Use Of Prenatal Diagnosis Research Articles

Evolution of the MRT method and current possibilities of its use in prenatal diagnosis of foetal anomalies (literature review)

Evolution of the MRT method and current possibilities of its use in prenatal diagnosis of foetal anomalies (literature review)

The Effect of Resolution Level and Targeted Design in the Diagnostic Performance of Prenatal Chromosomal Microarray Analysis

Introduction: This study was performed to assess the optimal resolution for prenatal testing by array comparative genomic hybridization (aCGH), aiming to balance between maximum diagnostic yield and minimal detection of variants of uncertain significance (VOUS). Methods: This was a prospective study using data of 2,336 fetuses that underwent invasive prenatal diagnosis, and the samples were analyzed by aCGH. In total, six different aCGH platforms were studied; four different resolutions (0.18 Mb, 0.5 Mb, 1 Mb, and 2 Mb) and two platform designs (whole-genome [WG] and targeted). The results of these designs were compared based on their diagnostic yield and VOUS rate. The performance of the different designs was further analyzed according to indication for invasive testing. Results: The diagnostic yield of copy number variants increased with increasing level of analysis. The detection rates of clinically significant chromosomal abnormalities were almost the same across our targeted array designs; 7.2% with 0.18 Mb backbone/0.05 Mb versus 7.1% with 0.5 Mb backbone/0.05 Mb (p >0.05). However, a significant difference in the rate of VOUS was observed; 9.4% with 0.18 Mb backbone/0.05 Mb versus 6% with 0.5 Mb backbone/0.05 Mb (p <0.001). After analyzing the results across different indications for testing, we found that the application of non-targeted platform designs and lower levels of resolution analysis (such as 1 Mb WG or 0.5 MbL/1 MbG WG) would offer similar diagnostic yield in most cases with major congenital anomalies, with lower VOUS rates. However, the sample size for many indication groups was too small to extract robust associations. Conclusion: It appears that the targeted array platform with 0.5 Mb backbone resolution and 0.05 Mb on targeted gene-rich regions is optimal for routine chromosomal microarray analysis use in prenatal diagnosis. It may be beneficial to individualize the minimum resolution in specific referral indications as the indications for invasive prenatal testing may be quite heterogeneous.

Reconstruction of the fetus face from three-dimensional ultrasound using a newborn face statistical shape model

Background and objectiveThe fetal face is an essential source of information in the assessment of congenital malformations and neurological anomalies. Disturbance in early stages of development can lead to a wide range of effects, from subtle changes in facial and neurological features to characteristic facial shapes observed in craniofacial syndromes. Three-dimensional ultrasound (3D US) can provide more detailed information about the facial morphology of the fetus than the conventional 2D US, but its use for pre-natal diagnosis is challenging due to imaging noise, fetal movements, limited field-of-view, low soft-tissue contrast, and occlusions. MethodsIn this paper, we propose the use of a novel statistical morphable model of newborn faces, the BabyFM, for fetal face reconstruction from 3D US images. We test the feasibility of using newborn statistics to accurately reconstruct fetal faces by fitting the regularized morphable model to the noisy 3D US images. ResultsThe results indicate that the reconstructions are quite accurate in the central-face and less reliable in the lateral regions (mean point-to-surface error of 2.35 mm vs 4.86 mm). The algorithm is able to reconstruct the whole facial morphology of babies from US scans while handle adverse conditions (e.g. missing parts, noisy data). ConclusionsThe proposed algorithm has the potential to aid in-utero diagnosis for conditions that involve facial dysmorphology.

PRE- AND POSTNATAL DIAGNOSIS OF DOWN SYNDROME

The article presents an analysis of live births and abortions with confirmed Down syndrome (DS) in Kyiv in 2018-2020. During this period, 86 children with DS were born in Kyiv, which corresponds to an average frequency of 8.6 per 10,000 live births. The frequency of births of children with DS decreased from 10.4 in 2018 to 6.5 in 2020 per 10,000 live births. The percentage of male probands is 59 %, and female – 41 %. Timely diagnosis of DS in live births allows for surgical correction in the presence of congenital malformations and reduces mortality in early childhood.&#x0D; Diagnosis of DS at the prenatal stage allows doctors to make decisions on abortion at the request of the woman. The analysis of cases of abortions for the period 2018-2020 shows a tendency to increase the number of aborted pregnancies. The rate of abortions with DS in Kyiv was 40 % in 2018, in 2019 – 52 %, and in 2020 – 67 %. and reached the mark of Western Europe. The high rate of aborted pregnancies correlates with a decrease in the number of births of children with DS during this period. The data show an increase in public awareness of hereditary pathology, an increase in referrals to a geneticist and an increase in the effectiveness of prenatal diagnosis.&#x0D; During the period: 2018-2020, there is an increase in medical coverage; genetic counseling; and invasive interventions to establish the karyotype in high-risk women who were included in the high-risk group as a result of combined prenatal screening or had been diagnosed with birth defects or have ultrasound markers of chromosomal pathology. It is established that this pathology occurs in mothers of any age, not only in women over 35 years, which indicates the feasibility of mass use of prenatal diagnosis in all age groups.&#x0D; The presented statistical data makes the case to use prenatal testing and how to rationally distribution financial resources. The prospect of further research is to analyze cases of live births and abortions with confirmed DS at the national level.

INDICATIONS FOR PRENATAL KARYOTYPING

The article provides an analysis of the results of prenatal diagnosis (174 cases) performed at the Center for Genetic Diagnostics "AFGEN" for 2015-2017. Chromosomal abnormalities were detected in 5.1% of cases. The most frequent anomaly in our own material was trisomy XXI (Down's disease), in the second place were balanced translocations. Based on the results, the need for wider use of prenatal diagnosis in the region was indicated. Only in this way can chromosomal abnormalities in the fetus be detected in a timely manner and the birth of children with gross malformations can be prevented.

In This Issue

https://doi.org/10.1038/s41436-018-0087-4 Prenatal exome sequencing can enable molecular diagnoses when standard genetic testing yields no diagnosis to families searching for answers. In their review article, Vora and Hui cover the landscape of advanced prenatal ’omics—both its promise and pitfalls. The authors cover both genomic and transcriptomic technologies, which have both revealed new insights into human development. The technologies have begun to assist in fetal diagnosis and have advanced to the point that placental function can be noninvasively sampled through maternal plasma cell-free RNA. Excitement surrounds the possibilities, but the authors point out that variant interpretation and pre- and posttest counseling remain highly challenging for clinicians. While the American College of Medical Genetics and Genomics and other professional organizations do not recommend exome sequencing for routine use in prenatal diagnosis, in select prenatal cases in which standard approaches have failed to offer an informative finding, exome sequencing can be offered as another option. When a fetus has structural abnormalities or homozygosity indicates consanguinity (or closer parental relatedness) on microarray, exome sequencing can also play a role. In addition, the technique can be more cost effective than sequencing individual genes using a targeted molecular panel. The authors argue that, given the rate of discovery, it would be useful to the research community to have a shared prenatal database with genotype and phenotype information. A shared database would enable researchers to search for similar phenotypes and increase the confidence in pursuing novel gene discovery functional studies if there are multiple families with genotype/phenotype correlation. The review also covers transcriptomics and the use of RNA sequencing to study pre- and postimplantation embryology, stem cell biology, organogenesis, fetal maturation, and placental physiology. —Karyn Hede, News Editor https://doi.org/10.1038/gim.2017.199 When children born with metabolic disorders receive early treatment, their health outcomes are often much better than those of children who don’t receive early diagnosis and treatment. But demonstrating that benefit at the population level has been a challenge for state-run newborn-screening programs. Investigators in California are now reporting five-year follow-up data for infants born between 7 July 2005 and 31 December 2009. Their long-term data reveal the success of screening for health outcomes and provide a model for other states seeking resources for their own follow-up programs. The California Department of Public Health’s Genetic Disease Screening Program has tracked all newborns with initial screen-positive test results for 1 of 20 primary metabolic disorders and documented treatment received through a network of metabolic specialty care centers. The cohort reported in this issue represents an extension of the 3-year data reported in GIM (Genet Med 2014;16:484–490) in 2014. By age 5, more than half (n=235; 55.2%) of the original 426 patients remained in active care compared with 82.6% (n=352) in active care at age 1. Over the cumulative 5 years, 20.4% (n=87) of the 426 patients were lost to follow-up, 8.7% (n=37) moved out of state, 6.3% (n=27) were determined to require no further follow-up, 4.7% (n=20) refused follow-up, and 4.7% (n=20) died, with most (n=13; 65%) dying within two months of birth. The results for patients and families who stayed in active care versus those who dropped out of care were not influenced by demographic characteristics or ability to pay. Some of the data suggest that barriers to care exist for families that have transportation challenges or language barriers. The cost of collecting follow-up data is covered by revenue from the screening fees for approximately 500,000 newborns each year. The authors suggest that other states may wish to consider raising their test fees to cover collection of long-term follow-up data. —Karyn Hede, News Editor

Diagnosis for choroideremia in a large Chinese pedigree by next‑generation sequencing (NGS) and non‑invasive prenatal testing (NIPT).

To develop an effective strategy to isolate and use cell-free fetal DNA (cffDNA) for the combined use of next-generation sequencing (NGS) for diagnosing choroideremia and non-invasive prenatal testing (NIPT) for Y chromosome determination, a large Chinese family with an X-linked recessive disease, choroideremia, was recruited. Cell-free DNA was extracted from maternal plasma, and SRY polymerase chain reaction amplification was performed using NIPT. Sanger sequencing was subsequently used for fetal amniotic fluid DNA verification. A nonsense mutation (c.C799T:p.R267X) of the CHM gene on the X chromosome of the proband (IV:7) and another 5 males with choroideremia were detected, while 3 female carriers with no symptoms were also identified. The fetus (VI:7) was identified as female from the cffDNA, and the same heterozygous nonsense mutation present in her mother was also confirmed. At one and a half years of age, the female baby did not present with any associated symptoms of choroideremia. Therefore, cffDNA was successfully used for the combined use of NGS for diagnosing choroideremia in a large Chinese pedigree, and NIPT for Y chromosome determination. This approach should result in a markedly increased use of prenatal diagnosis and improvement, and more sophisticated clinical management of diseases in China and other developing countries. The establishment of a highly accurate method for prenatal gene diagnosis will allow for more reliable gene diagnosis, improved genetic counseling, and personalized clinical management of our patients.

Detection of Hemophilia A Carriers in Azeri Turkish Population of Iran

Hemophilia A (HA) is an inherited X-linked coagulation disorder caused by the deficiency of factor VIII (FVIII). Linkage analysis is a common indirect method for the detection of female carriers in families with HA. In the current study, 173 patients from 30 unrelated families with HA were recruited from the Azeri Turkish population of northwest Iran and analyzed for BclI and HindIII markers by polymerase chain reaction-restriction fragment length polymorphism. We investigated the potential of using these markers for the detection of mutation in carriers through linkage analysis, which would be of tremendous use in prenatal diagnosis. Among the tested women, 47% and 35% were found to be heterozygous for BclI and HindIII polymorphic markers, respectively. The BclI and HindIII markers were informative for the detection of 63% and 17% potential carriers, respectively, demonstrating the effectiveness of the BclI marker for the detection of HA carriers among the Azeri Turkish population.

Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: a challenge for couples with hereditary breast and ovarian cancer

How do couples with a BRCA1/2 mutation decide on preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) for hereditary breast and ovarian cancer syndrome (HBOC)? BRCA couples primarily classify PGD and/or PND as reproductive options based on the perceived severity of HBOC and moral considerations, and consequently weigh the few important advantages of PGD against numerous smaller disadvantages. Awareness of PGD is generally low among persons at high risk for hereditary cancers. Most persons with HBOC are in favour of offering PGD for BRCA1/2 mutations, although only a minority would consider this option for themselves. Studies exploring the motivations for using or refraining from PGD among well-informed BRCA carriers of reproductive age are lacking. We studied the reproductive decision-making process by interviewing a group of well-informed, reproductive aged couples carrying a BRCA1/2 mutation, regarding their decisional motives and considerations. This exploratory, qualitative study investigated the motives and considerations taken into account by couples with a BRCA1/2 mutation and who have received extensive counselling on PGD and PND and have made a well-informed decision regarding this option. Eighteen couples took part in focus group and dyadic interviews between January and September 2012. Semi-structured focus groups were conducted containing two to four couples, assembled based on the reproductive method the couple had chosen: PGD (n = 6 couples) or conception without testing (n = 8 couples). Couples who had chosen PND for BRCA (n = 4) were interviewed dyadically. Two of the women, of whom one had chosen PND and the other had chosen no testing, had a history of breast cancer. None of the couples who opted for PGD or conception without testing found the use of PND, with possible pregnancy termination, acceptable. PND users chose this method because of decisive, mainly practical reasons (natural conception, high chance of favourable outcome). Motives and considerations regarding PGD largely overlapped between PGD users, PND users and non-users, all mentioning some significant advantages (e.g. protecting the child and family from the mutation) and many smaller disadvantages (e.g. the necessity of in vitro fertilization (IVF), low chance of pregnancy by IVF/PGD). For female carriers, the safety of hormonal stimulation and the time required for PGD before undergoing preventive surgeries were important factors in the decision. Non-users expressed doubts about the moral justness of their decision afterwards and emphasized the impact the decision still had on their lives. The interviewed couples were at different stages in their chosen trajectory, up to 3 years after completion. This may have led to recall bias of original motives and considerations. Couples who did not actively seek information about PGD were excluded. Therefore the results may not be readily generalizable to all BRCA couples. The perceived severity of HBOC and, for female carriers, the safety of hormonal stimulation and the time frames for PGD planning before preventive surgeries are essential items BRCA couples consider in reproductive decision-making. The emotional impact of this decision should not be underestimated; especially non-users may experience feelings of doubt or guilt up to several years afterwards. PGD counselling with tailored information addressing these items and decisional support in order to guarantee well-informed decision-making is needed. This study was funded by the Dutch breast cancer foundation Stichting Pink Ribbon, grant number 2010.PS11.C74. None of the authors have competing interests to declare. Not applicable.

604: Cell-free fetal DNA isolated from amniotic fluid supernatant can be used for genome wide array as an alternative analytic method in prenatal diagnostics

Fetal testing in case of anomalies on ultrasound is increasingly done through genome-wide array analysis, replacing karyotyping. Array is commonly performed on DNA derived from uncultured amniocytes. However, in early pregnancy, amniocytes need to be cultured to obtain sufficient DNA. Amniotic fluid (AF) supernatant contains cell-free fetal (cff) DNA and mRNA, which might offer possibilities for its use in prenatal diagnosis. We aimed to explore the use of cff DNA isolated from AF supernatant as a source for genome-wide array analysis.

Microarray comparative genomic hybridization in prenatal diagnosis: a review

G-band chromosomal karyotyping of fetal cells obtained by invasive prenatal testing has been used since the 1960s to identify structural chromosomal anomalies. Prenatal testing is usually performed in response to parental request, increased risk of fetal chromosomal abnormality associated with advanced maternal age, a high-risk screening test and/or the presence of a congenital malformation identified by ultrasonography. The results of karyotyping may inform the long-term prognosis (e.g. aneuploidy being associated with a poor outcome or microscopic chromosomal anomalies predicting global neurodevelopmental morbidity). Relatively recent advances in microarray technology are now enabling high-resolution genome-wide evaluation for DNA copy number abnormalities (e.g. deletions or duplications). While such technological advances promise increased sensitivity and specificity they can also pose difficult challenges of interpretation and clinical management. This review aims to give interested clinicians without an extensive prior knowledge of microarray technology, an overview of its use in prenatal diagnosis, the literature to date, advantages, potential pitfalls and experience from our own tertiary center.

An urgent need for a change in policy revealed by a study on prenatal testing for Duchenne muscular dystrophy.

Prenatal diagnosis for Duchenne muscular dystrophy (DMD) was introduced in the Netherlands in 1984. We have investigated the impact of 26 years (1984–2009) of prenatal testing. Of the 635 prenatal diagnoses, 51% were males; nearly half (46%) of these were affected or had an increased risk of DMD. As a result 145 male fetuses were aborted and 174 unaffected boys were born. The vast majority (78%) of females, now 16 years or older, who were identified prenatally have not been tested for carrier status. Their average risk of being a carrier is 28%. We compared the incidences of DMD in the periods 1961–1974 and 1993–2002. The incidence of DMD did not decline but the percentage of first affected boys increased from 62 to 88%. We conclude that a high proportion of families with de novo mutations in the DMD gene cannot make use of prenatal diagnosis, partly because the older affected boys are not diagnosed before the age of five. Current policy, widely accepted in the genetic community, dictates that female fetuses are not tested for carrier status. These females remain untested as adults and risk having affected offspring as well as progressive cardiac disease. We see an urgent need for a change in policy to improve the chances of prevention of DMD. The first step would be to introduce neonatal screening of males. The next is to test females for carrier status if requested, prenatally if fetal DNA is available or postnatally even before adulthood.

Diagnóstico prenatal y array-CGH II: gestaciones de bajo riesgo

The array-CGH technique has recently been established as a first-tier diagnostic test for studying patients with congenital anomalies, idiopathic mental retardation and other neurological disorders. However, its use in prenatal diagnosis is still being evaluated, especially in low-risk pregnancies. A study was conducted on a population of 530 low-risk pregnancy women using both conventional karyotype and array-CGH for prenatal diagnosis. Whereas conventional karyotype detected 3 foetuses (0.5%) with unbalanced cytogenetic aberrations (one of them was undefined), array-CGH detected 8 foetuses with copy number aberrations (1.5%), and positively identified the undefined cytogenetic aberration detected using karyotype. In conclusion, this study proposes array-CGH as a useful tool in prenatal diagnosis for low-risk pregnancies.

Mutation spectrum of and founder effects affecting the PTS gene in East Asian populations

The enzyme 6-pyruvoyl-tetrahydropterin synthase (PTPS, gene symbol: PTS) is involved in the second step of the de novo biosynthesis of tetrahydrobiopterin (BH4), which is a vital cofactor of nitric oxide synthases and three types of aromatic amino acid hydroxylases; the latter are important enzymes in the production of neurotransmitters. We conducted a study of PTS mutations in East Asia, including Taiwan, Mainland China, Japan, South Korea, the Philippines, Thailand and Malaysia. A total of 43 mutations were identified, comprising 22 previously reported mutations and 21 new discovered mutations. Among these, the c.155A>G, c.259C>T, c. 272A>G, c.286G>A and c.84-291A>G mutations were the most common PTS mutations in East Asia, while the c.58T>C and c.243G>A mutations were, respectively, specific to Filipinos and Japanese originating from Okinawa. Further studies demonstrated that each of the mutations listed above was in linkage disequilibrium to a specific allele of polymorphic microsatellite marker, D11S1347. These results suggest the presence of founder effects that have affected these frequent mutations in East Asia populations. In this context, D11S1347 should become one of the most reliable polymorphic markers for use in prenatal diagnosis among PTPS deficient families, especially where mutations are yet to be identified.

Clinical Presentation of Klinefelter's Syndrome: Differences According to Age

The aim of the study was to establish the characteristics of presentation of 94 patients with Kinelfelter's syndrome (KS) referred to the endocrinologist at different ages. The diagnosis of KS was more frequent in the age group between 11 and 20 years (46.8%). Most of the patients (83.7%) showed the classic 47,XXY karyotype and 7.1% showed a 47,XXY/46,XY mosaicism. Half of the patients younger than 18 years presented mild neurodevelopmental disorders. The most frequent clinical findings were cryptorchidism in prepubertal patients, and small testes, cryptorchidism, and gynecomastia in pubertal patients. FSH, LH, AMH, and inhibin B levels were normal in prepubertal patients and became abnormal from midpuberty. Most adults were referred for small testes, infertility, and gynecomastia; 43.6% had sexual dysfunction. Testosterone levels were low in 45%. Mean stature was above the 50th percentile, and 62.5% had BMI ≥25.0 kg/m2. In conclusion, the diagnosis of Klinefelter syndrome seems to be made earlier nowadays probably because pediatricians are more aware that boys and adolescents with neuro-developmental disorders and cryptorchidism are at increased risk. The increasing use of prenatal diagnosis has also decreased the mean age at diagnosis and allowed to get insight into the evolution of previously undiagnosed cases, which probably represent the mildest forms. In adults average height and weight are slightly higher than those in the normal population. Bone mineral density is mildly affected, more at the spine than at the femoral neck level, in less than half of cases.

Copy-number changes in prenatal diagnosis

Until recently, the prenatal detection of genetic disease was available to only a subset of the pregnant population deemed to be at an increased risk for chromosomal abnormalities or, more rarely, other genetic disorders, based on family history, multiple-marker screening or ultrasound findings. Guided by recent data that indicate that screening for Down syndrome has improved and that risks of invasive procedures are smaller than previously ascertained, the American College of Obstetricians and Gynecologists has recommended that all women have access to invasive prenatal diagnosis. The parallel development of newer genetic diagnostic technologies, such as chromosomal microarray analysis, has made it feasible to simultaneously test for more conditions than was possible with standard karyotype analysis complemented by targeted fluorescence in situ hybridization or mutation detection for specific conditions. In the pediatric and adult population, chromosomal microarray analysis has already been thoroughly evaluated and is now recommended as a first-line diagnostic test for clinically suspected genetic disorders. In this article, we review the current status of array-based comparative genomic hybridization use for prenatal diagnosis and predict that, in the future, it will replace karyotyping as a first-line test for detecting chromosomal abnormalities in the prenatal setting.

Gene expression analysis of amniotic fluid: New biomarkers and novel antenatal treatments

Over the past thirty years there has been a significant increase in the use of prenatal diagnosis to improve perinatal outcome. Frequently, at least in developed countries, this involves prenatal sonography to image fetal anatomy and detect congenital anomalies. This has led to a primarily surgical approach to fetal and neonatal treatment. While effective, this strategy has revealed little about fetal functional development. Since 2005, our laboratory has explored the hypothesis that valuable fetal developmental gene expression information is present in amniotic fluid (AF). In pilot studies performed using large quantities of amniotic fluid obtained from pregnancies complicated by polyhydramnios, we showed that cell-free fetal messenger RNA (cff mRNA) could be successfully hybridized to gene expression microarrays. Comparative analyses of the arrays from different subjects demonstrated that fetal gene expression changes could be detected as a result of fetal sex, gestational age, and disease status [1]. Furthermore, we showed that cff mRNA in AF originated from the fetus and not the placenta, which suggested that AF could be used directly to analyze fetal development and well-being. AF is widely available but generally under-utilized [2]. It is obtained primarily for fetal chromosome analysis and alpha-fetoprotein measurement to diagnose open neural tube defects. AF is an excellent source of material for research, as large quantities of supernatant are obtained for clinical diagnosis and then discarded, samples generally have correlated medical record and karyotype information available, and there is no contamination by maternal nucleic acids [2]. AF provides a way to directly query fetal development from as early as 15 weeks of gestation. We have used cff mRNA in AF to identify new biomarkers of fetal disease, develop new insights into fetal pathophysiology, and to suggest new approaches to fetal treatment.

Attitudes toward genetic testing in childhood and reproductive decision-making for familial adenomatous polyposis

Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA testing, PND and PGD among members of families at high risk for FAP. In this nationwide, cross-sectional study, questionnaires were sent to individuals from families at high risk for FAP assessing attitudes toward and experiences with childhood testing, PND and PGD, as well as several sociodemographic, clinical and psychosocial variables. Of the individuals from FAP families invited to participate in the study, 525 members participated (response rate=64%). Most parents who had children who were minors (n=93) (82%) were satisfied with the DNA testing procedure. One-third of all individuals wanted DNA testing for their children before age 12. Forty percent of FAP patients indicated that the disease influenced their desire to have children. Only 15% considered termination of pregnancy for FAP acceptable. Approximately 30% of individuals with a FAP diagnosis and their partners considered PND and PGD as acceptable for themselves. A positive attitude was associated with higher levels of guilt and a positive attitude toward termination of pregnancy. Importantly, of those with FAP at childbearing age, 84% had had no previous information at all about either PND or PGD. Future efforts should be aimed at educating FAP family members about reproductive options, allowing them to make an informed choice about family planning. Routine discussion of all reproductive options with a medical specialist should be encouraged.

3D/4D Volumetry in the Second and Third Trimester of Pregnancy

ABSTRACT Purpose of the review The technological improvements have greatly progressed on three-dimensional ultrasonography. This review summarizes these technical changes and the latest advances of their use in prenatal diagnosis. Material and methods Review of the literature. Results The new technical aspects of the volumetry, improvement of different render modes, the postprocessing modalities, and innovations on volume calculations are extensively described, as well as detailed, organ based diagnosis of different malformations in the second and third trimester are summarized. Conclusion Though the traditional 2D ultrasound with high resolution provides a great diagnostic tool in detection of fetal malformations, there is no doubt that the 3D/4D technique offers a new power in prenatal diagnosis. Three-dimensional ultrasound can assist in the diagnosis of different, rare malformations because it offers a potential benefit of understanding spatial relationships of normal and abnormal fetal anatomy.

Diagnosing Chromosomal Abnormalities From “Big” to “Small” With Molecular Cytogenetic Technology

We reviewed the available molecular cytogenetic techniques and their potential use in prenatal diagnosis of fetuses with multiple congenital anomalies and a “normal” standard chromosomal karyotype. We searched Medline to identify reports published after 1995 that were related to molecular prenatal diagnosis. After review, we reached the following conclusions:1.In fetuses with a normal standard karyotype result, common chromosomal microdeletion syndromes may be suspected based on the pattern of congenital anomalies seen on prenatal ultrasound.2.When a microdeletion syndrome is suspected based on the pattern of fetal anomalies, FISH testing for the specific molecular locus should be undertaken.3.Routine chromosome analysis, which has been the gold standard for prenatal cytogenetic diagnosis, may in the future be replaced by microarray technology with increased diagnostic capability for smaller, submicroscopic genetic alterations associated with postnatal morbidity.4.Microarray technology has been shown to increase our ability to make a diagnosis of known or new chromosomal deletion syndromes in pediatric populations with developmental delay. The use of this technology for prenatal diagnosis is currently limited but is likely to expand.