Amniocentesis is the most common invasive prenatal procedure for detection of fetal chromosomal abnormalities.
In this study, abnormal MSS was the most common indication. This finding was similar to the results of previous studies (Choi et al. 2005;Jang et al. 2007;Han et al. 2008). In contrast, recent studies performed in Egypt showed that previous history of an abnormal child was the most common indication for amniocentesis (Helmy et al. 2009;Atef et al. 2011). This difference reflects the increased awareness of our patients about the importance of prenatal serum screening tests. It should be considered that MGC is a private laboratory, and most of our patients come from high social class families, when compared to the previous studies performed at governmental hospitals where free or minimum charge prenatal diagnosis is provided for high risk group only.
Previous reports on prenatal diagnosis of amniocentesis, consisting of various numbers of cases, have revealed that the incidence of chromosomal abnormalities ranges from 1% and 6.7% (Tseng et al. 2006;Han et al. 2008which was similar to the data from Egyptian study by Shawky et al. 2009.
In this study, DS was the most common abnormality detected (5%) by prenatal diagnosis and at the same year 2009, 429 (8.7%) live- birth DS were diagnosed postnatally in the MGC. Prenatal diagnosis of DS is not available for most of pregnant women in Egypt and the National DS cytogenetic register is not yet developed to compare our results. However, there are several reports on the increased incidence of DS from different parts of the world, with respect to ethnicity and maternal age (Warburton et al. 2004;Lamb et al. 2005). An earlier study in Egypt have reported the incidence of DS as, 1 per 700 births and 98.4% of cases were diagnosed postnatal and only 1.56% were detected prenatally with an estimated risk of 2285 DS births annually (El-Sobky and Elsayed 2004). Our result suggests an increased awareness of our group of patients about the importance of antenatal screening for DS. On the other hand, the MOHP in Egypt did not adopt proper antenatal screening as a public policy till today (El-Gilany et al. 2011;Shalaby 2011).
There are two factors known to influence the number of live births with DS- the underlying incidence of the syndrome to the distribution of maternal age, and the number of pregnancies that are detected antenatal and subsequently terminated (Shalaby 2011;Morris and Alberman 2009). In this work, the mean age of mothers was advanced (35.6 years) when compared to the mean maternal age in Egypt (21.9 ± 3.45 years, 2008), (Finaly et al. 2011).
Traditionally, screening for trisomy 21 was based on maternal age and biochemical testing of second trimester (14–18 weeks) maternal serum AFP (Snijders et al. 1998). However, it can now be provided effectively by a combination of the ultrasonography measurement of fetal NT thickness, absence/presence of nasal bone (NB) in conjunction with biochemical testing for PAPP-A and hCG at 11 weeks to 13 weeks and six days (13 + 6 weeks) of gestation. The detection rate of these combined methods is about 85-90% in regard to trisomy 21 and 18, for a false positive rate of 5% (Agnieszka et al. 2007).
In previous studies (El-Sobky 2007;Tseng et al. 2006;Yang et al. 1999), the AU findings showed the highest detection rate for chromosomal abnormalities in prenatal diagnosis. In the present study, of the 17 cases with AU findings, 4 cases resulted in chromosomal abnormalities, which showed the highest positive predictive value (23%) among the indications. Nowadays, highly sensitive ultrasonic technology can detect fetal anomalies which eventually necessitate amniocentesis.
In this study, (90%) of amniocentesis performed for patients showed normal result. For this large group of parents, RAS using FISH excluded the possibility of foetal DS and relieved anxiety within 1–2 days. However, the final and conclusive result was not available until a full karyotype was obtained in the week following the FISH finding, in which abnormalities not detectable by FISH was unveiled.
Currently, most prenatal diagnosis units offer either traditional karyotyping only or RAS in addition to karyotyping. If cost is not an issue, the latter appears ideal. However in publicly funded system, money spent in one area means deprivation in another.
There is an ongoing debate surrounding whether RAS should be employed as an adjunct to karyotyping or whether it could be used as a stand-alone test in selected group of women (Leung et al. 2003;Caine 2005;Leung 2005;Bui 2007). The controversy is due to the residual probability of a chromosome abnormality (both balanced and unbalanced) when RAS demonstrates a normal result.
In this work, the result obtained by RAS for common aneuploidies and the banding cytogenetic were in complete accordance with no false positive or false negative results. Similar results were obtained by (Pergamnet et al. 2000;Lim et al. 2002;Settin et al. 2007;Neagos et al. 2011). The relatively small number of cells needed for diagnosis (practically 50), gave a much better option to be more selective in cell quality and was a major factor in the efficiency and accuracy of the tests.
Although RAS using FISH is highly sensitive and specific method in the detection of aneuploidy, one of the disadvantages of FISH is that maternal and fetal XX cells per se are indistinguishable by FISH, rendering maternal cell contamination undetectable from female fetuses. However, maternal cell contamination is readily detectable with male fetuses, as a mixture for XX and XY cells are seen. In contrast to the situation of FISH, maternal cell contamination is readily detected by careful comparison with profiles from maternal blood sample in QF-PCR amplification of STR (short tandem repeats) (Bui 2007;Hulten et al. 2003). For safety, we and many laboratories discard any heavily contaminated samples with respect to RAS.
In contrast to the RAS, the array-based comparative genomic hybridization (a CGH) is a comprehensive, high resolution, genome-wide screening strategy for obtaining DNA copy number information in a single measurement which can be rapid and less laborious than karyotyping as it is readily amenable to automation. While currently high costs of the technology need to be addressed before it can be used in prenatal diagnosis, it is likely to become an important tool with the potential of replacing karyotyping in the future (Bui 2007).
The feasibility of the RAS stand-alone approach depends on the indication for the invasive prenatal test. With the presence of major ultrasound-detected foetal anomalies, traditional karyotyping should be performed to look for structural chromosomal abnormalities apart from aneuploidies. The RAS stand-alone approach is best when the invasive prenatal test is performed for an identified increased risk of Down syndrome from a positive screening test (Leung et al. 2008).
For most women, when the indication for prenatal diagnosis is AMA (in isolation or combined with maternal serum and ultrasonographic screening for fetal (NT), this risk is usually relatively low, in order of 0.1-0.2% (Grimshaw et al. 2007). In other words, in the low risk group of women, the abnormality detection rate is around 99.9-99.8%. In contrast, once a structural abnormality of the fetus has been diagnosed using ultrasonography, the risk may be substantially increased. The risk of fetal chromosome abnormality is increased when either parent is a carrier of a chromosome rearrangement such as translocation, inversion, or insertion. Neither FISH nor QF-PCR aneuploidy assay are applicable. Either karyotyping or specific molecular testing is mandatory (Chen et al. 2001).
Our findings show that all clinically significant numeric cytogenetic abnormalities (trisomy 21, trisomy 13, and trisomy 18, and sex chromosome abnormalities) can be detected if RAS was used as a stand-alone approach. On the other hand, to carry out RAS FISH, amniocentesis or CVS still needs to be performed. These invasive techniques carry an intrinsic risk of miscarriage of 0.5% and 1% respectively. With small as such risk may be, it would seem prudent to have a thorough karyotype analysis to reveal the maximum information possible (Gekas et al. 2011).
While the use of RAS to give a rapid result for the common aneuploidies as adjunct to karyotyping is recommended for routine prenatal diagnosis, this combined approach clearly increases the cost of prenatal diagnosis. However, the quality of life and anxiety measurements show a significantly increased health status after diagnosis with RAS, and RAS allows earlier decision making in cases where the fetus has a detected chromosomal abnormality (Gekas et al. 2011).
In addition, a joint statement by the American College of Medical genetics and the American society for Human genetics reaffirmed that all RAS tests results must be followed up with karyotyping reports indicated that 15-30% of cytogenetic abnormality detected by karyotyping would not be detected by RAS, but the number of these cytogenetic abnormality with risk of adverse outcome above background levels are much lower, and the relevance of diagnosing them via DS screening programs is debated owing their clinical significance (Lim et al. 2010).
On the other hand, the termination of pregnancy remains a contentious issue in many societies, despite the socially acceptable view of abortion as immoral; many Muslims would personally accept prenatal testing technology and may opt for termination of pregnancy for conditions perceived to be burdensome for the child (Ahmad et al. 2013). While this may be acceptable to literate Muslims, much of the Muslim population depend on the local Imams (Muslim leaders), most of whom are strongly against termination of life (Salihu 1997).
The Egypt population has reached 91 million by the end of August 2012, and with the increase in the average growth rate to reach 2, we expect to have an added 2850 DS birth every year. Considering suffering family members, it means that an average of 11,400 family member suffering both social and psychological, especially with the very limited resources for handicapped children.
In economically developed countries, life expectancy for individuals with DS continues to rise, and significant, if uneven, progress has been made in education provision and employment prospects for those with an intellectual disability (Glasson et al. 2002). In contrast, the limited literature from economically developing countries tends to characterize life for people with intellectual disability and their families as burdensome and stigmatized (Ghai 2001). A large number of individuals cannot afford medical insurance and make use of the free-of-charge state sector medical services; nonetheless, the utilization of these services is impeded by transport costs, bureaucracy and complex management patterns. Therefore, the only public health measure available to reduce the incidence of DS births is antenatal screening followed by invasive prenatal genetic diagnosis and selective therapeutic abortion of affected fetuses (Scott et al. 2013).