Placental microRNA dataset of monochorionic twin pregnancies with and without selective fetal growth restriction.
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ABSTRACT:
SUBMITTER: Meng M
PROVIDER: S-EPMC7132057 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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Placental microRNA dataset of monochorionic twin pregnancies with and without selective fetal growth restriction.
Meng Meng M Cheng Yvonne Kwun Yue YKY Wu Linda Ling LL Chaemsaithong Piya P Leung Maran Bo Wah MBW Chim Stephen Siu Chung SSC Sahota Daljit Singh DS Li Wei W Poon Liona Chiu Yee LCY Wang Chi Chiu CC Leung Tak Yeung TY
Data in brief 20200309
To compare the whole genomic microRNA (miRNA) between the selective fetal growth restriction (sFGR) twin and the normally growing (control) co-twin in monochorionic (MC) twin pregnancies. MC twin pregnancies with or without sFGR were recruited, and their placental miRNAs were profiled by microarray. The ratio of the placental miRNA of the sFGR twin to that of the normally larger co-twin were calculated and compared to that of the control twin pairs. The miRNA microarray intensity amongst normal ...[more]
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Project description:BACKGROUND:Selective fetal growth restriction in monochorionic twin pregnancies is associated with an increased risk of perinatal mortality and morbidity and represents a clinical dilemma. Interventions include expectant management with early preterm delivery if there are signs of fetal compromise, selective termination of the compromised twin, fetoscopic laser coagulation of the communicating placental vessels or termination of the whole pregnancy. Previous studies evaluating interventions have reported many different outcomes and outcome measures. Such variation makes comparing, contrasting, and combining results challenging, limiting ongoing research on this uncommon condition to inform clinical practice. We aim to produce, disseminate, and implement a core outcome set for selective fetal growth restriction research in monochorionic twin pregnancies. METHODS:An international steering group, including professionals, researchers, and lay experts, has been established to oversee the development of this core outcome set. The methods have been guided by the Core Outcome Measures in Effectiveness Trials Initiative Handbook. Potential core outcomes will be developed by undertaking a systematic review of studies evaluating interventions for selective fetal growth restriction in monochorionic twin pregnancies. Potential core outcomes will be entered into a three-round Delphi survey and key stakeholders including clinical professionals, researchers, and lay experts will be invited to participate. Repeated reflection and rescoring of individual outcomes should encourage group and individual stakeholder convergence towards consensus outcomes which will be entered into a modified Nominal Group Technique to finalize the core outcome set. Once core outcomes have been agreed, we will establish standardized definitions and recommend high-quality measurement instruments for each outcome. DISCUSSION:The development, dissemination, and implementation of a core outcome set for selective fetal growth restriction should ensure that future research protocols select, collect, and report outcomes and outcome measures in a standardized manner. Data synthesis will be possible on a broad level and rigorous implementation should advance the quality of research studies and their effective use in order to guide clinical practice, improve patient care, maternal, short-term perinatal outcomes, and long-term neurodevelopmental outcomes. TRIAL REGISTRATION:Core Outcome Measures in Effectiveness Trials (COMET) registration number: 998. International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42018092697 . 18th April 2018.
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Project description:BackgroundSelective fetal restriction growth (sFGR) is one of the common diseases of monochorionic diamniotic (MCDA) twin pregnancies, resulting in many adverse outcomes. At present, second trimester ultrasonography is widely used in the prenatal diagnosis of sFGR, but the diagnostic effectiveness is still uncertain. The aim of this study is to assess the diagnostic accuracy of second trimester Doppler ultrasound measurements for sFGR.MethodsA retrospective study included 280 pregnant women (118 with and 162 without sFGR) with MCDA pregnancies was conducted in the fetal medicine center from Leiden University Medical Center from January 2008 to December 2013. The women participating had already undergone an ultrasound examination in the second trimester. The postnatal criteria of sFGR was a single birth weight (BW) < 3 rd percentile in a twin, or birth weight discordance (BWD)≥25% between two twins, while the BW of the smaller twin < 10th percentile. Early prenatal diagnosis of sFGR was defined as a single EFW < 3 rd percentile in a twin, or at least 2 of the following 4 parameters must be met (fetal weight of one fetus < 10th percentile, AC of one fetus <10th percentile, EFW discordance≥25%, UA pulsatility index (PI) of the smaller fetus > 95th percentile). According to the diagnosis of sFGR after birth, we evaluate diagnostic effectiveness of Doppler ultrasound in the second trimester for sFGR.ResultsOf these 280 participants, the mean age was 32.06 ± 4.76 years. About 43.9% of pregnant women were primiparas. The ability of second trimester Doppler ultrasound to accurately diagnosed sFGR is 75.4%, missed diagnosis rate and the misdiagnosis rate were 24.6% and 10.5% respectively. The ROC curve indicated that the combination of AC discordance, EFW discordance, and small fetal UA blood flow was the best diagnostic indicator of sFGR in MCDA pregnancy with the AUC was 0.882 (95%CI, 0.839-0.926).ConclusionsSecond trimester Doppler and ultrasound measurements is an effective method for early prenatal diagnosis of sFGR. The combined indicator of AC discordance, EFW discordance, and the small fetal UA blood flow reaches highest diagnostic value.
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Project description:Background and purposeMonochorionic twin pregnancies complicated by the IUFD of 1 twin are associated with substantial morbidity to the survivor twin. The aim of this study was to determine whether fetal sonography, T2 MR imaging, and DWI can diagnose acute cerebral lesions in the survivor of an MC twin pregnancy shortly after fetal death of the co-twin.Materials and methodsDuring the study period (2007-2010) 34 cases of single IUFD were evaluated. Group A included 6 cases complicated by spontaneous IUFD. Group B had 10 cases of fetal death shortly after treatment of severe TTTS. These were compared with group C, with 18 pregnancies treated by selective termination due to severe complications in MC pregnancies.ResultsAltogether 9/34 patients had abnormal prenatal cerebral findings. In group A, in 2/6 of pregnancies with spontaneous death, MR imaging showed findings of severe cerebral infarct, while cerebral damage was not evident by sonography. In another case, the surviving fetus was found to be hydropic on sonography, while MR imaging findings were normal. In group B, in 1/10 cases, cerebral infarct was demonstrated only by DWI. In 2 other cases, sonographic findings were normal, but MR imaging showed germinal matrix bleeding. In group C, in 1/18 cases, only DWI showed bilateral cerebral ischemia. In 2 other cases, MR imaging findings suggested germinal matrix bleeding and focal changes in the basal ganglia. In both cases, fetal sonographic findings were normal.ConclusionsIn our study, early manifestations of cerebral ischemia in monochorionic twin pregnancies were better diagnosed with MR imaging, especially with DWI.
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Project description:Selective intrauterine growth restriction (sIUGR) is a severe complication in monochorionic (MC) twin pregnancies, and it carries increased risks of poor prognosis. Current data suggest that vascular anastomoses and unequal placental sharing may be the key contributor to discordant foetal growth. While MC twins derive from a single zygote and have almost identical genetic information, the precise mechanisms remain unknown. DNA hydroxymethylation is a newly discovered epigenetic feature associated with gene regulation and modification. Here, we investigate discordant hydroxymethylation patterns between two placental shares of sIUGR and analyse the potential role of aberrant hydroxymethylation of angiopoietin-like 4 (ANGPTL4) in placental dysplasia. Hydroxymethylation DNA immunoprecipitation (hMeDIP)-chip and mRNA sequencing were performed to identify hydroxymethylation-associated genes. Real-time qPCR, western blotting, and immunohistochemistry were used to confirm ANGPTL4 expression. The mechanisms regulating ANGPTL4 were investigated by cell migration assay, invasion assay, viability assay, and apoptotic ratio assays, western blotting and hMeDIP-qPCR. Decreased ANGPTL4 was detected in the smaller placental shares of sIUGR. ANGPTL4 knockdown suppressed trophoblast invasiveness and migration, which possibly occurred through hypoxia inducible factor 1α (HIF-1α) and HIF-1 signalling pathway. Hypoxia leads to aberrant expression of ANGPTL4 and HIF-1α, positively correlated with their aberrant hydroxymethylation levels in promoter regions. Aberrant hydroxymethylation of ANGPTL4 may contribute to placental impairment by the HIF-1 signalling pathway in smaller placental shares of sIUGR.
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Project description:BackgroundPlacental mitochondrial DNA (mtDNA) has been proposed to be an indicator for placental hypoxia. This study was designed to evaluate the effect of vascular anastomoses between monochorionic (MC) twins on placental mtDNA.MethodsIn this study, twin-twin transfusion syndrome (TTTS) treated with laser therapy and MC twins without TTTS (without laser therapy) resulting in two live babies were included in this study. The placental mtDNA fold changes (FC) between the small and large twins were analyzed using real-time quantitative PCR. TTTS twins with selective intrauterine growth restriction (sIUGR) are categorized as group 1, TTTS without sIUGR as group 2, MC twins without TTTS but with sIUGR as group 3, and MC twins without both TTTS and sIUGR as group 4.ResultsThere were seven cases in group 1, eight in group 2, 26 in group 3, and 24 in group 4 cases. The placental mtDNA FC were significantly higher in group 1 (1.57?±?0.9) compared to that of the group 3 (0.86?±?0.6).ConclusionIn MC twin pregnancies with sIUGR, the placental mtDNA FC between the small and large twins are different between cases with and without inter-twin anastomoses. These findings suggest that the inter-twin anastomoses in the MC twins with sIUGR may provide rescue perfusion from the appropriate-for-gestational-age twin to the sIUGR one.
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Project description:BackgroundSeeking an optimal time point for ultrasound examination is important for the diagnosis of late selective intrauterine growth restriction (sIUGR) at birth in monochorionic diamniotic (MCDA) twin pregnancies. We aimed to assess the role of ultrasound characteristics at 19-24 weeks as predictive tools for late sIUGR at birth in MCDA twin pregnancies.MethodsWe retrospectively recruited 32 sIUGR and 56 normal patients with MCDA twin pregnancies. Ultrasound indexes of these included subjects at 19-24 weeks, including the middle cerebral artery peak systolic velocity (MCA-PSV), umbilical artery pulsatility index (UA-PI), middle cerebral artery pulsatility index (MCA-PI), and cerebroplacental ratio (CPR) were assessed. Receiver operating characteristic (ROC) curves were used to ascertain the predictive value of ultrasound characteristics discrepancy for such complications, and the relationship between the ultrasound characteristics and sIUGR was assessed by a logistic regression analysis.ResultsDifferences were found in the MCA-PI, UA-PI, and CPR discordances between the normal MCDA and sIUGR subjects. CPR discordance was the most effective characteristic for predicting sIUGR [area under the ROC curve (AUC) =0.883; 95% CI: 0.795-0.948], followed by UA-PI discordance (AUC =0.772; 95% CI: 0.685-0.829), and MCA-PI discordance (AUC =0.746; 95% CI: 0.681-0.823), respectively. Additionally, the optimal cutoff value of CPR discordance was 21.65, and the corresponding sensitivity and specificity were 0.750 and 0.929, respectively. The correlation analysis revealed that gestational age (GA) at ultrasound scan but not at delivery was significantly correlated with the MCA-PSV (r=0.55, P<0.01), UA-PI (r=0.55, P<0.01), MCA-PI (r=0.49, P<0.01), and CPR (r=0.55, P<0.01) in sIUGR, while GA at both ultrasound scan and birth was significantly correlated with MCA-PSV (r=0.65, P<0.01), UA-PI (r=0.49, P<0.01), MCA-PI (r=0.48, P<0.01), and CPR (r=0.63, P<0.01) in normal MCDA.ConclusionsIncreased MCA-PI, UA-PI, and CPR discordances were found in fetuses with sIUGR. CPR discordance could serve as a predictive index for sIUGR. An early ultrasound examination may be more accurate than biochemical modality for sIUGR prediction.
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Project description:As twin-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR) are both prevalent complications of monochorionic (MC) twin pregnancies, its coexistence is not uncommon. The aim of this study is to evaluate the short and long-term outcome in TTTS with and without sFGR prior to fetoscopic laser coagulation. All TTTS cases treated with laser surgery at our center between 2001-2019 were retrospectively reviewed for the presence of sFGR, defined as an estimated fetal weight (EFW) <10th centile. We compared two groups: TTTS-only and TTTS + sFGR. Primary outcomes were perinatal survival and long-term severe neurodevelopmental impairment (NDI). Of the 527 pregnancies eligible for analysis, 40.8% (n = 215) were categorized as TTTS-only and 59.2% (n = 312) as TTTS + sFGR. Quintero stage at presentation was higher in the TTTS + sFGR group compared to the TTTS-only group (57% compared to 44% stage III). Separate analysis of donors showed significantly lower perinatal survival for donors in the TTTS + sFGR group (72% (224/311) compared to 81% (173/215), p = 0.027). Severe NDI at follow-up in long-term survivors in the TTTS-only and TTTS + sFGR group was present in 7% (13/198) and 9% (27/299), respectively (p = 0.385). Both sFGR (OR 1.5;95% CI 1.1-2.0, p = 0.013) and lower gestational age at laser (OR 1.1;95% CI 1.0-1.1, p = 0.001) were independently associated with decreased perinatal survival. Thus, sFGR prior to laser surgery is associated with a more severe initial presentation and decreased donor perinatal survival. The long-term outcome was not affected.
| S-EPMC6679158 | biostudies-literature
Project description:BackgroundIn twin pregnancies complicated by selective fetal growth restriction (sFGR), if the smaller twin is in the state of impending intra-uterine death (IUD), immediate delivery will reduce the risk of IUD of the smaller twin while exposing the larger twin to iatrogenic preterm birth (PTB). Therefore, the management options would either be to maintain pregnancy for the maturation of the larger twin despite the risk of IUD of the smaller twin or immediate delivery to prevent IUD of the smaller twin. However, the optimal gestational age of management transition from maintaining pregnancy to immediate delivery has not been established. The objective of this study was to evaluate the physician's perspective on the optimal timing of immediate delivery in twin pregnancies complicated by sFGR.MethodsAn online cross-sectional survey was performed with obstetricians and gynecologists (OBGYN) in South Korea. The questionnaire asked the following: (1) whether participants would maintain or immediately deliver a twin pregnancy complicated by sFGR with signs of impending IUD of the smaller twin; (2) the optimal gestational age of management transition from maintaining pregnancy to immediate delivery in a twin pregnancy with impending IUD of the smaller twin; and (3) the limit of viability and intact survival in general preterm neonates.ResultsA total of 156 OBGYN answered the questionnaires. In a clinical scenario of dichorionic (DC) twin pregnancy complicated by sFGR with signs of impending IUD of the smaller twin, 57.1% of the participants answered that they would immediately deliver the twin pregnancy. However, 90.4% answered that they would immediately deliver the pregnancy in the same scenario for monochorionic (MC) twin pregnancy. The participants designated 30 weeks for DC twin and 28 weeks for MC twin pregnancies as the optimal gestational age of management transition from maintaining pregnancy to immediate delivery. The participants regarded 24 weeks as the limit of viability and 30 weeks as the limit of intact survival in general preterm neonates. The optimal gestational age of management transition for DC twin pregnancy was correlated with the limit of intact survival in general preterm neonates (p < 0.001), but not with the limit of viability. However, the optimal gestational age of management transition for MC twin pregnancy was associated with both the limit of intact survival (p = 0.012) and viability with marginal significance (p = 0.062).ConclusionsParticipants preferred to immediately deliver twin pregnancies complicated by sFGR with impending IUD of the smaller twin at the limit of intact survival (30 weeks) for DC twin pregnancies and at the midway between the limit of intact survival and viability (28 weeks) for MC twin pregnancies. More research is needed to establish guidelines regarding the optimal delivery timing for twin pregnancies complicated by sFGR.
| S-EPMC10176903 | biostudies-literature
Project description:BackgroundSerial growth scans are routinely recommended for twin pregnancies to identify fetal growth restriction (defined as an estimated fetal weight of <10th percentile), which can result in increased perinatal morbidity and mortality. However, the clinical significance of early intertwin growth discordance in the absence of fetal growth restriction remains unclear.ObjectiveThis study aimed to compare the rates of small-for-gestational-age infants among twin pregnancies with intertwin growth discordance in the absence of fetal growth restriction with that among twin pregnancies with concordant, normal growth identified by ultrasound between 24 0/7 and 31 6/7 weeks' gestation.Study designThis was a retrospective cohort study of twin deliveries at a single hospital from 2010 to 2019. Pregnancies without fetal growth restriction were categorized as discordant or concordant using the earliest prenatal growth ultrasound between 24 0/7 and 31 6/7 weeks' gestation. Discordance was defined as an estimated fetal weight difference of ≥18% between twins. Pregnancies with major fetal anomalies, no growth ultrasound between 24 0/7 and 31 6/7 weeks' gestation, or twin-twin transfusion syndrome were excluded. The cohort was stratified by chorionicity. Our primary outcome was small-for-gestational-age defined as <10th percentile per the Fenton growth curve at delivery. Secondary outcomes included gestational age at delivery, mode of delivery, neonatal intensive care unit admission, length of stay, and neonatal complications and placental pathology.ResultsOf the 707 twin pregnancies that met the inclusion criteria, 558 (79%) were dichorionic and 149 (21%) were monochorionic. Most pregnancies were concordant on ultrasound between 24 0/7 and 31 6/7 weeks' gestation (dichorionic, 93%; monochorionic, 87%). Regardless of chorionicity, twin pregnancies with discordance at ultrasound, were more likely to have a small-for-gestational-age infant than concordant twin pregnancies (dichorionic: 51% vs 29%; P=.002; monochorionic: 65% vs 24%; P<.001). Furthermore, women with twin pregnancies with discordance were delivered at an earlier gestational age (dichorionic: 36 weeks [interquartile range, 33-36] vs 34 weeks [interquartile range, 34-38]; P<.001; monochorionic: 34 weeks [interquartile range, 32-34] vs 36 weeks [interquartile range, 34-37]; P=.003). Pregnancies with growth discordance were more likely to be delivered by cesarean delivery (dichorionic: 90% vs 72%; P=.01; monochorionic: 65% vs 60%; P=.70), although this was only statistically significant for dichorionic twin pregnancies. Neonates of pregnancies with growth discordance had a higher incidence of respiratory distress syndrome (dichorionic: 54% vs 37%; P=.04; monochorionic: 70% vs 45%; P=.04) and neonatal intensive care unit admission (dichorionic: 71% vs 50%; P=.01; monochorionic: 90% vs 65%; P=.03). Furthermore, dichorionic infants had longer neonatal intensive care unit stays (30 [interquartile range, 18-61] vs 18 [interquartile range, 10-35] days; P=.02).ConclusionRegardless of chorionicity, twin pregnancies with discordance without fetal growth restriction identified on growth ultrasound between 24 0/7 and 31 6/7 weeks' gestation were nearly twice as likely to develop small-for-gestational-age neonates, deliver earlier in gestation, and experience greater neonatal morbidity than twin pregnancies without discordance. Patients with pregnancies complicated by isolated intertwin discordance between 24 0/7 and 31 6/7 weeks' gestation will need counseling regarding adverse perinatal outcomes.
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