Intrauterine growth restriction

Intrauterine growth restriction

Micrograph of villitis of unknown etiology,

aplacental 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

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.
Contents
[hide]

1 Symmetrical vs. asymmetrical

2 Causes
o

2.1 Maternal

2.2 Uteroplacental

2.3 Fetal

3 Pathophysiology
3.1 Neurological Development Postpartum

3.1.1 Cerebral Changes

3.1.2 Neural Circuitry and Brain Networks

4 Outcomes and clinical significance

5 Sheep

6 References
Symmetrical vs. asymmetrical[edit]
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, EhlersDanlos 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[edit]
Maternal[edit]

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[edit]

preeclampsia

multiple gestation

uterine malformations

Placental insufficiency

Fetal[edit]

chromosomal abnormalities

Vertically transmitted infections

Pathophysiology[edit]
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
ofglycogen 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[edit]
IUGR is associated with a wide range of short- and long-term neurodevelopmental disorders
Cerebral Changes[edit]

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[edit]
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[edit]
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[edit]
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[edit]
1.

Jump up^ Lawn JE, Cousens S, Zupan J (2005). "4 million neonatal deaths:
when? Where? Why?".The Lancet 365: 891900. doi:10.1016/s0140-6736(05)71048-5.

2.

Jump up^ Small for gestational age (SGA) at MedlinePlus. Update Date:
8/4/2009. Updated by: Linda J. Vorvick. Also reviewed by David Zieve.

3.

Jump up^ "Intrauterine Growth Restriction". Archived from the original on

2007-06-09. Retrieved 2007-11-28.

4.

Jump up^ "Intrauterine Growth Restriction: Identification and Management August 1998 - American Academy of Family Physicians". Retrieved 2007-11-28.

5.

Jump up^ 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.

6.

Jump up^ Batalle D, Eixarch E, Figueras F, Muoz-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.

7.

Jump up^ Geva R, Eshel R, Leitner Y, Valevski AF, Harel S (2006).

"Neuropsychological Outcome of Children With Intrauterine Growth Restriction: A 9Year Prospective Study". Pediatrics118 (1): 91100. doi:10.1542/peds.2005-2343.

8.

Jump up^ Black L, Long J, Georgieff M, Nelson C (2004). "Electrographic

imaging of recognition memory in 3438 week gestation intrauterine growth restricted
newborns". Experimental Neurology 190: 7283. doi:10.1016/j.expneurol.2004.05.031.

9.

Jump up^ Barker, D. J. P., ed. (1992). Fetal and infant origins of adult disease.
London: British Medical Journal. ISBN 0-7279-0743-3.
^ Jump up to:a b Vatnick I., G. Ignotz, B. W. McBride and A. W. Bell. 1991. Effect

10.

of heat stress on ovine placental growth in early pregnancy. J. Devel. Physiol. 16: 163166.
11.

Jump up^ 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: 32893299.

12.

^ Jump up to: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:
433442.doi:10.1677/joe.0.1620433.

13.

Jump up^ Ehrhardt R. A., Bella A. W. (1995). "Growth and metabolism of the
ovine placenta during mid-gestation". Placenta 16: 727741. doi:10.1016/01434004(95)90016-0.

14.

Jump up^ 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". Sci38: 613626.

15.

Jump up^ Wallace J. M. (2000). "Nutrient partitioning during pregnancy:

adverse gestational outcome in overnourished adolescent dams". Proc. Nutr. Soc. 59:
107117.doi:10.1017/s0029665100000136.

16.

^ Jump up to: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. Physiol565: 1926. doi:10.1113/jphysiol.2004.082032.

17.

Jump up^ 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.

18.

Jump up^ 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.

19.

Jump up^ 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.