Clinical relevance of fetal hemodynamic monitoring: Perinatal implications

Seminars in Fetal & Neonatal Medicine xxx (2015) 1e8

Contents lists available at ScienceDirect

Seminars in Fetal & Neonatal Medicine journal homepage: www.elsevier.com/locate/siny

Review

Clinical relevance of fetal hemodynamic monitoring: Perinatal implications Jay D. Pruetz a, b, *, Jodie Votava-Smith a, David A. Miller b a b

Division of Cardiology, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Department of Obstetrics & Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

s u m m a r y Keywords: Fetal monitoring Antepartum testing Prenatal diagnosis Neonatal critical care Perinatal management Doppler velocimetry

Comprehensive assessment of fetal wellbeing involves monitoring of fetal growth, placental function, central venous pressure, and cardiac function. Ultrasound evaluation of the fetus using 2D, color Doppler, and pulse-wave Doppler techniques form the foundation of antenatal diagnosis of structural anomalies, rhythm abnormalities and altered fetal circulation. Accurate and timely prenatal identification of the fetus at risk is critical for appropriate parental counseling, antenatal diagnostic testing, consideration for fetal intervention, perinatal planning, and coordination of postnatal care delivery. Fetal hemodynamic monitoring and serial assessment are vital to ensuring fetal wellbeing, particularly in the setting of complex congenital anomalies. A complete hemodynamic evaluation of the fetus gives important information on the likelihood of a smooth postnatal transition and contributes to ensuring the best possible outcome for the neonate. © 2015 Published by Elsevier Ltd.

1. Introduction The fetal circulation involves oxygenation within the placenta and two functional ventricles pumping in parallel along with three shunts: the ductus venosus, foramen ovale, and ductus arteriosus. Major disturbances of organ development involving the heart and lungs can be well tolerated by the fetus as long as the placental circulation and shunts remain intact with at least one patent inflow and outflow tract, and one ventricle capable of supporting combined cardiac output (CO). However, certain extracardiac malformations (ECMs), severe forms of congenital heart disease (CHD), and acquired conditions have the potential to disrupt maternal, placental, or fetal circulation, thus posing a threat to fetal wellbeing. Ultrasound evaluation of the fetus using 2D, color Doppler, and pulse-wave Doppler techniques form the foundation of antenatal diagnosis of structural anomalies, rhythm abnormalities, and altered fetal circulation. Comprehensive assessment of fetal wellbeing involves monitoring of fetal growth, placental function, central venous pressure, and cardiac function. Accurate and timely

* Corresponding author. Address: Keck School of Medicine, University of Southern California, Division of Pediatric Cardiology, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop #34, Los Angeles, CA 90027, USA. Tel.: þ1 323 361 4657; fax: þ1 323 361 1513. E-mail address: [email protected] (J.D. Pruetz).

prenatal identification of the fetus at risk is critical for appropriate parental counseling, antenatal diagnostic testing, assessment for fetal intervention, perinatal planning, and co-ordination of postnatal care delivery. This article reviews the essential tools and techniques used for hemodynamic monitoring of the fetus and their clinical importance from the obstetricians', perinatologists', neonatologists', and pediatric sub-specialists' perspective. 2. Methods of fetal evaluation 2.1. Fetal biometry Consistent fetal growth that is appropriate for gestational age (GA) is one of the most important markers of fetal wellbeing. Sonographic evaluation of fetal growth incorporates standard measurements of the fetal head, abdomen, and femur, that can be used to estimate fetal weight by formulas such as those by Shepard or Hadlock [1,2]. Abnormalities of fetal growth can be caused by placental dysfunction, primary growth failure of the fetus (i.e. genetic anomaly) or secondary to a disease state in the fetus. For example, chronic placental dysfunction is characterized by a recognizable pattern of asymmetric fetal growth. Fetal blood containing oxygen and nutrients is shunted preferentially to the vital organs of the brain, heart and adrenal glands at the expense of the limbs, kidneys, intestine and liver. The resulting limitation of

http://dx.doi.org/10.1016/j.siny.2015.03.007 1744-165X/© 2015 Published by Elsevier Ltd.

Please cite this article in press as: Pruetz JD, et al., Clinical relevance of fetal hemodynamic monitoring: Perinatal implications, Seminars in Fetal & Neonatal Medicine (2015), http://dx.doi.org/10.1016/j.siny.2015.03.007

2

J.D. Pruetz et al. / Seminars in Fetal & Neonatal Medicine xxx (2015) 1e8

hepatic growth and glycogen storage contributes to an asymmetrically smaller abdominal circumference relative to the fetal head measurements. Growth of the long bones may also be affected. Reduced renal perfusion and urine production may result in reduction of amniotic fluid volume. Fetal growth restriction usually is classified as an estimated fetal weight below the 10th or 5th percentile for GA. For the purposes of obstetric management, Doppler velocimetry usually is reserved for the setting of fetal growth restriction, in which it is used as an adjunct to traditional methods of antepartum fetal surveillance, including fetal heart rate (FHR) monitoring, ultrasound evaluation of fetal biophysical variables, and amniotic fluid volume assessment.

reported a corrected fetal loss rate of 3.2/1000 and FNR of 1.9/1000 [4]. Corresponding rates with the CST were 0.4/1000 and 0/1000. Manning reported an average FNR of 6.4/1000 among nine large clinical trials using the NST as the primary method of surveillance [10]. Assessment of FHR characteristics other than reactivity (baseline rate, variability, decelerations) may improve the sensitivity of the test. Decelerations may be observed in 33e50% patients undergoing weekly NSTs and reactive tests accompanied by variable decelerations were associated with rates of meconium passage and cesarean for fetal indications similar to those encountered with non-reactive tests [11e13].

2.2. Fetal heart rate monitoring

2.5. Biophysical profile

Normal central nervous system (CNS) regulation of the FHR is an essential marker of fetal wellbeing. Normal baseline rate, normal FHR variability, and heart rate accelerations are highly predictive of normal fetal oxygenation. On the other hand, FHR decelerations usually reflect a transient decrease or interruption of fetal oxygenation, often secondary to uterine contractions or intermittent compression of the umbilical cord. Antepartum testing is reserved for pregnancies at increased risk for interruption of fetal oxygenation. Common indications include maternal hypertension, post-term pregnancy, and suspected or confirmed fetal growth restriction. The goals of antepartum testing are (i) to identify interruption of fetal oxygenation so that permanent injury or death might be prevented and (ii) to identify normally oxygenated fetuses so that unnecessary intervention can be avoided. The effectiveness of an antepartum test is measured by the false-negative rate (FNR) and false-positive rate (FPR). The FNR is defined as the incidence of fetal death within one week of a normal antepartum test. The FPR is defined as the incidence of abnormal tests that prompts delivery, but that are not associated with evidence of acute or chronic suboptimal fetal oxygenation.

The biophysical profile (BPP), as described by Manning et al., assesses five biophysical variables [14]. Fetal movement, breathing, tone, and NST reflect acute CNS function, whereas amniotic fluid volume serves as a marker of the longer-term adequacy of placental function. Two points are assigned for each normal variable and zero points for each abnormal variable, for a maximum score of 10. A BPP score of 8e10, with normal amniotic fluid volume, is considered normal. A score of 6 is equivocal and usually warrants repeat testing the following day. Scores <6 are associated with increased perinatal morbidity and mortality, and usually warrant hospitalization for further evaluation or delivery. One study reported FNR of 0.6/1000 among 12,620 women tested weekly with the BPP [15]. Another study reported significantly lower rates of cesarean delivery for “fetal distress” (3% vs 22%), low 5 min Apgar scores, and meconium aspiration syndrome when the last BPP before delivery was normal rather than when it was abnormal [16]. When normal, the BPP is a reliable predictor of normal fetal oxygenation. The FNR is superior to that of the NST alone and compares favorably with the FNR of the CST. When all ultrasound variables are normal, addition of the NST does not alter the discriminative accuracy of the test.

2.3. Contraction stress test and the oxytocin challenge test

2.6. Modified biophysical profile

The first antepartum testing technique, the contraction stress test (CST) or oxytocin challenge test (OCT), arose from intrapartum observations linking late FHR decelerations with poor perinatal outcome. The test sought to identify transient fetal hypoxemia by demonstrating late decelerations in fetuses exposed to spontaneous (CST) or induced (OCT) uterine contractions. Late decelerations occurring during spontaneous uterine contractions were associated with increased rates of fetal death, growth retardation and neonatal depression [3]. Similar observations were made by other investigators using oxytocin or nipple stimulation to provoke uterine contractions. CST testing on 4600 women has shown FNR of 0.4/1000 whereas the reported FPR ranges from 8% to 57% with an average of ~30% [4,5]. 2.4. Non-stress test Fetal heart rate accelerations that occur in association with fetal movements form the basis of the non-stress test (NST). A normal or “reactive” NST usually is defined by two accelerations in a 20 min period, each lasting 15 s and peaking 15 beats/min above the baseline. Before 32 weeks, acceleration is defined as a rise of 10 beats/min lasting 10 s [6,7]. In most institutions, the test is repeated once or twice weekly. Boehm reported that the latter approach yielded a three-fold reduction in the incidence of fetal death [8]. An acceleration of the FHR, either spontaneous or in response to fetal stimulation, is highly predictive of normal fetal pH [9]. Among 1542 women tested weekly with the NST, Freeman

The modified biophysical profile (MBPP) utilizes the NST as a short-term marker of fetal status and the amniotic fluid index (AFI) as a marker of longer-term placental function. The AFI is calculated as the sum of the deepest vertical cord-free pockets of amniotic fluid in each of the four uterine quadrants. Normal AFI is 10 cm. Low normal AFI is >5 cm but <10 cm. Low AFI, or oligohydramnios is 5 cm. The presence of oligohydramnios constitutes an abnormal MBPP, regardless of other findings. Nageotte et al. evaluated 2774 high-risk pregnancies with twice-weekly MBPPs and reported one unexplained fetal death within one week of a normal test result, yielding FNR of 0.36/1000 [17]. Another study reported 54,617 MBPPs in 15,482 high-risk pregnancies that yielded a fetal death rate that was nearly seven-fold lower than that in the untested, “low-risk” population [18]. The overall FNR of the MBPP was 0.8/ 1000, and the FPR was 60%. Large studies reveal the FNR of the MBPP to be similar to that of the CST and the complete BPP.

2.7. Doppler velocimetry Doppler velocimetry of fetal vessels, including the umbilical artery and vein, middle cerebral artery, and ductus venosus represents another important set of tools for fetal hemodynamic evaluation and has been the focus of intensive study. The most common Doppler indices are the systolic-to-diastolic velocity ratio (S:D ratio), the resistance index (RI), and the pulsatility index (PI), calculated as summarized:

Please cite this article in press as: Pruetz JD, et al., Clinical relevance of fetal hemodynamic monitoring: Perinatal implications, Seminars in Fetal & Neonatal Medicine (2015), http://dx.doi.org/10.1016/j.siny.2015.03.007

J.D. Pruetz et al. / Seminars in Fetal & Neonatal Medicine xxx (2015) 1e8

S : D ratio ¼

3

Systolic velocity Diastolic velocity

RI ¼

Systolic velocity  Diastolic velocity Systolic velocity

PI ¼

Systolic velocity  Diastolic velocity Average velocity

2.8. Doppler of umbilical vessels Doppler interrogation of the umbilical vessels can provide important insights into the fetaleplacental circulation. During most of the second half of pregnancy, approximately one-third of fetal CO is directed through the umbilical arteries (UAs) to the placenta, falling to approximately one-fifth near term [19]. Placental development involves progressive branching of chorionic villi and associated villous blood vessels, expanding the villus vascular space, and lowering resistance downstream from the UAs [20]. This results in a progressive increase in UA diastolic velocity and a corresponding decrease in the umbilical artery S:D ratio, RI, and PI. Conditions that increase resistance downstream from the interrogated segment of umbilical cord can contribute to reduced placental function, limitation of delivery of oxygen and nutrients to the fetus, and subsequent fetal growth restriction with its attendant morbidities. At the level of the umbilical cord, such conditions include thrombus, embolus, atherosis and inflammation, as well as mechanical compression from abnormal cord insertion into the placenta as seen in the setting of velamentous placental cord insertion. At the level of the arterioles, capillaries, and venules of the chorionic villi, resistance can be increased by thrombus, embolus, hemorrhage, medial hyperplasia, inflammation, vasculitis, maldevelopment of the villous vascular tree, or apoptosis related to placental aging. UA resistance can also be increased by conditions affecting the intervillous space, such as thrombus, infarct, or abruptio placentae. Beyond the second trimester, reported values for normal UA S:D ratio range from 3 to 3.5. When resistance downstream from the UA is severely elevated, Doppler interrogation of a segment of cord may reveal absence of flow toward the placenta during diastole. In extreme cases, flow may be reversed during diastole. Both of these conditions signal placental dysfunction and significantly increase the risk of perinatal morbidity and mortality [21]. Some studies have reported statistically significant improvement in perinatal outcome with the use of Doppler ultrasonography in pregnancies complicated by fetal growth restriction [21,22]. Although severe restriction of UA blood flow e as evidenced by absent or reversed flow during diastole e has been correlated with fetal growth restriction, acidosis and adverse perinatal outcome, the predictive values of less-extreme deviations from normal remain unclear (Fig. 1). In the absence of fetal growth restriction, UA Doppler velocimetry does not appear to be a useful screening test for the detection of fetal compromise. Therefore it is not recommended for use as a screening test in the general obstetric population [22,23]. In growth-restricted fetuses with abnormal umbilical or middle cerebral artery Doppler velocimetry, the presence of pulsatile flow in the umbilical vein (UV) has been reported to be associated with worse perinatal outcome [24]. In growthrestricted fetuses, Doppler velocimetry of the umbilical vessels is used as an adjunct to traditional measures of fetal condition, including fetal heart rate monitoring, biophysical profile, and amniotic fluid volume assessment.

Fig. 1. (A) Normal umbilical artery (UA) Doppler waveform characterized by an initial antegrade peak corresponding with ventricular systole (S) and a post-systolic trough that corresponds to diastole (D) that does not reach or go below the baseline. When resistance downstream from the UA is severely elevated, Doppler interrogation of the UA may reveal absent or reversed flow (arrow, B) suggesting placental dysfunction. Normal umbilical vein (UV) Doppler waveform (A) is characterized by a continuous Doppler flow signal above the baseline. Pulsations or notching of the UV Doppler waveform (arrowhead, B) usually denote severely elevated central venous resistance or pressure in the fetus.

2.9. Middle cerebral artery Doppler Under normal conditions, blood flow in the middle cerebral artery (MCA) is characterized by a peak systolic velocity (PSV) of 20e30 cm/s in early pregnancy that increases progressively to 40e65 cm/s by the late third trimester [25]. The MCA PSV increases significantly in the setting of fetal anemia and can predict moderate-to-severe anemia with sensitivity and negative predictive values [26]. Peak systolic velocities >1.5 multiples of the median (MoM) for gestational age identify fetuses at increased risk for anemia who may be candidates for cordocentesis and intrauterine transfusion [26]. In growth-restricted fetuses with abnormal UA velocimetry, there is some evidence that elevated MCA PSV can improve prediction of adverse outcome [27]. Resistance in the MCA normally decreases with advancing GA. Diastolic velocities are characteristically low, but may rise due to redistribution of brain blood flow in the setting of suboptimal fetal oxygenation. The “brain-sparing” effect of fetal hypoxemia likely results from a combination of sympathetic reflex-centralization of circulating blood volume, and altered cerebral autoregulation in the setting of lowered fetal blood oxygen content [28]. If decreased fetal oxygenation is attributable to increased resistance to fetal perfusion of the placenta, resistance indices in the umbilical artery will increase, whereas resistance indices in the MCA will move in the opposite direction. These phenomena led to the description of the cerebroplacental ratio (CPR), a calculation that uses the MCA PI as the numerator and the umbilical artery PI as the denominator. By expressing opposite-direction resistance changes as a ratio, the CPR magnifies them, making them more apparent. Among 123 women referred for evaluation of fetal growth restriction, Bahado-Singh et al. identified 87 with normal CPR findings and 36 with CPR

Please cite this article in press as: Pruetz JD, et al., Clinical relevance of fetal hemodynamic monitoring: Perinatal implications, Seminars in Fetal & Neonatal Medicine (2015), http://dx.doi.org/10.1016/j.siny.2015.03.007

4

J.D. Pruetz et al. / Seminars in Fetal & Neonatal Medicine xxx (2015) 1e8

<0.5 MoM for gestational age. Compared to the group with normal CPR measurements, those with abnormal CPR had significantly higher rates of low birth weight, cesarean for fetal distress, prolonged neonatal intensive care stay, perinatal death, and total complications [29]. In a recent study of 881 growth-restricted fetuses, low CPR (<1) conferred an 11-fold increase in the risk of adverse perinatal outcome when compared to cases with normal CPR [30]. When used in the setting of fetal growth restriction to assess the status of fetal oxygenation, MCA Doppler is used as an adjunct to traditional tests of fetal condition, including FHR monitoring, biophysical profile, and amniotic fluid volume. 2.10. Ductus venosus The ductus venosus (DV) is a vascular shunt within the parenchyma of the liver that allows ~25% of umbilical venous blood flow to bypass the liver and enter the inferior vena cava. The DV Doppler waveform is characterized by an initial antegrade peak that corresponds to ventricular systole (S-wave), a brief post-systolic trough (vwave), a second antegrade peak that corresponds to early diastole (Dwave), and finally a second trough that corresponds to atrial systole (a-wave). Increased resistance to venous flow toward the heart can produce abnormal DV waveforms. Conditions such as decreased ventricular compliance, abnormal contractility or increased afterload can cause absent or reversed flow during atrial systole (Fig. 2). In the setting of fetal growth restriction with normal fetal cardiac anatomy, progressive reduction in antegrade DV velocity during atrial systole may signal reduced ventricular compliance, reduced cardiac emptying against increasing afterload that can accompany rising placental resistance, and/or progressive dilation of the ductus venosus [31]. Antepartum and peripartum decision-making integrates the results of standard tests of fetal status with the results of appropriate Doppler studies. Irrespective of fetal growth restriction,

Fig. 2. (A) Normal ductus venosus Doppler waveform is characterized by an initial antegrade peak that corresponds to ventricular systole (S-wave), a brief post-systolic trough (V-wave), a second antegrade peak that corresponds to early diastole (Dwave), and finally a second trough that corresponds to atrial systole (A-wave). (B) Abnormal ductus venosus Doppler waveform is characterized by a deeper V-wave, diminished D-wave, and absent or reversed A-wave, suggesting increased central venous resistance or pressure usually secondary to decreased ventricular compliance, abnormal contractility, or increased afterload.

evaluation of fetal Doppler flow patterns can help guide management in conditions that may be complicated by structural and/or functional cardiac defects, including twinetwin transfusion syndrome (TTTS), hydrops fetalis or fetal cardiac arrhythmias. 3. Approach to complex CHD and ECM In the setting of complex CHD or ECMs, decisions regarding the most effective method of antepartum surveillance, as well as the timing, route, and location of delivery may require specialized evaluations unique to the specific malformation. ECMs and complex CHD can increase the risk for development of hydrops fetalis, a life-threatening fetal state that involves extravascular fluid collections in at least two body compartments. Several features unique to fetal fluid dynamics and fetal myocardium make them extremely sensitive to increases in central venous pressure (CVP), which underlies their proclivity to develop hydrops. First, fetuses have greater body water content, greater proportion of extracellular fluid, lower tissue turgor, lower colloid osmotic pressure with lower albumin concentration, increased capillary permeability, and baseline dependence on lymphatic drainage to remove fluid from the interstitial tissue spaces. Consequently, elevations in CVP of only 2e3 mmHg can sharply increase fetal extracellular fluid volume [32]. Second, the fetal myocardium is less compliant than that of a mature heart, as it contains fewer sarcomeres per myocyte, disorganized orientation of myocytes, immature T-tubule system that impairs calcium uptake, and less sympathetic innervation due to lower beta-adrenergic receptor concentration. Therefore, the fetal heart may have decreased ability to respond to stressors such as increases in preload and afterload [32]. Fetuses with known or suspected cardiac or extracardiac disease should undergo a comprehensive anatomic ultrasound as well as fetal echocardiogram [33]. Assessment of ventricular function can be qualitative as well as quantitative by a number of measures (Table 1). Note that quantitative assessment does have limitations in the prenatal setting owing to small size of the structures measured, fetal motion, and imaging difficulties. Diastolic function is assessed by pulsed Doppler of the tricuspid and mitral valve inflows as well as by Doppler assessment of systemic veins including the DV, hepatic veins, inferior vena cava, and UV. Cardiac biometry includes measurement of cardiac structures such as valve annulus dimensions, with calculation of Z-scores based on normative data for GA; knowledge of whether the fetus is normal for GA based on fetal biometry aides this assessment. The cardiothoracic ratio, measured at an axial four-chamber view of the fetal heart in diastole, performed either by comparison of cardiac to thoracic area (normal range: 0.20e0.35) or circumference (normal: <0.5), is a way to quantify cardiomegaly. This assessment is less accurate in the setting of thoracic masses such as congenital pulmonary airway malformation (CPAM) or congenital diaphragmatic hernia (CDH) secondary to a deviated cardiac axis, and the thorax can be smaller in the setting of oligohydramnios when lung volumes may be low. The cardiovascular (CV) profile score is a tool that scores five categories on a two-point scale, including hydrops, venous Dopplers, heart size, cardiac function, atrioventricular (AV) valve regurgitation, and arterial Dopplers. A lower score (7) has been found to correlate with pre- and postnatal survival in fetuses with CHD and ECM, and the scoring system can be used to identify fetuses at risk for impending compromise [34e36]. Cardiac defects that have the potential to alter CVP may put fetuses at risk for development of fetal heart failure and hydrops. These defects usually involve a significant degree of AV valve regurgitation (i.e. Ebstein's anomaly, tricuspid valve dysplasia, and AV septal defects). Atrioventricular valve regurgitation has the potential to cause right ventricular volume overload and diastolic

Please cite this article in press as: Pruetz JD, et al., Clinical relevance of fetal hemodynamic monitoring: Perinatal implications, Seminars in Fetal & Neonatal Medicine (2015), http://dx.doi.org/10.1016/j.siny.2015.03.007

J.D. Pruetz et al. / Seminars in Fetal & Neonatal Medicine xxx (2015) 1e8

5

Table 1 Quantitative measures of fetal cardiac function. Parameter

Method of acquisition

Calculation

Shortening fraction Myocardial performance index Cardiac output (of LV or RV)

M-mode or 2D ultrasound Doppler or tissue Doppler Doppler of outflow and 2D measurement of valve annulus. Doppler measurement of heart rate. Doppler of AV valve inflow

(End diastolic volume  End systolic volume)/End diastolic volume (Isovolumic contraction time þ Isovolumic relaxation time) ejection time Valve radius2  p  VTI of valve outflow  Heart rate. Can summate RV and LV outputs to yield combined cardiac output.

Ventricular filling Inferior vena cava or hepatic venous flow Cardiothoracic ratio Strain and Strain rate

Doppler of vessel 2D ultrasound 2D speckle tracking. Tissue Doppler

E and A wave velocity E/A wave ratio Reverse flow VTI/Forward flow VTI Area ratio ¼ Area of heart/Area of chest. Circumference ratio ¼ Circumference of heart/circumference of chest. Vendor dependent, not yet standardized at this time

AV, atrioventricular; LV, left ventricle; RV, right ventricle; VTI, velocity time integral; 2D, two-dimensional.

dysfunction, as well as to elevate right atrial pressure, which can impair DV flow. Abnormalities of the ventricular myocardium, including cardiomyopathies and myocarditis, can increase CVP via diastolic dysfunction, and impair CO due to systolic dysfunction. Diastolic dysfunction in fetuses with cardiomyopathy is a risk factor for in-utero demise [37]. Both brady- and tachyarrhythmias can also elevate right atrial pressure, affect venous inflow and ventricular filling, and impair CO. Forms of CHD with a functional single ventricle can often continue to provide adequate fetal circulation if the single ventricle can adapt to handle the entire combined CO. However, CHD with a single ventricle in combination with AV valve regurgitation, myocardial dysfunction, or heart rhythm disturbances may have diminished CO leading to heart failure, hydrops, and in-utero demise over time. Furthermore, CHD associated with genetic syndromes (such as chromosomal trisomies, Noonan's syndrome, and monosomy X) as well as CHD in combination with ECM place fetuses at higher risk of in-utero demise, possibly as a result of additional alterations in CVP and anomalies of lymphatic drainage associated with these conditions. Several disorders can create a high CO state in the fetus and increase the risk of developing fetal heart failure. These include arteriovenous malformation (AVM), teratoma, placental chorioangioma, twin-reversed arterial perfusion (TRAP) sequence, and both immune and non-immune causes of anemia. Certain fetal malformations may affect CVP via a direct mass-effect, such as CPAM and CDH. Surveillance of fetal CV function and whether a disease state is causing a potential life-threatening derangement to fetal hemodynamics is important not only for purposes of counseling, but also because there may be a possibility to intervene or to deliver. Because hydrops is an end stage and carries a high risk of in-utero as well as postnatal demise, making an earlier determination that a fetus is at risk is important to allow time for therapeutic fetal intervention.  A diagnosis of ECM or CHD increases fetal risks and should prompt a comprehensive anatomic ultrasound as well as fetal echocardiogram.  Several features of fetal fluid dynamics and fetal myocardium make fetuses uniquely sensitive to increased venous pressure and place them at greater risk for the development of hydrops.  Specialized ultrasound tools can assist in the evaluation of fetal CV status in cases of CHD and ECMs.

sacrococcygeal teratoma (SCT) and myelomeningocele. Additional techniques include laser photocoagulation of fetal vessels, radiotherapy ablation, shunt placement, umbilical cord occlusion, tracheal occlusion, balloon dilatation, “amniopatch” procedure, amniotic band dissection, and sclerotherapy among others. Detailed discussion of these procedures, their indications and prognoses, is beyond the scope of this article. Box 1 summarizes some fetal conditions that may warrant fetal intervention. The decision to undertake a fetal intervention must take into consideration the risks of fetal mortality/morbidity without treatment versus the risks of fetal loss and perceived benefit from the fetal intervention. Fetal hydrops is often a primary indication for fetal intervention in cases of fetal ECM such as a large CPAM or pleural effusion due to the high risk of fetal demise [38,39]. Sometimes

Box 1 Potential conditions for fetal intervention.

Acardiac twins Alloimmune thrombocytopenia Alloimmunization and fetal anemia Amniotic band syndrome Bronchopulmonary sequestration (BPS) Cardiac abnormalities of the fetus Chorioangioma Congenital diaphragmatic hernia (CDH) Congenital pulmonary airway malformation of the lung (CPAM) Iatrogenic preterm premature rupture of membranes Lower urinary tract obstruction (LUTO) Myelomeningocele Pleural effusions Sacrococcygeal teratoma (SCT) Selective intrauterine growth restriction (IUGR)

4. Special cases with consideration for fetal therapy

Twin-reversed arterial perfusion sequence (TRAP)

Contemporary methods of fetal therapy range from needle procedures, such as fetal blood transfusion via the umbilical cord for fetal anemia, to open fetal surgery for conditions such as

Vasa previa

Twinetwin transfusion syndrome (TTTS)

Please cite this article in press as: Pruetz JD, et al., Clinical relevance of fetal hemodynamic monitoring: Perinatal implications, Seminars in Fetal & Neonatal Medicine (2015), http://dx.doi.org/10.1016/j.siny.2015.03.007

6

J.D. Pruetz et al. / Seminars in Fetal & Neonatal Medicine xxx (2015) 1e8

there is no single criterion for intervention such as elevated MCA Doppler peak systolic velocity in fetal anemia, but rather a constellation of findings suggesting that the fetus is at risk, such as the CV profile score used in cases of fetal heart failure and complex CHD [36]. In the case of TTTS there are multiple, complex staging systems used in determining severity of disease and estimating risks in both the donor and recipient twin based on hemodynamic findings [40,41]. An in-depth discussion of the diagnostic criteria for all of the fetal diseases needing interventions is too lengthy for this report, but several diagnostic examples will serve to highlight the various decision-making tools involved. 4.1. Twinetwin transfusion syndrome This complication of monochorionicediamniotic twin pregnancies results in unbalanced exchange of blood through vascular communications in the monochorionic placenta with preferential shunting of blood from one twin (donor) to the other twin (recipient) [42]. The Quintero staging system is a useful tool for confirming the diagnosis of TTTS and assessing risk prior to intervention [43]. Recipient twins can develop progressive volume and pressure overload, heart failure, and hydrops with fetal echocardiographic findings such as cardiomegaly, valve regurgitation, ventricular hypertrophy and dysfunction [44]. Multiple complex scoring systems have been created to better quantify the severity of CV pathology in TTTS and to guide decision-making for intervention in Quintero Stage I disease [34,40,41]. New evidence suggests that early Doppler findings of decreased right ventricular diastolic filling time with monophasic tricuspid valve inflow Doppler may predict progression of TTTS, leading to earlier diagnosis and intervention [45,46]. The current preferred fetal therapy is selective laser coagulation of the communicating vessels that effectively separates the twin placental circulations and normalizes the blood volume in both twins, resulting in improved perinatal survival and improved neurologic outcomes [47,48]. 4.2. Fetal lung mass Large CPAM can cause mediastinal shift with cardiac axis deviation and possible compression of system veins in the fetus, leading to a tamponade-like physiology resulting in hydrops and fetal loss in some cases. Progression can be serially monitored by assessing Doppler patterns of ratio of early ventricular filling to atrial contraction (E/A ratio) in the ventricles and of increased reversal with atrial contraction in the IVC, both of which can suggest increasing right atrial filling pressures and impaired ventricular compliance over time [49]. Intervention can be taken at the earliest sign of impaired ventricular filling, either via open fetal surgery to remove the mass or via percutaneous direct injection of the mass with a sclerosing agent to shrink the size of the mass [50,51]. CDH also causes mediastinal shift and cardiac axis deviation, but in addition can cause abnormal lung development resulting in severe pulmonary hypoplasia at birth [52,53]. Prenatal measurement of lung area:head circumference ratio <1 at 22e28 weeks' GA and liver herniated into the chest may predict a survival rate of <10% [54,55]. Clinical trials are underway using endoscopic tracheal occlusion in attempts to ameliorate stunted lung development in the fetus with CDH [56,57]. Early results show some promise for improved lung growth and better neonatal outcomes [58,59]. Evaluation of pulmonary artery Doppler waveforms both pre and post balloon occlusion have been helpful in determining improved flow to the affected lung, and maternal hyperoxygenation tests have predicted those fetuses at greatest risk for postnatal pulmonary hypoplasia [60e62].

4.3. Sacrococcygeal teratoma Similar to fetal anemia, large vascularized tumors such as SCT or cerebral AVMs can cause high-output cardiac failure in the fetus, resulting in hydrops and fetal loss [63,64]. Serial evaluation of the combined CO via Doppler interrogation of the fetal outflow tracts and umbilical artery Doppler can help determine prognosis [65]. As combined CO increases in the fetus with SCT, the corresponding CV profile score decreases, which may signify the need for fetal intervention prior to the onset of severe CHF or hydrops. Thus, confirmation of a CVPS of >8 suggested survival without intervention [66]. Fetuses with increased CT ratio >0.35, combined CO >550 mL/min/kg, atrioventricular valve regurgitation, and aortic or mitral Z-scores >2 should be considered high risk [65]. Treatment options include open fetal surgery with resection of the SCT or fetoscopic laser embolization of feeding vessels to the tumor, both of which have shown some success [67,68].  The criteria for fetal intervention continue to be refined.  New fetal interventions are on the horizon, including minimally invasive procedures for myelomeningocele.  Perioperative and postoperative fetal hemodynamic monitoring with echocardiography is a current area of study.  Neuroprotection in severe congenital anomalies, especially CHD, is an emerging field of research. 5. Perinatal decision-making for optimal postnatal transition A prenatal diagnosis of a complex or life-threatening fetal condition has serious implications to both fetal and neonatal survival or long-term postnatal outcome, which may result in the decision to perform a fetal intervention as noted above or may result in premature delivery for expedited care or prevention of fetal demise. The fetal-to-postnatal adaptation in cardiac and extracardiac fetal disease is at highest risk in situations where a neonate cannot oxygenate effectively using the airway and pulmonary circulation after removal from placental oxygenation. Diagnoses that often lead to greater consideration of delivery planning and active perinatal management include but are not limited to complex CHD, fetal arrhythmia, obstructive airway lesions, and severe gastrointestinal and neurologic anomalies. Important perinatal planning decisions include location, timing, and mode of delivery. Confirming fetal wellbeing in order to decrease neonatal morbidity/mortality is the goal, and thus timing and mode of delivery are often determined by the serial monitoring techniques mentioned above. Evidence of growth restriction, abnormal FHR monitoring, non-reassuring NST, BPP and/or Doppler indices may all lead to changes in perinatal management including premature delivery, elective cesarean, or change in delivery institution. The presence of a severe ECM or complex CHD may also influence perinatal decision-making. Recent studies have shown that elective delivery of healthy infants prior to 39 weeks increases mortality and morbidity [69,70]. The impact is even greater in cases with complex congenital anomalies such as CHD, neural tube defects and gastroschisis delivered prematurely [71,72]. Unfortunately, prenatal diagnosis can often lead to premature delivery at <37 weeks and higher rates of cesarean with no evidence of improved survival [73e75]. In fact, several studies have now shown that a vaginal delivery at term is preferred and elective cesarean should only be reserved for cases with a high likelihood for immediate postnatal intervention [76,77]. Perinatal and immediate postnatal management of fetuses with congenital birth defects are based on severity of fetal diagnosis, level of care needed, access to specialists, likelihood for rapid decompensation (hemodynamic instability) and need for immediate postnatal intervention with a lifesaving procedure. At many

Please cite this article in press as: Pruetz JD, et al., Clinical relevance of fetal hemodynamic monitoring: Perinatal implications, Seminars in Fetal & Neonatal Medicine (2015), http://dx.doi.org/10.1016/j.siny.2015.03.007

J.D. Pruetz et al. / Seminars in Fetal & Neonatal Medicine xxx (2015) 1e8

institutions, in an effort to assure timely delivery of optimal medical and invasive management, the prenatal detection of a complex fetal anomaly often leads to delivery at a tertiary care center equipped to provide optimal and complete postnatal care [78]. Furthermore, close co-ordination among all teams involved in the immediate perinatal and postnatal care is critical, including obstetrics, neonatology, and pediatric sub-specialists. The true impact of perinatal management decision-making on postnatal course and neonatal outcomes in CHD remains controversial [73,79]. There have been attempts to develop a standardized perinatal approach to prenatally diagnosed CHD with the goal of improving care delivery and postnatal outcomes by addressing safest mode of delivery, level of neonatal intensive care required, and acceptable wait time to intervention based on the postnatal acuity level and need for emergent neonatal cardiac intervention [80]. Furthermore, a recent guideline published by the American Heart Association details a level of care assignment and co-ordinating action plan for various forms of CHD [33]. Obviously, each individual case has to be taken into consideration and antepartum testing may dictate a deviation from the preferred algorithm. 6. Conclusion Comprehensive assessment of fetal wellbeing involves monitoring of fetal growth, placental function, central venous pressure, and cardiac function. Fetal hemodynamic monitoring and serial assessment are vital to ensuring fetal wellbeing, particularly in the setting of complex congenital anomalies. Specialized fetal monitoring tools and techniques can help in the determination of need for fetal intervention as well as preparation, co-ordination and implementation of an appropriate perinatal management care plan. A complete hemodynamic evaluation of the fetus can ensure a smooth postnatal transition and the best possible outcomes for the neonate. Conflict of interest statement None declared. Funding source None.

 Perinatal management is a field of current study as fetuses with a number of complex anomalies may be prone to deliver early and via C-section.  Tolerance of labor in cases of severe birth defects is not well understood.  Optimal mode of delivery is also not clear in ECMs and complex CHD.  The accuracy and usefulness of perinatal recommendation action plans are yet to be determined and are areas of great interest for future research.

References [1] Shepard MJ, Richards VA, Berkowitz RL, Warsof SL, Hobbins JC. An evaluation of two equations for predicting fetal weight by ultrasound. Am J Obstet Obstet Gynecol 1982;142:47e54. [2] Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK. Estimation of fetal weight with the use of head, body, and femur measurements e a prospective study. Am J Obstet Obstet Gynecol 1985;151:333e7.

7

[3] Kubli FW, Hon EH, Khazin AF, Takemura H. Observations on heart rate and pH in the human fetus during labor. Am J Obstet Obstet Gynecol 1969;104: 1190e206. [4] Freeman RK, Anderson G, Dorchester W. A prospective multi-institutional study of antepartum fetal heart rate monitoring. II. Contraction stress test versus nonstress test for primary surveillance. Am J Obstet Obstet Gynecol 1982;143:778e81. [5] Lagrew Jr DC. The contraction stress test. Clin Obstet Gynecol 1995;38:11e25. [6] Anonymous. Electronic fetal heart rate monitoring: research guidelines for interpretation. National Institute of Child Health and Human Development Research Planning Workshop. Am J Obstet Obstet Gynecol 1997;177: 1385e90. [7] American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Clinical Management Guidelines for ObstetricianeGynecologists, Number 70, December 2005 (replaces Practice Bulletin Number 62, May 2005). Intrapartum fetal heart rate monitoring. Obstet Gynecol 2005;106:1453e60. [8] Boehm FH, Salyer S, Shah DM, Vaughn WK. Improved outcome of twice weekly nonstress testing. Obstet Gynecol 1986;67:566e8. [9] Skupski DW, Rosenberg CR, Eglinton GS. Intrapartum fetal stimulation tests: a meta-analysis. Obstet Gynecol 2002;99:129e34. [10] Manning FA, Morrison I, Lange IR, Harman C. Antepartum determination of fetal health: composite biophysical profile scoring. Clin Perinatol 1982;9: 285e96. [11] Phelan JP, Platt LD, Yeh SY, Trujillo M, Paul RH. Continuing role of the nonstress test in the management of postdates pregnancy. Obstet Gynecol 1984;64:624e8. [12] Meis PJ, Ureda JR, Swain M, Kelly RT, Penry M, Sharp P. Variable decelerations during nonstress tests are not a sign of fetal compromise. Am J Obstet Obstet Gynecol 1986;154:586e90. [13] Phelan JP, Lewis Jr PE. Fetal heart rate decelerations during a nonstress test. Obstet Gynecol 1981;57:228e32. [14] Manning FA, Platt LD, Sipos L. Antepartum fetal evaluation: development of a fetal biophysical profile. Am J Obstet Obstet Gynecol 1980;136:787e95. [15] Manning FA, Morrison I, Lange IR, Harman CR, Chamberlain PF. Fetal assessment based on fetal biophysical profile scoring: experience in 12,620 referred high-risk pregnancies. I. Perinatal mortality by frequency and etiology. Am J Obstet Obstet Gynecol 1985;151:343e50. [16] Johnson JM, Harman CR, Lange IR, Manning FA. Biophysical profile scoring in the management of the postterm pregnancy: an analysis of 307 patients. Am J Obstet Obstet Gynecol 1986;154:269e73. [17] Nageotte MP, Towers CV, Asrat T, Freeman RK. Perinatal outcome with the modified biophysical profile. Am J Obstet Obstet Gynecol 1994;170: 1672e6. [18] Miller DA, Rabello YA, Paul RH. The modified biophysical profile: antepartum testing in the 1990s. Am J Obstet Obstet Gynecol 1996;174:812e7. [19] Kiserud T, Ebbing C, Kessler J, Rasmussen S. Fetal cardiac output, distribution to the placenta and impact of placental compromise. Ultrasound Obstet Gynecol 2006;28:126e36. [20] Kingdom J, Huppertz B, Seaward G, Kaufmann P. Development of the placental villous tree and its consequences for fetal growth. Eur J Obstet Gynecol Reprod Biol 2000;92:35e43. [21] O'Dwyer V, Burke G, Unterscheider J, Daly S, Geary MP, Kennelly MM, et al. Defining the residual risk of adverse perinatal outcome in growth-restricted fetuses with normal umbilical artery blood flow. Am J Obstet Obstet Gynecol 2014;211:420.e1e5. [22] Alfirevic Z, Neilson JP. Doppler ultrasonography in high-risk pregnancies: systematic review with meta-analysis. Am J Obstet Obstet Gynecol 1995;172: 1379e87. [23] Maulik D. Doppler ultrasound velocimetry for fetal surveillance. Clin Obstet Gynecol 1995;38:91e111. [24] Baschat AA, Gembruch U, Reiss I, Gortner L, Weiner CP, Harman CR. Relationship between arterial and venous Doppler and perinatal outcome in fetal growth restriction. Ultrasound Obstet Gynecol 2000;16:407e13. [25] Mari G, Adrignolo A, Abuhamad AZ, Pirhonen J, Jones DC, Ludomirsky A, et al. Diagnosis of fetal anemia with Doppler ultrasound in the pregnancy complicated by maternal blood group immunization. Ultrasound Obstet Gynecol 1995;5:400e5. [26] Mari G, Deter RL, Carpenter RL, Rahman F, Zimmerman R, Moise KJ, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses. N Engl J Med 2000;342: 9e14. [27] Mari G, Detti L, Oz U, Zimmerman R, Duerig P, Stefos T. Accurate prediction of fetal hemoglobin by Doppler ultrasonography. Obstet Gynecol 2002;99: 589e93. [28] Mari G, Hanif F, Kruger M, Cosmi E, Santolaya-Forgas J, Treadwell MC. Middle cerebral artery peak systolic velocity: a new Doppler parameter in the assessment of growth-restricted fetuses. Ultrasound Obstet Gynecol 2007;29: 310e6. [29] Bahado-Singh RO, Kovanci E, Jeffres A, Oz U, Deren O, Copel J, et al. The Doppler cerebroplacental ratio and perinatal outcome in intrauterine growth restriction. Am J Obstet Obstet Gynecol 1999;180(3 Pt 1):750e6. [30] Morales-Rosello J, Khalil A, Morlando M, Bhide A, Papageorghiou A, Thilaganathan B. Poor neonatal acidebase status in term fetuses with low cerebroplacental ratios. Ultrasound Obstet Gynecol 2015;45:156e61.

Please cite this article in press as: Pruetz JD, et al., Clinical relevance of fetal hemodynamic monitoring: Perinatal implications, Seminars in Fetal & Neonatal Medicine (2015), http://dx.doi.org/10.1016/j.siny.2015.03.007

8

J.D. Pruetz et al. / Seminars in Fetal & Neonatal Medicine xxx (2015) 1e8

[31] Baschat AA. Ductus venosus Doppler for fetal surveillance in high-risk pregnancies. Clin Obstet Gynecol 2010;53:858e68. [32] Rudolph AM. Congenital diseases of the heart: clinicalephysiological considerations. 3rd ed. Chichester, UK/Hoboken, NJ: WileyeBlackwell; 2009. [33] Donofrio MT, Moon-Grady AJ, Hornberger LK, Copel J, Sklansky MS, Abuhamad A, et al. Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association. Circulation 2014;129: 2183e242. [34] Hofstaetter C, Hansmann M, Eik-Nes SH, Huhta JC, Luther SL. A cardiovascular profile score in the surveillance of fetal hydrops. J MaternaleFetal Neonatal Med 2006;19:407e13. [35] Makikallio K, Rasanen J, Makikallio T, Vuolteenaho O, Huhta JC. Human fetal cardiovascular profile score and neonatal outcome in intrauterine growth restriction. Ultrasound Obstet Gynecol 2008;31:48e54. [36] Wieczorek A, Hernandez-Robles J, Ewing L, Leshko J, Luther S, Huhta J. Prediction of outcome of fetal congenital heart disease using a cardiovascular profile score. Ultrasound Obstet Gynecol 2008;31:284e8. [37] Pedra SR, Smallhorn JF, Ryan G, Leshko J, Luther S, Huhta J. Fetal cardiomyopathies: pathogenic mechanisms, hemodynamic findings, and clinical outcome. Circulation 2002;106:585e91. [38] Miller JA, Corteville JE, Langer JC. Congenital cystic adenomatoid malformation in the fetus: natural history and predictors of outcome. J Pediatr Surg 1996;31:805e8. [39] Adzick NS, Harrison MR, Crombleholme TM, Flake AW, Howell LJ. Fetal lung lesions: management and outcome. Am J Obstet Obstet Gynecol 1998;179: 884e9. [40] Rychik J, Tian Z, Bebbington M, Xu F, McCann M, Mann S, et al. The twinetwin transfusion syndrome: spectrum of cardiovascular abnormality and development of a cardiovascular score to assess severity of disease. Am J Obstet Obstet Gynecol 2007;197:392.e1e8. [41] Shah AD, Border WL, Crombleholme TM, Michelfelder EC. Initial fetal cardiovascular profile score predicts recipient twin outcome in twinetwin transfusion syndrome. J Am Soc Echocardiogr 2008;21:1105e8. [42] Duncan KR, Denbow ML, Fisk NM. The aetiology and management of twinetwin transfusion syndrome. Prenat Diagn 1997;17:1227e36. [43] Quintero RA, Morales WJ, Allen MH, Bornick PW, Johnson PK, Kruger M. Staging of twinetwin transfusion syndrome. J Perinatol 1999;19(8 Pt 1): 550e5. [44] Fesslova V, Villa L, Nava S, Mosca F, Nicolini U. Fetal and neonatal echocardiographic findings in twinetwin transfusion syndrome. Am J Obstet Gynecol 1998;179:1056e62. [45] Moon-Grady AJ, Rand L, Gallardo S, Gosnell K, Lee H, Feldstein VA. Diastolic cardiac pathology and clinical twinetwin transfusion syndrome in monochorionic/diamniotic twins. Am J Obstet Obstet Gynecol 2011;205: 279.e1e279.e11. [46] Divanovic A, Cnota J, Ittenbach R, Tan X, Border W, Crombleholme T, et al. Characterization of diastolic dysfunction in twinetwin transfusion syndrome: association between Doppler findings and ventricular hypertrophy. J Am Soc Echocardiogr 2011;24:834e40. [47] Chmait RH, Kontopoulos E, Quintero R, Consortium US. Dual twin survival after laser surgery for twinetwin transfusion syndrome. Ultrasound Obstet Gynecol 2014;44:244. [48] Vanderbilt DL, Schrager SM, Llanes A, Hamilton A, Seri I, Chmait RH. Predictors of 2-year cognitive performance after laser surgery for twinetwin transfusion syndrome. Am J Obstet Obstet Gynecol 2014;211:388.e1e7. [49] Mahle WT, Rychik J, Tian ZY, Cohen MS, Howell LJ, Crombleholme TM, et al. Echocardiographic evaluation of the fetus with congenital cystic adenomatoid malformation. Ultrasound Obstet Gynecol 2000;16:620e4. [50] Adzick NS, Flake AW, Crombleholme TM. Management of congenital lung lesions. Semin Pediatr Surg 2003;12:10e6. [51] Bermudez C, Perez-Wulff J, Arcadipane M, Bufalino G, Gomez L, Flores L, et al. Percutaneous fetal sclerotherapy for congenital cystic adenomatoid malformation of the lung. Fetal Diagn Ther 2008;24:237e40. [52] Bargy F, Beaudoin S, Barbet P. Fetal lung growth in congenital diaphragmatic hernia. Fetal Diagn Ther 2006;21:39e44. [53] Datin-Dorriere V, Rouzies S, Taupin P, Walter-Nicolet E, Benachi A, Sonigo P, et al. Prenatal prognosis in isolated congenital diaphragmatic hernia. Am J Obstet Obstet Gynecol 2008;198:80.e1e5. [54] Lipshutz GS, Albanese CT, Feldstein VA, Jennings RW, Housley HT, Beech R, et al. Prospective analysis of lung-to-head ratio predicts survival for patients with prenatally diagnosed congenital diaphragmatic hernia. J Pediatr Purg 1997;32:1634e6. [55] Jani J, Peralta CF, Van Schoubroeck D, Deprest J, Nicolaides KH. Relationship between lung-to-head ratio and lung volume in normal fetuses and fetuses with diaphragmatic hernia. Ultrasound Obstet Gynecol 2006;27:545e50. [56] Gucciardo L, Deprest J, Done E, Van Mieghem T, Van de Velde M, Gratacos E, et al. Prediction of outcome in isolated congenital diaphragmatic hernia and

[57]

[58]

[59]

[60]

[61]

[62]

[63]

[64]

[65]

[66]

[67] [68]

[69]

[70] [71]

[72]

[73]

[74]

[75]

[76]

[77]

[78]

[79]

[80]

its consequences for fetal therapy. Best practice and research. Clin Obstet Gynaecol 2008;22:123e38. Deprest J, Gratacos E, Nicolaides KH, FETO Task Group. Fetoscopic tracheal occlusion (FETO) for severe congenital diaphragmatic hernia: evolution of a technique and preliminary results. Ultrasound Obstet Gynecol 2004;24: 121e6. Peralta CF, Jani JC, Van Schoubroeck D, Nicolaides KH, Deprest JA. Fetal lung volume after endoscopic tracheal occlusion in the prediction of postnatal outcome. Am J Obstet Obstet Gynecol 2008;198:60.e1e5. Jani JC, Flemmer AW, Bergmann F, Gallot D, Roubliova X, Muensterer OJ, et al. The effect of fetal tracheal occlusion on lung tissue mechanics and tissue composition. Pediatr Pulmonol 2009;44:112e21. Cannie MM, Jani JC, De Keyzer F, Allegaert K, Dymarkowski S, Deprest J. Evidence and patterns in lung response after fetal tracheal occlusion: clinical controlled study. Radiology 2009;252:526e33. Cruz-Martinez R, Hernandez-Andrade E, Moreno-Alvarez O, Done E, Deprest J, Gratacos E. Prognostic value of pulmonary Doppler to predict response to tracheal occlusion in fetuses with congenital diaphragmatic hernia. Fetal Diagn Ther 2011;29:18e24. Gucciardo L, Deprest JA, Vaast P, Favre R, Gallot D, Huissoud C, et al. [Antenatal prediction of pulmonary hypoplasia and intrauterine treatment by endoscopic fetal tracheal occlusion in severe isolated congenital diaphragmatic hernia]. Bull Acad Natl Med 2008;192:1589e607 [discussion 1607e9]. Henrich W, Fuchs I, Buhrer C, van Landeghem FK, Albig M, Stoever B, et al. Isolated cardiomegaly in the second trimester as an early sign of fetal hydrops due to intracranial arteriovenous malformation. J Clin Ultrasound 2003;31: 445e9. Wilson RD, Hedrick H, Flake AW, Johnson MP, Bebbington MW, Mann S, et al. Sacrococcygeal teratomas: prenatal surveillance, growth and pregnancy outcome. Fetal Diagn Ther 2009;25:15e20. Byrne FA, Lee H, Kipps AK, Brook MM, Moon-Grady AJ. Echocardiographic risk stratification of fetuses with sacrococcygeal teratoma and twin-reversed arterial perfusion. Fetal Diagn Ther 2011;30:280e8. Statile CJ, Cnota JF, Gomien S, Divanovic A, Crombleholme T, Michelfelder E. Estimated cardiac output and cardiovascular profile score in fetuses with high cardiac output lesions. Ultrasound Obstet Gynecol 2013;41:54e8. Adzick NS. Open fetal surgery for life-threatening fetal anomalies. Semin Fetal Neonatal Med 2010;15:1e8. Ruano R, Duarte S, Zugaib M. Percutaneous laser ablation of sacrococcygeal teratoma in a hydropic fetus with severe heart failure e too late for a surgical procedure? Fetal Diagn Ther 2009;25:26e30. Clark SL, Miller DD, Belfort MA, Dildy GA, Frye DK, Meyers JA. Neonatal and maternal outcomes associated with elective term delivery. Am J Obstet Obstet Gynecol 2009;200:156.e1e4. McIntire DD, Leveno KJ. Neonatal mortality and morbidity rates in late preterm births compared with births at term. Obstet Gynecol 2008;111:35e41. Costello JM, Polito A, Brown DW, McElrath TF, Graham DA, Thiagarajan RR, et al. Birth before 39 weeks' gestation is associated with worse outcomes in neonates with heart disease. Pediatrics 2010;126:277e84. Carnaghan H, Pereira S, James CP, Charlesworth PB, Ghionzoli M, Mohamed E, et al. Is early delivery beneficial in gastroschisis? J Pediatr Surg 2014;49: 928e33 [discussion 933]. Trento LU, Pruetz JD, Chang RK, Detterich J, Sklansky MS. Prenatal diagnosis of congenital heart disease: impact of mode of delivery on neonatal outcome. Prenat Diagn 2012;32:1250e5. Walsh CA, MacTiernan A, Farrell S, Mulcahy C, McMahon CJ, Franklin O, et al. Mode of delivery in pregnancies complicated by major fetal congenital heart disease: a retrospective cohort study. J Perinatol 2014;34:901e5. Case AP, Colpitts LR, Langlois PH, Scheuerle AE. Prenatal diagnosis and cesarean section in a large, population-based birth defects registry. J MaternaleFetal Neonatal Med 2012;25:395e402. Jowett VC, Sankaran S, Rollings SL, Hall R, Kyle PM, Sharland GK. Foetal congenital heart disease: obstetric management and time to first cardiac intervention in babies delivered at a tertiary centre. Cardiol Young 2014;24: 494e502. Cnota JF, Gupta R, Michelfelder EC, Ittenbach RF. Congenital heart disease infant death rates decrease as gestational age advances from 34 to 40 weeks. J Pediatr 2011;159:761e5. Nasr A, Langer JC, Canadian Paediatric Surgery Network. Influence of location of delivery on outcome in neonates with gastroschisis. J Pediatr Surg 2012;47: 2022e5. Mirlesse V, Cruz A, Le Bidois J, Diallo P, Fermont L, Kieffer F, et al. Perinatal management of fetal cardiac anomalies in a specialized obstetricepediatrics center. Am J Perinatol 2001;18:363e71. Pruetz JD, Carroll C, Trento LU, Chang RK, Detterich J, Miller DA, et al. Outcomes of critical congenital heart disease requiring emergent neonatal cardiac intervention. Prenat Diagn 2014;34:1127e32.

Please cite this article in press as: Pruetz JD, et al., Clinical relevance of fetal hemodynamic monitoring: Perinatal implications, Seminars in Fetal & Neonatal Medicine (2015), http://dx.doi.org/10.1016/j.siny.2015.03.007