Fetal Echocardiography and Magnetocardiography

Number: 0106

Policy

1. Aetna considers fetal echocardiograms, Doppler and color flow mapping medically necessary after 12 weeks gestation for any of the following conditions:

   1. A mother with type 1 diabetes or pregestational type 2 diabetes on insulin during the first trimester; or
   2. A mother with systemic lupus erythematosus; or
   3. As a screening study in families with a first-degree relative of a fetus with congenital heart disease; or
   4. Fetal nuchal translucency measurement of 3.5 mm or greater in the first trimester; or

   5. Following an abnormal or incomplete cardiac evaluation on an anatomic scan, 4-chamber study

      Note: When the 4-chambered view is adequate and there are no other indications of a cardiac abnormality, a fetal echocardiogram is not considered medically necessary; or

   6. For ductus arteriosus dependent lesions and/or with other known complex congenital heart disease; or
   7. For pregnancies conceived by in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI); or
   8. In cases of persistent right umbilical vein; or
   9. In cases of single umbilical artery; or
   10. In cases of suspected or known fetal chromosomal abnormalities; or
   11. In suspected or documented fetal arrhythmia: to define the rhythm and its significance, to identify structural heart disease and cardiac function; or
   12. In members with autoimmune antibodies associated with congenital cardiac anomalies [anti-Ro (SSA)/anti-La (SSB)]; or
   13. In members with familial inherited disorders associated with congenital cardiac abnormalities (e.g., Marfan syndrome); or
   14. In cases with monochorionic twins; or
   15. In cases of multiple gestation and suspicion of twin-twin transfusion syndrome; or
   16. In members with seizure disorders, even if they are not presently taking anti-seizure medication; or
   17. In cases with non-immune fetal hydrops or unexplained severe polyhydramnios; or 
   18. When members' fetuses have been exposed to drugs known to increase the risk of congenital cardiac abnormalities including but not limited to:
       
       
       • Anti-seizure medications; or
       • Excessive alcohol intake; or
       • Lithium; or
       • Paroxetine (Paxil); or
       • Retinoids; or
         

   19. When other structural abnormalities are found on ultrasound; or 

2. Aetna considers repeat studies of fetal echocardiograms, Doppler and color flow mapping medically necessary for any of the following: 

   1. When the initial screening study indicates any of the following:

      1. A ductus arteriosus dependent lesion; or
      2. Structural heart disease with a suggestion of hemodynamic compromise; or
      3. Tachycardia other than sinus tachycardia or heart block; or

   2. Fetal surveillance (e.g., congenital heart block) in mother with documented diagnosis of Sjögren’s syndrome. Frequency of testing: Doppler fetal echocardiography may be repeated every 1 to 2 weeks starting at 16 weeks gestation continuing through 28 weeks gestation, then every other week until 32 weeks gestation to detect fetal (congenital) heart block.

3. Aetna considers fetal echocardiograms experimental and investigational for all other indications including the following (not an all-inclusive list) because their effectiveness for these indications has not been established.

   • As a screening test in advanced maternal age; or
   • Gestational diabetes even if requiring insulin after the first trimester; or
   • Pregnant women receiving selective serotonin reuptake inhibitors (except paroxetine); or
   • Suspected cystic fibrosis.

4. Aetna considers fetal magnetocardiography experimental and investigational because its effectiveness has not been established.

Background

Definition of fetal cardiac structures is currently possible at 12 weeks of gestation with the use of vaginal probes with high-resolution transducers.  With current technologies, accurate segmental analysis of cardiac structures and blood flow across valves, shunts, and the ductus arteriosus is possible with a conventional transabdominal approach by 16 to 18 weeks of gestation.

According to the American Institute for Ultrasound in Medicine (AIUM), fetal echocardiography is commonly performed between 18 and 22 weeks’ gestational age. Some forms of congenital heart disease may even be recognized during earlier stages of pregnancy (AIUM, 2013). Newer technology including endovaginal transducers can obtain images of the heart as early as 12 weeks gestation (AHA, 2018).

Hutchinson et al. (2017) states that early fetal echocardiography (FE), performed at 12 to 16 weeks' gestational age (GA), can be used to screen for fetal heart disease similar to that routinely performed in the second trimester; however, the efficacy of FE at earlier GAs has not been as well explored, particularly with recent advances in ultrasound technology. Pregnant women were prospectively recruited for first-trimester FE. All underwent two-dimensional (2D) cardiac imaging combined with color Doppler (CD) assessment, and all were offered second-trimester fetal echocardiographic evaluations. Fetal cardiac anatomy was assessed both in real time during FE and additionally offline by two separate reviewers. Very early FE was performed in 202 pregnancies including a total of 261 fetuses, with 92% (n = 241) being reassessed at greater than or equal to 18 weeks' GA. Transabdominal scanning was used in all cases, and transvaginal scanning was used additionally in most at less than 11 weeks' GA (n = 103 of 117 [88%]). There was stepwise improvement in image resolution of the fetal heart in those pregnancies that presented at later gestation for assessment. CD assisted with definition of cardiac anatomy at all GAs. A four-chambered heart could be identified in 52% of patients in the eighth week (n = 12 of 23), improving to 80% (n = 36 of 45) in the 10th week and 98% (n = 57 of 58) by the 11th week. The inferior vena cava was visualized by 2D imaging in only 4% (n = 1 of 23) in the eighth week, increasing to 13% (n = 6 of 45) by the 10th week and 80% (n = 25 of 31) by the 13th week. CD improved visualization of the inferior vena cava at earlier GAs to greater than 80% (n = 37 of 45) from 10 weeks. Pulmonary veins were not visualized by either 2D imaging or CD until after the 11th week. Both cardiac outflow tracts could be visualized by 2D imaging in the minority from 8+0 to 10+6 weeks (n = 18 of 109 [16%]) but were imaged in most from 11+0 to 13+6 weeks (n = 114 of 144 [79%]). CD imaging improved visualization of both outflow tracts to 64% (n = 29 of 45) in the 10th week. On 2D imaging alone, both the aortic and ductal arches were seen in only 29% of patients in the 10th week (n = 13 of 45), increasing to 58% when CD was used (58% [n = 26 of 45]) and to greater than 80% (n = 47 of 58) using CD in the 11th week. The authors concluded that very early FE, from as early as 8 weeks, can be used to assess cardiac structures; however, the ability to image fetal heart structures between 6 and 8 weeks is currently nondiagnostic. The use of CD significantly increases the detection of cardiac structures on early FE. The ideal timing of complete early FE, excluding pulmonary vein assessment, appears to be after 11 weeks' GA.

Ventriglia et al. (2016) state that there is a growing body of evidence that most of the major cardiac abnormalities can be diagnosed from 12-16 weeks of gestation (compared with the usual 18-22 weeks). Furthermore, the reason for performing early fetal echocardiography (EFEC) is that "the combined EFEC-NT (nuchal translucency) approach (11th-13th week) gives a 60-70% increase in detection rate for CHD. Combined EFE-NT analysis is also justified by the high CHD frequency in genetic syndromes and the similarity of anatomic relations between cardiac structures at 11-13 wks GA and those of the second trimester." "The technical limits of EFEC are CRL < 50 mm, an increase of maternal Body mass index (BMI), unfavorable fetal position and a possible progression of cardiac disease especially in outflow obstructions. This means that the pregnant women should be informed about the limits of early screening and also recommended to have a further scan as from 18 weeks for a more complete diagnosis."

Patients are referred for fetal echocardiography because of an abnormality of structure or rhythm noted on ultrasound examination or because the patient is in a high-risk group for fetal heart disease.  Treatment of the patient is facilitated by the early recognition of the exact nature of the cardiac problem in the fetus.  The correct diagnosis may be difficult because of fetal physiology, the effect on flow across defects and valves, inability to see the fetus for orientation reference, and inability to examine the fetus for clinical findings.  For these reasons, fetal echocardiography should be performed only by trained fetal echocardiographers.

The umbilical cord normally contains two arteries and one vein embedded in Wharton's jelly.The umbilical cord "achieves its final form by the 12th week of gestation". Initially during umbilical cord development, there are two umbilical arteries and two umbilical veins, in which the two veins (left and right) converge into one. Obliteration of the right umbilical vein by the end of the 6th week of gestation results in a single persisting left umbilical vein (Spurway et al, 2012). However, persistence of the right umbilical vein in the fetus is a variant of the intra-abdominal umbilical venous connection. The estimated prevalence of an intrahepatic persistent right umbilical vein is 1 per 786 births; which may be an underestimated calculation in populations that do not undergo targeted sonographic examinations. In addition, the variation in anatomy can be subtle (Lide et al, 2016).

Lide et al (2016) provided a comprehensive review of the current data surrounding an intra-hepatic persistent right umbilical vein in the fetus, including associated anomalies and outcomes, to aid practitioners in counseling and management of affected pregnancies.  These investigators performed a Medline, Embase, Cochrane Central Register of Controlled Trials, and Northern Light database search for articles reporting outcomes on prenatally diagnosed cases of a persistent right umbilical vein.  Each article was independently reviewed for eligibility by the investigators.  Thereafter, the data were extracted and validated independently by 3 investigators.  A total of 322 articles were retrieved, and 16 were included in this systematic review.  The overall prevalence of an intra-hepatic persistent right umbilical vein was found to be 212 per 166,548 (0.13 %).  Of the 240 cases of an intra-hepatic persistent right umbilical vein identified, 183 (76.3 %) were isolated.  The remaining cases had a co-existing abnormality, including 19 (7.9 %) cardiac, 9 (3.8 %) central nervous system, 15 (6.3 %) genito-urinary, 3 (1.3 %) genetic, and 17 (7 %) placental/cord (predominantly a single umbilical artery).  The authors concluded that a persistent right umbilical vein is commonly an isolated finding but may be associated with a co-existing cardiac defect in 8 % of cases.  Therefore, consideration should be given to fetal echocardiography in cases of a persistent right umbilical vein.

Canavan et al (2016) stated that a fetal persistent intrahepatic right umbilical vein has been linked to anomalies and genetic disorders but can be a normal variant.  These researchers conducted a retrospective review to determine other sonographic findings that can stratify fetuses for further evaluation.  A total of 313 fetuses had a persistent intra-hepatic right umbilical vein identified on 17- to 24-week sonography.  The outcome was any major congenital anomaly or an adverse neonatal outcome, which was defined as aneuploidy, fetal demise, or neonatal death.  A total of 217 patients (69.3 %) had a normal neonatal outcome; 69 patients (22.0 %) were lost to follow-up; 5 fetuses (2.1 %) had aneuploidy; 4 of the 5 had additional sonographic findings, and 1 had an isolated persistent intra-hepatic right umbilical vein; 24 fetuses had a major anomaly in association with the persistent right umbilical vein; 26 additional fetuses had soft sonographic markers associated with karyotypic abnormalities but were chromosomally normal.  Of those with adverse neonatal outcomes, 12 had a congenital heart defect (57 %).  An additional sonographic finding with a persistent intra-hepatic right umbilical vein was predictive of a congenital anomaly or an adverse neonatal outcome (p < 0.001), with a positive predictive value of 44.0 % (95 % confidence interval[ CI]: 30.0 % to 58.7 %).  An isolated persistent intra-hepatic right umbilical vein had a 0.4 % risk for a congenital anomaly or an adverse neonatal outcome.  The authors concluded that a persistent intra-hepatic right umbilical vein should prompt an extended anatomic survey and a fetal cardiac evaluation.  If the survey and cardiac anatomy are reassuring, no further follow-up is needed. If additional findings are identified, genetic counseling and invasive testing should be considered.

Kumar et al (2016) appraised the incidence and significance of persistent right umbilical vein (PRUV), the most common fetal venous aberration.  Based on a South Indian antenatal cohort, these researchers identified 23 cases of PRUV amongst 20,452 fetuses of consecutive pregnancies, from 2009 to 2014, yielding an incidence of 1 in 889 total births (0.11 %).  The median maternal age was 24 (inter-quartile range [IQR], 22 to 26) years, and median gestational age at diagnosis was 23 (IQR, 22 to 24) weeks.  Intra-hepatic drainage of PRUV was seen in 91.3 % cases.  In 3 cases (13 %), ductus venosus was absent.  In 52.2 % of the cases, additional major abnormalities were observed - predominantly cardiovascular (39.1 %).  The common minor marker was single umbilical artery (SUA; 13 %).  The karyotype was found to be normal in 6 cases (26 %) that underwent invasive testing.  When associated anomalies were inconsequential or absent, the post-natal outcome was good, which reflected in 60.9 % of these cases.  Fetal echocardiography was one of the keywords listed in this study.

In a prospective, observational study, Hill et al (1994) reviewed their experience with antenatal detection and subsequent neonatal outcome of fetuses with a persistent right umbilical vein.  A total of 33 cases of persistent right umbilical vein were detected during 15,237 obstetric ultrasound examinations performed after 15 weeks' gestation.  Persistent right umbilical vein was detected at a rate of 1 per 476 obstetric ultrasound examinations; 6 of 33 (18.2 %) fetuses with a persistent right umbilical vein had additional important congenital malformations.  The authors concluded that careful 2nd- and 3rd-trimester ultrasound examinations can detect a persistent right umbilical vein.  When this particular anomaly is detected, a thorough fetal anatomic survey, including echocardiography, should be performed to rule out more serious congenital malformations.

Wolman et al (2002) conducted a prospective evaluation of the incidence and neonatal outcome of fetuses with persistent right umbilical vein.  This condition had traditionally been considered to be extremely rare and to be associated with a very poor neonatal prognosis, but later evidence has raised some doubts about the veracity of these contentions.  Between August 1995 and November 1998, a total of 8,950 low-risk patients were prospectively evaluated at 2 medical centers.  The sonographic diagnosis of a persistent right umbilical vein was made in a transverse section of the fetal abdomen when the portal vein was curved toward the stomach, and the fetal gall bladder was located medially to the umbilical vein.  Persistent right umbilical vein was detected in 17 fetuses during the study; 4 of them had additional malformations, of which 3 had been detected antenatally.  The authors established that the incidence of persistent right umbilical vein in a low-risk population was 1:526.  They believed that the sonographic finding of this anomaly was an indication for conducting targeted fetal sonography and echocardiography.  When the persistent right umbilical vein was connected to the portal system and other anomalies were ruled out, the prognosis can generally be expected to be favorable.

Martínez et al (2012) described the ultrasound findings, maternal and perinatal variables in cases with a prenatal diagnosis of persistence of right umbilical vein. This was a descriptive analysis of cases with prenatal diagnosis of persistence of right umbilical vein in the Fetal Medicine Unit, Department of Obstetrics and Gynecology, Hospital Universitario Severo Ochoa.  These investigators described ultrasound findings, maternal and perinatal variables.  They examined 9,198 fetuses and 6 cases (0.06 %) were diagnosis prenatally of persistent right umbilical vein, between 20 and 29 weeks of gestation.  The male/female ratio was 1/1.  Ductus venosus was presented in all cases; 2  fetuses (33 %) were proved to have other structural anomalies and their parents opted for termination of the pregnancy.  All cases had no chromosomal anomaly associated and after birth, neonatal developments were favorable.  The authors concluded that based on these findings and a literature review, after prenatal diagnosis of persistent right umbilical vein, an exhaustive morphological study, which included a fetal echocardiography, is mandatory in order to rule out other structural malformations.  Indication for fetal karyotype study has to be individualized considering persistence right umbilical vein type and other ultrasound findings.

A single umbilical artery (SUA) is present in 0.2 % to 0.6 % of live births, occurring more frequently in twins and in small for gestational age and premature infants.  In infants with SUA, there is an increased rate of chromosomal and other congenital anomalies.  Studies have shown that 20 % to 30 % of neonates with SUA had major structural anomalies, frequently involving multiple organs (Palazzi and Brandt, 2009; Thummala et al, 1998).  The most commonly affected organ is the heart.  Single umbilical artery is an isolated finding in the remaining 70 % to 80 % of infants.

Conception by in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) has been associated with an increased incidence of fetal heart defects.  A meta-analyses on the prevalence of birth defects in infants conceived following IVF and/or ICSI compared with spontaneously conceived infants reported a 30 % to 40 % increased risk of birth defects associated with IVF and/or ICSI (Hansen et al, 2005).  Researchers have reported that infants conceived with the use of IVF and/or ICSI have a 2-to-4-fold increase of heart malformations compared with naturally conceived infants.

Kurinczuk and Bower (1997) examined the prevalence of birth defects on 420 liveborn infants who were conceived after ICSI in Belgium compared with 100,454 liveborn infants in Western Australia delivered during the same period.  Infants born after ICSI were twice as likely as Western Australian infants to have a major birth defect [odds ratio (OR) 2.03, 95 % confidence interval (CI): 1.40 to 2.93); p = 0.0002] and nearly 50 % more likely to have a minor defect (OR 1.49 (0.48 to 4.66); p = 0.49).  Secondary data-led analyses found an excess of major cardiovascular defects (OR 3.99).

Koivurova et al (2002) evaluated the neonatal outcome and the prevalence of congenital malformations in children born after IVF in northern Finland in a population-based study with matched controls.  Children born after IVF (n = 304) in 1990 to1995 were compared with controls (n = 569), representing the general population in proportion of multiple births, randomly chosen from the Finnish Medical Birth Register (FMBR) and matched for sex, year of birth, area of residence, parity, maternal age and social class.  Plurality matched controls were randomly chosen from the FMBR and analyzed separately.  Additionally, IVF singletons were compared with singleton controls. The prevalence of heart malformations was four-fold in the IVF population than in the controls representing the general population (OR 4.0, 95 % CI: 1.4 to 11.7). 

Reefhuis et al (2009) analyzed data from the National Birth Defects Prevention Study, a population-based, multi-center, case-control study of birth defects.  Included were mothers of fetuses or live-born infants with a major birth defect (case infants) and mothers who had live-born infants who did not have a major birth defect (control infants), delivered during the period October 1997 to December 2003.  Mothers who reported IVF or ICSI use were compared with those who had unassisted conceptions.  Among singleton births, IVF or ICSI use was associated with septal heart defects (adjusted odds ratio [aOR] = 2.1, 95 % CI: 1.1 to 4.0).

As fetal heart disease is typically associated with structural abnormalities and consequent aberrant blood flow through the heart, it is necessary to perform Doppler studies and color flow mapping when such abnormalities are detected with 2D fetal echocardiography.

The American College of Obstetricians and Gynecologists' Committee Opinion on the treatment with selective serotonin reuptake inhibitors during pregnancy (ACOG, 2006) noted that paroxetine use among pregnant women and women planning pregnancy should be avoided, if possible.  Fetal echocardiography should be considered for women who were exposed to paroxetine in early pregnancy.

In a practice bulletin on screening for fetal chromosomal anomalies, ACOG (2007) has stated that patients who have a fetal nuchal translucency measurement of 3.5 mm or greater in the first trimester, despite a negative result on an aneuploidy screen, normal fetal chromosomes, or both, should be offered a targeted ultrasound examination, fetal echocardiogram, or both, because such fetuses are at a significant risk for non-chromosomal anomalies, including congenital heart defects, abdominal wall defects, diaphragmatic hernias, and genetic syndromes.

Twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic (1 placenta) twin pregnancies, characterized by the development of unbalanced chronic blood transfer from one twin, defined as donor twin, to the other, defined as recipient, through placental anastomoses.  If left untreated, TTTS is associated with very high peri-natal mortality and morbidity rates; and fetuses who survive are at risk of severe cardiac, neurological, and developmental disorders.

The American Society of Echocardiography's guidelines and standards for performance of the fetal echocardiogram (Rychik et al, 2004) stated that multiple gestation and suspicion of TTTS is an indication of fetal echocardiography.

Bahtiyar et al (2007) noted that congenital heart defects (CHDs) affect approximately 0.5 % of all neonates.  Recent literature points to a possible increase in the CHD prevalence among monochorionic/diamniotic (MC/DA) twin gestations.  These researchers hypothesized that MC/DA twin pregnancy is a risk factor for CHD.  A systematic review of all published English literature was conducted on MEDLINE (Ovid and PubMed) from January 2000 through April 2007 using the medical subject heading terms "congenital heart defect" and "monozygotic twins".  Four observational studies were included in the final analysis.  Published historical data were used for the population background risk of CHD.  Relative risk (RR) estimates with 95 % confidence intervals (CIs) were calculated by fixed and random effect models.  These investigators included a total of 40 fetuses with CHDs among 830 fetuses from MC/DA twin gestations.  Compared with the population, CHDs were significantly more prevalent in MC/DA twins regardless of the presence of TTTS (RR, 9.18; 95 % CI: 5.51 to 15.29; p < 0.001).  Monochorionic/diamniotic twin gestations affected by TTTS were more likely to be complicated by CHDs than those that did not have TTTS (RR, 2.78; 95 % CI: 1.03 to 7.52; p = 0.04).  Ventricular septal defects were the most frequent heart defects.  Pulmonary stenosis and atrial septal defects were significantly more prevalent in pregnancies complicated with TTTS.  The authors concluded that MC/DA twin gestation appears to be a risk factor for CHDs.  Conditions that lead to abnormal placentation may also contribute to abnormal heart development, especially in MC/DA twin pregnancies complicated with TTTS.  Fetal echocardiography may be considered for all MC/DA twin gestations because ventricular septal defects and pulmonary stenosis are the most common defects.

The Royal College of Obstetricians and Gynaecologists' clinical practice guidelines on "Management of monochorionic twin pregnancy" (RCOG, 2008) stated that a fetal echocardiographic assessment should be considered in the assessment of severe TTTS.

Pregnant Women Receiving Selective Serotonin Reuptake Inhibitors

Reefhuis and colleagues (2015) followed up on previously reported associations between peri-conceptional use of selective serotonin reuptake inhibitors (SSRIs) and specific birth defects using an expanded dataset from the National Birth Defects Prevention Study.  These researchers performed a Bayesian analysis combining results from independent published analyses with data from a multi-center population based case-control study of birth defects.  A total of 17,952 mothers of infants with birth defects and 9,857 mothers of infants without birth defects, identified through birth certificates or birth hospitals, with estimated dates of delivery between 1997 and 2009 were included in this analysis; exposures were citalopram, escitalopram, fluoxetine, paroxetine, or sertraline use in the month before through the 3rd month of pregnancy.  Posterior OR estimates were adjusted to account for maternal race/ethnicity, education, smoking, and pre-pregnancy obesity.  Main outcome measure was 14 birth defects categories that had associations with SSRIs reported in the literature.  Sertraline was the most commonly reported SSRI, but none of the 5 previously reported birth defects associations with sertraline was confirmed.  For 9 previously reported associations between maternal SSRI use and birth defect in infants, findings were consistent with no association.  High posterior ORs excluding the null value were observed for 5 birth defects with paroxetine (anencephaly 3.2, 95 % CI: 1.6 to 6.2; atrial septal defects 1.8, 95 % CI: 1.1 to 3.0; right ventricular outflow tract obstruction defects 2.4, 95 % CI: 1.4 to 3.9; gastroschisis 2.5, 95 % CI: 1.2 to 4.8; and omphalocele 3.5, 95 % CI: 1.3 to 8.0) and for 2 defects with fluoxetine (right ventricular outflow tract obstruction defects 2.0, 95 % CI: 1.4 to 3.1 and craniosynostosis 1.9, 95 % CI: 1.1 to 3.0).  The authors concluded that these data provided reassuring evidence for some SSRIs; but suggested that some birth defects occurred 2 to 3.5 times more frequently among the infants of women treated with paroxetine or fluoxetine early in pregnancy.

A 2015 study by the Centers for Disease Control and Prevention (CDC) used new data to examine previous reported links between use of specific SSRIs medications just before or during early pregnancy and the occurrence of certain birth defects.  Researchers looked at links with 5 different SSRI medications: citalopram, escitalopram, fluoxetine, paroxetine, and sertraline.  Although the new data confirmed the risks seen with paroxetine, it did not appear to suggest that the risk is across the board with all SSRIs.  Therefore, fetal echocardiography is still recommended for women exposed to paroxetine, but there doesn’t seem to be enough evidence to recommend coverage of fetal echocardiograms for all pregnant members receiving any SSRI.  The study concluded that despite the increased risks for certain birth defects from some SSRIs found in this study, the actual risk for a birth defect among babies born to women taking one of these medications is still very low.  Because these specific types of birth defects are rare, even doubling the risk still results in a low absolute risk.  For example, the risks for heart defects with obstruction of the right ventricular outflow tract could increase from 10 per 10,000 births to about 24 per 10,000 births among babies of women who are treated with paroxetine early in pregnancy. 

Fetal Magnetocardiography

Fetal magnetocardiography (fMCG) is a new, non-invasive technique used to monitor the spontaneous electrophysiological activity of the fetal heart.  Hrtankova and associates (2015) reviewed the evidence on the clinical value of fMCG.  These investigators performed an analysis of the literature using database search engines PubMed, and SCOPE in field of fMCG.  Compared to cardiotocography and fetal electrocardiography, fMCG is a more effective method with a higher resolution.  The signal obtained from the fetal heart is sufficiently precise and the quality allows an assessment of PQRST complex alterations, and to detect fetal arrhythmia.  Thanks to early diagnosis of fetal arrhythmia, there is the possibility for appropriate therapeutic intervention and the reduction of unexplained fetal death in late gestation.  These investigators also noted that fMCG with high temporal resolution also increased the level of clinical trials that recorded fetal heart rate (FHR) variability.  According to the latest theories, FHR variability is a possible indicator of fetal status and enabled the study of the fetal autonomic nervous system indirectly. The authors concluded that fMCG is an experimental method that requires expensive equipment; it has yet to be shown in the future if this method will get any application in clinical practice.

Eswaran and colleagues (2017) stated that fMCG provides the requisite precision for diagnostic measurement of electrophysiological events in the fetal heart.  Despite its significant benefits, this technique with current cryogenic based sensors has been limited to few centers, due to high cost of maintenance.  In this study, these researchers demonstrated that a less expensive non-cryogenic alternative, optically pumped magnetometers, can provide similar electrophysiological and quantitative characteristics when subjected to direct comparison with the current technology.  They concluded that further research can potentially increase its clinical use for fMCG.

Furthermore, an UpToDate review on "Overview of the general approach to diagnosis and treatment of fetal arrhythmias" (Levine and Alexander, 2017) states that "Magnetocardiography shifts the electrical signals into an evoked magnetic signal that can be processed to create a beat-to-beat magnetocardiogram that looks much like a traditional electrocardiogram (ECG).  Continuous recordings can be performed for relatively sustained periods and have permitted elegant demonstration of arrhythmia onset/offset and more direct observation of mechanisms.  The equipment is not widely available, requires careful shielding and requires skilled technical support, so the technology remains investigational".

Fetal Surveillance in Sjögren’s Syndrome

Gupta and Gupta (2017) state that studies show a high incidence of poor fetal outcomes for women with Sjögren’s syndrome; however pregnancy outcomes in these women have not been extensively studied. The authors conducted a literature review to evaluate Sjögren’s syndrome and pregnancy.  Gupta and Gupta found that well-known fetal outcomes in Sjögren syndrome-complicated pregnancies include neonatal lupus and congenital heart block (CHB), of which CHB is the most severe fetal complication. CHB is thought to occur because of damage to the atrioventricular node by anti-SS-A or anti-SS-B antibodies, or both. The reported prevalence of CHB in the offspring of an anti-SS-A-positive woman is 1% to 2%. The recurrence rate in a patient with antibodies, who has a previous child affected, is approximately 10 times higher. Based on Gupta’s review, frequent surveillance by serial echocardiograms and obstetric sonograms between 16 to 20 weeks of gestation and thereafter is required for at-risk pregnancies, with the goal of early diagnosis and early treatment of incomplete CHB, thus improving the outcome for the fetus.

Although there are no formal guidelines for type or frequency of testing to detect fetal heart block, it is recommended that pregnant women with Sjögren’s syndrome receive weekly pulsed Doppler fetal echocardiography from the 18th through the 26th week of pregnancy and then every other week until 32 weeks. "The most vulnerable period for the fetus is during the period from 18 to 24 weeks gestation. Normal sinus rhythm can progress to complete block in seven days during this high-risk period. New onset of heart block is less likely during the 26th through the 30th week, and it rarely develops after 30 weeks of pregnancy" (eviCore, 2018).

A scientific statement from the American Heart Association by Donofrio et al. (2014) states that maternal factors of Sjögren’s syndrome are associated with the absolute risk of 1 to 5 percent of live births that will have congenital heart block (CHB), risk increases to 11 to 19 percent for prior affected child with CHB or neonatal lupus. It is recommended that fetal echocardiography be performed at 16 weeks, then weekly or every other week to 28 weeks. The authors state that studies have suggested that high SSA values (≥50 U/mL) correlate with increased fetal risk, and that concern for late myocardial involvement may justify additional assessments in the third trimester. In addition to abnormalities in the conduction system, up to 10% to 15% of SSA-exposed fetuses with conduction system disease may also develop myocardial inflammation, endocardial fibroelastosis, or  atrioventricular (AV) valve apparatus dysfunction. "Although the value of serial assessment for the detection of the progression of myocardial inflammation or conduction system disease from first-degree block (PR prolongation) to CHB has not been proved, serial assessment at 1- to 2-week intervals starting at 16 weeks and continuing through 28 weeks of gestation is reasonable to perform because the potential benefits outweigh the risks. For women who have had a previously affected child, more frequent serial assessment, at least weekly, is recommended."

Fetal Echocardiography for Prediction of Fetal Demise After Laser Coagulation for Twin-Twin Transfusion Syndrome

In a systematic review and meta-analysis, Gijtenbeek and colleagues (2019) examined the value of echocardiography and Doppler before fetoscopic laser coagulation for TTTS in the prediction of intra-uterine fetal demise (IUFD).  These investigators compared pre-operative parameters between fetuses with and without demise following laser surgery.  A total of 18 studies were included.  Recipient twins have an increased risk of demise in case of pre-operative absent/reversed flow (A/REDF) in the umbilical artery (OR 2.76, 95 % CI: 1.78 to 4.28), absent or reversed a-wave in the ductus venosus (OR 2.32, 95 % CI: 1.70 to 3.16), or a middle cerebral artery peak systolic velocity of greater than 1.5 multiples of the median (MoM) (OR 7.59, 95 % CI: 2.56 to 22.46).  In donors, only A/REDF in the umbilical artery (OR 3.40, 95 % CI: 2.68 to 4.32) and absent or reversed a-wave in the ductus venosus (OR 1.66, 95 % CI: 1.12 to 2.47) were associated with IUFD.  No association was found between donor-IUFD and pre-operative myocardial performance index (MPI).  Two studies found an association between abnormal MPI and recipient demise.  With this study, these researchers identified a set of pre-operative Doppler parameters predictive of fetal demise following laser surgery.  The authors concluded that the utility of pre-operative parameters that reflect cardiac function such as the MPI in predicting IUFD remains unclear; more research is needed to examine the utility of pre-operative echocardiographic parameters such as the MPI in predicting IUFD.

The authors stated that this was the first review and meta‐analysis of pre-operative echocardiography and Doppler in the prediction of IUFD following fetoscopic laser surgery.  To maximize the sample size, these researchers included all studies that examined fetal demise before birth, not only early‐IUFD (less than 7 days).  Other causes of demise such as placental insufficiency or IUGR could therefore have influenced these findings, even though the majority of IUFD following laser occurred in the 1st week after laser surgery.  Other drawbacks of this study included the following: Most studies were single-center reports, 50 % of the reports were retrospective studies.  In all but 1 study, selective coagulation was used for all or for a proportion of cases.  It is known that incomplete laser coagulation is a risk factor for recurrent TTTS or post‐laser twin anemia polycythemia sequence (TAPS) and therewith for possible subsequent fetal demise.  Finally, these investigators did not include fetal growth discordance, selective fetal growth restriction (sFGR), or TAPS prior to laser surgery in this study.  They noted that future large‐scale prospective studies could allow for multi-variate analysis into the interference of sFGR and TAPS on fetal echocardiography and Doppler parameters for IUFD.  Incorporating signs of sFGR or TAPS, and factors such as Quintero stage, hydrops, and gestational age at TTTS diagnosis, into a prediction model together with the before‐mentioned Doppler parameters could be useful in daily clinical care in cases where the risk of fetal demise turns out to be high, to spend additional counseling time on cord occlusion as a back‐up plan if laser surgery appears technically challenging.  A prediction model could also be useful in future clinical trials investigating innovations in treatment of TTTS.

Appendix

Documentation Requirements for Fetal Echocardiography

According to guidelines from the American Institute for Ultrasound in Medicine (AIUM), fetal echocardiography should include the following cardiac images:

• Aortic arch;
• Ductal arch;
• Four-chamber view;
• Inferior vena cava;
• Left ventricular outflow tract;
• Right ventricular outflow tract;
• Short-axis views ("low" for ventricles and "high" for outflow tracts);
• Superior vena cava; and
• Three-vessel and trachea view.

According to the 2013 AIUM's practice parameter for the "Performance of Fetal Echocardiography", indications for fetal echocardiography are often based on a variety of parental and fetal risk factors for congenital heart disease.  However, most cases are not associated with known risk factors.  Common indications for a detailed scan of the fetal heart include but are not limited to:

Maternal Indications Associated with Congenital Heart Disease

• Autoimmune antibodies [anti-Ro (SSA)/anti-La (SSB)]
• Familial inherited disorders (e.g., 22q11.2 deletion syndrome)
• In-vitro fertilization
• Metabolic disease (e.g., diabetes mellitus and phenylketonuria)
• Teratogen exposure (e.g., lithium and retinoids)

Fetal Indications

• Abnormal cardiac screening examination
• Abnormal heart rate or rhythm
• Fetal chromosomal anomaly
• Extra-cardiac anomaly
• First-degree relative of a fetus with congenital heart disease
• Hydrops
• Increased nuchal translucency
• Monochorionic twins

This AIUM (2013) practice parameter was published in conjunction with the American College of Obstetricians and Gynecologists (ACOG), and the Society for Maternal-Fetal Medicine (SMFM), and the American Society of Echocardiography (ASE).  Furthermore, this practice parameter was endorsed by the American College of Radiology (ACR).

Source: AIUM Practice Parameter – Fetal Echocardiography (2013).

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered if selection criteria are met:
76825	Echocardiography, fetal, cardiovascular system, real time with image documentation (2D), with or without M-mode recording;
76826	follow-up or repeat study
76827	Doppler echocardiography, fetal, cardiovascular system, pulsed wave and/or continuous wave with spectral display; complete
76828	follow-up or repeat study
+93325	Doppler echocardiography color flow velocity mapping (List separately in addition to codes for echocardiography)
CPT codes not covered for indications listed in the CPB:
0475T	Recording of fetal magnetic cardiac signal using at least 3 channels; patient recording and storage, data scanning with signal extraction, technical analysis and result, as well as supervision, review, and interpretation of report by a physician or other qualified health care professional
0476T	patient recording, data scanning, with raw electronic signal transfer of data and storage
0477T	signal extraction, technical analysis, and result
0478T	review, interpretation, report by physician or other qualified health care professional
0541T - 0542T	Myocardial imaging by magnetocardiography (MCG) for detection of cardiac ischemia, by signal acquisition using minimum 36 channel grid, generation of magnetic-field time-series images, quantitative analysis of magnetic dipoles, machine learning–derived clinical scoring, and automated report generation
Other HCPCS codes related to the CPB:
Q9950	Injection, sulfur hexafluoride lipid microspheres, per ml
Maternal ICD-10 codes covered if selection criteria are met:
B97.10, B97.89	Unspecified viral infection
D68.61	Antiphospholipid syndrome
E10.10 - E13.9	Diabetes mellitus [do not report for gestational diabetes]
F10.20 - F10.29	Alcohol dependence
G40.001 - G40.919	Epilepsy and recurrent seizures
I34.0 - I37.9	Mitral valve disorders, aortic valve disorders, tricuspid valve disorders and pulmonary valve disorders, specified as nonrheumatic,
I42.3	Endomyocardial (eosinophilic) disease
I42.4	Endocardial fibroelastosis
I42.6	Alcoholic cardiomyopathy
I50.1 - I50.9	Heart failure
I51.7	Cardiomegaly
I78.0	Hereditary hemorrhagic telangectasia
L93.0 - L93.2	Lupus erythematosus
M05.40 - M06.9	Rheumatoid arthritis
M32.0 - M32.9	Systemic lupus erythematosus
M34.0 - M34.9	Systemic sclerosis [scleroderma]
M35.00 - M35.09	Sicca syndrome [Sjögren]
M35.9, M36.8	Unspecified diffuse connective tissue disease
O24.011 - O24.019, O24.111 - O24.119 O24.311 - O24.319, O24.811 - O24.819 O24.911 - O24.919	Diabetes mellitus in pregnancy [pre-existing, excludes gestational diabetes]
O30.001 - O30.93	Multiple gestation
O36.8310 - O36.8399	Maternal care for abnormalities of the fetal heart rate or rhythm
O98.411 - O98.419, O98.511 - O98.519	Viral hepatitis and other viral diseases complicating pregnancy
O98.611 - O98.619, O98.711 - O98.719 O98.811 - O98.819, O99.830	Other specified infectious and parasitic diseases complicating pregnancy
O98.911 - O98.93	Unspecified maternal infectious and parasitic diseases complicating pregnancy, childbirth and the puerperium
099.111 - O99.119	Other diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism complicating pregnancy with brackets stating [Antiphospholipid syndrome]
O99.350 - O99.353	Diseases of the nervous system complicating pregnancy [epilepsy]
O99.411 - O99.419	Diseases of the circulatory system complicating pregnancy
O99.89	Other specified diseases and conditions complicating pregnancy, childbirth and the puerperium [Systemic lupus erythematosus (SLE)]
Q20.0 - Q28.9	Congenital malformations of the circulatory system
Q79.6	Ehlers-Danlos syndrome
Q87.40 - Q87.43	Marfan's syndrome
Q89.3	Situs inversus
Q89.7	Multiple congenital malformations, not elsewhere classified
Q90.0 - Q90.9	Down syndrome
Q91.0 - Q91.3	Trisomy 18 [Edward's syndrome]
R56.1	Post traumatic seizures
R56.9	Unspecified convulsions [seizure disorder NOS]
R93.1, R93.8	Abnormal findings on diagnostic imaging of heart and coronary circulation and other body structures
T42.1x5+, T42.5x5+ T42.6x5+, T42.75x+	Adverse effects of other and unspecified anticonvulsants
Z3A.13 - Z34.49	13 - 49 Weeks of gestation of pregnancy
Z82.79	Family history of other congenital malformations, deformations and chromosomal abnormalities
Z98.89	Other specified postprocedural states
Fetal ICD-10 codes covered if selection criteria are met:
O09.811 - O09.819	Supervision of pregnancy resulting from assisted reproductive technology
O33.6xx0 - O33.6xx9	Maternal care for disproportion due to hydrocephalic fetus
O35.0xx0 - O35.0xx9	Maternal care for (suspected) central nervous system malformation in fetus
O35.10X0 to O35.19X9	Maternal care for (suspected) chromosomal abnormality in fetus
O35.2xx0 - O35.2xx9	Maternal care for (suspected) hereditary disease in fetus
O35.3xx0 - O35.3xx9	Maternal care for (suspected) damage to fetus from viral disease in mother
O35.4xx0 - O35.4xx9	Maternal care for (suspected) damage to fetus from alcohol
O35.5xx0 - O35.5xx9	Maternal care for (suspected) damage to fetus from drugs
O35.8xx0 - O35.8xx9	Maternal care for (suspected) fetal abnormality and damage
O35.9xx0 - O35.9xx9	Maternal care for (suspected) fetal abnormality and damage, unspecified
O35.AXX0 - O35.HXX9	Maternal care for other (suspected) fetal abnormality and damage
O36.0110 - O36.0999	Maternal care for rhesus isoimmunization
O36.1110 - O36.1999	Maternal care for other isoimmunization
O36.20x0 - O36.23x9	Maternal care for hydrops fetalis
O36.8310 - O03.8399	Maternal care for abnormalities of the fetal heart rate or rhythm
O40.1XX0 - O40.3XX9	Polyhydramnios
O43.011 - O43.029	Placenta transfusion syndromes
Q27.0	Congenital absence and hypoplasia of umbilical artery
ICD-10 codes covered if selection criteria are met:
O09.811 - O09.819	Supervision of pregnancy resulting from assisted reproductive technology
O24.011 - O24.019, O24.111 - O24.119 O24.311 - O24.319, O24.811 - O24.819 O24.911 - O24.919	Diabetes mellitus in pregnancy [pre-existing, excludes gestational diabetes]
O33.6xx0 - O33.6xx9	Maternal care for disproportion due to hydrocephalic fetus
O35.0xx0 - O35.0xx9	Maternal care for (suspected) central nervous system malformation in fetus
O35.10X0 to O35.19X9	Maternal care for (suspected) chromosomal abnormality in fetus
O35.2xx0 - O35.2xx9	Maternal care for (suspected) hereditary disease in fetus
O35.3xx0 - O35.3xx9	Maternal care for (suspected) damage to fetus from viral disease in mother
O35.4xx0 - O35.4xx9	Maternal care for (suspected) damage to fetus from alcohol
O35.5xx0 - O35.5xx9	Maternal care for (suspected) damage to fetus from drugs
O35.8xx0 - O35.8xx9	Maternal care for (suspected) fetal abnormality and damage
O35.9xx0 - O35.9xx9	Maternal care for (suspected) fetal abnormality and damage, unspecified
O35.AXX0 - O35.HXX9	Maternal care for other (suspected) fetal abnormality and damage
O36.0110 - O36.0999	Maternal care for rhesus isoimmunization
O36.1110 - O36.1999	Maternal care for other isoimmunization
O40.1xx0 - O40.1xx9	Polyhydramnios
O43.011 - O43.029	Placenta transfusion syndromes
O76	Abnormality in fetal heart rate and rhythm complicating labor and delivery
O98.411 - O98.419, O98.511 - O98.519	Viral hepatitis and other viral diseases complicating pregnancy
O98.611 - O98.619, O98.711 - O98.719 O98.811 - O98.819, O99.830	Other specified infectious and parasitic diseases complicating pregnancy
O98.911 - O98.919	Unspecified maternal infectious and parasitic diseases complicating pregnancy
O99.411 - O99.419	Diseases of the circulatory system complicating pregnancy
Q27.0	Congenital absence and hypoplasia of umbilical artery
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
O09.511 - O09.519	Supervision of elderly primigravida
O09.521 - O09.529	Supervision of elderly multigravida
O24.410 - O24.419	Gestational diabetes mellitus in pregnancy [not covered even if requiring insulin after the first trimester]
O99.810 - O99.815	Abnormal glucose complicating pregnancy, childbirth and the puerperium
Z13.228	Encounter for screening for other metabolic disorders
Repeat studies of Doppler and color flow mapping:
CPT codes covered if selection criteria are met:
76826	Echocardiography, fetal, cardiovascular system, real time with image documentation (2D), with or without M-mode recording; follow-up or repeat study
76828	Doppler echocardiography, fetal, cardiovascular system, pulsed wave and/or continuous wave with spectral display follow-up or repeat study
+93325	Doppler echocardiography color flow velocity mapping (List separately in addition to codes for echocardiography)
ICD-10 codes covered if selection criteria are met:
I51.0 – I51.9	Complications and ill-defined descriptions of heart disease [Structural heart disease with a suggestion of hemodynamic compromise]
M35.00 – M35.09	Sjogren syndrome
Q25.0	Patent ductus arteriosus
Z87.74	Personal history of (corrected) congenital malformations of heart and circulatory system

The above policy is based on the following references: