Special Feature: Enlightened Management of IUGR
By John C. Hobbins, MD
Intrauterine Growth Restriction (IUGR) complicates between 5% and 10% of all pregnancies. Although undergrown fetuses/infants have a higher perinatal mortality rate than appropriate for gestational age babies, this rate has dropped over the past few years. Unfortunately, these babies are predisposed to substantial perinatal morbidity. Immediate problems after birth include hypothermia, hypoglycemia, hypocalcemia, polycythemia, and later, necrotizing enterocolitis.
At various times after discharge from the nursery, neurological sequelae can surface in as many of 35% of IUGR infants. Also, Barker and others have shown that cardiovascular disease and diabetes are more likely to appear in adults who were growth restricted at birth. For years, the thrust of management of IUGR has been to use standard tests of fetal surveillance to affect delivery before intrauterine demise occurs. Today the goal of obstetrical management should be to optimize future neurological function by monitoring fetal condition with more sophisticated testing so that delivery can be accomplished with exquisite timing.
Diagnosis of IUGR
The strict definition of small-for-gestational age (SGA) is "an infant who is in or below the 10th percentile of mean weight for gestation." When formulas became available for estimation of fetal weight (EFW), the same definition was used in utero to identify SGA fetuses. For practical purposes, IUGR and SGA have been used interchangeably, but from a physiologic standpoint IUGR generally connotes a fetus/infant that is deprived.
As previously stated in an earlier OB/GYN Clinical Alert, standard formulas for EFW are within 10% of the fetal weight 80% of the time, and nomograms for fetal weight are available to identify the fetus who is SGA. We have found that after 30 weeks our fetuses are about 5% heavier per gestational age than neonates used to construct a neonatal nomogram in Denver. A technique to single out undergrown fetuses commonly used in Europe is the abdominal circumference (AC). Since IUGR fetuses have small livers and less subcutaneous fat, the AC is the best biometric measurement to predict IUGR. Fortunately, all small babies are not necessarily either deprived or in jeopardy since some are simply genetically programmed to be small, but they have been lumped together for practical purposes with those fetuses that are. Also, many fetuses that are deprived are missed by a 10th percentile cutoff. These are fetuses genetically destined to be in the 80th percentile who end up being in the 15th percentile because of a placental inadequacy. These fetuses would only be identified by serial scanning, something that third-party payers are reluctant to support if there are no risk factors.
Management of IUGR
Nonstress Test (NST): This test has been used extensively in pregnancies complicated by IUGR to warn the clinician of impending fetal demise. Many studies have shown that it is very unlikely for a fetus to die of placental insufficiency within a short time of a reassuring NST. The 2 shortcomings of the test are that it is replete with false-positives and it may not be sensitive enough to tell us when the fetus is in danger of neurological handicap.
Biophysical Profile (BPP): The BPP has been used in conjunction with the NST to manage patients with undergrown fetuses. The intent of monitoring fetal movements and fetal respirations is to provide the clinician with evidence that the fetus is not hypoxic or acidotic enough to be delivered at the time the test is conducted. Assessment of amniotic fluid provides the clinician with indirect information about the chronicity of compromise, and in the case of IUGR, it helps to distinguish between a fetus that is attempting to adapt to a hostile intra-uterine environment from one that does not have to.
The problem with both tests is that they are indirect reflections of the acid base status and the adaptive circulatory capacity of the fetus. Recent evidence strongly suggests that Doppler waveform analysis is more precise in assessing fetal status by directly monitoring the circulatory dynamics in the fetus.
Doppler-Umbilical Artery: The umbilical arteries are the only tributaries out to the placenta from the fetus. They branch into many sub-branches comprising the villous architecture of the placenta. Each of the many fetal units responsible for the transfer of oxygen and nutrients has a network of arterioles, venules, and capillaries. The richer the fetal arterial arborization, the lower the placental resistance and the higher the end diastolic flow upstream in the umbilical arteries. There is now compelling evidence that in most IUGR pregnancies there are fewer terminal villi (and small placental arteries) than in normal pregnancies. This would explain why low-end diastolic flow seen in some pregnancies complicated by IUGR can be a steady state phenomenon but does not explain completely why sometimes waveforms improve with bedrest and why some waveforms can worsen over short intervals.
Basically, when assessing umbilical artery waveform one is determining by a ratio of systole to diastole or resistance index, how far away from diastole is the systolic peak. The lower the end diastolic flow (EDF), the higher the placental resistance and an S/D ratio of > 3.0 after 30 weeks in a small fetus is a worrisome sign. Absent EDF is generally an indicator of substantial compromise and reverse EDF (below the waveform baseline) is an extremely ominous sign of impending death or morbidity.
The bottom line is that many investigators have found that deceased EDF in the umbilical arteries represents the earliest sign of fetal compromise in IUGR, and may precede a nonreassuring NST by 3 weeks.
Soothill followed fetuses designated as growth restricted by AC measurements of > 2 SDs below the mean with umbilical artery Doppler examinations. He found that those SGA fetuses that had normal umbilical artery waveforms had similar outcomes to control AGA fetuses. However, SGA fetuses with abnormal umbilical artery Dopplers were delivered significantly earlier and spent significantly more time in the nursery than the other 2 groups.
Middle Cerebral Artery (MCA)
Many IUGR fetuses will shuttle blood to their brains in the face of early hypoxia. This will result in an increase in EDF in the MCA. The usual relationship of peak systole-to-diastole is 6, but in many cases of IUGR the ratio drops below 1:4. However, this is sometimes an isolated finding and, without change in the umbilical arteries, is not indicative of severe hypoxia or acidosis but simply a sign of fetal adaptation. Virtually always we have found that an increase in EDF in the MCA and oligohydramnios go hand-in-hand, since the fetal kidneys get shortchanged in a fetus that is "sparing" his/her brain. However, if the umbilical arteries have a normal waveform, brain sparing is not an indication for delivery in a preterm fetus.
Table Algorithm for the Management of IUGR 25-27 Weeks
It is unclear whether the complications of prematurity from early delivery are a greater threat to an IUGR fetus than intrauterine hypoxia in a pregnancy allowed to continue. Therefore, decisions cannot be made by a simple algorithm and depend upon nursery capability, patient desires, physician comfort, etc.
26-34 weeks—NST & Doppler Studies
NST Reassuring
Umb A Doppler Reassuring®
Repeat in 1 weekUmb A Doppler NonReassuring®
Venous DopplerVenous Doppler Reassuring®
Repeat in 1 weekVenous Doppler NonReassuring®
DeliverNST NonReassuring
Umb A Doppler Reassuring®
Repeat in 1 weekUmb A Doppler NonReassuring®
Deliver34-36 Weeks—NST & Doppler Studies
Both Tests Reassuring®
Repeat in 1 week OR® Test for Lung MaturityIf Immature®
Repeat in 1 weekIf Mature®
DeliverEither Test NonReassuring®
Deliver36 Weeks
Deliver
The Venous System
Investigators are now beginning to analyze waveforms from the ductus venous (DV) and inferior vena cava (IVC) in an effort to assess cardiac function in the fetus compromised by IUGR. Succinctly, the greater the negative deflection (representing regurgitant flow) during atrial contraction, the greater the chance of fetal metabolic acidosis. The latter has a strong correlation with neurological sequelae in the infant. Evidence is accumulating to suggest that, while decreased EDF in the umbilical artery is a sign of very early compromise in IUGR, abnormal waveforms from the DV or IVC will predict compromise capable of causing neurological sequelae in pregnancies to be allowed to continue. If further studies bear this out, then the DV can be used to time delivery in a serially Doppler-monitored IUGR pregnancy.
Evidence of the use of Doppler measurement of umbilical artery in the management of IUGR comes from a study published in the New England Journal of Medicine in 1993 by Pardi and associates. Acid base status was determined in IUGR fetuses through cordocentesis prior to delivery. When both Doppler and NSTs were normal, no fetus was hypoxic or acidotic. If NST was normal and the Dopplers were abnormal, less than 5% were hypoxic and/or acidotic. If both were abnormal, 60% were acidotic.
Further evidence of Doppler’s superiority in predicting fetal jeopardy comes from our collaborators at the University of Milan. In a yet unpublished study, it was found that the umbilical artery waveform often became abnormal 3 weeks before the NST results pointed toward delivery in serially monitored IUGR pregnancies. Also, the best predictor of neurological outcome was the DV.
Based on these data and others, we have developed a management algorithm for IUGR that we are using at the University of Colorado. I will pass this along.
Suggested Reading
1. Barker DJ. Theriogenology. 2000;53(2):555-574.
2. Hobbins, JC. OB/GYN Clinical Alert. 2001;18(6):47.
3. Pardi G, et al. N Engl J Med. 1993;328(10):728-729.
4. Soothill PW, et al. Obstet Gynecol. 1999;13:225-228.
Reader Letter
Dear Editors:
". . .We do not have anything good to screen for ovarian cancer. [The ovaries] are hard to feel on bimanual exam. Ultrasound helps but . . . I can’t imagine that any gynecologist does not inspect the ovaries carefully so we know they are grossly normal." — Evan F. Evans, MD, Ogden, Utah.
Kenneth L. Noller, MD, responds:
You are certainly correct in stating that we do not have "anything good" for ovarian cancer screening. CA-125 is expensive and causes far more concern than is warranted; ultrasonography if performed by an excellent technician with high-quality equipment is more sensitive but still remains nonspecific.
Unfortunately, the most inaccurate method for assessing the ovaries is bimanual examination. No one has ever shown that it is useful for screening for ovarian cancer. Unfortunately, when we can feel ovarian cancer it is almost always stage III or IV. Of course we all have the occasional (extremely rare) patient in whom we have detected an ovarian cancer that turned out to be only stage I. Unfortunately, such findings are more lucky than good.
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