First and second trimester screening for fetal structural anomalies.

Fetal structural anomalies are found in up to 3% of all pregnancies and ultrasound-based screening has been an integral part of routine prenatal care for decades. The prenatal detection of fetal anomalies allows for optimal perinatal management, providing expectant parents with opportunities for additional imaging, genetic testing, and the provision of information regarding prognosis and management options. Approximately one-half of all major structural anomalies can now be detected in the first trimester, including acrania/anencephaly, abdominal wall defects, holoprosencephaly and cystic hygromata. Due to the ongoing development of some organ systems however, some anomalies will not be evident until later in the pregnancy. To this extent, the second trimester anatomy is recommended by professional societies as the standard investigation for the detection of fetal structural anomalies. The reported detection rates of structural anomalies vary according to the organ system being examined, and are also dependent upon factors such as the equipment settings and sonographer experience. Technological advances over the past two decades continue to support the role of ultrasound as the primary imaging modality in pregnancy, and the safety of ultrasound for the developing fetus is well established. With increasing capabilities and experience, detailed examination of the central nervous system and cardiovascular system is possible, with dedicated examinations such as the fetal neurosonogram and the fetal echocardiogram now widely performed in tertiary centers. Magnetic resonance imaging (MRI) is well recognized for its role in the assessment of fetal brain anomalies; other potential indications for fetal MRI include lung volume measurement (in cases of congenital diaphragmatic hernia), and pre-surgical planning prior to fetal spina bifida repair. When a major structural abnormality is detected prenatally, genetic testing with chromosomal microarray is recommended over routine karyotype due to its higher genomic resolution.

Resultados perinatales y obstétricos en fetos con translucencia nucal incrementada / Perinatal and obstetric outcomes in fetuses with increased nuchal translucency

El objetivo es analizar los resultados perinatales y obstétricos de las gestaciones en cuya ecografía del primer trimestre se objetivó translucencia nucal incrementada. Obtuvimos 170 translucencias nucales aumentadas (mayor o igual a 3,5 mm), en 62 casos (36,47%) el cariotipo fue normal, en 84 casos (49,41%) fue patológico y en 24 casos (14,11%) no se realizó técnica invasiva. Del total de cariotipos normales (62 casos), 47 gestaciones llegaron a término con parto en nuestro centro y recién nacido normal, dos abortos tras realización de técnica invasiva y hubo diez interrupciones legales del embarazo. Los hallazgos ecográficos encontrados son los siguientes: un caso con megavejiga (2,12%), un caso con onfalocele (2,12%), dos casos de higroma quístico (4,3%), dos hidrops fetales severos, ambos con canal aurícoventricular completo, dos ausencias del hueso nasal (4,3%) y cuatro comunicaciones interventriculares (8,5%). En cuanto al total de translucencia nucal incrementada, 39 casos se correspondieron con trisomía del par 21 (23%), 18 con de trisomía 18 (10,6%), 10 con trisomía 13 (5,9%), 14 con 45XO (8,2%), 1 con 47XXX, (0,7% ), 1 con trisomía 10 (0,7%) y 1 con translocación balanceada 45 XX (t 8;21) (p11;q11)(0,7%). El incremento del grosor de la translucencia nucal entre las 11 y 13 semanas y seis días constituye una expresión fenotípica común de las aneuploidías y una gama de malformaciones fetales y síndromes genéticos. En los fetoseuploides, la prevalencia de las anormalidades fetales y los resultados perinatales adversos aumenta con el incremento de la translucencia nucal (AU)

The objective was to analyze the perinatal and obstetric outcomes of pregnancies, in which increased NT was detected onfirst-trimesterroutine ultrasoundstudy. A total of 170 cases of increased nuchal translucency (equal to or higher than 3.5mm)were detected. Within these cases, 62 (36,47%) had normal karyotype, 84 (49,41%) had aneuplody and 24 (14,11%) were not subjected to invasive techniques. From the group of patients with augmented nuchal translucency and normal karyotype (62), 47 reached full-term delivery at our hospital and the newborns were normal; 2 ended in miscarriage after undergoing an invasive technique, 10 ended in legal termination of pregnancy and 3 did not give birth at our hospital and their data were not available. Ultrasound findings in these patients included: one case of megacystis (2,12%), one case of omphalocele (2,12%), two cases of cystic hygroma (4,3%), two cases of severe hydrops fetalis both with complete AV canal (4,3%), two cases of absent nasal bone (4,3%) and four cases of interventricular communication (IVC) (8,5%). From the total of cases of increased nuchal translucency, 39 corresponded to trisomy-21 (23%); 18 (10,6%) to trisomy-18; 10 to trisomy-13 (5,9%); 14 to Turner’s syndrome (8,2%), 1 to karyotype 47XXX (0,7%); 1 to trisomy-10 (0,7%) and 1 to balanced translocation 45 XX (t 8;21) (p11;q11) (0,7%). Nuchal translucency thickening between weeks 11 and 13+6 days is a common phenotypical manifestation of a neuploidy and a wide range of fetal malformations and genetic syndromes. In euploid fetuses, the prevalence of fetal abnormal findings and adverse perinatal outcome increases with the nuchal translucency value (AU)

Non-invasive prenatal testing for aneuploidy: current status and future prospects.

Non-invasive prenatal testing (NIPT) for aneuploidy using cell-free DNA in maternal plasma is revolutionizing prenatal screening and diagnosis. We review NIPT in the context of established screening and invasive technologies, the range of cytogenetic abnormalities detectable, cost, counseling and ethical issues. Current NIPT approaches involve whole-genome sequencing, targeted sequencing and assessment of single nucleotide polymorphism (SNP) differences between mother and fetus. Clinical trials have demonstrated the efficacy of NIPT for Down and Edwards syndromes, and possibly Patau syndrome, in high-risk women. Universal NIPT is not cost-effective, but using NIPT contingently in women found at moderate or high risk by conventional screening is cost-effective. Positive NIPT results must be confirmed using invasive techniques. Established screening, fetal ultrasound and invasive procedures with microarray testing allow the detection of a broad range of additional abnormalities not yet detectable by NIPT. NIPT approaches that take advantage of SNP information potentially allow the identification of parent of origin for imbalances, triploidy, uniparental disomy and consanguinity, and separate evaluation of dizygotic twins. Fetal fraction enrichment, improved sequencing and selected analysis of the most informative sequences should result in tests for additional chromosomal abnormalities. Providing adequate prenatal counseling poses a substantial challenge given the broad range of prenatal testing options now available.

The impact of utilization of early aneuploidy screening on amniocenteses available for training in obstetrics and fetal medicine.

OBJECTIVE: First-trimester aneuploidy screening has high detection rates and low false-positive rates. Their use as well as the implementation of non-invasive prenatal testing may affect specialty training in prenatal diagnosis procedures. STUDY DESIGN: Descriptive study of first-trimester aneuploidy screening and amniocentesis in an obstetric training program. Screening methods were tracked from their introduction in 2004 through 2011. The volume of amniocentesis procedures from 2000 to 2011 was evaluated. RESULTS: First-trimester screening tests increased from 283 to 1225 between 2005 and 2011, whereas genetic amniocenteses declined from 460 to 168 during the same period. The percent of older women who chose a first-trimester screen test rose from 12.7% to 44.2% CONCLUSION: First-trimester screening options reduce genetic amniocenteses available for training. Fetal medicine and general obstetrics training programs need to evaluate their clinical experience and determine whether simulation training methods are needed for education.

Invasive prenatal diagnostic practice in Denmark 1996 to 2006.

The Danish National Board of Health recommended in 2004 routine ultrasound scanning in week 12 with nuchal translucency measurement, combined with the double test to all pregnant women. Those who were found to have a risk of trisomy 21 higher than 1:300 were offered amniocentesis or chorionic villus sampling (CVS). The total number of pregnancies in Denmark with an invasive prenatal procedure decreased from 6,929 in 1996 to 3,103 in 2006, the percentage of CVS increased from 45 to 69%, and the percentage of women below 35 years among those undergoing invasive procedures increased from 38 to 52%. The mean gestational age at which the procedures were done increased--for CVS from week 11 to 13, and for amniocentesis from week 16 to 17. We thus achieved to more than double the offer of prenatal screening and at the same time reduce the number of invasive procedures by 55%.

Use of the genetic sonogram in the United States in 2001 and 2007.

OBJECTIVE: The purpose of this study was to determine whether there have been changes in the use of second-trimester genetic sonograms and in the second-trimester sonographic markers used to screen for fetal aneuploidy by maternal-fetal medicine specialists in the United States from 2001 to 2007. METHODS: A survey was mailed to Society for Maternal-Fetal Medicine members in the United States in April 2007 inquiring about their practice patterns regarding the genetic sonogram. Specific sonographic markers used for risk adjustment as part of the genetic sonogram were also assessed. The responses from 2007 were compared with responses from a similar survey administered in 2001 (Am J Obstet Gynecol 2002; 187:1230-1234) using descriptive statistics, the chi(2) test, and the Wilcoxon rank sum test. RESULTS: A total of 991 responses were analyzed: 543 of 1638 (32%) in 2001 and 448 of 1756 (26%) in 2007. Significant increases (P < .0001) were noted in the number of specialists who used the genetic sonogram as a screening tool for Down syndrome and for every single sonographic marker used to adjust a woman's risk for having a fetus with Down syndrome during a genetic sonogram, except for choroid plexus cyst, clinodactyly, sandal gap toes, and widened pelvic angle. CONCLUSIONS: Practitioners in the United States are using an increasing number of second-trimester sonographic markers to help identify aneuploid fetuses. The growing acceptance of sonography to screen for fetal aneuploidy and the recommendation by the American College of Obstetricians and Gynecologists for universal screening suggest that more resources may be necessary to meet the growing demand for second-trimester sonograms.

First trimester diagnosis and screening for fetal aneuploidy.

Maternal serum screening for neural tube defects and fetal aneuploidy in the second trimester has been incorporated into obstetrical practice over the past two decades. Now, as a result of several multicenter trials, first trimester screening between 11 and 14 weeks has been shown to be an effective and reliable screening test for Down syndrome and trisomy 18. Benefits of first trimester screening include earlier identification of the pregnancy at risk for fetal aneuploidy and anatomic defects, in particular, cardiac anomalies, and the option of earlier diagnosis by chorionic villus sampling, if available. This policy updates the American College of Medical Genetics policy statement entitled Second Trimester Maternal Serum Screening for Fetal Open Neural Tube Defects and Aneuploidy (2004) and complements the sections of American College of Medical Genetic's Standards and Guidelines for Clinical Genetics Laboratories entitled "Prenatal screening for Down syndrome that includes first trimester biochemistry and/or ultrasound measurements."

[Recent advances in prenatal diagnostics]. / Neue Möglichkeiten in der pränatalen Diagnostik.

During the last years, technical improvements have increased the possibilities in prenatal ultrasound. During the eighties and nineties, fetal malformations were increasingly detected and specified. Since a few years, the measurement of the fetal nuchal translucency between 11 and 14 weeks of gestation has been implemented to calculate the individual risk, in combination with most recent biochemical markers. Today, the sonographic measurement of the nuchal translucency is regarded as a valuable screening tool for chromosomal anomalies in prenatal medicine. Beside standardized examinations, a profound information and counseling of the pregnant women should be emphasized. With the improvement of the specific maternal risk calculation, using the sonographic measurement of the nuchal translucency, the biochemical markers and the maternal age, unnecessary invasive examinations may be prevented and their overall number can significantly be reduced. The same trend is seen in the whole field of prenatal medicine, illustrated by the detection of the fetal rhesus D status from the maternal blood and the use of Doppler ultrasound in the management of fetal anemia.