Intrauterine growth restriction
|Intrauterine growth restriction|
|Classification and external resources|
Micrograph of villitis of unknown etiology, a placental pathology associated with IUGR. H&E stain.
Intrauterine growth restriction (IUGR) refers to poor growth of a baby 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, demonstrating that under-nutrition is already a leading health problem at birth.
The term IUGR is not synonymous with Small for Gestational Age (SGA). SGA refers to a birth weight that is below the 10th percentile for gestational age. Not all fetuses with IUGR are classified as SGA, and vice versa. IUGR is used to describe a pattern of intrauterine fetal growth that deviates from expected norms, whereas SGA is a category assigned based on birth weight.
Symmetrical vs. asymmetrical 
There are 2 major categories of IUGR: symmetrical and asymmetrical.
Asymmetrical IUGR is more common. In asymmetrical IUGR, there is restriction of weight followed by length. The head continues to grow at normal or near-normal rates (head sparing). This is a protective mechanism that may have evolved to promote brain development. This type of IUGR is most commonly caused by extrinsic factors that affect the fetus at later gestational ages.
Symmetrical IUGR is less common and is more worrisome. This type of IUGR usually begins early in gestation. Since most neurons are developed by the 18th week of gestation, the fetus with symmetrical IUGR is more likely to have permanent neurological sequela.
- pre-pregnancy weight and nutritional status
- poor weight gain during pregnancy
- poor nutrition
- alcohol and/or drug use
- maternal smoking
- recent pregnancy
- pre-gestational diabetes
- gestational diabetes
- pulmonary disease
- cardiovascular disease
- renal disease
- chromosomal abnormalities
- intrauterine infection
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. Reorganization has been linked to learning and memory differences between children born at term and those born with IUGR.
Studies have shown that children born with IUGR had lower [intelligence quotient|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. 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 
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. Hormonal effects appear implicated in the reduced placental development. Although early reduction of placental development is not accompanied by concurrent reduction of fetal growth; it tends to limit fetal growth later in gestation. Normally, ovine placental mass increases until about day 70 of gestation, 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.)
In adolescent ewes (i.e. ewe hoggets), overfeeding during pregnancy can also cause intrauterine growth restriction, by altering nutrient partitioning between dam and conceptus. 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. 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.
In both of the above models of IUGR in sheep, the absolute magnitude of uterine blood flow is reduced. Evidence of substantial reduction of placental glucose transport capacity has been observed in pregnant ewes that had been heat-stressed during placental development.
- Lawn 2005
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- Batalle D, Eixarch E, Munoz-Moreno, Bargallo N. Altered small-world topology of structural brain networks in infants with intrauterine growth restriction and its association with later neurodevelopmental outcome. NeuroImage. 2012;60:1352-1366.
- Geva R, Eshel R, Leitner Y, Valevski AF, Harel S. Neuropsychological Outcome of Children With Intrauterine Growth Restriction: A 9-Year Prospective Study. Pediatrics. 2006;118(1):91-100.
- Black L, deRegnier R-A, Long J, Georgieff M, Nelson C. Electrographic imaging of recognition memory in 34–38 week gestation intrauterine growth restricted newborns. Experimental Neurology. 2004;190:72-83.
- Lawn, JE (2005) "4 million neonatal deaths: when? Where? Why?" Lancet.