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The aim of this study was to present prenatal ultrasound findings, molecular testing results and pregnancy outcomes of cases with 22q11.2 deletion (del22q11.2) diagnosed prenatally. A total of 76 foetuses were included. All cases were diagnosed by using chromosomal microarray analysis. Data on prenatal diagnosis, ultrasound findings, pregnancy outcomes and inheritance of del22q11.2 were reviewed. Congenital heart defects (CHDs) were the most common indications (47/76, 61.8%) for prenatal testing and were isolated in 52.6% (40/76). The constitution of CHDs comprised predominantly of conotruncal defects (61.7%; 29/47). Other cardiac anomalies were encountered in 38.3% (18/47) of cases. Extracardiac findings, including unilateral multicystic dysplastic kidney, clubfoot, increased nuchal translucency, intrauterine growth retardation and polyhydramnios, were found in 31.6% (24/76) of cases, and were combined with CHDs in 7 cases. Twelve cases had normal sonographic scans at the time of prenatal diagnosis. Foetal CHDs, especially conotruncal defects, are the most predictive association with del22q11.2. The information about del22q11.2 should also be part of the contents in comprehensive pre-test counselling even for those who are referred for diagnostic testing with foetal extracardiac findings.Impact statement What is already known on this subject? 22q11.2 deletion (del22q11.2) is the most common microdeletion syndrome in humans. At present, the main indications for prenatal testing for del22q11.2 are pregnancies of abnormal sonographic findings, especially foetal congenital heart defects. What do the results of this study add? Many extracardiac malformations, including some lethal or mildly non-specific ones, could be associated with foetal del22q11.2. There were also del22q11.2 foetuses had normal sonographic scans at the time of prenatal diagnosis. What are the implications of these findings for clinical practice and/or further research? The information about del22q11.2 should also be part of the contents in comprehensive pre-test counselling even for those who are referred for diagnostic testing with indications other than foetal cardiac anomalies.

The 17q12 deletion syndrome is a chromosomal anomaly resulting from the interstitial microdeletion of the long arm of chromosome 17. The aim of this study was to present the experience on prenatal diagnosis of 17q12 deletion to further define the prenatal phenotypes of this syndrome. Eleven pregnancies with foetal 17q12 deletion detected by chromosomal microarray (CMA) were retrospectively included at a single Chinese tertiary medical centre. Clinical data were reviewed for these cases, including the maternal demographics, foetal ultrasound findings, CMA results and pregnancy outcomes. The deletion sizes of 17q12 ranged from 1.42 to 1.94 Mb. The deletion had arisen de novo in 10 cases and inherited from one of the parents in one case. Variable kidney abnormalities were found by ultrasound in all of the cases, with bilateral or unilateral hyperechogenic kidneys being the most common findings. This study indicates that a strikingly high correlation between prenatal hyperechogenic kidneys and 17q12 deletion, and prenatal testing with CMA should be offered to the foetal cases of hyperechogenic kidneys. Impact statement What is already known on this subject? 17q12 deletion syndrome is a cause of renal abnormalities, maturity-onset diabetes of the young and neurodevelopmental disorders. Prenatal diagnosis has been reported in several isolated cases with the use of microarray-based technologic means. What do the results of this study add? The results provide further evidence that a strikingly high correlation between prenatal hyperechogenic kidneys and 17q12 deletion, and genetic testing should be offered to foetal cases with hyperechogenic kidneys. A rare prenatal case of 17q12 deletion with multiple structural malformations and anhydramnios is presented. What are the implications of these findings for clinical practice and/or further research? There should be a high index of suspicion of carriers in parents when 17q12 deletion is confirmed prenatally. An extremely wide phenotype spectrum of this deletion should be emphasised in the prenatal counselling.

The aim of this study was to evaluate which chromosomal abnormalities in our cohort of foetuses with increased nuchal translucency (NT) in the first trimester of pregnancy could be detected by cell free (cf)DNA screening as well. There were 775 singleton pregnancies referred for cytogenetic testing due to an increased NT (≥3.0 mm). Chromosome aberrations were investigated using karyotyping or chromosomal microarray analysis (CMA). Karyotyping had been chosen for foetal cytogenetic testing by 446 patients, and CMA by 329 patients. Common aneuploidies (trisomies 21, 18, 13 and sex aneuploidies) were detected in 2.2% (99/446) and 1.8% (59/329) cases, respectively. In 329 with CMA testing, clinically significant copy number variations (CNVs) other than common aneuploidies were detected in 2.7% cases; among these, five had a pathogenic microscopic CNV, which could have been detected by karyotyping. There were four cases (1.2%) having a pathogenic submicroscopic CNV, which could have been missed by karyotyping. The total CMA detection rate (23.4%) was not statistically different from that (24.2%) by karyotyping (p > .05). The percentage of chromosomal aberrations, which cfDNA screening would miss in patients with increased NT in the first trimester, might be the same as in those with normal NT. Impact statement What is already known about this topic? First trimester NT is a powerful marker for screening for common aneuploidies. cfDNA screening is more accurate than any standard screening with NT. The need of NT in the era of prenatal screening using cfDNA is debated. What does this study add? An increased NT did not identify any additional aneuploidies that were detected by cfDNA screening. What are the implications of these findings for clinical practice and/or further research? The percentage of chromosomal aberrations which cfDNA screening would miss in patients with increased NT might be the same as in those with normal NT.

The aim of this study was to describe the risk of aneuploidy, associated structural anomalies and clinical outcome in pregnancies with the prenatal double bubble sign. A retrospective study on ultrasound reports and pregnancy outcomes was performed in 71 foetuses with double bubble sign, who were examined at the Guangzhou Women and Children Medical Center during a five-year period. Forty-nine patients had the regular prenatal care since first trimester; of these, 20 had the sonographic sign before 24 weeks and the remaining 29 had the sonographic diagnosis after 24 weeks. Twenty-two patients presented beyond 24 weeks and the sonographic diagnosis was late. Fetal trisomy 21 was found in one of the 49 patients who had early and regular prenatal visits, but was confirmed in six out of the 22 patients who had late prenatal care. Only one out of the 49 cases had additional malformation. In the 22 subset cases, seven had additional malformations. Two pregnancies ended in intrauterine foetal demise and five patients opted for termination of pregnancy because of additional anomalies or abnormal karyotype. There were 63 live births. Postnatal verification revealed duodenal obstruction secondary to intrinsic or extrinsic cause in 60 cases; three cases excluded duodenal obstruction. The implementation of first trimester screening programme has significantly reduced the number of duodenal obstruction cases with trisomy 21 and associated malformations. Impact statement What is already known on this subject: The double bubble sign is strongly indicative of duodenal atresia. More than one-half of foetuses with duodenal atresia have associated anomalies, especially trisomy 21. What the results of this study add: The clinical outcome of foetuses with double bubble sign was first reported in mainland China. The implementation of first trimester screening programme has significantly reduced the number of duodenal atresia cases with trisomy 21 and associated malformations. What the implications are of these findings for clinical practice and/or further research: The early diagnosis of duodenal obstruction, as well as of other associated anomalies, will allow complementary investigation, immediate and proper care at birth and family counselling.

We present prenatal diagnosis and chromosomal microarray analysis (CMA) of 9q34.3 microdeletion in a foetus with an increased nuchal translucency (NT). Conventional G-banding analysis showed a de novo translocation: 45, XX, dic (9;13)(q34;p13). CMA revealed a 3.6 Mb 9q34.3 microdeletion encompassing an OMIM gene of EHMT1 consistent with the diagnosis of Kleefstra syndrome and 9q subtelomeric deletion syndrome. We suggest an application of CMA at prenatal diagnosis in pregnancies with increased NT and an apparent balanced translocation on conventional karyotype.

The aim of this study was to describe our experience with prenatal diagnosis of thalassemia in twin pregnancies at a tertiary referral centre in mainland China. All cases of twin pregnancies at risk of α- or β-thalassemias were followed over an eight-year period. There were 32 twin pregnancies at a mean gestation of 14 weeks (range, 11-21 weeks) at risk of thalassemias, including 19 at risk of α-thalassemia and 13 at risk of β-thalassemia. Chorionicity was determined by ultrasound before prenatal diagnosis. In 19 twin pregnancies at risk of α-thalassemia, there were four where both foetuses were affected, 13 where both foetuses were not affected, and two where one foetus was affected and the other one was not affected. In 13 twin pregnancies at risk of β-thalassemia, there were five where both foetuses were affected, six where both foetuses were not affected, and two where one foetus was affected and the other one was not affected. The pregnancies with two affected foetuses were aborted (including four affected by α-thalassemia and five affected by β-thalassemia), and in pregnancies with one normal twin and one affected twin, the affected foetuses were selectively aborted (including two twins affected by α-thalassemia, and two twins affected by β-thalassemia). Efforts should be taken to reduce the risks of the mother and foetuses in prenatal diagnosis without compromising the precise diagnosis.

The purpose of this study was to evaluate the performance of the 1st-trimester combined screening test for trisomy 21 in different maternal age groups in a Chinese population. In this retrospective study, data on the 1st-trimester combined screening test (maternal age, fetal nuchal translucency, free β-human chorionic gonadotrophin, pregnancy-associated plasma protein-A) were analysed. The study population of 17,556 pregnant women was subdivided into three groups according to maternal age: 16,113 were < 35 years of age; 1,228 were 35-39 years of age; and 215 were ≥ 40 years of age. The detection and false-positive rates of the 1st-trimester screening test for trisomy 21 or trisomy 18 in the three groups of women were 89.5 and 1.7%; 90.9 and 6.8%; and 100 and 22.3%, respectively. With increasing maternal age, the odds of being affected given a positive result (OAPR) were increased. The balance between the detection rate and false-positive rate of the 1st-trimester combined screening test is more favourable in women < 36 years with comparable OAPR. Although the false-positive rate increases with increasing maternal age, the performance of the 1st-trimester combined screening test in women ≥ 35 years is more effective than screening based on maternal age alone.

Thanatophoric dysplasia (TD) is the most frequent form of lethal skeletal dysplasia. Prenatal diagnosis is commonly accomplished in the second-trimester scan, but occasionally TD is found to be associated with increased nuchal translucency (NT) at first-trimester screening for aneuploidies. TD may not be clearly distinguished from the other skeletal dysplasias. A definite diagnosis can be established by molecular genetic analysis to find out the abnormal mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We reported a case of TD type 1 detected by first-trimester NT measurement, and confirmed by molecular analysis of FGFR3 gene using high-resolution melting analysis.

The aim of this study was to describe the experience of transabdominal chorionic villus sampling (CVS) at a mainland Chinese hospital. During a 7-year period, 1,172 pregnant women chose to have CVS for prenatal diagnosis. Details and outcome of all of these cases were reviewed. The median maternal age was 29 years (range 19-45). The median gestational age was 12 weeks (range 10-14). Fetal karyotyping and thalassaemia couples were the main indications (97.2%). Overall, 112 (9.7%) chromosomal abnormalities were identified. There were 91 (7.8%) major chromosomal abnormalities, including autosomal trisomy in 70 patients, sex chromosomal abnormalities in 17, triploidy in two and unbalanced chromosomal rearrangement abnormality in two. Additionally, 137 fetuses with severe thalassaemia syndrome were found, including 86 homozygous β-thalassaemia, and 51 homozygous α-thalassaemia or non-deletional haemoglobin H disease. The procedure failed to obtain an adequate sample in four (0.3%) patients. There were 229 pregnancies terminated for medical indications after CVS. There were three (0.3%) potentially procedure-related fetal losses. CVS is a safe and reliable prenatal diagnostic technique. It should be one of the options available to pregnant women who require prenatal diagnosis.

The aim of this study is to assess the initial indications, frequency and termination rates of pregnancies with sex chromosome aneuploidies (SCAs), at a mainland Chinese hospital. A total of 56 cases (0.9%) with SCAs were identified in 6,515 pregnancies referred for fetal karyotyping. Turner syndrome was the most commonly diagnosed SCA in prenatal diagnosis (48.2%). The most common referral reason for pregnancies with Turner syndrome was cystic hygroma on ultrasonography. The main reasons for fetal karyotyping in other types of SCAs were a positive prenatal screening test and advanced maternal age. A total of 47 (84%) of the pregnancies with SCAs were terminated and nine (16%) continued. This study first reported the rate of SCAs detected at prenatal diagnosis and the outcomes of these pregnancies in mainland China, and showed a very high termination rate for pregnancies with SCAs.