.

If the cause of IUGR is intrinsic to the fetus, growth is restricted due to genetic factors or as a sequela of infection.

Neurological Development Postpartum

IUGR is associated with a wide range of short- and long-term neurodevelopmental disorders

Cerebral Changes

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.

grey matter effects – Grey matter was also shown to be decreased in infants with IUGR at one year corrected age.

Neural Circuitry and Brain Networks

Children with IUGR are often found to exhibit brain reorganization including neural circuitry.^[6] Reorganization has been linked to learning and memory differences between children born at term and those born with IUGR.^[7]

Studies have shown that children born with IUGR had lower IQ. They also exhibit other deficits that point to [frontal lobe] dysfunction.

IUGR infants with brain-sparing show accelerated maturation of the hippocampus which is responsible for memory.^[8] This accelerated maturation can often lead to uncharacteristic development that may compromise other networks and lead to memory and learning deficiencies.

Outcomes and clinical significance

IUGR affects 3-10% of pregnancies. 20% of stillborn infants have IUGR. Perinatal mortality rates are 4-8 times higher for infants with IUGR, and morbidity is present in 50% of surviving infants.

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 rich in food it may be more prone to metabolic disorders, such as obesity and type II diabetes.^[9]

Sheep

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.^[10]^[11]^[12] Hormonal effects appear implicated in the reduced placental development.^[12] Although early reduction of placental development is not accompanied by concurrent reduction of fetal growth;^[10] it tends to limit fetal growth later in gestation. Normally, ovine placental mass increases until about day 70 of gestation,^[13] 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 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 kg at day 140, a few days before parturition.^[14])

In adolescent ewes (i.e. ewe hoggets), overfeeding during pregnancy can also cause intrauterine growth restriction, by altering nutrient partitioning between dam and conceptus.^[15]^[16] 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.^[16] 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 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 kg/day.^[17]

In both of the above models of IUGR in sheep, the absolute magnitude of uterine blood flow is reduced.^[16] Evidence of substantial reduction of placental glucose transport capacity has been observed in pregnant ewes that had been heat-stressed during placental development.^[18]^[19]

References

^ Lawn JE, Cousens S, Zupan J (2005). "4 million neonatal deaths: when? Where? Why?". The Lancet 365: 891–900. doi:10.1016/s0140-6736(05)71048-5.
^ Small for gestational age (SGA) at MedlinePlus. Update Date: 8/4/2009. Updated by: Linda J. Vorvick. Also reviewed by David Zieve.
^ "Intrauterine Growth Restriction". Archived from the original on 2007-06-09. Retrieved 2007-11-28.
^ "Intrauterine Growth Restriction: Identification and Management - August 1998 - American Academy of Family Physicians". Retrieved 2007-11-28.
^ Tersigni, C.; Castellani, R.; de Waure, C.; Fattorossi, A.; De Spirito, M.; Gasbarrini, A.; Scambia, G.; Di Simone, N. (2014). "Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms". Human Reproduction Update 20 (4): 582–593. doi:10.1093/humupd/dmu007. ISSN 1355-4786. PMID 24619876.
^ Batalle D, Eixarch E, Figueras F, Muñoz-Moreno E, Bargallo N, Illa M, Acosta-Rojas R, Amat-Roldan I, Gratacos E (2012). "Altered small-world topology of structural brain networks in infants with intrauterine growth restriction and its association with later neurodevelopmental outcome". NeuroImage 60 (2): 1352–66. doi:10.1016/j.neuroimage.2012.01.059.
^ Geva R, Eshel R, Leitner Y, Valevski AF, Harel S (2006). "Neuropsychological Outcome of Children With Intrauterine Growth Restriction: A 9-Year Prospective Study". Pediatrics 118 (1): 91–100. doi:10.1542/peds.2005-2343.
^ Black L, Long J, Georgieff M, Nelson C (2004). "Electrographic imaging of recognition memory in 34–38 week gestation intrauterine growth restricted newborns". Experimental Neurology 190: 72–83. doi:10.1016/j.expneurol.2004.05.031.
^ Barker, D. J. P., ed. (1992). Fetal and infant origins of adult disease. London: British Medical Journal. ISBN 0-7279-0743-3.
^ ^a ^b Vatnick I., G. Ignotz, B. W. McBride and A. W. Bell. 1991. Effect of heat stress on ovine placental growth in early pregnancy. J. Devel. Physiol. 16: 163-166.
^ Bell A. W., McBride B. W., Slepetis R., Early R. J., Currie W. B. (1989). "Chronic heat stress and prenatal development in sheep. I. Conceptus growth and maternal plasma hormones and metabolites. J. Anim". Sci 67: 3289–3299.
^ ^a ^b Regnault T. R. H., Orbus R. J., Battaglia F. C., Wilkening R. B., Anthony R. V. (1999). "Altered arterial concentrations of placental hormones during maximal placental growth in a model of placental insufficiency". J. Endocrinol 162: 433–442. doi:10.1677/joe.0.1620433.
^ Ehrhardt R. A., Bella A. W. (1995). "Growth and metabolism of the ovine placenta during mid-gestation". Placenta 16: 727–741. doi:10.1016/0143-4004(95)90016-0.
^ Rattray P. V., Garrett W. N., East N. E., Hinman N. (1974). "Growth, development and composition of the ovine conceptus and mammary gland during pregnancy. J. Anim". Sci 38: 613–626.
^ Wallace J. M. (2000). "Nutrient partitioning during pregnancy: adverse gestational outcome in overnourished adolescent dams". Proc. Nutr. Soc. 59: 107–117. doi:10.1017/s0029665100000136.
^ ^a ^b ^c Wallace J. M., Regnault T. R. H., Limesand S. W., Hay Jr., Anthony R. V. (2005). "Investigating the causes of low birth weights in contrasting ovine paradigms". J. Physiol 565: 19–26. doi:10.1113/jphysiol.2004.082032.
^ Morris, S. T., P. R. Kenyon and D. M. West. 2005. Effect of hogget nutrition in pregnancy on lamb birthweight and survival to weaning. N. Z. J. Agr. Res. 48: 165-175.
^ Bell, A. W., R. B. Wilkening and G. Meschia. 1987. Some aspects of placental function in chronically heat-stressed ewes. J. Dev. Physiol 9: 17-29.
^ Thureen, P. J., K. A. Trembler, G. Meschia, E. L. Makowski and R. B. Wilkening. 1992. Placental glucose transport in heat-induced fetal growth retardation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 263: R578-R585.

UpToDate Contents

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1. 胎児の発育遅延：評価およびマネージメント fetal growth restriction evaluation and management
2. 胎児（子宮内）発育遅延が認められる胎児 infants with fetal intrauterine growth restriction
3. 胎児発育遅延：診断 fetal growth restriction diagnosis
4. 妊娠月齢に比して小さい小児に対する成長ホルモン治療 growth hormone treatment for children born small for gestational age
5. 単一臍動脈 single umbilical artery

English Journal

Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism.

Wu YM1, Luo HW2, Kou H1, Wen YX2, Shen L1, Pei LG1, Zhou J1, Zhang YZ3, Wang H4.
Toxicology and applied pharmacology.Toxicol Appl Pharmacol.2015 Nov 15;289(1):109-16. doi: 10.1016/j.taap.2015.09.007. Epub 2015 Sep 12.
It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mecha
PMID 26367767

Intrauterine low-functional programming of IGF1 by prenatal nicotine exposure mediates the susceptibility to osteoarthritis in female adult rat offspring.

Tie K1, Zhang X1, Tan Y1, Deng Y1, Li J1, Ni Q1, Wang H2, Chen L2.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology.FASEB J.2015 Oct 23. pii: fj.15-274399. [Epub ahead of print]
This study aimed to evaluate whether female adult offspring born with intrauterine growth retardation induced by prenatal nicotine exposure (PNE) are susceptible to osteoarthritis (OA) and to explore the underlying programming mechanisms. Pregnant rats were treated with nicotine or saline at 2.0 mg/
PMID 26499267

Radiation dose to the fetus during CyberKnife radiosurgery for a brain tumor in pregnancy.

Pantelis E1, Antypas C2, Frassanito MC3, Sideri L4, Salvara K4, Lekas L4, Athanasiou O4, Piperis M4, Salvaras N4, Romanelli P5.
Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB).Phys Med.2015 Oct 21. pii: S1120-1797(15)01000-5. doi: 10.1016/j.ejmp.2015.09.014. [Epub ahead of print]
PURPOSE: Pregnancy during radiosurgery is extremely rare in clinical practice. We report fetal dose results during CyberKnife radiosurgery for a brain tumor in pregnancy.METHODS AND MATERIALS: A 26 year old pregnant woman with a rapidly growing deep-seated grade-III glioma was treated during the thi
PMID 26508017

Japanese Journal

Placenta with Old, Diffuse Infarction that Was Difficult to Differentiate from a Placental Tumor

Miyake Hidehiko,Miyazaki-Igarashi Miwa,Suzuki Shunji
Journal of Nippon Medical School 82(3), 156-158, 2015
… Placental lesions, including placental infarction, are associated with fetal and neonatal mortality and morbidity. … We present a case of fetal growth restriction associated with an old, diffuse placental infarction. … At 31 weeks of gestation, a cesarean delivery was performed because of fetal growth arrest and breech presentation. …
NAID 130005085402

Pregnancy and Delivery in Women With Congenital Heart Disease

Warnes Carole A.
Circulation Journal 79(7), 1416-1421, 2015
… For women with complex CHD, pregnancy poses an increased risk for both the mother, with complications of arrhythmias and heart failure being the most common, and the baby, with a higher chance of miscarriage, intrauterine growth retardation, and the need for early delivery. … Optimum outcomes in these complex patients are achieved when a multidisciplinary approach is used, involving maternal-fetal medicine specialists, cardiologists with expertise in CHD and obstetric anesthesia. …
NAID 130005083965

Pregnancy and Delivery in Women With Congenital Heart Disease

Warnes Carole A.
Circulation Journal advpub(0), 2015
… For women with complex CHD, pregnancy poses an increased risk for both the mother, with complications of arrhythmias and heart failure being the most common, and the baby, with a higher chance of miscarriage, intrauterine growth retardation, and the need for early delivery. … Optimum outcomes in these complex patients are achieved when a multidisciplinary approach is used, involving maternal-fetal medicine specialists, cardiologists with expertise in CHD and obstetric anesthesia. …
NAID 130005074878

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★リンクテーブル★

リンク元	「胎児発育遅延」「small-for-gestational-age」「胎児成長遅滞」「胎児発育遅滞」
関連記事	「fetal」「grow」「growth retardation」「retardation」「fetal growth」

「胎児発育遅延」

Intrauterine growth restriction
	Micrograph of villitis of unknown etiology, a placental pathology associated with IUGR. H&E stain.
Classification and external resources
Specialty	pediatrics
ICD-10	P05.9
ICD-9-CM	764.9
DiseasesDB	6895
MedlinePlus	001500
eMedicine	article/261226
Patient UK	Intrauterine growth restriction
MeSH	D005317