Intrauterine growth restriction (IUGR)
Intrauterine growth restriction (IUGR) is defined as a failure of the fetus to attain its pre-determined growth potential. That is, the baby does not grow at the normal, expected rate. The image below shows a normally-grown baby (right) and a growth-restricted baby (left).
We have recently published a comprehensive review entitled Screening, Diagnosis and Management of IUGR in the Journal of Obstetrics & Gynecology Canada (JOGC, 2012, 34(1):17-28). Permission to post this article on the Placenta Clinic website has been provided courtesy of the Society of Obstetricians and Gynaecologists of Canada.
IUGR is usually a disorder of placental insufficiency where the placenta is not providing sufficient nutrients to the baby to sustain normal growth. However, IUGR can also be caused by other factors, including:
- Abnormal chromosomes
- Abnormalities in a cluster of genes or a single gene
- Silencing of normal genes (called epigenetic gene silencing)
- Syndromes with an unknown but presumed genetic basis
- Infections passed to the fetus (congenital infections)
- Substance abuse (including smoking)
- Pregnancy at high altitude
- Starvation (very rare in developed countries)
- Anemia (low blood count)
- Other more rare causes
While IUGR can be apparent visually (maternal characteristics), it can also be diagnosed using the ultrasound imaging techniques and Doppler imaging studies available to obstetricians and Maternal-Fetal Medicine specialists.
Symptoms and Signs
Poor maternal weight gain
Development of hypertension (up to 50% of mothers with IUGR pregnancies develop hypertension due to associated placental insufficiency)
Reduced fetal activity
Small-for-dates pregnancy (determined by the symphysis-fundal height, SFH). Normal pregnancies progress at 1cm/week, so 30cm at 30 weeks. Any SFH that is 3cm or more behind dates requires ultrasound investigations.
Ultrasound scanning techniques are used to monitor fetal growth and record fetal biometry. These are useful for the estimation of fetal weight and measuring of body proportions (ex. abdominal circumference vs head circumference).
Estimated fetal weight (EFW)
The EFW is estimated by measuring the bi-parietal diameter (BPD) and head circumference (HC) of the baby's head, abdominal (belly) circumference (AC), and femur (thigh bone) length (FL) on ultrasound. The average size of male and female Canadian babies (including all ethnic backgrounds and heights of parents) are used as a reference to determine if the developing baby is too small (see Canadian growth centiles). If the baby is below the 10th percentile, this is termed small-for-gestational age (SGA) and a proportion of these babies will be found to have true IUGR.
Monitoring of fetal body proportions
Babies with IUGR caused by placental insufficiency often develop asymmetrically, that is, the ratio of the baby's head circumference (HC) to the baby's abdominal circumference (AC) is elevated (the head remains the normal size while the abdomen becomes smaller because the body organs, like the liver, grow slower). Asymmetrical growth also includes short femur length (FL). Small babies in healthy mothers with a normal HC/AC ratio and normal FL may simply be smaller than normal due to their mother's size and ethnicity. For example, a baby predicted to be 6lb near birth might be normal for a slim 5’ tall South Asian woman, but would likely be true IUGR if born to a 5’ 10” tall Caucasian woman.
Doppler studies are used to study blood flow to the baby. Early-onset IUGR pregnancies (typically found <32 weeks’ gestation) have high resistance to flow in the umbilical arteries. They may also have:
- Brain redistribution: abnormal flow in the baby's brain characterized by increased flow in the middle cerebral artery or MCA;
- Abnormal flow in the ductus venosus (a channel within the liver that sends oxygenated blood from the umbilical vein/placenta at high speed across the heart to go up to the baby's brain);
- Uteroplacental vascular insufficiency: a small and/or damaged placenta characterized by abnormal blood supply to the placenta via the maternal uterine arteries;
By contrast, in the more common late-onset IUGR (found after 36 weeks), the uterine and umbilical artery Doppler studies are mostly normal. However, late onset-IUGR babies may have abnormal middle cerebral artery (MCA) Doppler and/or very mature (Grannum grade 3) placentas.
If we suspect that the developing baby is small, the following steps may be taken:
- Confirm that the pregnancy dating is correct: the fetus might be incorrectly classified as small, but is actually a perfectly healthy baby that is 3 or 4 weeks younger than stated in the ultrasound report. The earliest ultrasound examinations available will provide the most accurate dating.
- If the developing baby is genuinely smaller than average, it may be small and healthy because its parents are smaller than average and of an ethnicity where birth weight is generally less than the average for Caucasians (this is called a constitutionally-small fetus). This is identified by customization of the growth curve based on parental characteristics and the weights of previous babies. For example, a baby weighing 1,200 g at 32 weeks on the 5th centile for the average Canadian may actually be of average size for a South Indian woman who is 5’ 1” tall.
- Review of maternal and pregnancy risk factors for abnormal placental function. These include: maternal age, use of in-vitro fertilization, IPS blood tests, obesity, smoking, previous medical conditions, and new-onset problems in the current pregnancy, such as pre-eclampsia, recurrent vaginal bleeding, or reduced fetal activity.
- Investigate non-placental causes of IUGR:
- If available, review fetal anatomy ultrasound (performed at 18-20 weeks) for any potential birth defects. A birth defect would suggest that a chromosomal or other genetic abnormality is causing the growth restriction. If the fetus is genuinely IUGR, then an anatomical ultrasound is repeated to ensure there are no birth defects.
- A maternal blood test termed the ToRCH screen may be performed. This is to determine if the mother has an infection that can slow the baby's growth.
- Review any information from a previous invasive test (amniocentesis or chorionic villus sampling [CVS]). If such a test has not been performed, then the risk of a possible chromosome disorder will be assessed based on the following information: the new detailed ultrasound findings, maternal age, abnormal IPS test results, and any evidence that the IUGR is placental problem.
- If there is no evidence of non-placental causes of IUGR, placental function testing is performed (see below for more information). Placental problems are much more common than the other genetic causes of IUGR.
- A plan of serial monitoring is then developed (see below).
- Pediatric consultation before delivery. This is a useful step when delivery is anticipated with an estimated fetal weight <2,500 g and/or any fetal abnormalities are suspected on ultrasound. The consultation allows the pediatric staff to plan post-natal tests and follow up of the newborn if it is not admitted to a neonatal unit.
- Antenatal steroids (glucocorticoids): steroids are administered to a growth restricted fetus to accelerate pulmonary maturity (since the lungs develop later than other organ systems), since the infant will likely be born before term. However, there is controversy over the use of glucocorticoids for an IUGR fetus. Administration of glucocorticoids usually results in a temporary improvement in end diastolic flow in the umbilical arteries. When this is observed by serial Doppler studies, delivery can be delayed. In about one third of severe IUGR pregnancies, the opposite may occur (development of reversed end-diastolic flow) because the fetus does not tolerate the medication and delivery must then be imminent. Therefore, we only prescribe antenatal steroids with intensive daily monitoring in an inpatient setting.
Placental function testing is very useful to directly diagnose the placental basis of IUGR. The following may suggest a placental cause of IUGR:
- A false-positive IPS test result: the IPS test is positive for an abnormality (Down Syndrome or spina bifida), but that these abnormalities were not actually present (ruled out by amniocentesis or chorionic villus sampling). As such, the positive test result may indicate abnormal placental function. (see the section on Maternal Biochemistry in placental function testing for more information);
- Presence of maternal risk factors for placental dysfunction (described above);
- New-onset hypertension;
- Abnormal uterine and umbilical artery Doppler, and/or abnormalities of placental size, shape and texture. These findings are illustrated below and are described in further detail in placental function testing.
Image © by Leslie Proctor, 2009
Serial ultrasound assessments of fetal growth, fetal well-being, and amniotic fluid volume, in addition to Doppler tests of umbilical and uterine arteries are essential. The frequency of these assessments should be determined based on the severity of IUGR.
- Serial fetal weight assessments: fetal weight is estimated based on a published formula, using a variety of measurements (femur length, head circumference, abdominal circumference, etc.). We have published an article on this topic which showed that a different formula for estimating fetal weight should be used when the baby displays IUGR.
- Biophysical profile: used to monitor the well-being of the fetus. This assessment includes evaluation of amniotic fluid volume, fetal movements, fetal tone (e.g. flexion/extension of limb, or opening/closing of hand), and fetal breathing movements.
- Amniotic fluid volume: lower levels of amniotic fluid volume than what is expected for gestational age (also known as oligohydramnios) in IUGR babies can be associated with poor fetal outcome.
- Doppler assessment: absent or reversed of end diastolic flow in the umbilical artery, using Doppler assessment, is indicative of poor fetal prognosis.
- The pregnancy may require delivery by Caesarean section. If so, attempts at future pregnancies should be deferred for at least 1 year to allow for full recovery.
- In some cases of severe early-onset IUGR, the Caesarean section may require a vertical uterine incision (called the classical Caesarean section), because the baby is too small for the normal horizontal incision. Women who require a classical Caesarean section are not able to safely have a normal vaginal delivery in the future.
- The emotional health of the mother, her partner, and surrounding family may be challenged by the admission of a new small baby to a neonatal intensive care unit (NICU). The NICU staff are trained to recognize and support mothers and families in this situation and can direct them to helpful resources.
- Some women will remain hypertensive after delivery and may need to take blood pressure medications (by mouth) for 4-8 weeks. A small number of women with persistent hypertension require further medical tests for underlying causes of hypertension by internal medicine physicians linked to a high risk pregnancy unit.
- Birth control should be discussed following an IUGR delivery.
- Most IUGR babies progress very well following delivery. They will exhibit 'catch-up' growth to babies born at higher birth weights during their first year of life.
- If an IUGR baby needs to be admitted to a pediatric special care unit (birth weight 2,000-2,500g) or a NICU (birth weight <2,000g), he/she will undergo tests to see why the baby was born small. In addition, the baby's vision and hearing will be assessed. Most pediatric units, like Mount Sinai Hospital, have a follow-up program with a pediatrician that has expertise in infant development.
- A small proportion of IUGR babies may develop abnormalities of movement of the limbs (cerebral palsy), abnormal vision (retinopathy of prematurity), deafness, or may be slow to attain their developmental milestones. Well-planned resources to recognize these alterations from normal, together with interventions to assist the child and family, can make a big difference to childhood development and health.
- IUGR can recur in future pregnancies, but the risk of recurrence depends on: i) the underlying cause; and ii) the mother's health;
- Placental insufficiency can be inferred from a review of the ultrasounds, together with the newborn assessment and development. Review of placental pathology can be very helpful to prove the diagnosis;
- Severe placental insufficiency has a 10% recurrence risk in otherwise healthy women with the same partner;
- The risk of recurrent IUGR due to placental insufficiency is increased in the following circumstances:
o Persistent (chronic) hypertension
o Advanced maternal age (>35 years)
o Maternal kidney or autoimmune disease
o Maternal clotting disorders
o Maternal obesity (body mass index [BMI] >30)
o Maternal smoking
o Certain medications required by the mother long-term
- Therefore, women who have had an IUGR pregnancy (especially if the infant was born by Caesarean section and <32 weeks or <1,500g, or with risk factors listed above) should consider having a pre-pregnancy consultation either with their delivery obstetrician or with a maternal fetal medicine specialist.