Objective:To compare the pregnancy outcomes of surviving fetuses in monochorionic diam-niotic(MCDA)twin pregnancies after selective feticide or spontaneous single intrauterine fetal demise(sIUFD),and to explore the influencing factors of prognosis.Methods:A total of 219 cases of intra-uterine death of one fetus in MCDA twin pregnancies admitted to Peking University Third Hospital from September 2010 to August 2021 were collected.According to the mode of fetal death,they were divided into the spontaneous sIUFD group(120 cases)and the selective feticide group(99 cases).Data on the maternal conditions during pregnancy,the situation of the intrauterine-dead fetus,and pregnancy out-comes were collected for retrospective case-analysis.Results:The live-birth rates of surviving fetuses in the spontaneous sIUFD group and the selective feticide group were 85.0％and 81.8％respectively,and the total perinatal survival rates of surviving fetuses were 73.3％and 81.8％respectively,and there were no statistically significant differences.Compared with the spontaneous sIUFD group,the selective feticide group had a greater gestational week at delivery,and lower rate of preterm birth before 37 weeks,neonatal asphyxia,and early neonatal mortality.Using the gestational week at delivery as the outcome variable,Cox regression analysis showed that the mode of fetal death was not a risk factor affecting the gestational week at delivery of the surviving fetus,while gestational hypertension and the gestational week of fetal death were independent risk factors affecting the gestational week at delivery of the surviving fetus.Using preterm birth before 37 weeks,intrauterine death of the surviving fetus,and abnormal neonatal cranial ultrasound as outcome variables respectively,unconditional logistic regression analysis showed that the mode of fetal death,the gestational week of fetal death,the position of the dead fetus,and fetal complications were independent risk factors affecting the outcomes of the above-mentioned survi-ving fetuses.According to the results of the univariate analysis,the above risk factors were included in the multivariate regression analysis,and the results were the same as those of the univariate analysis.Conclusion:For MCDA twin pregnancy patients with severe twin-related complications,the prognosis of surviving fetuses after selective feticide is better.The proactive intrauterine intervention and treatment are of great significance for improving the prognosis of surviving fetuses.

Objective:To investigate the risk factors for severe postpartum hemorrhage (SPPH) during vaginal delivery of twin pregnancy.Methods:A retrospective analysis was conducted on clinical data from twin pregnancies ≥28 weeks′ gestation undergoing vaginal delivery at Peking University Third Hospital between January 2016 and December 2023. The twin pregnant women were divided into the SPPH group (postpartum hemorrhage ≥1 000 ml within 24 hours) with 22 cases and the non-SPPH group with 171 cases. The differences between the two groups were compared and the risk factors for SPPH were analyzed.Results:(1) The incidence of SPPH during vaginal delivery in twin pregnancies was 11.4% (22/193). The causes of SPPH included 12 cases (54.5%, 12/22) of simple uterine atony, 4 cases (18.2%, 4/22) of uterine atony combined with vaginal lacerations after forceps delivery, and 6 cases (27.3%, 6/22) of uterine atony combined with placental factors. (2) The age and postpartum hospital stay in the SPPH group were significantly higher than those in the non-SPPH group (all P<0.05). Compared to the non-SPPH group, the proportion of hypertensive disorders in pregnancy, accreta placenta implantation, and anemia in the SPPH group were significantly increased, and the birth weight of newborn 1st, the sum of the birth weights of two newborns, the duration of the second stage of labor, and the proportion of labor followed induction were also significantly increased (all P<0.05). (3) Multivariate analysis showed that age ≥38 years ( OR=16.785, 95% CI: 2.679-105.166; P=0.003), the second stage of labor ≥90 minutes ( OR=9.670, 95% CI: 2.532-36.930; P=0.001), hypertensive disorders in pregnancy ( OR=5.945, 95% CI: 1.702-20.761; P=0.005), and anemia ( OR=8.048, 95% CI: 2.086-31.049; P=0.002) were independent risk factors for SPPH in twin pregnancies during vaginal delivery. Conclusions:Anemia should be actively corrected during twin pregnancy. For twin pregnant women with advanced age, hypertensive disorders in pregnancy, or other risk factors of SPPH, if vaginal delivery is chosen, attention should be paid to the management of labor duration, dynamic assessment of the risk of postpartum hemorrhage, and proactive measures should be taken to ensure a smooth vaginal delivery and effectively reduce the incidence of SPPH.

Objective:To investigate the risk factors for severe postpartum hemorrhage (SPPH) during vaginal delivery of twin pregnancy.Methods:A retrospective analysis was conducted on clinical data from twin pregnancies ≥28 weeks′ gestation undergoing vaginal delivery at Peking University Third Hospital between January 2016 and December 2023. The twin pregnant women were divided into the SPPH group (postpartum hemorrhage ≥1 000 ml within 24 hours) with 22 cases and the non-SPPH group with 171 cases. The differences between the two groups were compared and the risk factors for SPPH were analyzed.Results:(1) The incidence of SPPH during vaginal delivery in twin pregnancies was 11.4% (22/193). The causes of SPPH included 12 cases (54.5%, 12/22) of simple uterine atony, 4 cases (18.2%, 4/22) of uterine atony combined with vaginal lacerations after forceps delivery, and 6 cases (27.3%, 6/22) of uterine atony combined with placental factors. (2) The age and postpartum hospital stay in the SPPH group were significantly higher than those in the non-SPPH group (all P<0.05). Compared to the non-SPPH group, the proportion of hypertensive disorders in pregnancy, accreta placenta implantation, and anemia in the SPPH group were significantly increased, and the birth weight of newborn 1st, the sum of the birth weights of two newborns, the duration of the second stage of labor, and the proportion of labor followed induction were also significantly increased (all P<0.05). (3) Multivariate analysis showed that age ≥38 years ( OR=16.785, 95% CI: 2.679-105.166; P=0.003), the second stage of labor ≥90 minutes ( OR=9.670, 95% CI: 2.532-36.930; P=0.001), hypertensive disorders in pregnancy ( OR=5.945, 95% CI: 1.702-20.761; P=0.005), and anemia ( OR=8.048, 95% CI: 2.086-31.049; P=0.002) were independent risk factors for SPPH in twin pregnancies during vaginal delivery. Conclusions:Anemia should be actively corrected during twin pregnancy. For twin pregnant women with advanced age, hypertensive disorders in pregnancy, or other risk factors of SPPH, if vaginal delivery is chosen, attention should be paid to the management of labor duration, dynamic assessment of the risk of postpartum hemorrhage, and proactive measures should be taken to ensure a smooth vaginal delivery and effectively reduce the incidence of SPPH.

Objective:To compare the pregnancy outcomes of surviving fetuses in monochorionic diam-niotic(MCDA)twin pregnancies after selective feticide or spontaneous single intrauterine fetal demise(sIUFD),and to explore the influencing factors of prognosis.Methods:A total of 219 cases of intra-uterine death of one fetus in MCDA twin pregnancies admitted to Peking University Third Hospital from September 2010 to August 2021 were collected.According to the mode of fetal death,they were divided into the spontaneous sIUFD group(120 cases)and the selective feticide group(99 cases).Data on the maternal conditions during pregnancy,the situation of the intrauterine-dead fetus,and pregnancy out-comes were collected for retrospective case-analysis.Results:The live-birth rates of surviving fetuses in the spontaneous sIUFD group and the selective feticide group were 85.0％and 81.8％respectively,and the total perinatal survival rates of surviving fetuses were 73.3％and 81.8％respectively,and there were no statistically significant differences.Compared with the spontaneous sIUFD group,the selective feticide group had a greater gestational week at delivery,and lower rate of preterm birth before 37 weeks,neonatal asphyxia,and early neonatal mortality.Using the gestational week at delivery as the outcome variable,Cox regression analysis showed that the mode of fetal death was not a risk factor affecting the gestational week at delivery of the surviving fetus,while gestational hypertension and the gestational week of fetal death were independent risk factors affecting the gestational week at delivery of the surviving fetus.Using preterm birth before 37 weeks,intrauterine death of the surviving fetus,and abnormal neonatal cranial ultrasound as outcome variables respectively,unconditional logistic regression analysis showed that the mode of fetal death,the gestational week of fetal death,the position of the dead fetus,and fetal complications were independent risk factors affecting the outcomes of the above-mentioned survi-ving fetuses.According to the results of the univariate analysis,the above risk factors were included in the multivariate regression analysis,and the results were the same as those of the univariate analysis.Conclusion:For MCDA twin pregnancy patients with severe twin-related complications,the prognosis of surviving fetuses after selective feticide is better.The proactive intrauterine intervention and treatment are of great significance for improving the prognosis of surviving fetuses.

OBJECTIVE To prepare reactive oxygen species(ROS)-responsive methotrexate(MTX)-modified paclitaxel(PTX)/icariin(ICA)micelles(MTX-oxi-Ms@PTX/ICA),and perform technology optimization and in vitro anti-tumor effect evaluation.METHODS Synergistic toxicity concentration range of PTX and ICA was screened by synergistic toxicity test.The micelles were prepared by thin film hydration method,and their technology was optimized by response surface methodology.The fundamental characteristics of the micelles prepared by the optimal technology were evaluated.The micelles'cytotoxicity,targeting ability to renal carcinoma RENCA cells of mice,and their inhibitory effects on invasion and migration were assessed.RESULTS Results of synergistic toxicity experiments demonstrated that the strongest synergistic effect occurred when PTX concentrations ranged from 2.5 to 10 μmol/L and ICA concentrations ranged from 5 to 15 μmol/L.The optimal technology of MTX-oxi-Ms@PTX/ICA was determined to include 80 mg Soluplus?,Soluplus? and TPGS1000 mass ratio of 4:1(mg/mg),2 mg DSPE-PEG2000-TK-PEG5000,2 mg DSPE-PEG2000-MTX,1 mg PTX,and 1.5 mg ICA,with a hydration temperature of 35 ℃ and a formulation volume of 5 mL.Under the optimal conditions,average encapsulation efficiency of PTX and ICA in 3 batches of MTX-oxi-Ms@PTX/ICA reached 92.75％,the critical micelle concentration(CMC)was 0.007 9 mg/mL,the particle size was(62.09±1.68)nm,the polydispersity index(PDI)was 0.046±0.032,and the Zeta potential was(-2.47±0.15)mV.Within 30 days of placement,there was no significant change in particle size and polydispersity index of micelle.In vitro release experiments showed that MTX-oxi-Ms@PTX/ICA released drugs more rapidly in oxidative environments.The half maximal inhibitory concentration of MTX-oxi-Ms@PTX/ICA against RENCA cells was(5.170±0.036)μmol/L.In vitro cellular uptake experiments indicated that compared with unmodified micelles,MTX modified micelles had stronger targeting effects on cancer cells,and also significantly enhanced the inhibitory ability of invasion and migration of RENCA cells(P＜0.05).CONCLUSIONS MTX-oxi-Ms@PTX/ICA micelles are successfully prepared,which exhibit high encapsulation efficiency,low critical micelle concentration,and good stability.These micelles demonstrate significant cytotoxicity against RENCA cells and effectively inhibit cancer cell invasion and migration.

Objective:To investigate the effect of prenatal dexamethasone on short-term outcomes and long-term neurological development in late preterm infants with twin pregnancy.Methods:A total of 315 pregnant women with twin pregnancy and their preterm infants who delivered in Peking University Third Hospital from January 2019 to December 2022 were retrospectively analyzed. The clinical data of pregnant women and preterm infants were collected. They were divided into non-medication group (93 pregnant women and 186 preterm infants), medication after 34 weeks group (123 pregnant women and 246 preterm infants), and medication before 34 weeks group (99 pregnant women and 198 preterm infants). Short-term outcomes of preterm infants were analyzed, including the incidence of neonatal respiratory distress syndrome (NRDS), wet lung, hypoglycemia, neonatal septicemia, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD) and neonatal necrotizing enterocolitis (NEC). "Ages and Stages Questionnaire-Third Edition (ASQ-3) scale" was used to follow up the late neurological development of preterm infants at the corrected age of 6-54 months, and the level of neurological development was compared.Results:(1) General conditions: the gestational age at delivery in the non-medication group [36.1 weeks (35.6, 36.6 weeks)] was later than that in the medication after 34 weeks group [36.1 weeks (35.2, 36.4 weeks)] and medication before 34 weeks group [35.2 weeks (34.2, 36.2 weeks)] groups, and the differences were statistically significant (all P<0.05). After correcting for gestational age, there was no significant difference in birth weight among the three groups ( H=3.808, P=0.149). There were no significant differences in gender and the proportion of small for gestational age among the three groups (all P>0.05). (2) Short-term outcome: the incidence of wet lung was 7.0% (13/186), 11.0% (27/246) and 16.2% (32/198) in the non-medication group, medication after 34 weeks group and medication before 34 weeks group, respectively, and the difference was statistically significant ( P=0.018). There were no significant differences in the incidence rates of NRDS, hypoglycemia, sepsis, IVH, BPD, and NEC among the three groups (all P>0.05). Logistic regression analysis with gestational age and newborn birth weight as confounding factors showed that early gestational age ( OR=0.884, 95% CI: 0.837-0.933, P<0.001) and increased incidence of selective intrauterine growth restriction type I ( OR=2.967, 95% CI: 1.153-7.639, P=0.024) could both lead to an increased incidence of wet lung. (3) Long-term outcomes: a total of 109 pregnant women completed the follow-up, and 218 preterm infants with a corrected age of 6-54 months at the end of follow-up were enrolled, including 86 cases in the non-medication group, 66 cases in the medication after 34 weeks group, and 66 cases in the medication before 34 weeks group. There were no significant differences in the scores of communication, gross motor, fine motor, problem solving and personal-social among the three groups (all P>0.05). Conclusion:Prenatal administration of a single course of dexamethasone does not affect the neonatal birth weight and short-term outcomes of twin late preterm infants, and has no adverse effect on the neurological development of twin late preterm infants with a corrected age of 6-54 months.

Objective::To establish the Chinese population's amniotic fluid deepest vertical pocket (DVP) reference curves for dichorionic twin pregnancies and to investigate DVP links with adverse perinatal outcomes.Methods::This retrospective cohort study, conducted at Peking University Third Hospital from August 2011 to December 2020, used data from 375 women aged 20 to 45 years who had dichorionic twin pregnancies that were confirmed through first-trimester ultrasound. After exclusions, reference curves were developed using 318 women with 3,299 DVP scans, and the data analyzed included maternal demographics, pregnancy outcomes, ultrasound measurements, and neonatal information. DVPs were assessed via ultrasound at regular intervals and grouped by gestational age (GA) for analyses. Linear mixed models were used to create amniotic fluid reference curves. Associations between abnormalities and adverse perinatal outcomes were examined using Chi-squared or Fisher's exact tests. Logistic regression provided both crude and adjusted odds ratios, adjusting for pre-pregnancy weight, age, ethnicity, parity, and conception mode. Significance was set at P < 0.05 with 95% confidence intervals (CI), and the analyses were conducted using SPSS ver. 26.0 (IBM Corp., Armonk, NY) and SAS ver. 9.4 (SAS Institute Inc., Cary, NC, USA) software. Results::DVP increased from the first trimester to a maximum at 26 weeks (95% confidence interval ( CI), 2.7-8.3 cm for twin 1 and 2.8-7.9 cm for twin 2) and then decreased gradually toward term. Differences between twins 1 and 2 were significant after 26 weeks (95% CI for twin 1: 5.3, 5.5; 95% CI for twin 2: 4.4, 4.5; P < 0.010). Polyhydramnios of twin 1 increased the risk of large for GA. Oligohydramnios of twin 1 increased the risk of small for GA. Polyhydramnios of twin 2 increased the risk of small for GA, premature birth, and neonatal complications. Oligohydramnios of twin 2 increased the risk of preeclampsia, hypertensive disorder complicating pregnancy, and premature rupture of membranes. Conclusion::Reference curves for twin amniotic fluid volumes vary by GA and differ between twins, with potential implications for pregnancy outcomes.

Objective::To establish the Chinese population's amniotic fluid deepest vertical pocket (DVP) reference curves for dichorionic twin pregnancies and to investigate DVP links with adverse perinatal outcomes.Methods::This retrospective cohort study, conducted at Peking University Third Hospital from August 2011 to December 2020, used data from 375 women aged 20 to 45 years who had dichorionic twin pregnancies that were confirmed through first-trimester ultrasound. After exclusions, reference curves were developed using 318 women with 3,299 DVP scans, and the data analyzed included maternal demographics, pregnancy outcomes, ultrasound measurements, and neonatal information. DVPs were assessed via ultrasound at regular intervals and grouped by gestational age (GA) for analyses. Linear mixed models were used to create amniotic fluid reference curves. Associations between abnormalities and adverse perinatal outcomes were examined using Chi-squared or Fisher's exact tests. Logistic regression provided both crude and adjusted odds ratios, adjusting for pre-pregnancy weight, age, ethnicity, parity, and conception mode. Significance was set at P < 0.05 with 95% confidence intervals (CI), and the analyses were conducted using SPSS ver. 26.0 (IBM Corp., Armonk, NY) and SAS ver. 9.4 (SAS Institute Inc., Cary, NC, USA) software. Results::DVP increased from the first trimester to a maximum at 26 weeks (95% confidence interval ( CI), 2.7-8.3 cm for twin 1 and 2.8-7.9 cm for twin 2) and then decreased gradually toward term. Differences between twins 1 and 2 were significant after 26 weeks (95% CI for twin 1: 5.3, 5.5; 95% CI for twin 2: 4.4, 4.5; P < 0.010). Polyhydramnios of twin 1 increased the risk of large for GA. Oligohydramnios of twin 1 increased the risk of small for GA. Polyhydramnios of twin 2 increased the risk of small for GA, premature birth, and neonatal complications. Oligohydramnios of twin 2 increased the risk of preeclampsia, hypertensive disorder complicating pregnancy, and premature rupture of membranes. Conclusion::Reference curves for twin amniotic fluid volumes vary by GA and differ between twins, with potential implications for pregnancy outcomes.

Objective:To evaluate the outcome of laser coagulation under fetoscope for placental chorioangioma (CA).Methods:The clinical data of three pregnant women with giant CA treated by laser coagulation under fetoscope in Peking University Third Hospital from January 2018 to December 2020 were analyzed retrospectively. Relevant articles up to September 2022 were retrieved from Wanfang Database, China National Knowledge Infrastructure and PubMed, and the clinical data of all patients were retrospectively summarized. Indications and intervention effects of fetoscopic laser therapy were analyzed. Descriptive statistics was used to describe the data.Results:Thirteen patients were involved in this study including 10 cases retrieved from the databases. The average age of the pregnant women was (30.3±6.2) years old. There were 12 cases of single pregnancy and one case of twin pregnancy (monochorionic diamnionic twin pregnancy). Except for cases for which data were not available in the literatures, at the diagnosis of CA, the average gestational age was (19.9±4.5) weeks ( n=7) and the average maximum diameter of the mass was (6.1±4.1) cm ( n=6). The patients underwent fetoscopic laser therapy at an average gestational age of (25.0±2.0) weeks ( n=13) with the average maximum tumor diameter of (7.6±2.8) cm ( n=9). After treatment, the amniotic fluid volume of three cases decreased to normal. In one case, the amniotic fluid volume decreased but was still above the upper limit of the normal range. Moreover, the maximum tumor diameter decreased in four cases; the peak systolic velocity of the fetal middle cerebral artery decreased to normal in one case; fetal heart function became normal in two cases and fetal edema was relieved in one case. Among the three patients treated in our hospital, the blood supply of CA disappeared after treatment. Intrauterine fetal death occurred in two cases. The other 11 patients gave birth to live babies at the gestational age of (36.6±3.8) weeks with five through cesarean section (5/11), five through vaginal delivery (4/11) and two not reported. The birth weight of the neonates was (2 712±1 023) g and all of them survived. The gender of five neonates were reported and all were females, two of them were monochorionic diamnionic twins. No abnormality was found in the three neonates delivered in our hospital during a six-month follow-up. No abnormality was reported in the other neonates during ten days to six months of follow-up. Conclusions:Fetoscopic laser coagulation may help reduce the size of CA, decrease complications and improve pregnancy outcomes.

Objective:To analyze the clinical value of noninvasive prenatal testing (NIPT) in vanishing twin (VT) pregnancies.Methods:A total of 164 VT pregnancies that underwent NIPT in Peking University Third Hospital from January 2017 to December 2020 were enrolled. Gestational age at onset of vanishing, results of NIPT and invasive prenatal diagnosis, blood sampling time points, and pregnancy outcomes were retrospectively analyzed using two independent samples t test and Chi-square test. Results:(1) Of the 164 cases, six had positive results for NIPT, but negative results for karyotype analysis or single nucleotide polymorphism genotyping, with a false positive rate of 3.7% (6/164) for NIPT and all of them were delivered at term. Four pregnancies terminated in the second trimester, including two fetal malformation cases and one unexplained intrauterine death whose single nucleotide polymorphisms results are all normal and one inevitable abortion case due to premature rupture of membrane who refused amniocentesis. The other 154 women all gave birth to normal phenotype babies including 12 preterm ones. (2) The false-positive rate of NIPT was lower in VT pregnancies diagnosed at less than eight gestational weeks than those diagnosed after [1.5% (2/134) vs 13.3% (4/30), χ2=6.68, P=0.010]. The false-positive rate was 6.9% (4/58) in women diagnosed at or below eight weeks between the occurrence of VT and blood sampling and was 1.9% (2/106) in those with interval more than eight weeks, but without significant difference ( χ2=1.44, P=0.231). Conclusions:Although VT pregnancies exist false-positive results in NIPT, screening is still recommended based on fully informed consent to reduce unnecessary invasive prenatal diagnosis. The earlier the onset of VT, the lower the NIPT false positive rate, but whether extending the sampling interval would reduce the risk of false-positive needs further study.