Intrauterine growth restriction (IUGR)

 Summary

• Intrauterine growth restriction (IUGR) or foetal growth restriction (FGR) is a term used to designate a foetus that has not reached its growth potential.
• IUGR or FGR describes a group of unborn babies (foetuses) who are too small in proportion to their gestational age. IUGR usually results in the birth of an infant who is small for its gestational age (SGA).
• A SGA baby is an infant whose weight at birth is less than expected for its gestational age, whether preterm, term or post-term.
• SGA infants are associated with more complications and risks compared to those who are appropriate for gestational age (AGA).
• A SGA baby may be genetically small but healthy, or it may be an IUGR baby, also being small but sick because its growth inside the uterus is restricted by specific conditions.
• IUGR babies, in spite of their small size, have physical characteristics similar to those of normal-sized infants of the same gestational age.
• IUGR is associated with increased complications during pregnancy and delivery, but the outcome is generally good.

What is intrauterine growth restriction (IUGR)?

Intrauterine growth restriction (IUGR) or foetal growth restriction (FGR) is the terminology used to describe a group of foetuses (unborn babies) who do not reach their growth potential, who are therefore too small in proportion to their gestational age. This means that their foetal growth rate, the pace at which they grow, is too slow. In contrast the term small for gestational age (SGA) is a descriptive term, which implies that, the foetal size and hence the weight at birth is less than expected, regardless of the cause. In other words, IUGR or FGR refers to the growth rate of the unborn foetus, while SGA refers to the physical size, the birth weight of the infant, irrespective of the of the growth rate.

It is important to realize that these definitions require two very important factors, firstly an appropriate reference table (which means an acceptable growth chart to monitor the foetus/infant) and secondly an accurate gestational age.

Any infant whose weight is below the 10th percentile for gestational age, whether preterm, term or post-term, is regarded as SGA. The percentiles are growth charts, which have been worked out for particular populations of children and are used to measure acceptable growth from birth to adolescence.

The importance with SGA infants is to differentiate a baby who is genetically small but healthy (and will also be a small individual in later life) from a small sick baby due to IUGR. IUGR is most commonly due to a compromised placenta (afterbirth) and can, in severe cases, be associated with intrauterine death. Once delivered, these babies despite their small size do not necessarily suffer the problems related to immature organ systems, which may be present in babies born prematurely.

However, a diagnosis of IUGR often cannot be made until the baby is delivered because gestational age is uncertain in 20 to 50% of women, and the birth weight varies greatly according to the community into which the child is born. But, having said all that, it is important that IUGR is suspected before birth, since this influences the management of the pregnancy.

What causes SGA and IUGR?

When IUGR is suspected, it is necessary to distinguish between foetuses that are small but otherwise healthy (i.e. constitutionally small, and therefore not growth-restricted) and those that are a consequence of an abnormal condition. These abnormal conditions leading to IUGR can be categorized into foetal, placental or maternal factors. Placental conditions are the most frequent cause of IUGR.

Although it is not always possible to determine the underlying cause of poor growth, it is of vital significance to estimate the risk of recurrence. Short overviews of the most common possible causes are as follows:

• Foetal Factors. Firstly genetic factors can play a significant role. Although maternal (from the mother) genes influence birth weight more than paternal (from the father) genes, both have an effect. Also SGA women themselves have a risk of IUGR in their offspring. Secondly congenital anomalies where the foetus has a physical abnormality are associated with failure to maintain normal growth. The combination of structural and chromosomal abnormalities and IUGR is common. In multiple gestations, where the mother is expecting more than one baby, IUGR has a direct relationship to the number of foetuses present. In these pregnancies the growth is similar to that of singletons until mid to late pregnancy, when growth slows down. This is due to the inability of the environment to meet the nutritional demands of the multiple foetuses. Also pregnancy-associated complications are more common in these women with multiple pregnancies. Lastly infections (mostly viral and parasitic) in early pregnancy have the greatest effect on subsequent growth, but account for less than 5% of all IUGR.
• Placental Factors. Many cases of IUGR, especially recurrent cases, are the results of placental disease. Any mismatch between foetal nutrition or respiratory demand and placental supply can results in impaired foetal growth. Many pregnancy-associated complications have their origins in placental maldevelopment, for instance pre-eclampsia.
• Maternal factors. Adequate uteroplacental blood flow (blood flow to the placenta through the uterus) is of vital importance to foetal growth. Maternal medical conditions (i.e. hypertension, diabetes, kidney disease etc.) or pregnancy-associated conditions (pre-eclampsia) can disrupt or diminish this blood flow. Then nutritional deficiencies can also have an effect on birth weight. Pre-pregnancy weight, weight gain during pregnancy and poor dietary intake can be responsible for a disruption in foetal weight. If IUGR was caused by malnutrition in the mother, the baby may demonstrate remarkable “catch-up” growth after delivery if receiving adequate amounts of food. Hypoxemia (poor oxygen levels in the blood flow circulation) is also associated with poor foetal growth. Women with heart conditions, severe lung conditions and severe anaemia (low blood count) are prone to hypoxemia. Substance use and abuse (cigarette smoking, alcohol consumption, illicit drugs, etc.) can cause IUGR, either by a direct toxic effect on the foetus or through inadequate nutrient delivery to the foetus. Other toxin exposure, including some medications can cause IUGR with specific physical abnormalities. Lastly uterine (womb) abnormalities may also play a role in the development of IUGR. 

These causes can at times overlap and the management of these pregnancies, including planning subsequent pregnancies, will need specialized attention.

What are the signs of IUGR?

Once again the recognition of IUGR begins with an accurate gestational age (GA). In spite of their small size, IUGR babies have physical characteristics similar to those of normal-sized infants of the same gestational age. Although appearing ‘normal’ SGA infants look thin with loose skin and decreases skeletal muscle mass, with very little subcutaneous fat tissue. Their faces may at times appear shrunken and the umbilical cord is usually thin.

 The earliest sign of IUGR can sometimes be found on clinical assessment, and for this reason it is acceptable to use a clinical assessment as a screening tool (to look for complicated pregnancies). The symphysis-fundal height measurement (a measurement of the distance between the upper edge of the pubic symphysis and the top of the uterus), using a tape measure is performed to detect foetuses that are poorly grown. The first suspicion of IUGR often arises when this length is noted to be shorter than the expected size for that specific gestation. Although the accuracy of this symphysis-fundal height measurement is controversial it remains the corner stone for the initial evaluation of foetal growth.

It is widely accepted that once the suspicion of IUGR has arisen sonographic (ultrasound based) techniques should be used to confirm the diagnosis and try to look for maternal, placental, or foetal disorders associated with impaired foetal growth. Customized and individualized growth curves may improve the diagnostic performance of the sonographic evaluation.

On sonographic examination a morphometric (body measurement) evaluation including ratio’s (body proportions) of these measurements are done. Sonographic estimation of foetal weight is the single best test to screen for and diagnose FGR. The amniotic fluid (the fluid around the foetus) volume is then evaluated. Oligohydramnios (a low amniotic fluid volume less than expected for gestational age) is one of the sequelae of IUGR. Then Doppler ultrasound is a non-invasive technique commonly used to evaluate maternal and foetal haemodynamics (blood-flow patterns). For normal foetal growth, continuous, adequate perfusion is necessary on both the maternal and foetal sides. In foetuses with IUGR, abnormal Doppler waveforms patterns is typically noted in both uterine (womb) and foetal vessels.

Nowadays three-dimensional ultrasound is being evaluated for assessment of pregnancies complicated by IUGR. This modality has shown very promising results in the evaluation of the IUGR foetus. Not only does it appear to provide more precise information regarding structural abnormalities and organ size, but also appears to be more accurate in estimating the foetal weight and amniotic fluid volume than standard two-dimensional techniques. However, this is based on small studies and has not been adequately assessed in large or controlled studies.

Complications of IUGR

The  main problems in these babies are:

• Foetal distress (during delivery also referred to as “birth asphyxia”), which means that the foetus suffers from insufficient oxygen and nutritional supply, something that can occur during labour or already during pregnancy. If foetal distress develops during labour, each contraction will reduce the blood supply to the placenta still further, which may necessitate rapid delivery by caesarean section.
• Impaired thermoregulation (temperature control). SGA infants have difficulty in controlling their temperature due to increased heat loss and reduced heat production. This is largely due to the reduced subcutaneous fat.
• Hypoglycaemia (low blood sugar). A newborn suffering from IUGR is very prone to hypoglycaemia in the first hours and days after birth because of low stores of glycogen (a stored form of sugar) in its body.
• Polycythaemia (high blood cell count) and hyperviscosity (sticky blood). Due to the low oxygen levels (hypoxia) that are thought to play a role in IUGR, there is a stimulus to produce more blood cells to try and compensate. This results in the blood becoming thicker, and carries a risk of poor blood flow in the newborn.
• Impaired immune function. IUGR infants in the newborn period and though childhood struggle with impaired cellular immunity, carrying the risk of infections.
• Meconium aspiration, The meconium is the baby’s first stool. Passing meconium before birth is usually a sign that the baby is in some distress. Every baby normally inhales amniotic fluid inside the uterus, but if the amniotic fluid is mixed with meconium and becomes aspirated, this can cause breathing difficulties and pneumonia in the newborn.

Infants with IUGR often also necessitate an early delivery and therefore those babies who are delivered before term also may have complications due to prematurity – most commonly cognitive and neurodevelopmental abnormalities. Lastly these babies also carry a higher rate of death and severe disability, when compared to the average for gestational age infants.  

The outcome for an IUGR baby

The outcome of these infants is largely dependent on the cause or underlying conditions that predisposes the foetus to IUGR, on the gestation of onset of the IUGR, and lastly the timeous pick-up and management (including timeous delivery) of these infants.  SGA infants are at risk for impaired growth and neurodevelopment. Subsequent disorders in their adult life may also result from IUGR.

Firstly, SGA infants have different patterns of growth, depending upon the aetiology and the severity of growth restriction. In most moderately affected infants, growth during the first 6 to 12 months after birth may be accelerated, resulting in attainment of normal size in most children. In comparison, severely affected SGA infants frequently weigh less and are shorter than AGA infants throughout childhood and adolescence.

Secondly, SGA infants appear to be at increased risk for neurodevelopmental abnormalities and decreased cognitive performance. It has been noted that when complications such as birth asphyxia are avoided, term SGA infants have a good prognosis for cognitive and neurologic development.

Lastly, adults who were SGA infants may be at increased risk for ischemic heart disease and related disorders. This proposed association between IUGR and adult coronary and vascular disease is based upon the assumption that foetal under nutrition results in changes in vascular development that predisposes to adult disease, such as hypertension, stroke, diabetes, and hypercholesterolemia.

Previously reviewed by Prof B. Schaetzing MD, FCOG(SA), FRCOG, PhD. Part-time Consultant, Dept of Obstetrics & Gynaecology, Faculty of Health Sciences, University of Stellenbosch

Reviewed by Dr JL van der Merwe, Dept of Obstetrics & Gynaecology, Tygerberg Hospital and Faculty of Health Sciences, Stellenbosch University, (November 2010)