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The fetal heart typically is examined during the routine 18-20 week obstetric ultrasound screening, and pregnancies with abnormalities on this routine scan are referred for detailed fetal echocardiography. Per multiple practice guidelines, patients deemed to be at high risk of congenital heart defects (CHDs) are referred for fetal echocardiography as well between 18 and 24 weeks’ gestation.
However, with technological advancements in ultrasound, it is possible for obstetricians to detect many major CHDs well before 16 weeks’ gestation. First-trimester fetal heart assessment – and early detection of CHDs – has numerous advantages: It enables early genetic testing, early decision making about continuation or termination of pregnancy, and earlier planning for appropriate management during and after pregnancy. Perioperative outcomes are improved.
At least 75% of CHDs occur in pregnancies with no identifiable maternal, familial, or fetal risk factors. It only seems fitting, therefore, that we check the structure of the fetal heart in all women at the time of their first-trimester screening and sonography at 11-14 weeks. In addition to a determination of fetal viability and gestational age, nuchal translucency measurement, and a check of basic anatomy, .
The value of early detection
Women who have diabetes, congenital defects, in vitro fertilization pregnancies, twin and multiple pregnancies, and certain medication and drug exposures are at high risk for their fetus having a CHD and should undergo fetal echocardiography. Lupus, Sjögren’s, and other medical disorders also are risk factors, as are abnormal biochemical test results.
During the last 10 years, the first-trimester fetal heart evaluation has been performed for all patients who come for a first-trimester screening scan at the University of Maryland’s fetal heart program, part of the Center for Advanced Fetal Care. Approximately 45% of indications for detailed first-trimester fetal heart evaluation have been driven by maternal history, and almost 40% by abnormal basic first-trimester ultrasound findings such as increased nuchal translucency, tricuspid regurgitation, abnormal ductus venosus blood flow, and other structural anomalies.
An estimated 50%-60% of serious cardiac malformations can be detected with a four-chamber heart view during routine first-trimester ultrasound. When the outflow tract relationship and three-vessel views also are examined in the first trimester – as is now recommended in guidelines for second-trimester protocols – an estimated 85%-95% of major CHDs can be detected. One should see the great arteries originating from the left and right sides and crisscrossing each other by a transabdominal scan, or by a transvaginal scan if the transabdominal approach fails to show these features of the fetal heart.
Early sonography not only has been shown to have a high sensitivity but also a specificity of greater than 95% in identifying CHDs. Multiple studies also have demonstrated high negative predictive values in cases with normal findings.1
When defects seen or suspected on routine obstetric ultrasound are then confirmed and diagnosed with detailed fetal echocardiography, women are counseled about outcomes, management options, and mortality – and some patients will choose to terminate their pregnancies.
Psychologically, for the mother, earlier termination is less traumatic. A cross-sectional study of 254 women conducted 2-7 years after pregnancy termination for fetal anomalies found that advanced gestational age at termination was associated with higher levels of grief and posttraumatic stress symptoms, and that long-term psychological morbidity was rare when termination occurred before 14 weeks’ gestation.2 Others studies have shown similar results, with grief and posttraumatic stress time shorter with earlier termination.
First-trimester termination also involves significantly less maternal morbidity and risk, as shown in a retrospective study of 844 patients who underwent a termination of pregnancy after a positive amniocentesis or chorionic villus sampling. Hemorrhages, transfusions, infections, and other complications were significantly higher in second-trimester terminations than in earlier terminations.3
Early fetal heart evaluation can reassure high-risk patients – and low-risk patients as well – when a normal four-chamber heart and great arteries are seen. And when defects are spotted, early evaluation allows appropriate time to test for associated chromosomal abnormalities and genetic syndromes, which in turn improves management. It also gives patients and providers more time to plan and prepare for delivery, surgery, and other specific needs at delivery and after birth.
In our fetal heart program, patients are cared for by a multidisciplinary team of perinatologists with special expertise in the fetal heart, geneticists, cardiologists, cardiac surgeons, and neonatologists. Perioperative outcomes are improved when CHDs are diagnosed prenatally. One meta-analysis showed that prenatal diagnosis reduced the risk of death prior to planned cardiac surgery by about one-fourth relative to patients with a comparable postnatal diagnosis.4
Prenatal diagnosis appears to have generally been improving, although rates remain too low overall. According to the National Institute for Cardiovascular Outcomes Research, which collects data from centers across the United Kingdom and Republic of Ireland, prenatal detection rates of CHDs requiring a procedure in the first year of life moved from about 25% in 2004-2005 to just over 50% between 2010 and 2016.5 More complex lesions, such as hypoplastic left heart syndrome, were more likely to be detected prenatally (80%).
Trends in the United States appear to be similar. A study utilizing the Society of Thoracic Surgeons Congenital Heart Surgery Database found that prenatal detection increased from 26% in 2006 to 42% in 2012.6
A first-trimester evaluation cannot replace the second-trimester echocardiography that currently is performed for high-risk patients, because a small percentage of CHDs – aortic coarctation, valve stenosis, mild tetralogy of Fallot, and hypoplastic left heart, for instance – have the potential to evolve past the first trimester. High-risk patients whose first-trimester evaluations are normal still should undergo another evaluation at 18-20 weeks. The fetal heart completes its embryologic development over the first 8 weeks of gestation, and the majority of CHDs are present at the time of the first-trimester screening (11-14 weeks).
Early evaluation of the fetal heart does not appear to be impacted by obesity. We compared the early evaluation of fetal heart landmarks using two-dimensional sonography with color/power Doppler in obese and nonobese women and found that there were no significant differences in experienced sonographers’ ability to evaluate the four-chamber view, outflow tract relationship, and transverse arches views.
In about 6% of obese women, the evaluation at 11-14 weeks’ gestation required additional imaging with transvaginal sonography. The chances of needing transvaginal ultrasound rose as body mass index rose.1 The median scan time was only 5 minutes longer in the obese group, however, so there is no reason that obesity should be a contraindication to look at the fetal heart.
In fact, it is extremely important that we do early fetal heart evaluations in women who are obese, because the risk of having a fetus with CHD is increasingly being found to be higher in obese women, and because fetal heart assessment with transvaginal ultrasound is an option only in early gestation, when the fetal heart is within the depth of penetration of the vaginal probe. With advancing gestational age, a combined abdominal/transvaginal approach becomes increasingly difficult. Our study also demonstrated a dose-response relationship between maternal obesity and CHD risk.
Preexisting diabetes mellitus, which can occur in conjunction with obesity, has been found to increase the risk for all types of CHDs, especially conotruncal abnormalities. While the pathophysiology is not completely understood, elevated oxidative stress is believed to be the primary trigger.7
First-trimester echocardiography benefits
Patients referred to our fetal heart program for detailed first-trimester fetal heart evaluation – again, a significant number of whom have been found on standard 2-D ultrasound to have increased nuchal translucency thickness or other abnormalities – undergo a four-dimensional fetal echocardiographic technique that utilizes spatiotemporal image correlation and tomographic ultrasound imaging display (STIC-TUI echo) along with color Doppler. The heart is swept from top to bottom in about 10 seconds, and tomographic ultrasound imaging is used offline, after the patient leaves, to develop volume datasets that simultaneously display multiple cross-sectional images.
This method has been implemented into our routine scan at the first trimester as well, and all of our staff have been trained to perform it. Obtaining STIC-TUI by color Doppler allows us to assess all of the important landmarks of the cardiac anatomy in one picture.
In a prospective study of 164 fetuses from 152 patients, we found that first-trimester STIC-TUI echo had 91% sensitivity and 100% specificity for the detection of CHD. Most anomalies were evident in the four-chamber view plane of the TUI display, and the rest were diagnosed in the outflow tract planes. Two cases of CHD missed by this first-trimester evaluation were diagnosed on second-trimester echo and neither involved a major CHD.8
Dr. Turan is associate professor of obstetrics, gynecology, and reproductive sciences, and director of the fetal heart program at the University of Maryland, Baltimore.
References
1. J Ultrasound Med. 2019 May;38(5):1269-77.
2. Prenat Diagn. 2005 Mar;25(3):253-60.
3. J Perinat Med. 2018 May 24;46(4):373-8.
4. Ultrasound Obstet Gynecol. 2015 Jun;45(6):631-8.
5. National Congenital Heart Disease Audit Report 2013-2016.
6. Pediatrics. 2015. doi: 10.1542/peds.2014-3783.
7. Echocardiography. 2018 Feb;35(2):244-57.
8. Ultrasound Obstet Gynecol. 2014 Nov;44(5):562-7.
The fetal heart typically is examined during the routine 18-20 week obstetric ultrasound screening, and pregnancies with abnormalities on this routine scan are referred for detailed fetal echocardiography. Per multiple practice guidelines, patients deemed to be at high risk of congenital heart defects (CHDs) are referred for fetal echocardiography as well between 18 and 24 weeks’ gestation.
However, with technological advancements in ultrasound, it is possible for obstetricians to detect many major CHDs well before 16 weeks’ gestation. First-trimester fetal heart assessment – and early detection of CHDs – has numerous advantages: It enables early genetic testing, early decision making about continuation or termination of pregnancy, and earlier planning for appropriate management during and after pregnancy. Perioperative outcomes are improved.
At least 75% of CHDs occur in pregnancies with no identifiable maternal, familial, or fetal risk factors. It only seems fitting, therefore, that we check the structure of the fetal heart in all women at the time of their first-trimester screening and sonography at 11-14 weeks. In addition to a determination of fetal viability and gestational age, nuchal translucency measurement, and a check of basic anatomy, .
The value of early detection
Women who have diabetes, congenital defects, in vitro fertilization pregnancies, twin and multiple pregnancies, and certain medication and drug exposures are at high risk for their fetus having a CHD and should undergo fetal echocardiography. Lupus, Sjögren’s, and other medical disorders also are risk factors, as are abnormal biochemical test results.
During the last 10 years, the first-trimester fetal heart evaluation has been performed for all patients who come for a first-trimester screening scan at the University of Maryland’s fetal heart program, part of the Center for Advanced Fetal Care. Approximately 45% of indications for detailed first-trimester fetal heart evaluation have been driven by maternal history, and almost 40% by abnormal basic first-trimester ultrasound findings such as increased nuchal translucency, tricuspid regurgitation, abnormal ductus venosus blood flow, and other structural anomalies.
An estimated 50%-60% of serious cardiac malformations can be detected with a four-chamber heart view during routine first-trimester ultrasound. When the outflow tract relationship and three-vessel views also are examined in the first trimester – as is now recommended in guidelines for second-trimester protocols – an estimated 85%-95% of major CHDs can be detected. One should see the great arteries originating from the left and right sides and crisscrossing each other by a transabdominal scan, or by a transvaginal scan if the transabdominal approach fails to show these features of the fetal heart.
Early sonography not only has been shown to have a high sensitivity but also a specificity of greater than 95% in identifying CHDs. Multiple studies also have demonstrated high negative predictive values in cases with normal findings.1
When defects seen or suspected on routine obstetric ultrasound are then confirmed and diagnosed with detailed fetal echocardiography, women are counseled about outcomes, management options, and mortality – and some patients will choose to terminate their pregnancies.
Psychologically, for the mother, earlier termination is less traumatic. A cross-sectional study of 254 women conducted 2-7 years after pregnancy termination for fetal anomalies found that advanced gestational age at termination was associated with higher levels of grief and posttraumatic stress symptoms, and that long-term psychological morbidity was rare when termination occurred before 14 weeks’ gestation.2 Others studies have shown similar results, with grief and posttraumatic stress time shorter with earlier termination.
First-trimester termination also involves significantly less maternal morbidity and risk, as shown in a retrospective study of 844 patients who underwent a termination of pregnancy after a positive amniocentesis or chorionic villus sampling. Hemorrhages, transfusions, infections, and other complications were significantly higher in second-trimester terminations than in earlier terminations.3
Early fetal heart evaluation can reassure high-risk patients – and low-risk patients as well – when a normal four-chamber heart and great arteries are seen. And when defects are spotted, early evaluation allows appropriate time to test for associated chromosomal abnormalities and genetic syndromes, which in turn improves management. It also gives patients and providers more time to plan and prepare for delivery, surgery, and other specific needs at delivery and after birth.
In our fetal heart program, patients are cared for by a multidisciplinary team of perinatologists with special expertise in the fetal heart, geneticists, cardiologists, cardiac surgeons, and neonatologists. Perioperative outcomes are improved when CHDs are diagnosed prenatally. One meta-analysis showed that prenatal diagnosis reduced the risk of death prior to planned cardiac surgery by about one-fourth relative to patients with a comparable postnatal diagnosis.4
Prenatal diagnosis appears to have generally been improving, although rates remain too low overall. According to the National Institute for Cardiovascular Outcomes Research, which collects data from centers across the United Kingdom and Republic of Ireland, prenatal detection rates of CHDs requiring a procedure in the first year of life moved from about 25% in 2004-2005 to just over 50% between 2010 and 2016.5 More complex lesions, such as hypoplastic left heart syndrome, were more likely to be detected prenatally (80%).
Trends in the United States appear to be similar. A study utilizing the Society of Thoracic Surgeons Congenital Heart Surgery Database found that prenatal detection increased from 26% in 2006 to 42% in 2012.6
A first-trimester evaluation cannot replace the second-trimester echocardiography that currently is performed for high-risk patients, because a small percentage of CHDs – aortic coarctation, valve stenosis, mild tetralogy of Fallot, and hypoplastic left heart, for instance – have the potential to evolve past the first trimester. High-risk patients whose first-trimester evaluations are normal still should undergo another evaluation at 18-20 weeks. The fetal heart completes its embryologic development over the first 8 weeks of gestation, and the majority of CHDs are present at the time of the first-trimester screening (11-14 weeks).
Early evaluation of the fetal heart does not appear to be impacted by obesity. We compared the early evaluation of fetal heart landmarks using two-dimensional sonography with color/power Doppler in obese and nonobese women and found that there were no significant differences in experienced sonographers’ ability to evaluate the four-chamber view, outflow tract relationship, and transverse arches views.
In about 6% of obese women, the evaluation at 11-14 weeks’ gestation required additional imaging with transvaginal sonography. The chances of needing transvaginal ultrasound rose as body mass index rose.1 The median scan time was only 5 minutes longer in the obese group, however, so there is no reason that obesity should be a contraindication to look at the fetal heart.
In fact, it is extremely important that we do early fetal heart evaluations in women who are obese, because the risk of having a fetus with CHD is increasingly being found to be higher in obese women, and because fetal heart assessment with transvaginal ultrasound is an option only in early gestation, when the fetal heart is within the depth of penetration of the vaginal probe. With advancing gestational age, a combined abdominal/transvaginal approach becomes increasingly difficult. Our study also demonstrated a dose-response relationship between maternal obesity and CHD risk.
Preexisting diabetes mellitus, which can occur in conjunction with obesity, has been found to increase the risk for all types of CHDs, especially conotruncal abnormalities. While the pathophysiology is not completely understood, elevated oxidative stress is believed to be the primary trigger.7
First-trimester echocardiography benefits
Patients referred to our fetal heart program for detailed first-trimester fetal heart evaluation – again, a significant number of whom have been found on standard 2-D ultrasound to have increased nuchal translucency thickness or other abnormalities – undergo a four-dimensional fetal echocardiographic technique that utilizes spatiotemporal image correlation and tomographic ultrasound imaging display (STIC-TUI echo) along with color Doppler. The heart is swept from top to bottom in about 10 seconds, and tomographic ultrasound imaging is used offline, after the patient leaves, to develop volume datasets that simultaneously display multiple cross-sectional images.
This method has been implemented into our routine scan at the first trimester as well, and all of our staff have been trained to perform it. Obtaining STIC-TUI by color Doppler allows us to assess all of the important landmarks of the cardiac anatomy in one picture.
In a prospective study of 164 fetuses from 152 patients, we found that first-trimester STIC-TUI echo had 91% sensitivity and 100% specificity for the detection of CHD. Most anomalies were evident in the four-chamber view plane of the TUI display, and the rest were diagnosed in the outflow tract planes. Two cases of CHD missed by this first-trimester evaluation were diagnosed on second-trimester echo and neither involved a major CHD.8
Dr. Turan is associate professor of obstetrics, gynecology, and reproductive sciences, and director of the fetal heart program at the University of Maryland, Baltimore.
References
1. J Ultrasound Med. 2019 May;38(5):1269-77.
2. Prenat Diagn. 2005 Mar;25(3):253-60.
3. J Perinat Med. 2018 May 24;46(4):373-8.
4. Ultrasound Obstet Gynecol. 2015 Jun;45(6):631-8.
5. National Congenital Heart Disease Audit Report 2013-2016.
6. Pediatrics. 2015. doi: 10.1542/peds.2014-3783.
7. Echocardiography. 2018 Feb;35(2):244-57.
8. Ultrasound Obstet Gynecol. 2014 Nov;44(5):562-7.
The fetal heart typically is examined during the routine 18-20 week obstetric ultrasound screening, and pregnancies with abnormalities on this routine scan are referred for detailed fetal echocardiography. Per multiple practice guidelines, patients deemed to be at high risk of congenital heart defects (CHDs) are referred for fetal echocardiography as well between 18 and 24 weeks’ gestation.
However, with technological advancements in ultrasound, it is possible for obstetricians to detect many major CHDs well before 16 weeks’ gestation. First-trimester fetal heart assessment – and early detection of CHDs – has numerous advantages: It enables early genetic testing, early decision making about continuation or termination of pregnancy, and earlier planning for appropriate management during and after pregnancy. Perioperative outcomes are improved.
At least 75% of CHDs occur in pregnancies with no identifiable maternal, familial, or fetal risk factors. It only seems fitting, therefore, that we check the structure of the fetal heart in all women at the time of their first-trimester screening and sonography at 11-14 weeks. In addition to a determination of fetal viability and gestational age, nuchal translucency measurement, and a check of basic anatomy, .
The value of early detection
Women who have diabetes, congenital defects, in vitro fertilization pregnancies, twin and multiple pregnancies, and certain medication and drug exposures are at high risk for their fetus having a CHD and should undergo fetal echocardiography. Lupus, Sjögren’s, and other medical disorders also are risk factors, as are abnormal biochemical test results.
During the last 10 years, the first-trimester fetal heart evaluation has been performed for all patients who come for a first-trimester screening scan at the University of Maryland’s fetal heart program, part of the Center for Advanced Fetal Care. Approximately 45% of indications for detailed first-trimester fetal heart evaluation have been driven by maternal history, and almost 40% by abnormal basic first-trimester ultrasound findings such as increased nuchal translucency, tricuspid regurgitation, abnormal ductus venosus blood flow, and other structural anomalies.
An estimated 50%-60% of serious cardiac malformations can be detected with a four-chamber heart view during routine first-trimester ultrasound. When the outflow tract relationship and three-vessel views also are examined in the first trimester – as is now recommended in guidelines for second-trimester protocols – an estimated 85%-95% of major CHDs can be detected. One should see the great arteries originating from the left and right sides and crisscrossing each other by a transabdominal scan, or by a transvaginal scan if the transabdominal approach fails to show these features of the fetal heart.
Early sonography not only has been shown to have a high sensitivity but also a specificity of greater than 95% in identifying CHDs. Multiple studies also have demonstrated high negative predictive values in cases with normal findings.1
When defects seen or suspected on routine obstetric ultrasound are then confirmed and diagnosed with detailed fetal echocardiography, women are counseled about outcomes, management options, and mortality – and some patients will choose to terminate their pregnancies.
Psychologically, for the mother, earlier termination is less traumatic. A cross-sectional study of 254 women conducted 2-7 years after pregnancy termination for fetal anomalies found that advanced gestational age at termination was associated with higher levels of grief and posttraumatic stress symptoms, and that long-term psychological morbidity was rare when termination occurred before 14 weeks’ gestation.2 Others studies have shown similar results, with grief and posttraumatic stress time shorter with earlier termination.
First-trimester termination also involves significantly less maternal morbidity and risk, as shown in a retrospective study of 844 patients who underwent a termination of pregnancy after a positive amniocentesis or chorionic villus sampling. Hemorrhages, transfusions, infections, and other complications were significantly higher in second-trimester terminations than in earlier terminations.3
Early fetal heart evaluation can reassure high-risk patients – and low-risk patients as well – when a normal four-chamber heart and great arteries are seen. And when defects are spotted, early evaluation allows appropriate time to test for associated chromosomal abnormalities and genetic syndromes, which in turn improves management. It also gives patients and providers more time to plan and prepare for delivery, surgery, and other specific needs at delivery and after birth.
In our fetal heart program, patients are cared for by a multidisciplinary team of perinatologists with special expertise in the fetal heart, geneticists, cardiologists, cardiac surgeons, and neonatologists. Perioperative outcomes are improved when CHDs are diagnosed prenatally. One meta-analysis showed that prenatal diagnosis reduced the risk of death prior to planned cardiac surgery by about one-fourth relative to patients with a comparable postnatal diagnosis.4
Prenatal diagnosis appears to have generally been improving, although rates remain too low overall. According to the National Institute for Cardiovascular Outcomes Research, which collects data from centers across the United Kingdom and Republic of Ireland, prenatal detection rates of CHDs requiring a procedure in the first year of life moved from about 25% in 2004-2005 to just over 50% between 2010 and 2016.5 More complex lesions, such as hypoplastic left heart syndrome, were more likely to be detected prenatally (80%).
Trends in the United States appear to be similar. A study utilizing the Society of Thoracic Surgeons Congenital Heart Surgery Database found that prenatal detection increased from 26% in 2006 to 42% in 2012.6
A first-trimester evaluation cannot replace the second-trimester echocardiography that currently is performed for high-risk patients, because a small percentage of CHDs – aortic coarctation, valve stenosis, mild tetralogy of Fallot, and hypoplastic left heart, for instance – have the potential to evolve past the first trimester. High-risk patients whose first-trimester evaluations are normal still should undergo another evaluation at 18-20 weeks. The fetal heart completes its embryologic development over the first 8 weeks of gestation, and the majority of CHDs are present at the time of the first-trimester screening (11-14 weeks).
Early evaluation of the fetal heart does not appear to be impacted by obesity. We compared the early evaluation of fetal heart landmarks using two-dimensional sonography with color/power Doppler in obese and nonobese women and found that there were no significant differences in experienced sonographers’ ability to evaluate the four-chamber view, outflow tract relationship, and transverse arches views.
In about 6% of obese women, the evaluation at 11-14 weeks’ gestation required additional imaging with transvaginal sonography. The chances of needing transvaginal ultrasound rose as body mass index rose.1 The median scan time was only 5 minutes longer in the obese group, however, so there is no reason that obesity should be a contraindication to look at the fetal heart.
In fact, it is extremely important that we do early fetal heart evaluations in women who are obese, because the risk of having a fetus with CHD is increasingly being found to be higher in obese women, and because fetal heart assessment with transvaginal ultrasound is an option only in early gestation, when the fetal heart is within the depth of penetration of the vaginal probe. With advancing gestational age, a combined abdominal/transvaginal approach becomes increasingly difficult. Our study also demonstrated a dose-response relationship between maternal obesity and CHD risk.
Preexisting diabetes mellitus, which can occur in conjunction with obesity, has been found to increase the risk for all types of CHDs, especially conotruncal abnormalities. While the pathophysiology is not completely understood, elevated oxidative stress is believed to be the primary trigger.7
First-trimester echocardiography benefits
Patients referred to our fetal heart program for detailed first-trimester fetal heart evaluation – again, a significant number of whom have been found on standard 2-D ultrasound to have increased nuchal translucency thickness or other abnormalities – undergo a four-dimensional fetal echocardiographic technique that utilizes spatiotemporal image correlation and tomographic ultrasound imaging display (STIC-TUI echo) along with color Doppler. The heart is swept from top to bottom in about 10 seconds, and tomographic ultrasound imaging is used offline, after the patient leaves, to develop volume datasets that simultaneously display multiple cross-sectional images.
This method has been implemented into our routine scan at the first trimester as well, and all of our staff have been trained to perform it. Obtaining STIC-TUI by color Doppler allows us to assess all of the important landmarks of the cardiac anatomy in one picture.
In a prospective study of 164 fetuses from 152 patients, we found that first-trimester STIC-TUI echo had 91% sensitivity and 100% specificity for the detection of CHD. Most anomalies were evident in the four-chamber view plane of the TUI display, and the rest were diagnosed in the outflow tract planes. Two cases of CHD missed by this first-trimester evaluation were diagnosed on second-trimester echo and neither involved a major CHD.8
Dr. Turan is associate professor of obstetrics, gynecology, and reproductive sciences, and director of the fetal heart program at the University of Maryland, Baltimore.
References
1. J Ultrasound Med. 2019 May;38(5):1269-77.
2. Prenat Diagn. 2005 Mar;25(3):253-60.
3. J Perinat Med. 2018 May 24;46(4):373-8.
4. Ultrasound Obstet Gynecol. 2015 Jun;45(6):631-8.
5. National Congenital Heart Disease Audit Report 2013-2016.
6. Pediatrics. 2015. doi: 10.1542/peds.2014-3783.
7. Echocardiography. 2018 Feb;35(2):244-57.
8. Ultrasound Obstet Gynecol. 2014 Nov;44(5):562-7.