Amniocentesis For Advanced Maternal Age Research Articles

A prenatal case misunderstood as specimen confusion: 46,XY/46,XY chimerism

Chimerism results from the fusion of two zygotes in a single embryo, whereas mosaicism results from mitotic errors in a single zygote. True human chimerism is rare, with fewer than 100 cases reported in the literature. Here, we report a case in which the fetus was identified as having tetragametic chimerism based on short tandem repeat - polymerase chain reaction analysis of the family observed during amniocentesis for advanced maternal age. The chimerism occurred via the fertilization of two ova by two spermatozoa, followed by the fusion of early embryos. The genotypes of the two amniotic fluid samples obtained successively by one puncture were completely different, and the sex chromosomes were XY. Karyotyping and copy number variation sequencing showed no abnormalities. The fetus was delivered at term and the phenotype of the newborn was normal.

Metabolic characterization of amniotic fluids of fetuses with enlarged nuchal translucency.

Background In prenatal diagnosis, a thickened nuchal translucency (NT) is one of the most sensitive and specific markers for several defects but it may also be found in 5% of healthy fetuses. The pathophysiological causes that lead to an increase in NT are not yet fully understood. Metabolomics represents a new promising approach, useful for studying different metabolites in biological organisms in response to environmental stressors. The aim of our study was to investigate the metabolomic profile of the amniotic fluid samples (AFS) of euploid fetuses with enlarged nuchal translucency (ENT) compared to a control group (C group). Methods This study was carried out on a group of women who underwent second-trimester amniocentesis for advanced maternal age (C group) or for NT ≥95th percentile (ENT group) found during first-trimester aneuploidy screening. AFS were analyzed with proton nuclear magnetic resonance (1H-NMR) and high-performance liquid chromatography (HPLC), and subsequent multivariate and univariate statistical analyses were conducted, followed by pathway analysis. Results In total, 67 AFS from the C group and 23 from the ENT group were analyzed. Partial least square discriminate analysis was carried out (R2X=0.784, R2Y=0.658, Q2=0.622, P<0.0001). A different metabolic profile was observed in the ENT group compared with the C group, suggesting an energetic shift to a glycolytic phenotype in an oxidative environment in the ENT group compared to the C group. Conclusion Metabolomic studies enable the identification of metabolic alterations occurring in fetuses with ENT. These findings may provide a new basis for better understanding the pathophysiological mechanisms in this prenatal phenomenon.

EP09.01: Introduction of non‐invasive prenatal testing (NIPT): did it impact the parental choice of prenatal examinations?

In Japan, In order to establish minimally biased ethical decisions and educational counselling for patients prior to the NIPT, a consortium was formed in 2013. NIPT is currently provided under the scheme of clinical research by selected clinical centres. However, the public interest in this test has grown rapidly. We started to provide NIPT in our hospital from April 2014. The objective of this study is to investigate the changes of the parental choice or demand on genetic screening and diagnosis after the adoption of NIPT. We investigated the pregnant women who had undergone maternal serum marker screening test (SM), NIPT or amniocentesis (AC) before 22 weeks of gestation in our hospital from April 2008 to December 2014 by chart-review. During the 8 years before NIPT, 9,448 deliveries were managed. During that period 1,663 women (17.6% of total deliveries) of over the age of 35 underwent SM and 1,504 (15.9%) of under 35 year-old underwent SM. Among 667 of AC cases, 399 (4.2%) of over 35 year-old women without any past history or fetal findings underwent AC because of advanced maternal age (AMA) and 58 (0.61%) of under 35 just for anxiety. During the 9 months after NIPT, 1,380 deliveries were managed and 95 women(6.9% of total deliveries) had NIPT. SM over 35 year-old (147 cases, 10.7%) and AC for AMA (35 cases, 2.5%) decreased. However SM under 35 year-old (225 cases, 16.3%) showed no fluctuation, AC just for anxiety (10 cases, 0.72%) slightly increased. The rates of abnormal karyotype by AC were 7.8% before NIPT and 8.9% after NIPT. No abnormality was detected in the group of AC just for anxiety. Women of advanced age who undergo SM or AC decreased due to the provision of NIPT. The phenomenon that women of younger age who undergo SM or AC remained or slightly increased indicates that the trend in prenatal genetic screening is rising regardless of maternal age. Every perinatologist should readily offer appropriate information and treatment to meet the public demands.

Pericentric Inversion of Human Chromosome 9 Epidemiology Study in Czech Males and Females

Pericentric inversion of human chromosome 9 [inv(9)] is a relatively common cytogenetic finding. It is largely considered a clinically insignificant variant of the normal human karyotype. However, numerous studies have suggested its possible association with certain pathologies, e.g., infertility, habitual abortions or schizophrenia. We analysed the incidence of inv(9) and the spectrum of clinical indications for karyotyping among inv(9) carriers in three medical genetics departments in Prague. In their cytogenetic databases, among 26,597 total records we identified 421 (1.6 %) cases of inv(9) without any concurrent cytogenetic pathology. This study represents the world’s largest epidemiological study on inv(9) to date. The incidence of inv(9) calculated in this way from diagnostic laboratory data does not differ from the incidence of inv(9) in three specific populationbased samples of healthy individuals (N = 4,166) karyotyped for preventive (amniocentesis for advanced maternal age, gamete donation) or legal reasons (children awaiting adoption). The most frequent clinical indication in inv(9) carriers was “idiopathic reproductive failure” – 37.1 %. The spectra and percentages of indications in individuals with inv(9) were further statistically evaluated for one of the departments (N = 170) by comparing individuals with inv(9) to a control group of 661 individuals with normal karyotypes without this inversion. The proportion of clinical referrals for “idiopathic reproductive failure” among inv(9) cases remains higher than in controls, but the difference is not statistically significant for both genders combined. Analysis in separated genders showed that the incidence of “idiopathic reproductive failure” could differ among inv(9) female and male carriers.

Case 2: A premature infant with ambiguous genitalia

An infant born at 30 weeks’ gestation to a 39-year-old G2P0A1 mother presented with ambiguous genitalia. The infant’s mother was a smoker, but was otherwise healthy. She was not on any medication and had received routine prenatal care. A maternal serum screen predicted low risk for Down syndrome and spina bifida. Amniocentesis for advanced maternal age demonstrated a 46XY fetus. Ultrasounds during the pregnancy demonstrated severe intrauterine growth restriction (IUGR), decreased amniotic fluid and abnormal genitalia. Birth weight was 630 g, length was 30.7 cm and head circumference was 24 cm (all <<3rd percentile). Physical examination revealed a wasted infant with severe hypospadias and micropenis. The penile length was 7 mm, more than 2 SD below the mean for 30 weeks’ gestation (–2 SD = 17mm). The testicles were palpable within both inguinal canals. The baby did not exhibit dysmorphic features. The patient’s electrolytes and glucose levels were normal. Testosterone (T) and dihydrotestosterone (DHT) levels, measured two days after birth, were both normal for the infant’s age. An ultrasound showed no evidence of female reproductive organs. Further diagnostic tests at two months of age suggested a probable diagnosis.

Cephalothoracopagus, janiceps, disymmetros, monoomphalian conjoined twins undiagnosed until early second trimester

Cephalothoracopagus is the less common type of conjoined twins (CTs) with an incidence estimated at one in three million births or one in 58 conjoined twins. Maternal gene Vg1, a member of the TGF-beta family of cell-signalling molecules which are implicated in dorsoanterior development, and specific actions of Hox and Pax genes that are implicated in very early embryogenesis may be identified as aetiologic factors. A prenatal diagnosis of cephalothoracopagus CTs diagnosed at 17 weeks in a woman undergoing amniocentesis for advanced maternal age is reported. Although first-trimester diagnosis of CTs is feasible and has been reported as early as 8 weeks's gestation, CTs may be misdiagnosed with monoamniotic twins, lymphangioma, teratoma, and/or neoplasm and may be undiagnosed until early second trimester. Three-dimensional and color Doppler ultrasound enabled precise prenatal visualization of the fusion site. Ultrafast MR imaging should be considered an adjunct to ultrasound for antenatal characterization of structural anomalies and for planning surgical separation in selected cases. Echocardiography is mandatory in all cases of CTs as congenital heart defects are seen in 20-30% and polyhydramnios in 50-75%. Neural tube and midline fusion defects, diaphragmatic hernia, and imperforate anus are the frequently associated abnormalities. Prognosis among survivors is usually poor (44% die in the neonatal period) and is dependent upon the type of conjunction, degree of involvement of the shared organs, and presence or absence of associated anomalies, with the worst prognosis in case of twins sharing liver and heart.

Prenatal diagnosis and prognosis of triple X syndrome: 47, XXX

Triple X syndrome is a relatively common sex chromosomal abnormality occurring in 0,1% of live-born female infants. Most of these infants have a normal phenotype and only a few cases with 47, XXX karyotype have congenital malformations. We report three cases of triple X syndrome that were diagnosed prenatally by genetic amniocentesis for advanced maternal age and have been observed from birth to age of 3 to 12 years. A description of their growth and development is presented. The birth weight was normal in all patients and one of them had facial dysmorphism with right microphtalmia and auricular septal defect. During the first 2 years of life, the neuromotor development of these infants was not distinguishable from chromosomally normal children. By 3 years of age, two patients have a moderate developmental delay in speech and language. One girl 12-year-old had normal schooling. The diagnosis of the triple X syndrome can be never made because clinical demonstrations are not rather important to arouse the demand of a karyotype. Prenatal diagnosis is often made in front of the advanced maternal age. Expectant parents must be counseled as to the significance of this 47, XXX karyotype and prognostic information must be given.

Diagnostic anténatal de la trisomie 21: expérience du service A du centre de maternité de Tunis

Down syndrome (Trisomy 21) is the most common fetal chromosomal abnormality in humans. Its clinical signs are now well known. Methods for prenatal screening have advanced substantially in the past two decades. To describe our experience with prenatal diagnosis of Down syndrome, including the indications, methods and results. This retrospective study examined cases over a 4-year period. We adopted a sequential screening strategy for patients followed in our department since the beginning of their pregnancies after informed consent. We proposed first trimester ultrasound that measured nuchal translucency thickness and followed it with maternal serum screening. Some patients underwent screening during the second trimester or third trimester ultrasound. To assess the results, we studied the mothers' epidemiological characteristics and analysed the circumstances of prenatal diagnosis of trisomy 21 (T21). We identified 22 cases of T21 during the study period, for a total prevalence of 0.98 per thousand. The diagnosis was prenatal in 13 cases, mainly due to ultrasound signs. Of the 14 patients seen prenatally, only 8 were followed from early pregnancy. Five had enlarged nuchal translucency (> 95th percentile). Three had positive second trimester serum screening tests. One patient had amniocentesis planned because of her age (table 1). T21 was diagnosed in the second trimester in two cases and in the third trimester in three. The major morphological abnormalities observed were cardiac. We found an atrioventricular canal defect in four cases, and fetal hydrops in two cases (Table 2). The median gestational age at diagnosis of T21 in this study was 21 weeks. The diagnosis was missed in one patient followed throughout pregnancy in our unit. The median gestational age at termination of pregnancy was 22 weeks. Only one patient chose not to terminate the pregnancy. Her fetus, delivered at term, had no major pathologies. The establishment of a screening strategy for trisomy 21 in Tunisia is necessary to reduce handicaps. It should begin by expanding first-trimester ultrasound with nuchal translucency measurement. At the same time, serum marker testing should be offered to all patients. Routine amniocentesis for advanced maternal age should be avoided.

Complex chromosome rearrangement and recombinant balanced translocation in a mother and a daughter with the same phenotypic abnormalities

We report on the diagnosis of a complex chromosome rearrangement in a mother and the transmission of a simplified translocation in her fetus. The mother had mental retardation, short stature, facial dysmorphism, and hydronephrosis, but was never investigated before she was pregnant. A blood sample was taken for karyotyping at the time of amniocentesis for advanced maternal age. The mother's karyotype revealed two translocations involving chromosome 5, chromosome 16 twice, and chromosome 20 as follow: 46,XX,t(5;16;20)(5pter-->5q11.2::16q12.1-->16q23::20p11.2-->20pter;16pter-->16q12.1::5q11.2-->5qter;16qter-->16q23::20p11.2-->20qter). The amniocentesis revealed a female karyotype with an apparently balanced translocation: 46,XX,t(16;20)(q23;p11.2). The translocation of the fetus probably resulted from a meiotic recombination between the derived 5 and the normal 16 in the mother. The baby was born and presented the same facial dysmorphism and hydronephrosis. The simplification of a complex rearrangement through recombination into a balanced product has only been rarely described and it is to our knowledge the first time that both the carrier of the complex rearrangement and her descendant with a simplified rearrangement share phenotypic abnormalities.

Impact of Second-Trimester Maternal Serum Screening on Prenatal Diagnosis of Down Syndrome and the use of Amniocentesis in the Taiwanese Population

Summary Objective To investigate the impact of second-trimester maternal serum screening on prenatal diagnosis of Down syndrome and the use of amniocentesis in the Taiwanese population. Materials and Methods From 1990 to 2000, 166,419 amniocenteses were analyzed cytogenetically in the Taiwanese population. Among these, 58.85% were for advanced maternal age, 4.5% for abnormal ultrasound findings, 26.17% for abnormal maternal serum screening results, 1.82% for a previous child with congenital anomaly, 1.02% for a family history of chromosome aberrations, and 7.63% for other purposes. Chromosome aberrations were detected in 4,217 cases (2.53%), of which 1,277 (30.28%) were Down syndrome. Of the Down syndrome cases, 65.86% were detected by amniocentesis for advanced maternal age, 5.95% for abnormal ultrasound findings, 21.14% for abnormal maternal serum screening results, 1.25% for a previous child with congenital anomaly, 1.18% for a family history of chromosome aberrations, and 4.62% for other purposes. Results There was a prominent increase in the number of women undergoing amniocentesis in the Taiwanese population between 1990 and 2000. There was an 8.9-fold increase in the number undergoing amniocentesis for advanced maternal age, a 6.3-fold increase in that for abnormal ultrasound findings, a 46.2-fold increase in that for abnormal maternal serum screening results, a 2.9-fold increase in that for a previous child with congenital anomaly, a 5.6-fold increase in that for a family history of chromosome aberrations, and a 4.4- fold increase in that for other purposes. There was also a 35.7-fold increase in the number of prenatally detected Down syndrome cases, from seven in 1990 to 250 in 2000. The highest rates of Down syndrome were found in cases with abnormal ultrasound findings (1/99 tests). Down syndrome was 0.72-fold as common in amniocenteses performed because of positive serum screening results (1/161 tests) compared with the rate seen in the advanced maternal age group (1/116 tests). The detection rates increased from 1/449 tests in 1990, through 1/198 tests, 1/203 tests, 1/158 tests, 1/215 tests, 1/229 tests, 1/169 tests, 1/143 tests, 1/90 tests, 1/92 tests, to 1/123 tests in 2000. Conclusion Both the number of women undergoing amniocentesis and the number of detected cases of Down syndrome increased during these years. Amniocentesis in this population no longer led to a significant improvement in the detection rate of Down syndrome. In view of the effective use of amniocentesis as a diagnostic procedure for Down syndrome, efforts should be made to use more efficient prenatal screening programs and to reduce the number of unnecessary amniocenteses.

Prospective study of parental choice for aneuploidy screening in assisted conception versus spontaneously conceived twins

The aim of this study was to evaluate and compare parental choice towards the use of aneuploidy screening and diagnostic techniques after assisted conception versus spontaneously conceived pregnancy. A total of 193 patients with consecutive twin pregnancies participated in the study, including 143 who spontaneously conceived and 50 who conceived following assisted reproduction treatment. Patients were investigated prospectively for their choice in the prenatal screening/diagnosis of aneuploidy. In the group of patients who conceived spontaneously, 111 (77.6%) opted initially for the non-invasive screening based on nuchal translucency measurements, whereas in the assisted conception group, 44 (88%) opted for the non-invasive screening. In the spontaneous conception group, 32 (22.4%) presented because they had a positive serum screening test or because they had opted for a chorionic villus sampling (CVS) or an amniocentesis for advanced maternal age. In the assisted conception group only six patients (12%) opted for amniocentesis. The difference in choice of non-invasive versus invasive screening between those with spontaneous and those with assisted conception was not significant, but those who had conceived spontaneously after the age of 37 years were significantly more likely ( P < 0.05) to request an invasive diagnostic procedure through all maternal age groups. When needed, an amniocentesis was preferred to CVS. These data also indicate that the antenatal counselling needs to be adapted to couples presenting with an assisted conception twin pregnancy.

Les alternatives à l’amniocentèse pour âge maternel

Screening strategies of Down’s syndrome should be re-evaluated. Amniocentesis for advanced maternal age has been proposed in the 70’s because no other screening test was available. Maternal serum screening and first trimester nuchal translucency are now well validated, including in women over 38. The sequential and independent use of different screening tests leads to a dramatic increase of the false positive rate and thus of iatrogenic fetal losses. Maternal age remains the major risk factor for chromosomal anomalies, but it should be included in risk calculation strategies (ideally combining serum screening and nuchal translucency), and not taken as an isolated information. These screening strategies require strict quality control and audit, which is currently better achieved with serum screening than ultrasound screening. A complete information about Down’s syndrome screening strategies should be given to women, regardless of their age, and their personal choice should be respected. For women of advanced maternal age, a policy of selective rather than routine amniocentesis is likely to reduce the risk of iatrogenic fetal loss and yet to allow for a reasonable sensitivity.

Is Routine Amniocentesis for Advanced Maternal Age Still Indicated?

Objective: To evaluate a policy of selective rather than routine use of amniocentesis for advanced maternal age. Method: A consecutive series of 359 pregnant women aged 38–47 underwent nuchal translucency measurement (NTM) at 10–14 weeks, maternal serum screening (MSS) by α-fetoprotein (AFP) and human chorionic gonadotropin (hCG) at 15–17 weeks, and second trimester ultrasound at 21–23 weeks. Women with NTM <3 mm, MSS-derived risk <1/250, and a normal second trimester sonography were considered at low risk and were suggested not to have an amniocentesis. Results: Either the NTM or MSS test was positive in 130 women; 105 (81%) of them elected to have an amniocentesis, versus 122 (53%) of 229 in whom both tests were negative (p < 0.001). Nineteen (5%) of 359 patients had NTM ≧3 mm; all 7 cases of Down’s syndrome were in this group; 122 (34%) of 359 patients had a MSS-derived risk ≧1/250; 6 of the 7 cases of Down’s syndrome were in this group: Ten patients had an abnormal second trimester ultrasound, 1 of which had trisomy 18. Of the 219 patients with MSS-derived risk <1/250, a NTM <3 mm, and a normal second trimester ultrasound, none had a baby with a chromosomal abnormality (95% confidence interval: 0–1.4%). Conclusion: Amniocentesis may be offered on a selective rather than routine basis in women over 38, based upon the results of noninvasive screening tests.

Hyperglycosylated Human Chorionic Gonadotropin (Invasive Trophoblast Antigen) Immunoassay: A New Basis for Gestational Down Syndrome Screening

Serum human chorionic gonadotropin (hCG) and hCG free beta-subunit tests are used in combination with unconjugated estriol and alpha-fetoprotein in the triple screen test, and with the addition of inhibin-A in the quadruple marker test for detecting Down syndrome in the second trimester of pregnancy. These tests have a limited detection rate for Down syndrome: approximately 40% for hCG or free beta-subunit alone, approximately 60% for the triple screen test, and approximately 70% for the quadruple marker test, all at 5%, or a relatively high, false-positive rate. New tests are needed with higher detection and lower false rates. Hyperglycosylated hCG (also known as invasive trophoblast antigen or ITA) is a new test. It specifically detects a unique oligosaccharide variant of hCG associated with Down syndrome pregnancies. We evaluated this new Down syndrome-directed test in prenatal diagnosis. Hyperglycosylated hCG was measured in urine samples from women undergoing amniocentesis for advanced maternal age concerns at 14-22 weeks of gestation, 1448 with normal karyotype and 39 with Down syndrome fetuses. The median hyperglycosylated hCG value was 9.5-fold higher in Down syndrome cases (9.5 multiples of the normal karyotype median). The single test detected 80% of Down syndrome cases at a 5% false-positive rate. Urine hyperglycosylated hCG was combined with urine beta-core fragment (urine breakdown product of serum hCG free beta-subunit), serum alpha-fetoprotein, and maternal age-related risk. This urine-serum combination detected 96% of Down syndrome cases at a 5% false-positive rate, 94% of cases at a 3% false-positive rate, and 71% of cases at a 1% false-positive rate. These detection rates exceed those of any previously reported combination of biochemical markers. Hyperglycosylated hCG is a new base marker for Down syndrome screening in the second trimester of pregnancy. The measurement of hyperglycosylated hCG can fundamentally improve the performance of Down syndrome screening protocols.

Prevalence of congenital anomalies at birth among offspring of women at risk for a genetic disorder and with a normal second-trimester ultrasound.

The goal of this study was to determine the prevalence and the nature of congenital anomalies found at birth in offspring of women who had a normal second-trimester ultrasound and/or amniocentesis. Two groups of women were studied in our prenatal diagnosis clinic between 1991-1997. Group 1 consisted of pregnant women who had an amniocentesis for advanced maternal age (AMA), or for familial chromosomal or monogenic disorders. Group 2 consisted of pregnant women attending the prenatal diagnosis clinic and who had no indication for amniocentesis. Those with an abnormal ultrasound and/or amniocentesis were excluded. At the time of delivery, a questionnaire was sent pertaining to perinatal complications and the anomalies detected during the neonatal period. From a total of 15, 370 questionnaires sent from 1991-1997, 10,823 (group 1, n = 8,877; group 2, n = 1,946) were returned (overall response rate, 70.4%). Mean maternal age was 36 years in group 1 and 29 years in group 2. The prevalence of perinatal complications was similar in the two groups. In each group, the prevalence of all unforeseen anomalies was 2.9%. In group 1, the distribution of those anomalies was: major anomalies, 67.7%; minor anomalies, 23.9%; and multiple congenital anomalies (MCA), 8.3%. In group 2, the distribution was: major anomalies, 70.7%; minor anomalies, 24.1%; and MCA, 5.2%. In patients at risk for a genetic disease and consulting in a prenatal diagnosis clinic, the prevalence of all anomalies diagnosed at birth was 2.9%, even if the second-trimester ultrasound and amniocentesis results were normal. Therefore, it is important to inform those couples of this remaining risk.

THE RELATIONSHIP BETWEEN SECOND-TRIMESTER AMNIOTIC FLUID INSULIN AND GLUCOSE LEVELS AND SUBSEQUENT GESTATIONAL DIABETES

Associations between elevated amniotic fluid glucose and insulin levels in the second trimester and the subsequent development of gestational diabetes have been reported. We conducted a case-control study to determine which analyte best predicts future maternal glucose intolerance. Thirty-nine women diagnosed with gestational diabetes (criteria of Carpenter and Coustan, Am. J. Obstet. Gynecol., 144, 768, 1982) who had undergone genetic amniocentesis for advanced maternal age were matched with euglycaemic controls. Glucose and insulin concentrations were determined by analysis of stored amniotic fluid samples. No significant difference was detected between cases and controls for amniotic fluid glucose concentrations. Amniotic fluid insulin concentrations were significantly higher in cases (mean rank 4.44, P < 0.01, using matched rank analysis of variance, where 1 is the lowest and 6 is the highest rank). After conversion to multiples of the median, 20 per cent of women with subsequent gestational diabetes were found to have amniotic fluid glucose levels at or above the 90th centile, while 35 per cent of cases had similarly elevated amniotic fluid insulin levels. We conclude that second-trimester amniotic fluid insulin is a more sensitive predictor of impending glucose intolerance than amniotic fluid glucose, although neither is sufficiently powerful to use alone as a screening test.

Second-trimester minor ultrasound anomalies: impact on the risk of aneuploidy associated with advanced maternal age

To determine the impact of the presence or absence of minor ultrasound anomalies for the risk of aneuploidy in patients already at high risk because of advanced maternal age. Eleven hundred forty-four women having amniocentesis for advanced maternal age were divided into those with minor ultrasound anomalies (n = 62) and those without (n = 1082). Two hundred fifty-nine women younger than 35 years but with minor anomalies on ultrasound were also included. Fetal aneuploidy was found in six of 62 (9.7%) women of advanced maternal age with minor ultrasound anomalies, in five of 1082 (0.5%) women older than 35 years with normal ultrasound results, and in five of 259 (1.9%) women younger than 35 years with minor ultrasound anomalies. Minor ultrasound anomalies increase considerably the risk of aneuploidy in women older than 35 years, and their absence lowers that risk slightly. Minor ultrasound anomalies in the fetuses of women younger than 35 raises their risk to that of a 39-year-old women in her second trimester. Ultrasound can be used to modify genetic risks at counseling and may help patients in their decision to have invasive testing.

Early amniocentesis and fetal nuchal translucency in women requesting karyotyping for advanced maternal age

Fetal nuchal translucency was measured at 11-14 weeks' gestation in 97 pregnancies referred for early amniocentesis for advanced maternal age. The nuchal translucency was abnormal in 11 fetuses and the fetal karyotype was abnormal in five of these 11 cases. The karyotype was normal in 86 cases with normal nuchal translucency. The culture failure and miscarriage rates associated with early amniocentesis were 3.3 per cent and 2.2 per cent respectively. Amniotic fluid leakage occurred in 6 per cent of cases. In women requesting fetal karyotyping for advanced maternal age without additional biochemical screening, fetal nuchal translucency should be measured at 11-14 weeks. If the nuchal thickness is > or = 3 mm, a first-trimester diagnostic procedure is indicated; however, if it is < 3 mm, amniocentesis should be delayed until 16 weeks' gestation.

Comparion of multiple-marker screening with amniocentesis for the detection of fetal aneuploidy in women ≥35 years old

OBJECTIVE: Our purpose was to compare the multiple-marker screening test with elective amniocentesis for the detection of fetal Down syndrome and other aneuploidies in women aged ≥35. STUDY DESIGN: Our database included the multiple-marker screening test (maternal serum α-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and maternal age) and genetic amniocentesis results from 1942 women aged ≥35. A Down syndrome risk ≥1:190 was considered screen positive. An algorithm to detect trisomy 18 was also used. RESULTS: The multiple-marker screening test Down syndrome screen-positive rate was 26.1% ( 507 1942 ). The Down syndrome detection rate was 75% ( 33 44 ); the trisomy 18 detection rate was 75% ( 3 4 ). However, the multiple-marker screening test detection rate for all aneuploidies was only 61%. Missed aneuploidies included trisomy 21, sex chromosome abnormalities, trisomy 13, trisomy 22, and trisomy 18. CONCLUSIONS: The multiple-marker screening test fails to detect approximately 39% of all fetal aneuploidies in women aged ≥35. These data should be provided to women considering prenatal diagnosis so that they can make an informed decision regarding the multiple-marker screening test versus amniocentesis for advanced maternal age.

Fetal hyperechogenic bowel following intra-amniotic bleeding.

To test the hypothesis that increased echogenicity of the fetal bowel at second-trimester scans results from intra-amniotic bleeding. We studied 726 patients undergoing second-trimester amniocentesis for advanced maternal age. Three groups were identified according to the color of the amniotic fluid (AF) obtained: clear fluid, blood-stained fluid, and dark brown fluid. Two to 4 weeks after the amniocentesis, all patients had a targeted ultrasound examination for the detection of fetal structural anomalies and markers of chromosomal abnormalities, which included a survey of the fetal bowel. The incidence of hyperechogenic bowel in each group was compared by Fisher exact test. P < .05 was considered significant. In 694 cases, the AF was clear (95%), in 20 blood-stained (3%), and in 12 dark brown (2%). Hyperechogenic bowel was detected in 14 fetuses with clear fluid (2%), in two with blood-stained fluid (10%), and in three with dark brown fluid (25%). Fetuses with proven intra-amniotic bleeding (ie, dark brown or blood-stained AF at amniocentesis) had a significantly higher incidence of hyperechogenic bowel compared to those with clear AF (five of 32 [15.6%] and 14 of 694 [2.0%], respectively; P < .001, 95% confidence interval for the difference in proportions 6.3-17.6%). Our study demonstrates that intra-amniotic bleeding is associated with an increased incidence of fetal hyperechogenic bowel at second-trimester ultrasound scans. This sonographic phenomenon may be due to the presence of blood in the fetal bowel caused by fetal swallowing of bloody AF.