 |
|
Brief Reports Indian Pediatrics 2003; 40:659-664 |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Atrioventricular Septal Defect - Associated Anomalies and Aneuploidy in Prenatal Life |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Atrioventricular septal defect (AVSD) is synonymous with endocardial cushion defect (ECD), the anomaly forming a spectrum from ostium primum atrial septal defect (OP-ASD) to complete common atrioventricular canal defect (CAVC)(1). It is a common cardiac defect in prenatal life and being a lethal cardiac anomaly, most of the affected fetuses do not survive to term(2). It can be diagnosed easily in fetal echo cardiography by non-visualization of the ‘crux’ of the heart in a four-chamber view(3). An altered shape of the heart and observation of the abnormal atrioventricular valve (AV) motion in real-time provide further clues to this anomaly. Studies indicate 40-60% association of AVSD with chromosomal anomalies, especially trisomy 21(4-6). It is also commonly present with other cardiac(3) and extracardiac anomalies(6), Hence, it is considered imperative that a thorough search for associated anomalies is made by ultra-sound and fetal karyotyping whenever AVSD is diagnosed. An early diagnosis of AVSD, with determination of its severity, presence of cardiac, other systemic chromosomal anomalies plays a crucial role in prenatal decision-making. Our aim in this paper is to assess the frequency of other cardiac and (extracardiac anomalies) with AVSD diag-nosed by ultrasound and with chromosomal anomalies detected by fetal karyotyping. Subjects and Methods Mediscan Systems, a referral center, has been offering ultrasound diagnosis to approximately 7000 pregnant women per year from 1982. Cases are predominantly women from Tamil Nadu and to a lesser extent from other South Indian states. From the year 1988 the four-chamber view and from 1990 the outflow tracts are routinely imaged in every fetus irrespective of high risk or low risk, as 90% of the congenital cardiac anomalies occur in low risk patients(3). A combination of both high risk and low risk cases are referred for various indications and also for fetal well-being and growth assessment. A case is considered as high risk for congenital heart disease (CHD) when anyone of the following criteria is met: (i) previous history of a congenital anomaly (including CHD) in the sibling, (ii) family history of CHD, (iii) maternal diabetes, (iv) maternal age >35 years, (v) any anomaly suspected in the previous scan, (vi) consanguineous marriage or (vii) other risk factors like intrauterine growth retardation or liquor abnormalities. The following equipments were used for performing the obstetric scan and fetal echocardiography: HDI 3000 (Color Doppler) and HDI 5000 (Advanced Technology Laboratories Inc., Bothell, WA, USA), Echocee Color Doppler SSA-340A (Toshiba corporation, Tochiken, Japan), Aloka SSD-1700 and Aloka SSD-620 (Aloka Co., Ltd, Tokyo, Japan) and GE logic 400 (GE Medical Systems, Wisconsin, USA). Fetal four- chamber view and outflow tracts are imaged in every fetus. Four-chamber view is obtained in a transverse section of the thorax just above the diaphragm(7) and outflow tracts are imaged by cephalad angulation and rotation of the transducer from the four-chamber view. The team consisted of five physicians and five sonographers with a minimum of eight years experience in sonography. A senior operator always reviews every case before the diagnosis is finalized. The lower part of the interatrial septum, the atrioventricular septum, the inflow portion of the interventricular septum and the septal insertion of the atrioventricular (AV) valve together form the crux of the heart seen in the four-chamber view during fetal echocardio-graphy. In AVSD, the crux is distorted and a common five-leaflet AV valve separates the atria from the ventricles. The degree to which the valve is partitioned into a distinct right and left orifice forms a spectrum. In OP-ASD the division is complete, while in CAVC no partitioning exists. AVSD is diagnosed when the crux of the heart is not visualized in a four-chamber view. Endocardial cushion defect, ostium primum atrial septal defect, atrioventricular septal defect and complete atrioventricular canal defect were used as search terms to retrieve data from our database during the 54 months period extending from November 1997 to May 2002. Fetuses, where AVSD was given as the primary diagnosis were included in the analysis and not those where it was in the differential. When the diagnostic terminology was ambiguous, e.g., "single AV valve", we reviewed the ultrasound images and offered a fresh diagnosis. Fetal karyo-typing was done using either amniotic fluid or fetal blood as samples. When associated anomalies were analyzed, situs defects were considered as a separate category. Cleft lip and cleft palate were classified under gastrointestinal anomalies and anterior abdominal wall defects (omphalocele) and anomalies of the diaphragm were grouped under musculo-skeletal anomalies as defined in ICD-10. For calculation, the number of cases was taken as the denommator and not the number of anomalies. We also analysed the presence of ultrasound markers of chromosomal anoma-lies such as increased nuchal thickness, cho-roid plexus cyst, minimal ventriculomegaly, intracardiac echogenic foci, echogenic bowel and pyelectasis in fetuses with AVSD. A marker is a transient ultrasound feature and not a malformation by itself. Its presence with a major structural anomaly increases the risk of chromosomal anomaly in the fetus. Results During the study period, AVSD was detected in 103 fetuses; of which OP-ASD was present in nine fetuses and CAVC was present in the rest. Thirty-five cases were indicated for routine scan and rest of them were referred for various other conditions (Table I). The mean gestational age at diagnosis was 26.6 weeks (SD ± 6.37; range 16-42). The mean maternal age at diagnosis was 25 years (SD ± 5.1; range 17-41). Table I Indications for performing fetal Echocardiography.
*Congenital heart disease; N Oligohydramnios, polyhydramnios & Intrauterine growth retardation Thirteen cases of AVSD were isolated and the remaining 90 had either other cardiac or extracardiac anomalies. Other cardiac anomalies were found in 56 fetuses and extracardiac anomalies in 75 fetuses with AVSD. Among the extracardiac anomalies, musculoskeletal anomalies were present in 31 fetuses (Table II). Among specific anomalies that occurred with AVSD, outflow tract anomalies were found in 30 fetuses, followed by Dandy Walker malformation in 11 (Table II). Twenty-two fetuses had undergone karyotyping; no metaphase was seen in one fetus and hence it was excluded from the analysis. In the remaining 21, 15 fetuses had normal chromosomes and six (28.6%) were aneuploid, of which three had trisomy 18, two had trisomy 13 and one had trisomy 21. Table II System Specific and Individual Anomalies with AVSD.
* A case can have more than one anomaly and hence the number of anomalies will exceed the total number
When ultrasound markers for chromo-somal anomalies were analysed, there were two cases with increased nuchal skin fold thickness, two with choroid plexus cysts, two with echogenic bowel and one fetus with minimal ventriculomegaly observed in the six chromosomally abnormal fetuses. None of them were observed in chromosomally normal fetuses. The other two ultrasound markers for chromosomal anomalies i.e., intracardiac echogenic foci and pyelectasis were not observed in any of the 21 fetuses that had undergone karyotyping. Discussion In these 103 unselected cases of AVSD, we found that extracardiac anomalies were more frequent than other-cardiac anomalies. The system-wise frequency of extracardiac anomalies in our series was, musculoskeletal, central nervous and genitourinary system, observed in that order. When we looked at the specific lesions, cardiac outflow tract anomalies were most common, followed by the Dandy Walker malformation, polydactyly, short limbs and cleft lip and cleft palate. Of the 103 fetuses, 22 were karyotyped among which six were aneuploid and all of them presented with one or more ultrasound markers that are considered indicators of chromosomal abnormality. In our study, 91% of the AVSDs were constituted by the CAVC defect, which is comparable with the study by Machado et al.(4) Studies reveal that in 27-53% of the cases, AVSD is the isolated cardiac defect(3-5), which was also observed in our study (45.6%). Outflow tract lesions were the common associated other-cardiac defects (29.1%) in our study, which has also been the case in other studies(4,5). Our study differs from other studies in a few aspects. AVSD was associated with complete heart block in 5.8% of our cases, as opposed to 38% in the study by Machado et al.(4). We observed that AVSD was associated with atrial isomerism in 17.5% of the cases, which contrasts with others (3,4). Evidence from case series studies indicate that 40-60% AVSDs are associated with chromosomal abnormalities of which trisomy 21 forms 50-80%(4-6) of the cases and hence, prenatal karyotyping has been recommended for all cases of AVSD. However, our results show that AVSD was less frequently (28.5%) associated with chromosomal anomalies. Among them trisomy 21 was the least frequent (4.8%). The reason for the low frequency of trisomy 21 in our series could be because of the lower maternal age of our population. It is well known fact that advanced maternal age increases the risk of having a fetus with trisomy 21. The mothers in our series were younger when compared to the study by Delisle, et al.(5) where an advanced maternal age could have been a confounding factor for the increased prevalence of trisomy 21. This brings into question the relevance of routine karyotyping in all fetuses diagnosed with AVSD. In our series, there were six mothers with age ³35 years, but their fetuses had not undergone karyotyping and hence their chromosomal status was not known. In our series, choroid plexus cyst (CPC) was present in two of the three (66.7%) cases of trisomy 18. It has been shown that the risk of trisomy 18 is high when CPC is found with other structural anomalies(7). Increased nuchal thickness was present in the two (100%) cases of trisomy 13. Echogenic bowel and minimal ventriculomegaly were observed independently in two cases of trisomy 18. Echogenic bowel was also observed in the fetus with trisomy 21. None of these ultra-sound markers were observed in chromoso-mally normal fetuses. Although the number of cases that had undergone karyotyping was small (20.4%), our study demonstrates that these ultrasound features could be used as surrogate markers for suspecting chromoso-mal aneuploidy in fetuses with AVSD. The sensitivity and specificity of diag-nosing AVSD is high as compared to other congenital cardiac defects by ultrasound(8). The false-positive rate for prenatal diagnosis of AVSD has been estimated to vary from 3%-20%(4,5,9), being inversely related to operator expertise(4,9). As all our operators have more than eight years experience, we expect a low false positive rate in our center. However, one limitation in our study is the absence of autopsy or postnatal echocardio-graphy for all the cases to validate our diagnosis. Eight still born/terminated fetuses prenatally diagnosed with AVSD had the diagnosis confirmed at autopsy conducted at the department of perinatal pathology in our center. This justifies our ability to diagnose AVSD prenatally. We conclude that AVSD almost always occurs with other-cardiac or extracardiac anomalies, though the pattern may differ between populations. It seems to be less frequently associated with chromosomal anomalies (especially trisomy 21) in South India. The genetics of AVSD underscores the importance of a thorough understanding of the target population in prenatal decision-making. Acknowledgement We would like to acknowledge Mrs. Vijayalakshmi Raja, Senior Sonographer, Mediscan Systems for reviewing the ultra-sound pictures for offering a fresh diagnosis and Dr. P. Manickam, National Institute of Epidemiology, Chennai, for his suggestions and advice in drafting the manuscript. Contributors: MA and GT participated in the concept and design of the study. GT analysed the data. MA and GT drafted the manuscript with the help from SI and SS. SI and SS are the guarantors of this study. Funding: None. Competing interests: None stated.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
References | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
