Added: Alberto Chittum - Date: 23.11.2021 23:32 - Views: 16571 - Clicks: 9770
Try out PMC Labs and tell us what you think. Learn More. Aneuploidies are a major cause of perinatal morbidity and mortality. Therefore, it is the most common indication for invasive prenatal diagnosis. Initially, screening for aneuploidies started with maternal age risk estimation.
Later on, serum testing for biochemical markers and ultrasound markers were added. Women detected to be at high-risk for aneuploidies were offered invasive testing. New research is now focusing on non-invasive prenatal testing using cell-free fetal DNA in maternal circulation. The advantage of this technique is the ability to reduce the risk of miscarriage associated with invasive diagnostic procedures. However, this new technique has its own set of technical limitations and ethical issues at present and careful consideration is required before broad implementation.
Screening is the process of surveying a population, using a specific marker or markers and defined screening cut-off levels, to identify the individuals in the population at higher risk for a particular disorder. Screening is applicable to a population; diagnosis is applied at the individual patient level. A couple may approach the doctor seeking preconception or early pregnancy genetic advice for a variety of reasons, including:. The couple is from a population group with a high frequency of certain genetic diseases.
The couple is anxious about reproductive risks, even though there is no specific indication that they are at increased risk. Aneuploidies are major causes of perinatal death and childhood handicap. Consequently, the detection of chromosomal disorders constitutes the most frequent indication for invasive prenatal diagnosis.
Multiple marker screening uses a combination of maternal age and two or more biochemical tests, with or without an ultrasound examination, to produce a single result for risk of Down syndrome, trisomy 18, and open neural tube defects ONTDs , which is used to offer options for clinical management. A screen is positive when the risk of one or more of the screened disorders falls above a deated risk cut-off. Counseling and further testing options are offered when a screen is positive. The internet search was accompanied by a detailed search of our library database.
The articles were then reviewed and summarized in a comprehensive manner. When prenatal diagnosis is being considered in genetic counseling, several basic factors must be examined, but the most important is whether the couple concerned actively wish for prenatal diagnosis; all too often it is suggested simply because it may be technically feasible and without adequate information. These are self-evident, but as in most clinical situations, cases of real doubt may occur.
This is beyond doubt in most of the disorders for which prenatal diagnosis is employed, including Down syndrome and other autosomal trisomies, ONTD and the rare neurodegenerative metabolic disorders. Other conditions may be more questionable, especially those where physical abnormalities e.
Albinism, which has few general health implications in northern climates, may, because of the likelihood of skin cancer, be a fatal disorder in tropical countries. Such variable are increasing, particularly as molecular analysis increasingly recognizes specific mutations with relatively mild clinical effects, and this may present difficult decisions, the outcome of which will vary from family to family, and between different societies.
Treatment may be clear-cut and satisfactory in some disorders that might otherwise be considered for prenatal diagnosis. Thus, in phenylketonuria, now detectable prenatally by molecular analysis, most children treated from birth have near normal health and intelligence, at least in countries where dietary treatment is available. In contrast, in galactosaemia, liver damage is occasionally present at birth and the long-term outlook for the infant is less clear.
Whether prenatal diagnosis is undertaken here will probably depend on the attitudes and experience of the parents. In congenital adrenal hyperplasia the outlook with treatment for a second child is much better than for the first-born, in whom delayed diagnosis commonly in death or serious morbidity, while treatment in utero is also a possibility. The acceptability of termination of pregnancy to a couple must be determined before any prenatal procedures are contemplated. In some cases, it is unacceptable on religious grounds or because of the prevailing attitude of the community; in others, it is a more personal ethical view.
Acceptability may be a relative phenomenon. Thus, in the past many couples found fetal sexing by amniocentesis—with late termination of a male pregnancy which might be normal—unacceptable, whereas these same individuals may accept first-trimester termination, following chorionic villus sampling CVS , of a definitely affected male pregnancy. Similarly, in some religious traditions, early termination may be allowable, while late termination is forbidden.
It is essential to know the attitude of a couple before pregnancy occurs because this may well affect their decision whether or not to have further children. Unacceptability of termination should not be considered as automatically ruling out prenatal diagnosis. In rare instances, parents may feel that they will gain by being able to prepare for an affected child, although this is exceptional, especially when the risk of prenatal procedures is pointed out. Serious potential ethical problems arise if prenatal diagnosis is undertaken for a late-onset disorder and the pregnancy continues.
The feasibility of diagnosis is something that continues to change rapidly with scientific advances, so it cannot be too strongly stressed that the person giving genetic counseling must obtain accurate information on this point before suggesting the possibility to a couple, and must be satisfied that the technique is reliably applicable as a service rather than just as a research procedure.
Failure to do this is as reprehensible as submitting a patient to some new surgical procedure without enquiring as to its benefit and mortality. This is especially relevant when using new molecular advances, where the boundary between research discovery and established techniques can be hard to define, especially for very rare disorders, or those where the gene has been recently isolated. Nuchal translucency refers to the subcutaneous layer of fluid behind the fetal neck and lower cranium, which can be visualized on ultrasound. Increased nuchal translucency in the fetus is associated with increased risk of chromosomal abnormality and other diseases.
Prerequisites for an interpretable nuchal thickness measurement include operator qualification, choice of appropriate duration of investigation, and technical considerations. Detection rate of trisomy ten plotted against the type of screening parameters and tests used. In trisomy 18, levels of all the three markers are decreased.
Raised MSAFP levels should be offered genetic counselling and targeted ultrasound for further evaluation. In an effort to further improve performance, the first and second trimester screening tests have been combined into a process called IPS.
Ultrasound dating should be performed if menstrual or conception dating is unreliable. For any abnormal serum screen serum IPS, quad calculated using menstrual dating, an ultrasound should be done to confirm gestational age. The concept of contingent screening has been suggested by Wright et al. In contingent screening, the majority of women receive their result after FTS.
Sequential screening selects women for second trimester testing on the basis of their FTS . Women found to be at high-risk on the basis of the FTS e. Those with a risk lower than the cut-off are offered additional serum screening in the second trimester.
The removal of screen positive affected cases in the first trimester decreases the prevalence of Down syndrome in the second trimester and consequently lowers the PPV of second trimester serum screening. A substantial proportion of rural women with at-risk pregnancies go through their pregnancy period without ificant modern antenatal care.
This is inconvenient for the women as well as causes delay in diagnosis. Furthermore, expertise for NT is not available in all centers, thereby, limiting the detection of aneuploidies in FTS. In particular, the majority of ONTDs should be detected by this ultrasound. When used alone, second trimester ultrasound soft markers do not effectively discriminate between unaffected fetuses and fetuses with Down syndrome, because of the high positive rate from the large of potential markers.
Ultrasound soft markers and anomalies identified in the week ultrasound can be used to modify any a priori risk established by age or prior screening. In the absence of soft markers and anomalies, a reduction of risk can be applied. The biochemical markers in twin pregnancies are on average twice that in singleton pregnancies. The risk is evaluated as for singleton pregnancy. This does decrease the sensitivity of the screening test compared to singleton pregnancy, however, remains a useful approach for evaluation.
An alternative to screening is invasive prenatal diagnosis by CVS or amniocentesis which directly assesses the chromosome constitution of the fetus through cells from the pregnancy. The advantage is the diagnostic certainty of detecting trisomy 21, 18, and In addition, testing fetal cells and the amniotic fluid may allow for the detection of other chromosome abnormities, genetic conditions, or ONTDs [ Table 2 ]. In contrast to fetal cells, cffDNA is rapidly cleared from the maternal circulation with a half-life of 16 min and is undetectable after 2 h of delivery.
Different published clinical trials validated cell free DNA analysis to detect common aneuploidies with a high sensitivity and specificity [ Table 3 ]. The basic principle in extracting the cffDNA is to take initially maternal plasma, separate cellular matter by centrifugation, followed by isolation and purification of all cell-free DNA, followed by exploiting the small differences between the fetal and maternal DNA sequences in order to make a specific fetal diagnosis. One of the applications of NIPT that appears to be close to clinical implementation is a test for fetal-chromosome abnormalities, notably Down syndrome.
This testing is envisaged as being available to all women in the first trimester of pregnancy and would potentially replace current screening and diagnostic methods. Recently, NIPT by analysis of cffDNA in maternal blood has shown promise for highly accurate detection of common fetal autosomal trisomies. In a recently published article of NIPT of fetal trisomies in a routinely screened first trimester population showed that NIPT with a chromosome-selective sequencing approach is highly accurate for fetal aneuploidy detection with very low FPR.
There is less confidence in NIPT as a screen for trisomy 13 due to technical issues and the infrequency of the condition. However, false positives have been reported so at this time it is recommended that positive be followed with confirmatory testing by CVS or amniocentesis.
This has important recurrence risk implications for the parents and other family members. Fetal anatomic ultrasound can also be a helpful tool for pregnancies that test positive on NIPT, looking for additional ultrasound findings that support the diagnosis.Sex Dating Struble
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Discordant fetal sex on NIPT and ultrasound