Baby Steps

How ultrasound advances are improving fetal and neonatal care

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(©istockphoto.com/Greg Christman)

Once a concealed and mysterious entity, a fetus is now truly considered a patient within a patient. Fetal anatomy, physiology, and behavior are all open for investigation and even intervention.

Although some experts considered ultrasound to be a passing fad in the obstetrical field several decades ago, little has revolutionized care to the same degree as the increased sophistication and applications of perinatal ultrasound.

Tremendous advances in image quality and ultrasound safety have occurred during the last decade. Current technologies have improved resolution and image quality, and increased capabilities for imaging and diagnostic testing. Anomalies that would have gone unnoticed even a few years ago are being recognized.

Developments in managing maternal conditions, such as Rh isoimmunization and pre-eclampsia, have improved perinatal morbidity and mortality. Advances in anomaly detection have expanded prenatal genetic diagnosis, as well as fetal and neonatal care.

Three areas have enjoyed tremendous achievements recently: first trimester fetal ultrasound; Doppler ultrasound applications; and using ultrasound to guide fetal interventions in single and multiple pregnancies.

Signs of Trouble

Research on the anatomy of the first trimester fetus has allowed defects and syndromes to be discovered earlier in a pregnancy. Previously, these situations may have gone undiagnosed until well into the second trimester. For many women who are carrying a fetus with lethal chromosomal
anomalies, this detection has provided the ability to have safer, earlier terminations.

In addition, the ability to diagnose Down syndrome reliably in the first trimester has broadened options for women or enabled them to begin preparing for the child’s special needs. By making these types of diagnoses early in pregnancy, obstetricians can consider fetal conditions and pursue other areas of investigation, or alter medical care as indicated by ultrasound findings. 

Kypros Nicolaides first reported on the efficacy of the nuchal translucency measurement in the first trimester as a screening test for aneuploidy in 1995. The nuchal translucency is a single measurement of thickness of the nuchal space, an image taken with the fetus in a midsagittal plane, with the fetal head in a neutral position. Once a fetus is properly positioned, the image is magnified and calipers are placed at the point of maximum thickness.

Clinicians must avoid inadvertent measurements of the distance to the amnion, which can be confused with the skin edge of the fetus. Accuracy and superior technique are imperative to a reliable measurement and screen result. As such, practitioners using nuchal translucency screening should undergo vigilant certification before performing the procedure.

When a nuchal translucency is performed in isolation, it is approximately 75 percent sensitive detecting Trisomy 21. However, when combined with two serum analytes, beta-hCG and PAPP-A, the sensitivity of the first trimester combined screening increases to 87 percent (FASTER trial) at a 5-percent false positive rate. Other combinations that include incorporating the quad screen and anatomy survey of the fetus into risk calculations have achieved an improved 95-percent sensitivity.

There have been many benefits that have arisen from incorporating first trimester screenings, especially into the higher risk category of women of advanced maternal age. Many fetuses with chromosomal aneuploidy are being detected and diagnosed earlier. In addition, the rate of invasive testing is decreasing as many women in higher risk categories, such as women over age 35 and even 40, are opting out of these procedures, based on reassuring screen results. The risk of aneuploidy is greater than 1 percent to 2 percent in the high-risk age groups. 

One study published by Chervenak et al. in 2004 found the rate of chorionic villous sampling fell dramatically in patients over age 35 by implementing first trimester screening. Nadel et al. found a similarly dramatic decrease in the rate of amniocentesis – from 40 percent to 14 percent – mostly attributable to women opting for screening over proceeding directly to invasive testing.

Although the rate of pregnancy loss secondary to complications of amniocentesis is estimated to be 1 in 1,000, this dramatic reduction in invasive procedures can result in fewer pregnancy losses.

However, current screening strategies have come under some criticism. For instance, the combination of two specialized ultrasounds and six blood markers is an expensive screening test. In addition, a false positive screening can produce unnecessary anxiety, and the complexity of the testing violates, in many circumstances, the desired accessibility standard for screening.

In addition to first trimester screening for aneuploidy, the boundaries of anatomical evaluations of early fetal anatomy are also expanding. It is now common to assess for other fetal abnormalities, such as cardiac defects, ventral wall defects, limb deformities and urogenital abnormalities into the first trimester.

In fact, with vaginal imaging, many experts believe that with morbidly obese patients, the first trimester vaginal ultrasound is the ideal time to anatomically screen the fetus.

Detecting with Doppler

A second area in obstetrical ultrasound that has progressed is the understanding and utilization of Doppler blood flow patterns through the mother and fetal circulation to diagnose maternal/fetal disease and guide therapy. The management of growth restriction, isoimmunization, pre-eclampsia, twin-twin transfusion and other causes of fetal anemia have drastically changed with a better understanding of Doppler physiology.    

Several trials have demonstrated the ability of uterine artery Dopplers to predict women at high risk for severe pre-eclampsia, growth restriction and placental abruption. Sampling of the uterine Dopplers for the presence of a characteristic “notch,” and resistive index greater than 0.6 is predictive for developing serious perinatal complications. A uterine notch is an early diastolic notch in the right or left, or bilateral, uterine artery. The resistance index is the peak systolic flow in the uterine artery, minus the end diastolic flow, divided by the peak systolic flow velocity.

A recent Cochrane meta-analysis of 64 studies that examined the ability of Doppler indices to screen for pre-eclampsia determined an elevated resistance index or the presence of unilateral/bilateral notching in the uterine arteries were more than 60 percent sensitive predicting pre-eclampsia. As preventive and therapeutic strategies for managing pre-eclampsia continue to develop, predicting severe pre-eclampsia may play a vital role in obstetrical care.

Doppler velocimetry of the fetal circulation has also given new insight into normal and abnormal physiology and pathology. Umbilical cord Dopplers are routinely used to evaluate the presence of placental pathology. In essence, the placenta should represent a low resistance circulation for the fetus. With the development of placental pathology; however, increased resistance in the placenta impedes diastolic blood flow in the umbilical artery. With increasing resistance, flow can slow, become absent, or even be reversed. Blood flow during diastole is highly predictive of impending mortality if the fetus remains undelivered.

Likewise, sampling the middle cerebral artery can also provide an important understanding of fetal physiology and pathology. In fetuses with growth restrictions, fetal circulation is “centralized” with decreased flow to the kidneys, gastrointestinal tract and extremities, and increased central flow.

This centralization can be easily evaluated by sampling the velocimetry through the circle of Willis. The fetal artery that is the most reliably and accurately sampled is the middle cerebral artery. The artery is sampled near its branch point from the circle of Willis, with no more than a 10-degree angle of insonation. As fetal circulation is redistributed, there is a centralization of flow and a decreasing resistance and pulsatility index. The exact cut-offs of normal values vary by gestational age, but they can easily be calculated.

In addition to evaluating fetal growth restriction, flow through the middle cerebral artery has been important to evaluate fetal anemia. In fact, using middle cerebral Dopplers has revolutionized the care of patients carrying fetuses at high risk for anemia. The classical pathology is Rh isoimmunization. In mothers that have become Rh sensitized, historically multiple invasive amniocentesis procedures would evaluate the ?OD-450 to determine the amount of bilirubin in the amniotic fluid to estimate the degree of fetal hemolysis. By using middle cerebral Dopplers, the need for invasive testing has dramatically decreased.

In a landmark study by Mari in 2000, The New England Journal of Medicine published data that velocimetry of the middle cerebral Doppler was 100-percent sensitive for detecting moderate or severe anemia. Since that initial report, several other reports have supported middle cerebral Doppler for evaluating fetal anemia.

Given the basic physical principle that thin fluids flow more quickly, the peak systolic velocity can provide information regarding overall viscosity of the fetal blood, and hence the degree of fetal anemia. Although they reported a few false positive screens, all fetuses with moderate or severe anemia, those potentially treated by percutaneous, periumbilical blood transfusion, were detected. Although the classic etiology of fetal anemia is Rh isoimmunization, this method of evaluation has proven beneficial in other sources of fetal anemia, such as parvovirus B19 infection, thalassemia, fetal bleeding, and twin-twin transfusion syndrome, in addition to Rh isoimmunization.

Several other fetal vessels, such as the umbilical vein, ductus venosus, inferior vena cava, ductus arteriosis, and mesenteric arteries can be sampled. 

Early Intervention

A third area of tremendous advance in perinatal ultrasound has been fetal care and therapeutic intervention for the anomalous fetus. The fetus as a patient was a foreign concept in the early years of ultrasound.

Most anomalies went undetected, and were not characterized or understood prior to birth. Amniocentesis was the only means of accessing the fetal compartment. Not surprisingly, fetal loss rates approached 1 percent, which limited applications. Now with ultrasound guidance, smaller needles and increased operator experience, loss rates in perinatal centers occur in fewer than 1 in 1,000 procedures.

Improved resolution on ultrasound has allowed fetal care providers to access the fetal thorax and bladder for drainage of these structures for therapeutic and diagnostic purposes. Previously ominous diagnoses, such as cystic adenomatoid malformations of the fetal lung and diaphragmatic hernia, can be risk-stratified using various ultrasound measures – CPAM volume ratio, lung-head ratio, and calculated lung volumes. Large pleural effusions can be accessed,
tested and drained.

Syndromes once considered lethal, such as posterior urethral valves, can now potentially be treated in utero. Sonographic pediatric cardiology techniques, including the combined ventricular cardiac output and Tei myocardial performance index, allow fetal care teams to do a better job identifying a fetus at risk for cardiac decompensation and aid delivery planning. As a result, clinicians can devise more focused medical management.

The improved accuracy of ultrasound has allowed a more complete identification of all fetal anomalies in a fetus. These facts, coupled with genetic information, have allowed dysmorphologists an earlier opportunity to develop a differential diagnosis for the fetal condition and alter care accordingly.

Tremendous advances in using ultrasound in perinatal medicine have enhanced the knowledge of maternal and fetal disease, and modified treatment regimens to optimize outcomes. As imaging technologies and interventional strategies become more sophisticated, treating fetal disease will continue to expand, leading to improved perinatal outcomes for fetuses with pathological conditions.

– Carri R. Warshak, MD, is assistant professor of obstetrics-gynecology and a maternal fetal medicine physician at University of Cincinnati (UC) Health in Ohio. She is also director of the Perinatal Center and Fetal Ultrasound at UC Health University Hospital. Ronald Jaekle, MD, is a professor of obstetrics-gynecology at UC Health. He specializes in perinatal, neonatal, and maternal-fetal medicine. Direct comments and questions to editorial@rt-image.com.