Objective:To investigate the feasibility and safety of fetal intravascular transfusion via the intrahepatic vein in the treatment of fetal anemia.Methods:This was a retrospective analysis of all fetuses requiring intrauterine transfusion (IUT) in the Shanghai First Maternity and Infant Hospital between January 2010 and December 2019. According to the different ways of IUT, they were divided into intrahepatic venous transfusion group and umbilical venous transfusion group, fetal outcomes and the incidence of procedure-related complications between the two groups were compared.Results:A total of 97 IUTs were performed on 48 fetuses. Among them, 16 cases were performed in the intrahepatic vein (31 transfusions), 32 cases were performed in the cord of the umbilical vein (66 transfusions).There were no significant differences between the two groups in age, labor history and the proportion of fetal hydrops before the first transfusion. In the intrahepatic venous transfusion group, the posterior placenta was 14/16, which was significantly higher than 78% (25/32) in the umbilical venous transfusion group ( P<0.01). The live-birth rates of the two groups were 13/16 and 75% (24/32). There was no significant difference between the two groups ( P>0.05). Before intrahepatic venous transfusion, the proportion of fetal hydrops was significantly higher than that of umbilical venous transfusion [55% (17/31) vs 24% (16/66), P<0.05]. Puncture success rate of intrahepatic venous transfusion and umbilical venous transfusion were both 100%. In the umbilical venous transfasion group, the incidence of needle slippage (5%, 3/66) and the abnormality of fetal heart rate (11%, 7/66) were higher than those in the intrahepatic venous transfasion group [0 and 3% (1/31)], but there were no significant differences between the two groups (all P>0.05). There were no cases of fetal loss within 24 hours, premature rupture of membranes, infection within 7 days and emergency cesarean section after IUT in both groups. Conclusions:Fetal intravascular transfusion via the intrahepatic vein is safe and feasible in the treatment of fetal anemia. But the requirements of puncture technique are relatively high, so it is recommended to be carried out in experienced fetal treatment center.

To assess the perinatal outcomes following selective feticide through radiofrequency ablation (RFA) in complex monochorionic pregnancies. Methods In this retrospective observational study, 34 cases of complex monochorionic pregnancies treated with RFA for selective feticide and delivered at the Shanghai First Maternity and Infant Hospital between January 1, 2012 and December 31, 2013, were included. Gestational age at RFA, the number of RFA cycles, maternal and fetal complications, gestational age at delivery, neonatal outcomes at 28 days after birth and neonatal development after birth were recorded. Fetal survival rate were defined as the number of survivors at 28 days after birth divided by the number of remaining fetuses after RFA. Factors affecting fetal survival rate were also analyzed. Statistical analysis was performed using Fisher's exact test. Results (1) The process for RFA:The gestatinal age for the procedure was (20.7±3.1) weeks(16+1-27+6 weeks). The successful rate of procedures was 100%(34/34) and the cycle number for RFA was 1-6 times. (2)Fetal complications and survival rate of remaining fetuses after RFA:there were six pregnant women suffering from premature rupture of membrane (PROM) before 28 weeks. Among those women, one had miscarriaged at 25 weeks, one chose to terminate at 26 weeks and the remaining four chose to continue the pregnancy. There were three remaining fetuses developing fetal severe anemia with hydrops after RFA. Two of them had fetal demises 2 days after the procedures and one chose to have termination. Another two cases with discordant fetal anomalies had fetal demises with unknown reasons one day after RFA. There were 27 remaining fetuses after RFA who survived until 28 days after birth. The mean gestational age at delivery was(36.4±4.1)weeks (26+4-40 weeks) and the mean birth weight was (2 913± 978) g (1 080-4 600 g). The overall fetal survival rate 28 days after birth was 79%(27/34). There were no abnormal findings in antenatal magnetic resonance imaging (MRI) four weeks after the procedure and no abnormal development of nervous system in the surviving neonates between 3 months old and 1.5 years old. (3) Factors affecting fetal survival rate :There were no significant differences identified in the rate of fetal severe anemia and fetal demise (2/15, 2/13 and 1/6), the rate of PROM before 28 weeks (1/15, 4/13 and 1/6) and survival rate of 28 days after birth (13/15, 10/13 and 4/6)among three groups with different gestational age (16+1-, 20- and 24-27+6 weeks) for RFA(all P>0.05). The indications for RFA included severe selective intrauterine growth restriction (50%, 17/34), discordant for fetal abnormalities(24%, 8/34) , twin reversed arterial perfusion sequence(18%, 6/34)and dichorionic or monochorionic triamniotic pregnancy (9%, 3/34). There were also no significant differences noted in the rate of fetal complications and fetal demise(3/17, 2/8, 0/6, 0/3), the rate of PROM before 28 weeks (3/17, 0/8, 2/6, 1/3)and survival rate of 28 days after birth among different groups (12/17, 6/8, 6/6, 3/3) with different indications for RFA(all P>0.05) . No significant differences observed in the rate of fetal complications and fetal demise(10% and 2/5)and the rate of PROM before 28 weeks (17%and 2/5)between two groups with different cycle numbers for RFA (<3 times and≥3 times, all P<0.05), while the group with cycle number ≥ 3 times had lower survival rate 28 days after birth than the group with cycle number<3 times for RFA (2/5 vs 86%, P<0.05). Conclusions RFA is one of effective and safe procedures for selective feticide in complex monochorionic pregnancies.

Objective To review the diagnosis,monitoring,management and perinatal outcomes of monochorionic monoamniotic (MCMA) twin pregnancy.Methods From July 2010 to August 2013,there were 17 MCMA twin pregnancies diagnosed and delivered in Shanghai First Maternity and Infant Hospital.According to the MCMA management protocol,induced abortion,elective fetal reduction,and anticipant pregnancy were optional.For those anticipant pregnancies,fetal lung underwent maturation promotion at gestational weeks 28; hospitalization with 40 min/day continual fetal electronic monitoring and umbilical blood monitoring twice weekly at gestational weeks 28-30; 40 min continual fetal electronic monitoring twice daily and umbilical blood monitoring once every other day at gestational weeks 30-32; and 40 min continual fetal electronic monitoring three times daily and umbilical blood monitoring once daily at gestational weeks 32-34; and pregnancy ended on time.The presence of umbilical cord entanglement,congenital malformation,intrauterine fetal death,complications exclusive to monochorionic twins (e.g.selective fetal growth restriction,twin reversed arterial perfusion sequence and twin-twin transfusion syndrome) and the perinatal outcomes were retrospectively analyzed.Results Average maternal age of women with 17 MCMA twins was (29.0±2.7) years,and all were primiparas.They were diagnosed at (18.6± 5.5) weeks on average (11 +5-28+1 weeks).Umbilical cord entanglements were detected in all cases by ultrasonography and confirmed postnatally.There were three cases of complications specific to monochorionic twins,including two with selective fetal growth restriction and one with twin reversed arterial perfusion sequence.There were seven women with fetal congenital malformation; four of whom chose induced abortion; one case of anencephaly chose radiofrequency ablation fetal reduction,and the remaining two cases with congenital malformation and ten cases without chose anticipant pregnancy,and there were no abnormal ultrasonography signs during pregnancy.Among these 12 cases,intrauterine fetal death of both fetuses occurred in two cases at 16 and 21+1 weeks gestation and they were aborted.Intrauterine fetal death of a single fetus occurred in one case at 30+2 weeks gestation (another fetus was delivered by emergency cesarean section).There were a total of eleven live births delivered by cesarean section (four by emergency cesarean section) at a median gestational age of (32.7± 1.6) weeks.There were 20 live neonates with a mean birth weight of (1 850±496) g.Sixteen neonates were transferred to the neonatal intensive care unit and hospitalized for (37.9± 16.4) days.Nine neonates suffered from respiratory distress syndrome but were eventually cured.Conclusions MCMA twin pregnancy has high morbidity and mortality.Early ultrasonography helps to clarify the diagnosis and enhance the monitoring,thus improving the perinatal outcomes.

Objective To investigate the association between placental sharing,vascular anastomoses,cord insertion and perinatal outcome in uncomplicated monochorionic diamniotic (MCDA) placentas.Methods Between January 1,2012 and July 31,2013,60 uncomplicated (seclective fetal growth restriction,twin anemia-polycythemia sequence and twin-twin transfusion dyndrome) MCDA placentas were studied.These uncomplicated MCDA placentas were divided into the placenta equally shared group with placental territory discordance (PTD) ＜0.25 and the placenta unequally shared group with PTD ≥ 0.25.Angioarchitecture,cord insertion type and the distance between two cord insertions were compared using the Chi-square test and nonparametric test.Results Mean maternal age was (30.3±4.1) years.There were 39 cases (65％) in the placenta equally shared group and 21 (35％) in the placenta unequally shared group.Vascular anastomoses were observed in all placentas,arterioarterial anastomoses in 58 placentas (97％),and venovenous anastomoses in 17 placentas (28％).The overall diameter and the maximum diameter of arterioarterial anastomoses in the placenta equally shared group were (0.19±0.11) cm and (0.18±0.09) cm,respectively,and were lower than those in the placenta unequally shared group [(0.27±0.11) cm and (0.27±0.12) cm,respectively] (T were-2.39 and-2.94,P＜0.05,respectively).No significant differences in the number,the overall diameter and the maximum diameter of venovenous anastomoses were observed between the two groups (all P＞0.05).The incidence of cord velamentous insertion and cord velamentous insertion plus cord marginal insertion were 14％ (11/78) and 42％ (33/78),respectively,in the placenta equally shared group,and were similar to those in the placenta unequally shared group [14％ (6/42) and 33％ (14/42),x2 were 1.00 and 0.43,P＞0.05,respectively].The mean distance between two cord insertions was shorter in the placenta unequally shared group than in the placenta equally shared group [(14.3±6.3) cm vs (18.2±6.0) cm,T=2.37,P＜0.05].Conclusions In cases with unequally shared placenta,the distance between two cord insertions is shorter and the diameter of arterioarterial anastomoses is larger,which may compensate for their unequal placental territories,leading to no complications in these MCDA twin.

We hereby reported a fetus with abnormal head shape, ventricular septal defect, gallbladder enlargement, low-set ears and local umbilical cord glial edema at 22 and 25 weeks of gestation ultrasound scan. A 15.318 Mb heterozygous microdeletion on chromosome 1p32.1p31.1, arr[GRCh37]1p32.1p31.1(61,279,239-76,597,189)×1, was indentified by chromosomal microarray analysis. The chromosome karyotype of the fetus was 46,XY,del(1)(p32.1p31.1). Therefore, this case was diagnosed as 1p32p31 microdeletion syndrome and proved to be a de novo variation based on routine G-banding analysis and chromosomal microarray analysis of the normal parents. This syndrome might present with abnormalities in the head shape, kidney, bladder and central nervous system. The couple decided to terminate the pregnancy after genetic counseling concerning the possible poor outcomes of the fetus.

Objective:To assess the safety and efficacy of radiofrequency ablation (RFA) in the treatment of twin reversed arterial perfusion (TRAP) sequence.Methods:This was a retrospective study of all TRAP sequence cases treated by RFA in Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, between January 1, 2012, and December 31, 2018. Perioperative complications, short- and long-term perinatal outcomes, and maternal complications were analyzed by analysis of variance, Kruskal-Wallis test, Chi-square test, or Fisher's exact test. Results:(1) This study recruited 59 pregnant women with an average age of (28.4±4.0) years. The mean gestational age at TRAP sequence diagnosis was (17.0±4.1) weeks, and 23 (39.0%) were diagnosed before 16 weeks. (2) The 59 cases consisted of 45 (76.2%) monochorionic diamniotic (MCDC) twins, five (8.5%) monochorionic monoamniotic (MCMA) twins, four (6.8%) monochorionic triamniotic (MCTA) triplets and five (8.5%) dichorionic triamniotic (DCTA) triplets. Fifty-four cases (91.5%) were acardius acephalus, four (6.8%) were acardius anceps, and one (1.7%) was acardius amorphous. (3) Preterm premature rupture of membranes (PPROM) was a leading complication following RFA with an overall incidence of 25.4% (15/59). PPROM before 28 and at 28-34 gestational weeks occurred in seven (11.9%) and five (8.5%) cases, respectively, leading to fetal loss in six cases. The cumulative incidence of PPROM within one week, two weeks, and one month after RFA was 5.1% (3/59), 6.8% (4/59) and 10.2% (6/59), respectively. No chorioamnionitis, blood transfusion due to hemorrhage, placental abruption, sepsis, bowel perforation, or other maternal complications were reported during or after the procedure. (4) No abnormalities of the nervous system were found in any fetus on postoperative MRI during pregnancy. The mean interval from treatment to delivery was (14.9±7.1) weeks. Twelve pump twins (20.3%) were lost after RFA, while the other 47 (79.7%) were delivered and survived until 28 days after birth, including 18 premature infants and 29 full-term infants. Eight premature infants were admitted to the neonatal intensive care unit (NICU). Intraventricular hemorrhage, neonatal respiratory distress syndrome (NRDS), and NRDS complicated by necrotizing enterocolitis occurred in three different babies who recovered after appropriate treatment. (5) Of the 59 patients, 56 (94.9%) received intrauterine interventions after 16 gestational weeks, and the survival rate of the pump twins was 78.6% (44/56). Three patients (5.1%) received intrauterine interventions before 16 weeks of gestation with all pump twins survived. (6) Of the 45 MCDA twins, 37 (82.2%) survived and were born at a mean gestational age of 38.0 (26.5-41.0) weeks. Three out of the five MCMA twins survived with the median gestational age at birth of 33.5 (32.0-37.0) weeks. Of the nine triplets, seven survived and delivered at the median gestational age of 37.1 (29.2-40.0) weeks. (7) The needle pierced through the placenta during RFA in 23 (39.0%) cases, but not in the rest 36 (61.0%) cases. After excluding four cases opting for pregnancy termination, statistical analysis showed no significant difference in the incidence of PPROM or intrauterine death, or the 28-day survival rate of the pump twins when comparing those cases with the needle going or not going through the placenta. (8) At the final follow-up (December 2019), 47 surviving pump infants were growing normally without any severe neurological sequelae.Conclusions:RFA appears to be a relatively safe and reliable technique in the treatment of TRAP sequence to improve the perinatal outcomes of pump twins.

Objective To investigate the pregnancy outcomes of non-immune hydrops fetalis (NIHF) in the era of intrauterine intervention. Methods We reviewed the medical records of 149 patients who were referred for NIHF and delivered at Fetal Medicine Unit, Shanghai First Maternity and Infant Hospital between March 2012 and March 2017. After systematic evaluation and consultation, 102 cases chose to terminate their pregnancies, 47 cases (31.5％) chose to continue their pregnancies, among which two cases were lost to follow-up. The rest 45 cases were divided into two groups according to whether they received intrauterine interventions or not, the intrauterine intervention group (n=18) and the control group (n=27), and the clinical characteristics and pregnancy outcomes were compared. Independent samples t-test or Kruskal-Wallis test, Chi-square test or Fisher exact test were applied for statistical analysis. Results The mean gestational age of the intervention group at diagnosis of NIHF was lower than that of the control group [26.5(23.4-30.0) weeks vs 30.3(29.0-32.0) weeks, χ2=7.427, P=0.006]. Compared with the control group, the intrauterine fetal death rate was slightly lower [25.9％(7/27) vs 1/18], the neonatal survival rate was slightly higher [37.0％(10/27) vs 11/18] in the intrauterine intervention group, although no statistically significance was observed (Fisher exact, P>0.05). In the intrauterine intervention group, the incidence of low Apgar score (<4) at both 1 and 5 min was 1/17 and 0/17, respectively, which was much lower than those of the control group [45％(9/20) and 35％(7/20), Fisher exact, both P<0.05]. Conclusions After overall prenatal evaluation, appropriate intrauterine interventions may improve the pregnancy outcomes in NIHF.

Objective To assess the positive predictive value (PPV) of fetal sex chromosome aneuploidy (SCA) identified by non-invasive prenatal testing (NIPT) and investigate families' acceptance of SCA fetus. Methods All suspected SCA cases screened by NIPT from singletons were reviewed in Prenatal Diagnosis Center of Shanghai First Maternity and Infant Hospital from April 1, 2015 to October 31, 2017. Maternal age, NIPT indications, prenatal diagnosis protocols, testing results and their pregnancy determinations were analyzed. Results NIPT was provided to 35827 singletons and 86 suspected SCA cases were identified out of 35823 successful ones, giving a positive detection rate of 0.24％. The average maternal age was (31.5±5.0) years. After genetic counseling, 20 patients declined prenatal diagnosis,the rest 66 cases proceeded with aminiocentesis and fetal chromosomal testing, of which 32 were cytogenetically diagnosed as SCA with the PPV of 48.5％ . The SCA fetus consisted of 25 sex chromosome trisomies (seven cases of 47,XXX, three cases of 47,XYY and 15 cases of 47,XXY), one monosomy X (45,X), three mosacisms (47,XXY/48,XXYY, 47,XXX/45,X, 45,X/46,XX, one for each) and three microdeletions/microduplications. Besides, two false positive NIPT cases were proved to be low level of maternal mosacism (45,X/46,XX, 5％ and 10％ for each). After genetic counseling, 17 out of 20 who declined prenatal diagnosis and 9 out of 32 who diagnosed fetal SCAs continued their pregnancies, with a combined proportion of continued pregnancy of 50％. Thirty-four pregnancies were also continued after exclusion of SCA. Interestingly, the proportion of continued pregnancy among those sex chromosomal trisomy fetuses was only 32％(8/25). Conclusions As a safe and rapid prenatal testing for common autosomal aneuploidies, NIPT could also identify some types of SCA, but with relatively low PPV. More long-term researches are required to determine its sensitivity and specificity. For some types of SCA with mild phenotypes, some family would continue the pregnancy. Therefore, limitations of NIPT should be appropriately explained during both pre- and post-testing counseling.

Objective To evaluate the safety and perinatal outcomes of thoracoamniotic shunting in the treatment of fetuses with severe primary hydrothorax. Methods 22 cases of suspected severe primary fetal hydrothorax which underwent thoraco-amniotic shunting in Shanghai First Maternity and Infant Hospital,Fetal Medicine Unit and Prenatal Diagnosis Center from January 2012 to December 2017 were analyzed retrospectively. Hydrothorax associated with structural or chromosomal abnormalities, infections and immune fetal hydrops were excluded. Results Totally ,28 shunts were placed in 22 fetuses. The median gestational age at TAS was 31.3 weeks. Preterm membrane rupture within 7 days after the procedure occurred in 9.1％(2/22) cases. Catheter displacement occurred in 18％(4/22) cases. The interval from shunting to delivery was 26.0 days. One fetus ended in induced abortion; 21(95％,21/22) babies were born alive, and their median gestational age at delivery was 34.4 weeks. 62％(13/21)newborns required ventilator supports; 4 neonatal deaths were attributed to pulmonary hypoplasia. The overall perinatal survival rate was 81％(17/21). The perinatal survival rate with hydrops and without hydrops were 10/13 and 7/8 respectively. Conclusion Thoraco-amniotic shunting is a safe procedure for intrauterine therapy and could improve the perinatal outcomes of severe primary fetal hydrothorax.