Obstetrical Doppler: the evidence today

Doppler capability and pathophysiological background

For years, it has been known through animal studies that, when affected by chronic hypoxemia, the fetus adapts to the adverse condition by actuating hemodynamic changes [5]. The possibility of also assessing and monitoring these changes in humans was very exciting. In the beginning, the methodology used was complicated and not very reproducible. Following the technical improvements in ultrasound equipment (better resolution and color flow mapping) and the introduction of so-called angle independent parameters, it also became possible to identify and sample very tiny vessels. As a consequence, Doppler assessment of blood flow in arterial and venous vessels was of major interest for investigation and has been introduced as an almost routine procedure in clinical practice. The number of published studies on obstetric Doppler is impressive. Searching PubMed for the following keywords returns the following results: Fetal Doppler: 7397; obstetrical Doppler: 5598; fetal aorta Doppler: 682; umbilical vein Doppler: 769; ductus venosus: 470; fetal vena cava: 277; middle cerebral arteries: 1324; and so on. A very comprehensive map of feto-placental hemodynamic patterns in normal and abnormal conditions is available. The principal factor influencing fetal hemodynamics is represented by chronic fetal hypoxemia (CFH), which affects between 30% and 35% of fetuses presenting with intrauterine growth restriction (IUGR), a condition associated with increased perinatal mortality and morbidity. The most important cause of IUGR is obliterative vasculopathy of the placenta, which reduces first the nutrient and then the oxygen supply to the fetus.

Because of its ability to assess hemodynamic conditions and their changes, Doppler technology has been mainly applied for studying IUGR cases both for investigational and for clinical purposes. Practically, it is possible to identify the causes of IUGR by sampling the uterine arteries, which supply the placenta, or the umbilical arteries, where altered hemodynamics are proportional to the obliteration of the placental vascular bed, which is responsible for the reduced maternal-fetal exchanges. Moreover, the presence or absence of CFH can be assessed by studying fetal vessels and, if present, the level of fetal compromise can be monitored.

In summary, the expected results of using obstetric Doppler in clinical practice are as follows: (1) detection of CFH, and (2) optimization of the timing of the delivery in case of CFH.

For a better understanding of the possibilities and limitations of obstetric Doppler, it is necessary to keep in mind some aspects of Doppler patterns.

The most commonly used Doppler parameters in clinical practice today are based on the ratio between systolic and diastolic blood flow velocity. They are the pulsatility index (PI), the resistance index (RI) and the systolic-to-diastolic ratio (S/D). The majority of studies refer to the PI, which also takes into consideration the mean blood flow velocity, thus offering a more comprehensive view of Doppler velocity wave forms (DVWFs).

When applied to an artery, DVWFs are mainly influenced by the peripheral resistance downstream of the explored segment of vessels. Moreover, other patterns of DVWFs of particular significance can be observed: absent end diastolic flow (AEDF) or reverse flow in diastole (RF), often considered together as ARED flow, and the presence of a “notch” mainly in uterine arteries.

When applied to venous vessels, DVWF is mainly influenced by the characteristics of the cardiac activity and, in abnormal conditions, can present an altered PI reverse flow or pulsation.

Reversed flow in diastole in the inferior vena cava of the fetus can be considered as a physiological condition.

In the case of placental obliterative vasculopathy, peripheral resistance is increased at the level of the umbilical and uterine arteries. The level of resistance and, consequently, the PI are proportional to the obliteration of the placental vascular bed [7]. If CFH is present, blood flow redistribution occurs and impedance to blood flow is increased at the level of the somatic and splanchnic arteries and reduced at the level of the cerebral arteries (brain-sparing effect). The latter is a mechanism of defense. A sparing effect has also been observed at the level of the coronary, adrenal and splenic arteries.

Peripheral resistance can also be increased in the uterine and spiral arteries.

Today’s evidence

The majority of, if not all, the vessels of the feto-uteroplacental circulation have been the object of Doppler studies in normal and complicated pregnancies. In this way, a better understanding of the pathophysiological background of the fetal response and the adaptation to CFH has been achieved. What is necessary today is to extract from these large amounts of information data that are of value based on evidence in clinical practice.

Unfortunately, the majority of published studies on clinical application are of limited evidence and it is therefore not easy to propose firm recommendations.

In order to at least partially overcome this limitation, systematic reviews and meta-analysis have been conducted. Their results offer the best available evidence for clinical application of obstetric Doppler at the moment.

Alfirevic et al. [2] in 2010 concluded that the use of fetal and umbilical Doppler ultrasound in normal pregnancy does not confer any benefits to the mother or to the fetus; therefore its routine use is not recommended. On the contrary, the same authors in 2013 concluded that, in high-risk pregnancies, fetal and umbilical Doppler ultrasound is recommended as it reduces perinatal mortality and the number of obstetric interventions [3].

Moreover, the same methodology of evaluation has been applied to selected vascular districts. It has been concluded that Doppler study of the uteroplacental circulation does not offer any benefits to the mother and fetus [14]. Abnormal ductus venosus Doppler shows only a moderate predictive value for fetal compromise [13], and abnormal middle cerebral artery Doppler has a limited predictive accuracy for fetal compromise [12]. One randomized controlled study (RCT) (the TRUFFLE study) has been carried out with the task to compare ductus venosus Doppler to computerized cardiotocography for the management of fetuses with IUGR presenting with abnormal Doppler patterns in the umbilical arteries between 26 and 32 weeks. Only preliminary results without conclusion have been published so far [8].

Finally, two other systematic review and meta-analysis studies have reached the same conclusions. The first one published in 2010 stated that “Doppler studies of the umbilical artery should be incorporated in the protocol for fetal monitoring in high-risk pregnancies… use of more sophisticated Doppler tests (middle cerebral or ductus venosus) cannot be recommended in routine clinical practice” [1]. The second one was performed in 2013 and concluded that “Doppler studies of other vessels than the umbilical artery for assessment of fetal well-being should be reserved for research protocols” [4].

Conclusions

Placental obliterative vasculopathy is the most frequent cause of IUGR and CFH. Hemodynamic changes occurring in this condition at the level of the feto-uteroplacental circulation have been documented by a large number of Doppler studies in humans, allowing a better understanding of the pathophysiology of this severe complication. IUGR is the second leading cause of perinatal mortality and morbidity after prematurity, and the two conditions are often associated. The only known effective treatment of CFH is delivery, and, therefore, in order to improve the clinical outcome, a timely recognition of CFH and an optimal timing of the delivery are crucial, neither too early nor too late. Actually, the gestational age at birth also plays a fundamental role in the neonatal outcome in the case of CFH.

According to the evidence available today, Doppler study of the umbilical arteries (UAs) is the only test that has shown to improve the outcome, reducing perinatal mortality and reducing obstetric interventions.

Doppler ultrasound of the UAs has only shown efficacy when applied to high-risk pregnancies, and it should be routinely used in these cases, although it is not recommended as a screening test in pregnancies without maternal or fetal complications.

As far as CFH recognition is concerned, increased PI in UAs is a warning sign, which indicates a reduction of maternal-fetal exchanges and suggests the necessity of a close monitoring of the fetal well-being by also using other tests.

For the timing and the choice of the way of delivery, Doppler alone is of limited value. Also, in case of UA PI over the second S/D but with diastolic flow present, vaginal delivery, with close monitoring, is possible in 20–40% of the cases [9, 11]. In contrast, when ARED flow is observed, a prompt delivery should be taken into consideration. The approach should be different if AEDF or RF is present [10].

Perinatal mortality and morbidity are significantly different in the two conditions. In case of AEDF, immediate delivery is not always necessary and, under strict control, it is possible to wait some time before allowing maternal corticosteroid administration in case of low gestational age.

On the contrary, in case of RF, if no contraindications are present (large prematurity, malformations, etc.), immediate delivery should be considered.

In conclusion, Doppler study of the feto-uteroplacental circulation in case of placental obliterative vasculopathy is capable of detecting the causes and effects of CFH. Evidence of efficacy of its use in clinical practice is, at the moment, available only for the umbilical arteries. At any rate, it is necessary to remember that “no evidence” of harm or benefit is different from “evidence of no” harm or benefit. Because of the capability of Doppler, it is advisable that well-designed RCTs on other vessels be conducted in order to assess their efficacy in improving perinatal outcome and possibly becoming part of the protocols for the clinical management of fetuses affected by CFH.