简介：Thepresentstudywasconductedtoinvestigatethepotentialembryo-fetaltoxicityofArtesunate,anantimalarialdrug,inSprague-Dawleyrats.Thetestitemwasorallyadministeredbygavagetopregnantrats(22femalespergroup)fromgesta-tionalday(GD)6through15atdoselevelsof0,2,4and8mg/kg,AlldamsweresubjectedtocaesareansectiononGD20andtheirfetuseswereexaminedforexternal,visceral,andskeletalabnormalities.Therewerenotreatment-relatedclinicalsigns,bodyweightsandfoodconsumptioninanyofthetreatmentg...

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：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：AbstractThe obstetric issues and management styles in China are different from that in Western countries. Chinese medical education, residency training, obstetric care structure, and management of common obstetric complications are briefly reviewed and compared to the United States. Maternal-fetal medicine (MFM) is rapidly developing in China, but the development of MFM may not follow the same trajectory as in the West. Understanding the difference between China and the West may facilitate communication and foster mutual development.

简介：AbstractThis paper provides ethical guidance for the professionally responsible clinical investigation of maternal-fetal investigation for fetal or neonatal benefit and its transition into clinical practice. We present an ethical framework based on the ethical principles of beneficence, respect for autonomy, and justice, the professional virtue of integrity, and the ethical concept of the fetus as a patient. We identify the implications of this ethical framework for the qualifications that centers for maternal-fetal intervention should satisfy. These centers have the ethical obligation to provide prospective review and oversight of both innovation (an experiment undertaken to benefit an individual patient) and research (an experiment undertaken to create generalizable knowledge). We describe ethically justified criteria for innovation and early-phase research, for randomized clinical trials, and for the responsible transition into clinical practice. We also identify the elements of the informed consent process, including measures to prevent therapeutic misconception by pregnant patients during the informed consent process. The scientific, clinical, and ethical requirements of maternal-fetal investigation are demanding. However, the commitment to safety and quality requires that they be met. Fulfilling this commitment will result in well-documented professionally responsible investigation of maternal-fetal intervention for fetal and neonatal benefit.

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：obtainaninitialoverviewofgenediversityandexpressionpatterninporcinethymus,11,712ESTs(ExpressedSequenceTags)from100-day-oldporcinethymus(FTY)weresequencedand7,071cleanedESTswereusedforgeneexpressionanalysis.ClusteredbythePHRAPprogram,959contigsand3,074singletswereobtained.Blastsearchshowedthat806contigsand1,669singlets(totally5,442ESTs)hadhomologuesinGenBankand1,629ESTswerenovel.AccordingtotheGeneOntologyclassification,36.99%ESTswerecatalogedintothegeneexpressiongroup,indicatingthatalthoughthefunctionalgene(18.78%indefensegroup)ofthymusisexpressedinacertaindegree,the100-day-oldporcinethymusstillexistsinadevelopmentalstage.Comparativeanalysisshowedthatthegeneexpressionpatternofthe100-day-oldporcinethymusissimilartothatofthehumaninfantthymus.

简介：AbstractGamete production is essential for mammalian reproduction. In the ovaries, the primordial follicle, which is the basic reproductive unit, is formed either perinatally or during the second pregnancy stage in humans. However, some oocytes die before the establishment of the primordial follicle pool. Consequently, it is essential to uncover how the size of the primordial follicle pool is determined and how the programmed cell death of oocytes is performed under potential surveillance. According to recent studies, the fate of oocytes in the fetal ovary seems to be determined by different protective strategies through the timely control of apoptosis or autophagy. In this review, we discuss at least three oocyte-derived protective biomarkers, glycogen synthase kinase 3 beta, X-linked inhibitor of apoptosis, and Lysine-specific demethylase 1 (also known as KDM1A), responsible for surveilling the developmental quality of fetal oocytes to coordinate primordial follicle formation in the fetal ovary. This review contributes to a better understanding of the secrets of the female reproductive reserve under physiological conditions.

简介：AbstractSince the 1970s, electronic fetal monitoring (EFM) also known as cardiotocography (CTG) has been used extensively in labor around the world, despite its known failure to help prevent many babies from developing neonatal encephalopathy and cerebral palsy. Part of EFM’s poor performance with respect to these outcomes arises from a fundamental misunderstanding of the differences between screening and diagnostic tests, subjective classifications of fetal heart rate (FHR) patterns that lead to large inter-observer variability in its interpretation, failure to appreciate early stages of fetal compromise, and poor statistical modeling for its use as a screening test. We have developed a new approach to the practice and interpretation of EFM called the fetal reserve index (FRI) which does the following: (1) breaking FHR components down into 4 components, (heart rate, variability, accelerations, and decelerations); (2) contextualizing the metrics by adding increased uterine activity; (3) adding specific maternal, fetal, and obstetric risk factors. The result is an eight-point scoring metric that, when directly compared with current American College of Obstetricians and Gynecologists EFM categories, even in version 1.0 with equal weighting of variables, shows that the FRI has performed much better for identifying cases at risk before damage had occurred, reducing the need for emergency deliveries, and lowering overall Cesarean delivery rates. With increased data, we expect further refinements in the specifics of scoring that will allow even earlier detection of compromise in labor.

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.

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简介：Seventy-eightcasesofretinoblastoma(Rb)diagnosedattheEyeENTHospital,ShanghaiMedicalUniversityfrom1953to1985werestudied.Theresultsofmultiplelogisticregressionanalysisandconditionalprobabilitymodelshowedthathighfetalorderhadamoderaterisk(OR=1.28,P<0.05)ofdevelopingunilateralRb.Bothunilateralandbilateralcaseswereindependentofparentalages,andnointeractioncouldbefoundbetweenfetalorderandpaternalofmaternalage;also,theeffectoffetalorderwasnotconfoundedbyparentalages.

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简介：AbstractBackground:Prenatal evaluation of fetal lung maturity (FLM) is a challenge, and an effective non-invasive method for prenatal assessment of FLM is needed. The study aimed to establish a normal fetal lung gestational age (GA) grading model based on deep learning (DL) algorithms, validate the effectiveness of the model, and explore the potential value of DL algorithms in assessing FLM.Methods:A total of 7013 ultrasound images obtained from 1023 normal pregnancies between 20 and 41 + 6 weeks were analyzed in this study. There were no pregnancy-related complications that affected fetal lung development, and all infants were born without neonatal respiratory diseases. The images were divided into three classes based on the gestational week: class I: 20 to 29 + 6 weeks, class II: 30 to 36 + 6 weeks, and class III: 37 to 41 + 6 weeks. There were 3323, 2142, and 1548 images in each class, respectively. First, we performed a pre-processing algorithm to remove irrelevant information from each image. Then, a convolutional neural network was designed to identify different categories of fetal lung ultrasound images. Finally, we used ten-fold cross-validation to validate the performance of our model. This new machine learning algorithm automatically extracted and classified lung ultrasound image information related to GA. This was used to establish a grading model. The performance of the grading model was assessed using accuracy, sensitivity, specificity, and receiver operating characteristic curves.Results:A normal fetal lung GA grading model was established and validated. The sensitivity of each class in the independent test set was 91.7%, 69.8%, and 86.4%, respectively. The specificity of each class in the independent test set was 76.8%, 90.0%, and 83.1%, respectively. The total accuracy was 83.8%. The area under the curve (AUC) of each class was 0.982, 0.907, and 0.960, respectively. The micro-average AUC was 0.957, and the macro-average AUC was 0.949.Conclusions:The normal fetal lung GA grading model could accurately identify ultrasound images of the fetal lung at different GAs, which can be used to identify cases of abnormal lung development due to gestational diseases and evaluate lung maturity after antenatal corticosteroid therapy. The results indicate that DL algorithms can be used as a non-invasive method to predict FLM.

简介：AbstractObjective:We aim to assess the clinical performance of cell-free fetal DNA (cffDNA) testing for detecting common fetal aneuploidies as well as subchromosomal deletions/duplications and explore the pregnancy decisions in screen-positive cases.Methods:A cohort of 19,531 pregnant women was offered cffDNA testing for detection of trisomies 21, 18, and 13 (T21, T18, and T13); sex chromosome aneuploidies (SCAs); and subchromosomal deletions/duplications. Screen-positive cases were confirmed by karyotyping and single-nucleotide polymorphism array analysis.Results:A total of 47 cases failed the test. The overall screen-positive rate of chromosomal abnormalities was 1.07% (208/19,484), including 57 cases with T21, 18 cases with T18, 7 cases with T13, 106 cases with SCAs, and 20 cases of subchromosomal deletions/duplications. Positive predictive values were 91.30% (42/46), 38.46% (5/13), 33.33% (2/6), 41.33% (31/75), and 27.78% (5/18), respectively. There was no significant difference in the screening of fetal chromosomal aneuploidies in the high-risk group compared with the low-risk group (P > 0.05). All of the pregnant women who had confirmed fetal T21, T18, or T13 terminated their pregnancies, except for a case of T13 mosaic, whereas 45.16% (14/31) of women with fetal SCAs continued their pregnancies. Furthermore, 17 pregnant women with positive screens for T21, T18, or T13 without a subsequent diagnosis chose to terminate their pregnancy, whereas 29 of 31 women with SCAs chose to continue their pregnancies.Conclusions:CffDNA testing exhibited good screening accuracy for T21, T18, and T13 and also contributed to detecting fetal SCAs and subchromosomal deletions/duplications. Pregnant women with fetal 47, XXX or 47, XYY were more willing to terminate their pregnancy than those with fetal 45, X or 47, XXY.

简介：Sincetheendofthecoldwar,theworldhasundergoneextensive,complexandprofoundchanges.Thefeaturesofsuchchangesaremulti-polarization,globalizationand