The Value of Fetal Echocardiography for Early Detection of Congenital Heart Defects: A Report of our Experience in a Great Referral Heart Center in Iran

Background: Prenatal diagnosis of cardiac defects in fetus is of paramount importance to enable a better monitoring of heart defects and to allow planning a proper management. We reported our experience on fetal heart echocardiography in a great referral heart center in Iran with the approach to assessment of the diagnostic value of this tool for detecting Congenital Heart Diseases (CHDs).

Methods: This retrospective cohort study included 234 pregnant women attended at a great referral heart center in Tehran, Iran between 2012 and 2016 for heart abnormalities screening. All women were evaluated by trans-abdominal fetal echocardiography from 12 weeks of gestation to term and after birth.

Results: Fetal echocardiography showed different types of CHDs in 5.9%. CHDs detected in 9.9% of neonates by echocardiography after birth. The most common heart abnormalities detected was VSD in 4.3%. Considering echocardiography findings after birth as the reference, fetal echocardiography had a sensitivity of 92.8%, a specificity of 66.6%, a positive predictive value of 59.8%, a negative predictive value of 86.6%, and an accuracy of 84.1% for detection of heart defects.

Conclusion: Fetal heart echocardiography is a sensitive tool for detection of CHDs, but its specificity is moderate.

Congenital Heart Disease (CHD) is now identified as one of the main reasons of infant mortality at birth with a reported prevalence of 4 out of every thousand newborns [1]. Many CHDs are treatable now, but there are also complex heart anomalies that are incurable leading high mortality [2]. Therefore, prenatal diagnosis of these defects has a significant impact on the quality of care the infant needs. Because the heart is a complex organ, it can be difficult to form in the early weeks of pregnancy. Such congenital problems include the creation of hazards to the heart as well as abnormal connections between the right and left parts of the heart and eventually the malformation of the heart valves [3]. However, if timely diagnosis of these diseases in uterus, in addition to prompt treatment, pregnancy can be terminated if complicated by forensic coordination and family opinion. As an important point, because CHDs are the main cause for 40% of perinatal deaths and also for 20% of all deaths occur within the first month of life [4,5], early detection of such anomalies can significantly reduce economic burden, allow monitoring other non-cardiac molecular and structural anomalies, counsel about pregnancy management options such as termination, decide on future pregnancies as well as achieve the psychological wellbeing of the families [6]. Fetal cardiac echocardiography is one of the methods for the diagnosis of CHDs, which can examine the structure of the fetal heart and detect many major defects before birth [7]. The best time to carry out echocardiography is week 6 to 13 of gestation [8]. The main indications for performing fetal echocardiography include family history (in family or previous offspring) of CHDs, in families with parents or children who have had a history of non-cardiac congenital abnormalities, mothers with serious metabolic diseases including diabetes, phenylketonuria or lupus, history of recurrent miscarriages, history of infertility and the use of assisted reproductive methods, mothers who have a history of drug use, especially a history of nervous medication (such as lithium), pregnancy history of severe infectious diseases within pregnancy, hydrops fetalis, use of teratogenic drugs during pregnancy, abnormal ultrasound findings such as suspected cardiac or extracardiac disease, fetal heart rhythm abnormality, amniotic fluid disorders, or fetal growth retardation, or diagnosis of chromosomal diseases in the embryo [9,10]. During fetal echocardiography, it is possible to scan two- and even three-dimensional assessment of the fetal heart and its-related structures and even assess blood flow status [11]. According to the literature, the sensitivity of this tool during the embryo has been reported in the range of 60% to 100% [12-14], but this accuracy may be interacted by different parameters especially expert experience, mothers’ health condition and gestational age [15]. Herein, we report our experience on fetal echocardiography in a great referral heart center in Iran with the approach to assessment of the diagnostic value of this tool for detecting CHDs.

This retrospective cohort study included pregnant women attended at a great referral heart center in Tehran, Iran between 2012 and 2016 for heart abnormalities screening. The baseline information as well as echocardiography data of a total of 234 consecutive women was entered in an especial data registry at our center. At the first visit, all women were interviewed about medical history (such as diabetes mellitus or heart diseases), parental relationship, any disorders within gestation, medications, history of hard or difficult pregnancy, history of miscarriage, number of children, the use of pregnancy assistance devices, any inheritance or congenital disorders in the family or relatives, history of CHDs in the family, or serious systemic disorders. The births occurred outside the maternity of the hospital and twin pregnancies were considered as the exclusion criteria. Also, on admission, all subjects recommended to genetic counseling to detect any chromosomal or genetic deviations. The study was approved by the ethics committee of the Tehran University of Medical Sciences. Obstetric or morphological ultrasound was performed before the fetal echocardiography. Then all women were evaluated by trans-abdominal fetal echocardiography from 12 weeks of gestation to term and after birth. All the cardiac scan digital video-clips recorded were stored in the ultrasound equipment and subsequently collected and analyzed. The study endpoint was to first describe echocardiography findings of fetal heart and then to determine the value of fetal heart echocardiography to detect any CHD considering echocardiography assessment after birth as the diagnostic reference.

For statistical analysis, results were presented as mean ± Standard Deviation (SD) for quantitative variables and were summarized by frequency (percentage) for categorical variables. Continuous variables were compared using t test or Mann-Whitney test whenever the data did not appear to have normal distribution or when the assumption of equal variances was violated across the study groups. Categorical variables were, on the other hand, compared using chi-square test. The cross-tabulation method was used to test the value of fetal echocardiography to detect CHDs with applying the tool diagnostic accuracy assessment formulas. p ≤ 0.05 were considered statistically significant. For the statistical analysis, the statistical software SPSS version 23.0 for windows (IBM, Armonk, New York) was used.

A total of 234 pregnant women with the average gestational age of 5.96 ± 1.32 months (ranged 3 to 9 months) were evaluated. Overall, 12.8% were diabetics and history of maternal heart diseases was reported in 5.6%. Interestingly, history of abortion and still birth were found in 31.2% and 38.9% respectively. Also, 7.3% of participants had history of congenital heart disease in the family. The mean number of children currently was 1.42 ± 0.65. The average of last recorded fetal heart rate was 146.90 ± 9.85 pulses per minute that was over 160 pulses per minute in 2.5%.

Fetal echocardiography showed different types of CHDs in 14 fetuses (5.9%). The most common heart abnormalities detected was VSD in 4.3%. The others defects included ASD in 0.4%, mild thickening of aortic valve in 0.4%, turbulent flow in duct in 0.4%, and mild TR in 0.4%. In echocardiography assessment after birth, 7 cases (3.0%) were born dead and 26 cases (11.1%) were not available for evaluation. In the remaining people, CHDs detected in 20 out of 201 neonates with the prevalence rate of 9.9%. The echocardiography findings in neonates are summarized in table 2. None of the baseline variables including gestation age, medical history in mother, familial relationship, history of still birth or abortion, or history of heart disease in the family could predict CHDs assessed within early postnatal period. Considering echocardiography findings after birth as the reference, fetus echocardiography had a sensitivity of 92.8%, a specificity of 66.6%, a positive predictive value of 59.8%, a negative predictive value of 86.6% and accuracy of 84.1%.

Although the overall incidence of CHDs is estimated to be about 0.004, but confirming it among those fetus suspected to these phenomena is considerably higher. As revealed in our study, the prevalence of CHDs in those fetus suspected to CHDs was 5.9% as assessed by fetal echocardiography. In most cases, also, the found defects were also demonstrated by echocardiography after birth yielding high sensitivity, specificity and accuracy of this device for assessment of cardiac anomalies even in gestational period. Unfortunately, reviewing the literature shows no homogeneity in pooled assessment of the diagnostic value of fetal echocardiography for detection of cardiac defects. In other words, a wide range of sensitivity and specificity is expected for this tool and with this aim [16-18]. In a systematic review and meta-analysis on the published studies, the sensitivity and specificity of fetal echocardiography has been reported to be in the range of 60% to 100% probably dependent to the population-based risk stratification, scanning regimes, operator skills and severity of CHD [19]. In a recent survey on 96 neonates suspected to CHDs, the antepartum echocardiography demonstrated a sensitivity of 97.7%, a specificity of 88.9%, and accuracy of 93% in the diagnosis of congenital heart disease [20]. Bakiler AR, et al. [21] in 2007 also showed that specificity and specificity of fetal echocardiography for cardiac abnormalities were found to be 98 and 42% respectively with the positive predictive value and the negative predictive value of 90% and 93%, respectively indicating a partially low specificity. In another systematic review by Zhang, et al. [22] in 2015, the pooled sensitivity and specificity were 68.5% and 99.8% respectively showing low sensitivity. Interestingly, the sensitivity was affected by the age of pregnancy so that the pooled sensitivity of the prenatal echocardiographic diagnosis of CHD during the first trimester, second trimester, the second to third trimester were 60.3%, 60.9%, and 77.4%, respectively. Summing the results indicates that although in our study, we showed no significant association between the baseline variables such as mother’s clinical condition and history of complicated pregnancy, but it seems that the diagnostic performance of this tool to assess CHDs in fetus is dependent to various factors that might be divergent in different populations. Overall, our experience on detecting CHDs in our population seemed to be successful with acceptable sensitivity and specificity.

It should be pointed that early and minutely detection of CHDs particularly before birth is very necessary with respect to planning for screening among family members and relatives, for planning a choice treatment intervention with the goal of obtaining an infant with the least cardiac complications and physical disability. Of course, the main indications for fetus echocardiography should be also considered. As a rule, any suspicion to excising heart and vascular defects is routinely considered for early echocardiography assessment. In this regard, some authors think that the indications for doing a fetal echocardiography should be restricted to situations considered of risk. However, it is now globally accepted that the prenatal diagnosis of cardiac defects is of paramount importance to enable a better monitoring of the fetus, allowing planning the birth of the cardiopathic fetus in a center of reference, improving the survival of the newborn [23-25].

As a final conclusion, our experience on the detection of CHDs during pregnancy aided by fetal heart echocardiography yielded to 5.9% of different varieties of anomalies, while echocardiography assessment after birth showed such anomalies in 9.9% with an acceptable sensitivity but a moderate specificity for this tool to detect prenatal heart defects. It seems that the diagnostic value of fetal heart echocardiography is potentially interacted by different fetal, maternal, and technical factors that should be recognized to achieve more appropriate planning for early monitoring and diagnosing CHDs, although relatively low number of cases is a potential factor for low power of the fetal heart echocardiography for detecting cardiac anomalies in fetus.

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