Investigation of maternal blood enriched for fetal cells: Role in screening and diagnosis of fetal trisomies

Prenatal diagnosis of chromosomal abnormalities relies on assessment of risk followed by invasive testing in the group with highest risk. Assessment of risk by a combination of maternal age and fetal nuchal translucency and invasive testing in the 5% of the population with the highest risk would identify about 80% of trisomy 21 pregnancies. Preliminary reports suggest that chromosomal abnormalities can also be diagnosed by fluorescent in situ hybridization (FISH) in maternal blood enriched for fetal cells. This study examines the potential role of this method on the prenatal diagnosis of fetal trisomies. Maternal blood was obtained before invasive testing in 230 pregnancies at 10–14 weeks of gestation. After enrichment for fetal cells, by triple density centrifugation and anti-CD71 magnetic cell sorting, FISH was performed and the proportion of cells with positive signals in the chromosomally normal and abnormal groups was determined. Fetal karyotype was normal in 150 cases and abnormal in 80 cases, including 36 with trisomy 21. Using a 21 chromosome-specific probe, three-signal nuclei were present in at least 5% of the enriched cells from 61% of the trisomy 21 pregnancies and in none of the normal pregnancies. For a cut-off of 3% of three-signal nuclei the sensitivity for trisomy 21 was 97% for a false positive rate of 13%. Similar values were obtained in trisomies 18 and 13 using the appropriate chromosome-specific probe. Examination of fetal cells from maternal blood may provide a noninvasive prenatal diagnostic test for trisomy 21 with the potential of identifying about 60% of affected pregnancies. Alternatively, this technique can be combined with maternal age and fetal nuchal translucency as a method of selecting the high-risk group for invasive testing. Potentially, 80% of trisomy 21 pregnancies could be identified after invasive testing in less than 1% of the pregnant population. Am. J. Med. Genet. 85:66–75, 1999. © 1999 Wiley-Liss, Inc.     

Early transvaginal embryo aspiration: a safer method for selective reduction in high order multiple gestations.

Assisted reproduction technologies and ovulation induction for treatment of infertility continue to cause high order multiple gestations. Increased perinatal morbidity and mortality, as well as maternal morbidity, may complicate these pregnancies. Selective fetal reduction, an acceptable therapeutic approach in these cases, is usually performed at or after the ninth week of gestation, with KCl injected in the vicinity of the fetal heart, and is associated with a total pregnancy loss rate of 11.7%. We report our experience with 90 women who underwent early (mean 7.5 weeks gestation, range 7. 0-8.0 weeks) transvaginal selective embryo aspiration. The mean number of viable embryos before and after reduction was 3.5 and 2.1 respectively. Six (6.7%) pregnancies were lost before 24 gestational weeks. One miscarriage occurred at the tenth gestational week. The other five pregnancies were aborted at 17.3-21.6 weeks gestation. Additional interventions were performed in three of these pregnancies: genetic amniocentesis in two cases and cervical suture in one case. In the subset of 39 patients with>/=4 embryos, only one (2.6%) pregnancy loss was recorded. This loss rate is significantly lower (P < 0.05) than the 15.3% loss rate in patients with >/=4 fetuses calculated from other work. Four (4.4%) other pregnancies were complicated by premature delivery (25-28 weeks gestation). Mean gestational age of delivered pregnancies in our series was 35.7 weeks. In conclusion, early transvaginal embryo aspiration is a simple and relatively safe method for multiple pregnancy reduction. The overall pregnancy loss rate associated with early embryo aspiration is similar to that of procedures performed at later gestational age, but is significantly lower when the initial number of embryos is four or greater.     

Sonographic measurement of the fetal pancreas in women with gestational diabetes

IntroductionMaternal glycemic state is positively correlated with fetal insulin secretion. Randomized control studies have shown that treatment during pregnancy inhibits to some degree this glycemic effect. Our study aimed to assess fetal pancreas size in a population of treated mothers with gestational diabetes.Material and methodsA cross-sectional, prospective observational study was conducted. Pregnant women at 19–36 weeks of gestation with pre-gestational diabetes receiving insulin therapy or with gestational diabetes receiving either insulin or oral hypoglycemic therapy were recruited. The fetal pancreas circumference was measured and compared to the normal reference range. The Z score of the difference between measured and normal predicted mean pancreas circumference, the regression analysis throughout pregnancy, and the correlation between estimated fetal weight centile and pancreas circumference were calculated.ResultsNinety-one women who had gestational diabetes and thirty-four women who had pre-gestational diabetes were included in the study. For both groups, fetal pancreas circumference correlated significantly with abdominal circumference, estimated fetal weight and gestational age. The mean Z score between the predicted pancreas circumference in the group of women diagnosed with gestational diabetes and the predicted pancreas circumference in a normal population peaked at around 24 weeks of gestation (1.1) and decreased gradually afterward to a value of zero at 37 weeks. The mean Z score between the predicted pancreas circumference in the group of women with pre-gestational diabetes and the predicted pancreas circumference in a normal population constantly decreased with duration of pregnancy. It was positive until the 25^th week of gestation and then presented negative values towards the term.ConclusionsThe presented preliminary data suggest a possible correlation between glycemic control treatment, pancreas size, and gestational age.     

Spontaneous fetal loss rates in a non‐selected population

The objective of this work was to determine the rate of spontaneous fetal loss up to 28 weeks of gestation in uncomplicated pregnancies of a low‐risk population after sonographically identified intact intrauterine pregnancy during the first trimester. Transvaginal ultrasounds were given to 2,534 women at between six and 12 weeks of gestation. Inclusion criteria were a positive fetal cardiac activity and no antecedent signs of vaginal bleeding. Gestational age was confirmed by measurement of the crown‐rump length and/or biparietal diameter (BIP). Patients were followed until delivery or up to a fetal loss. The mean fetal loss rate between 12 and 28 weeks was 3.86% (n = 99). Fetal loss increased with maternal age: fetal loss rate under 20 yr: 2.94% (OR 0.75; CI 0.23–2. 46), 20–24 yr: 3.20% (OR 0.77; CI 0.48–1.23), 25–29 yr: 3.39% (OR 0.77; CI 0.50–1.19), 30–34 yr: 3.89% (OR 1.01; CI 0.59–1.71), 35–39 yr: 7.82% (OR 2.13; CI 1.04–4.32), 40–45 y: 50% (OR 13.84; CI 6.67–28.72) and > 45 yr: 50% (OR 13.05; CI 1.96–86.71) respectively. The frequency of spontaneous fetal loss before 28 weeks gestation was assessed systematically in a low‐risk population. There was a very clear correlation with advancing maternal age. These data now can be used as background loss rate information for evaluating the safety of invasive prenatal diagnosis, and they will be more valid for this purpose than the available data taken from selected cohorts of women, such as those from hospital clinics or from infertility programs. © 2001 Wiley‐Liss, Inc.     

Increased nuchal translucency in trisomy 13 fetuses at 10–14 weeks of gestation

In a multicenter screening study for trisomy 21 involving ultrasonographic measurement of fetal nuchal translucency thickness (NT) at 10–14 weeks of gestation, 100,311 singleton pregnancies with a live fetus were examined. There were 46 cases of trisomy 13, and in 33 (72%) of these, the NT was above the 95th centile. The estimated risk for trisomy 21, based on maternal age-related risk for this chromosomal abnormality and fetal NT, was above 1 in 300 in 37 (80.1%) of the trisomy 13 fetuses. The fetal crown-rump length was significantly reduced, but the fetal heart rate was increased, being above the 95th centile in 64% of cases. Additionally, 24% of trisomy 13 fetuses had holoprosencephaly and 10% had exomphalos. This study has demonstrated that at 10–14 weeks of gestation, about 80% of fetuses with trisomy 13 can be identified in a screening program for trisomy 21, based on a combination of maternal age and fetal NT. Am. J. Med. Genet. 86:205–207, 1999. © 1999 Wiley-Liss, Inc.     

Delivery of a severely anaemic fetus after partial molar pregnancy: clinical and ultrasonographic findings

The incidence of a normal live fetus and a partial molar placenta is extremely rare. Although triploidy is the most frequent association, a fetus with normal karyotype can survive in cases of partial molar pregnancy. We report a case of partial molar placenta in which a live female baby was delivered at 32 weeks gestation by a 30-year-old woman. At the 18th week, ultrasonographic examination revealed a normal fetus with a huge, multicystic placenta. Chromosomal evaluation by amniocentesis revealed a normal female karyotype (46,XX), and serial biometric measurement of the fetus showed normal growth during pregnancy. There were no obstetric complications until the 32nd gestational week when preterm rupture of the membranes occurred. The electronic fetal heart beat tracing showed a repeated sinusoid pattern and late deceleration after admission. The patient underwent emergency Caesarean section and delivered a 1551-g, anaemic female baby with an Apgar score of 1, 4 and 6 at 1, 5 and 10 min, respectively. The baby recovered within 2 weeks after respiratory support and transfusion of packed red blood cells. Although anaemia is one of the risk factors that jeopardize the fetus in the case of partial molar pregnancy, termination is not indicated when the fetus is normal and no complications have occurred.     

Increased fetal erythroblasts in women who subsequently develop pre-eclampsia

In pregnancies complicated by pre-eclampsia (PET) and/or intrauterine growth restriction (IUGR) there is an increased number of fetal cells in the maternal circulation. The aim of this study was to investigate whether this increase in fetal cells precedes the onset of these pregnancy complications. Doppler ultrasound studies at 24 weeks gestation have shown that increased impedance to flow in the uterine arteries identifies pregnancies with impaired placental perfusion that subsequently develop PET and/or IUGR. We obtained maternal blood from 18 pregnancies with abnormal Doppler results at 22-24 weeks gestation and from 10 normal controls. Fetal erythroblasts were enriched from maternal blood by triple density gradient centrifugation and magnetic cell sorting with CD71 antibody, and the percentage of these erythroblasts was determined. The median proportion of fetal erythroblasts in the group with abnormal Doppler results was 4.5% (range 1-12%), which was significantly higher than in the control group [median 1% (range 0-3%; P < 0.001)]. Furthermore, within the group with abnormal Doppler the median proportion of fetal erythroblasts was higher in the 10 cases which subsequently developed PET and/or IUGR [median 5.5% (range 3-12%)], than in those with normal pregnancy outcome [median 2% (range 1-5%; P < 0.01)]. These findings suggest that impaired placental perfusion is associated with an increase in feto-maternal cell traffic, which precedes the onset of PET and/or IUGR by several weeks.     

Triply discordant triplets: Probability,management options,and risks

The spontaneous occurrence of triplets is rare. With increased utilization of “assisted reproductive technologies,” multifetal gestations have become more common. The empiric fetal risk for major malformation is ～ 3%. In a triplet pregnancy each fetus independently carries this risk so that the probability of having at least one malformed fetus is ～ 9%. It is much less likely to have 2 or 3 simultaneously but discordantly malformed fetuses in a multizygotic triplet gestation (.09% and .0027% risk, respectively). We report on the first case, to our knowledge, of an ovulation-stimulated triplet pregnancy complicated by 3-way discordance for major malformations diagnosed in the late second trimester by ultrasound. Fetus A was affected by congenital diaphragmatic hernia and trisomy 21; fetus B had encephalocele, a midline facial defect, and a cleft palate; and fetus C had evidence of unilateral claw hand but an otherwise normal fetal survey. At 19 weeks of gestation, fetus A was found to have spontaneously died, and a selective termination of triplet B was performed. We conclude: (1) the finding of a single major malformation in one fetus should lead to extensive search for malformations in all members of the pregnancy, and (2) the simultaneous occurrence of major malformations in more than one member of a multifetal gestation is a circumstance under which multiple selective termination deserves consideration. In this article we discuss important issues and caveats in the performance of selective termination for abnormal members of multifetal gestations. © Wiley-Liss, Inc.     

Secular trends in congenital anomaly‐related fetal and infant mortality in Canada, 1985–1996

Prenatal diagnosis of major congenital anomalies and subsequent termination of affected pregnancies has been widely available as part of routine obstetric care in recent years. In this study, vital statistical data on stillbirths, live births, and infant deaths were used to examine secular trends in gestational age‐specific and category‐specific fetal and infant mortality due to congenital anomalies in Canada (excluding Ontario and Newfoundland) from 1985–1996. Comparisons of the rates between 1985–1987 and 1994–1996 were made using relative risks and 95% confidence intervals (CI). The overall fetal mortality rate due to congenital anomalies increased significantly, from 68.0 per 100,000 total births in 1985–1987 to 78.6 per 100,000 total births in 1994–1996, while the overall infant mortality rate due to congenital anomalies decreased significantly over the same period, from 2.47 to 1.79 per 1,000 live births. The fetal death rate due to congenital anomalies at 20–21 weeks of gestation increased approximately five‐fold (relative risk [RR] = 4.83, 95% CI = 3.28–7.11) from 4.5 to 21.5 per 100,000 fetuses at risk, while the rate at 37–41 weeks decreased by 30% (RR = 0.70, 95% CI = 0.50–0.97). Fetal death rates among pregnancies at 20–25 weeks of gestation increased in all categories of congenital anomaly except anencephaly and respiratory system anomalies. Congenital anomaly‐related fetal and infant deaths have increased at early gestation but declined at later gestation in Canada. These changes suggest an increase in prenatal diagnosis and selective termination of pregnancies with congenital anomalies in recent years. © 2001 Wiley‐Liss, Inc.     

Fetal cells in the maternal circulation: isolation by multiparameter flow cytometry and confirmation by polymerase chain reaction.

During pregnancy, nucleated fetal erythrocytes enter the maternal circulation and can be isolated efficiently from the maternal cells by multiparameter flow cytometry. Male DNA, implying presence of a male fetus, can be identified in flow-sorted maternal blood by polymerase chain reaction with oligonucleotide primers flanking single-copy Y-specific DNA sequences. Among flow-sorted samples, we correctly identified fetal sex in 17/18 (94%) pregnancies of 10-21 weeks gestation. Maternal blood thus provides a potential opportunity for prenatal diagnosis that could preclude the need for invasive procedures in current use.     

A nation-wide fetal RHD screening programme for targeted antenatal and postnatal anti-D

In the Netherlands, since 1 July 2011, both antenatal anti-D immunoprophylaxis (1000 IU in the 30^th week of gestation) and postnatal prophylaxis (1000 IU) is administered to only those women for whom a fetal RHD typing, performed in week 27 of pregnancy, predicts the presence of a D-positive child. The fetal RHD screening is part of the antenatal Screening Programme for Infectious diseases and Erythrocyte immunisation (PSIE), offered to all pregnant women early in pregnancy at their first antenatal visit, preferably before 12 weeks of gestation. Currently, the compliance to the fetal RHD screening programme and the performance of the fetal RHD typing test is evaluated in a nation-wide study. At the start of the programme, it was determined that the number of false negative test results should be below 0·25%. In the first seven months after introduction of the fetal RHD screening programme, the number of false-negative results was below the critical threshold and the number of false positives around 1·1%. The compliance to the programme was in this period >95%. Our first analysis confirms that, in a centralised setting, it is possible to guide both antenatal and postnatal anti-D immunoprophylaxis by fetal RHD screening in maternal blood obtained at 27 week of gestation. The current analysis, however, is based on the cord blood samples received by Sanquin only. A longer period of nation-wide evaluation of the fetal RHD screening programme, including all (also locally typed) cord blood serology results obtained in a one-year time period, will provide insight in the robustness of the fetal RHD screening programme.     

Fetal biometry in the Brachmann-de Lange syndrome

The Brachmann-de Lange syndrome (BDLS) is diagnosed in children on the basis of a distinctive clinical phenotype which includes retarded physical growth. Because there are no genetic or biochemical tests at present, the antenatal detection of the syndrome may depend upon identification of some aspect of the phenotype in the fetus using ultrasound imaging. We studied the growth of 23 subsequently diagnosed fetuses with the BDLS using standard biometric parameters defined by prenatal ultrasound imaging. Sonographic studies were obtained through a national parents' group, the Cornelia de Lange Syndrome Foundation. Assessment of fetal growth was made using four standardized measurements: the biparietal diameter, head circumference, femur length, and abdominal circumference. These values were compared to established tables of normal fetal growth and established rations of fetal body proportions. The cross-sectional growth curve derived using all measurements collected as a composite group indicates that growth retardation would be first detected as early as 25 weeks. In five fetuses with measurements both before and after 25 weeks of gestation, longitudinal growth curves indicated that the diagnosis of “small for gestational age” would have been suggested between 20 and 25 weeks. The mean fetal weight estimates closely followed the fifth centile curve of normal fetuses both before and after 25 weeks. Cephalic indices in BDLS fetuses indicated either frank brachycephaly (25%), or were at the upper portion of the normal range. Femur lengths were relatively short (less than 90% of their expected length ) in 4 of the 11 fetuses where such information could be obtained. BDLS fetuses demonstrate early and symmetric intrauterine growth retardation. We conclude that fetal biometry can provide a valuable index in the assessment of a pregnancy suspected to be at risk for a severely affected BDLS child. © 1993 Wiley-Liss, Inc.     

The direct early diagnosis of cystic fibrosis by the detection of the deltaF508 CFTR gene mutation in a prematurely delivered boy

The suspicion of prenatal meconium ileus syndrome was raised in a pregnancy in a family with no history of cystic fibrosis because of significantly higher maternal serum alpha-fetoprotein in the 16th and 19th week of gestation, dispersed areas with increased echogenity in the fetal abdomen, slight fetal ascites in the 24th-25th weeks of gestation, decreased amniotic fluid gamma-glutamyltranspeptidase (GGT) activity and alpha-fetoprotein level in the 25th-26th weeks, and normal 46,XY karotype of the fetus. The detection of a homozygous deltaF508 cystic fibrosis transmembrane regulator (CFTR) gene mutation, by means of PCR from a small amount of white blood cells and urine sediment cells, substantiated the diagnosis of cystic fibrosis in a prematurely delivered boy in the 28th week of gestation. The repeated sweat test was unsuccessful. The autopsy examination confirmed the diagnosis of cystic fibrosis. Fetal meconium ileus syndrome was complicated by peritonitis and by formation of a meconium pseudocyst. Direct PCR typing improves postnatal diagnostic possibilities in the early neonatal period in prematurely delivered babies when the sweat test is difficult to perform.     

特异性抗体标记法检测母血中的胎儿细胞

目的　探讨免疫组化法检测孕妇外周血中胎儿有核红细胞 (nucleated red blood cell,NRBC)进行产前基因诊断的可行性。方法　对 30名孕 8～ 2 6周孕妇外周血进行密度梯度离心 ,初步富集胎儿 NRBC,细胞涂片离心机制片 ,胎儿血红蛋白 (fetal hemoglobin,Hb F)特异性抗体标记、识别 ,显微操作法获取全部阳性细胞 ,经全基因组扩增后 ,产物进行性别检测及杜氏肌营养不良 (Duchenne musculardystrophy,DMD)的基因诊断。结果　 30名孕 8～ 2 6周孕妇外周血中均发现与 Hb F呈阳性反应的胎儿NRBC。性别检测结果 30名孕妇中共检出 17名男性胎儿 ,13名女性胎儿 ,结果经孕妇引产及羊水细胞对照证实准确率达 10 0 % ,并完成 8例 DMD的产前基因诊断。结论　免疫组化法以胎儿血红蛋白 Hb Fγ链抗体标记胎儿的 NRBC进行产前基因诊断是一种很有应用前景的方法。     

Increased nuchal translucency in trisomy 13 fetuses at 10-14 weeks of gestation.

In a multicenter screening study for trisomy 21 involving ultrasonographic measurement of fetal nuchal translucency thickness (NT) at 10-14 weeks of gestation, 100,311 singleton pregnancies with a live fetus were examined. There were 46 cases of trisomy 13, and in 33 (72%) of these, the NT was above the 95th centile. The estimated risk for trisomy 21, based on maternal age-related risk for this chromosomal abnormality and fetal NT, was above 1 in 300 in 37 (80.1%) of the trisomy 13 fetuses. The fetal crown-rump length was significantly reduced, but the fetal heart rate was increased, being above the 95th centile in 64% of cases. Additionally, 24% of trisomy 13 fetuses had holoprosencephaly and 10% had exomphalos. This study has demonstrated that at 10-14 weeks of gestation, about 80% of fetuses with trisomy 13 can be identified in a screening program for trisomy 21, based on a combination of maternal age and fetal NT.     

Multiple pregnancy induction and selective fetal reduction in high genetic risk couples

Couples at risk for an inherited disorder often have severalpregnancy interruptions because of affected fetuses and difficultyin achieving their desired family. We evaluated the efficiencyand acceptability of selective fetal reduction after chorionicvillus sampling (CVS) of multiple pregnancy induced by ovarianstimulation and gamete intra-Fallopian transfer (GIFT). Thisapproach has been offered to nine patients at risk of Mendeliandiseases and one patient carrier of reciprocal translocation.The acceptance has been very high (90%). One patient at riskof an autosomic recessive disease opted for artificial donorinsemination, one conceived spontaneously, and one was a poorresponder to ovarian stimulation. Seven patients actually underwenta single GIFT procedure with six achieving pregnancy (86%),all but two being a multiple pregnancy (67%). All pregnanciesconcluded uneventfully at term and newborns were alive and healthy.Prenatal diagnosis, including fetal karyotyping in all cases,was performed at 8.5–11.5 weeks of gestation and confirmedeither on amniotic fluid aspirated at reduction or at birth.The number of fetuses was reduced to one or two because thegenetic disease was present and/or to reduce the risk of prematuredelivery and improve the likelihood of successful pregnancy.The new approach seems to be highly effective and might be considereda practical and useful alternative to preimplantation geneticdiagnosis.     

A survey of health professionals’ views on acceptable gestational age and termination of pregnancy for fetal anomaly

Termination of pregnancy for fetal anomaly is legal in the UK with no upper limit, if two doctors, in good faith, agree “there is a substantial risk that if the child were born it would suffer from such physical or mental abnormalities as to be seriously handicapped”. This is Clause E of the Human Fertlisation and Embryology Act. The most commonly sighted Clause is C, which states “the pregnancy has not exceeded its twenty-fourth week and that the continuance of the pregnancy would involve risk, greater than if the pregnancy were terminated, of injury to the physical or mental health of the pregnant woman”. This study aimed to investigate health professionals’ views on gestational age and acceptable termination of pregnancy for fetal anomaly (TOPFA).We undertook a questionnaire survey of UK health professionals working in fetal medicine, obstetrics and gynaecology and neonatology. A study pack consisting of a self-completion questionnaire, an invitation letter, participant information sheet, and a stamped addressed return envelope, were sent to health professionals. We used four fetal anomalies as case study examples in the questionnaire: isolated cleft lip, hypoplastic left heart, spina bifida and trisomy 21. These anomalies were chosen as they differed in terms of the type of anomaly, the type of impairment, and the perceived severity.Forty-one study packs were returned. For anomalies deemed less serious, later gestational ages were an important consideration when deciding acceptable TOPFA. The prognosis of an anomaly was considered an important factor in deciding whether a TOPFA was acceptable alongside gestational age. Clause C of the current UK legislation, which allows a legal termination prior to 24 weeks gestational age if continuing with the pregnancy would impact the mental health of the mother, was deemed a reasonable option for termination when parents are requesting a TOPFA. For each case study example, health professionals responded that TOPFA at ‘25 weeks and over’ was acceptable (cleft lip n?=?1; hypoplastic left heart n?=?19; spina bifida n?=?13 and Trisomy 21 n?=?10). Professionals also distinguished between their personal and professional views.These findings offer new insight into how gestational age considerations influence professionals’ conceptualisation of acceptable TOPFA.     

Clinical Practice Guidelines for Prenatal Aneuploidy Screening and Diagnostic Testing from Korean Society of Maternal-Fetal Medicine: (2) Invasive Diagnostic Testing for Fetal Chromosomal Abnormalities

The Korean Society of Maternal Fetal Medicine proposed the first Korean guideline on prenatal aneuploidy screening and diagnostic testing, in April 2019. The clinical practice guideline (CPG) was developed for Korean women using an adaptation process based on good-quality practice guidelines, previously developed in other countries, on prenatal screening and invasive diagnostic testing for fetal chromosome abnormalities. We reviewed current guidelines and developed a Korean CPG on invasive diagnostic testing for fetal chromosome abnormalities according to the adaptation process. Recommendations for selected 11 key questions are: 1) Considering the increased risk of fetal loss in invasive prenatal diagnostic testing for fetal genetic disorders, it is not recommended for all pregnant women aged over 35 years. 2) Because early amniocentesis performed before 14 weeks of pregnancy increases the risk of fetal loss and malformation, chorionic villus sampling (CVS) is recommended for pregnant women who will undergo invasive prenatal diagnostic testing for fetal genetic disorders in the first trimester of pregnancy. However, CVS before 9 weeks of pregnancy also increases the risk of fetal loss and deformity. Thus, CVS is recommended after 9 weeks of pregnancy. 3) Amniocentesis is recommended to distinguish true fetal mosaicism from confined placental mosaicism. 4) Anti-immunoglobulin should be administered within 72 hours after the invasive diagnostic testing. 5) Since there is a high risk of vertical transmission, an invasive prenatal diagnostic testing is recommended according to the clinician''s discretion with consideration of the condition of the pregnant woman. 6) The use of antibiotics is not recommended before or after an invasive diagnostic testing. 7) The chromosomal microarray test as an alternative to the conventional cytogenetic test is not recommended for all pregnant women who will undergo an invasive diagnostic testing. 8) Amniocentesis before 14 weeks of gestation is not recommended because it increases the risk of fetal loss and malformation. 9) CVS before 9 weeks of gestation is not recommended because it increases the risk of fetal loss and malformation. 10) Although the risk of fetal loss associated with invasive prenatal diagnostic testing (amniocentesis and CVS) may vary based on the proficiency of the operator, the risk of fetal loss due to invasive prenatal diagnostic testing is higher in twin pregnancies than in singleton pregnancies. 11) When a monochorionic twin is identified in early pregnancy and the growth and structure of both fetuses are consistent, an invasive prenatal diagnostic testing can be performed on one fetus alone. However, an invasive prenatal diagnostic testing is recommended for each fetus in cases of pregnancy conceived via in vitro fertilization, or in cases in which the growth of both fetuses differs, or in those in which at least one fetus has a structural abnormality. The guidelines were established and approved by the Korean Academy of Medical Sciences. This guideline is revised and presented every 5 years.     

Quantitation of fetal DNA in maternal serum during the first trimester of pregnancy by the use of a DAZ repetitive probe

Cell-free fetal DNA in maternal plasma or serum is at present widely investigated as a source of fetal genetic material, both in studies of pregnancy-related disorders and in planning strategies for non-invasive prenatal diagnosis. Despite the number of trials already performed on the quantitation of fetal DNA, data about the amount of DNA at the beginning of pregnancy, in particular in the first trimester, remain limited. A new probe mapping on the deleted in azoospermia (DAZ) repetitive region of the Yq chromosome was designed for an early assessment of fetal DNA concentration in maternal serum. Among 57 pregnant women prospectively studied in their first trimester, fetal DNA was detected already by the 5th gestational week, with the analysis becoming reliable by the 8th week of gestation when a 100% accuracy in fetal sex determination was achieved. Moreover, in the three cases of pregnancy ending in fetal loss, the amount of fetal DNA apparently decreased before the abortion was diagnosed, whereas it consistently showed an increasing trend in normal pregnancies. Real-time PCR with the use of DAZ multilocus probe can efficiently quantitate free fetal DNA in the maternal serum at the beginning of pregnancy.