简介：AbstractFetal growth restriction (FGR) has a prevalence of about 10% worldwide and is associated with an increased risk of perinatal mortality and morbidity. FGR is commonly caused by placental insufficiency and can begin early (<32 weeks) or in late (≥32 weeks) gestational age. A false positive antenatal diagnosis may lead to unnecessary monitoring and interventions, as well as cause maternal anxiety. Whereas a false negative diagnosis exposes the fetus to an increased risk of stillbirth and renders the pregnancy ineligible from the appropriate care and potential treatments. The clinical management of FGR pregnancies faces a complex challenge of deciding on the optimal timing of delivery as currently the main solution is to deliver the baby early, but iatrogenic preterm delivery of infants is associated with adverse short-and long-term outcomes. Early and accurate diagnosis of FGR could aid in better stratification of clinical management, and the development and implementation of treatment options, ultimately benefiting clinical care and potentially improving both short-and long-term health outcomes. The aim of this review is to present the new insights on biomarkers of placenta insufficiency, including their current and potential value of biomarkers in the prediction and prevention for FGR, and highlight the association between biomarkers and adverse outcomes in utero to explore the specific mechanism of impaired fetal growth that establish the basis for disease later in life.

简介：AbstractFetal growth restriction (FGR) is associated with multiple adverse perinatal outcomes, such as increased risk of intrauterine death, neonatal morbidity and mortality, and long-term adverse outcomes. Genetic etiological factors are critical in fetuses with intrauterine growth restriction, including chromosomal abnormalities, copy number variants, single gene disorders, uniparental disomy, epigenetic changes, and confined placental mosaicism. This paper aims to provide an overview of genetic defects related to FGR and to highlight the importance of prenatal genetic counseling and testing for precise diagnosis and management of FGR.

简介：AbstractFetal growth restriction (FGR) is the condition in which a fetus does not reach its intrinsic growth potential and in which the shortterm and long-term risks of severe complications are increased. FGR is a frequent complication of pregnancy with a complex etiology and limited management options, other than timely delivery. The most common pathophysiological mechanism is placental insufficiency, due to many underlying causes such as maternal vascular malperfusion, fetal vascular malperfusion and villitis.Identifying truly growth restricted fetuses remains challenging. To date, FGR is often defined by a cut-off of the estimated fetal weight below a certain percentile on a population-based standard. However, small fetal size as a single marker does not discriminate adequately between fetuses or newborns that are constitutionally small but healthy and fetuses or newborns that are growth restricted and thus at risk for adverse outcomes. In 2016, the consensus definition of FGR was internationally accepted to better pinpoint the FGR population.In this review we will discuss the contemporary diagnosis and management issues. Different diagnostic markers are considered, like Doppler measurements, estimated fetal growth, interval growth, fetal movements, biomarkers, and placental markers.

简介：AbstractSelective fetal growth restriction (sFGR) is a severe condition that complicates 10% to 15% of all monochorionic diamniotic (MCDA) twin pregnancies. Pregnancies complicated with sFGR are at high risk of intrauterine demise or adverse perinatal outcome for the twins. Three clinical types have been described according to the umbilical artery (UA) Doppler pattern observed in the smaller twin: type I, when the UA Doppler is normal; type II, when there is persistent absent or reversed end-diastolic blood flow in the UA Doppler; and type III, when there is intermittent absent and/or reversed end-diastolic blood flow in the UA Doppler. Clinical evolution and management options mainly depend on the type of sFGR. Type I is usually associated with a good prognosis and is managed conservatively. There is no consensus on the management of types II and III, but in earlier and more severe presentations, fetal interventions such as selective laser photocoagulation of placental anastomoses or selective fetal cord occlusion of the smaller twin may be considered. This review aims to provide updated information about the diagnosis, evaluation, follow-up, and management of sFGR in MCDA twin pregnancies.

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简介：AbstractFetal growth restriction (FGR) is a common complication of pregnancy associated with higher rates of perinatal mortality and morbidity, as well as a variety of long-term adverse outcomes. To standardize the clinical practice for the management of FGR in China, Fetal Medicine Subgroup, Chinese Society of Perinatal Medicine, Chinese Medical Association and Maternal-Fetal Medicine Committee, Chinese Society of Obstetrics and Gynecology,Chinese Medical Association organized an expert committee to provide official consensus-based recommendations on FGR. We evaluated the evidence provided by relevant high-quality literature, performed a three-round Delphi study and organized face-to-face meetings with experts from multidisciplinary backgrounds. The consensus includes the definition, prenatal screening, prevention, diagnosis, monitoring and management of FGR.

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简介：AbstractObjective:To assess the clinical features of fetal growth restriction (FGR) in women with hypertensive disorders of pregnancy in China.Methods:This is a retrospective cohort study. The clinical data of 4 451 women with hypertensive disorders of pregnancy were retrospectively collected from 11 tertiary hospitals across ten provinces in China during January 2015 to December 2015. The mean maternal age was (31.0±5.4) years old. Participants were divided into FGR group (n= 670) and non-FGR group (n= 3 781). The incidence and clinical features of FGR, and its correlation with gestational age, previous FGR history, 24-hour urinary protein excretion, and hemolysis, elevated liver enzyme and low platelet count (HELLP) syndrome were analyzed. Student’s t-test and Chi-square test were used when comparing clinical features between FGR and non-FGR groups.Results:The overall incidence of FGR was 15.1% (670/4 451). The FGR incidence was 22.4% (433/1 937) in women with severe preeclampsia and 18.6% (68/365) in women with chronic hypertension with superimposed preeclampsia, respectively. FGR was more prevalent in women who had preterm births than those who had term births (22.8% (432/1 898) vs. 9.3% (238/2 553), P < 0.001). It was also more prevalent in women with early-onset preeclampsia than those with late-onset preeclampsia (18.4% (189/1 025) vs. 14.0% (481/3 426), P= 0.001). Women with a previous FGR history had a significantly higher FGR incidence than those without an FGR history (66.7% (4/6) vs. 15.7% (250/1 596), P= 0.007). The presence of abnormal results of the umbilical artery Doppler (13% (87/670) vs. 2.4% (89/3 781), P < 0.001) and the middle cerebral artery Doppler (3.3% (22/670) vs. 0.4% (15/3 781), P < 0.001) was higher in the FGR group compared with the non-FGR group, while the presence of increased uterine artery resistance was not statistically different (1.5% (10/670) vs. 0.8% (29/3 781), P= 0.072). The FGR group delivered earlier than the non-FGR group ((35.3±3.0) weeks vs. (36.4±4.3) weeks, P < 0.001) with lower birth weight (1 731.0±574.5) g vs. (2 753.9±902.1) g, P < 0.001, higher fetal or neonatal death (9.4% (63/670) vs. 4.2% (157/3 781), P < 0.001), and higher cesarean section rate (82.5% (553/670) vs. 70.2% (2 656/3 781), P < 0.001). In the FGR group, more neonates had 5-minute Apgar score ≤7 (7.9% (53/670) vs. 3.9% (149/3 780), P < 0.001), with higher neonatal intensive care unit admission rate (48.1 % (322/670) vs. 23.3% (881/3 781), P < 0.001). More cases of HELLP syndrome occurred in the FGR group (6.9% (46/670) vs. 3.2% (122/3 781), P < 0.001). Women with FGR had heavier 24-hour urinary protein excretion than those without FGR ((3.9±3.7) g vs. (3.1±4.2) g, P= 0.005).Conclusion:In pregnancies with hypertensive disorders, increased risks of FGR are associated with preterm birth, birth before 34 weeks, and a previous FGR history. FGR is related to higher occurrence of abnormal uterine artery Doppler and umbilical artery Doppler. When hypertensive disorders is complicated by FGR, there appears to be higher maternal morbidity including higher rate of HELLP syndrome, cesarean section, and heavier proteinuria, as well as worse neonatal outcomes.

简介：AbstractObjective:To investigate whether the fetal gender affects the incidence of pre-eclampsia (PE) and fetal growth restriction (FGR) in singleton and twin pregnancies.Methods:This was a 10-year single-center, retrospective, cohort study from January 2009 to January 2019. A total of 57,129 singleton and 3699 twin pregnancies aged between 18-55 years old were recruited at the Third Affiliated Hospital of Guangzhou Medical University, China. We used multivariable logistic regression to analyze the effect of fetal gender on the incidence of PE and FGR.Results:In singleton pregnancies, the incidence rates of PE and FGR with a female fetus were higher than those with a male fetus (6.4% (1713/26,793) vs. 5.9% (1803/30,336), P < 0.05 and 3.5% (932/26,793) vs. 2.4% (745/30,336), P < 0.05, respectively). A female fetus was an independent risk factor for either PE or FGR (adjusted odds ratio: 1.169 or 1.563; 95% confidence interval: 1.036-1.319 or 1.349-1.810, respectively). In twin pregnancies, the incidence of early-onset PE was greater in pregnancies with two females compared with two males or one male plus one female (4.6% (46/1003) vs. 4.1% (54/1305) vs. 2.4% (33/1391), P < 0.05). Female-female twins was an independent risk factor for PE (adjusted odds ratio: 1.367, 95% confidence interval: 1.011-1.849), especially early-onset PE.Conclusion:The female fetus was associated with PE in both singleton and twin pregnancies and was also a risk factor of FGR in singleton pregnancies.

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简介：AbstractObjective:To build a reference fetal growth chart for the Chinese population based on fetal ultrasound measurements.Methods:This was a multicenter, population-based retrospective cohort study. Longitudinal ultrasound measurement data were collected from 24 hospitals in 18 provinces of China from 1st September through 31st October of 2019. The estimated fetal weight (EFW) was calculated based on head circumference, abdominal circumference, and femur length using Hadlock formula 3. Fetal growth curves were estimated using a two-level linear regression model with cubic splines. All participants were divided into two groups: the northern group (n = 5829) and the southern group (n = 3246) based on the geographical division of China and male fetus group (n = 4775) and female fetus group (n = 4300) based on fetal gender. The EFW was compared by fetal gender and geographical group. All statistical models were adjusted for maternal sociodemographic characteristics.Results:A total of 9075 participants with 31,700 ultrasound measurement records were included in this study. Male fetuses demonstrated significantly larger EFW compared to female ones starting at 16 weeks of gestation and extending to delivery (global test P < 0.01). The overall geographic difference in EFW was significant (global test P = 0.03), and week-specific comparisons showed that the northern group had a greater EFW starting at 15 weeks of gestation and extending to 29 weeks of gestation, although this difference did not extend to the time of delivery. The Z-score of EFW confirmed that our Chinese fetal growth charts differed from previously published standards.Conclusion:This study provides EFW and ultrasound biometric reference measurements for Chinese fetuses and reveals differences from other fetal growth charts. The chart is worth promoting in more regions of China but should be tested prudently before use.

简介：AbstractChoosing a fetal growth standard or reference is crucial when defining normal and abnormal fetal growth. We reviewed the recently published standards and compared them with a customized fetal growth chart based on a nationwide population in China. There were substantial discrepancies in the fetal growth pattern, suggesting that these standards may not be applicable to Chinese fetuses. Developing a Chinese-specific standard may better meet our clinical requirements. We also discuss the steps to establish a Chinese fetal growth standard and the potential challenges, including regional disparities and accuracy of sonographic estimated fetal weight. Standardized ultrasound measurement protocol and the introduction of new ultrasonography technology may be helpful in developing a more precise standard than existing ones for the Chinese population.

简介：这篇文章在生长曲线模型题目为回归系数考虑线性评估者的考虑到不完全的椭圆体的限制。为分别地，在同类、非同类的线性评估者的班上可被考虑的线性评估者的必要、足够的条件在二次的损失功能下面被获得。他们是在文学的一些存在结果的归纳。

简介：AbstractBackground:The fetal growth charts in widest use in China were published by Hadlock >35 years ago and were established on data from several hundred of American pregnant women. After that, >100 fetal growth charts were published around the world. We attempted to assess the impact of applying the long-standing Hadlock charts and other charts in a Chinese population and to compare their ability to predict newborn small for gestational age (SGA).Methods:For this retrospective observational study, we reviewed all pregnant women (n = 106,455) who booked prenatal care with ultrasound measurements for fetal biometry at the Shenzhen Maternity and Child Healthcare Hospital between 2012 and 2019. A fractional polynomial regression model was applied to generate Shenzhen fetal growth chart ranges for head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL). The differences between Shenzhen charts and published charts were quantified by calculating the Z-score. The impact of applying these published charts was quantified by calculating the proportions of fetuses with biometric measurements below the 3rd centile of these charts. The sensitivity and area under the receiver operating characteristic curves of published charts to predict neonatal SGA (birthweight <10th centile) were assessed.Results:Following selection, 169,980 scans of fetal biometry contributed by 41,032 pregnancies with reliable gestational age were analyzed. When using Hadlock references (<3rd centile), the proportions of small heads and short femurs were as high as 8.9% and 6.6% in late gestation, respectively. The INTERGROWTH-21st standards matched those of our observed curves better than other charts, in particular for fat-free biometry (HC and FL). When using AC<10th centile, all of these references were poor at predicting neonatal SGA.Conclusions:Applying long-standing Hadlock references could misclassify a large proportion of fetuses as SGA. INTERGROWTH-21st standard appears to be a safe option in China. For fat-based biometry, AC, a reference based on the Chinese population is needed. In addition, when applying published charts, particular care should be taken due to the discrepancy of measurement methods.

简介：AbstractObjective:Metabolic disturbances in the folate cycle in mothers can lead to fetal growth retardation (FGR). This study was to analyze the role of intergenic interactions among maternal folate cycle genes in the development of FGR.Methods:This case-control study recruited 365 women in the third trimester of pregnancy, including 122 FGR patients and 243 controls. The women were genotyped for 5 polymorphisms of the 4 folate cycle genes: MTR (rs1805087), MTRR (rs1801394), serine hydroxymethyl transferase (SHMT1; rs1979277), and TYMS (rs699517 and rs2790). The SNP × SNP interactions in the two-, three-, and four-locus models were analyzed using the multifactor dimensionality reduction method and a modification of it (the model-based multifactor dimensionality reduction method).Results:Four loci of maternal folate cycle genes (rs1805087 MTR, rs2790 TYMS, rs1801394 MTRR, and rs1979277 SHMT1) were associated with FGR in 3 significant models of single nucleotide polymorphism (SNP) × SNP interactions (two-, three-, and four-locus models) (P <0.05). The highest contribution to FGR was made by polymorphic loci rs1979277 SHMT1 (1.70% of entropy), rs1805087 MTR (0.96%), and interactions between rs1979277 SHMT1 × rs1805087 MTR (-1.11%) and rs1801394 MTRR × rs1979277 SHMT1 (-0.64%). The four-locus maternal genotype combination AG rs1801394 MTRR × AA rs1805087 MTR × CT rs1979277 SHMT1 × AG rs2790 TYMS was associated with an increased risk of FGR (β = 2.69, P = 0.012). FGR-associated SNPs were correlated with the expression of 16 genes (MTR, MTRR, SHMT1, ALKBH5, CTD-2303H24.2, ENOSF1, FAM106A, FOXO3B, LGALS9C, LLGL1, MIEF2, NOS2P2, RP11-806L2.6, SMCR8, TOP3A, and USP32P2) in various tissues and organs related to FGR pathophysiology.Conclusion:SNP × SNP interactions of maternal folate cycle genes (MTR, MTRR, SHMT1, and TYMS) are associated with the development of FGR.

简介：AbstractBackground:Twin pregnancies continue to increase worldwide; however, the current clinical prenatal evaluation for the intrauterine growth of twins still relies on the growth standards of singletons. We attempted to establish a set of fetal biometric references for Chinese twin pregnancies, stratified by chorionicity and conception mode as spontaneously conceived monochorionic diamniotic (SC-MCDA), spontaneously conceived dichorionic diamniotic (SC-DCDA), and assisted reproductive technology dichorionic diamniotic (ART-DCDA) twins.Methods:From 2016 to 2019, the ultrasonographic fetal biometric measurements were longitudinally collected in pregnant women, including fetal weight, biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length. The linear mixed models were used to test the difference of growth patterns between groups, and the growth curve of each biometric parameter was modeled by a generalized additive model for location scale and shape.Results:A total of 929 twin pregnant women and 2019 singleton pregnant women, met the inclusion criteria. Among twin pregnancies, 148 were SC-MCDA, 215 were SC-DCDA, and 566 were ART-DCDA twins. Overall, SC-DCDA twins grew faster than SC-MCDA twins, while slower than ART-DCDA twins (all P < 0.05), and all of the three groups showed significant differences comparing with singletons, especially during the third trimester. Hence, the customized fetal growth charts of each fetal biometric parameter were, respectively, constructed for SC-MCDA, SC-DCDA, and ART-DCDA twins.Conclusions:The fetal biometric trajectories demonstrated characteristic patterns according to chorionicity and conception mode. To fill the gap, we modeled fetal biometric parameters for Chinese SC-MCDA, SC-DCDA, and ART-DCDA twin pregnancies, hoping to provide a reference for the further establishment of fetal growth reference values for Chinese twin fetuses.

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简介：我们证明为四元数海森堡组上的sublaplacian的限制操作员从Lp被围住到Lp如果1p$\tfrac{4}{3}$\tfrac{4}{3}。这与海森堡组，限制操作员没从Lp在上被围住到Lp不同除非p=1。

简介：<正>Inthispaper,weinvestigatethegeneralizedSublaplacian.Wegivetheexpressionoftherestrictionoperatorsexplicitly.Byintroducingthegeneralizedλ-twistedconvolutions,weobtaintheestimatesoftherestrictionoperatorsinthemixedL~Pspaces.Finally,wegetarestrictiontheoremassociatedwiththegeneralizedSublaplacian.

简介：Objective:Toinvestigatetheexpressionandpatternofvascularendothelialgrowthfactor(VEGF)anditsfetalliverkinase-1(Flk-1)receptorinspinalcordanddorsalrootgangliaafterneurotomyofsciaticnerveinrats.Methods:Forty-fiveadultmaleWistarratsweredividedrandomlyintoacontrolgroup(n=5)andanexperimentalgroup(n=40).ThebilateralsciaticnervesoftheratsintheexperimentalgroupunderwentneurotomyandtheL4-L6spinalcordandthecorrespondingdorsalrootgangliawereharvestedrespectivelyat8hours,and1,3,5,7,10,14and21days(8subgroupswith5ratseach)afteroperation.Theratsinthecontrolgrouponlyunderwentanexposureofsciaticnervewithoutneurotomy.ImmunohistochemistryandimageanalysiswereusedtostudytheexpressionofVEGFanditsFlk-1receptor.Results:BothVEGFandFlk-1receptorexpressedinthenormalratspinalcordanddorsalrootganglia.Inresponsetoneurotomy,theirexpressionreachedahigherlevelandpersistedforashorttimethendeclinedtothenormallevelrapidly.Besides,positivestainingofFlk-1wasobservedinbothglialcellsandnervefibers,whichlocatedinthewhitematterofthespinalcord.Conclusions:VEGFcanpromotetheregenerationofperipheralnervesfromtheangleofcentralneurons,whichestablishestheexperimentalandtheoreticalfoundationforVEGFtreatingperipheralnerveinjuries.