Efficacy and initial clinical evaluation of optical genome mapping in the diagnosis of structural variations / 中华预防医学杂志

To investigate the efficacy and value of optical genome mapping (OGM) in detecting chromosomal structural variations. In a clinical study about high-precision analysis of genomic structural variation for complex genetic diseases, a retrospective study was performed on the cases with karyotyping at the department of Obstetrics and Gynecology, and Endocrinology of Peking Union Medical College Hospital from January to December 2021. Ten cases with abnormal karyotype was detected by OGM. Partial cases were verified by fluorescence in situ hybridization (FISH), SNP array or CNV-seq. Results of ten cases, nine were detected with abnormality by OGM, including unbalanced chromosomal rearrangements (n=3), translocation (n=5) and paracentric inversion (n=1), and the results were in concordance with other standard assays. However, one case with breakpoint and reconnected at centromere has not been detected. In conclusion, ten samples were comprehensively analyzed by karyotyping, FISH, SNP array or CNV-seq, and OGM, and results demonstrated that optical genome mapping as a new technology can not only detect unbalanced rearrangements such as copy number variants as well as balanced translocations and inversions, but more importantly, it can refine breakpoints and orientation of duplicated segments or insertions. So it can contribute to the diagnosis of genetic diseases and prevent birth defect. However, the current technology is not yet capable of detecting breakpoints of balanced structural variations lying within unmapped regions.

A prospective study of correlation between serum leptin,resistin and adiponectin levels and preeclampsia / 中国实用妇科与产科杂志

OBJECTIVE: To investigate the relationship between serum leptin,resistin and adiponectin levels and preeclampsia.METHODS: The study was a case-control study.All enrolled pregnant women were selected from January2013 to June 2015 in Peking Union Medical College Hospital,Peking Union Medical College Peking Union Medical College Hospital.In the case group,74 patients were further divided into early-onset and late-onset subgroups(51 cases and 23 cases respectively).The control group enrolled 79 uncomplicated pregnant women who delivered full-term babies during the study period.Three adipokines were measured by enzyme linked immunosorbent assay.RESULTS: Leptin level8.98)μg/L,P<0.001).Positive correlation between leptin level and BMI was observed in normotensive pregnancies(r=0.651,P<0.001),but the correlation disappeared in preeclampsia patients.The serum resistin level in the case group was significantly higher than that in the control group(14.08±6.10)vs.(9.99±8.33)μg/L,P<0.001),and there was no correlation between serum resistin level and BMI.There was no significant difference in adiponectin level between the case group and the control group.CONCLUSION: Serum resistin and leptin in preeclampsia population are significantly higher than those in normotensive pregnancies,and the underlying mechanism of their elevation needs to be further investigated.The correlation between adiponectin and preeclampsia is not clear.

Preterm Births in Peking Union Medical College Hospital in the Past 25 Years / 中国医学科学院学报

Objective To investigate the changes in preterm birth rate,its gestational age distribution,and possible contributors in Peking Union Medical College Hospital (PUMCH) over the last 25-year period. Methods The clinical data of premature deliveries,both singleton and twins,in PUMCH from January 1,1990 to December 31,2014 were retrospectively analyzed. We counted the number of premature fetuses and assessed the changes of preterm birth rate and its gestational age distribution (including extremely preterm birth,early preterm birth,and late preterm birth) over time. The etiologies (including spontaneous and iatrogenic) of preterm birth were also surveyed. Results The overall preterm birth rate was 7.8% in PUMCH,showing a slightly up-trend in both singletons and twins. Twin prematurity accounted for 23.8% of total preterm births,increased from 15.1% to 28.5%. Preterm births subgrouped by gestational age included 26 cases (0.7%) of extreme prematurity (<28 weeks),1199 cases (33.9%) of early preterm birth (28- 33weeks),and 2310 cases (65.3%) of late preterm birth (34- 36weeks). The gestational age distribution in singletons and twins showed no significant difference(z=0.844,P=0.398). Changes in the proportion of preterm birth before 28 weeks was little,gradually increased in the 28- 33weeks group (from 23.8% to 36.1%) and gradually decreased in the 34- 36weeks group (from 75.5% to 63.3%). Trends of gestational age distribution of singleton and twins were similar to that of the total. Spontaneous preterm labor,preterm premature rupture of membrane,and medically indicated (iatrogenic) preterm birth accounted for 20.2%,38.9%,and 40.9% respectively. There was no difference in singletons and twins(χ=1.071,P=0.301).The proportion of iatrogenic preterm was increased. Common reasons for iatrogenic preterm birth included gestational hypertension,fetal indications (including fetal distress,fetal growth restriction),placenta previa,and pregnancy complicated by heart disease. Conclusions The overall preterm birth rate shows an upward trend in the general hospital as a result of more multifetal gestations and more medically indicated preterm births. Reducing multifetal gestations and effective control of pregnancy complications should be the priorieties in preterm birth intervention.

Obstetric outcomes in Chinese women with endometriosis: a retrospective cohort study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The effect of endometriosis on obstetric outcomes is still ambiguous. The aim of our study was to determine the association between endometriosis and adverse obstetric outcomes in a cohort of Chinese women.</p><p><b>METHODS</b>A retrospective cohort study was undertaken to compare obstetric outcomes between 249 women with endometriosis and 249 women without endometriosis. All women were nulliparous and achieved singleton pregnancies naturally. Women with endometriosis were diagnosed during surgery and confirmed histologically. Odds ratios (ORs) and 95% confidence intervals (CIs) of measures of obstetric outcomes were calculated.</p><p><b>RESULTS</b>Women with endometriosis showed significantly increased risks of preterm labor (adjusted OR, 2.42; 95% CI, 1.05-5.57), placenta previa (adjusted OR, 4.51; 95% CI, 1.23-16.50), and cesarean section (adjusted OR, 1.93; 95% CI, 1.31-2.84). No significant differences were observed in the incidence of pregnancy-induced hypertension, fetal growth restriction, small for gestational age, placental abruption, or luteal support in the first trimester between the two groups.</p><p><b>CONCLUSIONS</b>Women with endometriosis are at a higher risk of preterm labor, placenta previa, and cesarean section during pregnancy and need additional care.</p>

Genetic counseling, prenatal screening and diagnosis of Down syndrome in the second trimester in women of advanced maternal age: a prospective study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The incidence of autosomal trisomy in livebirths is strongly dependent on maternal age. Special consideration is given to the provision of prenatal screening and cytogenetic testing to women of advanced maternal age (AMA). The aim of this study was to evaluate the effectiveness of second trimester prenatal screening and amniocentesis for Down syndrome (DS) and compare the trends of choice of screening and amniocentesis among AMA women.</p><p><b>METHODS</b>A total of 5404 AMA patients with natural singleton pregnancy were recruited for this prospective study from January 2008 to December 2010. The gestational weeks were from 15 weeks to 20(+6) weeks. The patients referred were grouped into a screening group (2107 cases) and an amniocentesis group (3297 cases) by their own decision. The prevalence of DS was compared between the two groups by chi-square test. Choice rates for each maternal age with trends were compared by regression analysis.</p><p><b>RESULTS</b>There were 18 cases of fetal DS detected in the screening group with a prevalence of 8.54‰ (18/2107). Twenty-five cases of fetal DS were diagnosed in the amniocentesis group with a prevalence of 7.58‰ (25/3297). No statistical difference was observed in the prevalence of DS between the screening and amniocentesis group (P = 0.928). The invasive testing rate for DS in the amniocentesis group was 5.54 times higher than that of the screening group (1/131.88 vs. 1/23.78). With the increase of the maternal age, the choice of amniocentesis increased while the choice of the screening showed an opposite trend. The choice of the AMA women between the screening and amniocentesis was significantly age relevant (P = 0.012).</p><p><b>CONCLUSIONS</b>The second trimester serum screening in combination with maternal age was more effective than maternal age alone to screen for DS. We suggest educating the patients by recommending AMA women be informed of both screening and amniocentesis options.</p>

Management of pregnancy with ankylosing spondylitis / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To discuss the interaction between pregnancy and ankylosing spondylitis, and the management of pregnancy with ankylosing spondylitis.</p><p><b>METHODS</b>Twelve cases of pregnancy with ankylosing spondylitis in Peking Union Medical College Hospital from September 2004 to July 2011 were analyzed retrospectively, focusing on the arteritis condition, pregnancy complications, and outcomes.</p><p><b>RESULTS</b>All the 12 patients had full-term pregnancy. Five cases gave birth naturally, and 7 cases received cesarean section for maternity factors. No adverse pregnancy outcomes were encountered. Waist pain appeared in 2 cases in the second trimester, for both of which medication failed. One of the 2 cases had natural childbirth, while the other maintained pregnancy smoothly to cesarean section.</p><p><b>CONCLUSIONS</b>Pregnancy monitoring can help obtain favorable pregnancy outcomes. Attention should be paid to postpartum change of the illness.</p>

Association between vitamin D insufficiency and the risk for gestational diabetes mellitus in pregnant Chinese women / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the association between vitamin D deficiency and risk of gestational diabetes mellitus (GDM) in pregnant Chinese women.</p><p><b>METHODS</b>A nested case-control study was conducted. Clinical and biochemical data were analyzed for 200 subjects with GDM and 200 subjects with normal glucose tolerance (NGT).</p><p><b>RESULTS</b>The median (interquartile range) serum 25-hydroxyvitamin D (25OHD) levels were 22.39 (17.67, 29.38) and 25.86 (19.09, 34.88) nmol/L in the GDM and NGT groups, respectively. Rates of 25OHD deficiency or insufficiency were significantly higher in the GDM group than in the NGT group. Subjects with 25OHD levels <25 nmol/L had a 1.8-fold higher risk of GDM compared with subjects with higher vitamin D levels. In the GDM group, serum 25OHD was independently associated with HbA1c and insulin resistance after adjusting for confounding factors. In the NGT group, serum 25OHD was independently associated with fasting plasma glucose and systolic blood pressure after adjusting for maternal age and other confounding factors.</p><p><b>CONCLUSION</b>25OHD insufficiency is very common in Chinese women. Low 25OHD status may be associated with insulin resistance and act as a risk factor for GDM.</p>

Application of fluorescence in situ hybridization on detection of abnormal karyotypes from spontaneous abortion specimens / 中华围产医学杂志

Objective To investigate the effect of fluorescence in situ hybridization (FISH) in increasing the accuracy and detection rate of chromosome aneuploid from spontaneous abortion specimens.Methods Chromosome 13,21,16 and 22 single sequence probes and centromere probes of 18,X and Y chromosome probes were used to detect 100 cases of spontaneous abortion villi samples.The results were compared with conventional karyotype analysis.Results (1) Karyotype analysis:Among 89 successfully cultured villi samples,51 abnormal karyotypes (57.3％) were found,including 37 cases of autosomal aneuploidies,four sex chromosome aneuploidies,two triploids,one tetraploid,one 68,XX and six chromosome structural aberrations.(2) FISH:The detection rate of abnormal karyotype was 38.0％ (38/100),among which 25 cases were autosomal aneuploidies,five sex chromosome aneuploidies,three triploids,four XX chimeras and one triploid in chromosome 13,16,18 and 21.(3) Comparison of the two methods:Among the 11 samples which failed by conventional method,FISH found two abnormal samples.In specimens of 46,XY,three cases showed mosaicism by FISH.In specimens of 46,XX,two cases showed chromosomal abnormalities by FISH.FISH detected overall 65.5％ (38/58) of the chromosomal abnormalities.Conclusions FISH combined with conventional chromosome analysis could improve the accuracy and detection rate of abnormal karyotypes in spontaneous abortion specimens.

Cytogenetic and clinical analysis of 340 Chinese patients with primary amenorrhea / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To analyze the relationship between karyotypes and clinic features of patients with primary amenorrhea.</p><p><b>METHODS</b>G banding was done for 340 patients with primary amenorrhea to facilitate individual chromosome identification, and if specific staining for certain portions of the chromosome was necessary, C banding was used. The clinical data were recorded by physical examination and ultrasound scanning.</p><p><b>RESULTS</b>Karyotype analysis of the 340 patients revealed that 180 (52.94%) patients had normal female karyotypes and 160 (47.06%) patients had abnormal karyotypes. The abnormal karyotypes included abnormal X chromosome (150 patients), mosaic X-Y chromosome (4 patients), abnormal autosome (5 patients), and X-autosome translocation (1 patient). The main clinical manifestations in patients with primary amenorrhea were primordial or absent uterus (95.9%), invisible secondary sex features (68.8%), little or absent ovary (62.6%), and short stature (30.0%). The incidence of short stature in patients with X chromosome aberration (46%, 69/150) was significangly higher that in patients with 46, XX (9.44%, 17/180) as well as 46, XY (6.67%, 3/45; Chi square = 146.25, P=0.000). All primary amenorrhea patients with deletion or break-point at Xp1 1.1-11.4 were short statures.</p><p><b>CONCLUSIONS</b>One of the main reasons of primary amenorrhea is choromosome abnormality, especially heterosome abnormality. It implies the need to routinely screen chromosomal anomalies for such patients. There might be relationship between Xp1 1.1-11.4 integrity and height improvement.</p>

Influential and prognostic factors of small for gestational age infants / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Small for gestational age (SGA) infants are associated with a high rate of oligohydramnios, stillbirth and cesarean delivery. Among SGA patients there is a higher risk of neonatal complications, such as polycythemia, hyperbilirubinemia, and hypothermia. Additionally, the SGA infant is prone to suffer from major neurologic sequelae, as well as cardiovascular system disease, in later life. Proper monitoring and therapy during pregnancy are, therefore, of utmost importance. The present study aimed to investigate the influential and prognostic factors of SGA infants.</p><p><b>METHODS</b>From January 2001 to June 2007, a total of 55 SGA neonatal infants were included in a study group. All were born at Peking Union Medical College Hospital, with regular formal antenatal examinations. In addition, a total of 122 cases of appropriate for gestational age (AGA) infants were born at the same time and were registered into a control group. All cases were singleton pregnancies with detailed information of the maternal age, gravidity, parity, maternal height and weight, complications, uterine height and abdominal circumference, results from transabdominal ultrasonography between 32 - 38 gestational weeks, pregnancy duration, delivery manner, placenta, umbilical cord, and neonatal complications.</p><p><b>RESULTS</b>Significant differences were observed in placenta weight and neonatal malformations between the study and control groups. Multivariate analysis revealed increased parity, maternal hyperthyroidism and hyperthyroidism history as risk factors. Fetal abdominal circumferences less than 30 and 32 cm at 32 - 38 gestational weeks respectively, as determined by ultrasonography, resulted in a Youden index of 0.62.</p><p><b>CONCLUSIONS</b>SGA infants were associated with a greater risk of smaller placentas and infant malformations. Increased parity, maternal hyperthyroidism, and a hyperthyroid history were risk factors for SGA infants. Fetal abdominal circumference less than 30 cm at 32 gestational weeks and less than 32 cm at 38 weeks, as determined by ultrasonography, was considered an effective index for SGA.</p>

Pregnancy outcomes of repeat cesarean section in Peking Union Medical College Hospital / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the effect of elective repeat cesarean section on the maternal and neonatal outcomes.</p><p><b>METHODS</b>A retrospective clinic- and hospital-based survey was designed for comparing the maternal and neonatal outcomes of elective repeat cesarean section [RCS group (one previous cesarean section) and MRCS group (two or more previous cesarean sections)] and primary cesarean section (FCS group) at Peking Union Medical College Hospital from January 1998 to December 2007.</p><p><b>RESULTS</b>The incidence of repeat cesarean section increased from 1.26% to 7.32%. The mean gestational age at delivery in RCS group (38.1+/-1.8 weeks) and MRCS group (37.3+/-2.5 weeks) were significantly shorter than that in FCS group (38.9+/-2.1 weeks, all P<0.01). The incidence of complication was 33.8% and 33.3% in RCS group and MRCS group respectively, and was significantly higher than that in FCS group (7.9%, P<0.05). Dense adhesion (13.5% vs. 0.4%, OR=7.156, 95% CI: 1.7-30.7, P<0.01) and uterine rupture (1.0% vs. 0, P<0.05) were commoner in RCS group compared with FCS group. Neonatal morbidity was similar among three groups (P>0.05).</p><p><b>CONCLUSIONS</b>Repeat cesarean section is associated with more complicated surgery technique and increased frequency of maternal morbidity. However, the incidence of neonatal morbidity is similar to primary cesarean section.</p>

Postnatal and prenatal diagnosis of mucopolysaccharidosis type III (Sanfilippo syndrome) / 中华儿科杂志

<p><b>OBJECTIVE</b>Mucopolysaccharidosis (MPS) types IIIA, B, C, D are a group of autosomal recessive lysosomal storage disorders caused by mutations in one of four genes which encode enzyme activities required for the lysosomal degradation of heparan sulfate. MPSIIIA and MPSIIIB involve deficiencies of heparan N-sulfatase (SGSH) and alpha-N-acetylglucosaminidase (NAGLU). MPS IIIA and MPS IIIB are more common than MPS IIIC and IIID. The present study aimed to establish two enzyme assay methods for SGSH and NAGLU activities for carrying out postnatal and prenatal diagnosis of MPSIIIA and IIIB by means of SGSH and NAGLU activity assay on plasma, leukocyte, uncultured chorionic villi (CV) and cultured amniotic fluid cells (AF cell) using two newly synthesized substrates. Mutation analysis of SGSH gene was also performed.</p><p><b>METHODS</b>Two fluorigenic substrate (4-methylumbelliferyl-alpha-D-N-sulphoglucosaminide.Na and 4-methylumbelliferyl-alpha-N-acetylglucosaminide) were used for the assay of SGSH and NAGLU activity. SGSH activity in leukocyte was determined for diagnosis MPSIIIA proband. NAGLU activity was determined in plasma for diagnosis of MPSIIIB proband. Twelve cases with MPS III were enrolled in this study, 4 were female and 8 were male, age 3 - 10 years and were from 10 unrelated families. Eight exons of SGSH gene were amplified by PCR. The mutations of the patients were characterized by direct sequencing of the amplified DNA fragments. Prenatal diagnosis in 3 pregnancies at risk was carried out according to NAGLU activity on uncultured CV at 11th week or on cultured AF cell at 18th week of gestation.</p><p><b>RESULTS</b>The SGSH activities in leukocyte of normal controls were 4.4 - 8.1 nmol/(17 h.mg protein). The NAGLU activity in plasma of normal controls was 33.3 - 62.4 nmol/(4 h.ml). The NAGLU activities were 44.9 - 91.7 nmol/(17 h.mg protein) and 53.2 - 82.2 nmol/(17 h.mg protein) in CV and cultured AF cells respectively. Five cases of MPS IIIB and 7 cases of MPS IIIA were diagnosed. The mutation analysis of SGSH gene showed 6 mutations (G191R, D235N, R377C, E447K, R233X and D219Wfs264X), only one of which (D219Wfs264X) has not been previously reported. Prenatal diagnosis was performed on 3 pregnancies at risk. NAGLU activity of one affected fetus was 1.5 nmol/(17 h.mg protein) in AF cell.</p><p><b>CONCLUSIONS</b>The method using synthesized fluorigenic 4-methylumbelliferyl-substrates were sensitive, rapid and convenient assay of SGSH and NAGLU activity and were reliable for early prenatal diagnosis. Mutation analysis on MPS IIIA patients suggests new possibilities for molecular diagnosis of the disease.</p>

Screening by maternal serum markers for Down's syndrome / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the optimal method of screening for Down's syndrome (DS) with maternal serum mankers.</p><p><b>METHODS</b>Screening by maternal serum markers for Down's syndrome was offered to all 2886 pregnant women in Peking Union Medical Hospital during 1996.11-2001.3. Alpha-fetoprotein (AFP), human chorionic gonadotrophin (free beta-HCG) were used as markers during the first year of pregnancy. Alpha-fetoprotein, free human chorionic gonadotrophin (HCG) and pregnancy-associated plasma protein A (PAPP-A) were used as mid pregnancy and first-trimester markers in next three years. Amniocentesis and (CVS) were done in those defined as risk cases.</p><p><b>RESULTS</b>The detection rate of Down's syndrome by maternal serum markers was 3.8% (11/2886). The proportion of false positive results in group of triple markers (alpha FP, free beta-HCG, PAPP-A) was 5%.</p><p><b>CONCLUSIONS</b>The PAPP-A was a good marker to detect Down's syndrome in early pregnancy and may be used to predict the outcome during mid trimester of pregnancy. The AFP and free beta-HCG can be useful markers to detect Down's syndrome and fetal abnormality. While prenatal diagnostics can be shifted to an early pregnant period.</p>

Application of intrapartum fetal oxygen saturation rate monitoring / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the accuracy of the application of the intrapartum fetal oxygen saturation (FSO2) monitoring in predicting fetal acidosis and diagnosing intrauterine fetal distress.</p><p><b>METHODS</b>Continuous FSO2 monitoring as well as internal and external fetal heart rate monitoring were applied respectively in 60 women in labor during active phase of the first stage and the second stage. All the monitoring methods were validated with standard sensitivity, specificity, positive predictive value, negative predictive value, and accuracy on the bases of Apgar score and cord artery blood analysis.</p><p><b>RESULTS</b>The mean FSO2 in the active phase of the first stage were significantly higher than in the second stage of labor. FSO2 correlated with pH, PO2, PCO2, and base excess (BE) of cord blood to a significant degree. There was linear correlation between FSO2 and cord artery blood pH. Using 30% cutoff diagnosing intrauterine fetal distress, the sensitivity, specificity, and accuracy were 80%, 100% and 98.3%, respectively.</p><p><b>CONCLUSION</b>FSO2 monitoring is an effective method diagnosing intrauterine fetal distress.</p>

A technique of continuous medical image digital restoration / 中国医学科学院学报

<p><b>OBJECTIVE</b>To set up a new technique of continuous medical image digital restoration for electronic record management.</p><p><b>METHODS</b>According to Freeman's chain-code principle, 92 fetal cardiotocography were scanned, thinned, trailed, and chain-coded by computer system.</p><p><b>RESULTS</b>92 paper-recorded cardiotocography, were transformed to digital data and saved by computer, 23 parameters were produced, which could be used in further study.</p><p><b>CONCLUSION</b>Capacity of a restoring instrument can be greatly saved since the using of digitalized restoration, so that more useful data can be stored in doctor's workstation. Digitalized data can be much easier used in electronic record management, for convenient studies research.</p>

Study on the correlation of serum folate and red blood cell folate level with birth defects and unexplained recurrent pregnancy loss / 中华妇产科杂志

0.05). The RBC folate level of birth defect group except the urinary defect was significantly lower compared with the control group(233-547 vs 689 nmol/L,P

Clinical analysis of maternal and neonatal outcomes in uncomplicated term nulliparous after different routes of delivery / 中华妇产科杂志

Objective To compare maternal and neonatal outcomes after induction,elective cesarean section and spontaneous onset of labor in uncomplicated term nulliparous women.Methods A total of 3751 uncomplicated term nullipara who delivered in Peking Union Medical College Hospital from Sept 2002 to April 2007 were retrospectively analyzed.They were divided into three groups:the induction group, the elective cesarean section group,and the spontaneous onset of labor group.Their general conditions (such as age,weeks of pregnancy,hospital days and cost),postpartum complications(such as postpartum hemorrhage,puerperal morbidity,urinary retention,blood transfusion,delayed healing,and trauma),and Apgar score were compared by statistic methods.Results(1)Among 3751 women,501(13.3%)of them underwent induction(the induction group),1634(43.6%)delivered by cesarean section(cesarean section group),the other 1616(43.1%)women underwent spontaneous onset of labor(the spontaneous onset of labor group).(2)Results of general conditions:the spontaneous onset of labor group had the shortest hospital days,which was longer in the induction group,and the longest in the selective cesarean section group(P