Definition

Intrauterine growth restriction (IUGR) is a condition where a baby's growth slows or ceases when in it is in the uterus.

It is part of a wider group - small for gestational age (SGA) fetuses - which includes fetuses that have failed to achieve their growth potential and fetuses that are constitutionally small.
Approximately 50-70% of fetuses with a birthweight below tenth centile for gestational age are constitutionally small.^[1] The lower the centile for defining SGA, the greater the likelihood of IUGR. On the other hand, a fetus with growth restriction may not be SGA.^[2]

Aetiology

If the mother is small, it may be normal for her to have a small fetus; this is constitutional SGA, not IUGR.
Causes of IUGR can be maternal, placental or fetal.

Maternal causes

• Increasing maternal age.
• Hypertension or heart disease.
• Diabetes in pregnancy including gestational diabetes.
• Maternal alcohol abuse causing fetal alcohol syndrome or fetal alcohol effects.
• Maternal use of other drugs including cannabis.
• Maternal smoking (causes 30-40% of cases - if quit before 15 weeks should be normal).^[3]
• Renal disease in pregnancy.
• Undiagnosed coeliac disease.^[4]
• Thrombophilia.
• Drugs including warfarin, phenytoin and steroids.

Placental causes

• In many cases of IUGR, the placenta is small and doesn't provide sufficient nutrition to the growing baby. In IUGR pregnancies, blood flow to the placenta decreases as pregnancy progresses, compared with normal pregnancy when blood flow to the placenta increases throughout pregnancy to meet the growing baby's demand for oxygen and nutrition.
• Cell death (apoptosis); in pregnancies complicated by IUGR, the placenta contains a relatively high proportion of cells that have a shorter life than normal. This means the placenta functions less well, thereby transferring fewer nutrients and less oxygen both to and from the baby.
• Pre-eclampsia

Fetal causes

• In multiple pregnancy, one or more fetuses is often small. Twins show IUGR in 15-20% of cases.
• Chromosomal abnormalities including Down's syndrome, Edwards' syndrome, Patau's syndrome and Turner's syndrome.
• Congenital defects are associated with SGA.
• Intrauterine infection such as cytomegalovirus, toxoplasmosis, rubella and syphilis.

Differentiation

• When the problem is placental insufficiency, the head is not as restricted in size as the abdominal girth - head sparing. This represents preferential nutrition to the brain, with a lack of glycogen stored in the liver.
• If there is a fetal problem such as a chromosome abnormality, there is uniform restriction of growth.

There may be racial differences. Babies of Indian race tend to be a little smaller. If the fetus is in the lower centiles but continues to grow within those centiles, this is reassuring but, if growth is slow and the fetus is falling into lower centiles, this is cause for concern.

Risks associated with intrauterine growth restriction

There is increased risk of:

• Intrapartum fetal distress.
• Intrapartum asphyxia.^[5]
• Postnatal hypoglycaemia or hypocalcaemia-neonatal complications.
• Impaired neurodevelopment.^[6][7]
• Meconium aspiration.
• Intrauterine death.^[8]
• Possibly type 2 (non insulin-dependent) diabetes and hypertension in adult life.^[9]

The reason that studies on SGA fetuses have shown poor perinatal outcome is likely to be the high incidence of true IUGR in this group.^[10] However, the vast majority of term SGA infants have no appreciable morbidity or mortality.^[11]

Examination

Physical examination of the abdomen by inspection and palpation detects as little as 30% SGA fetuses.^[12][13] Therefore, if SGA is suspected, it is necessary to supplement abdominal palpation with ultrasound.
Correct assessment of gestational age is essential and so an ultrasound examination in the first trimester should be routine.
Symphyseal fundal height (SFH) measurement has limited diagnostic accuracy to predict an SGA neonate. A large study found the sensitivity and specificity to be 27% and 88% respectively.^[14] Serial measurements may improve sensitivity and specificity.^[15]

Investigations

Antepartum surveillance should be instituted once the possibility of extrauterine survival for the growth-restricted fetus has been determined. This may include Doppler scanning, stress or non-stress testing, and amniotic fluid volume assessment biophysical profile (BPP).

Ultrasound

The use of Doppler ultrasonography to measure umbilical artery waveforms should be considered a part of fetal evaluation once IUGR is suspected or diagnosed. Modern techniques give very accurate information. The triplex mode is used to assess umbilical venous blood flow. There is a colour Doppler picture of the umbilical vein, pulsed Doppler velocimetry, and real-time ultrasound to measure the diameter of the umbilical vein.

The AC measurement is the best single measurement to assess fetal growth because, where growth is restricted, the liver is usually affected. AC and estimated fetal weight (EFW) are the most accurate diagnostic measurements to predict SGA.
Oligohydramnios is an indicator of IUGR. Amniotic fluid of less than 5 cm, as measured in the four quadrants, is suggestive of oligohydramnios. Other causes of oligohydramnios include death in utero, renal agenesis, and premature rupture of membranes.
There is evidence that it is the trend (growth) that is of more value in predicting poor fetal outcome.^[16]

Management

General measures

When a small fetus is diagnosed, the risk of chromosomal defects should be assessed; up to 19% of fetuses with an AC and EFW less than the fifth centile may have chromosomal defects.^[17] The risk is higher when growth restriction is associated with structural abnormalities, a normal liquor volume or a normal uterine or umbilical artery Doppler.^[17] Therefore, all growth-restricted fetuses need an ultrasound anatomical survey as a minimum. It may also be appropriate to offer karyotyping.

Definitive management depends on the cause:

• If the cause is constitutional, there is no cause for alarm and pregnancy can continue as normal.
• Detailed ultrasound examination may show features of chromosome abnormalities. By the time that diagnosis is made, it is probably too late for termination of pregnancy, but the parents can be apprised of what to expect.
• If the problem is placental inadequacy, the risks of delivery versus prematurity have to be balanced.
• Umbilical artery Doppler to monitor high-risk fetuses (growth-restricted) reduces perinatal morbidity and mortality.^[18]
• The biophysical profile has not been shown to improve perinatal outcome but sufficient data do not exist to rule out its value. A Cochrane review found only four poor-quality studies with fewer than 3,000 patients.^[19] Authors of the review concede that to make a meaningful conclusion about the impact of biophysical profile on perinatal mortality, in excess of 10,000 women would need to be studied.

When to deliver?

The Growth Restriction Intervention Trial (GRIT) showed there is no evidence that early delivery to pre-empt severe hypoxia and acidosis reduces any adverse outcome. However it appeared that obstetricians currently make appropriate delivery decisions to minimise mortality.^[20][21]

• When end diastolic flow is present in the umbilical artery, delay delivery until at least 37 weeks, provided other surveillance findings are normal.
• When end diastolic flow is absent or reversed, admission, close surveillance and administration of steroids are required.^[22][23] Among preterm growth-restricted fetuses with absent end-diastolic blood flow in the umbilical artery, the umbilical artery/middle cerebral artery ratio is the best predictor of neonatal mortality or severe morbidity.^[24] If other surveillance results (biophysical profile, venous Doppler) are abnormal, delivery is indicated. If gestation is over 34 weeks, even if other results are normal, delivery may be considered.

Delivery

• Administer steroids if gestation is between 24+0 and 34+6 weeks. Antenatal steroids significantly reduce the incidence of respiratory distress syndrome.^[25] 
• Intrapartum monitoring with continuous cardiotocograph is recommended.^[26]
• Deliver in a unit where optimal neonatal expertise and facilities are available.^[27] A skilled resuscitator who is trained and competent in resuscitation of the newborn should be present at delivery.
• Where possible, an experienced neonatologist should be present if gestation is extremely preterm or growth restriction is severe.

Prognosis

• Babies that have been starved in utero tend to be hungry and feed enthusiastically to gain weight. As an adult they can expect normal or only slightly reduced stature.
• If there was slow head growth before 26 weeks they may show significant developmental delays at 4 years of age. It has also been shown to be associated with impaired executive cognitive function in young adults.^[28]
• An extremely low birth weight implies a high risk of perinatal mortality and neonatal morbidity, but the most significant variable that can be correlated to the long-term neurological outcome is the gestational age.^[29]
• Studies have shown that infants with birth weight below 2.5 kg have a three times increased risk of death due to coronary artery disease later in life.^[30] There seems to be an increased risk of hypertension,^[31] type 2 diabetes,^[32] and autoimmune thyroid disease.