Review

Authors: Cheryl Mei Jun Tan, Adam James Lewandowski

Formation of the human heart involves complex biological signals, interactions, specification of myocardial progenitor cells, and heart tube looping. To facilitate survival in the hypoxemic intrauterine environment, the fetus possesses structural, physiological, and functional cardiovascular adaptations that are fundamentally different from the neonate. At birth, upon separation from the placental circulation, the neonatal cardiovascular system takes over responsibility of vital processes for survival. The transition from the fetal to neonatal circulation is considered to be a period of intricate physiological, anatomical, and biochemical changes in the cardiovascular system. With a successful cardiopulmonary transition to the extrauterine environment, the fetal shunts are functionally modified or eliminated, enabling independent life. Investigations using medical imaging tools such as ultrasound and magnetic resonance imaging have helped to define normal and abnormal patterns of cardiac remodeling both in utero and ex utero. This has not only allowed for a better understanding of how congenital cardiac malformations alter the hemodynamic transition to the extrauterine environment but also how other more common complications during pregnancy including intrauterine growth restriction, preeclampsia, and preterm delivery adversely affect offspring cardiac remodeling during this early transitional period. This review article describes key cardiac progenitors involved in embryonic heart development; the cellular, physiological, and anatomical changes during the transition from fetal to neonatal circulation; as well as the unique impact that different pregnancy complications have on cardiac remodeling.

Topics: Female; Fetal Development; Fetal Heart; Heart; Hemodynamics; Humans; Infant, Newborn; Pregnancy

PubMed: 31533099
DOI: 10.1159/000501906

Meta-Analysis

Authors: J N Karim, E Bradburn, N Roberts...

OBJECTIVES

To determine the diagnostic accuracy of ultrasound at 11-14 weeks' gestation in the detection of fetal cardiac abnormalities and to evaluate factors that impact the detection rate.

METHODS

This was a systematic review of studies evaluating the diagnostic accuracy of ultrasound in the detection of fetal cardiac anomalies at 11-14 weeks' gestation, performed by two independent reviewers. An electronic search of four databases (MEDLINE, EMBASE, Web of Science Core Collection and The Cochrane Library) was conducted for studies published between January 1998 and July 2020. Prospective and retrospective studies evaluating pregnancies at any prior level of risk and in any healthcare setting were eligible for inclusion. The reference standard used was the detection of a cardiac abnormality on postnatal or postmortem examination. Data were extracted from the included studies to populate 2 × 2 tables. Meta-analysis was performed using a random-effects model in order to determine the performance of first-trimester ultrasound in the detection of major cardiac abnormalities overall and of individual types of cardiac abnormality. Data were analyzed separately for high-risk and non-high-risk populations. Preplanned secondary analyses were conducted in order to assess factors that may impact screening performance, including the imaging protocol used for cardiac assessment (including the use of color-flow Doppler), ultrasound modality, year of publication and the index of sonographer suspicion at the time of the scan. Risk of bias and quality assessment were undertaken for all included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.

RESULTS

The electronic search yielded 4108 citations. Following review of titles and abstracts, 223 publications underwent full-text review, of which 63 studies, reporting on 328 262 fetuses, were selected for inclusion in the meta-analysis. In the non-high-risk population (45 studies, 306 872 fetuses), 1445 major cardiac anomalies were identified (prevalence, 0.41% (95% CI, 0.39-0.43%)). Of these, 767 were detected on first-trimester ultrasound examination of the heart and 678 were not detected. First-trimester ultrasound had a pooled sensitivity of 55.80% (95% CI, 45.87-65.50%), specificity of 99.98% (95% CI, 99.97-99.99%) and positive predictive value of 94.85% (95% CI, 91.63-97.32%) in the non-high-risk population. The cases diagnosed in the first trimester represented 63.67% (95% CI, 54.35-72.49%) of all antenatally diagnosed major cardiac abnormalities in the non-high-risk population. In the high-risk population (18 studies, 21 390 fetuses), 480 major cardiac anomalies were identified (prevalence, 1.36% (95% CI, 1.20-1.52%)). Of these, 338 were detected on first-trimester ultrasound examination and 142 were not detected. First-trimester ultrasound had a pooled sensitivity of 67.74% (95% CI, 55.25-79.06%), specificity of 99.75% (95% CI, 99.47-99.92%) and positive predictive value of 94.22% (95% CI, 90.22-97.22%) in the high-risk population. The cases diagnosed in the first trimester represented 79.86% (95% CI, 69.89-88.25%) of all antenatally diagnosed major cardiac abnormalities in the high-risk population. The imaging protocol used for examination was found to have an important impact on screening performance in both populations (P < 0.0001), with a significantly higher detection rate observed in studies using at least one outflow-tract view or color-flow Doppler imaging (both P < 0.0001). Different types of cardiac anomaly were not equally amenable to detection on first-trimester ultrasound.

CONCLUSIONS

First-trimester ultrasound examination of the fetal heart allows identification of over half of fetuses affected by major cardiac pathology. Future first-trimester screening programs should follow structured anatomical assessment protocols and consider the introduction of outflow-tract views and color-flow Doppler imaging, as this would improve detection rates of fetal cardiac pathology. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Topics: Female; Fetal Diseases; Fetal Heart; Gestational Age; Heart Defects, Congenital; Humans; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Retrospective Studies; Ultrasonography, Prenatal

PubMed: 34369613
DOI: 10.1002/uog.23740

Meta-Analysis

Authors: A L Depla, L De Wit, T J Steenhuis...

OBJECTIVE

Maternal diabetes in pregnancy is associated with structural anomalies of the fetal heart, as well as hypertrophy and functional impairment. This systematic review and meta-analysis aimed to estimate the effect of maternal diabetes on fetal cardiac function as measured by prenatal echocardiography.

METHODS

We performed a search of the EMBASE, PubMed and The Cochrane Library databases, from inception to 4 July 2019, for studies evaluating fetal cardiac function using echocardiography in pregnancies affected by diabetes compared with uncomplicated pregnancies. Outcome measures were cardiac hypertrophy and diastolic, systolic and overall cardiac function as assessed by various ultrasound parameters. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Data on interventricular septal (IVS) thickness, myocardial performance index (MPI) and E/A ratio were pooled for the meta-analysis using random-effects models. For pregnancies with diabetes, results were reported overall and according to whether diabetes was pregestational (PDM) or gestational (GDM). Results were also stratified according to the trimester in which fetal cardiac assessment was performed.

RESULTS

Thirty-nine studies were included, comprising data for 2276 controls and 1925 women with pregnancy affected by diabetes mellitus (DM). Of these, 1120 had GDM, 671 had PDM and in 134 cases diabetes type was not specified. Fetal cardiac hypertrophy was more prevalent in diabetic pregnancies than in non-diabetic controls in 21/26 studies, and impaired diastolic function was observed in diabetic pregnancies in 22/28 studies. The association between DM and systolic function was inconsistent, with 10/25 studies reporting no difference between cases and controls, although more recent studies measuring cardiac deformation, i.e. strain, did show decreased systolic function in diabetic pregnancies. Of the studies measuring overall fetal cardiac function, the majority (14/21) found significant impairment in diabetic pregnancies. Results were similar when stratified according to GDM or PDM. These effects were already present in the first trimester, but were most profound in the third trimester. Meta-analysis of studies performed in the third trimester showed, compared with controls, increased IVS thickness in both PDM (mean difference, 0.75 mm (95% CI, 0.56-0.94 mm)) and GDM (mean difference, 0.65 mm (95% CI, 0.39-0.91 mm)) pregnancies, decreased E/A ratio in PDM pregnancies (mean difference, -0.09 (95% CI, -0.15 to -0.03)), no difference in E/A ratio in GDM pregnancies (mean difference, -0.01 (95% CI, -0.02 to 0.01)) and no difference in MPI in either PDM (mean difference, 0.04 (95% CI, -0.01 to 0.09)) or GDM (mean difference, 0.03 (95% CI, -0.01 to 0.06)) pregnancies.

CONCLUSIONS

The findings of this review show that maternal diabetes is associated with fetal cardiac hypertrophy, diastolic dysfunction and overall impaired myocardial performance on prenatal ultrasound, irrespective of whether diabetes is pregestational or gestational. Further studies are needed to demonstrate the relationship with long-term outcomes. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Topics: Adult; Diabetes, Gestational; Echocardiography; Female; Fetal Heart; Humans; Pregnancy; Pregnancy Trimesters; Pregnancy in Diabetics; Ultrasonography, Prenatal

PubMed: 32730637
DOI: 10.1002/uog.22163

Review

Authors: Emma J Agnew, Jessica R Ivy, Sarah J Stock...

Glucocorticoids are essential in mammals to mature fetal organs and tissues in order to survive after birth. Hence, antenatal glucocorticoid treatment (termed antenatal corticosteroid therapy) can be life-saving in preterm babies and is commonly used in women at risk of preterm birth. While the effects of glucocorticoids on lung maturation have been well described, the effects on the fetal heart remain less clear. Experiments in mice have shown that endogenous glucocorticoid action is required to mature the fetal heart. However, whether the potent synthetic glucocorticoids used in antenatal corticosteroid therapy have similar maturational effects on the fetal heart is less clear. Moreover, antenatal corticosteroid therapy may increase the risk of cardiovascular disease in adulthood. Here, we present a narrative review of the evidence relating to the effects of antenatal glucocorticoid action on the fetal heart and discuss the implications for antenatal corticosteroid therapy.

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adrenal Cortex Hormones; Animals; Fetal Development; Fetal Heart; Glucocorticoids; Humans; Premature Birth

PubMed: 29720513
DOI: 10.1530/JME-18-0077

Authors: T U K Dilek, A Oktay, E G Aygun...

BACKGROUND

Cardiac heart defects affect nearly 6-12 per 1000 live births in the general population and are more frequent than common trisomies.

AIM

To assess the efficacy and technical limitations of first-trimester fetal heart evaluation in the 11-14-weeks' scan and comparison with the second-trimester anatomical exam by ultrasound.

MATERIAL AND METHOD

Between April 2015 and July 2020, medical records and ultrasound data of 3295 pregnancies who underwent first-trimester fetal anatomy exams by ultrasound were reviewed retrospectively. All ultrasound exams were performed by the same two operators (TUKD, OP) with transabdominal transducers. Fetal situs, four-chamber view, outflow tracts, and three-vessel trachea view are the cornerstones of first-trimester fetal heart examination. Conventional grayscale mode and high-definition power Doppler mode were utilized. The same operators re-examined all cases between the 18 and 23 weeks of gestation by ISUOG guidelines.

RESULTS

We performed a combined transvaginal and transabdominal approach for only 101 cases (3.06%). The mean maternal age was 31.28 ± 4.43, the median gestational age at the first-trimester ultrasound exam was 12.4 weeks, and the median CRL was 61.87 mm (range was 45.1-84 mm). Even combined approach situs, cardiac axis, and four-chamber view could not be visualized optimally in 28 cases (0.7%). Outflow tracts were visualized separately in 80% (2636 in 3295) cases. Three vessel-trachea views were obtained in 85.4% (2814 in 3295) cases by high-definition Doppler mode. There were 47 fetuses with cardiac defects in 3295 pregnancies with the known pregnancy outcome. Ten cases had abnormal karyotype results. Thirty-two fetuses with cardiac anomalies (9.7 in 1000 pregnancies) were detected in the first-trimester examination, and the remaining 15 (4.55 in 1000 pregnancies) cases were diagnosed in the second-trimester examination. The prevalence of congenital cardiac anomalies was 14.25 in 1000 pregnancies. Fifteen cases were missed in the first-trimester exam. Also, ten fetuses which had abnormal cardiac findings in the first-trimester exam were not confirmed in the second-trimester exam. Sensitivity, specificity, positive, and negative predictive values were calculated as 65.3%, 99.7%, 66.8%, and 99.67%, respectively.

CONCLUSION

Late first-trimester examination of the fetus is feasible and allows earlier detection of many structural abnormalities of the fetus, including congenital heart defects. Suspicious and isolated cardiac abnormal findings should be re-examined and confirmed in the second-trimester exam. Previous abdominal surgery, high BMI, and subtle cardiac defects can cause missed cardiac abnormalities.

Topics: Female; Pregnancy; Humans; Infant; Pregnancy Trimester, Second; Retrospective Studies; Ultrasonography, Prenatal; Pregnancy Trimester, First; Heart Defects, Congenital; Fetal Heart; Gestational Age

PubMed: 37470654
DOI: 10.4103/njcp.njcp_757_22

Authors: L K Hornberger

Maternal diabetes mellitus significantly affects the fetal heart and fetal-placental circulation in both structure and function. The influence of pre-conceptional diabetes begins during embryonic development in the first trimester, with altered cardiac morphogenesis and placental development. It continues to have an influence on the fetal circulation through the second and third trimesters and into the perinatal and neonatal period.

Topics: Female; Fetal Heart; Heart Defects, Congenital; Humans; Myocardium; Placental Circulation; Pregnancy; Pregnancy in Diabetics

PubMed: 16698822
DOI: 10.1136/hrt.2005.083840

Authors: Lami Yeo, Roberto Romero

Congenital heart disease (CHD) is the leading organ-specific birth defect, as well as the leading cause of infant morbidity and mortality from congenital malformations. Therefore, a comprehensive screening examination of the fetal heart should be performed in all women to maximize the detection of CHD. Four-dimensional sonography with spatiotemporal image correlation (STIC) technology displays a cine loop of a complete single cardiac cycle in motion. A novel method known as Fetal Intelligent Navigation Echocardiography (or FINE) was previously developed to interrogate STIC volume datasets using "intelligent navigation" technology. Such method allows the automatic display of nine standard fetal echocardiography views required to diagnose most cardiac defects. FINE considerably simplifies fetal cardiac examinations and reduces operator dependency. It has both high sensitivity and specificity for the detection of CHD. Indeed, FINE has been integrated into several commercially available ultrasound platforms.Recently, eight novel and advanced features have been developed for the FINE method and they will be described herein. Such features can be categorized based upon their broad goals. The first goal is to simplify FINE further, and consists of the following features: (1) (or ); (2) ; (3) ; (4) volume; and (5) The second goal is to allow quantitative measurements to be performed on the cardiac views generated by FINE: (6) and (7) Finally, the last goal is to improve the success of obtaining fetal echocardiography view(s); and consists of (8) .

Topics: Biometry; Echocardiography; Echocardiography, Four-Dimensional; Female; Fetal Heart; Heart Defects, Congenital; Humans; Pregnancy; Ultrasonography, Prenatal

PubMed: 32375528
DOI: 10.1080/14767058.2020.1759538

Review

Authors: Nathalie Jeanne Bravo-Valenzuela, Alberto Borges Peixoto, Luciano Marcondes Nardozza...

In recent years, fetal echocardiography has been used for the screening and diagnosis of anatomical heart defects and for the detailed study of fetal cardiac function. This method is characterized by its easy implementation and good reproducibility, allowing the diagnosis of myocardial dysfunction even in its subclinical phase. The functional assessment of the fetal heart should be routinely performed in fetuses with congenital heart disease and those without anatomical malformation. Several extra-cardiac conditions may alter fetal cardiac function, by increased placental resistance, volume overload or hyperdynamic circulation, compression, or maternal systemic disease with involvement of the fetal myocardium. This review addresses the main ultrasound techniques and various Doppler echocardiographic parameters available for the analysis of fetal heart function, and correlates them with clinical applicability. Various parameters available for the assessment of fetal myocardium, including those that evaluate atrial dynamics, can be used in this analysis and should be selected considering specific conditions.

Topics: Female; Fetal Heart; Heart Defects, Congenital; Humans; Pregnancy; Reproducibility of Results; Ultrasonography, Prenatal

PubMed: 28180202
DOI: 10.11152/mu-934

Authors: Mariyan J Jeyarajah, Violet S Patterson, Gargi Jaju Bhattad...

Congenital heart defects are leading causes of neonatal mortality and are often associated with placental abnormalities, but mechanisms linking placenta and heart development are poorly understood. Herein, we investigated a potential signaling network connecting the placenta and nascent heart in mice. We found that fetal hearts exposed to media conditioned by placental tissue or differentiated wild-type trophoblast stem (TS) cells, but not undifferentiated TS cells, showed increased heart rate and epicardial cell outgrowth. This effect was not observed when hearts were exposed to media from TS cells lacking OVO-Like 2, a transcription factor required for trophoblast differentiation and placental development. Trophoblasts released abundant extracellular vesicles into media, and these vesicles were sufficient to mediate cardio-promoting effects. Our findings provide a potential mechanism whereby the placenta communicates with the fetal heart to promote cardiac morphogenesis, and offers insight into the link between poor placentation and a higher incidence of heart defects.

Topics: Animals; Extracellular Vesicles; Female; Pregnancy; Myocytes, Cardiac; Mice; Placenta; Fetal Heart; Cell Differentiation; Trophoblasts; Mice, Inbred C57BL

PubMed: 39363116
DOI: 10.1038/s42003-024-06938-4

Authors: J Rychik

Topics: Atrial Septum; Fetal Heart; Foramen Ovale; Humans

PubMed: 33259096
DOI: 10.1002/uog.23535