胎儿生长受限与印痕现象研究进展

胎儿生长受限（FGR）是围生期主要并发症之一．发生原因与妊娠妇女、胎儿及胎盘三种因素有关。研究表明，FGR儿在成人期易患冠心病、高血压、中风、糖尿病、肥胖等疾病．表明很多成年期疾病可能在胎儿发育期就已被编程，这种现象称为印痕现象。胎儿发育时期营养改变能直接或间接影响胎儿各器官系统生长和成熟；胎儿营养改变和宫内糖皮质激素暴露二者可能通过类似途径引起机体内环境长期变化，导致成年疾病风险增加。节俭表型假说、预言适应性反应假说及胎儿胰岛素假说有助于理解印痕现象。瘦素、儿茶酚胺、葡萄糖转运蛋白、胰岛素样生长因子-1、脂联素等可能是印痕现象发生的重要因子。对印痕现象的理解有助于对某些成年期疾病发生的认识．对FGR儿早期临床干预对降低其特定疾病风险系数有重要意义。     

孕早期胎儿生长受限与孕晚期胎儿生长受限的相关性研究

目的:探讨孕早期胎儿生长受限（FGR）与孕晚期FGR的相关性,为FGR的早期预防和管理提供依据。方法:选择2012年5月至2017年5月在广州市妇女儿童医疗中心进行定期产前检查并住院分娩的孕妇共9637例,计算孕早期(孕10+0～13+6周)顶臀径Z评分,<-1分定义为孕早期FGR组,≥-1为孕早期非FGR组,分析孕早期FGR与孕晚期FGR的相关性,并根据是否合并妊娠期糖尿病进行分层分析。结果:孕晚期FGR477例,发生率为4.9%。调整孕妇年龄、孕前体质量指数（BMI）、孕产史、受孕方式、PAPP-A MoM、β-hCG MoM、是否合并妊娠期糖尿病和是否合并妊娠期高血压等混杂因素后,Logistics回归分析显示,孕早期FGR组发生孕晚期FGR的风险是孕早期非FGR组的1.88倍（95%CI 1.51～2.34）;在无妊娠期糖尿病的孕妇中,孕早期FGR组发生孕晚期FGR的风险是孕早期非FGR组的1.73倍（95%CI 1.37～2.19）;而在合并妊娠期糖尿病的孕妇中,孕早期FGR组发生孕晚期FGR的风险是孕早期非FGR组的3.81倍（95%CI 1.97～7.39）。结论:孕早期FGR与孕晚期FGR发生风险增加相关,在合并妊娠期糖尿病的孕妇中这种关联更强,应重点关注孕早期顶臀径低于同孕龄的孕妇,以预防或早期发现孕晚期FGR。     

胎儿生长受限与死胎

死胎的发生与胎儿生长受限(FGR)有关。FGR是死胎发生的重要原因之一,两者病因和发病危险因素相似。但发生FGR因素复杂而非单一。识别FGR潜在的危险因素及早期发现、早期诊断、早期干预是降低各类因素FGR发生死胎的关键。     

胎儿生长受限病因研究进展

胎儿生长受限 (fetal growth restriction,FGR)是指胎儿体重低于其孕龄平均体重的第 10百分位数或低于其平均体重的 2个标准差 ,为产科常见疾病 ,发生率各家报道不一。据 1998年的资料估计 ,发展中国家每年约有 30 0 0万 FGR儿出生 ,占所有新生儿的 2 3.8%。瑞典等发达国家 FGR的发生率约为 2 %～ 3% ,全国出生缺陷协作组的调查表明 :我国 FGR发生率为 6 .39% ,围产儿死亡率占总围产儿死亡率的 4 2 .3% ,新生儿患病率升高 ,乃至以后的儿童期营养不良和成年后的糖尿病。FGR中约有 4 0 %属“原因不明”,现就感染、营养、遗传、免疫等几…     

胎儿生长受限分类与管理研究进展

胎儿的生长受母体疾病、胎盘功能、胎儿遗传等多因素影响。胎儿生长受限(FGR)是临床产科极具挑战的问题,围产期患病和死亡率较高,远期预后不良。回顾国内外FGR最新研究进展、指南及专家共识,重点针对非遗传因素FGR的定义分类、超声监测和分娩时机进行综述,为FGR的临床管理提供一定的科学依据,以期改善FGR胎儿的近、远期结局。     

选择性胎儿生长受限胎儿预后研究进展

单绒毛膜双胎中,10%～15%会发生选择性胎儿生长受限（selective fetal growth restriction,sFGR）。sFGR可通过脐动脉多普勒波形分为3种类型。sFGR胎儿宫内死亡的发生率高,出生胎龄小,可有脑损伤、心肌肥厚、右心室流出道梗阻、肠穿孔、胰岛素分泌异常等多系统不良预后,且不同分型的s...     

胎儿生长受限预测方法的研究进展

胎儿生长受限(FGR)是一种常见的妊娠并发症,其病因复杂,约40%的患者病因不明。妊娠期对FGR的诊断并不容易,往往需产后才能确诊,因此对其进行早期预测的方法一直是国内外研究的热点,尤其是孕期超声多普勒的异常及胎盘、血清中等多种生物分子的异常表达。现将对FGR早期预测的超声多普勒及生物学指标进行归纳综述。     

胎儿生长受限与成年胰岛素抵抗的研究进展

胎儿生长受限（fetal growth restriction，FOR），以前也称胎儿宫内发育迟缓（intrauterine growth retardation，IU—OR），是指胎儿出生体重低于相应孕周平均体重第10百分位数或低于平均体重两个标准差。近年来国内外研究表明FOR不仅影响胎儿期和儿童期的智力体格发育，成年后由于机体胰岛素抵抗（insulin resistance，IR）导致代谢综合征（包括2型糖尿病、高血压、高血脂、冠心病等）的易感性也明显增加。[第一段]     

胎儿生长受限的筛查

胎儿生长受限危害胎儿存活及健康,越来越受到围产工作者的关注,胎儿生长受限的筛查有助于针对筛查高风险孕妇加强监护,降低晚孕期死胎、死产和新生儿死亡。文章就目前胎儿生长受限筛查的意义和常见的筛查方法及进展作一综述。     

胎儿生长受限的管理新进展

胎儿生长受限(FGR)是妊娠期常见并发症,严重危害胎儿健康。目前,关于FGR的治疗方法有限、且疗效不显著,使得FGR的管理成为国内外产科关注的热点问题之一。本文基于最新观点,提出了FGR的诊断方法,有效监测胎儿生长发育的手段,并根据病情变化的不同阶段提出了如何选择最佳的分娩时机,以有利于改善新生儿的预后,对降低围产儿的发病率及死亡率至关重要。     

Placenta and fetal growth restriction

The placenta, as the vector for all maternal-fetal oxygen and nutrient exchange, is a principal influence on birthweight. Placental weight summarizes laterally expanding growth of the chorionic disc, and villous arborization yielding the nutrient exchange surface. These different growth dimensions alter fetoplacental weight ratio and ponderal index, and thus may modify placental functional efficiency. The placenta may show a range of histopathologies, some of which are also associated with fetal growth restriction. Different fetal intrinsic abilities to compensate for gross and histo-pathology may clarify the imperfect relationships between fetal growth and both intrauterine pathology, and the long-term health risks associated with poor fetal growth.     

Stillbirth and fetal growth restriction

Objective: To confirm the role of fetal growth restriction (FGR) as a cause of stillbirth, and to compare diagnostic accuracy of customized fetal growth and population-based standards in identifying FGR within a pathological population of early and late stillbirths. Methods: Retrospective study on a cohort of 189 stillbirths occurred in single pregnancy between January 2006 and September 2011. Unexplained stillbirths, defined by Aberdeen-Wigglesworth and ReCoDe classifications, were evaluated on the basis of fetal birthweight with both Tuscany population and Gardosi customized standards. Unexplained stillbirths have been classified as early or late depending on the gestational age of occurrence. Results: Aberdeen-Wigglesworth classification, applied to the 189 cases of stillbirth, left 94 unexplained cases (49.7%), whereas the ReCoDe classification left only 40 (21%). By applying population standards to the 94 unexplained stillbirths we have identified 31 FGRs (33% of sample), while customized standards identified 54 FGRs (57%). Customised standards identified a larger number of FGRs with respect to population standards during the third trimester (i.e. 51% vs. 25% respectively) than in the second trimester (73% vs. 54% respectively) (p = 0.05). Conclusions: Customized standards have a higher diagnostic accuracy in identifying FGRs especially during the third trimester.     

Thrombophilia and fetal growth restriction

OBJECTIVE: Genetic thrombophilia may represent a new risk factor for obstetrical complications. The aim of the study was to determine which subgroups may be associated with genetic thrombophilia for small for gestational age infants (SGA). METHODS: A case-control study was performed in three different maternity wards in Normandy. Cases (n=203) were women who had pregnancies complicated by unexplained SGA infants defined as a birth weight below the 3rd centile and control subjects (n=203) were women who had infants with birth weight > or =10th centile. Patients were tested in the immediate postpartum period and 2 months later for factor V Leiden mutation, and prothrombin 20210A mutation. Frequencies of these mutations were observed in different subgroups of SGA infants depending on pregnancy or neonatal outcomes usually associated with intrauterine growth restriction (IUGR), and were then compared with the overall prevalence for these mutations detected in the control group. RESULTS: Prevalences for factor V Leiden mutation (or=2.58; 95% confidence interval: 0.83-8.04), prothrombin 20210A mutation (or=2.03; 95% confidence interval: 0.51-8.01), were comparable between cases and controls (4.9% versus 1.9% and 2.9% versus 1.4%, respectively). Frequencies for these two polymorphisms significantly increased in subgroups of SGA infants with a normal Pourcelot index (13/133 versus 7/203; P=0.04), a gestational age > or =37 weeks of gestation (15/143 versus 7/203; P=0.01), a vaginal delivery (11/117 versus 7/203; P=0.04), a birth weight > or =2000 g (12/121 versus 7/203; P=0.03), no admission to paediatric ward (11/116 versus 7/203; P=0.01), a low Ponderal index <2.5(e) centile (6/45 versus 7/203; P=0.04), and normal head circumference >10th centile (7/53 versus 7/203; P=0.01) in comparison with the control group. CONCLUSIONS: An association was found between polymorphisms for factor V Leiden and prothrombin, and asymmetrical intrauterine growth restriction with immediate favourable neonatal outcomes.     

Placental pathology in fetal growth restriction

Objectives

One of the causes of intrauterine fetal growth restriction (FGR) can be pathology of the placenta. The aim of this study was to compare macroscopic and microscopic changes of the placentas from intrauterine growth restricted fetuses with those from normally developed fetuses, in order to test the hypothesis that vascular damage due to decreased maternal vascular perfusion may be responsible for FGR.

Study design

Between May 2007 and December 2008 we performed detailed macroscopic and histological examination of singleton placentas of 50 consecutive neonates with fetal growth restriction (FGR group) and compared them to 50 normal fetuses, born next to an FGR case, as a control group.

Results

Gestational age, birth weight, spontaneous delivery rate, mean weight of the placenta and the fetal-placental weight ratio were all lower in the FGR group than in the control group (p < 0.05). Thickening of the villous trophoblastic basal membrane, incidence of villous infarction, presence of thrombi or haematomas and the incidence of villitis were more common in the FGR group than in the controls (p < 0.05). There were, however, no significant differences in perivillous fibrin deposition, stromal fibrosis and cytotrophoblast proliferation between the groups. In FGR women who smoked, intervillous haematomas and villous infarction were more common (p < 0.05) than in controls.

Conclusions

All macroscopic and microscopic pathological changes associated with FGR were directly linked to reduction of placental blood flow. As smoking is a main risk factor for these placental abnormalities these results emphasize the need to persuade women to quit smoking not only during pregnancy, but even better long before pregnancy.     

Perinatal mortality and fetal growth restriction

Stillbirths are the largest component of perinatal mortality. Most are currently classified as 'unexplained', which is not helpful for counselling and individual care or for setting priorities for maternity services. The new ReCoDe classification reduces the number of stillbirths categorized as 'unexplained' from 66 to 14%. Both stillbirths and neonatal deaths are strongly associated with fetal growth restriction, and increased awareness of intrauterine growth is essential for any strategies which seek to avoid adverse perinatal outcome.     

Origins of fetal growth restriction

Regulation of growth of the fetus and its placenta begins before pregnancy. Early in pregnancy the mother sets the rate of growth of the fetus on a trajectory, which may be modified by events later in pregnancy.Low maternal weight for height, history of previous small babies, maternal undernutrition, pregnancy disorders, e.g. pre-eclampsia, are associated with low birthweight. Maternal smoking is a major factor in developed countries; infections and undernutrition in developing countries.Recently, there has been emphasis on adverse long-term outcomes including ischaemic heart disease, hypertension and diabetes associated with poor fetal growth. Experimental studies in animals show that some of these outcomes can readily be induced by restriction of fetal growth.Progress in determining successful treatments to improve the growth of the fetus has lagged behind these epidemiological and experimental findings. However, nutrient supplements improve growth in undernourished women and smoking cessation also improves fetal size and outcome.     

Screening for fetal growth restriction

Since antenatal detection of fetal growth restriction, defined as birth weight <10% for gestational age, can reduce perinatal morbidity with antepartum testing and use of Doppler, it is imperative that there be a greater effort to detect the growth abnormality. According to a well-conducted randomized clinical trial, all uncomplicated pregnancies should have sonographic assessment of birth weight at 30-32 weeks and at 36-37 weeks. An increased awareness not only of the risk factors but also of the associated probability of abnormal growth can identify the cohorts that would benefit from uterine artery Doppler in 2nd trimester. Among patients at risk for suboptimal growth, Doppler of the umbilical artery improves the detection rate.