Intrauterine growth restriction
Intrauterine growth restriction (IUGR), or fetal growth restriction, is the poor 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.[5] The causes of IUGR are broad and may involve maternal, fetal, or placental complications.[6]
Intrauterine growth restriction
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 abnormalities,[7] demonstrating that under-nutrition is already a leading health problem at 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.[8] At the end of pregnancy, it can result in a low birth weight.
Management[edit]
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.[6] In addition to evaluating the fetal growth velocity, the fetus should primarily be monitored by ultrasonography every 3–4 weeks.[6] An additional monitoring technique is an Doppler velocimetry. Doppler velocimetry is useful in monitoring blood flow through the uterine and umbilical arteries, and may indicate signs of uteroplacental insufficiency.[25] This method may also detect blood vessels, specifically the ductus venosus and middle cerebral arteries, which are not developing properly or may not adapt well after birth.[25] Monitoring via Doppler velocimetry has been shown to decrease the risk of morbidity and mortality before and after parturition among IUGR patients.[26] Standard fetal surveillance via nonstress tests and/or biophysical profile scoring is also recommended.[25][6] Bed rest has not been found to improve outcomes and is not typically recommended.[27] There is currently a lack of evidence supporting any dietary or supplemental changes that may prevent the development of IUGR.[6]
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[6] 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.[26] Fetuses with an anticipated delivery before 34 weeks gestation are recommended to receive corticosteroids to facilitate fetal maturation.[6][28] Anticipated births before 32 weeks should receive magnesium sulfate to protect development of the fetal brain.[29]
Outcomes[edit]
Postnatal complications[edit]
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 stillborn infants exhibit IUGR. Perinatal mortality rates are 4-8 times higher for infants with IUGR, and morbidity is present in 50% of surviving infants.[30] Common causes of mortality in fetuses/infants with IUGR include: severe placental insufficiency and chronic hypoxia, congenital malformations, congenital infections, placental abruption, cord accidents, cord prolapse, placental infarcts, and severe perinatal depression.[5]
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 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.[31]
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.[32] Furthermore, rapid metabolic and physiologic changes in the first few days after birth can yield susceptibility to hypocalcemia, polycythemia, immunologic compromise, and renal dysfunction.[33][34]
Long-term consequences[edit]
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 type II diabetes.[35]
Infants with IUGR may continue to show signs of abnormal growth throughout childhood. Infants with asymmetric IUGR (head-sparing) typically have more robust 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.[36]
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.[37][38]
Catch-up growth can alter fat distribution in children diagnosed with IUGR as infants and increase risk of metabolic syndrome.[39] Infants with IUGR may be susceptible to long-term dysfunction of several endocrine processes, including growth hormone signaling, the hypothalamic-pituitary-adrenal axis, and puberty.[40] Renal dysfunction, disrupted lung development, and impaired bone metabolism are also associated with IUGR.[41]
Animals[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.[42][43][44] Hormonal effects appear implicated in the reduced placental development.[44] Although early reduction of placental development is not accompanied by concurrent reduction of fetal growth;[42] it tends to limit fetal growth later in gestation. Normally, ovine placental mass increases until about day 70 of gestation,[45] 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.[46])
In adolescent ewes (i.e. ewe hoggets), overfeeding during pregnancy can also cause intrauterine growth restriction, by altering nutrient partitioning between dam and conceptus.[47][48] 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.[48] 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.[49]
In both of the above models of IUGR in sheep, the absolute magnitude of uterine blood flow is reduced.[48] Evidence of substantial reduction of placental glucose transport capacity has been observed in pregnant ewes that had been heat-stressed during placental development.[50][51]