Fetal Intrauterine Growth Restriction (IUGR)
This program is supported by a grant from GE Ultrasound
|The Institute for Advanced Medical Education is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
The Institute for Advanced Medical Education designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit(s) TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.
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Faculty: Dr. Helen Kay, Professor of OB-GYN , Director, Division of Maternal-Fetal Medicine , University of Wisconsin Meriter Hospital, Madison, Wisconsin
Course: Fetal Intrauterine Growth Restriction (IUGR)
Target Audience: Physicians, sonographers and others who perform and/or interpret OB ultrasound.
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Estimated Time for Completion of tutorial: approximately 50 minutes Date of Release: April 18, 2001 Date of Review : June 20, 2005 Expiration Date: June 20 , 2008
Disclosure: In compliance with the Essentials and Standards of the ACCME, the author of this CME tutorial is required to disclose any significant financial or other relationships they may have with the manufacturer(s) of any commercial product(s) or provider(s) of any commercial service(s) discussed in this program.
Dr. Kay is a consultant to GE Ultrasound on obstetric ultrasound.
IAME discloses no relevant financial relationships with commercial interests.
Fetal Intrauterine Growth Restriction (IUGR)
If a definition of 2SD below the mean is used, only infants below the 3rd percentile would be considered growth restricted. Since there is no definition of growth restriction currently uniformly accepted, there will be some false positive fetuses monitored and the benefits of antenatal identification and monitoring will be difficult to assess. At present, the best approach is to be consistent with one definition in order that fetuses at risk can be identified and monitored even at the expense of monitoring normal fetuses. Ultimately, those associated with true pathology will benefit from this exercise.
There are two main types of IUGR fetuses, those that are symmetrically impaired and those that are asymmetrically impaired. Symmetrically growth restricted fetuses tend to have impaired head growth earlier and is more often encountered in fetuses with infection or genetic and anatomic defects. Their mortality risk and intrapartum fetal distress risks are higher, in the range of 40-50% (Lin, 1991). Asymmetric IUGR fetuses tend to have head growth which increases appropriately until late pregnancy and then lags behind. This accounts for two thirds of all cases of IUGR and involves many etiologies.
Fetuses with trisomies, particularly 18 and 13, often have IUGR. Others including sex chromosome abnormalities, such as 45 XO fetuses, and those with mosaic cell lines are often seen with growth restriction. Overall, chromosomal and genetic causes of IUGR account for 5-15 percent of growth restricted fetuses and are more often seen with symmetric than asymmetric IUGR.
Congenital abnormalities with or without chromosomal abnormalities are also seen with IUGR. Most common are cardiac malformations such as tetralogy of Fallot and transposition of the great vessels. Other abnormalities including gastroschisis and omphalocele are also seen with altered fetal growth.
Among the agents that cause fetal IUGR, some of the strongest associations are infections due to rubella, cytomegalovirus and toxoplasmosis. These infections involve multiple organs of the fetus that lead to growth restriction. Infections account for 5-10 % of all IUGR cases.
In multiple gestation, IUGR results from abnormal placental development and possibly abnormal cord insertions. In addition, nutritional factors and uteroplacental blood flow variations contribute to growth restriction. One of the most common reasons for IUGR in twins is the twin-twin transfusion syndrome whereby blood from a "donor" twin is circulated to the "recipient" twin via placental anastomoses resulting in one large and one much smaller fetuses.
Abnormal placental factors include the accepted phenomenon of poor trophoblast invasion in the second trimester. This serious defect leads to third trimester manifestations of IUGR. Additionally, abnormal placental cord insertions, such as velamentous insertions into the membranes, have been reported with IUGR. A placental disc abnormality known as a membranous placenta and a thickened circumvallate placenta have both been associated with IUGR due to poor uteroplacental perfusion. Placental location within the uterus also plays a role in IUGR. Placenta previa has been reported with IUGR. Chorangioma is a placental tumor that may act like a vascular arteriovenous malformation. This abnormality in blood flow within the placenta could lead to fetal growth restriction. Finally, infarcts that compromise the surface area of flow between the intervillous space and the fetal vascular compartment could lead to IUGR.
Among the most significant maternal factors are nutritional deficiencies, particularly of protein intake, and maternal medical diseases including cardiovascular, endocrine such as diabetes and thyroid, autoimmune and renal. Environmental agents can pose significant risks to fetal growth and include adverse effects from cigarette smoking, ethanol and cocaine abuse. Women who work in factories exposed to organic solvents and other toxins have similar risks for IUGR. High altitude leads to an increase in the fetal hematocrit which is compensation for the relative hypoxia encountered in those pregnancies. In the absence of obvious risks, however, the constitutionally smaller fetus should not be considered pathologic and every effort should be make to distinguish that from a truly abnormal condition.
It is important to identify the etiology for fetal growth restriction whenever possible because there are often additional benefits to the patient from having that information. For instance, knowing that there may be a chromosomal or genetic etiology may enable better counseling for the patient in terms of delivery preparations and future pregnancy planning, particularly when genetic syndromes are encountered. This is also true when fetal anomalies are present. Infections that cause IUGR can be treated, such as toxoplasmosis. Maternal nutrition can also be improved during pregnancy since we know that protein restriction leads to significant growth restriction (Lechtig, 1975). Cigarette smoking can be stopped, or at least encouraged to be stopped (Haworth, 1980). Velamentous cord insertions into the placenta can also be accompanied by fetal distress in labor due to the unprotected vessels. Knowing in advance that there is such a condition could prevent such mishaps as cord avulsion at the time of delivery. Identifying IUGR prenatally could lead to diagnosis of a placenta previa which has significant implications should bleeding occur. Abnormal utero-placental perfusion might be improved with bedrest and control of maternal blood pressure. Should the etiology be related to environmental toxins or substances such as alcohol, efforts can be made to remove them. Finally, multiple gestations benefit from identification due to better monitoring for twin discordance and to appropriate and timely delivery.
Clinical - Maternal weight gain and fundal height may be used but are not very sensitive with a low positive predictive value. (Beazley and Underhill, 1970). Clinical estimates of fetal weight are notoriously inaccurate especially in the lower fetal weight ranges.
Ultrasound - The most common determination of fetal growth restriction is based on the estimated fetal weight, EFW, determined from a combination of BPD and AC (Campbell,1975). Fetal measurements using formulas incorporating more than one body part, such as BPD, HC, AC and FL, have the highest accuracy for in utero weight estimation. However, they are also subject to error since there are multiple measurements involved. Thresholds have been defined for all measurements although these are statistically defined rather than outcome based. They use a percentile ranking or a number of standard deviations from the mean for diagnosis since direct fetal weight measurements cannot be done. Growth curves based on ultrasound estimates are clearly different from growth curves generated from birth weights. Nonetheless, weight estimates will usually fall within 15% to 18% of the actual newborn weight in 95% of case (Benson, 1991). Whenever possible, it is prudent to use a growth curve that is gender and fetal number specific. Using a sonographic EFW below the 10th percentile for appropriate population based cross sectional growth charts, approximately 70% of infants identified as IUGR will be normally or constitutionally small and not IUGR (Ott, 1988) and therefore are not at increased risk for poor outcome.
A compromise is to use an individualized growth model which is not dependant on population based normative data and allows true detection of an individual fetus's growth restriction. The disadvantage is that it requires an early estimate of gestational age, prior to 20 weeks preferably, and an additional scan later to establish growth potential for an individual morphometric parameter. A third scan is then performed to confirm that a growth abnormality exists. In essence, it is less important to determine the fetal percentile weight. Rather, it may be more important to determine that there is consistent and linear fetal growth.
The best interval for serial scanning is every 2-3 weeks. This is due to normal dynamics of fetal growth plus limitations in the technical components of the measurements.
Other ultrasound parameters of use in the diagnosis of IUGR include ratios of various measurements such as HC/AC which normally exceeds 1.0 before 32 weeks, is approximately 1.0 at 32-34 weeks and falls below 1.0 after 34 weeks. In asymmetric IUGR, the HC remains larger compared to the AC because of the brain sparing growth phenomenon. In symmetric IUGR, the HC and AC are both reduced and therefore, the HC/AC ratio is not helpful. One other ratio that may be useful is the FL/AC ratio. In asymmetric IUGR, the FL is spared in comparison to the AC measurements from 21 weeks on and therefore, a ratio greater than 23.5 suggests the presence of IUGR.
Fluid measurements -Decreased amniotic fluid volume has been associated with IUGR. This is due to poor perfusion of the fetal kidneys and therefore decreased urine production. A quantitative measurement is the amniotic fluid index (AFI) which sums up the vertical dimensions of the amniotic fluid pockets in 4 quadrants of the uterus. Oligohydramnios is associated with a higher rate of intrapartum complications. (Manning, 1981)
Unfortunately, HC/AC ratios, FL/AC ratios and low amniotic fluid volume have at best a 50-80% sensitivity with a 50-60% positive predictive value (Benson, 1986). Although the negative predictive value in most cases are high, greater than 90%, this is only a reflection of the low prevalence of IUGR in the general population, 90%, which implies that there is a reasonable chance that any average test will be able to exclude the presence of IUGR.
Doppler - Doppler studies of the fetal, placental and uterine vasculature were developed in the 1980's and have since become an integral part of protocols used to assess IUGR. These studies utilize a non-invasive ultrasound method, based on the doppler principle, to evaluate velocities of red blood cells within arteries. In the umbilical artery, rising ratios of the systolic/diastolic frequency in a cardiac cycle reflect an increasing amount of impedance to flow in the placenta. This is due to increased placental circulatory resistance as a result of a reduced number of tertiary villous arteries, mostly resulting from maternal vascular disease such as hypertension. (Giles, 1985). Decreasing diastolic flow, absent diastolic flow and reversed diastolic flow during a cardiac cycle are signs of worsening IUGR.
Similary, an abnormal flow velocity waveform in the uterine arteries demonstrating a persistent diastolic notch beyond 24 weeks gestation reflect abnormal resistance downstream and in this case, that would be the uteroplacental vascular bed. Persistent abnormalities in these uterine artery waveforms have been seen with IUGR and are predictive of the onset of preeclampsia (Bower, 1993).
In extreme cases of fetal hypoxia, a phenomenon known as "brain sparing" is seen with dilation of the fetal intracranial vessels namely, the middle cerebral artery, which provide protected blood flow to the brain at the expense of other organs. The presence of such compensation suggests a compromised fetus (Scherjon, 1993).
Together, these three arteries have provided the best doppler information in the assessment of fetal IUGR and should become a routine part of IUGR assessment. However, the overall sensitivity for doppler prediction of IUGR tends to be low, 40-80% (Benson, 1988).
One additional fetal vessel that may be informative in the presence of IUGR is the ductus venosus. The waveform encountered in that vessel includes a first and second peak coinciding with ventricular systole and early diastole when there is passive filling of the ventricles. Following this second peak is the nadir before the onset of the next systole. This nadir of brief diminished forward flow coincides with atrial contractions during late diatole. In IUGR when there is progressive hypoxia and worsening contractility of the ventricles and atria, this waveform shows a progressive decrease in forward flow due to an increasing pressure gradient in the right atrium. In such cases, a reversal of flow in the inferior vena cava eventually leads to reversal of flow in the ductus venosus. Abnormalities in this waveform have been associated with worsening fetal hypoxemia and acidemia which may precede abnormalities in the fetal heart rate (Ozcan, 1998). Although the pulsatility index has been used to quantify the degree of compromise, in our experience, the most useful finding is that of decreased or reversal of flow during atrial contractions, i.e. the nadir between systoles.
The best approach to identifying the at risk IUGR fetus is by using ultrasound estimations of weight. Additional corroborative evidence can include FL/AC and HC/AC ratios and amniotic fluid volumes. With suspicions for IUGR, doppler studies should then be used not only to confirm the presence of IUGR but to assess for the degree of pathology. Those fetuses with absent diastolic or reverse flow in the umbilical artery, increased flow in the middle cerebral artery and abnormal flow in the uterine arteries are clearly more compromised than a fetus with only borderline measurements and normal doppler studies. Those small fetuses with normal doppler evaluations could represent the constitutionally small, but not pathologically small fetuses.
of Doppler ultrasound
Once the correct Doppler waveform unique to the vessel being studied is identified, attempts are made to obtain several consistently shaped waveforms not affected by fetal breathing which tends to distort the waveforms. The high-pass filter is kept to a minimum in order not to obscure absent or reverse end-diastolic flow when present. The low-pass filter should not be set inappropriately low to avoid eliminating valuable high frequency information in a high velocity circulation such as that in the fetal aorta.
Fetal umbilical arteries are studied in the free floating midportion of the cord. Waveforms at the abdominal cord insertion tend to be higher and those at the placental insertion tend to be lower than those at the midcord.
Fetal middle cerebral artery waveforms are best obtained with the cranium in a transverse position. The Circle of Willis is identified using color flow mapping and the middle cerebral artery should be perpendicular to the transducer with blood flow directly towards the transducer. The angle of insonation should be kept as close to 0 degrees as possible.
The uterine artery Doppler waveform is best obtained by first identifying the maternal internal iliac artery. The transducer is then moved slightly cephalad and medial until uterine vessels are seen in the myometrium by color mapping. The Doppler gate is then placed over the artery to obtain the Doppler waveform, which is easily recognized by its shape and the slower rate consistent with maternal pulse.
The ductus venosus can best be identified in a sagittal section or an oblique section through the upper fetal abdomen. It is seen as a continuation of the intraabdominal umbilical vein with a narrow inlet and a wider outlet and connects to the IVC. Once it is identified, color Doppler imaging can confirm it. The blood flow velocity recording can be made with the gate placed above the inlet of the ductus venosus.
Analyses of the Doppler waveforms are made by measuring the peak systolic (S) and end diastolic (D) frequencies. Various indices have been used for analysis including the simple systolic/diastolic (S/D) ratio, the pulsatility index (S-D/mean), and the resistive index (S-D/S). Although normative data have been established for all measurements, the S/D ratio is most commonly used to study the umbilical artery, the pulsatility index for the MCA and the resistive index for the uterine artery.
At the same time, a careful history and exam of the mother should be undertaken to exclude maternal factors associated with IUGR. These include the more common problems of hypertension, autoimmune and collagen vascular disease, and abusive habits such as cigarette and ethanol use.
A follow up ultrasound for fetal measurements should be performed every 2-3 weeks to follow growth and identify failure to grow. Lack of growth over 4 weeks is of concern and may justify early delivery. Once 32 weeks gestational age is achieved, testing for fetal well being may be initiated with nonstress testing and biophysical profiles. Nonstress tests should be performed twice weekly or weekly as part of the biophysical profile (Manning, 1990). Fetal hypoxia is the main risk sought after by these tests. When acute hypoxia is present, fetal breathing movements diminish along with a decrease in heart rate reactivity. Other less acute tests of hypoxia include decreased body movements, tone and amniotic fluid volume.
Doppler studies of the umbilical artery searching for decreasing diastolic flow and reverse flow along with worsening pulsatility index of the middle cerebral arteries are also part of the fetal surveillance undertaken once IUGR is identified. Reversed diastolic flow is an ominous finding and is seen with a high mortality rate within the subsequent 7 days of in utero life (Brar, 1988).
Therapy will depend on the underlying etiology and attempts should be made to address and modify them. Maternal hyperoxygenation has been shown to increase the umbilical artery pO2 and pH in the hypoxemic, acidotic and growth restricted fetus (Nicolaides, 1987)
The timing of delivery would obviously depend on the severity of the growth restriction. Amniocentesis to determine fetal lung maturity in anticipation of early delivery should be undertaken when there is tapering of fetal growth and an achieved gestational age of 34 weeks. If mature, definitive plans for delivery can be made.
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