Does Larger Fetal Ascending Aorta Than the Pulmonary Artery Indicate Major Cardiac Anomaly?

OBJECTIVE: This study investigated the cases in which the fetal ascending aorta is larger than the main pulmonary artery on the three-vessel view and aimed to determine the relationship between the larger ascending aorta and major cardiac anomalies. STUDY DESIGN: Pregnancies between 18-24 gestational weeks who underwent detailed secondtrimester screening during 2015-2019 were evaluated. Cases whose fetal ascending aorta diameter was larger than fetal main pulmonary artery diameter on the three-vessel view despite normal four-chamber view were analyzed. Prenatal and postnatal echocardiography studies were performed for each case. RESULTS: Fetal ascending aorta diameter larger than fetal main pulmonary artery diameter on the three-vessel view despite normal four-chamber view was detected in 21 fetuses in a total of 3810 pregnancies (0.55%), and 10 (47.6%) of them had major congenital heart disease. The diagnosis of Tetralogy of Fallot, double outlet right ventricle, ventricular septal defect, pulmonary valve stenosis, and moderate to severe tricuspid regurgitation were confirmed with prenatal/postnatal echocardiography studies. The highest ratio of ascending aorta/main pulmonary artery was 1.4 in a fetus with a double outlet right ventricle and pulmonary valve stenosis. CONCLUSION: The fetal ratio of ascending aorta/main pulmonary artery larger than 1 on the three-vessel view may be a sign of certain cardiac anomalies. Nevertheless, this rate is not an indicator of a serious cardiac defect in all cases. Fetal advanced echocardiography and early postnatal cardiac evaluation should be done to confirm the diagnosis.


Introduction
Congenital heart diseases (CHD) are the most common cause of congenital malformations. The newborn death caused

Material and Method
Retrospectively 3810 patients were evaluated who had obstetric ultrasound screening between 18-24 gestational weeks at Baskent University Adana Dr. Turgut Noyan Application and Research Center Perinatology Polyclinic between the years 2015-2019. Medical records were extracted from the Hospital Data Management Systems (Version 1.5, Datasel Information Systems, Ankara, Turkey; Nucleus Hospital Information Management System, Version 9.2.40, Monad Software and Counseling, Ankara, Turkey) and patients' files. Twenty-one pregnant who had fetal AA diameter larger than fetal MPA diameter (AA/MPA>1) at 3VV position, while they seemed to have normal four-chamber view results were included in the study. These cases were confirmed by fetal and postnatal echocardiography.
All ultrasonographic examinations were transabdominal scannings performed by a single operator with Voluson E8 (General Electric Healthcare, Little Chalfont, The UK, 5-8 MHz 3D transducer). In cardiac evaluation, upon capturing a clear 3VV, the image was scaled to the 2/3 of the screen. A satisfactory view demonstrated the following from left to right: MPA in direct communication with the ductus arteriosus, a transverse section of the aortic arch and the SVC. Four-chamber view (FCV), major vein outlets, 3VV, 3VV-T, aortic and ductal arches in the transverse section of the upper abdomen were monitored. When the five-chamber view was evaluated the use of fetal echocardiography, results reinforced cardiac pathologies. The sizes of inner spaces of MPA and AA were measured in a vertical position to ductal and aortic arches respectively (10). A single pediatric cardiologist performed fetal echocardiography with 4C convex probes and General Electric Vivid S5 (GE Health Medical, Horten, Norway).
Gestational weeks were calculated according to the first day of the last menstrual period of the pregnant women or by considering the ultrasonography that was performed in the first 3 months. Maternal and obstetric features, pregnancy results of the patients, and information about postnatal progress of cardiac defects were obtained from hospital records.

Results
As a result of obstetric ultrasonographic measurements, there were 21 fetuses (0.55%) with AA larger than MPA (AA/MPA>1). Major CHD was observed in 10 of them (47.6%). Figures 1 and 2 show the cases with the larger AA than MPA on 3VV. Mean sizes of AA, MPA sizes and AA/MPA ratios were detected as 3.6±1.05 mm, 3 ± 0.97 mm and 1.2±0.11, respectively. Cases in which ascending aorta was larger than MPA on 3VV are shown in Table I. The highest AA/MPA ratio (1.4) belongs to the case with double outlet right ventricle and pulmonary valve stenosis (DORV-PS).
Mean maternal age at the time of evaluation was 30±4.0 years, median gravidity was 2 and parity was 1. Four cases were multiple pregnancies and 7 pregnancies were achieved by assisted reproductive technologies. The double test was performed to twelve pregnant at first-trimester; all had a low risk for chromosomal anomalies except one. This case had a high risk and was diagnosed trisomy 21 by chorionic villus sampling later. Nine cases didn't prefer to take any tests. The mean gestational week of diagnosis was 20.5±0.5 weeks. Cesarean section was performed in 18 pregnancies. Mean birth weight was 2638±662.7 grams and mean gestational age at delivery was 36.6±3.0 weeks of gestation. First minute Apgar score was below 7 in 5 infants and 11 infants were admitted to the neonatal intensive care unit. A pediatrician evaluated all the neonates at birth. Postnatal echocardiography was applied to all newborns before their discharge from the hospital.  Table II demonstrates features of cardiac anomalies with fetal aorta larger than the main pulmonary artery on the threevessel view. Multiple congenital anomalies were detected in 4 cases. Two infants with severe Tetralogy of Fallot (TOF) had a palliative operation (Blalock Taussig shunt) after birth. Three infants, who were diagnosed as a ventricular septal defect, DORV, tricuspid valve dysplasia, and severe regurgitation, died. These cases had also extracardiac anomalies (intestinal obstruction, multiple anomalies, Zellweger syndrome).

Discussion
The heart can be considered normal in four-chamber positions especially in outlet VSDs with balanced cardiac ventri-cles and mild degrees of aorta overriding in malalignment VSDs in the early fetal period. The pulmonary artery should be greater than the aorta in the second or third trimester of pregnancy. In fetuses with the ratio of AA/MPA greater than 1, it needs to be recognized the pulmonary vascular anomaly and increased aortic flow should be recognized (11). Since obstructive lesions of the outflow tracts may progress later in pregnancy, mild to moderate stenosis of great vessels can be misdiagnosed as normal on the 3VV when evaluated at earlier weeks. In fetal circulation blood flows through the foramen ovale into the left atrium, passes to the left ventricle where it is ejected into the AA.   the aortic root causes enlargement of the AA in moderate to large perimembranous subaortic VSDs. This rate increases especially in pulmonary artery stenosis, which frequently accompanies malalignment VSDs, and some types of doubleoutlet right ventricle. In our series, the aorta was found to be wider on the 3VV due to the perimembranous subaortic VSD without pulmonary stenosis in 10 fetuses.
Cases with pulmonary stenosis and hypoplasia AA/MPA ratio increase, however in such cases as DORV-PS and Pink Fallot's Tetralogy physiology, which have milder stenosis AA/MPA, may be seen increased in the direction of the aorta in the fetal period. In our study, especially in cases with perimembranous subaortic VSDs and malalignment VSDs with mild aortic overriding, the first finding was greater AA-size rather than hypoplastic-stenotic pulmonary artery in the first cardiac screening. Repeated conventional ultrasound Doppler measurements for pulmonary stenosis progression were performed for each subject.
The reversal of this rate in the absence of VSD necessitates the exclusion of pulmonary valve stenosis and tricuspid valve diseases. Normal forward pulmonary artery flow at the initial examination may be decreased or retrograde flow may occur in association with the development of pulmonary stenosis at tricuspid valve diseases with significant tricuspid insufficiency (12). Therefore, evaluation of tricuspid valve morphology and function, and measurement of pulmonary artery flow with Doppler echocardiography should be performed periodically in patients with abnormal AA/MPA ratio.
In the study of Idilman et al., which is similar to our study, 2540 pregnancies were evaluated and when 17 of those pregnancies with AA>MPA on 3VV were examined, in 5 of them, postnatal normal cardiac results were detected (13). The fact that cases with AA larger than MPA are not necessarily related to a severe CHD is supported by this study as well. Comstock et al. have reported 316 healthy fetuses with a mean 1.09 MPA/AA ratio (0.75-1.43 ranges) in 14-39 gestational weeks. They found 4 fetuses with TOF with the ratio of MPA/AA 0.75, while four fetuses were normal with uncomplicated ventricular septal defects (14). In our study, the cardiac anomaly was detected in all patients with AA/MPA�1.1. On the other hand; Rollins et al have evaluated 2797 cases, and found cardiac anomalies in all of 31 fetuses who had AA-size greater than MPA despite a normal 4-chamber view (TOF, TOF variants, aortic valve anomaly, dilatation of AA) (7). Sensitivity and specificity were not evaluated in the Rollins' study similar to our study due to unknown healthy cases with larger AA than MPA at the second-trimester screening that is an important limitation of those studies. However few cases, whose AA is larger than the MPA on 3VV, have been reported in the literature. Therefore, we think that this series will help to consider the possible diagnoses.
In the study of Moon et al. it has been stated that MPA and AA change depending on the gestational week and physiologically while the diameter of AA is similar or a little smaller than MPA in the second trimester, it remains smaller in the progressive gestational weeks due to heavy right ventricle relative workload (10). For this reason, AA/MPA ratio should be evaluated according to the gestational week and in the progressive weeks, in the case of detection of AA>MPA, it is a must to be precautious regarding fetal CHD.
In the detection of major vessel outlet anomalies, the evaluation of 3VV together with FCV should be included in the routine perinatal scanning since it can be carried out easily and in a short time (11,15,16). In such cases requesting targeted advanced fetal echocardiography is going to enable the prediction of prenatal CHD's and improve the sensitivity and specificity of abnormal 3VV in fetal cardiac pathologies (17).
It has also been indicated that simply the scanning parameters are not adequate to diagnose cardiac defects at an early stage and cardiac evaluations consisting of four-chamber view, vessel outlets view and 3VV-T have a higher sensitivity (8,18). Additionally, it has been specified that although the FCV and 3VV are effective in detecting the structural anomalies, they do not suffice in screening valvular anomalies in a multicentric prospective study and such limitations can be overcome through the repetition of fetal cardiac scanning including 30. Gestational week color Doppler evaluation (19).
The result of this study, we detected 21 cases whose fetal AA was larger than MPA on 3VV despite the normal fourchamber view. The cardiac anomaly was detected in all cases, but only 10 of them (47.6%) had a major cardiac defect. In conclusion, fetal sonographic screening of the ratio of AA/MPA on 3VV is important; the ratio is greater than 1 despite a normal four-chamber appearance may indicate congenital heart disease. Comprehensive fetal echocardiography should be recommended when the ratio of AA/MPA is found to be larger than 1 on the three-vessel view but it should be kept in mind that it does not always prove a serious cardiac anomaly.
Author contributions: SYB and AA conceived and designed the project. SYB, SYS, SA and HK collected and analyzed the data. SYB, AA, and GDD wrote and finalized the paper.