Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model

Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.AIM To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM patients.METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively.Among these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis.The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.RESULTS Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,respectively.The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,respectively.High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent,and their combination can be used as an important index for the early prediction of FGR.

Long-term implications of fetal growth restriction

Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of intrauterine growth velocity in the curve of intrauterine growth.However,the FGR definition is still debated,and there is a lack of a uniform definition in the literature.True IUGR,compared to constitutional smallness,is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus.Infants with IUGR,compared to appropriately grown gestational age infants,have a significantly higher risk of mortality and neonatal complications with long-term consequences.Several studies have demonstrated how suboptimal fetal growth leads to long-lasting physiological alterations for the developing fetus as well as for the newborn and adult in the future.The long-term effects of fetal growth retardation may be adaptations to poor oxygen and nutrient supply that are effective in the fetal period but deleterious in the long term through structural or functional alterations.Epidemiologic studies showed that FGR could be a contributing factor for adult chronic diseases including cardiovascular disease,metabolic syndrome,diabetes,respiratory diseases and impaired lung function,and chronic kidney disease.In this review we discussed pathophysiologic mechanisms of FGR-related complications and potential preventive measures for FGR.

Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg taurine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neo- natal rats with intrauterine growth restriction undergoing taurine supplement were obtained for fur- ther experiments. The terminal deoxyribonucleotidyl transferase （TdT）-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. Immu- nohistochemical staining revealed that taurine supplement increased glial cell line-derived neuro- trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

Effect of Bushen Yiqi Huoxue Recipe on Placental Vasculature in Pregnant Rats with Fetal Growth Restriction Induced by Passive Smoking

Interactions of vascular endothelial growth factor （VEGF） with receptors VEGFR1/Fltl and VEGFR2/Flk1, and those of angiopoietins （Ang-1, Ang-2） with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation （D 15, D 18 and D21）. The rats were randomly assigned into 3 groups： normal group, model group [fetal growth restriction （FGR） model], and Bushen Tqi Huoxue （BYHR） recipe treatment group （BYHR group, the pregnant rats with FGR were treated with BYHR recipe）. Morphological analysis indicated that during initial villous formation, fetal nucle- ated erythrocytes （FNEs） appeared in maternal blood sinus （MBS）. Subsequently, FNEs were sur- rounded by endothelial cells to form fetal capillary （FC） and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining （EIS） in normal and BYHR groups. Whereas, villous formation was suppressed, normal in- crease in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flkl mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while de- creased on D21 in model group as compared with normal group and BYHR group. Immunohistochemi- cally, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D 15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.

Expression of soluble vascular endothelial growth factor receptor-1 and placental growth factor in fetal growth restriction cases and intervention effect of tetramethylpyrazine

Objective:To investigate the expression of soluble vascular endothelial growth factor receptor-1(sFlt-1) and placental growth factor(PLGF) in the fetal growth restriction(FGR) cases and the intervention mechanism of tetramelhylpyrazine.Methods:A total of 60 fetal growth restriction cases that admitted lo our hospital were randomly divided into ligustrazine intervention group(group A) and nutritional support group(group B).A total of 50 healthy pregnant women were also enrolled as control group(group C).Expression level of maternal serum sFlt1,FLGF and fetal growth parameters including HC,AC,FL,BPD,EFW as well as placenta PLGF,sFlt-1 mRNA expression were recorded and compared among the three groups.A total of 15 SD rats were selected and were divided into lliree groups.TMP group,alcohol and tobacco group and blank control group.Three groups of rats were dissected on the twentieth day of gestation.Result:Expression level of sFlt-1 and PLGF in group A was not significantly different from that of group C(P>0.05):but significant difference in SFlt1 and PLGF expression level was observed between group C and group B(P<0.05).Before treatment.HC,AC,FL,BPD and EFW of group A and group B were significant lower than those of group C.hut after treatment,those parameters in group A were significantly improved(P<0.05).In the animal experiment there was no significant difference in sFlt-1 between treatment group and FGR group without treatment or control group(P>0.05).There was significant difference in PLGF between FGR group with treatment and FGR group without treatment or control group(P<0.01).Conclusions:PLGF level is decreased and sFlt-1 increased in patients suffered from fetal growth restriction,and FGR rats show increased sFlt-1 and decreased PLGF.thus they can be indicator of the fetal growth restriction.Ligustrazinc can effectively improve sFlt-1,PLGF expression level in fetal growth restriction cases,which can be used as treatment for FGR.

Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood,Placental Size,and Risk for Fetal Growth Restriction:A Nested Case-control Study

Objective To explore the effects of prenatal exposure to polybrominated diphenyl ethers(PBDEs)on placental size and birth outcomes.Methods Based on the perspective Wenzhou Birth Cohort,this nested case-control study included 101 fetal growth restriction(FGR)and 101 healthy newborns.Maternal serum samples were collected during the third trimester and measured for PBDEs by gas chromatography tandem mass spectrometry.The basic information of mother-newborn pairs was collected from questionnaires,whereas the placental size and birth outcomes of newborns were obtained from hospital records.Results A total of 19 brominated diphenyle ether(BDE)congeners were detected in maternal serum samples.Higher concentrations of BDE-207,-208,-209,and∑19PBDEs were detected in FGR cases than in controls.Increased BDE-207,-208,-209,and∑19PBDEs levels in maternal serum were related to decreased placental length,breadth,surface area,birth weight,birth length,gestational age,and Quetelet index of newborns.After adjusting for confounders,BDE-207 and∑19PBDE concentrations in maternal serum were significantly associated with an increased risk of FGR.Conclusion A negative association was found between PBDE levels in maternal serum and placental size and birth outcomes.Prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth.

Effect of behavior training on learning and memory of young rats with fetal growth restriction

Objective: To investigate the effect of behavior training on the learning and memory of young rats with fetal growth restriction (FGR). Methods: The model of FGR was established by passive smoking method to pregnant rats. The new-born rats were divided into FGR group and normal group, and then randomly subdivided into trained and untrained group respectively. Morris water maze behavior training was performed on postnatal months 2 and 4, then learning and memory abilities of young rats were measured by dark-avoidance testing and step-down testing. Results: In the dark-avoidance and step-down testing, the young rats’ performance of FGR group was worse than that of control group, and the trained group was better than the untrained group significantly. Conclusion: FGR young rats have descended learning and memory abilities. Behavior training could improve the young rats’ learning and memory abilities, especially for the FGR young rats.

Impairments of spatial learning and memory in rat offspring with fetal growth restriction

Objective： Throughout the world, fetal growth restriction（FGR） is one of the most severe complications occurring during pregnancy. It is subsequently associated with neurologic abnormalities in chldren. Our aim was to investigate the spatial learning and memory ability of rat offspring born With FGR. Methods：A rat model of FGR was constructed using the method of passive smoking. Spatial learning and memory were studied in rat offspring born with FGR by assessing the animals＇ performance using the Morris water maze task. Results： At 1- and 2- months of age, both female and male offspring rats showed impairment of performance, while at 4 months of age, only female rats showed impaired performance. The FGR offspring spent a longer time swimming and used inefficient strategies（P〈 0.05, respectively）. However, there were no significant maze performance FGR effects in the 4 month old male rats. In all groups of FGR offspring, irrespective of age or sex, the time spent in the platform quadrant by the rat was significantly less than that in the control group（P〈 0.05）. Conclusion： The Morris water maze performance decreased in rat offspring born with FGR. It is suggested that FGR can cause impairments of spatial learning and memory in young animals.

Different Fetal and Neonatal Growth between Early- and Late-Onset Preeclampsia

Preeclampsia is a heterogeneous disease, and there are major differences in severity, fetal growth and poor placentation between early- and late-onset preeclampsia. Here, we examined the effect of onset period on fetal and neonatal growth in preeclampsia with a cross-sectional study including 102 pregnant women with preeclampsia visited Okayama University Hospital from 2009 to 2013. The subjects were retrospectively compared in terms of body mass index (BMI), weight gain during pregnancy, complications, weeks of delivery, neonatal body weight and BMI at birth, fetal growth restriction (FGR), small for gestational age (SGA), pathological findings in the placenta, and infant’s weight at 1 month after birth. Neonatal body weight and BMI at birth were significantly lower and the extent of FGR and the frequency of SGA were higher in early-onset group compared with late-onset group. Mean daily weight gain during the neonatal period was significantly lower in the early-onset group compared with the late-onset group, however the weight gain rate during the neonatal period in the early-onset group was higher than that in late-onset group. In conclusions, there are significant differences in fetal and neonatal growth between early- and late-onset preeclampsia and the catch up for growth might start during neonatal period.

miR-34c-5p靶向poFUT1对胎盘血管形成的影响

目的:探讨miR-34c-5p与poFUT1的靶向关系及对胎盘血管形成的影响。方法:利用ENCORI数据库预测miR-34c-5p与poFUT1的结合位点,采用双荧光素酶报告实验验证。随机选取2023年4至10月在郑州大学第三附属医院住院的胎儿生长受限(FGR)孕妇20例(FGR组),选择同期正常孕妇20例为对照。采用实时荧光定量PCR法检测两组胎盘组织中miR-34c-5p和poFUT1 mRNA的表达。取脐静脉内皮细胞,分组转染miR-34c-5p模拟物及其对照(NC)、miR-34c-5p抑制物及其NC、si-poFUT1 NC、si-poFUT1、si-poFUT1+miR-34c-5p抑制物,采用CCK-8法、Transwell实验以及成管实验检测细胞转染24、48、72、96 h后的增殖能力,转染48 h后的侵袭能力和成管能力。结果:FGR组和对照组胎盘组织中miR-34c-5p表达水平分别为(1.57±0.39)、(1.09±0.18),poFUT1 mRNA表达水平分别为(0.51±0.17)、(1.06±0.13),FGR组胎盘组织中miR-34c-5p表达水平高于对照组,poFUT1 mRNA表达水平低于对照组(P<0.05)。与miR-34c-5p模拟物NC组比较,模拟物组侵袭细胞数和管腔节点数减少,细胞增殖活性降低(P<0.05)。与miR-34c-5p抑制物NC组比较,抑制物组侵袭细胞数和管腔节点数增加,细胞增殖活性升高(P<0.05)。与si-poFUT1 NC组相比,si-poFUT1组侵袭细胞数和管腔节点数减少,细胞增殖活性降低(P<0.05),而si-poFUT1+miR-34c-5p抑制物组上述变化较si-poFUT1组部分逆转(P<0.05)。结论:miR-34c-5p可能通过调控poFUT1影响血管内皮细胞功能,从而影响胎盘的血管形成,参与FGR的发生。

胎儿生长受限患者胎盘组织中VEGFA、HIF-1α表达及临床意义

目的:探究胎儿生长受限(FGR)患者胎盘组织中血管内皮生长因子A(VEGFA)、缺氧诱导因子(HIF)-1α表达及临床意义。方法:选择2020年5月-2022年9月在本院确诊FGR并住院分娩的孕妇116例(FGR组)、分娩正常孕妇(新生儿正常)116例为对照组临床资料。qRT-PCR检测胎盘组织中VEGFA、HIF-1α的mRNA表达情况,免疫组化法检测VEGFA、HIF-1α的蛋白表达情况。Pearson相关性分析VEGFA与HIF-1α的相关性以及与FGR患者临床资料相关性;多因素logistic回归分析影响FGR发生的因素。结果:FGR组VEGFA蛋白阳性表达率(25.9%)低于对照组(64.7%),HIF-1α蛋白阳性表达率(67.2%)高于对照组(24.1%);FGR组胎盘组织中VEGFA mRNA表达水平(0.75±0.20)低于对照组(1.00±0.23),HIF-1α mRNA表达水平(1.26±0.25)高于对照组(1.01±0.19)(均P<0.05)。FGR患者胎盘组织中VEGFA mRNA与HIF-1α mRNA呈负相关(P<0.05)。FGR患者新生儿出生1 min Apgar评分、胎盘重量、胎盘体积、新生儿体重与VEGFA表达水平呈正相关,与HIF-1α表达水平呈负相关;HIF-1α升高为影响FGR发生的危险因素,VEGFA升高为保护因素(均P<0.05)。结论:FGR患者胎盘组织中VEGFA低表达、HIF-1α高表达,二者影响FGR的发生及新生儿出生质量。

三维能量多普勒超声参数联合胎盘生长因子对早发型胎儿生长受限的预测价值

目的探讨三维能量多普勒超声参数联合胎盘生长因子(PLGF)对早发型胎儿生长受限(FGR)的预测价值。方法选取早发型FGR孕妇80例为FGR组,另选取同期产检健康孕妇50例为对照组。在孕11~13周+6对所有研究对象进行三维能量多普勒超声检查,收集胎盘容积(PV)、血管化指数(VI)、血流指数(FI)、血管化-血流指数(VFI)等指标。在孕14~16周+6检测所有研究对象血清PLGF水平。结果FGR组的PV、VI、FI、VFI以及血清PLGF水平均低于对照组,差异有统计学意义(P<0.05)。多元Logistic回归方程分析显示,PV、VI、FI、VFI以及血清PLGF水平过低是早发型FGR的危险因素(P<0.05)。受试者工作特征(ROC)曲线分析显示,PV、VI、VFI以及血清PLGF均对早发型FGR有一定的预测价值,曲线下面积分别为0.723(95%CI:0.629~0.817)、0.776(95%CI:0.693~0.860)、0746(95%CI:0.653~0.839)、0.799(95%CI:0.713~0.884),FI对早发型FGR的预测价值一般,曲线下面积为0.625(95%CI:0.524~0.725)。经分析显示,PLGF联合VI以及PLGF联合VFI对早发型FGR的预测价值较好,PLGF联合VI的敏感度、特异度和约登指数分别为86.25%、76.00%、0.623,PLGF联合VFI的敏感度、特异度和约登指数分别为81.25%、80.00%、0.613。结论三维能量多普勒超声参数联合PLGF对早发型FGR有一定的预测价值,可用于临床筛查早发型FGR高风险人群。

血栓弹力图联合超声定量参数对胎儿生长受限的诊断效能研究

目的:研究血栓弹力图联合超声定量参数对胎儿生长受限(fetal growth restriction,FGR)的诊断效能。方法:收集2021年7月—2023年5月郑州市妇幼保健院收治的50例FGR孕妇(FGR组),并选取同期同年龄段胎儿发育正常的50例孕妇作为对照(对照组)。比较两组血栓弹力图指标[最大振幅(maximum amplitude,MA)、α角(Angle)、凝血时间(coagulation time,K)、凝血反应时间(coagulation response time,R)]、脐动脉与大脑中动脉阻力指数(resistance index,RI)、搏动指数(pulsation index,PI)、血流收缩末期/舒张末期峰值(end-systolic/end-diastolic peak value,S/D)、脑胎盘率(cerebroplacental rate,CPR)、体重、腹围,二元相关分析、偏相关分析研究血栓弹力图、超声定量参数与体重、腹围的关系,受试者工作特征(receiver operating characteristic,ROC)曲线分析血栓弹力图、超声定量参数及联合诊断FGR价值。结果:FGR组孕中期、孕晚期、分娩前R、K均低于对照组,Angle、MA高于对照组(P<0.05);FGR组孕中期、孕晚期、分娩前脐动脉S/D、脐动脉PI、脐动脉RI高于对照组,大脑中动脉S/D、大脑中动脉PI、大脑中动脉RI、CRP低于对照组(P<0.05);FGR组孕中期、孕晚期、分娩前体重、腹围低于对照组(P<0.05);二元相关分析显示,分娩前各血栓弹力图、超声定量参数与体重、腹围相关性更强(P<0.05);偏相关分析显示,分娩前R、K、大脑中动脉RI、CRP与体重、腹围呈正相关,Angle、MA、脐动脉S/D、脐动脉PI、脐动脉RI仍与体重、腹围呈负相关(P<0.05);分娩前血栓弹力图、超声定量参数联合诊断FGR的ROC曲线下面积高于各单一指标(P<0.05)。结论:FGR孕妇接受血栓弹力图联合超声定量检测,可有效监测孕产妇在不同时期凝血功能变化和胎儿血流动力学变化,其联合诊断FGR具有较高价值。

血栓弹力图在胎儿生长受限早期诊断中的应用意义

目的探讨血栓弹力图检测在胎儿生长受限(Fetal Growth Restriction,FGR)早期诊断中的应用意义。方法选择2021年1月—2023年11月本院收治的41例孕妇为研究对象,按32孕周以前是否发生FGR分为实验组(20例)和对照组(21例)两组。检测并观察所有研究对象的血栓弹力图(Thromboelastography,TEG)相关凝血参数[凝血反应时间(Reaction Time,R)、血凝块形成时间(kinetics time,K)、角度(Angle)和血栓最大振幅(Maximum Amplitude,MA)];血小板计数(Platelet Count,PLT)常规凝血指标参数[活化部分凝血活酶时间(Activated Partial Thromboplastin Time,APTT)、纤维蛋白原(Fibrinogen,Fib)、凝血酶原时间(Prothrombin Time,PT)、凝血酶时间(Thrombin Time,TT)、D-二聚体(D-dimer,D-Di)]以及标准化狼疮抗凝物比值(Normalized Lupus Anticoagulants Ratio,NLR),比较两组间各项指标差异。采用具有显著差异的凝血相关指标的受试者工作特征曲线(Receiver Operating Characteristic curve,ROC)下面积(Area Under Curve,AUC),得出凝血相关指标对早发型FGR的预测价值。结果两组各项凝血相关指标中,实验组PLT计数及MA高于对照组,差异具有统计学意义(P<0.05),其他凝血相关指标差异无统计学意义(P>0.05)。ROC曲线结果显示,MA诊断早发型FGR的曲线下面积(AUC)为0.823。实验组的MA与PLT呈正相关(r=0.5590,P=0.0104)。结论TEG检测对FGR早期诊断具有应用意义。

以胎儿生长受限为首发症状子痫前期的临床特征及危险因素

目的探讨以胎儿生长受限(FGR)为首发症状子痫前期的临床特征及危险因素,为产前咨询及处理提供参考。方法选取2018年1月至2023年1月至郑州大学第一附属医院产科住院的120例FGR患者为研究对象,其中40例患者并发子痫前期作为研究组,80例患者未并发子痫前期作为对照组,回顾性对比分析两组患者的一般特征、妊娠期合并症、母体及围产儿结局等资料。采用logistic回归模型分析FGR并发子痫前期的危险因素,并计算ROC曲线下面积分析预测子痫前期的效能。结果(1)一般特征:研究组与对照组孕前体重指数、诊断FGR时孕周比较,差异有统计学意义(P<0.05);两组年龄、初产妇占比、有无规律产检、是否辅助生殖、有无不良孕产史比较,差异无统计学意义(P>0.05)。(2)妊娠期合并症:研究组与对照组蛋白尿、抗磷脂抗体阳性率比较,差异有统计学意义(P<0.05);两组合并妊娠高血糖、甲状腺功能减退、脐带扭转、子宫畸形、羊水少、贫血比较,差异无统计学意义(P>0.05)。(3)母体妊娠结局:两组患者的妊娠并发症、住院天数、剖宫产率比较,差异有统计学意义(P<0.05)。(4)新生儿结局:研究组中医疗性引产6例,对照组4例;两组患者产时存活新生儿中早产、分娩孕周、新生儿体重比较,差异有统计学意义(P<0.05);研究组中新生儿并发症脑室出血、新生儿窒息、呼吸窘迫综合征、代谢性酸中毒的发生概率高于对照组,差异有统计学意义(P<0.05),但两组围产儿出生后死亡率比较差异无统计学意义(P>0.05)。(5)logistic回归分析显示:诊断FGR时孕周、孕前体重指数是以FGR为首发症状子痫前期的独立危险因素;ROC曲线分析显示,诊断FGR时孕周(AUC=0.817,95%CI为0.723~0.911)和孕前体重指数(AUC=0.714,95%CI为0.621~0.807)可用于子痫前期的风险预测,且两者联合预测(AUC=0.860,95%CI为0.785~0.934)的效能优于单一指标。结论FGR并发子痫前期可增加母儿不良妊娠结局,诊断FGR时孕周和孕前体重指数是子痫前期的独立危险因素,加强对预警因素的监测和处理,有助于早期识别子痫前期,改善母儿预后。

妊娠期糖尿病孕妇血清微小RNA-29a-3p、胰岛素样生长因子-1表达水平及其对胎儿生长受限的预测价值

目的探究妊娠期糖尿病(GDM)孕妇血清微小核糖核苷酸(micro RNA,miR)-29a-3p、胰岛素样生长因子-1(IGF-1)表达水平及其对胎儿生长受限的预测价值。方法选择2019年8月—2022年12月在本院202例就诊分娩的GDM患者(132例)及同期体检健康孕妇(70名)作为研究对象,就诊分娩的GDM患者为患病组,同期体检健康孕妇为对照组。根据GDM患者是否伴有胎儿生长受限分为GDM组和胎儿生长受限组,GDM组88例,胎儿生长受限组44例。qRT-PCR法检测血清miR-29a-3p水平,放射免疫法检测血清IGF-1表达。TargetScanHuman网站预测miR-29a-3p与IGF-1靶向关系。分析miR-29a-3p、IGF-1及其与胰岛素水平、新生儿体重、新生儿身长的相关性;Logistic回归分析GDM孕妇发生胎儿生长受限的影响因素;ROC曲线分析血清miR-29a-3p,IGF-1水平评估GDM孕妇发生胎儿生长受限的预测价值。结果患病组孕妇血清miR-29a-3p水平高于对照组,IGF-1水平低于对照组,差异有统计学意义(P<0.05);GDM组患者血清miR-29a-3p水平低于胎儿生长受限组,IGF-1水平高于胎儿生长受限组,差异有统计学意义(P<0.05);miR-29a-3p直接靶向作用于IGF-1表达;GDM组和胎儿生长受限组孕妇胰岛素、新生儿体重、新生儿身长比较,差异具有统计学意义(P<0.05)。相关性分析表明,血清miR-29a-3p与IGF-1水平呈负相关(r=-0.402,P<0.05);血清miR-29a-3p水平与新生儿体重、新生儿身长呈负相关,IGF-1与新生儿体重、新生儿身长呈正相关(P<0.05)。Logistic回归分析表明,miR-29a-3p,IGF-1是GDM孕妇发生胎儿生长受限的影响因素(P<0.05)。血清miR-29a-3p,IGF-1水平联合评估GDM孕妇发生胎儿生长受限的曲线下面积(AUC)为0.877(95%CI:0.808-0.928),显著高于两指标单独检测(Z_(miR-29a-3p-联合)=2.893,P=0.004;Z_(IGF-1-联合)=2.810,P=0.005)。结论GDM孕妇血清miR-29a-3p水平上调,IGF-1水平下调,与胎儿生长受限密切相关,二者联合对GDM孕妇发生胎儿生长受限有较好预测价值。

超声监测结合BUN、UA水平预测PE并发FGR孕产妇不良结局价值

目的:探讨超声胎儿监测结合血尿素氮(BUN)和尿酸(UA)水平预测子痫前期(PE)并发胎儿生长受限(FGR)患者不良结局价值。方法:回顾性收集2020年1月-2023年5月本院就诊的PE患者,其中并发FGR 106例为观察组,未并发FGR患者106例为对照组,比较两组血BUN、UA水平,超声胎儿静脉导管收缩期峰值速度(PSV)、舒张期峰值速度(EDV)、平均时间最大血流速度(Vmax),统计新生儿及孕妇不良结局。结果:观察组血BUN(5.03±1.22mmol/L)、UA(435.54±52.13mmol/L)高于对照组(4.01±1.30 mmol/L、391.60±60.88 mmol/L),PSV(0.85±0.12cm/s)、EDV(0.78±0.11cm/s)、Vmax(0.81±0.13cm/s)低于对照组(0.89±0.11 cm/s、0.96±0.14 cm/s、0.98±0.12 cm/s),新生儿不良结局总发生率(67.9%)高于对照组(15.1%),孕妇不良妊娠结局总发生率(38.7%)高于对照组(20.8%);观察组发生新生儿不良结局患者血BUN、UA高于未发生新生儿不良结局患者,而超声胎儿静脉血流参数均低于未发生新生儿不良结局患者(均P<0.05)。血BUN、UA、PSV、EDV、Vmax及联合预测新生儿不良结局的曲线下面积分别为0.735、0.760、0.643、0.809、0.670和0.706,联合预测的灵敏性达到100.0%。结论:PE并发FGR患者BUN、UA水平异常升高,超声胎儿静脉血流参数异常降低,上述超声及血指标预测新生儿不良结局有一定临床指导价值。

孕晚期超声S/D值联合尿酸水平预测子痫前期并发胎儿生长受限不良妊娠结局的临床价值

目的:探讨孕晚期超声脐动脉收缩期与舒张期峰值流速比(S/D)值联合尿酸水平预测子痫前期(PE)并发胎儿生长受限(FGR)不良妊娠结局的临床价值。方法:选取本院2018年1月-2023年5月收治的PE患者150例作为研究对象,根据患者是否并发FGR分为FGR组(n=54)和非FGR组(n=96),比较2组临床资料、孕晚期超声S/D值、血清生化指标[尿酸、白蛋白、乳酸脱氢酶(LDH)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肌酐]以及不良妊娠结局。采用logistic回归分析考察PE患者FGR的影响因素,并采用受试者工作特征(ROC)曲线分析孕晚期超声S/D值联合尿酸对PE并发FGR患者不良妊娠结局的预测价值。结果:FGR组S/D值,尿酸、LDH、ALT水平均高于非FGR组,白蛋白水平低于非FGR组(P<0.05)。Logistic回归分析结果显示,S/D值、尿酸为影响PE患者FGR的独立危险因素(P<0.05)。FGR组胎儿窘迫、新生儿窒息、围产儿死亡等不良妊娠结局的总发生率高于非FGR组(P<0.05);不良妊娠结局组S/D值、尿酸水平高于非不良妊娠结局组(P<0.05)。ROC曲线显示,S/D值联合尿酸预测PE并发FGR患者的不良妊娠结局的曲线下面积(AUC)为0.812,高于S/D值的0.779、尿酸的0.692。结论:孕晚期超声S/D值和尿酸是PE患者FGR的影响因素,二者联合可用于预测PE并发FGR患者不良妊娠结局。

母血DCN、sEng、PLGF水平与早发型胎儿生长受限的相关性分析

目的:分析母血核心蛋白聚糖(DCN)、可溶性内皮因子(sEng)、胎盘生长因子(PLGF)与早发型胎儿生长受限(FGR)的相关性。方法:选取2021年1—12月于湖南省妇幼保健院分娩的120例FGR孕妇作为研究对象,其中早发型FGR 42例纳入早发型FGR组,晚发型FGR 78例纳入晚发型FGR组。选取同期分娩正常胎儿的120例孕妇作为对照组。比较三组母血血清DCN、sEng、PLGF水平及三组新生儿生长发育指标,分析母血血清DCN、sEng、PLGF水平与早发型新生儿生长发育指标的相关性。结果:早发型FGR组DCN、sEng水平高于晚发型FGR组、对照组,PLGF水平低于晚发型FGR组、对照组,差异有统计学意义(P<0.05);晚发型FGR组、对照组DCN、sEng、PLGF水平比较,差异无统计学意义(P>0.05)。三组新生儿体质量、腹围、头围、股骨长比较,早发型FGR组<晚发型FGR组<对照组,差异有统计学意义(P<0.05)。DCN、sEng水平与早发型FGR新生儿体质量、腹围、头围、股骨长呈负相关(P<0.05);PLGF与早发型FGR新生儿体质量、腹围、头围、股骨长呈正相关(P<0.05)。结论:母血DCN、sEng、PLGF水平与早发型FGR存在相关性,可用于早发型FGR的筛查、诊断。