Intrauterine restriction (IUGR)

Perinatal mortality and morbidity is markedly increased in intrauterine growth restricted (IUGR) fetuses. Prenatal identification of IUGR is the first step in clinical management. For that purpose a uniform definition and criteria are required. The etiology of IUGR is multifactorial and whenever possible it should be assessed. When the cause is of placental origin, it is possible to identify the affected fetuses. The major complication is chronic fetal hypoxemia. By monitoring the changes of fetal vital functions it is thus possible to improve both management and outcome. The timing of delivery is crucial but the optimal management scheme has not yet been identified. When IUGR is identified at very early gestational ages, serial assessments of the risk of continuing the in utero fetal life under adverse conditions versus the risks of the prematurity should be performed. Delivery of IUGR fetuses should take place in centers where appropriate neonatal assistance can be provided. Careful monitoring of the IUGR fetus during labor is crucial as the IUGR fetus can quickly decompensate once uterine contractions have started.     

Intrauterine Growth Restriction: Screening,Diagnosis, and Management

BackgroundIntrauterine growth restriction (IUGR) is an obstetrical complication, which by definition would screen in 10% of fetuses in the general population. The challenge is to identify the subset of pregnancies affected with pathological growth restriction in order to allow intervention that would decrease morbidity and mortality.ObjectiveThe purpose of this guideline is to provide summary statements and recommendations and to establish a framework for screening, diagnosis, and management of pregnancies affected with IUGR.MethodsAffected pregnancies are compared with pregnancies in which the fetus is at an appropriate weight for its gestational age. History, physical examination, and laboratory investigations including biochemical markers and ultrasound characteristics of IUGR are reviewed, and a management strategy is suggested.EvidencePublished literature in English was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library in January 2013 using appropriate controlled vocabulary via MeSH terms (fetal growth restriction and small for gestational age) and key words (fetal growth, restriction, growth retardation, IUGR, low birth weight, small for gestational age). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.ValuesThe quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table).Benefits, harms, and costsImplementation of the recommendations in this guideline should increase clinician recognition of IUGR and guide intervention where appropriate. Optimal long-term follow-up of neonates diagnosed as IUGR may improve their long-term health.     

Intrauterine growth restriction (IUGR): biometric and Doppler assessment

Intrauterine growth restriction (IUGR) is a common complication in pregnancy and influences morbidity and mortality at all stages of life. Historically, the management of IUGR has been dependent on antenatal biophysical testing and umbilical artery Doppler studies. With recent Doppler studies of the fetal central circulation, including intracardiac flows and the ductus venosus, better timing of delivery to minimize morbidity may be possible. This review will provide the reader with tools to diagnose IUGR, more accurately date the IUGR pregnancy with poor dating criteria, and better assess the condition of the IUGR fetus. A brief review of animal models of IUGR is presented to demonstrate research directions for answering human clinical questions and potentially carrying therapeutic intervention from the bench to the bedside.     

胚胎宫内生长受限临床分析-附2例报告

目的总结和探讨孕早期胚胎宫内生长受限的临床过程和处理方法.方法对2例孕早期胚胎宫内生长受限的临床资料进行分析.结果宫内生长受限的胚胎给予治疗后能继续正常生长.结论孕早期存在胚胎宫内生长受限的现象.     

Intrauterine Growth Restriction in Spontaneously Hypertensive Rats

Objective: To determine whether a rise in systolic blood pressure (SBP) ≥ 30 mm Hg and/or diastolic blood pressure (DBP) ≥ 15 mm Hg in the absence of hypertension during pregnancy is associated with adverse pregnancy outcomes. Method: We conducted a retrospective, longitudinal study of 1498 pregnant women without hypertension or proteinuria in the first trimester. The blood pressure levels measured during the first (7.8 ± 2.3 weeks), second (20.7 ± 1.2 weeks), and third trimesters (38.6 ± 1.5 weeks) were analyzed. The perinatal outcome was compared between women who exhibited a rise in SBP ≥ 30 mm Hg and/or DBP ≥ 15 mm Hg during pregnancy (large Δ BP group) and women who did not (small Δ BP group) using one way analysis of variance, chi‐square test, or Fisher's exact test. The contribution of gestational hypertension and a large Δ BP to the development of adverse pregnancy outcomes was evaluated using multivariate logistic regression analysis. Results: Of 1441 women who remained normotensive (SBP < 140 mm Hg and DBP < 90 mm Hg) during pregnancy, 238 (16.5%) and 1203 (83.5%) belonged to the large Δ BP and small Δ BP groups, respectively. There were no significant differences between the two groups in the occurrence rate of gestational proteinuria, preterm deliveries, low‐birth‐weight infants, or small‐for‐gestational age infants. A large Δ BP was not a risk factor in itself for the occurrence of gestational proteinuria or small‐for‐gestational age infants after controlling for the effect of gestational hypertension. Conclusion: A rise in SBP ≥ 30 mm Hg and/or DBP ≥ 15 mm Hg is not a risk factor of adverse outcome among women who remain normotensive during pregnancy.     

Placental MRI in Intrauterine Fetal Growth Restriction

ObjectiveOur objectives were to determine if MR imaging of the placenta could demonstrate a specific placental phenotype in small for gestational age fetuses with increasing severity of fetal growth restriction, and if MRI findings at the time of scan could be used to predict fetal or neonatal mortality.MethodWe included singleton growth restricted fetuses with increasing severity of fetal growth restriction secondary to placental insufficiency. 20 growth restricted fetuses and 28 normal fetuses were scanned once during pregnancy at varying gestations. MRI scans were performed on a 1.5T system using ssFSE sequences through the uterus. Data was collected on the severity of fetal growth restriction and pregnancy outcome, including clinical neonatal details, perinatal mortality, and birthweight and centile. Placental volume, maximal placental thickness, the placental thickness to volume ratio, the placenta to amniotic fluid signal intensity ratio, and the presence of abnormal signal intensity consistent with placental pathology were noted. In a subset of patients, histopathological diagnosis was compared with the MRI appearance of the placenta.ResultsThere was a significant increase in the placental volume affected by pathology in growth restricted fetuses (p < 0.001). The placental appearance was also thickened and globular, with an increase in the placental thickness to volume ratio (p < 0.001). Although placental volume increased with increasing gestation, it remained reduced in the growth restricted fetuses (p = 0.003). There was a significant correlation between the severity of fetal growth restriction and the placental volume affected by pathology, the placental thickness to volume ratio, and the placental volume. ROC analysis showed that fetal or neonatal death was predicted by the percentage of abnormal signal intensity consistent with placental pathology (p = 0.002). The presence of a thickened, globular placenta and a maximal placental thickness to volume ratio above the 95% confidence limit for gestation was significantly associated with an increased incidence of fetal or neonatal mortality (relative risk = 1.615, p = 0.001 and relative risk = 7, p < 0.001).ConclusionsThe MRI appearance of the placenta provides an indication of the severity and underlying disease process in fetal growth restriction. In units where MRI imaging of the growth restricted fetus occurs, we suggest that the assessment of the placenta should also occur as it may contribute to management decisions in cases at the threshold of viability. It may have a role to play in monitoring disease severity, and the effect of future interventions designed to improve placental function.     

Low Aboriginal Birth-weight-Prematurity or Intrauterine Growth Restriction?

EDITORIAL COMMENT: We accepted this paper for publication because it explores the important question of whether low birth-weight in infants of Aboriginal mothers is due to prematurity or fetal growth-retardation. This paper reviews the previous literature, provides some interesting new information, and shows that a prospective study with verification of fetal maturity is required to resolve the problem. Readers will realize the difficulties that exist in compilation of prospective data with sufficient numbers of cases to answer this question.
Summary: Two thousand, nine hundred and twenty-eight consecutive singleton public births at Cairns Base Hospital were studied retrospectively. Contrary to popular clinical belief, there was no statistically significant difference in the birth-weights, corrected for gestational age between Aboriginal babies and Caucasian babies. There was a highly significant excess of preterm Aboriginal births, when compared with Caucasian births. This study suggests that any attempt to reduce the high incidence of low birth-weight births in Aboriginal people should be directed at reducing the incidence of preterm birth, rather than the supposed high incidence of intrauterine growth restriction.     

胎儿生长受限的病因研究进展

胎儿生长受限（FGR）又称宫内生长受限（IUGR）,是指胎儿在母体、胎儿自身以及环境因素影响下未达到其生长潜能,是产科常见疾病之一,也是我国围生儿死亡的主要原因之一。FGR可以引起多种围生儿不良妊娠结局,包括胎儿窘迫、低出生体质量儿、早产等,且与多种远期或成年疾病相关,如代谢综合征、心血管疾病。预防FGR的发生对于提高人口素质有重要意义,但引起FGR的因素众多,主要包括母体因素、胎儿因素及胎盘、脐带因素,各种因素并不只以单一的形式存在,全面了解其发生因素有助于预防该疾病的发生。对FGR的病因进行综述,以期为该疾病的预防提供理论基础。。     

Markers for Presymptomatic Prediction of Preeclampsia and Intrauterine Growth Restriction

Preeclampsia and intrauterine growth restriction are both characterized by placental malfunction. The pathological processes of abnormal trophoblast invasion, partial absence of maternal spiral artery modification, increased apoptosis of trophoblast cells, and placental ischemia are all associated with the release of specific molecules. These proteins, as well as cell‐free fetal DNA and RNA might be detected in the maternal peripheral circulation, quantified, and used for early identification and prediction of preeclampsia and intrauterine growth restriction, prior to the appearance of the clinical symptoms. As preeclampsia and intrauterine growth restriction are associated with increased maternal, perinatal, and neonatal morbidity and mortality, early identification of these pregnancy associated complications will permit the design of appropriate preventive measures. In this review a variety of factors reported to be useful as potential markers for early detection of pregnancies at increased risk will be discussed. Molecules associated with the establishment of the placenta and essential in fetal–maternal interactions, like interleukin 2‐receptor, insulinlike growth factor‐1, and insulinlike growth factor binding protein‐1, placenta growth factor, hepatocyte growth factor, inhibin A, activin A, and human chorionic gonadotrophin seem to be the most likely candidates for presymptomatic markers for preeclampsia and/or intrauterine growth restriction. Detection and discrimination of these molecules through the placental RNA in maternal plasma based strategy has become a realistic option.     

Intrauterine Growth Restriction: Implications for Placental Metabolism and Transport. A Review

Intrauterine growth restriction (IUGR) correlates with a specific placental phenotype, associated with defects in placental transport functions, that lead to fetal undernutrition. Both placental metabolism and transport may be affected, thus modifying the normal supply of nutrients. Models to investigate placental function may either couple or separate metabolism and transport. In human pregnancies, nutrient concentrations can be measured at the time of delivery or at cordocentesis in the umbilical vessels connecting the fetus to the placenta. The kinetics of placental transport can be evaluated in vivo using stable isotopes, i.e. infusing ¹³C labelled nutrient in the mother by bolus or steady state techniques prior to cordocentesis or cesarean section. In vitro studies, using the model of the dually perfused human placenta or investigating the activity of transporters in the placental membranes have also significantly contributed to our understanding of placental function.In IUGR, the placental supply of amino acids is significantly reduced independently from the severity of growth restriction and from the presence of hypoxia. Moreover, maternal–fetal gradients of glucose are increased in severe IUGR fetuses, i.e. those with alterations of umbilical blood flows, and reduced conversion ratios of long chain-polyunsaturated fatty acids (LC-PUFA) from their parent fatty acids have been demonstrated.This review summarizes the current knowledge about placental metabolism and transport in IUGR pregnancies and the relationship with severity of the disease.     

宫腔粘连临床病因学及诊疗研究进展

宫腔粘连是各种致病因素作用下的子宫内膜损伤性疾病,严重影响女性的生殖健康和生育功能。妊娠期宫腔操作是导致宫腔粘连的主要病因,宫腔感染、子宫内膜血流低灌注等也可能与该病发生密切相关。宫腔镜检查是诊断宫腔粘连的金标准,宫腔镜宫腔粘连分离术是治疗该病的首选方法,术后多需联用辅助治疗措施预防再粘连发生,但目前尚未对该病的最佳诊疗方案达成统一的评价标准。就宫腔粘连形成的临床病因及诊疗相关研究进行综述,旨在预防宫腔粘连,为早发现、早诊断并及时采取措施提供依据,避免对子宫内膜造成更严重的伤害,为宫腔粘连的治疗开辟新思路。     

Diagnosis of IUGR: traditional biometry

An important advance in obstetric medicine will be the improved ability to identify pathologic states of fetal growth, determine their consequences, and implement appropriate interventions. In response to utero-placental insufficiency and under nutrition, the fetus makes physiologic, metabolic, and hormonal adaptations which influence growth, including reducing metabolic dependence on glucose and increasing oxygenation of other nutritional substrates including amino acids and lactate. These endocrine changes combined with reduced nutrient supply divert amino acids from protein synthesis and tissue growth, resulting in impaired somatic growth and diminished growth of kidneys, liver, and heart-the developing organs with the highest rates of cellular turnover. The obstetrician must be able to recognize and accurately diagnosis the fetus with intrauterine growth restriction (IUGR). Ultrasonography is the accepted standard for monitoring fetal growth. Serial ultrasound measurements can provide a reasonable estimate of fetal gestational age and weight based on individual and composite fetal biometric measurements. The purpose of this chapter is to discuss those traditional biometric measurements as they relate to the diagnosis of IUGR.     

The Evaluation of the Oxidative State of Low-Density Lipoproteins in Intrauterine Growth Restriction and Preeclampsia

Objective. To evaluate the oxidative state of lipoproteins in pregnancies complicated by intrauterine growth restriction (IUGR) in comparison to preeclampsia (PE) and healthy pregnant control subjects (CN). Methods. Maternal serum of 20 PE, 29 IUGR, and 29 gestational age-matched CN were analyzed. Total cholesterol (TC), low-density lipoprotein (LDL)-bound cholesterol (LDL-C), and oxidized LDL (oxLDL) concentration were measured once between 25 and 34 weeks of gestation. Statistical estimates were performed by Student's t-test. Results. Serum concentrations of LDL-C and TC were significantly reduced in IUGR [LDL-C: CN – mean = 146 mg/dL, SD = ± 40.1; IUGR – mean = 102 mg/dL, SD = ± 27.3 (p < 0.0001); PE – mean = 130 mg/dL, SD = 38.8 mg/dL; TC: CN – mean = 259/dL, SD = ± 46.8; IUGR – mean = 218 mg/dL, SD = ± 35.0 (p < 0.001); PE – mean = 244 mg/dL, SD = 48.2]. There was no significant difference in oxLDL/LDL-C ratio within the three groups (CN: mean = 0.76, SD = 0.24; IUGR: mean = 0.74, SD = 0.12; PE: mean = 0.77, SD = 0.22). Conclusion. Our results show a lower maternal LDL-C and TC concentration in IUGR pregnancies. These data contribute to the hypothesis of a decreased cholesterol supply to the fetus in IUGR. However, we could not confirm the hypothesis of an altered oxidative state in neither IUGR nor PE.     

胎儿生长受限的超声诊断进展

胎儿生长受限（fetal growth restriction,FGR）是引起现代围生儿死亡、体弱的主要病因,不仅影响胎儿在母体内的发育,如果没有进行及时的干预治疗,也会直接影响胎儿的预后。简便、安全、无辐射的优点促进超声应用于妊娠期胎儿的检测,随着超声技术的发展,可以从结构到功能多方面评估胎儿的发育。综述超声下测量胎儿径线、血流动力学参数、胎盘体积、胸腺体积、小脑横径、脑胎盘比和肾上腺体积等对FGR的超声诊断,为临床诊疗提供可靠依据。