2. DISCUSSION
APVS is a rare congenital heart disease (CHD) with an incidence of 0.2%–0.4% in all live birth with CHD,characterized by absent or severe dysplasia of pulmonary valve leaflets[1-3]. APVS is commonly classified into two types: The majority of APVS fetuses is accompanied with TOF, so defined as TOF-type APVS; the minority is absent from VSD, defined as non-TOF-type APVS[3,4]. TOF-type APVS usually got stenosis of pulmonary valve annulus, post-narrow expansion of PA and absent PDA in the previous studies. The inflation of PA trunk and RPA may compress the airway to collapse and softening, which leads to respiratory distress and heart failure in neonatal period. The clinical manifestations are critical, coupled with extracardiac malformations and / or chromosomal abnormalities, the overall prognosis is poor. Non-TOF-type APVS is commonly associated with intact ventricular septum, tricuspid valve atresia or hypoplasia and PDA. The PA trunk usually does not expand, but shows hypoplasia, which proceeds to the immaturity of vessel and tissues in lung. The total mortality of APVS was 75%, including intrauterine death and postnatal death, only 25% were alive after postnatal surgery; therefore, prenatal diagnosis of APVS is significant[3]. Although the postoperative survival rate has improved in recent years, the heart surgery is still complicated. Sometimes heart transplantation is required in emergency[5]. So early diagnosis of APVS in utero is meaningful.
Most TOF-type APVS fetuses are diagnosed after 20 weeks of gestation by echocardiography. Except for positive grayscale images, Color doppler flow imaging (CDFI) shows color mosaic to-and-from blood flow in PA. Spectrum Doppler shows high-speed blood flow antegrade and retrograde in PA. In this study, based on the high resolution of ultrasound, APVS was suspected at 13 weeks of gestation by a skilled sonographer in the first trimester screening, and was confirmed 7 days later. Two weeks later, fetal echocardiography was performed again. In the last two checks, PA and PDA were found with obvious morphological change,which might be helpful in the study of mechanism and development of TOF-type APVS in early middle pregnancy.
In the past, absence of PDA has always been considered in company with dilation of PA in fetus with TOF-type APVS, because the insufficient pulmonary systemic shunt aggravated volume load of RV caused by to-and-from blood flow in PA [6,7]. However, such claims are practically based on the discoveries of TOF-type APVS after 20 weeks of gestation. The process and pathogenesis before 20 weeks were unclear with controversies in correlation between PA dilatation and PDA absence. In the present case at 14 weeks of gestation, the diameter of PDA was wide with unobstructed bidirectional shunt. PA expansion was not distinct. At 16 weeks of gestation, there was PA expansion without PDA absence, which was obviously inconsistent with previous study. The restriction of PDA might be associated with the dilation of PA trunk and PA branches, which leaded to the decrease of blood flow volume through PDA. It advocated the controversial hypothesis that APVS with TOF leads to depressed diastolic pressure of immature PDA and ultimately result in the restriction or closure at an early gestational age [8]. It suggested the dynamic pathological change of PDA in TOF-type APVS fetus in early middle pregnancy. If the fetus developed further in utero, disuse atrophy or atresia of PDA might occur in the future. In addition, it has been reported that several fetuses with TOF-type APVS had constricted PDA after 20 weeks of gestation. It also confirmed that the absence of PDA is not inevitable for the existence of TOF-type APVS. It further proves the rationality of the inference in this study.
APVS may be associated with fetal chromosomal abnormalities, among which 22q11 microdeletions, 13 trisomy and 18 trisomy are most common[9]. It is suggested that 70% of TOF-type APVS were associated with karyotype abnormality. In this case, 984.766kb deletion was detected at 20p12.2 by chromosome microarray analysis (CMA). JAG1 gene in this fragment is in autosomal dominant inheritance, and the deletion is related to TOF and Alagille syndrome. The parents of the fetus were in good health without genetic defects and the deletion of JAG1 gene in fetus was thought to be caused by gene mutation and lead to poor prognosis.
TOF-type APVS is combined with cardiac extracardiac malformations sometimes which is independent influencing factor of prognosis. In this case, a left renal cyst was found which might be sign of cystic dysplasia of kidney.
In this case, the pregnancy was terminated. Fetal autopsy confirmed the ultrasound diagnosis.