[Accidental discovery of copy number variation on chromosome 1 in a fetus with high risk of trisomy 13 suggested by NIPT].

OBJECTIVE: To validate a fetus with high risk for trisomy 13 suggested by non-invasive prenatal testing (NIPT). METHODS: The fetus was selected as the study subject after the NIPT detection at Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences on February 18, 2019. Clinical data of the pregnant woman was collected. Fluorescence in situ hybridization (FISH), chromosomal karyotyping analysis and chromosomal microarray analysis (CMA) were carried out on amniotic fluid and umbilical cord blood and the couple's peripheral blood samples. Copy number variation sequencing (CNV-seq) was also performed on the placental and amniotic fluid samples following induced labor. RESULTS: The pregnant woman, a 38-year-old G4P1 gravida, was found to have abnormal fetal development by prenatal ultrasonography. NIPT test suggested that the fetus has a high risk for trisomy 13. Chromosomal karyotyping analysis of fetal amniotic fluid and umbilical cord blood were 46,XN,add(13)(p10). The result of CMA was arr[hg19]1q41q44(223937972_249224684)×3, with the size of the repeat fragment being approximately 25.29 Mb, the fetal karyotype was thereby revised as 46,XN,der(13)t(1;13)(q41;p10). Chromosomal karyotyping analysis and CMA of the parents' peripheral blood samples showed no obvious abnormality. The CNV-seq analysis of induced placenta revealed mosaicisms of normal karyotype and trisomy 13. The CNV-seq test of induced amniotic fluid confirmed a duplication of chr1:22446001_249220000 region spanning approximately 24.75 Mb, which was in keeping with the CMA results of amniotic fluid and umbilical cord blood samples. CONCLUSION: NIPT may yield false positive result due to placenta mosaicism. Invasive prenatal diagnosis should be recommended to women with a high risk by NIPT test. And analysis of placenta can explain the inconsistency between the results of NIPT and invasive prenatal diagnosis.

Alterations in the Gut Microbiota in Pregnant Women with Pregestational Type 2 Diabetes Mellitus.

Human gut dysbiosis is associated with type 2 diabetes mellitus (T2DM); however, the gut microbiome in pregnant women with pregestational type 2 diabetes mellitus (PGDM) remains unexplored. We investigated the alterations in the gut microbiota composition in pregnant women with or without PGDM. The gut microbiota was examined using 16S rRNA sequencing data of 234 maternal fecal samples that were collected during the first (T1), second (T2), and third (T3) trimesters. The PGDM group presented a reduction in the number of gut bacteria taxonomies as the pregnancies progressed. Linear discriminant analyses revealed that Megamonas, Bacteroides, and Roseburia intestinalis were enriched in the PGDM group, whereas Bacteroides vulgatus, Faecalibacterium prausnitzii, Eubacterium rectale, Bacteroides uniformis, Eubacterium eligens, Subdoligranulum, Bacteroides fragilis, Dialister, Lachnospiraceae, Christensenellaceae R-7, Roseburia inulinivorans, Streptococcus oralis, Prevotella melaninogenica, Neisseria perflava, Bacteroides ovatus, Bacteroides caccae, Veillonella dispar, and Haemophilus parainfluenzae were overrepresented in the control group. Correlation analyses showed that the PGDM-enriched taxa were correlated with higher blood glucose levels during pregnancy, whereas the taxonomic biomarkers of normoglycemic pregnancies exhibited negative correlations with glycemic traits. The microbial networks in the PGDM group comprised weaker microbial interactions than those in the control group. Our study reveals the distinct characteristics of the gut microbiota composition based on gestational ages between normoglycemic and PGDM pregnancies. Further longitudinal research involving women with T2DM at preconception stages and investigations using shotgun metagenomic sequencing should be performed to elucidate the relationships between specific bacterial functions and PGDM metabolic statuses during pregnancy and to identify potential therapeutic targets. IMPORTANCE The incidence of pregestational type 2 diabetes mellitus (PGDM) is increasing, with high rates of serious adverse maternal and neonatal outcomes that are strongly correlated with hyperglycemia. Recent studies have shown that type 2 diabetes mellitus is associated with gut microbial dysbiosis; however, the gut microbiome composition and its associations with the metabolic features of patients with PGDM remain largely unknown. In this study, we investigated the changes in the gut microbiota composition in pregnant women with and without PGDM. We identified differential taxa that may be correlated with maternal metabolic statuses during pregnancy. Additionally, we observed that the number of taxonomic and microbial networks of gut bacteria were distinctly reduced in women with hyperglycemia as their pregnancies progressed. These results extend our understanding of the associations between the gut microbial composition, PGDM-related metabolic changes, and pregnancy outcomes.

Nontargeted metabolomics reveals the potential mechanism underlying the association between birthweight and metabolic disturbances.

AIMS: The aim of this study was to characterize the metabolites associated with small- and large-gestational-age newborns in maternal and cord blood, and to investigate potential mechanisms underlying the association between birthweight and metabolic disturbances. RESEARCH DESIGN AND METHODS: We recorded detailed anthropometric data of mother-offspring dyads. Untargeted metabolomic assays were performed on 67 pairs of cord blood and maternal fasting plasma samples including 16 pairs of small-for-gestational (SGA, < 10th percentile) dyads, 28 pairs of appropriate-for-gestational (AGA, approximate 50 percentile) dyads, and 23 pairs of large-for-gestational (LGA, > 90th percentile) dyads. The association of metabolites with newborn birthweight was conducted to screen for metabolites with U-shaped and line-shaped distributions. The association of metabolites with maternal and fetal phenotypes was also performed. RESULTS: We found 2 types of metabolites that changed in different patterns according to newborn birthweight. One type of metabolite exhibited a "U-shaped" trend of abundance fluctuation in the SGA-AGA-LGA groups. The results demonstrated that cuminaldehyde level was lower in the SGA and LGA groups, and its abundance in cord blood was negatively correlated with maternal BMI (r = -0.352 p = 0.009) and weight gain (r = -0.267 p = 0.043). 2-Methoxy-estradiol-17b 3-glucuronide, which showed enrichment in the SGA and LGA groups, was positively correlated with homocysteine (r = 0.44, p < 0.001) and free fatty acid (r = 0.42, p < 0.001) in maternal blood. Serotonin and 13(S)-HODE were the second type of metabolites, denoted as "line-shaped", which both showed increasing trends in the SGA-AGA-LGA groups in both maternal and cord blood and were both significantly positively correlated with maternal BMI before pregnancy. Moreover, cuminaldehyde, serotonin, 13(S)-HODE and some lipid metabolites showed a strong correlation between maternal and cord blood. CONCLUSIONS: These investigations demonstrate broad-scale metabolomic differences associated with newborn birthweight in both pregnant women and their newborns. The U-shaped metabolites associated with both the SGA and LGA groups might explain the U-shaped association between birthweight and metabolic dysregulation. The line-shaped metabolites might participate in intrauterine growth regulation. These observations might help to provide new insights into the insulin resistance and the risk of metabolic disturbance of SGA and LGA babies in adulthood and might identify potential new markers for adverse newborn outcomes in pregnant women.

Effects of a structural simulation curriculum for the repair of obstetrical anal sphincter injuries.

OBJECTIVE: To assess the short-term and skill-retention effects of a structural simulation curriculum for the repair of obstetrical anal sphincter injuries (OASIS). METHODS: This prepost experimental study recruited 31 obstetrics and gynecology residents from Peking Union Medical College Hospital. OASIS repair skill evaluations (at all timepoints) comprised a task-specific checklist (TSC), global rating scale (GRS), and pass/fail grade. A beef-tongue model was adopted in the simulation curriculum. After baseline testing, residents completed a structured 1-h workshop. Two weeks later, a second test was performed, followed by a one-to-one teaching workshop, with the proper completion of a checklist as the end-point. Three months later, residents completed a third test. RESULTS: The overall pass rate at baseline was 16.1%, with higher GRS scores (p = 0.035) in senior residents. Additionally, previewing the procedure before class and a history of OASIS repair observation were associated with higher TSC and GRS scores. Significant skill improvement was observed in the second and third tests, with pass rates of 96.8% and 93.5% respectively. Both TSC and GRS scores were improved compared with baseline (p < 0.001). CONCLUSION: A structural simulation curriculum integrating deliberate practice under supervision improves OASIS repair competence and achieves satisfactory skill retention.

Metabolomics Applied to Cord Serum in Preeclampsia Newborns: Implications for Neonatal Outcomes.

Preeclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality. However, it is still uncertain how PE affects neonate metabolism. We conducted an untargeted metabolomics analysis of cord blood to explore the metabolic changes in PE neonates. Umbilical cord serum samples from neonates with preeclampsia (n = 29) and non-preeclampsia (non-PE) (n = 32) pregnancies were analyzed using the UHPLC-QE-MS metabolomic platform. Different metabolites were screened, and pathway analysis was conducted. A subgroup analysis was performed among PE neonates to compare the metabolome between appropriate-for-gestational-age infants (n = 21) and small-for-gestational-age (SGA) infants (n = 8). A total of 159 different metabolites were detected in PE and non-PE neonates. Creatinine, N4-acetylcytidine, sphingomyelin (D18:1/16:0), pseudouridine, uric acid, and indolelactic acid were the most significant differential metabolites in the cord serum of PE neonates. Differential metabolite levels were elevated in PE neonates and were involved in the following metabolic pathways: glycine, serine, and threonine metabolism; sphingolipid, glyoxylate, and dicarboxylate metabolism; and arginine biosynthesis. In PE neonates, SGA neonates showed increased levels of hexacosanoyl carnitine and decreased abundance of 3-hydroxybutyric acid and 3-sulfinoalanine. Taurine-related metabolism and ketone body-related pathways were mainly affected. Based on the UHPLC-QE-MS metabolomics analysis, we identified the metabolic profiles of PE and SGA neonates. The abundance of metabolites related to certain amino acid, sphingolipid, and energy metabolism increased in the umbilical cord serum of PE neonates.

Maternal Serum Angiogenic Factor sFlt-1 to PlGF Ratio in Preeclampsia: A Useful Marker for Differential Diagnosis and Prognosis Evaluation in Chinese Women.

The ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) is elevated and proved to be useful in preeclampsia (PE) diagnosis. Its value in differential diagnosis with other pregnancy complications and prediction of pregnancy duration has yet to be clarified in Chinese population. We retrospectively analyzed 118 singleton pregnancies with suspected or diagnosed PE at the Peking Union Medical College Hospital (PUMCH) in China. Among these, 62 pregnancies were diagnosed as PE (48 early onsets and 14 late onsets, with 39 and 5 severe PE, respectively), 12 gestational hypertension (GH), 15 chronic hypertension (chrHTN), 16 autoimmune diseases, and 13 pregnancies with uncomplicated proteinuria. And 76 normal pregnancies were included as control. The results showed (1) the sFlt-1/PlGF ratio in early onset PE subgroup was significantly higher than that in GH, chrHTN, and control groups; the sFlt-1/PlGF ratio in late onset PE subgroup was significantly higher than that in chrHTN and control groups, but similar as GH group; the sFlt-1/PlGF ratio was similar among GH, chrHTN, and control groups. (2) The sFlt-1/PlGF ratio was significantly increased in the PE group compared with autoimmune disease and uncomplicated proteinuria pregnancies. (3) By ROC curve analysis, the cutoff value of the sFlt-1/PlGF ratio was less than 21.5 to rule out PE and higher than 97.2 to confirm the diagnosis of PE. (4) The sFlt-1/PlGF ratio was higher in PE pregnancies delivering within 7 days than those more than 7 days, either in early onset PE or severe PE. In conclusion, we show that maternal sFlt-1/PlGF ratio is an efficient biomarker in the diagnosis and differential diagnosis of PE. This ratio can be used to predict the timing of delivery for PE pregnancies.

Real-World Experience of Adding Metformin in Pregnant Women with Type 1 Diabetes in a Chinese Population: A Retrospective Cohort.

INTRODUCTION: Glycemic control in pregnant women with type 1 diabetes (T1D) is challenging with only insulin, and the incidence rate of adverse perinatal outcomes is high. Increasing data have indicated the safety and effect of metformin in pregnancy; however, no relevant data are available in pregnant women with T1D. We aimed to investigate glycemic control and perinatal outcomes in pregnant women with T1D in a Chinese population and explored the role of metformin in these patients. METHODS: We obtained data of 38 pregnant women with T1D who received regular antenatal care and delivered at Peking Union Medical College Hospital (PUMCH) between 1 January 2006 and 31 May 2018. The perinatal outcomes of T1D patients who added metformin as adjunct treatment and those who remained on insulin-alone therapy were compared retrospectively. RESULTS: Being overweight was common (35.1%) in pregnant women with T1D. On average, the insulin dose increased by 35.30 ± 22.60 unit/day during pregnancy. The cesarean delivery rate was high (65.8%), and fetal macrosomia was the main reason. The change of HbA1c in the metformin-insulin group was more prominent than in the insulin-only group (- 1.47 ± 1.17% vs. - 0.90 ± 1.13%, p = 0.05). There was no statistically significant difference in perinatal outcomes between the two groups. CONCLUSIONS: The incidence of adverse perinatal outcomes in pregnant women with T1D was high. This study innovatively suggested that metformin could be safe and could contribute to improving glucose management in pregnant women with T1D.

Characteristics and pregnancy outcomes of patients with severe pneumonia complicating pregnancy: a retrospective study of 12 cases and a literature review.

BACKGROUND: Pneumonia during pregnancy has been proven to be associated with increased maternal and fetal morbidity and mortality. The management of severe pneumonia in gravid patients is even more challenging. Thus, we summarized the characteristics and pregnancy outcomes of these patients and explored the probable risk factors and predictive factors for pneumonia during pregnancy and the appropriate timing of delivery in severe pneumonia patients. METHODS: A retrospective cohort study was conducted with 12 patients who were diagnosed with severe pneumonia complicating pregnancy at Peking Union Medical College Hospital between January 2010 and June 2017. The clinical features, treatment strategies, and pregnancy outcomes were collected from medical records and telephone calls. RESULTS: All 12 patients were in their late second or third trimester. The patients had a higher prevalence of anemia (50%) and preeclampsia (25%) than ordinary pregnant women. Delayed diagnoses were not uncommon. Two mothers died in our series, resulting in a mortality rate of 17%. Two intrauterine deaths were observed. Elective delivery was not performed in any of the four patients in their second trimester. Six of the seven patients who presented after 28 weeks of gestation and had live fetuses underwent emergency deliveries. Preterm births (6/7) and cesarean sections (5/7) were the two leading adverse outcomes in newborns. CONCLUSIONS: Anemia, advanced gestational age, and preeclampsia might be associated with the severity of pneumonia. Chest radiographs should be taken as soon as pneumonia is highly suspected to facilitate an early diagnosis. High incidences of adverse fetal outcomes were observed; thus, termination of the pregnancy is recommended for patients in their third trimester when respiratory function deteriorates progressively. However, it might be reasonable to continue pregnancy for those in their first or second trimester.

Effectiveness of different numbers of simulation training models on medical students' cervical examination performance.

OBJECTIVE: To estimate whether different numbers of simulation training models affect medical students' cervical examination performance. METHODS: In a prospective study at Peking Union Medical College Hospital, Beijing, China, between August 1, 2016, and April 30, 2017, fifth-year medical students without obstetric experience were randomly assigned to the large or small number training groups. Participants in the large number group performed cervical examinations on 10 dilation models and nine effacement/consistency models; those in the small number group practiced on four dilation models and three effacement/consistency models. In the examination, both groups evaluated 10 models in the same sequence and reported findings. Participants also completed confidence surveys. Mann-Whitney U test was used to compare the assessment accuracy and confidence improvement between the groups. RESULTS: There were 91 students randomized to the large (n=45) or small (n=46) number training groups. As compared with the small number group, the large number group demonstrated higher accuracy in assessing exact dilation (P=0.028), exact effacement (P=0.002), effacement within 0.5 cm (P=0.017), and consistency (P=0.045). There was no difference in assessing dilation within 1 cm or in confidence improvement between the groups. CONCLUSION: A small number of simulation training models was sufficient to improve students' accuracy and confidence in assessing cervical dilatation, although a large number was needed to improve accuracy in cervical effacement and consistency.

Serum levels of leptin, adiponectin and resistin in relation to clinical characteristics in normal pregnancy and preeclampsia.

BACKGROUND: Alterations in serum adipokines in preeclampsia remain vague. We investigated the roles of leptin, adiponectin and resistin and their relationships with clinical characteristics in normotensive and preeclamptic patients. METHODS: A case-control study was carried out in a cohort of 74 preeclampsia(PE) and 79 healthy pregnant women. Serum levels of leptin, adiponectin and resistin were measured by enzyme-linked immunosorbent assay. RESULTS: The mean body mass index(BMI), the serum leptin and resistin levels were significantly higher in the PE group than in the control group (p<0.001). The resistin/creatinine ratio was also higher in the PE group than in the control group (p=0.018). No significant difference was observed in the serum adiponectin level between both groups. Serum leptin levels were positively correlated with BMI (r=0.301, p<0.001) and negatively correlated with newborn birth weight (r=-0.435, p<0.001). Serum resistin levels were also negatively correlated with birth weight (r=-0.229, p=0.005) but were unrelated to BMI. Logistic regression showed that BMI≥28 and serum leptin levels were independent factors of PE. Leptin was a potential mediator between BMI and PE (p<0.001), and the mediating effect accounted for 22.54% of the total effect. CONCLUSIONS: Leptin, resistin, and obesity play important roles in the onset of PE. Leptin and resistin may have some impacts on the fetal growth and development.

[Analysis of differentially expressed genes in placental tissues of early-onset severe preeclampsia patients].

OBJECTIVE: To explore the differentially expressed genes(DEG)involved in the pathogenesis of preeclampsia (PE). METHODS: The gene expression profiles of placental tissues from 7 severe PE patients and 7 preterm controls from June to December 2012 were assessed using microarray. Gene ontology (GO) enrichment analysis and pathway analysis were performed to explore the genes and pathways involved in the pathogenesis of PE. Four DEG involved in these biological processes were further verified by quantitative real-time PCR. RESULTS: A total of 308 transcripts were significantly differentially expressed. Of these DEG, 81 genes(LEPTIN, PAPPA2, CRH, PLIN2, INHA, BCL6, FLT1, CCR7, etc) were up-regulated, and 227 genes (CXCL12, CXCL9, etc)were down-regulated. GO enrichment analysis indicated that the top 3 GO molecular functions were immune response (GO: 0006955, 17 DEG), positive regulation of apoptosis (GO: 0043065, 11 DEG) and inflammatory response (GO: 0006954, 11 DEG). Pathway analysis showed that the top 3 pathways were cell adhesion molecules (11 DEG), cytokine- cytokine receptor interaction (11 DEG), chemokine signaling pathway (8 DEG). Many genes (LEP, FLT1, TFRC, SH3PXD2A, CYP11A1, SEPP1, and so on) involved in oxidative stress were found to be significantly changed. Of these genes, LEP were significantly up- regulated with a fold change of 61.5. The fold changes of FLT1, SH3PXD2A, SEPP1, CYP11A1, TFRC were 8.6, 2.2, -2.0, 2.7 and -2.8. Four DEG involved in oxidative stress were further verified by quantitative real-time PCR. CONCLUSIONS: A DEG signature was identified in severe preeclampsia placentas compared with normal controls. The DEG mainly involved in the molecular mechanisms of immune response, oxidative stress and inflammatory response, and were closely associated with the pathogenesis of PE.

[Clinical features of recurrence of vulvar squamous cell carcinoma: analysis of 18 cases].

OBJECTIVE: To analyze the clinical characteristics of recurrence of vulvar squamous cell cancer and to explore the treatment thereof. METHODS: The clinical data of 18 patients vulvar squamous cell cancer, confirmed at the age 28-76, who developed recurrence were retrospectively analyzed. RESULTS: The overall recurrence rate was 21.3%. The time range between the primary operation and the discovery of primary recurrence was 2 months - 16 years. Local recurrence occurred in 11 of the 18 patients (61.1%). Recurrence in groin alone occurred in 4 of the 10 patients (22.2%) and recurrence in both the vulva and groin occurred in 3 of the 18 patients (16.7%). Local recurrence occurred more than 1 year after the primary treatment and inguinal recurrence occurred mostly within 1 year after the primary treatment. The survival time of the patients with vulvar recurrence was (63.2 +/- 8.1) months, significantly longer than that of the patients with groin recurrence [(10.7 +/- 1.6) months, P < 0.01]. CONCLUSION: The clinical characteristics and the prognosis of recurrent vulvar squamous cell cancer depend on the site of recurrence. The best treatment option for recurrence is surgery.

[Recurrent mature ovarian teratomas: retrospective analysis of 20 cases].

OBJECTIVE: To investigate the clinical characteristics and the rule of recurrence of mature ovarian teratoma. METHODS: The clinical data of 20 patients with recurrent mature ovarian teratoma treated 1965 approximately 2002 was analyzed retrospectively and compared with the data of 40 patients without recurrence who were randomly selected at the ratio of 1 patient with recurrence to 2 patients without recurrence and who underwent surgical treatment in the same operation dates as the corresponding patients with recurrence. RESULTS: The overall recurrence rate after The patients with recurrence was (26 +/- 7) years old on average at the onset of recurrence, significantly younger than those without recurrence [(30 +/- 6 yearly old, P < 0.05). There were no significant differences in gravidity, parity, and the cyst size, manner of surgery, and rupture during operation between the 2 groups (all P > 0.05). The incidence rates of bilateral or multilocular cysts in the patients with recurrence were significantly higher than those of the patients without recurrence (P < 0.05 or P < 0.01). The overall recurrence rate after conservative treatment was 2.5%. The mean period of recurrence was 8 +/- 7 years. CONCLUSION: Younger patients and patients bilateral or multiple dermoid cysts should be followed up closely. Laparoscopy is the best treatment choice for mature ovarian teratoma. Biopsy of the contralateral ovary is not recommended regularly in surgery.

[Study on posterior intra-vaginal slingplasty for pelvic floor reconstruction].

OBJECTIVE: To study the efficacy and safety of posterior intra-vaginal slingplasty (IVS) in the re-construction surgery of pelvic floor. METHODS: Eleven patients with vault prolapse and severe prolapse of uterus undergoing posterior IVS were prospectively studied. RESULTS: Average operation time was 55 min. Average blood loss was 86 ml. Average hospitalization time was 5.6 d. No severe complications occurred. According to subjective assessment of the outcome, all patients were cured. CONCLUSION: Posterior IVS is a minimally invasive, effective and safety surgery for re-construction of pelvic floor.