Research progress in neutrophil extracellular traps in obstetrics / 中华围产医学杂志

Neutrophils plays an essential role in innate immunity. Neutrophil extracellular traps (NETs) are released by activated neutrophils in response to infection. However, excessive NETs can result in body dysfunction and organ damage and participate in several pathological conditions. This paper mainly focuses on the formation, regulatory mechanism and role of NETs in obstetric diseases, such as preeclampsia, gestational diabetes mellitus and preterm birth, and listed the current medications used to block the formation of NETs in obstetrics.

Early recognition and management of sepsis during pregnancy and puerperium / 中华围产医学杂志

Sepsis and septic shock are obstetric emergencies, which bring clinical issues for obstetricians to pay attention to, such as early identification and emergency intervention before transferring the patients to intensive care. Physiological changes during pregnancy and puerperium result in difficulty in identifying the clinical features of sepsis. Simple bedside screening tools can be used for early identification and screening for possible sepsis. If initial sepsis screening is positive with suspected or evidence of infection, regardless of the presence of fever, further evaluation of organ damage is required for the diagnosis of sepsis. Bundle therapy should be initiated within 1 h after the identification of sepsis: For pregnant women or puerpera with suspected or confirmed sepsis, bacterial culture (blood, urine, respiratory tract, and other body fluids) and serum lactate level detection should be conducted promptly, moreover, empirical broad-spectrum antibiotics given within 1 h are recommended; For patients with sepsis complicated by hypotension or organ hypoperfusion, it is recommended to administer 1-2 L crystal solution as soon as possible for liquid resuscitation; For those with persistent hypotension and/or organ hypoperfusion despite fluid resuscitation, vasopressors are recommended to maintain mean arterial pressure ≥65 mmHg (1 mmHg=0.133 kPa), with norepinephrine as the first-line vasopressor. When sepsis is suspected or confirmed, the focus of infection should be actively sought to effectively control the source. Termination of pregnancy should be considered individually and comprehensively on the basis of obstetric indications, gestational age, and maternal and fetal conditions, but not depend on sepsis alone. If intrauterine infection is confirmed, pregnancy should be terminated immediately. Cesarean delivery usually requires general anesthesia for pregnant women with sepsis and intraspinal anesthesia is relatively contraindicated. The diagnosis and treatment of sepsis in pregnancy and puerperium should be individualized in accordance with the corresponding guidelines.

Detection of antiphospholipid antibody levels in normal pregnant women by chemiluminescence immunoassay and comparison between different trimesters / 中华围产医学杂志

Objective:Chemiluminescence immunoassay was used to detect the levels of anticardiolipin antibody (aCL) -IgA/IgG/IgM and anti-β2-glycoprotein Ⅰ antibody (aβ2GPⅠ) -IgA/IgG/IgM in healthy non-pregnant and pregnant women to explore the changes of antiphospholipid antibody in different pregnancy periods.Methods:This prospective study was conducted in Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, involving normal pregnant women who underwent prenatal examination and healthy non-pregnant women with no history of adverse pregnancy who underwent progestational eugenic health examination from April 2020 to August 2021. The levels of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM were detected using BIO-FLASH chemiluminescence immunoassay analyzer and P95 as well as P99 were calculated, respectively. The difference in the six data between non-pregnant and pregnant women was compared using Mann-Whitney U test. Kruskal-Wallis H test was used to compare the change of each antibody in different pregnancy periods and Spearman correlation was used to analyze the correlation between different trimester and the levels of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM. Results:A total of 454 cases met the inclusion criteria, and 435 cases were included in the analysis after excluding 19 cases, among them 110 were non-pregnant women and 325 were pregnant women, including 110 cases in the first trimester (≤13 +6 weeks), 110 cases in the second trimester(14 +0-27 +6 weeks), and 105 cases in the third trimester (≥28 weeks). P99 value of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM in the non-pregnant women were 7.31, 14.70, 7.92, 3.58, 13.60, and 4.95 CU, which in the pregnant women were 5.90, 12.78, 5.70, 1.60, 10.65, and 3.90 CU, and were all lower than the cut-off value of 20 CU that given by the analyzer manufacturer. The levels of aCL-IgA/IgG/IgM, and aβ2GPⅠ-IgG/IgM in the pregnant women were significantly decreased comparing with the non-pregnant women [aCL-IgA: 1.90 CU (1.40-2.70 CU) vs 2.90 CU (2.20-3.83 CU), Z=－7.14; aCL-IgG: 3.00 CU (2.20-4.50 CU) vs 6.10 CU (4.20-7.83 CU), Z=－10.26; aCL-IgM: 1.40 CU (1.10-2.30 CU) vs 2.65 CU (2.08-3.73 CU), Z=－8.87; aβ2GPⅠ-IgG: 3.50 CU (2.60-4.90 CU) vs 4.75 CU (3.60-5.93 CU), Z=－5.45; aβ2GPⅠ-IgM: 0.70 CU (0.50-1.20 CU) vs 1.00 CU (0.60-1.53 CU) , Z=－3.73; all P<0.001]. The aCL-IgA level in the third trimester was higher than those in the first and second trimester (both P<0.05). The levels of aCL-IgG/IgM in the second trimester and aβ2GPⅠ- IgG in the second and third trimesters were significantly decreased than those in the first trimester (all P<0.05). Spearman analysis showed that aCL-IgG/IgM, aβ2GPⅠ-IgA/IgM had no significant correlation with the pregnancy period (the first, second and the third trimester) (all P>0.05). However, a weak correlation between the aCL-IgA, aβ2GPⅠ- IgG and the pregnancy period was observed ( r=0.28 and－0.49, both P<0.001) Conclusions:P99 value of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM levels in normal pregnant women and non-pregnant women are lower than the cut-off value of 20 CU given by the analyzer manufacturer. The levels of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgG/IgM during pregnancy are lower than those before pregnancy and fluctuate with the pregnancy period, but have no significant correlation with the pregnancy period. The clinical diagnosis of antiphospholipid syndrome should be made according to the cut-off values of aCL-IgA/IgG/IgM and aβ2GPⅠ-IgA/IgG/IgM determined by each laboratory.

Effects of neutrophil extracellular traps on proliferation and apoptosis of human amniotic epithelial cells and its possible mechanisms / 中华围产医学杂志

Objective:To investigate the effects of neutrophil extracellular traps (NETs) on the proliferation and apoptosis of human amniotic epithelial cells.Methods:NETs were induced in vitro from the neutrophil cells obtained from the peripheral blood of normal pregnant women before elective cesarean section at full-term. Human amniotic epithelial cell lines (WISH cells) were cultured in vitro, and were divided into four groups:(1) control group: without any stimulus; (2) NETs group: WISH cells were stimulated with NETs (500 ng/ml); (3) NETs+SB203580 (p38 kinase inhibitor) group: WISH cells were pretreated with SB203580 (5 μmol/L) for 30 min and then NETs (500 ng/ml) was added; (4) SB203580 group: only SB203580 was added. After stimulating for 48 h, cell proliferation assay, lactate dehydrogenase(LDH) assay, and flow cytometry assay were used to detect the cell proliferation rate, LDH level of cell supernatant, and cell apoptosis rate among different groups. The results were analyzed and compared using one-way analysis of variance and LSD- t test. Results:(1) Cell proliferation: The cell proliferation ratio in the NETs group was lower than that in the control group [(9.379±0.775)% vs (36.560±1.208)%, LSD- t=20.78, P<0.001]; and the figure in the NETs+SB203580 group [(27.920±0.926)%] was higher than that in the NETs group (LSD- t=14.18, P<0.001). (2)LDH: There was an increased LDH level in the cell supernatant of the NETs group compared with the control group (1.518±0.038 vs 0.274±0.004, LSD -t=44.25, P<0.05), and the LDH level in the NETs+SB203580 group (0.857±0.009) was decreased than that in the NETs group (LSD -t=23.51, P<0.001). (3) Apoptosis: Compared with the control group, the cell apoptosis level of the NETs group was increased [(14.290±0.141)% vs (10.110±0.044)%, LSD- t=21.76, P<0.001]; but that in the NETs+SB203580 group [(10.500±0.218)%] was lower than in the NETs group (LSD- t=19.70, P<0.001). Conclusion:p38/mitogen-activated protein kinases signaling pathway may be involved in the process of NETs, inhibiting proliferation and promoting apoptosis of human amniotic epithelial cells.

Prenatal management of multifetal pregnancies containing monochorionic fetuses / 中华围产医学杂志

Multifetal pregnancies with monochorionicity are more complicated, for which pregnancy monitoring and intrauterine intervention are of great importance. For dichorionic triamniotic triplets with MC twin, multifetal pregnancy reduction measures included cardiac injection of potassium chloride at 11 to 14 weeks of gestation for reduction to monochorionic singleton, and radiofrequency ablation after 16 weeks of gestation to preserve the dichorionic diamniotic twins. Moreover no significant difference was observed in the pregnancy outcomes between the two methods. Fetalscopic laser surgery can significantly improve the perinatal prognosis of multiple pregnancies complicated by twin-to-twin transfusion syndrome. Umbilical occlusion and transection can be used for the reduction of triplets containing monochorionic monoamniotic twins to avoid fetal death caused by entanglement of the umbilical cord. Cardiac injection of potassium chloride is appropriate for reducing the two fetuses in the same chorionic sac for trichorionic quadruamniotic pregnancy. Selective fetal reduction is applicable for MC triplets or quadruplets pregnancy, however, relevant studies are all with a small sample size, which requires full consultation and individualized treatment.

Etiological diagnosis and clinical evaluation of isolated fetal ascites / 中华妇产科杂志

Objective:To explore the correlation between prenatal clinical data with etiological diagnosis and neonatal outcome in isolated fetal ascites.Methods:Totally, 36 pregnancy cases diagnosed as isolated fetal ascites by ultrasound in Provincial Hospital Affiliated to Shandong University from June 22nd, 2016 to September 28th, 2018 were collected. Invasive prenatal diagnosis was performed by taking fetal cord blood, amniotic fluid, and fetal ascites respectively for cytogenetics, molecular genetics and biochemical examination and the impact of intrauterine therapeutic procedures on neonatal outcomes was evaluated as well. The correlation among prenatal examination, pathogeny and prognosis was analyzed by Fisher′s exact test.Results:(1) The prognosis of isolated fetal ascites initially presenting ≥28 weeks was better than that before 28 weeks, survival rate of 1-year-old were 13/15 and 9/17,respectively, the difference was statistically significant ( P<0.05). (2) The etiologic diagnosis rate of ascites before delivery was 31%(11/36), which increased to 53%(19/36) totally after birth. Characteristics of cases which were defined prenatally were as follows: 8 cases of digestive tract diseases showed ultrasonic abnormalities, including echogenic bowel, bowel dilatation and polyhydramnios; platelet level in umbilical cord blood of fetuses infected with cytomegalovirus were below 100 × 10 9/L in 2 cases; 1 case of urinary system malformation showed megalocystis and hydronephrosis. Cases which were defined causes after birth included: 3 fetuses with chyloperitonium presented persistent fetal ascites; 3 cases of digestive-related causes were rectal duplication with infection, mesentery stenosis, and intestinal atresia; other causes included Pierre-Robin syndrome and Budd-Chiari syndrome. (3) The live birth rate was 72% (26/36) and survival rate of 1-year-old was 61% (22/36). And 9/10 of infants who underwent surgeries got good outcomes. Fetal ascites due to abdominal or pelvic factors turned well in 13/16 of cases. Conclusions:The pregnancy outcome of fetal isolated ascites depends mainly on primary causes. Gastrointestinal abnormality is one of the most common causes. Excluded intrauterine infection, chromosomal abnormality and abnormal systemic ultrasonic findings, fetus with reduced ascites as the pregnancy progresses will get good outcome.

Clinical application for pregnacy outcomes of radiofrequency ablation in complex multiple pregnancies / 中华妇产科杂志

Objective@#To investigate the safety and effectiveness of radiofrequency ablation (RFA) for selective fetal reduction in complex multiple pregnancies and analyze factors affecting perinatal outcomes.@*Methods@#This was a retrospective case series of 156 patients undergoing selective fetal reduction by RFA in Provincial Hospital Affiliated to Shandong University from July 22th, 2011 to September 12th, 2018. They were divided into five groups according to surgical indications, including 46 cases in the monochorionic twins discordant for fetal anomalies group, 42 cases in the multiple pregnancies for reducing fetal numbers group, 40 cases in the twin to twin transfusion syndrome (TTTS) group, 24 cases in the selective intrauterine growth restriction (sIUGR) group and 4 cases in the twin reversed arterial perfusion sequence (TRAPS) group. According to the gestational age at surgery, patients were divided into two groups: the gestational age at surgery <20 weeks group (75 cases) and the gestational age at surgery≥20 weeks group (81 cases). According to the cycles of RFA required for surgery, patients were divided into two groups: one cycle group (124 cases) and ≥2 cycles group (32 cases). Basic information of patients, surgical process, postoperative complications and pregnancy outcomes were recorded. The growth and development of survival newborns were also followed up. Factors affecting perinatal outcomes were analyzed.@*Results@#(1) The median gestational age at procedure of 156 patients was 20 weeks (14+5- 29+1 weeks). The median cycles of RFA was 1 cycle (1-3 cycles), of which one cycle accounted for 79.5% (124/156). (2) Eleven (7.1%, 11/156) patients experienced intrauterine fetal death, 27 (17.3%, 27/156) patients miscarried, and the overall survival rate was 75.6% (118/156). Premature birth rate before 34 weeks was 19.5% (23/118). There were 129 neonates. The median gestational age at delivery was 37+3 weeks (28+2- 41+1 weeks) with a mean birth weight of (2 657±700) g. (3) Analysis of pregnancy outcomes based on surgical indications found that, the gestational age at delivery [38 weeks (30+1-41+1 weeks), 36+4 weeks (29- 39 weeks), 36+4 weeks (28+2-39+5 weeks), 38 weeks (31-39+6 weeks), 38+3 weeks (30+4-38+4 weeks)] and neonatal birth weight [(2 820±671), (2 435±416), (2 497±843), (2 998±718), (2 517±1 087) g] were significantly different among fetal anomalies group, reducing fetal numbers group, TTTS group, sIUGR group and TRAPS group, respectively (all P<0.05). There were no significant differences in the pregnancy outcomes between gestational age at surgery <20 weeks group and gestational age at surgery ≥20 weeks group, or between one cycle group and ≥2 cycles group, respectively (all P>0.05).@*Conclusions@#RFA is a safe and effective procedure in treating complex monochorionic multiple pregnancies. Surgical indications would affect the gestational age at delivery and neonatal outcomes.

Safety and efficacy of radiofrequency fetal ablation for monozygotic triplet and quadruplet pregnancies / 中华围产医学杂志

Objective To investigate the safety and efficacy of radiofrequency fetal ablation (RFA) in the treatment of monozygotic triplet and quadruplet pregnancies. Methods We analyzed retrospectively the clinical data of eight gravidas, including seven monozygotic triplets and one monozygotic quadruplets admitted to the Department of Obstetrics, Shandong Provincial Hospital Affiliated to Shandong University from March 2014 to January 2017. All of the eight women accepted ultrasound-guided selective fetal reduction by RFA to reduce to twins. Descriptive methods were used to analyze the perioperative status of the gravidas, maternal and fetal outcomes and neonatal follow-up. Results (1) In seven cases, the fetuses were deprived of blood flow after one heating cycle of radiofrequency ablation, while in the other, blood flow was stopped after two heating cycles. Heart beats of the reduced fetuses slowed down gradually after RFA, and stopped at 10, 20-25 and 40 minutes after operation in one, four and three cases, respectively. The conserved fetus showed normal heartbeats. (2) All patients accepted regular obstetrical examination after RFA. One was diagnosed with gestational diabetes mellitus at 26 weeks, and hospitalized for 4 d because of preterm labor at 30+6weeks. One women was hospitalized to receive a two-week tocolysis treatment one day after surgery, and diagnosed with severe preeclampsia at 35 weeks. One patient who had a fever six days after surgery and was hospitalized for antiinfection treatment progressed to inevitable abortion on the day of admission. The other five pregnant women had no abnormalities. (3) Except for one miscarriage, the rest seven cases all continued the pregnancy until delivery by cesarean, among which two with preterm premature rupture of membranes eventually delivered before term (35+1and 33 weeks), one with severe preeclampsia also preterm delivered (35+4weeks) and four term deliveries. Apgar scores at 1 and 5 minutes of all newborns were over 7. Three of the 14 newborns were hospitalized and recovered, including one pathological jaundice, one laryngeal stridor and one premature. The last follow-up in September 2018 of all 14 babies did not show any abnormalities. Conclusions RFA is a feasible treatment for monozygotic triplets and quadruplets.

Result of prenatal diagnosis for 151 high-risk women by noninvasive prenatal screening based on high-throughput sequencing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of combined fetal karyotyping and chromosomal microarray analysis (CMA) for the verification of high-risk pregnancy signaled by noninvasive prenatal screening (NIPS) based on high-throughput sequencing.</p><p><b>METHODS</b>One hundred and fifty-one pregnant women with high risks for aneuploidies of chromosomes 13, 18, 21, X and Y or pathological copy number variations (CNVs) by NIPS were subjected to amniocytic karyotyping and CMA analysis.</p><p><b>RESULTS</b>One hundred and forty-two women were found to have a high risk for fetal chromosomal aneuploidies, which included 83 cases of trisomy 21, 17 cases of trisomy 18, 2 cases of trisomy 13, and 40 cases of sex chromosome aneuploidies. Amniocytic karyotyping and CMA analysis has confirmed 81 cases of trisomy 21, 15 cases of trisomy 18, 10 cases of 47,XXY, 4 cases of 47,XXX, 2 cases of 47,XYY and 1 case of 46,X,del(X)(q26.1). Two trisomy 21, two trisomy 18, 2 trisomy 13, and 23 cases of sex chromosomal aneuploidies were verified as false positives. For 9 women with pathological fetal CNVs detected by NIPS, combined fetal karyotyping and CMA has confirmed 1 case of chromosome 13 microdeletion, 1 case of chromosome 18 microduplication, and 1 case of chromosome 18 deletion. For a case with 30 Mb duplication of chromosome 2 and 25 Mb duplication of chromosome 8, CMA analysis had no positive finding, while fetal umbilical cord blood karyotyping has yielded a 46,XX,dup(2)(p23.1p25.3)[13]/46,XX[87] karyotype. The remaining 5 cases were confirmed as false positive results.</p><p><b>CONCLUSION</b>Combined fetal karyotyping and CMA has provided a powerful tool for verifying high-risk fetuses signaled by NIPS.</p>

Clinical analysis of pregnancy outcomes and fetal loss after fetal reduction of triplets to twins or singleton pregnancy / 中华妇产科杂志

Objective To investigate and evaluate the pregnancy outcomes and fetal loss after fetal reduction of triplets to twins or singleton pregnancy. Methods 282 cases of triplets who received multi-fetal pregnancy reduction (MFPR) at Shandong Provincial Hospital affiliated to Shandong University were recruited from Sep 2001 to Mar 2014. According to the remaining fetal number after MFPR, 231 cases were opted to reduce to twins (twins group) while 51 cases were opted to singleton pregnancy (singleton group).The indication of the former group was fetal abnormalities under ultrasound or on patients′ demand; while the indication for the later group included dichorionic triamniotic (DCTA) triplets or patients′ aspiration. Potassium chloride was injected into the targeted fetal heart until cardiac standstill was obtained. The pregnancy outcomes, gestational age at delivery, birth weight of newborns of the two groups were recorded. Successful pregnancy was defined as take-home at least one baby. Results (1)The overall rate of successful pregnancy was 91.5%(258/282).There were 413 neonates in the twins group, including 4 neonatal deaths and 409 live babies, with the successful rate of 90.5%(209/231). There were 49 neonates in the singleton group, including 2 cases of fetal loss. Thus the successful rate was 96.1%(49/51). There was no difference of successful pregnancy rate between the two groups(P>0.05).(2)The mean gestational age at operation for the twins group and singleton group were(16.5±3.5)weeks and (14.2±2.0) weeks, respectively. Each group was divided into three periods,11-13+6 weeks, 14-16+6 weeks and≥17 weeks.In the twins group, the cases in each time period were129(55.8%,129/231), 50(21.6%,50/231)and 52(22.5%,52/231), respectively. While in the singleton group, the cases in each time period were 27(53%,27/51), 16(31%, 16/51)and 8(16%,8/51).There was no difference between the two groups at each time period(P>0.05). (3)The fetal loss rate in the twins group were 7%(9/129), 12%(6/50), 10%(5/52) at each time period, respectively. While for the singleton group they were 4%(1/27), 0(0/16)and 1/8, respectively. There was no significant difference between the two groups at each time period(P>0.05).(4)The mean birth weight of the twins group was lower than the singleton group [(2 555±447) g vs (3 084±550) g, respectively, P0.05).(5)The gestational age at delivery of the twins group was earlier than the singleton group [(36.2 ± 2.4) weeks vs(38.3 ± 2.2)weeks, respectively,P0.05].Conclusions Reduction to one fetus led to significantly better outcome than two fetuses, with no significant difference in fetal loss rate. It is better to advise patients with triplets reduce to singleton pregnancy.

Values of Swansea criteria on diagnosis and severity evaluation of acute fatty liver of pregnancy / 中华围产医学杂志

Objective To explore the value of Swansea criteria on diagnosis and severity evaluation of acute fatty liver of pregnancy (AFLP).Methods Fifty-two AFLP patients were admitted to Shandong Provincial Hospital Affiliated to Shandong University between January 1,2000 and December 31,2011.All these cases were retrospectively reassessed by Swansea criteria.According to the severity,prognosis and whether continuous blood purification treatment was needed,these cases were classified as mild and severe cases.Differences between groups were detected by x2 or t test.Bivariate correlation analysis was used for Swansea criteria compliance and postnatal hemorrhage and days in hospital.Results After reassessing by Swansea criteria,31 cases could be diagnosed as AFLP (20 cases met seven or more criteria,11 cases met six criteria)and the other 21 cases could not (16 cases met five criteria,three cases met four,and two cases met three).For the 16 cases that met five Swansea criteria,they were confirmed as AFLP based on postnatal follow-up.The five cases that met four or three criteria were confirmed as AFLP because no other disease could explain their status.Among the patients who met seven or more Swansea criteria,the incidence of intrauterine fetal death was 40％ (8/20),and 65％ (13/20) needed continuous blood purification.These were higher than in patients who met six or fewer Swansea criteria [9％ (3/32) and 28％ (9/32),x2=6.921 and 6.857,P=0.014 and 0.011].Postpartum hemorrhage was positively correlated with Swansea criteria compliance (r2=0.286,P=0.040).Conclusion Patients who meet five Swansea criteria can be diagnosed as AFLP.Swansea criteria can be applied to the severity evaluation of AFLP.

Timing of selective multifetal pregnancy reduction in second trimester and pregnant outcomes / 中华围产医学杂志

Objective To compare the outcomes of multifetal pregnancy reduction (MFPR)performed at different gestational ages,and to analyze the influence on pregnancy outcomes.Methods Data of 302 women with multifetal pregnancies conceived after assisted reproductive technology (ART) from January 2002 to February 2012 in Department of Obstetrics and Gynecology of Provincial Hospital Affiliated to Shandong University were collected and divided into two groups.The study group involved 152 multifetal pregnancy cases (triplets or quadruplets),which were further divided into three subgroups according to the timing of MFPR to twins,12-13 +6 (n=91),14-15+6(n=32) and 16-24+6 gestational weeks (n=29).The control group involved 150 twin pregnancy cases.MFPR was performed by trans abdominal intra cardiac injection of 10％ potassium chloride (KCl) solution under ultrasound guidance.Gestational age of delivery,birth weight,incidence of gestational diabetes mellitus (GDM) and hypertensive disorder complicating pregnancy (HDCP) were analyzed by t test,one-way ANOVA or Chi-square test.Results Pregnancy loss rate of the study group (14.5％,22/152) was higher than that (6.7％,10/150) of control group,x2=4.857,P＜0.05.Pregnancy loss rate of the subgroup undergoing MFPR during 16-24+6 gestational weeks (31.0％,9/29) was higher than that during 12-13 +6 gestational weeks (8.8％,8/91,x2=7.212,P＜0.05) and that of control group (x2=12.749,P＜0.05).There were no differences in pregnancy loss rate between control group and MFPR during 12-13+6 gestational weeks (x2=0.370,P＞0.05),and during 14-15+6 gestational weeks (15.6％,5/32,x2 =1.739,P＞0.05).No statistically significant difference was found between the study group and control group in mean gcstational age at delivery[(36.9±l.8) weeksvs (37.0±1.8) weeks,t =-0.346,P＞0.05],mean birth weight of large babies [(2720.4±455.0) g vs (2729.1±413.8) g,t =-0.163,P＞0.05] and small babies [(2409.2±412.6) g vs (2416.2±436.8) g,t=-0.136,P＞0.05].There were no differences between the study group and control group in delivery rate at 28-34 gestational weeks [6.2％ (8/130)vs6.4％ (9/140),x2 =0.009,P＞0.05],birth weight discordance rate [12.3％ (16/130) vs11.4％ (16/140),x2=0.050,P＞0.05],GDMrate[3.1％ (4/130) vs2.1％ (3/140),x2 =0.659,P＞0.05] and HDCP rate [11.5％ (15/130) vs 8.6％ (12/140),x2 =0.010,P＞0.05].Conclusions There is risk of pregnancy loss after MFPR,but MFPR before 16 weeks of gestation might decrease the risk.

Safety and efficiency of radiofrequency fetal ablation in the treatment of complicated multiple gestations / 中华妇产科杂志

Objective To investigate the safety and efficiency of radiofrequency ablation (RFA) in the treatment of complicated multifetal gestations.Methods There were 6 multifetal pregnant women (gestational age ranged from 14+6 to 27 +2 weeks) diagnosed in the Department of Obstetrics,Provincial Hospital Affiliated to Shandong University:two with twin-twin transfusion syndrome (TTTS) stage Ⅳ,one with reversed arterial perfusion sequence,one with dichorionic triamniotic triplets,one with absence of a lower limb,one with severe intrauterine growth restriction.All of them accepted ultrasound-guided selective fetocide by RFA.Results (1) Blood flow of three reduced fetuses stopped completely after one RFA circulation,whereas the other three stopped after two circulations.One reduced fetus stopped heartbeating in 10 minutes after RFA; three reduced fetuses' heartbeats slowed down and stopped completely in 35 minutes after RFA ; and the heartbeats of the other two cases stopped completely within 3 to 7 minutes after RFA.The heartbeats of the reserved fetuses were normal.All of the operations succeeded.(2) The reserved fetuses received a series of ultrasound examinations after the operations.In Case 1,the ascites of the reserved fetus,which was 4.0 cm× 2.3 cm before RFA,disappeared two weeks later; and the umbilical artery systolic/diastolic (S/D) ratio,which was 3.35 before the operation,decreased to 2.70 six weeks later.Amniotic fluid depth decreased from 44.6 cm to normal two weeks after RFA.The reserved fetus received brain MRI three weeks after RFA and no abnormality was detected.In Case 2,the increased heart size (cardiothoracic ratio ＞ 0.35) of the reserved fetus recovered to normal size ten days after the operation ; and the umbilical artery S/D decreased from 4.69 to 3.39 seven days after the operation.Reserved fetuses of the other three cases were normal on ultrasound and MRI after the operations.In Case 6,the ascites of the reserved fetus,which was 2.3 cm × 1.5 cm before RFA,disappeared sixteen days after the operation.The brain MRI suggested normal three weeks after the procedure.Amniotic fluid depth reduced from 11.0 cm to normal two weeks after the operation.(3) Three women delivered normal premature babies,and the other three got healthy mature infants.At present,all children are still in follow-up,and their physical examinations suggest normal.Conclusions RFA is a safe,efficient,minimal invasive treatment,which provides a new choice for fetocide,especially for complicated monochorionic multifetal gestations.Fetocide by RFA can effectively improve the life quality of the reserved fetuses.

Comparative study of pregnancy outcomes between spontaneous twin pregnancies and twin pregnancies after fetal reduction in the second trimester / 中华妇产科杂志

Objective To compare the outcomes of multifetal pregnancy reduced to twins with initial twin pregnancy.Methods This study included all patients who had high-order multiple pregnancies from August 2007 to September 2010 ( n =567 ) in outpatient or inpatient of Department of Obstetrics and Gynecology,Provincial Hospital Affiliated to Shandong University.There were 478 initial twin pregnancys (non-reduced group ) and 89 multifetal pregnancy reduced to twins (reduced group).All fetal reduction procedures were performed after 12 weeks gestation.The maternal ages,gestational ages at delivery,pregnancy complications,birth weight of twins and neonatal outcomes were observed in all groups.Results ( 1 ) Average maternal ages and mean gestational ages at delivery:the average maternal ages were ( 29.7 ± 4.5) and (29.9 ± 5.0 ) years for the non-reduced and reduced groups,respectively,no statistical significance (P =0.755).The mean gestational ages at delivery in the nonreduced and reduced twins were (35.3 ± 3.9) and ( 34.4 ± 6.3 ) weeks,respectively ( P ＜ 0.01 ).( 2 ) Pregnancy complications:the rate of pre-eclampsia was 8.2％ ( 39/478 ) in the nonreduced group and 12.4％ (11/89) in the reduced group,no statistical significance ( P =0.199 ).The rates of gestational diabetes mellitus were 1.7％ ( 8/478 ) and 3.4％ ( 3/89 ),respectively,no statistical significance ( P =0.287 ).( 3 ) Neonatal outcomes:① the frequencies of birth weight discordances ＞ 400 g were 28.9％ for the nonreduced group and 27.0％ for the reduced group,no statistical significance ( P =0.715 ).The frequencies of birth weight discordances ＞ 100 g were 75.1％ for the nonreduced group and 75.3％ for the reduced group,no statistical significance (P =0.972).②The mean birth weight of the nonreduced twin group was significantly higher than that of the reduced group [ ( 2700 ± 468 ) g vs.( 2352 ± 602 ) g,respectively,P ＜ 0.0l ],there was statistical significance.The mean birth weight of gestational ages ＞ 36 +1 weeks at delivery of the nonreduced twin group was significantly higher than that of the reduced group [ (2809 ± 424) g vs.(2707 ± 506) g,respectively,P ＜0.01 ],there is statistical significance.③The rate of infant mortality( gestational ages ＞28 weeks at delivery) was 1.3％ ( 1/78 ) for the reduced group and 2.2％ ( 10/448 ) for the nonreduced group.The major morbidity rate was 3.8％ (3/78) for the reduced group and 4.0％ (18/448) for the nonreduced group,no statistical significance ( P =0.588,0.943 ).Conclusions Multiple pregnancies after fetal reduction were still associated with a mild increased risk when compared to initial twin pregnancies and their abortion rate is high.The gestational ages of the reduced group were affected by the initial number of fetuses,and the birth weights of reduced twins were lower than that of the nonreduced twins.

Combination of fetal cord blood coagulation factor Ⅷ activity assessment with gene sequencing in prenatal diagnosis of hemophilia A / 中华围产医学杂志

Objective To evaluate the assessment of fetal cord blood coagulation factor Ⅷ activity ( Ⅷ: C) combined with gene sequencing in prenatal diagnosis of high-risk fetuses of hemophilia A(HA). Methods Percutaneous umbilical blood sampling was performed in 79 pregnant woman with high risk of HA and male fetuses at 20-35 weeks of gestation and maternal peripheral blood was also taken. The plasma F Ⅷ: C was detected by one-stage method, and the concentration of von Willebrand factor antigen(vWF: Ag) was determined by ELISA. Long distance polymerase chain reaction(LD-PCR) was used in 6 fetuses to detect the intron 22 inversion in F8 gene, and LD-PCR was also applied for mothers with fetal carriers of intron 22 inversion and gene sequencing for those mother with fetuses without intron 22 inversion. Results The maternal concentration of FⅧ: C of these 79 women was 52%-139% with an average of (99.60±28. 10)%. For the fetuses, 23 were below 10%with an average of (2. 64±1.92)%, eight of which were ＜1% and 15 between 1% and 10%. Among the 12 fetuses with the concentration of FⅧ :C at 10%-30%, averagely (19. 78±6.71)%, five were induced and the rest seven pregnancies and the other 44 pregnancies with fetal FⅧ :C over 30%,average (58. 60± 12.12)%, were continued. All of the above 51 fetuses were followed up after birth without any abnormalities till present. Genetic diagnosis was offered for 6 fetuses, whose F Ⅷ: C concentration ＜ 10 % (three ＞ 1% and the other three ＜ 1% ), and intron 22 inversion was detected in two and no mutation was found among the rest four. Conclusions Fetal blood FⅧ: C and vWF: Ag concentrations determination may offer prenatal diagnosis of HA, and is accurate in detecting HA intron 22 inversion and its carriers when combined with LD-PCR.

Correlation of free fetal DNA with β-human chorionin gonadotropin in circulation in pregnant women with high-risk of Down's syndrome / 中华妇产科杂志

Objective To investigate significance and correlation of free fetal DNA (fDNA) and β-human chorionic gonadotropin(β-hCG) in circulation in pregnant women with high-risk of Down's syndrome (DS). Methods Pregnant women with a male fetus at second trimester screening for Down's syndrome were chosen, including 5 women with a trisomy 21 fetus (DS group), 21 women with DS high-risk pregnant women (DS high-risk group) matched with 22 normal pregnant women as control group. Free fDNA in maternal plasma were extracted. Male DYS14 gene was labled as fDNA, real-time PCR was used to detect fDNA expression. The concentration of β-hCG in maternal serum was detected by chemiluminescence immune assay. The relationship between level of free fDNA and β-hCG concentration was analyzed by Pearson correlation analysis. Results (1) The mean level of free fDNA was (127±58 ) GE/ml in DS group, which was significantly higher than (78±28) GE/ml in DS high-risk group and (48±21 ) GE/ml in control group,respectively (P<0.01). When compared the level of free fDNA between DS high-risk group and control group, it reached statistical difference (P<0.01). (2) The mean concentration of β-hCG was (97±43) kU/L in DS group, which was significantly higher than (58±25) kU/L in DS high-risk group and (38±19) kU/L in control group, respectively (P<0.01). The level of β-hCG in DS high-risk group was also significantly higher than control group (P<0.01). (3) The positive relationship between the level of free fDNA in maternal plasma and β-hCG concentration in maternal serum was observed amongthree groups (r=0.83,P<0.05;r=0.76,P<0.01;r=0.86,P<0.01). Conclusions Free fDNA in maternal plasma might be a candidate marker used for prenatal DS screening. However, its clinical value need to be evaluated because of positive correlation between free fDNA and β-HCG in maternal circulation.

The Histochemical Localization and Activities of Nitric Oxide Synthase in Placental Tissue from Pregnancies with Abnormal Umbilical Artery Flow Velocity Waveforms / 中华围产医学杂志

Objective To study the nitric oxide synthase(NOS)distribution and activity in placental villous,stem villous vessel and umbilical vessel from pregnancies with abnormal umbilical artery flow velocity waveforms and discuss the effect of NOS in the development of abnormal umbili- cal artery flow velocity waveforms.Methods Using NADPH-diaphorase histochemical method and colorimetry,we studied the distribution and activity of NOS in placental villous,stem villous vessel and umbilical vessel tissues from nine women with normal umbilical artery Doppler waveforms and eight women with abnormal umbilical artery Doppler waveforms.Results The NOS primarily dis- tributed in the syncytiotrophoblast and vessel endothelial cells.In the majority syncytiotrophoblast of normal group,the blue granules gathered to mass,appeared primarily basal in location.In the ma- jority syneytiotrophoblast of abnormal group,the blue granules diffused primarily around nucleus, the staining intension was weaker than normal.Placental villous from the abnormal group had signif- icantly lower activities of NOS than the normal group.Conclusions The lower activities and an abnormal distribution of NOS were found in the placental villous of women with abnormal umbilical artery flow velocity waveforms.The abnormity of NOS may contribute to the development abnormal umbilical artery flow velocity waveforms.