age of the fetus to yield a risk score for down syndrome, trisomy 18, and trisomy 13. first trimester combined test has a sensitivity (i.e. detection rate for abnormalities) of 82–87% and a false-positive rate of around 5%. cell-free fetal dna is also available during the first trimester of pregnancy. second trimester the anomaly scan is performed between 18 and 22 weeks of gestational age. the international society of ultrasound in obstetrics and gynecology (isuog) recommends that this ultrasound is performed as a matter of routine prenatal care, to measure the fetus so that growth abnormalities can be recognized quickly later in pregnancy, and to assess for congenital malformations and multiple pregnancies (i.e. twins). the scan can detect anencephaly, open spina bifida, cleft lip, diaphragmatic hernia, gastroschisis, omphalocele, congenital heart defect, bilateral renal agenesis, osteochondrodysplasia, edwards syndrome, and patau syndrome. a second-trimester quad blood test may be taken (the triple test is widely considered obsolete but in some states, such as missouri, where medicaid only covers the triple test, that's what the patient typically gets). with integrated screening, both a first trimester combined test and a triple/quad test is performed, and a report is only produced after both tests have been analyzed. however patients may not wish to wait between these two sets of tests. with sequential screening, a first report is produced after the first trimester sample has been submitted, and a final report after the second sample. with contingent screening, patients at very high or very low risks will get reports after the first-trimester sample has been submitted. only patients with moderate risk (risk score between 1:50 and 1:2000) will be asked to submit a second-trimester sample, after which they will receive a report combining information from both serum samples and the nt measurement. the first trimester combined test and the triple/quad test together have a sensitivity of 88–95% with a 5% false-positive rate for down syndrome, though they can also be analyzed in such a way as to offer a 90% sensitivity with a 2% false-positive rate. finally, patients who do not receive an nt ultrasound in the 1st trimester may still receive a serum integrated test involving measuring papp-a serum levels in the 1st trimester and then doing a quad test in the 2nd trimester. this offers an 85–88% sensitivity and 5% false-positive rate for down syndrome. also, a patient may skip the 1st-trimester screening entirely and receive only a 2nd-trimester quad test, with an 81% sensitivity for down syndrome and 5% false-positive rate. third trimester third-trimester prenatal testing generally focuses on maternal wellbeing and reducing fetal morbidity/mortality. group b streptococcal infection (also called group b strep) may be offered, which is a major cause of neonatal morbidity and mortality. group b strep is an infection that may be passed to an infant during birth. vaginal screening for gbs is performed between 34 and 37 weeks of gestational age, so that mothers that are positive for the bacterium can receive treatment before delivery. during the third trimester, some institutions may require evaluations of hemoglobin/hematocrit, syphilis serology, and hiv screening. also, before delivery, an assessment of fetal position and estimated fetal weight is documented. maternal serum screening first-trimester maternal serum screening can check levels of free β-hcg, papp-a, intact or beta hcg, or h-hcg in the woman's serum, and combine these with the measurement of nuchal translucency (nt). some institutions also look for the presence of a fetal nasalbone on the ultrasound. second-trimester maternal serum screening (afp screening, triple screen, quad screen, or penta screen) can check levels of alpha fetoprotein, β-hcg, inhibin-a, estriol, and h-hcg (hyperglycosolated hcg) in the woman's serum. the triple test measures serum levels of afp, estriol, and beta-hcg, with a 70% sensitivity and 5% false-positive rate. it is complemented in some regions of the united states, as the quad test (adding inhibin a to the panel, resulting in an 81% sensitivity and 5% false-positive rate for detecting down syndrome when taken at 15–18 weeks of gestational age). the biomarkers papp-a and β-hcg seem to be altered for pregnancies resulting from icsi, causing a higher false-positive rate. correction factors have been developed and should be used when screening for down's syndrome in singleton pregnancies after icsi, but in twin pregnancies such correction factors have not been fully elucidated. in vanishing twin pregnancies with a second gestational sac with a dead fetus, first-trimester screening should be based solely on the maternal age and the nuchal translucency scan as biomarkers are altered in these cases. advances in prenatal screening measurement of fetal proteins in maternal serum is a part of standard prenatal screening for fetal aneuploidy and neural tube defects. computational predictive model shows that extensive and diverse feto-maternal protein trafficking occurs during pregnancy and can be readily detected non-invasively in maternal whole blood. this computational approach circumvented a major limitation, the abundance of maternal proteins interfering with the detection of fetal proteins, to fetal proteomic analysis of maternal blood. entering fetal gene transcripts previously identified in maternal whole blood into a computational predictive model helped develop a comprehensive proteomic network of the term neonate. it also shows that the fetal proteins detected in pregnant woman's blood originate from a diverse group of tissues and organs from the developing fetus. development proteomic networks dominate the functional characterization of the predicted proteins, illustrating the potential clinical application of this technology as a way to monitor normal and abnormal fetal development. the difference in methylation of specific dna sequences between mother and fetus can be used to identify fetal-specific dna in the blood circulation of the mother. in a study published in the march 6, 2011, online issue of nature, using this non-invasive technique a group of investigators from greece and uk achieved correct diagnosis of 14 trisomy 21 (down syndrome) and 26 normal cases. using massive parallel sequencing, a study testing for trisomy 21 only, successfully detected 209 of 212 cases (98.6%) with 3 false-positives in 1,471 pregnancies (0.2%). with commercially available non-invasive (blood) testing for down syndrome having become available to patients in the united states and already available in china, in october 2011, the international society for prenatal diagnosis created some guidance. based on its sensitivity and specificity, it constitutes an advanced screening test and that positive results require confirmation by an invasive test, and that while effective in the diagnosis of down syndrome, it cannot assess half the abnormalities detected by invasive testing. the test is not recommended for general use until results from broader studies have been reported, but may be useful in high-risk patients in conjunction with genetic counseling. a study in 2012 found that the maternal plasma cell-free dna test was also able to detect trisomy 18 (edwards syndrome) in 100% of the cases (59/59) at a false-positive rate of 0.28%, and trisomy 13 (patau syndrome) in 91.7% of the cases (11/12) at a false-positive rate of 0.97%. the test interpreted 99.1% of samples (1,971/1,988); among the 17 samples without an interpretation, three were trisomy 18. the study stated that if z-score cutoffs for trisomy 18 and 13 were raised slightly, the overall false-positive rates for the three aneuploidies could be as low as 0.1% (2/1,688) at an overall detection rate of 98.9% (280/283) for common aneuploidies (this includes all three trisomies: down, edwards and patau). screening for chromosomal abnormalities the goal of prenatal genetic testing is to identify pregnancies at high risk of abnormalities, allowing for early intervention, termination or appropriate management and preparation measures. ultrasound imaging and serum markers as indications for genetic testing ultrasound imaging provides the opportunity to conduct a nuchal translucency (nt) scan screening for chromosomal abnormalities such as down syndrome (trisomy 21), edwards syndrome (trisomy 18), and patau syndrome (trisomy 13). using the information from the nt scan the mother can be offered an invasive diagnostic test for fetal chromosomal abnormalities. serum markers are utilized in a similar fashion to identify gestations that should be recommended for further testing. when the nt scan or serum markers arouse suspicion for chromosomal abnormalities the following genetic tests may be conducted on fetal or placental tissue samples: interphase-fluorescence in situ hybridization (fish), quantitative pcr and direct preparation of chromosomes from chorionic villi. fetal cell-free dna fetal cell-free dna testing allows for the detection of apoptotic fetal cells and fetal dna circulating in maternal blood for the noninvasive diagnosis of fetal aneuploidy. a meta-analysis that investigated the success rate of using fetal cell-free dna from maternal blood to screen for aneuploidies found that this technique detected trisomy 13 in 99% of the cases, trisomy 18 in 98% of the cases and trisomy 21 in 99% of the cases. failed tests using fetal cell-free dna are more likely to occur in fetuses with trisomy 13 and trisomy 18 but not with trisomy 21. previous studies found elevated levels of cell-free fetal dna for trisomy 13 and 21 from maternal serum when compared to women with euploid pregnancies. however, an elevation of cell-free dna for trisomy 18 was not observed. circulating fetal nucleated cells comprise only three to six percent of maternal blood plasma dna, reducing the detection rate of fetal developmental abnormalities. two alternative approaches have been developed for the detection of fetal aneuploidy. the first involves the measuring of the allelic ratio of single nucleotide polymorphisms (snps) in the mrna coding region in the placenta. the next approach is analyzing both maternal and fetal dna and looking for differences in the dna methylation patterns. digital pcr recently, it has been proposed that digital pcr analysis can be conducted on fetal cell-free dna for detection of fetal aneuploidy. research has shown that digital pcr can be used to differentiate between normal and aneuploid dna. a variation of the pcr technique called multiplex ligation-dependent probe amplification (mlpa), targeting dna, has been successively applied for diagnosing fetal aneuploidy as a chromosome- or gene-specific assay. shotgun sequencing fetal cell-free dna has been directly sequenced using shotgun sequencing technology. in one study, dna was obtained from the blood plasma of eighteen pregnant women. this was followed by mapping the chromosome using the quantification of fragments. this was done using advanced methods in dna sequencing resulting in the parallel sequencing of the fetal dna. the amount of sequence tags mapped to each chromosome was counted. if there was a surplus or deficiency in any of the chromosomes, this meant that there was a fetal aneuploid. using this method of shotgun sequencing, the successful identification of trisomy 21 (down syndrome), trisomy 18 (edward syndrome), and trisomy 13 (patau syndrome) was possible. this method of noninvasive diagnosis is now starting to be heavily used and researched further. other techniques fetal components in samples from maternal blood plasma can be analyzed by genome-wide techniques not only by total dna, but also by methylated dna immunoprecipitation (with tiling array), microrna (such as with megaplex) and total rna (rna-sequencing). patient acceptance research was conducted to determine how women felt about noninvasive diagnosis of fetal aneuploid using maternal blood. this study was conducted using surveys. it was reported that eighty-two percent of pregnant women and seventy-nine percent of female medical students view this type of diagnosis in a positive light, agreeing that it is important for prenatal care. overall, women responded optimistically that this form of diagnosis will be available in the future. ethical and practical issues non-genetic prenatal testing parents need to make informed decisions about screening, diagnosis, and any actions to be taken as a result. many screening tests are inaccurate, so one worrisome test result frequently leads to additional, more invasive tests. if prenatal testing confirms a serious disability, many parents are forced to decide whether to continue the pregnancy or seek an abortion. the "option" of screening becomes an unexpected requirement to decide. see wrongful abortion. in some genetic conditions, for instance cystic fibrosis, an abnormality can only be detected if dna is obtained from the fetus. usually an invasive method is needed to do this. ultrasound of a fetus, which is considered a screening test, can sometimes miss subtle abnormalities. for example, studies show that a detailed 2nd-trimester ultrasound, also called a level 2 ultrasound, can detect about 97% of neural tube defects such as spina bifida . ultrasound results may also show "soft signs," such as an echogenic intracardiac focus or a