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.

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.

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.

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.

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, P<0.05].The rates of low birth weight infants(<2 499 g)in the twins group and the singleton group were 45.5%(188/413)and 8%(4/49), respectively(P<0.05).The rate of very low birth weight infants(≤1 499 g) was 3.9%(16/413)in the twins group compared with 0(0/49)in the singleton group(P>0.05).(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,P<0.05]. The labor rate of the two groups was significantly different for both 34-36+6 weeks and≥37 weeks(P<0.05).The full-term delivery rate in the twins group was 47.6%(110/231), and was 88.2%(45/51)in the singleton group(P<0.05). The fetal loss rate before 28 weeks did not differ between the two groups[8.7%(20/231)vs 3.9%(2/51), P>0.05].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.

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.

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.

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.

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.

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.