Pregnancy and birth outcomes of multiple gestations with PPROM occurred within 24 h after fetal reduction: A case series.

OBJECTIVE: The study aims to analyze the pregnancy outcomes of multiple gestations with preterm premature rupture of membranes (PPROM) that occurred within 24 h after fetal reduction with potassium chloride (KCL). MATERIALS AND METHODS: We identified and evaluated the outcomes of 16 retrospectively recorded multigestational pregnancies that met the inclusion criteria between 2006 and 2016, from the Obstetrics Department of Shandong Provincial Hospital. A total of 16 patients carrying twins or higher order multiple gestations experienced PPROM within 24 h after fetal reduction, and all of them received expectant management after understanding the relevant risks. The maternal and neonatal records were retrospectively collected and reviewed. Every surviving child was followed up to at least 2 years old. RESULT: Of the 16 cases, 12 cases (75%) ended in successful pregnancy, resulting in the delivery of at least 1 child surviving from a multiple gestational pregnancy. All cases of successful pregnancies were either term (≥37 weeks) or near-term (36+5 weeks) at delivery. And of those 20 infants delivered, only 3 were low birth weight infants (<2500g) (15%), None of the 16 women had fever, or other clinical symptoms and signs of chorioamnionitis during hospital stay. Postnatal follow-up of the surviving babies showed no obvious sequelae thus far. No newborn baby had neonatal complications, or needed to be transferred to neonatal intensive care unit. CONCLUSION: Overall, our data demonstrate that dichorionic diamniotic (DCDA) twins or higher-order gestations who experienced PPROM of the reduced fetus within 24 h after selective reduction with KCL had relatively good outcomes with expectant management alone.

Safety and Efficacy of Higher Order Multifetal Pregnancy Reduction: A Single-Center Retrospective Study.

Objective This research was aimed to study the safety and efficacy of higher order multifetal pregnancy reduction (MFPR). Study Design This was a retrospective study of patients from an academic maternity center between 2005 and 2015. We evaluated outcomes of 131 consecutive patients who underwent higher order MFPR (quadruplets and greater). MFPR was performed at 11 to 18 weeks of gestation in all cases. In total, 122 of 131 cases of higher order multiple pregnancy were reduced to twins. We discuss the perinatal outcomes of patients who underwent higher order MFPR, followed by a comparative analysis between the 122 cases of MFPR that were reduced to twins and 101 cases of nonreduced twin pregnancies. Results The study included 104 sets of quadruplets, 20 sets of quintuplets, 5 sets of sextuplets, 1 set of septuplets, and 1 set of octuplets. The perinatal outcomes of the 131 cases were as follows: pregnancy loss, preterm deliveries at 28 to 33 (+ 6/7 ) weeks, and preterm deliveries at 34 to 36 (+ 6/7 ) weeks occurred in 23.66, 9, and 37% of cases, respectively. The mean time of delivery was 36.56 ± 1.77 weeks, and mean birth weight was 2,409.90 ± 458.16 g, respectively. A total of 122 cases that were reduced to twins were compared with nonreduced twins. The pregnancy loss rate for reduced twins was significantly higher than that for nonreduced twins. The preterm labor rate, mean delivery week, mean birth weight, birth-weight discordance, incidence of gestational diabetes mellitus, and pregnancy-induced hypertension were not significantly different between the groups ( p > 0.05). Conclusion Perinatal outcomes were significantly improved by reducing the number of fetuses in higher order multifetal pregnancies. This study involved a large, diverse sample population, and the results can be used as a reference while conducting prenatal counseling.

LRP6 regulates Rab7-mediated autophagy through the Wnt/ß-catenin pathway to modulate trophoblast cell migration and invasion.

Pre-eclampsia is a common complication during pregnancy; however, the underlying mechanisms of the crosstalk between low-density lipoprotein receptor-related protein 6 (LRP6) and autophagy in trophoblast cells are still not fully explored. Messenger RNA (mRNA) and protein levels of LRP6, beclin 1, Unc-51-like autophagy activating kinase 1 (ULK1), p62, vimentin, matrix metallopeptidase-9 (MMP-9), ß-catenin, c-Myc, and Rab7, as well as the ratio of LC3-II/LC3-I, were analysed by quantitative real-time polymerase chain reaction or Western blot analysis, respectively. An MTT assay was used to measure cell growth, and transwell and wound healing assays were carried out to evaluate the invasion and migration abilities of the trophoblasts used. An immunofluorescence assay was used to measure LC3. The mRFP-GFP-LC3 tandem fluorescence assay was applied to detect autophagic flow. LRP6 overexpression was achieved by constructing pcDNA3.1-LRP6 vectors. LRP6 was expressed at low levels in HTR-8/SVneo cells under hypoxia/reoxygenation (H/R) conditions. H/R inhibited the activation of autophagy. LRP6 overexpression promoted cell proliferation and activated autophagy, which led to the upregulation of beclin 1 and ULK1, as well as the ratio of LC3-II/LC3-I and the downregulation of p62. Furthermore, LRP6 overexpression elevated the migration and invasion abilities of the indicated cells and increased vimentin and MMP-9 expression levels. Furthermore, LRP6 upregulated Rab7 and activated autophagy through the Wnt/ß-catenin pathway. The late autophagy inhibitor bafilomycin A1 (Baf-A1) and the Wnt/ß-catenin pathway inhibitor PKF115-584 reversed the effects of LRP6 on trophoblast autophagy, migration and invasion. LRP6 promotes Rab7-mediated autophagy by activating the Wnt/ß-catenin pathway, which leads to increasing migration and invasion of trophoblast cells. Our study paves a new avenue for clinical treatment, and LRP6 may serve as an essential target in pre-eclampsia.

Comparisons between two methods of multifetal pregnancy reduction in women with a dichorionic triamniotic triplet pregnancy.

OBJECTIVE: To compare the different pregnancy outcomes of women with a reduced dichorionic triamniotic (DCTA) triplet managed with radiofrequency ablation (RFA) or potassium chloride (KCL). MATERIALS AND METHODS: This was a retrospective cohort study. We studied 30 women of DCTA triplets managed with RFA as well as 85 managed with KCL. We compared the mean neonatal birthweight, median gestational age and perinatal mortality of two groups. RESULTS: The mean neonatal birthweight of children in RFA group was 2572.4 g (SD, 407.0), vs 2899.3 g (SD, 554.9) in KCL group (P < 0.001). The rate of low birth weight infants was 23 (42.6%) vs. 16 (18.0%), respectively, (p < 0.005). However, there was no statistically significant difference in the median gestational age of delivery, premature birth before 32&37 weeks' gestation, neonatal brain injury or successful pregnancy between two groups. (We define the successful pregnancy as the condition that at least one child survives for a specific woman, while the failed one as no child survives.) CONCLUSION: What we took it for granted was that pregnancy outcomes in women with a reduced DCTA triplet managed with RFA was riskier than with KCL, however, we proved that it is not accurate. For women with a reduced DCTA triplet, managed with RFA is not much riskier than with KCL. What's more, most women have two children survived in RFA group, while in KCL group, only one child survives for most women. This result may change the management alternative for those women with DCTA triplet pregnancies who choose reduction, especially for women who desire to have two surviving and healthy fetuses.

Association study between variants in LHCGR DENND1A and THADA with preeclampsia risk in Han Chinese populations.

Objective: To evaluate the association between preeclampsia and three single nucleotide polymorphisms (rs13405728 in LHCGR gene; rs13429458 in THADA gene, and rs2479106 in DENND1A gene) which were identified to be genetic variants of polycystic ovary syndrome (PCOS) by genome-wide association study in Han Chinese populations. Methods: A total of 784 northern Han Chinese women (378 controls and 406 cases) were genotyped for the three genetic variants by polymerase chain reaction and direct sequencing. Unconditional logistic regression analysis was used to adjust the impact of prepregnancy body mass index, primiparas, and maternal age. Results: No significant difference was found in the allele frequencies of the three genetic variants between cases and controls (p > .05), but genotype frequency of the SNP rs2479106 was significantly differ between cases and controls when analyzed under recessive models (p = .02). There was also a substantial difference in the genotype frequencies of the SNP rs13429458 between cases and controls under additive models (p = .01). Conclusions: Genetic variants of PCOS (rs13405728 in LHCGR gene; rs13429458 in THADA gene and rs2479106 in DENND1A gene) may not be involved in the development of preeclampsia in Han Chinese women.

Radiofrequency ablation for selective reduction in complex monochorionic multiple pregnancies: A case series.

OBJECTIVE: To determine the safety and efficacy of radiofrequency ablation (RFA) for selective fetal reduction in complex monochorionic multiple pregnancies. MATERIALS AND METHODS: From July 2011 to January 2015, data on all cases treated with RFA were collected prospectively in our hospital. Indications, procedure details, cause of fetal demise and pregnancy outcomes were analyzed. Sonography and magnetic resonance imaging were performed to detect fetal brain damage. Information regarding development after birth was collected according to the Gesell Development Schedule®. RESULTS: There were 22 cases of twins (6 presenting with twin-twin transfusion syndrome, 10 with malformations, 4 with selective intrauterine growth restriction, and 2 with twin reversed arterial perfusion sequence); and 11 cases of triplets (9 dichorionictriamniotic, 2 monochorionictriamniotic). All surgeries were completed with one puncture. No maternal complications presented during RFA procedure, and the PPROM rate before 32 w was 9% (3/33). There were 3 cases of intrauterine fetal demise and 4 twin cases where pregnancy was terminated. The fetal survival rate was 77% (17/22) in twins, 91% (20/22) in triplets. Total fetal survival rate was 84% (37/44). The neurodevelopmental follow-up investigations showed no abnormalities in any of the survivors. CONCLUSION: RFA for selective fetal reduction in complex monochorionic multiple pregnancies is effective, minimally invasive, and safe.

Dydrogesterone has no effect on uterine fibroids when used to prevent miscarriage in pregnant women with uterine fibroids.

OBJECTIVES: To analyse the effect of dydrogesterone use during pregnancy on uterine fibroids, pregnancy complications, and pregnancy outcome. MATERIAL AND METHODS: In all, 372 pregnant women with uterine fibroids who were treated at the Affiliated Provincial Hospital of Shandong University were included in this study. Thirty-three of these women received dydrogesterone and constituted the treatment group, and the 27 women who were found to have uterine fibroids during the first trimester but did not receive intervention to prevent miscarriage composed the control group. The changes in uterine fibroids before and after pregnancy and the pregnancy complications were recorded; immunohistochemistry was used to detect the expression of progesterone receptor (PR) and proliferation- and apoptosis-related proteins in the uterine fibroid tissue. RESULTS: No significant difference was observed in the change in uterine fibroid volume during pregnancy between the treatment group and the control group (p > 0.05). The percentage of uterine fibroids with red degeneration was lower in the treatment group than in the control group, but the difference was not statistically significant. No significant difference was observed in newborn weight, height, Apgar score, threatened miscarriage, or premature birth, among other characteristics, between the two groups (p > 0.05). Immunohistochemistry showed no significant difference in the expression of PR, cyclinD1, insulin-like growth factor (IGF1), or B-cell lymphoma 2 (Bcl2) between the two groups. CONCLUSIONS: The use of dydrogesterone during pregnancy has no significant effect on uterine fibroids, pregnancy progression, or pregnancy outcomes in pregnant patients with uterine fibroids.

Noninvasive Swansea criteria are valuable alternatives for diagnosing acute fatty liver of pregnancy in a Chinese population.

BACKGROUND: This study aims to assess the diagnostic and prognostic value of Swansea criteria in diagnosing acute fatty liver of pregnancy (AFLP) in a Chinese population. METHODS: A retrospective study was conducted on 52 Chinese women diagnosed with AFLP. All selected cases were reassessed using the Swansea criteria with special focus on the noninvasive criteria, since performing a liver biopsy for this indication is rare in a Chinese population. RESULTS: Ninety point four percent of patients fulfilled five or more of the Swansea criteria. Thirty-one cases were positive for six or more Swansea criteria, but there were no significance differences between patients when using a cutoff criteria <6 or >6. When patients were positive for less than seven criteria, frequency of stillbirth, continuous blood purification (CBP) treatment, hysterectomy, and postpartum hemorrhage were not increased. However, patients who were positive for seven or more criteria had a significantly higher risk of stillbirth and a higher rate of CBP treatment (p < 0.05). Areas under the receiver operating characteristic (ROC) curve of postpartum hemorrhage was 0.670, which reached a statistical significance (p = 0.040). We observed a significantly elevated postpartum hemorrhage along with positivity of the Swansea criteria (p = 0.040). CONCLUSIONS: Swansea criteria without liver biopsy are good screening tools for AFLP diagnosis, and may be useful for assessing disease severity.

Role of UMOD Promoter Polymorphism in the Etiology of Preeclampsia.

AIMS: To evaluate the association between preeclampsia (PE) and the single nucleotide polymorphism (SNP) rs13333226, located in the promoter region of the UMOD gene. METHODS: A total of 1248 pregnant Han Chinese women (716 controls and 532 patients with PE) were included in this study. Genotyping of the rs13333226 polymorphism was performed by real-time PCR using a TaqMan-minor groove binder (MGB) probe assay. RESULTS: No significant differences were detected in the allele (p = 0.62, OR = 1.08, 95% CI = 0.81-1.44) and genotype frequencies of rs13333226 (padditive = 0.38, pdominant = 0.45, precessive = 0.31) between cases and controls. When patients were divided into subgroups, no association was found with mild preeclampsia (M PE), severe preeclampsia (S PE), early onset PE, or late-onset PE. Furthermore, no significant differences were detected in the genotype and allele frequencies of rs1333226 between patients with M PE and S PE (p > 0.05) or between patients with late and early onset of the disease (p > 0.05). CONCLUSIONS: UMOD rs13333226 does not appear to be associated with PE in Han Chinese women.

Recurrent miscarriage is associated with a decline of decidual natural killer cells expressing killer cell immunoglobulin-like receptors specific for human leukocyte antigen C.

AIM: To investigate the relationship between natural killer (NK) cell phenotype and recurrent miscarriage (RM). METHODS: We studied killer cell immunoglobulin-like receptor (KIR) expression on decidual NK cells in women with RM. RESULTS: The expression of KIR2DL1/S1 on CD56(+) CD16(-) NK cells in the deciduas of these women was significantly lower than in that of control subjects (P = 0.026). There was a significant decline in the frequency of CD56(+) CD16(-) NK cells staining for KIR2DL1/S1 and KIR2DL2/S2/L3 throughout the first trimester in patients (P < 0.05). Furthermore, by stratification of the women in three groups according to gestational stage, it was found that KIR2DL1/S1 expressing NK cells were significantly decreased in all groups, especially around gestational days 50-70 (P = 0.010). CONCLUSION: This is the first report to demonstrate that RM is associated with a decline in the frequency of decidual NK cells expressing KIR specific for human leukocyte antigen (HLA)-C, and in which gestational stage was considered. The results suggest that KIR phenotype contributes to the pathogenesis of the disease, and that assessment of KIR may serve as a diagnostic tool.

The common single-nucleotide polymorphism rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women.

Preeclampsia, characterized by hypertension and proteinuria, remains a leading cause of maternal morbidity and mortality. Recently, a genome-wide association study (GWAS) identified the single-nucleotide polymorphism, rs2681472, as a new hypertension susceptibility genetic variant. The purpose of this study was to evaluate the association between preeclampsia and rs268172 in a Northern Han Chinese population. We genotyped 1218 unrelated Northern Han Chinese women, including 515 patients with preeclampsia and 703 healthy controls. No significant differences were detected in the allele frequencies between patients and controls (P = .23). When patients were divided into early-onset and late-onset preeclampsia according to gestational age of disease onset, the allele frequencies significantly differed between controls and patients with early-onset preeclampsia (P = .02). Genotype frequencies also were significantly different between controls and patients early-onset preeclampsia when data were analyzed under additive (P = .03) and dominant (P = .009) models. We replicated this association in an independent Northern Han Chinese population and observed a significant difference in the allele frequencies between patients with early-onset preeclampsia and controls (P = .011). We report that rs2681472 is associated with early-onset preeclampsia in Northern Han Chinese women.

The common variant rs11646213 is associated with preeclampsia in Han Chinese women.

BACKGROUND: Preeclampsia, characterized by hypertension and proteinuria, is a multifactorial disease caused by complex interactions between environmental and genetic factors. A recent genome-wide association study of blood pressure reported an association between hypertension and rs11646213. This study evaluated the association between preeclampsia and rs11646213. METHODS: A total of 454 cases and 460 controls were recruited to participate in this study. The single nucleotide polymorphism (SNP) rs11646213 was genotyped by polymerase chain reaction (PCR) and direct sequencing. RESULTS: The allele frequency of rs11646213 was significantly different between the preeclampsia and control groups (P = 0.017, OR = 1.36, 95% CI = 1.06-1.76). Differences were particularly significant in the severe preeclampsia subgroup (P = 0.002, OR = 1.54, 95% CI = 1.17-2.03) and the early-onset preeclampsia subgroup (P = 0.004, OR = 1.57, 95% CI = 1.16-2.13). Genotyping analysis showed that the T allele of rs11646213 could confer a risk for preeclampsia, severe preeclampsia and early-onset preeclampsia. CONCLUSIONS: Rs11646213 upstream of the CDH13 gene is associated with preeclampsia in Han Chinese women.

[Safety and efficiency of radiofrequency fetal ablation in the treatment of complicated multiple gestations].

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.

Successful pregnancies with uterine leiomyomas and myomectomy at the time of caesarean section.

OBJECTIVE To ascertain the impact of uterine leiomyomas on pregnancy outcome, and to determine the effectiveness of myomectomy at the time of caesarean delivery. METHODS A retrospective study was conducted on pregnant women with uterine leiomyomas. Clinical information including the course of the pregnancy, mode of delivery, pathology findings, and postpartum course were extracted from medical records and analysed for statistical significance. RESULTS There were 50 pregnancies associated with uterine leiomyomas. During pregnancy, the leiomyomas grew >2 cm in 46% of cases. Only 6% were affected by symptoms of red degeneration. There were 2% mid trimester inductions of labour, 6% vaginal deliveries, and 92% caesarean sections. Of the 46 caesarean sections, 47% were due to obstetrical factors and 89% of patients underwent myomectomy at the time of caesarean delivery. The mean blood loss from myomectomy at the time of caesarean section was 260 ml (200-700 ml), and 5% of patients who underwent myomectomy were transfused. CONCLUSIONS It is possible to carry a pregnancy successfully to term when the pregnancy is complicated by uterine leiomyomas. When caesarean delivery is needed, myomectomy can be performed at the time of caesarean section routinely without significant complications.

[Comparative study of pregnancy outcomes between spontaneous twin pregnancies and twin pregnancies after fetal reduction in the second trimester].

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 pregnancy (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). 2) The 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 < 0.01], 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. 3) The 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.

[Correlation of free fetal DNA with beta-human chorionin gonadotropin in circulation in pregnant women with high risk of Down's syndrome].

OBJECTIVE: To investigate significance and correlation of free fetal DNA (fDNA) and beta-human chorionic gonadotropin (beta-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 beta-hCG in maternal serum was detected by chemiluminescence immune assay. The relationship between level of free fDNA and beta-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 beta-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 beta-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 beta-hCG concentration in maternal serum was observed among three 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 beta-HCG in maternal circulation.

Use of maternal plasma for non-invasive prenatal diagnosis of fetal ABO genotypes.

BACKGROUND: Measurement of free fetal DNA in maternal plasma opened a door for non-invasive prenatal diagnosis. Prenatal diagnosis of fetal ABO genotypes can provide a basis for the prevention and therapy of maternal-fetal incompatibility. We identified fetal ABO genotypes using fetal DNA in plasma from pregnant women with blood group O. The aim of the study was to investigate the accuracy and feasibility of this method. METHODS: A total of 105 blood group O women in middle or late pregnancy were enrolled. Fetal DNA in maternal plasma and genomic DNA in umbilical vein blood from newborns were extracted using a QIAamp DNA Blood Kit. DNA was amplified to identify ABO genotypes by PCR with sequence-specific primers (PCR-SSP). The genotype results were evaluated using serologic tests for ABO phenotyping. RESULTS: Using DNA from umbilical vein blood, ABO genotypes of 105 newborns were successfully identified by PCR-SSP. Using fetal DNA from maternal plasma, 88.6% (93/105) fetal ABO genotypes was correct; 12 false results were from 66 pregnant women with fetuses of type non-O. The accuracy in middle pregnancy was lower than that in late pregnancy, although the difference was not significant (0.05

Detection of genomic imbalances by comparative genomic hybridization in Chinese fetuses with malformations.

AIM: The purpose of the study was to evaluate the feasibility and reliability of comparative genomic hybridization (CGH) in the detection of genomic imbalances in Chinese malformed fetuses. METHODS: Genomic DNA was extracted from umbilical cord blood or fresh amniotic fluid of 9 malformed fetuses and labeled with SpectrumGreen dUTP or SpectrumRed dUTP. A pair of CGH analyses in which the fluorochromes were exchanged was carried out for each sample. RESULTS: Samples from 9 malformed fetuses were analyzed successfully by CGH. Numerical chromosome aberrations were detected in samples from cases 4, 8 and 9, and were verified by fluorochrome-exchanged CGH. Trisomy 21q was detected in case 4, del 2p24-pter and dup 12p13 was detected in case 8, and del 1p33-pter and del 22q11-12 were detected in case 9. CONCLUSION: CGH is a reliable technique for the detection of genomic imbalances. Fluorochrome-exchanged CGH can reduce inconsistencies in the results caused by deviations in the process of DNA labeling and hybridization, and increase the accuracy and reliability in cases when conventional cytogenetic analysis is unavailable.

[Clinical study of selective multifetal pregnancy reduction in second trimester].

OBJECTIVE: To investigate the operative indication, timing, method, selective standards of feticided fetus and the number of reduced fetuses of selective multifetal pregnancy reduction in second trimester, and the pregnancy outcome of multifetal pregnancy by this operation. METHODS: Trans-abdominal selective multifetal pregnancy reductions in 37 cases of multiple pregnancy (twins 6 cases, triplets 21 cases, quadruplets 8 cases, and quintuplets 2 cases) during 12(+1) - 25 weeks were performed under ultrasound guidance. The fetus to be reduced was injected potassium chloride (KCl) intracardiacally until the fetal heartbeat stopped gradually. Totally 46 fetuses were reduced. Periodic prenatal examination and monitoring of coagulation function were carried out after the procedure. The pregnancy complications and pregnancy outcome of all cases were recorded. RESULTS: (1) The successful ratio of reduction was 100% (46/46 fetuses) and the successful pregnancy ratio was 88.9% (24/27). (2)Among all the 37 cases, fifteen delivered after 36 weeks, seven delivered in 32 - 36 weeks, three delivered in 28 - 32 weeks, two aborted after feticide, and ten cases were in pregnancy at the time of this study. The mean gestational age of all was (34.9 +/- 4.1) weeks, and the delivery ratio after 28 weeks was 92.6% (25/27). (3) The mean birth weight of singletons was (3014 +/- 640) g, and of twins was (2557 +/- 573) g. The neonates of three triplets all died except for in one case two fetuses were alive. (4) Except in two cases after reducing one fetus of monoamniotic twins, another one died within 24 hours, the remaining fetuses were all alive. (5) Pre-eclampsia occurred in three cases. None of the cases had blood coagulation disturbances. CONCLUSION: (1) Selective multifetal pregnancy reduction in second trimester can feticide the abnormal fetus objectively or reduce the fetal number effectively. It is a safe procedure to decrease the complications of multifetal pregnancy and increase the birth weight. (2) If the intention is reducing the fetal number, we choose the fetus who lies in the fundus uteri and reduce the multifetal pregnancy to twins. (3) It is advised to aviod performing the procedure during vaginal bleeding. We reduce fetus after vaginal bleeding stops for one or more weeks. (4) Selective second-trimester multifetal pregnancy reduction will not result in the disturbance of blood coagulation and the death of remaining fetus. The incidence of pre-eclampsia is decreased after multifetal pregnancy reduction.