Contribution of ultrasonographic examination to the prenatal detection of chromosomal abnormalities in 19 centres across Europe.

The objective of this study was to evaluate the prenatal detection of chromosomal abnormalities by fetal ultrasonographic examination in a large database provided by 19 Registries of Congenital Anomalies from 11 European countries. This study included 1738 cases of chromosomal abnormalities, liveborn, stillborn or termination of pregnancy regardless of maternal age from a population of 664,340 births during the period 1996 - 1998. The most frequent chromosomal anomalies were Down syndrome (n=1050), trisomy 18 (n=191), Turner syndrome (n=125), trisomy 13 (n=86), and triploidy (n=56). Fetal ultrasonographic examination resulted in the prenatal detection of 37.7% of the chromosomal abnormalities, thereby resulting in a reduction of 28.6% in their prevalence at birth due to terminations of pregnancy. The detection rate by ultrasound examination varied according to local policies of prenatal diagnosis : it was lower in countries where routine scan were not performed and higher in countries in which at least one routine anomaly scan during the second trimester of pregnancy was performed. The ultrasound detection varied according to the specific chromosomal anomaly and was lowest for Klinefelter syndrome (5.7%) and highest for triploidy (78.6%). For Down syndrome it was 26.4%. Termination of pregnancy was performed in 75.9% of the cases. Among the 655 cases detected by ultrasound, the most frequent ultrasound signs by category of chromosomal abnormalities were analysed. This study shows that ultrasound screening is an important tool in the prenatal detection of chromosomal abnormalities in Europe, leading to a significant reduction in the prevalence of livebirth children with chromosomal anomalies.     

Cystic fibrosis carrier population screening in the primary care setting.

To determine the receptivity of prenatal care providers and their patients to carrier testing for cystic fibrosis (CF), we offered free carrier screening, followed by genetic counseling of carriers, to all prenatal care providers in Rochester, NY, for all their female patients of reproductive age, pregnant or not. Of 124 prenatal care providers, only 37 elected to participate, but many of these offered screening only to pregnant women. The acceptance rate among pregnant women was approximately 57%. The most common reasons for accepting screening were to obtain reassurance (50.7%) and to avoid having a child with CF (27.8 %). The most common reasons for declining screening were not intending to terminate a pregnancy for CF (32.4%) and believing that the chance of having a CF child was very low (32.2%). Compared with decliners, acceptors were more likely to have no children, regarded having a child with CF as more serious, believed themselves more susceptible to having such a child, knew more about CF, would be more likely to terminate a pregnancy if the fetus were shown to have CF, and more strongly supported offering CF screening to women of reproductive age. Of 4,879 women on whom results were obtained, 124 were found to be carriers. Of these 124 carriers, the partners of 106 were tested. Of the five at-risk couples, four requested prenatal diagnosis and one requested neonatal diagnosis. No woman found to be a carrier whose partner tested negative requested prenatal diagnosis. Except for the imperfect knowledge of those testing negative, none of the adverse outcomes predicted for CF carrier testing in the general population were observed in this study.     

Prenatal screening for cystic fibrosis carriers: an economic evaluation.

The cloning of the CFTR gene has made it technically possible to avert the unwanted birth of a child with cystic fibrosis (CF). Several large trials offering prenatal CF carrier screening suggest that such screening is practical and that identified carriers generally use the information obtained. Therefore, a critical question is whether the cost of such screening is justified. Decision analysis was performed that used information about choices that pregnant women were observed to make at each stage in the Rochester prenatal carrier-screening trial. The cost of screening per CF birth voluntarily averted was estimated to be $1,320,000-$1,400,000. However, the lifetime medical cost of the care of a CF child in today's dollars was estimated to be slightly>$1,000,000. Therefore, despite both the high cost of carrier testing and the relative infrequency of CF conceptions in the general population, the averted medical-care cost resulting from choices freely made are estimated to offset approximately 74%-78% of the costs of a screening program. At present, if it is assumed that a pregnancy terminated because of CF is replaced, the marginal cost for prenatal CF carrier screening is estimated to be $8,290 per quality-adjusted life-year. This value compares favorably with that of many accepted medical services. The cost of prenatal CF carrier screening could fall to equal the averted costs of CF patient care if the cost of carrier testing were to fall to $100.     

Cystic fibrosis heterozygote screening in 5,161 pregnant women.

A screening program for cystic fibrosis (CF) heterozygotes was conducted in a large HMO prenatal population, to evaluate the level of interest among eligible patients, the effectiveness of prescreening education, attitudes toward the screening process, psychological effects, and utilization of prenatal diagnosis and its outcomes. The heterozygote identification rate and frequency of specific CFTR mutations were also assessed. Identified carriers were offered genetic counseling and testing of male partners. Prenatal diagnosis was offered if both parents were identified as carriers. A total of 5,161 women underwent carrier testing; 947 others completed survey instruments only. The acceptance rate of screening was high (78%), and pretest education by videotape was generally effective. Adverse psychological effects were not reported. Participants generally found screening to be desirable and useful. Screening identified 142 female heterozygotes, 109 couples in which the male partner was not a carrier, and 7 high-risk couples. The incidence of R117H mutations was much higher than expected. The number of identified carriers was much lower in Hispanics than in Caucasians. We conclude that large-scale prenatal screening for CF heterozygotes in the absence of a family history of CF is an acceptable method for identifying couples at risk for affected fetuses. Sufficient pretest education can be accomplished efficiently, test insensitivity is well accepted, adverse psychological events are not observed, and general patient satisfaction is high.     

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.     

Prevention of homozygous beta-thalassemia by carrier screening and prenatal diagnosis in Sardinia.

We report here results of a 3-year pilot voluntary screening program coupled with prenatal diagnosis directed to the prospective prevention of homozygous beta-thalassemia (beta-thal) in Sardinia. The screening program took two approaches: outreach community testing and hospital testing on request after a period of sensibilization. The outreach testing was very effective as, taking into account the already known number of couples at risk with an affected proband (20), 74% of the couple at risk expected (61) on the basis of the carrier rate were identified. Less effective was the hospital testing in which half of the couples at risk expected were detected (502 with the 199 without an affected proband). After nondirective genetic counseling, approximately 85% of the couples at risk, which had a pregnancy, with no statistically significant difference between those with and those without a proband, requested prenatal testing. This figure showed a steadily increase from the beginning in 1977 to 1980. All the pregnancies (42), but two carrying homozygous fetuses, were terminated on parental request. A continuous hospital survey of thal-major admissions in the different hospitals of the counties showed a steady decline in the incidence figure at birth from 1976 (1:213) to 1978 (1:290). These results showed that even in a medium-developed, rural, Catholic population screening coupled with prenatal diagnosis can be successful in the control of a fatal, recessively inherited disorder.     

Congenital pulmonary lymphangiectasia

Congenital pulmonary lymphangiectasia (PL) is a rare developmental disorder involving the lung, and characterized by pulmonary subpleural, interlobar, perivascular and peribronchial lymphatic dilatation. The prevalence is unknown. PL presents at birth with severe respiratory distress, tachypnea and cyanosis, with a very high mortality rate at or within a few hours of birth. Most reported cases are sporadic and the etiology is not completely understood. It has been suggested that PL lymphatic channels of the fetal lung do not undergo the normal regression process at 20 weeks of gestation. Secondary PL may be caused by a cardiac lesion. The diagnostic approach includes complete family and obstetric history, conventional radiologic studies, ultrasound and magnetic resonance studies, lymphoscintigraphy, lung functionality tests, lung biopsy, bronchoscopy, and pleural effusion examination. During the prenatal period, all causes leading to hydrops fetalis should be considered in the diagnosis of PL. Fetal ultrasound evaluation plays a key role in the antenatal diagnosis of PL. At birth, mechanical ventilation and pleural drainage are nearly always necessary to obtain a favorable outcome of respiratory distress. Home supplemental oxygen therapy and symptomatic treatment of recurrent cough and wheeze are often necessary during childhood, sometimes associated with prolonged pleural drainage. Recent advances in intensive neonatal care have changed the previously nearly fatal outcome of PL at birth. Patients affected by PL who survive infancy, present medical problems which are characteristic of chronic lung disease.     

PCR-based screening for cystic fibrosis carrier mutations in an ethnically diverse pregnant population.

As the most common lethal autosomal recessive disorder in North America, cystic fibrosis (CF) is an obvious candidate for general population carrier screening. Although the identification of the causative gene has made detection of asymptomatic carriers possible, the extreme heterogeneity of its mutations has limited the sensitivity of the available DNA screening tests and has called into question their utility when they are applied to patients with no family history of the disease. The purpose of this study was to determine the technical feasibility, patient acceptance and understanding, and psychosocial impact of large-scale CF carrier screening in an ethnically diverse pregnant population. A total of 4,739 pregnant women attending prenatal clinics located in both an academic medical center and a large HMO were invited in person to participate. Of this group, 3,543 received CF instruction and assessments of knowledge and mood, and 3,192 underwent DNA testing for the six most common CF mutations, by means of a noninvasive PCR-based reverse-dot-blot method. Overall participation rates (ranging from 53% at the HMO to 77% at the academic center) and consent rates for DNA testing after CF instruction (>98%) exceeded those of most other American studies. The PCR-based screening method worked efficiently on large numbers of samples, and 55 carriers and one at-risk couple were identified. Understanding of residual risk, anxiety levels, and overall satisfaction with the program were acceptable across all ethnic groups. Our strategy of approaching a motivated pregnant population in person with a rapid and noninvasive testing method may provide a practical model for developing a larger CF screening program targeting appropriate high-risk groups at the national level, and may also serve as a paradigm for population-based screening of other genetically heterogeneous disorders in the future.     

Prevalence of neural tube defects in South Australia, 1966-91: effectiveness and impact of prenatal diagnosis.

OBJECTIVE--To determine trends in total prevalence of neural tube defects in South Australia during 1966-91, the impact of prenatal diagnosis on birth prevalence, and the effectiveness of prenatal screening for neural tube defects in 1986-91. DESIGN--All births and terminations of pregnancy affected by neural tube defects and information on prenatal screening were ascertained from multiple sources including the South Australian perinatal and abortion statistics collections, birth defects register, and state maternal serum alpha fetoprotein screening programme. SETTING--Southern Australia. SUBJECTS--All 1058 births and terminations of pregnancy affected by neural tube defects in 1966-91. MAIN OUTCOME MEASURES--Total prevalence and birth prevalence of individual and all neural tube defects. The proportion of screened cases detected prenatally. RESULTS--Total prevalence of neural tube defects during 1966-91 was 2.01/1000 births with no upward or downward trend. However, birth prevalence fell significantly (by 5.1% a year), with an 84% reduction from 2.29/1000 births in 1966 to 0.35/1000 in 1991 (relative risk = 0.16, 95% confidence interval 0.07 to 0.34). The fall was 96% for anencephaly and 82% for spina bifida. 85% of defects, both open and closed, were detected before 28 weeks'' gestation in women screened by serum alpha fetoprotein or mid-trimester ultrasonography, or both, in 1986-91 (99.0% for anencephaly and 75.7% for spina bifida). CONCLUSIONS--While the total prevalence of neural tube defects in South Australia remained stable, prenatal diagnosis and termination of pregnancy resulted in an 84% fall in birth prevalence during 1966-91. Screening detected over four fifths of cases in 1986-91.     

Screening for cystic fibrosis: feasibility of molecular genetic analysis of dried blood specimens

Direct genotypic analysis for the common Caucasian cystic fibrosis mutation (delta F508) was performed using dried blood specimens in a filter paper matrix (neonatal screening blotter). DNA was obtained from dried and liquid blood samples, amplified, and analyzed by polyacrylamide gel electrophoresis. Additionally, intact 4-mm-diameter punched discs from blotters containing dried blood specimen were used in the amplification reactions and analyzed by electrophoresis. The results agreed completely between these three sample types, demonstrating the feasibility of molecular genetic confirmation of the delta F508 mutation from the neonatal screening blotter among those with positive CF screening results. Such a program could reduce follow-up testing by at least 50% in a CF newborn screening program and would identify immediately those families who would benefit from carrier detection for the delta F508 allele.     

Cystic fibrosis newborn screening: a pilot study to maximize carrier screening

Newborn screening for cystic fibrosis (CF) is expanding because early diagnosis has been shown to result in improved nutrition and growth. Most newborns identified by a mutation panel have a single detected mutation and require sweat testing to exclude an additional undetected mutation. The resulting identification of CF carrier newborns, although not the primary purpose of screening, has three potential benefits, (1) the detection of trait-trait couples, (2) presymptomatic testing of these couples' previously born children who may have undetected CF, and (3) a carrier parent alerting his/her extended family members to the chance of also being a CF carrier. Reaping each benefit requires genetic counseling of parents and their accepting carrier testing. The purpose of this study was to utilize the sweat testing visit to educate parents about the value of carrier testing for themselves and their blood relatives. We compared special care (genetic counseling after explaining the sweat test result and offering of parental DNA testing, all on the sweat test visit) versus standard care (sweat test result reported by phone to the parents the next day by the newborn's physician, ideally with the recommendation to arrange genetic counseling and parental carrier testing). In the first year of New York State CF screening, 64 newborns with one detected mutation were reported in the nine-county region that includes Rochester. Of these, parents of 39 agreed to participate in the study and to be randomized to special or standard care. Sixty-one parents completed both the initial and 1-year follow-up questionnaires (30 couples and one mother). Of the 61 parents, 23 had carrier testing after the birth of the baby. The frequency of such parental testing was significantly higher in the special care group (17/34 or 50%) than in the standard care group (6/27 or 22%) (p < 0.05). This is the first evidence from a randomized trial that genetic counseling and offering carrier testing to parents on the sweat test visit increases identification of carrier parents. Such identification detects trait-trait parents and facilitates carrier testing among relatives.     

The incidence of Down's syndrome and progress towards its reduction

Down's syndrome is the most common autosomal aberration and single cause of mental retardation in man. There is a close relation between advanced maternal age and Down's syndrome. The limitation of family size has made a considerable impact on the incidence of Down's syndrome. In Denmark in the 1950s, 50% of Down's syndrome cases were born to mothers over the age of 35. The percentage went down to 25% in the 1970s and was reduced by prenatal diagnosis to 8% in the 1980s. For the period 1980-85 we followed the birth prevalence closely for different maternal age groups. The birth prevalence was lowered for the age group over 35, but there was a steady rise for the age groups below 35. Early diagnosis, high rate of survival of light-for-date babies and babies with congenital heart defect, and, possibly, exogenous factors working on gametogenesis might be an explanation. To achieve a reduction in incidence, maternal alpha-fetoprotein (AFP)-serum screening for low values may be a possibility. So far, avoidance, but not primary prevention, of Down's syndrome is available.     

超声检测胎儿先天性心脏病存在问题分析

目的探讨并分析产前超声筛查胎儿先天性心脏病临床应用中存在的问题。方法回顾性分析本院近三年来599例胎儿先天性心脏病超声检查情况。结果确诊49例先天性心脏病,43例于产前确诊,产前心超敏感性为87．7％。漏诊5例,漏诊率10．2％。误诊1例,误诊率2．04％。49例先心病者中,产前确诊后失访的32例,失访率高达65％。检查孕周为17周-39．5周,平均28．4周。结论虽然超声筛查胎儿先天性心脏病具有无创性、敏感性高等优点,但仍存在漏诊、误诊、诊断时间过晚等问题,值得引起注意。     

Carrier screening for cystic fibrosis in a prenatal setting

Maternal prenatal cystic fibrosis (CF) screening was offered from September, 1997, to April, 1999, at the Ghent University Hospital, to couples undergoing prenatal diagnosis (amniocentesis) for reasons not related to CF. Fifteen minutes were devoted to explaining CF, CF screening, and the study protocol. The purpose was to assess the short- and long-term knowledge of CF, the attitude towards carrier screening, and carriership. A total of 314 couples entered the pilot study; 13 female CF carriers were identified. None of their partners carried an identifiable mutation. Our survey results show that information about CF and CF screening can be given effectively as part of antenatal care because most couples recalled important medical and genetic issues, valued the genetic test for CF, and seemed to cope well with the results. Risk estimates and actual numbers were more difficult to process and recall. From the small number of couples in which the woman alone was found to be a carrier, there was little or no evidence of marked distress.     

Prenatal diagnosis of trisomy 21: registration results from a single genetic center

This is a retrospective review of all collected amniotic fluid samples, chorionic villus samples and other fluid-aspirations (hygroma colli fluid/urine from megacystis) over an 11-year period (1996-2006) in a single Genetic Center (University Hospital Gasthuisberg, Leuven), looking at the prenatal diagnosis of trisomy 21. In this study a total of 404 diagnoses of trisomy 21 were made on 29696 samples (1.4%). The prenatal diagnosis of trisomy 21 increased over the years with 0.88% (21/2363) in 1996 and 1.99% (50/2512)in 2006. Also the type of invasive testing changed over the years with an increase of the proportion of trisomy 21- diagnoses by chorionic villussampling from 2001. Looking at the registry for perinatal activities in Flanders for the year 2006 the live birth incidence for trisomy 21 was 1/1782 and this is lower than the often reported incidence oftrisomy 21 at birth of 1/800: it is likely that the use of more sensitive screening methods for the prenatal detection of trisomy 21 and the election of termination for most affected pregnancies affects the birth incidence oftrisomy 21.     

Prenatal sonographic diagnosis of skeletal dysplasias. A report of 47 cases

The purpose of this study was to evaluate the foetal sonographic efficiency for prenatal diagnosis of osteochondrodysplasias. Forty-seven prenatal and postnatal cases diagnosed between January 1993 and December 1998 in the referral sonographic centres of Strasbourg were studied. All cases were reviewed retrospectively and the prenatal ultrasound findings and diagnosis were compared to the postnatal or post-mortem diagnosis. Each case was studied by ultrasonographers, geneticists, radiologists, and foetopathologists. Final diagnosis was based on clinical examination, skeletal survey and molecular testing as deemed necessary. Routine screening and dating was the indication for foetal sonography in 72% (32/47) of our cases. The most likely time of diagnosis was between 16 and 24 weeks of gestation (17 out of 47 cases, 36%), which corresponds to the time of foetal anomaly sonographic scan in France. The other cluster of cases (12 among 47, 26%) was disclosed before 16 weeks of gestation. These results illustrate the importance of a detailed evaluation of the limbs during sonographic examinations of first and second trimesters of pregnancy. While the identification of skeletal dysplasias was relatively easy in our study, the ability to make an accurate specific antenatal diagnosis was more difficult. An accurate diagnosis was proposed in 28 of the 47 cases (60%). In 19% of the cases (9/47), the prenatal diagnosis was not accurate; in 21% of the cases (10/47), the prenatal diagnosis was imprecise. In 45 of the 47 cases (96%) prenatal foetal scan correctly predicted the prognosis.     

产前经腹灰阶联合彩色血流超声多参数对胎盘植入性疾病的诊断效能研究

摘要 目的：探究产前经腹灰阶联合彩色血流超声多参数对胎盘植入性疾病的诊断效能。方法：2019年11月-2021年12月于我院收治的产前超声诊断为前置胎盘的孕妇共计62例,其中44例超声诊断合并了胎盘植入的孕妇。所有孕妇产前均进行经腹灰阶检查、经腹彩色超声检查和二者联合检查胎盘植入性疾病,通过分析胎盘植入性疾病筛查结果,评价产前超声经腹灰阶联合彩色血流超声多参数对胎盘植入性疾病的筛查效能。结果：（1）通过灰阶超声诊断检出胎盘植入的灵敏度为73.42 %,特异度为86.54 %;（2）通过彩色超声诊断检出胎盘植入的灵敏度为76.89%,特异度为89.07 %;（3）经腹灰阶联合彩色血流超声多参数诊断检出胎盘植入的灵敏度为87.79 %,特异度为90.36 %;（4）经腹灰阶检查、经腹彩色超声检查和二者联合检查对胎盘植入性疾病筛查阳性率分别为56.45 %、62.90 %和67.74 %,二者联合检查对产前胎盘植入性疾病筛查阳性率显著高于经腹灰阶检查和经腹彩色超声检查（P<0.05）。（5）二者联合检查的敏感度为72.26 %,特异度为90.54 %,阳性比为95.55 %,诊断比值比为78.89 %。结论：产前经腹灰阶联合彩色血流超声多参数对胎盘植入性疾病的诊断有较高的灵敏度和特异度,值得临床推广应用。     

Impact of prenatal diagnosis on livebirth prevalence of children with congenital anomalies

The objectives of this study were to describe the impact of prenatal diagnosis on the birth prevalence of congenital anomalies over 21 years (1979-1999) in a well defined population in northeastern France (13,500 births per year). The material for this study came from the analysis of data from multiple sources on births and terminations of pregnancy after prenatal diagnosis of congenital anomalies in 279,642 consecutive pregnancies of known outcome. The study period was divided into three subgroups 1979-1988, 1989-1993 and 1994-1999. Between 1979-1988, 1989-1993 and 1994-1999, prenatal detection of congenital anomalies increased, respectively, from 12.0% to 25.5% and to 31.7%. Termination of pregnancy (TOP) increased in the same proportions during the three time periods. However, the increase of TOP was much higher for chromosomal anomalies than for nonchromosomal congenital anomalies. The birth prevalence of Down's syndrome fell by 80% from 1979-1988 to 1994-1999. Sensitivity of prenatal detection of congenital anomalies and TOPs were lower for isolated cases (only one malformation present in the fetus) than for multiple malformations in the same fetus. Sensitivity varied with the type of malformations: it was high for neural tube defect (79.7%) and urinary anomalies (50.7%) and low for congenital heart defects (16.4%). In conclusion, the introduction of routine prenatal diagnosis has resulted in a significant fall in the birth prevalence of children with congenital anomalies. However, this fall varied with the types of congenital anomalies.     

产前超声在中孕期胎儿严重先天性心脏病筛查中的应用

目的:探究产前超声检查在中孕期胎儿严重先天性心脏病(CHD)筛查中的应用。方法:选择2012年1月至2014年1月在我院妇产科进行产前常规超声检查的孕妇12076例,年龄22-41岁,平均(28.6±8.3)岁,孕周20-36周,平均(25.2±6.7)周。将符合纳入排除标准的孕妇8953例作为研究对象,其中初产妇6023例,经产妇2930例。对纳入研究的孕妇行彩色多普勒超声检查,并对妊娠结局进行追踪,将确诊情况与筛查结果进行比较分析。结果:产前彩色多普勒超声诊断出胎儿CHD38例,经尸检或新生儿彩色多普勒超声检查均确诊为CHD,对胎儿期未筛查出CHD的孕妇进行新生儿彩色多普勒超声检查,确诊4例,产前超声检查胎儿CHD检出率为90.48%(38/42),检出准确率100%(38/38)。结论:彩色多普勒超声筛查孕中期胎儿CHD,灵敏度和特异性高,安全无创伤,操作简便快速,值得推广为产前筛查的首选方法。     

孕中期超声联合无创产前基因筛查在检出染色体异常胎儿中的应用价值

摘要 目的：孕中期超声联合无创产前基因筛查（NIPT）在染色体异常胎儿检出中的应用价值。方法：选取2019年8月～2021年12月在石家庄市妇幼保健院产前检查的2000例孕中期孕妇,均接受超声检查和NIPT筛查。以羊水穿刺或引产后高通量测序结果为金标准,四格表法分析孕中期超声联合NIPT在染色体异常胎儿检出中的应用价值。结果：2000例孕中期孕妇中,超声检查共检出软指标异常37例,结构指标异常30例。NIPT筛查检出高风险孕妇17例,其中21-三体综合征11例、18-三体综合征6例。超声软指标和结构指标联合NIPT诊断胎儿染色体异常的灵敏度、特异度、阳性预测值、阴性预测值、漏诊率、误诊率、准确率分别为95.00%、99.95%、95.00%、99.95%、5.00%、0.05%、99.90%。结论：联合孕中期超声和NIPT可提高检出高风险染色体异常胎儿的灵敏度,降低漏诊率,对于早发现染色体异常胎儿具有重要价值,进而提高生育质量。