Objective To investigate chromosomal abnormalities in fetuses with conotruncal defects(CTD).Methods From January 2013 to February 2017,107 fetuses (singleton pregnancy) prenatally diagnosed as CTD in Beijing Anzhen Hospital were enrolled.Umbilical cord specimens of these fetuses were collected after termination of pregnancy and analyzed by low coverage whole gene sequencing to detect chromosomal aneuploidy and copy number variations.Types of chromosomal abnormalities in these cases were analyzed.Chi-square test was used for statistical analysis.Results Twenty-two cases (21％,22/107) were identified with chromosomal abnormalities.The most common seen chromosomal abnormalities were found in those with interrupted aortic arch (2/2),followed by those with tetralogy of Fallot and pulmonary atresia/stenosis accompanied with ventricular septal defect (28％,12/43).No chromosomal abnormalities were detected in fetuses with aortopulmonary septal defect (0/2).Differences were shown in the detection rates of chromosomal abnormalities among different types of CTD (x2=12.744,P=0.026).Among the 22 fetuses with chromosomal abnormalities,there were seven with abnormal aneuploidy (three trisomy-13s,two trisomy-18s,one trisomy-21 and one 45,X) and 15 with pathogenic copy number variations [11 cases with 22q11.2 microdeletion syndrome,two with 17p12p11.2 microdeletion (Smith-Magenis syndrome),one with 8p23.3p21.3 microduplication and one with 2p23.1p25.2 microdeletion].Of the 15 cases with pathogenic copy number variations,12 segments of microdeletion/microduplications were de novo and one was paternally inherited,while the causes of the other two were not clear because their parents refused chromosomal testing.Conclusions Fetal CTD are likely to be accompanied with aneuploidy abnormalities and chromosome microdeletions/microduplications and the detection rate of chromosomal abnormalities varied with the type of CTD.Microdeletion and microduplication,especially de novo microdeletions/duplications,are the common chromosomal abnormalities.Chromosome analysis is recommended for fetuses prenatally diagnosed with CTD.

Objective To investigate the value of bacterial artificial chromosome-on-beads(BoBs) technology in the genetic analysis of early missed abortion chorionic villi. Methods Early missed abortion chorionic villi were detected with both conventional karyotyping method and BoBs technology in Peking Union Medical Hospital from July 2014 to March 2015. Compared the results of BoBs with conventional karyotyping analysis to evaluate the sensitivity, specificity and accuracy of this new method. Results (1) A total of 161 samples were tested successfully in the technology of BoBs, 131 samples were tested successfully in the method of conventional karyotyping.(2)All of the cases obtained from BoBs results in(2.7 ± 0.6) days and obtained from conventional karyotyping results in (22.5 ± 1.9) days. There was significant statistical difference between the two groups(t=123.315, P<0.01).(3)Out of 161 cases tested in BoBs, 85(52.8%, 85/161)cases had the abnormal chromosomes, including 79 cases chromosome number abnormality, 4 cases were chromosome segment deletion, 2 cases mosaic. Out of 131 cases tested successfully in conventional karyotyping, 79(60.3%, 79/131)cases had the abnormal chromosomes including 62 cases chromosome number abnormality, 17 cases other chromosome number abnormality, and the rate of chromosome abnormality between two methods was no significant differences(P=0.198).(4)Conventional karyotyping results were served as the gold standard, the accuracy of BoBs for abnormal chromosomes was 82.4%(108/131), analysed the normal chromosomes (52 cases) and chromosome number abnormality (62 cases)tested in conventional karyotyping, the accuracy of BoBs for chromosome number abnormality was 94.7%(108/114). Conclusion BoBs is a rapid reliable and easily operated method to test early missed abortion chorionic villi chromosomal abnormalities.

Objective To study the clinical presentations,diagnosis and managements of primary hyperparathyroidism (pHPT) in pregnancy.Methods A total of five cases of pHPT in pregnancy were enrolled from January 2005 to December 2014 in Peking Union Medical College Hospital.Their clinical presentations,managements,maternal-fetal complications and pregnancy outcomes were retrospectively analyzed.Results The median age was 32 (29,41) years.Of the five cases,three were diagnosed in the second trimester,one was before pregnancy and one was after delivery.Most of the clinical symptoms were nonspecific to pHPT,such as nausea,vomiting and loss of appetite.Frequent urination and nocturia occurred in one;unconsciousness and manifestations of acute pancreatitis and eclampsia relevant symptoms were complained of by one.The common maternal complications were nephrolithiasis and hydronephrosis (3/5),osteoporosis (2/5),anemia (2/5) and kaliopenia (2/5),while the severe complications were hypercalcemic crisis (2/5),acute pancreatitis (1/5),eclampsia (1/5),HELLP (hemolysis,elevated liver enzymes and low platelets) syndrome (1/5),disscminated intravascular coagulation (DIC) (1/5),cerebral infarction (1/5) and intrauterine fetal death of one twin (1/5).The median level of calcium in serum samples was 3.70 (2.78,4.50) mmol/L;the median level of parathyroid hormone (PTH) in serum samples was 294 (151,634) pg/ml.All of the five cases were positive for parathyroid ultrasonography.Four cases received parathyroid radionuclide imaging and had positive results.One asymptomatic patient received no specific treatment,whereas the neonate presented with hypocalcemia after birth.Two cases received surgical resections in the second trimester;one of them had a live birth without fetal complication,while the other had induced abortion.Two cases received postpartum surgery;one asymptomatic patient had a live birth without fetal complication,whilc thc other with twin pregnancy suffered stillbirths (one intrauterine fetal death and one neonatal death).Pathologic diagnosis were solitary parathyroid adenomas in four cases who received surgery.Their operations were effective except that one case,which was improved after treatment,was complicated with secondary hypoparathyroidism.Conclusions The symptoms of pHPT in pregnancy are often nonspecific,but it can cause maternal and fetal morbidity and mortality.Early diagnosis of pHPT,followed by appropriate managements,has been shown to significantly reduce the complications.Surgical management should be a safe and effective choice.

Objective To evaluate the residual risk (i.e.failure risk in detecting aneuploidies abnormalities except for chromosome 13,18,21,X and Y) of cytogenetic abnormalities using interphase fluorescence in situ hybridization (FISH) for the second-trimester amniocytes.Methods The results of interphase FISH and conventional karyotyping of 2 837 consecutive amniotic fluid specimens were analyzed retrospectively.Probes for chromosomes 13,18,21,X and Y were used.The detection rate and residual risk for interphase FISH were calculated for the following three major clinical indications for prenatal diagnosis (advanced maternal age,abnormal maternal serum screening indicating an increased risk for trisomy 18 or trisomy 21,and ultrasound abnormalities).Results Consecutive interphase FISH and karyotyping of second-trimester amniocytes for prenatal diagnosis were performed from January 1,2010 to July 31,2013.Among the 2 837 cases,85 (3.0％) cases with abnormal karyotypes were found,including 73 cases of aneuploidies involving chromosome 13,18,21,X and Y,which were considered detectable by interphase FISH; 12 cases of chromosomal anomalies,other than aneuploidies of chromosome 13,18,21,X and Y,were diagnosed after karyotyping and were not detected by interphase FISH,including six cases of balanced rearrangements,five cases of imbalanced rearrangements,and one case of pseudomosaic of trisomy 20.Of these 12 chromosomal anomalies,three cases of imbalanced rearrangements involving chromosome 21 showed positive FISH results,and the other nine cases showed negative FISH results among which four case of hereditary balanced rearrangemerts and two cases of novel balanced rearrangements.The total detection rate for interphase FISH was 89.4％ (76/85),the misdiagnosis rate of chromosome abnormalities was 14.1％(12/85),and the residual risk was 0.43％ (12/2 761) following interphase FISH of the second-trimester amniocytes.Conclusions Interphase FISH is a useful adjunct to conventional karyotyping,but should not be regarded as a replacement for karyotyping as too many structural chromosomal abnormalities will be missed.Providing patients with a detection rate and residual risk during counselling may help them understand the advantages and limitations of interphase FISH in their prenatal diagnostic evaluation.

Objective To investigate the prenatal diagnosis and prenatal genetic conselling of pseudomosaic trisomy 20. Methods One case of pseudomosaic trisomy 20 was analyzed and relative literatures were reviewed. Results A 31-year-old gravid 1, para 0 woman underwent amniocentesis at 18 weeks of gestation due to high risk of trisomy 21 during maternal serum screening in September, 2012. Interphase fluorescence in situ hybridization (FISH) of amniocytes with probes GLP13/GLP21/CSP18/CSPX/CSPY showed a normal result, while cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XY,+20[7]/46,XY[9]. The level of trisomy in the cultured amniocytes was 7/16. Cordocentesis revealed a karyotype of 46,XY in cultured cord blood cells. Interphase FISH analysis was performed using the probes D20Z1 (20p11.1-q11.1) and D20S1157/20QTEL14 (20 per/qter). Each probe showed two signals in all uncultured amniocytes. The prenatal ultrasound findings were unremarkable. The mosaicism was considered to be pseudomosaicism. After genetic counseling, the parents selected to continue the pregnancy. A healthy male baby was delivered at 39 weeks of gestation. Postnatal cytogenetic analysis revealed a karyotype of 46,XY in peripheral blood lymphocytes. Interphase FISH analysis of the uncultured buccal cast-off cells using the probes D20Z1 and D20S1157/20QTEL14 showed normal results in 100%cells. There was no phenotypic abnormality at the age of seven months. Conclusions When mosaic trisomy 20 is identified in amniocytes, further evaluation and genetic counseling are required. Interphase FISH of the uncultured amniocytes with a chromosome-specific probe is a useful tool for confirmation of the prenatal diagnosis of mosaicism. Genetic analysis of multiple tissues is required postnatally.

Great efforts have been made in the prenatal screening and prenatal diagnosis of aneuploidy in China.Nevertheless,the coverage percentage of screening is still low,and the capability of diagnosis is far from enough.To elevate the efficacy of prenatal screening,developing fast aneuploidy diagnositic techniques is quite important.Cell-free DNA testing is believed to be a confirmatory screening test of aneuploidy.Fluorescence in situ hybridization,fluorescence quantitative PCR might be used in the prenatal diagnosis in high risk women.Chromosomal microarray analysis has high sensitivity in the diagnosis of microdeletion and microduplication.The era of cytomolecular diagnosis is coming.

Objective To evaluate the maternal and fetal outcomes of pregnant women with lupus nephritis (LN) and the risk factors.Methods Ninety-three patients with 97 pregnancies from January 1st,1990 to December 31st,2012 in Peking Union Medical College Hospital were evaluated retrospectively.Objects of study were divided into three groups:stable lupus before pregnancy (stable group,52 cases),active lupus before pregnancy (active group,26 cases),and newly diagnosed LN during pregnancy (19 cases).Adverse maternal outcomes included exacerbated disease during pregnancy,preeclampsia,increased proteinuria and impaired renal function during pregnancy or postpartum,maternal death,thrombocytopenia and hypocomplementemia.Adverse fetal or neonatal outcomes included therapeutically termination of pregnancy,fetal loss,neonatal death,preterm labor,small gestational age and asphyxia.Statistical analysis was performed by Chi-square test or Fisher's exact test.A binary logistic regression model was used to evaluate the risk factors for adverse maternal and fetal outcomes.Results (1) Adverse maternal outcomes:There was no significant difference between exacerbated cases during pregnancies in stable group and that in active group [53.8 ％ (28/52) vs 61.5 ％ (16/26),x2 =0.417,P＞0.05].After deleting abortions before 20 weeks of gestation (5 cases in stable group and 4 cases in active group),there was no significant difference between preeclampsia incidence in stable group and that in active group [36.2％ (17/47) vs 59.1％ (13/22),x2 =3.204,P＞0.05].In nineteen newly diagnosed LN women,eighteen cases were over 20 weeks of gestation,during which preeclampsia incidence was 6/18.(2) Adverse fetal or neonatal outcomes:Therapeutically termination of pregnancy rate was higher in active group than that in stable group[42.3％(10/26) vs 7.7％(4/52),Fisher's exact test,P＜0.01].After deleting patients who required termination of pregnancy (three cases in stable group) and therapeutically termination of pregnancy (four cases in stable group and ten cases in active group),the rate of fetal loss and neonatal death was higher in active group than that in stable group [5/16 vs 6.7％(3/45),Fisher's exact test,P＜0.05].The rate of adverse fetal or neonatal outcomes was higher in active group than that in stable group [92.3％(24/26) vs50％(26/52),x2=13.483,P＜0.001].Among the nineteen newly diagnosed LN cases during pregnancy,the numbers of therapeutically termination of pregnancy and fetal loss were five and three cases respectively; among eleven live birth cases,two newborns died from severe asphyxia,and nine cases were preterm birth.(3) Binary logistic regression analysis showed that the independent risk factors for exacerbated lupus during pregnancy were hypocomplementemia (OR =0.300,95％ CI:0.104-0.863) and thrombocytopenia (OR =0.054,95％CI∶0.007-0.439).The independent risk factors for preeclampsia in LN pregnant women were thrombocytopenia (OR=0.151,95％CI:0.046-0.499) and LN recurrence or first diagnosed during pregnancy (OR=0.135,95％CI:0.027-0.679).The independent risk factors for adverse fetal or neonatal outcomes were preeclampsia (OR=0.134,95％CI:0.028-0.637) and lupus active during pregnancy (OR =0.026,95 ％ CI:0.005-0.138).Conclusions Active lupus before pregnancy is associated with poor maternal and fetal outcomes in lupus nephritis pregnancy.All pregnancies with LN should be planned,preferably after more than six months of quiescent disease.Blood pressure,renal function,proteinuria and level of platelet and serum complements should be closely monitored.

Objective To investigate the relationship between abnormalities of maternal serum markers in Down syndrome screening in second trimester and adverse pregnancy outcome.Methods Totally,1935 pregnant women were screened for Down syndrome with maternal serum tri marker with time-resolved fluorescence assay,including alpha fetoprotein (AFP),free β-human chorionic gonadotropin (β-hCG) and unconjugated estriol (uE3),between 15 and 20+6 gestational weeks at Peking Union Hospital from January 1,2009 to January 31,2011,and were followed up till delivery.The relationship between incidence of adverse pregnancy outcomes and women with normal or abnormal levels of serum markers in Down syndrome screening was investigated.T-test or Chi-square test were applied for statistical comparison.Results (1) Among the 1935 pregnant women,normal levels of serum markers were found in 1255(normal group) and 680 were abnormal(abnormal group),in which 577 with only one abnormal serum marker,89 with two and 14 with three abnormal serum markers.According to the serum marker level,the 577 women with one abnormal serum marker were further divided into five groups,including high AFP group (n=17),low AFP group (n=114),high β-hCG group (n=242),low β-hCG group (n=139) and low uE3 group (n=65).The birth weight of infants in lower AFP group and the gestational age at delivery in low β-hCG group were greater than those in normal group [(61.3±9.1) kg vs (59.5±8.3) kg,(272.6±11.8) d vs (274.4±10.1) d,t=2.21 and 1.99,both P＜0.01].(2) The incidence of adverse pregnancy outcome in normal group was 42.8％(537/1255),while comparing with the abnormal group(43.7％,297/680),no statistical significance was shown (RR =1.02,P =0.71).While comparing with the normal group,the incidences of placenta previa [25.5％ (32/1255) vs 2/17,RR=4.61,P＜0.05] and abnormal placental morphology were higher in high AFP group [4.1％ (51/1255) vs 5/17,RR=7.24,P＜ 0.05],the incidence of gestational diabetes mellitus (GDM) was higher in low AFP group [8.1％ (101/1255) vs 14.4％(16/114),RR=1.74,P＜0.05],the incidence of placenta and membrane retention was higher in high β-hCG group [3.5％ (44/1255) vs 6.2％(15/242),RR=1.77,P＜0.05],the incidence of pre-eclampsia was higher in low β-hCG group [1.7％ (21/1255) vs 6.5％ (9/ 139),RR=3.87,P＜0.05].(3) There were 89 women with two abnormal serum markers.Comparing with the normal group,the incidences of small for gestional age (SGA) infants,oligohydramnios,abruptio placenta were higher in women with low AFP but high β-hCG [SGA infants:6.9％(2/29) vs 1.8％(22/1255),RR=3.94; oligohydramnios:20.7％(6/29) vs 6.4％(80/ 1255),RR=3.24; both P＜0.05],the incidences of oligohydramnios was higher in women with both low AFP and low uE3[3/14 vs 6.4％(80/1255),RR=3.36,P＜0.05],the incidence of premature birth and GDM were higher in women with both low β-hCG and low uE3 [premature birth:2/6 vs 4.3％(54/1255),RR=7.75; GDM:3/6 vs 8.0％ (101/1255),RR=6.21; both P＜0.05].(4) There were 14 women with three abnormal serum markers.The relationship between adverse outcome and abnormal serum markers did not show any statistical significance.Conclusions The abnormality of serum markers of Down syndrome screening is closely related to adverse pregnancy outcomes,and women with abnormal serum markers should be carefully monitored during pregnancy.

Objective To calculate the incidence of chromosomal abnormalities at second trimester in women who were 35 or older at their expected date of birth.Methods The amniocentesis and karyotyping results in Peking Union Medical College Hospital from January 1st,2001 to June 30th,2011 were retrospectively analyzed.The only indication for amniocentesis in these group of woman was advanced maternal age.A total of 6584 cases Were included in this study and were divided into two groups according to maternal age,ie.35-39 and ≥40 year old group.The incidences of fetal 47,+ 21,47,+ 18 and sex aneuploidies were calculated and compared between two groups by Chi-square test.Results Altogether,121 cases were diagnosed to be abnormal chromosome,and the overall incidence was 18.38‰ (121/6584).The abnormal karyotypes included 111 cases of aneuploidies (mosaicism included) and 10 cases of structural abnormalities.The aneuploidies included 59 cases of 47,+21 (8.96‰,59/6584),25 cases of 47,+18 (3.80‰,25/6584),2 cases of 47,+13 (0.30‰,2/6584) and 25 cases of sex aneuploidies (3.80‰,25/6584).Fetal 47,+21 was the most frequent chromosomal abnormality,accounting for 53.15％ (59/111) of all aneuploidies.The incidence of fetal 47,+21 was significantly higher in ≥40 year-old group than that of 35-39 year old group[13.99‰(16/1144) vs 7.90‰(43/5440),x2=3.937,P=0.047].There were no statistical differences of the incidences of fetal 47,+ 18 and sex aneuploidies between the two groups.Conclusions The main fetal chromosomal abnormalities in women aged 35 and older are the aneuploidies of chromosome 21,18,13 and sex chromosomes.The incidence of fetal 47,+21 is significantly increased in the women aged 40 years and older.So prenatal screening should be provided first to women at 35-39 years of age and amniocentesis should be the first choice of prenatal diagnosis for women over 40 years old.

Abnormal thyroid function is high risk for pregnancy.Studies from clinical observation and animal experiments have indicated that maternal sub clinical hypothyroidism during the first gestational term may lead to impairment of brain development of offspring,and early diagnosis and effective treatment may prevent the damage.Therefore,it is suggested that screening thyroid function before gestational 8 weeks in pregnant women is initiated.The changes in thyroid function during pregnancy are related to these changes in maternal thyroid physiology can lead to confusion in the diagnosis or evaluation of thyroid abnormalities.Establishment of trimester-specific reference ranges is urgently needed.Local iodine nutritional statue and testing reagent effect the measured value of thyroid function in general population,so it is recommend that all regions and hospitals should establish their own pregnancy reference ranges.