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：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：AbstractBackground:Gestational weight gain (GWG) is associated with the risk of gestational diabetes mellitus (GDM). However, the effect of weight gain in different trimesters on the risk of GDM is unclear. This study aimed to evaluate the effect of GWG on GDM during different trimesters.Methods:A birth cohort study was conducted from 2017 to 2020 in Shenzhen, China. In total, 51,205 participants were included comprising two models (early pregnancy model and middle pregnancy model). Gestational weight (kg) was measured at each prenatal clinical visit using a standardized weight scale. Logistic regression analysis was used to assess the risk of GDM. Interaction analysis and mediation effect analysis were performed in the middle pregnancy model.Results:In the early pregnancy model, the risk of GDM was 0.858 times lower (95% confidence interval [CI]: 0.786, 0.937) with insufficient GWG (iGWG) and 1.201 times higher (95% CI: 1.097, 1.316) with excessive GWG after adjustment. In the middle pregnancy model, the risk of GDM associated with iGWG increased 1.595 times (95% CI: 1.418, 1.794) after adjustment; for excessive GWG, no significant difference was found (P = 0.223). Interaction analysis showed no interaction between GWG in early pregnancy (GWG-E) and GWG in middle pregnancy (GWG-M) (F = 1.268; P = 0.280). The mediation effect analysis indicated that GWG-M plays a partial mediating role, with an effect proportion of 14.9%.Conclusions:eGWG-E and iGWG-M are associated with an increased risk of GDM. Strict control of weight gain in early pregnancy is needed, and sufficient nutrition should be provided in middle pregnancy.

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简介：AbstractWe present an unusual and, until now, unreported case of vesicoallantoic cyst associated with multiple malformations in a fetus. A differential diagnosis is discussed, including the hypothesis of a genetic disorder.

简介：AbstractObjective:To investigate the safety and efficacy of internal electronic fetal heart rate (FHR) monitoring during labor.Methods:This was a retrospective case-control study, which was an analysis of monitoring FHR with a fetal scalp electrode or a Doppler probe (94 pregnant women per group). In the internal monitoring group, when the opening of the uterine orifice was ≥3 cm, the fetal scalp electrode was placed after natural or artificial rupture of the membrane. FHR was simultaneously monitored using a Doppler probe. In the external monitoring group, continuous FHR monitoring was performed using an ultrasound Doppler transducer fixed on the maternal abdomen. The toco transducer was used to record uterine contractions. Pathological examination of the placenta was performed prospectively in 49 and 48 cases in the internal electronic FHR monitoring group and control group, respectively. Maternal-infant outcomes (e.g. fever, puerperal infection, puerperal morbidity, delivery mode, Apgar score, and scalp injury) were recorded. Umbilical artery blood was extracted for blood gas analysis. Differences between the two groups were compared using the paired t-test, χ2 test, Yates corrected χ2 test or Fisher exact test.Results:Non-statistically significant differences between the internal and external monitoring groups were observed in the incidence of neonatal acidosis (1/94 (1.06%) vs. 3/94 (3.19%), respectively; χ2= 0.255, P= 0.613), cesarean section/operative vaginal delivery (8/94 (8.51%) vs. 15/94 (15.96%), respectively; χ2 = 2.427, P= 0.181), fever during labor (18/94 (19.15%) vs. 15/94 (15.96%), respectively; χ2=0.331, P= 0.565), puerperal morbidity (2/94 (2.13%) vs. 3/94 (3.19%), respectively; χ2= 0.000, P= 1.000), chorioamnionitis (9/49 (18.37%) vs. 7/48(14.58%), respectively; χ2= 0.252, P= 0.616), and neonatal asphyxia (0/94 (0.00%) vs. 1/94 (1.06%), respectively; χ2= 0.000, P= 1.000). There were no puerperal infections, neonatal scalp injuries, or scalp abscesses found in either group. Using the internal monitoring value as reference, the incidence of FHR false deceleration in external FHR monitoring was 20.21% (19/94 women).Conclusion:Internal FHR monitoring during labor does not increase the incidence of adverse perinatal outcomes. External monitoring was associated with FHR false decelerations.

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.

简介：AbstractViral infections during pregnancy are associated with adverse pregnancy outcomes, including maternal and fetal mortality, pregnancy loss, premature labor, and congenital anomalies. Mammalian gestation encounters an immunological paradox wherein the placenta balances the tolerance of an allogeneic fetus with protection against pathogens. Viruses cannot easily transmit from mother to fetus due to physical and immunological barriers at the maternal-fetal interface posing a restricted threat to the fetus and newborns. Despite this, the unknown strategies utilized by certain viruses could weaken the placental barrier to trigger severe maternal and fetal health issues especially through vertical transmission, which was not fully understood until now. In this review, we summarize diverse aspects of the major viral infections relevant to pregnancy, including the characteristics of pathogenesis, related maternal-fetal complications, and the underlying molecular and cellular mechanisms of vertical transmission. We highlight the fundamental signatures of complex placental defense mechanisms, which will prepare us to fight the next emerging and re-emerging infectious disease in the pregnancy population.

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.

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：摘要Background and objectiveCloser monitoring and treatment is vital for pregnant carbon monoxide (CO) poisoning cases due to fetal poisoning component. Permanent damage can occur in both the mother and the baby. It may cause stillbirth even though no serious clinical symptoms occur in the mother. Hyperbaric oxygen (HBO) treatment is advised for all pregnant patients regardless of their clinical symptoms. Pregnant CO poisoning patients that received HBO treatment and their fetal status were evaluated in this study.MethodsPregnant patients poisoned with CO treated in the same hyperbaric clinic were evaluated. Pregnant patients that received HBO treatment in a multiplace chamber were evaluated in terms of clinical status, demographic structure, laboratory tests, fetal effects and progress of the fetus until birth and 6 months postpartum.ResultsA total number of 32 pregnant cases were treated. COHb values were over 20% (min 6.9- max 40.2) in 23 patients, 11 patients had a history of syncope. All patients took HBO treatment under 2.4 ATA pressure for 120 min. 3 patients received more than 1 session of HBO treatments due to fetal stress; all other cases took 1 session of HBO treatment. No spontaneous abortus occurred in early follow-ups; only 4 babies were born prematurely. 2 of the babies were lost in the early phases after birth, due to causes non-related to CO poisoning complications (cyanotic heart disease, necrotizing enterocolitis). No significant difference were observed in the comparison of laboratory results of patients with syncope and of those who did not have syncope and comparison of patients with COHb value higher than 20% and patients with COHb value lower than 20% (P>0.05)．ConclusionHBO is not advisable for pregnant patients except for CO poisoning. In this study it is observed that HBO treatment under 2.4 ATA pressure for 120 min has no harmful effects on the mother and the fetus. It is observed that continuation of HBO treatment in the cases with fetal distress findings has beneficial effects. COHb levels and syncope were shown to have no significant effect on clinical symptoms and on blood tests.

简介：AbstractObjective:This study investigates the efficacy of analyzing fetal heart rate (FHR) signals based on Artificial Intelligence to obtain a baseline calculation and identify accelerations/decelerations in the FHR through electronic fetal monitoring during labor.Methods:A total of 43,888 cardiotocograph(CTG) records of female patients in labor from January 2012 to December 2020 were collected from the NanFang Hospital of Southern Medical University. After filtering the data, 2341 FHR records were used for the study. The ObVue fetal monitoring system, manufactured by Lian-Med Technology Co. Ltd., was used to monitor the FHR signals for these pregnant women from the beginning of the first stage of labor to the end of delivery. Two obstetric experts together annotated the FHR signals in the system to determine the baseline as well as accelerations/decelerations of the FHR. Our cardiotocograph network (CTGNet) as well as traditional methods were then used to automatically analyze the baseline and acceleration/deceleration of the FHR signals. The results of calculations were compared with the annotations provided by the obstetric experts, and ten-fold cross-validation was applied to evaluate them. The root-mean-square difference (RMSD) between the baselines, acceleration F-measure (Acc.F-measure), deceleration F-measure (Dec.F-measure), coefficient of synthetic inconsistency (SI) and the morphological analysis discordance index (MADI) were used as evaluation metrics. The data were analyzed by using a paired t-test.Results:The proposed CTGNet was superior to the best traditional method, proposed by Mantel, in terms of the RMSD.BL (1.7935 ± 0.8099 vs. 2.0293 ± 0.9267, t=-3.55 , P=0.004), Acc.F-measure (86.8562 ± 10.9422 vs. 72.2367 ± 14.2096, t= 12.43, P <0.001), Dec.F-measure (72.1038 ± 33.2592 vs. 58.5040 ± 38.0276, t= 4.10, P <0.001), SI (34.8277±20.9595 vs. 54.8049 ± 25.0265, t=-9.39, P <0.001), and MADI (3.1741 ± 1.9901 vs. 3.7289 ± 2.7253, t= -2.74, P= 0.012). The proposed CTGNet thus had significant advantages over the best traditional method on all evaluation metrics.Conclusion:The proposed Artificial Intelligence-based method CTGNet delivers good performance in terms of the automatic analysis of FHR based on cardiotocograph data. It promises to be a key component of smart obstetrics systems of the future.

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简介：AbstractBackground:Chromosomal abnormalities are important causes of ventriculomegaly (VM). In mild and isolated cases of fetal VM, obstetricians rarely give clear indications for pregnancy termination. We aimed to calculate the incidence of chromosomal abnormalities and incremental yield of chromosomal microarray analysis (CMA) in VM, providing more information on genetic counseling and prognostic evaluation for fetuses with VM.Methods:The Chinese language databases Wanfang Data, China National Knowledge Infrastructure, and China Biomedical Literature Database (from January 1, 1991 to April 29, 2020) and English language databases PubMed, Embase, and Cochrane Library (from January 1, 1945 to April 29, 2020) were systematically searched for articles on fetal VM. Diagnostic criteria were based on ultrasonographic or magnetic resonance imaging (MRI) assessment of lateral ventricular atrium width: ≥10 to <15 mm for mild VM, and ≥15 mm for severe VM. Isolated VM was defined by the absence of structural abnormalities other than VM detected by ultrasonography or MRI. R software was used for the meta-analysis to determine the incidence of chromosomal abnormalities and incremental yield of CMA in VM, and the combined rate and 95% confidence interval (CI) were calculated.Results:Twenty-three articles involving 1635 patients were included. The incidence of chromosomal abnormalities in VM was 9% (95% CI: 5%-12%) and incremental yield of CMA in VM was 11% (95% CI: 7%-16%). The incidences of chromosomal abnormalities in mild, severe, isolated, and non-isolated VM were 9% (95% CI: 4%-16%), 5% (95% CI: 1%-11%), 3% (95% CI: 1%-6%), and 13% (95% CI: 4%-25%), respectively.Conclusions:Applying CMA in VM improved the detection rate of abnormalities. When VM is confirmed by ultrasound or MRI, obstetricians should recommend fetal karyotype analysis to exclude chromosomal abnormalities. Moreover, CMA should be recommended preferentially in pregnant women with fetal VM who are undergoing invasive prenatal diagnosis. CMA cannot completely replace chromosome karyotype analysis.

简介：AbstractObjective:To investigate the efficacy of in-phase and quadrature (IQ) demodulation in electronic fetal heart rate monitoring (EFM) to reduce false reports of fetal heart rate (FHR) doubling or halving.Methods:This is a prospective cohort study. A total of 263 full-term pregnant women who delivered at Peking University Shenzhen Hospital between August 2019 and July 2020 were prospectively enrolled in the study. FHR monitoring began when the cervix was dilated to 2-3 cm and continued until delivery. Raw fetal Doppler audio signals and internal and external cardiotocography curves from internal electrode monitoring, EFM with conventional demodulation (external), and EFM with IQ demodulation (external) were acquired to compare FHR doubling and halving time. In cohort 1, FHR was compared between IQ demodulation and conventional demodulation. In cohort 2, FHR was compared between IQ demodulation, conventional demodulation, and internal FHR monitoring. Count data were statistically analyzed using the Chi-squared test, and measurement data were statistically analyzed using t-test for correlation coefficients, and Bland-Altman analysis for concordance ranges.Results:To compare IQ demodulation and conventional demodulation, 225 pregnant women were monitored for a total of 835,870 seconds. The beat-to-beat interval of FHRs in raw fetal Doppler audio signals was used as the reference. The results showed a doubling time of 3401 seconds (0.407%, 3401/835,870) and a halving time of 2918 seconds (0.349%, 2918/835,870) with conventional demodulation, compared to 241 seconds (0.029%, 241/835,870) and 589 seconds (0.070%, 589/835,870), respectively, with IQ demodulation. IQ demodulation reduced FHR doubling by approximately 93% (3160/3401) and FHR halving by approximately 80% (2329/2918) compared to conventional demodulation (P < 0.01).To compare IQ demodulation, conventional demodulation, and internal FHR monitoring, 38 pregnant women were monitored for a total of 98,561 seconds. FHR from internal electrode monitoring was used as the reference. The results showed a doubling time of 238 seconds (0.241%, 238/98,561) and a halving time of 235 seconds 0.238%, 235/98,561) with conventional demodulation, compared with 30 seconds (0.030%, 30/98,561) and 81 seconds (0.082%, 81/98,561), respectively, with IQ demodulation (P < 0.05). No significant difference was observed in doubling or halving time between IQ demodulation and internal FHR monitoring (P > 0.05). IQ demodulation was more closely correlated with internal FHR monitoring than conventional demodulation (0.986 vs. 0.947). The Bland-Altman analysis showed that the concordance range of IQ demodulation vs. internal FHR monitoring was significantly narrower than that of conventional demodulation vs. internal FHR monitoring ((-5.32,6.01) vs. (-10.87,11.46)).Conclusion:EFM with IQ demodulation significantly reduces false FHR doubling and halving, with an efficacy similar to that of internal FHR monitoring.