Incidence of fetal chromosome abnormalities in 2264 low-risk women

Among a population of 6305 pregnant women, aged 25 to 34 years and estimated to be at no increased risk of genetic disease in the fetus, 4606 women participated in a randomized controlled trial of genetic amniocentesis between 1980 and 1984. In the study group having amniocentesis (2264 women), 23 fetal chromosome abnormalities (1.0 per cent) were found: eight autosomal aneuploidies, seven sex chromosome aneuploidies, seven balanced structural rearrangements and one case of a marker chromosome. The structural rearrangements and the marker chromosome were all shown to be inherited. The study group seemed representative for the whole population of younger women at low genetic risk. Therefore, a 1.0 per cent total rate of fetal chromosome abnormalities, consisting of one-third autosomal aneuploidies, one-third sex chromosome aneuploidies and one-third structural rearrangements, may be expected in the second trimester in younger low-risk women. In the same period of time, 562 women in the same age group were offered amniocentesis because of an estimated increased risk of fetal genetic disease. The total rate of fetal chromosome abnormality in this 'high-risk' group was 0.9 per cent and thus no different from the rate in the low-risk group.     

羊水细胞染色体产前诊断3495例结果分析

目的 探讨各种细胞遗传学产前诊断指征与胎儿染色体异常的关系。方法 2011年1月至2013年4月于重庆医科大学附属第一医院妇产科在知情同意的前提下,由超声引导对3495例孕中期高危孕妇（孕16~21+6周）行羊膜腔穿刺术,抽取适量羊水进行细胞培养及染色体核型分析。比较不同产前诊断指征与胎儿染色体异常核型检出率的关系。 结果 羊水培养成功3494例,成功率99.97%。检出异常核型120例,异常率为3.43%（120/3494）,其中染色体数目异常70例,结构异常31例,其他异常19例。各种产前诊断指征中,单纯高龄（分娩时孕妇年龄≥35岁）1498例,检出异常核型47例,异常检出率为3.14%;母血清学筛查高风险1560例,异常核型38例,检出率2.44%;无创产前DNA检测高风险38例,异常核型30例,检出率78.95%,后者检出率分别与前两者相比差异有统计学意义（P<0.05)。结论 掌握好各种产前诊断指征,对高危孕妇进行羊膜腔穿刺及染色体核型分析可有效提高胎儿染色体病的检出率,减少出生缺陷的发生。     

Infant outcome following mid-trimester amniocentesis: development and physical status at age six months

Summary. Ninety-one infants whose mothers had had amniocentesis, because age increased their risk for a fetal chromosome abnormality, were compared with 53 infants whose mothers chose not to have the test. Mental and motor development and temperament were studied to assess potential influence of amniocentesis on the brain. Physical growth was assessed and the infants were examined for orthopaedic abnormalities and needle injury. The results indicated that amniocentesis does not appear to influence infant mental and motor development, temperament, physical growth or the risk of orthopaedic abnormalities. However, amniocentesis is not entirely free of risk because several of the infants had needle marks. Reassessment of the cohort at age 4 and 7 years and will provide information on the potential longer term consequences of mid-trimester amniocentesis.     

Infant outcome following mid-trimester amniocentesis: development and physical status at age six months

Ninety-one infants whose mothers had had amniocentesis, because age increased their risk for a fetal chromosome abnormality, were compared with 53 infants whose mothers chose not to have the test. Mental and motor development and temperament were studied to assess potential influence of amniocentesis on the brain. Physical growth was assessed and the infants were examined for orthopaedic abnormalities and needle injury. The results indicated that amniocentesis does not appear to influence infant mental and motor development, temperament, physical growth or the risk of orthopaedic abnormalities. However, amniocentesis is not entirely free of risk because several of the infants had needle marks. Reassessment of the cohort at age 4 and 7 years and will provide information on the potential longer term consequences of mid-trimester amniocentesis.     

The implications of a false positive second-trimester serum screen for Down syndrome

OBJECTIVE: To investigate the genetic and obstetric implications of false positive Down syndrome serum screening results. METHODS: The study population comprised 162774 women underwent triple marker screening in the Ontario Maternal Serum Screening program between October 1995 and September 1998, with outcomes obtained from the Canadian Institute of Health Information. The study compares the incidence of chromosomal abnormalities other than Down syndrome in screen positive women with background incidence from the literature. It also compares the risks of having a fetus with congenital abnormalities or of developing obstetric complications in 11549 screen positive women with their matched controls. RESULTS: A higher incidence of trisomy 13 (12.4 per 10000) was seen in screen positive women; the incidence of other chromosomal abnormalities in screen positive women was not increased relative to the general population. The higher incidence of trisomy 13 may have been biased by the selective uptake of amniocentesis in women who had high risks for Down syndrome or abnormal ultrasound findings. Incidences of fetal congenital abnormality in screen positive and negative women were similar. Women who screened positive for Down syndrome had increased risk of spontaneous fetal loss (odds ratio 1.80; 95% confidence interval 1.54, 2.07) but no other obstetric complications. CONCLUSION: Among women who screened positive for Down syndrome, we found a higher number of spontaneous fetal losses and a possibly higher risk of having a fetus with trisomy 13. We did not find an increased risk for other chromosomal abnormalities, congenital abnormalities, or other adverse obstetric outcomes.     

Second trimester maternal serum screening using alpha fetoprotein, free beta human chorionic gonadotropin and maternal age specific risk: result of chromosomal abnormalities detected in screen positive for Down syndrome in an Asian population.

BACKGROUND: This study was to determine the incidence of chromosome abnormalities in Taiwanese women undergoing prenatal chromosome analysis after a second trimester Down syndrome screening by using maternal age and serum dual-marker testing (alpha-fetoprotein and free-beta unit human chorionic gonadotropin). METHODS: A total of 10,098 Taiwanese women with pregnancy between 15 and 23 weeks' gestation received second-trimester Down syndrome risk evaluation by dual-marker and maternal age specific risk testing in a single medical center. The study took 22 months. Ninety-seven percent of this study population was less than 34 years old. Ninety-six percent of our cases were screened between 15-20 weeks of gestation. This population was included only after a routine ultrasonography scan for correction of gestational age and exclusion of major structural anomalies. By using an algorithm to detect Down's syndrome, with a risk of 1:270 as a cut-off value, 816 patients were screen-positive for Down syndrome (screen-positive rate 8.0%). Karyotypes were reviewed for 670 (82.1%) mothers who received prenatal karyotype analysis. RESULTS: Twelve cases of Down syndrome were identified in the screen positive group with an estimated detection rate of 67% (false positive rate 8%). Three cases of Down syndrome were detected in late trimester among the screen-negative group. Seven other fetal chromosome abnormalities were also found among the screen-positive pregnancy. In addition, seven cases were screen-positive for trisomy 18; all of these patients received amniocentesis and only one case was confirmed. CONCLUSION: These findings indicate that this screening program combining alpha-fetoprotein (AFP), free beta human chorionic gonadotropin (free-hCG) and maternal age-specific would achieve a screening efficiency in Taiwanese populations as comparable to those obtained in Caucasian populations. Our results also suggest that approximately 3% of pregnancies with a positive dual marker and maternal age-specific screen results will have a chromosome abnormality despite having a normal routine ultrasound scan. Mothers with positive screening results should be made aware of the implications of a positive result.     

Fetal malformations and chromosome abnormalities diagnosed at the Center of Prenatal Diagnosis of the University of Aquila in the 1995-1998 triennium

BACKGROUND: Over the past few years numerous techniques have been developed, allowing an evaluation of fetal physiopathology that was unthinkable until recently. The authors describe 20 cases of fetal malformations and chromosomal abnormalities diagnosed by scan and amniocentesis at the Centre for Diagnosis and Obstetric Prophylaxis at L'Aquila University. METHODS: Between January 1995 and April 1998 a total of 1180 amniocentesis and 4000 obstetric scans were performed in a group of 1650 pregnant women. RESULTS: Of the patients examined using ultrasound scan, 8 presented manifest fetal pathologies, of which 5 were associated with chromosome abnormalities: 1) left ventricular hypoplasia, common atrium, tricuspid dysplasia; 2) omphalocele; 3) Morgagni-Stewart-Morel syndrome; 4) plurilobate cystic hygroma; 5) duodenal atresia; 6) Dandy-Walker syndrome; 7) cystic hygroma and hydrops; 8) cystic hygroma, hydrops, cardiopathy and Dandy-Walker syndrome. Among the pregnant women undergoing amniocentesis without a prior diagnosis of fetal malformation, 12 presented pathological fetal karyotypes: 2 cases of Turner's syndrome; 2 cases of Edward's syndrome; 2 cases of Klinefelter's syndrome, of deletion of a stretch of chromosome 8; 1 case of Down's syndrome; 2 cases of supernumerary marker chromosome; 1 twin pregnancy with Klinefelter's syndrome in one twin and paracentric inversion of chromosome 13 in the other; 1 twin pregnancy with a small supernumerary marker chromosome in both twins. CONCLUSIONS: Ultrasonography often enables the diagnosis of congenital abnormalities not associated with chromosome pathologies. However, karyotype studies play an essential role in pregnancies with a high genetic risk.     

不同指征介入性产前诊断的异常染色体检出率及其安全性分析

目的 探讨不同指征介入性产前诊断(羊膜腔穿刺和脐血管穿刺)的异常染色体检出率以及介入性产前诊断技术的安全性. 方法回顾性分析本中心1264例介入性产前诊断(1082例羊膜腔穿刺和182例脐血管穿刺)的手术指征、不同指征的异常染色体检出率及穿刺相关并发症.结果 1264例介入性产前诊断中,穿刺指征分别为:血清学筛查高风险651例(51.5%)、孕妇高龄(年龄≥35岁)318例(25.2%)、超声胎儿结构异常136例(10.8%)、不良妊娠史88例(6.9%)、血清学筛查一项或两项标志物MoM值异常52例(4.1%)和夫妇一方染色体平衡易位携带19例(1.5%).共检出有临床意义的染色体异常37例,其穿刺指征依次为:超声提示胎儿结构异常20例(20/136,14.7%),血清学筛查高风险12例(12/651,1.8%),至少一项标志物MoM值异常1例(1/52,1.9%),不良妊娠史1例(1/88,1.1%),夫妇一方染色体平衡易位携带3例(3/19,15.8%),孕妇年龄≥35岁者未检出有临床意义的染色体异常(0/318).1264例介入性产前诊断中共有5例自然流产,其中与羊膜腔穿刺相关的胎儿丢失率为0.28%(3/1082),与脐血管穿刺相关的胎儿丢失率为1.09%(2/182),两者相比差异无统计学意义(P=0.154).脐血管穿刺后孕妇心慌、腹痛以及胎心减慢等并发症的发生率明显高于羊膜腔穿刺组(9.89%和0.18%,P=0.001). 结论超声发现胎儿结构异常应常规检查胎儿核型;单纯高龄作为介入性产前诊断的指征值得商榷;介入性产前诊断从安全性角度应首选羊膜腔穿刺术.     

Adverse pregnancy outcome following post-chorionic villus sampling amniocentesis compared to chorionic villus sampling

OBJECTIVE: To assess the adverse pregnancy outcome of post-chorionic villus sampling (CVS) amniocentesis and chorionic villus sampling. METHODS: Adverse pregnancy outcomes of 32 post-CVS amniocentesis cases and 264 CVS only cases were compared. The base-line characteristics were comparable in the 2 groups. RESULTS: One (3.1%) chromosomal abnormality was detected in the post-CVS amniocentesis group, compared to 5 (1.8%) in the CVS only group (p > 0.05). The fetal loss rate (spontaneous abortions and stillbirths) among continuing pregnancies was 3.2% in the post-CVS amniocentesis group and 3.5% in the CVS only group (p > 0.05). No statistically significant difference was found in the incidence of neonatal death, preterm delivery, fetal growth restriction, or congenital anomalies between the 2 groups. CONCLUSION: Adverse pregnancy outcome occurred at a similar frequency in the post-CVS amniocentesis group as in the CVS only group. Therefore, a subsequent amniocentesis after CVS can be considered as a safe procedure that does not introduce any additional adverse pregnancy outcome compared to that of CVS only.     

不同产前筛查方案对胎儿染色体异常检出效率的比较

目的 探讨不同产前筛查方案对胎儿染色体异常的检出效率.方法 应用时间分辨免疫荧光法对24986例孕妇进行母体血清学二联筛查,根据风险值及后续的检查方案不同将人群分为高风险直接进行羊水穿刺组(A1组)、高风险行无创产前检测(non-invasive prenatal testing,NIPT)组(A2组)、临界风险进行超...     

Midtrimester amniocentesis. An analysis of 923 cases with neonatal follow-up

Maternal, fetal, and neonatal results and complications were analyzed after 923 genetic amniocenteses. Maternal age of 35 years and beyond was associated with a 2.0% risk of fetal trisomy 21 and a 3.0% risk of all major chromosome abnormalities. Comparable rates for women aged 40 and beyond were 4.8% and 7.2%. Neural tube defects were detected in 0.15% of procedures done for maternal age and 3.4% of those done for a previous involved child. The risk of spontaneous abortion as a result of amniocentesis was 0.2% to 1.4%. Mahogany or green fluid was associated with a 29% rate of fetal loss. Unexplained midtrimester elevations of maternal serum alpha-fetoprotein were associated with a 38% risk of a subsequent low-birth weight infant. The only neonatal complication associated with amniocentesis was an apparent marked increase in the incidence of lower-extremity orthopedic abnormalities.     

产前诊断指征在胎儿染色体异常诊断中的价值探讨

目的:探讨产前诊断指征在胎儿染色体异常诊断中的价值及其对妊娠结局的指导意义.方法:对439例有产前诊断指征的孕妇,在超声引导下经腹羊膜腔穿刺抽取羊水检查染色体核型,比较不同产前诊断指征的胎儿染色体异常检出率,分析各组染色体异常类型与妊娠结局的关系.结果:①胎儿染色体异常检出15例,总的异常检出率3.42%.夫妇平衡易位组胎儿染色体异常检出率最高为66.67%,与高龄组、唐氏高危组、不良孕产史(夫妇染色体检查正常)组比较,差异有统计学意义(P<0.05);而高龄组、唐氏高危组、不良孕产史组和超声检查异常组的胎儿染色体异常检出率分别为5.22%、2.28%、1.54%、16.67%、,组间两两比较差异均无统计学意义(P>0.05).②15例染色体异常中.高龄组占40.00%,唐氏高危组占33.33%.染色体数目异常6例,5例行孕中期引产;结构异常7例,1例行孕中期引产,1例流产;嵌合体2例均行孕中期引产;余6例足月分娩.结论:对具有产前诊断指征的孕妇进行羊水细胞培养及染色体核型分析,不仅能及时发现胎儿染色体异常,为孕妇是否继续妊娠提供科学依据,而且有利于降低出生缺陷发生率.     

234例羊膜腔穿刺诊断胎儿染色体异常的研究

目的评价羊水穿刺术在产前诊断胎儿染色体异常中的应用。方法对234例有产前诊断指征的孕妇在超声引导下经腹羊膜腔穿刺抽取羊水检查染色体核型,并比较不同产前诊断指征分组的异常染色体检出率。结果全部病例穿刺均成功,羊水细胞培养成功率97.86%,染色体异常检出率5.68%。其中超声示胎儿异常组染色体异常检出率(33.33%)明显高于21-三体高风险组(4.54%)、不良孕产史组的检出率(9.09%)(P<0.05)。结论超声引导下经腹羊膜腔穿刺抽取羊水在产前诊断中是成熟有效的操作技术,孕妇血清学筛查异常、不良孕产史、超声示胎儿异常是有效的穿刺指征,其中胎儿异常的超声监测对产前诊断提示胎儿染色体异常具有较好的预测性。     

Genetic aspects of miscarriage.

Fetal chromosome abnormalities account for about 50% of first-trimester pregnancy losses. Most of these abnormalities are numerical abnormalities (86%) and a low percentage is caused by structural abnormalities (6%) or other genetic mechanisms, including chromosome mosaicism (8%). The recurrence risk of numerical abnormalities is low, so karyotyping of fetal material in case of a miscarriage does not seem worthwhile in daily practice.Half of the structural abnormalities may be inherited from a parent carrying a balanced chromosome translocation or inversion. Parental carriership is found in 4-6% of the couples with recurrent miscarriage. In case of parental carriership of a balanced structural chromosome abnormality, a next pregnancy may result in a child with an unbalanced structural chromosome abnormality. This child can have multiple congenital malformations and/or a mental handicap. Prenatal diagnosis is therefore recommended.Conventional laboratory techniques, such as tissue culturing and karyotyping, or (semi-)direct chromosome technique of chorionic villi, and the recently developed laboratory techniques such as fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH), are described successively.Until now, not enough evidence has been available about the role of other genetic mechanisms, such as single-gene abnormalities, uniparental disomy, genomic imprinting, multifactorial disorders and skewed X chromosome, in the occurrence of miscarriages.     

Risk of fetal chromosomal anomalies in patients with elevated maternal serum alpha-fetoprotein.

When elevated maternal serum alpha-fetoprotein (MSAFP) results lead to diagnostic amniocentesis, a decision of whether to karyotype fetal cells must be made. We examined our experience with MSAFP screening in 71,563 unselected pregnancies in which karyotyping was performed when amniocentesis was done because of MSAFP elevations. A total of 727 women (1.0%) underwent amniocentesis because of elevated MSAFP values and among this group, seven chromosomal anomalies (incidence one in 104) were detected. Of the 727 women, 658 (91%) had normal amniotic fluid AFP. In this group, there were six (one in 109) chromosomally abnormal fetuses: three with triploidy, two with 47,XXX, and one with 46,XX,1q-. Among the 69 pregnancies with elevated amniotic fluid AFP, one fetal chromosomal anomaly (trisomy 13) was diagnosed. The incidence of all chromosomal anomalies observed in women undergoing amniocentesis because of elevated MSAFP is comparable to that reported in women 36 years of age undergoing testing because of advanced maternal age. We believe that chromosome analysis should be performed on amniotic fluid samples obtained because of elevated MSAFP unless there are compelling financial circumstances that preclude this. Even in such cases, cell cultures should be established until the amniotic fluid AFP result is available. Chromosome analysis is essential when the amniotic fluid AFP is elevated because of the known association between open fetal defects (spina bifida, omphalocele, and scalp defects) and trisomies 13 and 18.     

Cystic fibrosis and chromosome abnormalities associated with echogenic fetal bowel.

OBJECTIVE: To determine the prevalence of cystic fibrosis mutations and chromosome abnormalities in the fetuses of a heterogeneous population of pregnant women referred for prenatal testing for echogenic fetal bowel. METHODS: Fetal or parental samples obtained after a second-trimester sonographic finding of echogenic fetal bowel were submitted to a referral diagnostic laboratory during a 2-year period. Results of DNA testing and karyotyping on these samples were analyzed to determine the prevalence of cystic fibrosis transmembrane reductase gene mutations and chromosome abnormalities. RESULTS: Of 244 cases tested, two fetuses were positive for two cystic fibrosis mutations. This rate (0.8% or two of 244) is 20 times higher than the general white population rate of one per 2500. In a third case, both parents were carriers but the fetus was not tested. Nine (8%) of 113 fetuses tested had one cystic fibrosis mutation. Of 106 fetuses for whom chromosome results were available, three (2.8%) fetuses had a chromosomal abnormality: two had trisomy 21 and one had Klinefelter syndrome. A fourth fetus carried a de novo, apparently balanced, 5;12 translocation. CONCLUSION: These laboratory results are representative of a broad spectrum of clinical settings and indicate a generalized increased risk associated with this sonographic finding. Therefore, when a second-trimester sonographic diagnosis of fetal echogenic bowel is made, fetal testing for both cystic fibrosis and chromosome abnormalities is warranted.     

Re-evaluation of risk for Down syndrome by means of the combined test in pregnant women of 35 years or more

OBJECTIVE: Evaluation of combined test in pregnant women 35 years of age and over to detect fetal Down syndrome. MATERIALS AND METHODS: The study population included 408 pregnant women of 35 years and over, who requested the combined test (nuchal translucency, PAPP-A, free beta hCG, maternal age, cut-off 1:250) before deciding whether to undergo amniocentesis. RESULTS: The test was positive in 66 women who then requested amniocentesis for fetal karyotype determination; the other women had a negative test and declined amniocentesis. False-positives increased with maternal age from 6.6% at 35 years to about 50% at 40 to 41 and 100% in women over 41. Six cases of Down syndrome and two cases of trisomy 18 were detected. Not a single case of Down syndrome or trisomy 18 was missed, and other chromosome abnormalities were detected as well. CONCLUSIONS: The application of the combined test reduced the need for invasive testing to only 14% of the studied pregnant population, without missing any of the fetuses with trisomy 21 or 18.     

Prevalence and significance of isolated fetal choroid plexus cysts detected in early pregnancy by transvaginal sonography in women of advanced maternal age

This study examines the prevalence of isolated fetal choroid plexus cysts (CPCs) detected in early pregnancy by transvaginal sonography in an increased genetic risk population and their association with abnormal fetal karyotype. A prospective study was performed on 1692 pregnant women (>37 years) who underwent transvaginal scan at 11-16 weeks' gestation before genetic amniocentesis. The prevalence of isolated CPCs in our population was 1.48 per cent. An abnormal fetal karyotype was found in one case (4 per cent). It was concluded that if fetal CPCs are apparently isolated, genetic amniocentesis is not mandatory and additional risk factors such as advanced maternal age should be the main indication for fetal karyotyping.     

Prenatal cytogenetic diagnosis in Taiwan: a nationwide population-based study

Purpose: The goal of this study was to gain a better understanding of the status of advanced maternal age among criteria for provision of amniocentesis in pregnant women in Taiwan.

Materials and method: Data of 315 670?second-trimester amniocenteses from 28 national certified cytogenetics laboratories were retrospectively analyzed from the Prenatal Genetic Diagnosis Declaring and Database System of the Health Promotion Administration, Ministry of Health and Welfare in Taiwan between 2006 and 2013.

Results: The number of pregnant women undergoing amniocentesis in Taiwan between 2006 and 2013 increased, and the most common three indications for amniocentesis were advance maternal age (75.11%), abnormal second trimester maternal serum screening (13.22%) and abnormal sonographic finding (8.00%). Down syndrome was the most common autosomal abnormality identified (25.74%); Turner syndrome was the most common sex chromosome abnormality (7.04%). Of structural rearrangements, 26.93% were balanced translocations and 17.10% were unbalanced translocations. The greatest proportion of fetal chromosomal abnormalities was found in cases where parents were also affected (38.02%).

Conclusions: Clinical workers should provide detailed genetic diagnostic information to pregnant women, especially those with the common amniocentesis indications, which will enable them to determine a birth plan.     

Prenatal diagnosis of congenital cytomegalovirus infection

OBJECTIVE: To assess prospectively the diagnostic reliability and prognostic significance of prenatal diagnosis of cytomegalovirus (CMV) infection. METHODS: One hundred ten pregnant women (four with twin pregnancies) with a risk of congenital CMV infection were investigated. Prenatal diagnosis was carried out by amniocentesis and fetal blood sampling (n = 75) or amniocentesis alone (n = 35). Serial ultrasonographic examinations were performed from time of referral until pregnancy end. All infected neonates were given long-term follow-up. Autopsy was performed in all cases of termination of pregnancy. RESULTS: Nearly 23% (26 of 114) of fetuses were infected and prenatal diagnosis was positive in 20 cases. Sensitivity of prenatal diagnosis was 77% and specificity 100%. In eight cases, parents requested termination of pregnancy on the basis of abnormal ultrasonographic findings and/or biologic abnormalities in fetal blood. In 12 cases, parents decided to proceed with the pregnancy. In this group, one intrauterine and one neonatal death were observed. In one case, prenatal diagnosis revealed an abnormal cerebral sonography and the infant had bilateral hearing loss at birth. In 15 cases (nine positive and six false-negative prenatal diagnoses), no apparent lesion was present at birth, nor did it develop during the follow-up period (mean 31 months). In 88 (77.2%) of 114 infants, no evidence of vertical transmission was found during the pre- or postnatal period. CONCLUSION: Prenatal diagnosis provides the optimal means for both diagnosing fetal infection (amniocentesis) and identifying fetuses at risk of severe sequelae (ultrasound examination, fetal blood sampling), thus allowing proper counseling.