Fetal growth restriction: a workshop report (original) (raw)

Pathophysiology of placental-derived fetal growth restriction

American journal of obstetrics and gynecology, 2018

Placental-related fetal growth restriction arises primarily due to deficient remodeling of the uterine spiral arteries supplying the placenta during early pregnancy. The resultant malperfusion induces cell stress within the placental tissues, leading to selective suppression of protein synthesis and reduced cell proliferation. These effects are compounded in more severe cases by increased infarction and fibrin deposition. Consequently, there is a reduction in villous volume and surface area for maternal-fetal exchange. Extensive dysregulation of imprinted and nonimprinted gene expression occurs, affecting placental transport, endocrine, metabolic, and immune functions. Secondary changes involving dedifferentiation of smooth muscle cells surrounding the fetal arteries within placental stem villi correlate with absent or reversed end-diastolic umbilical artery blood flow, and with a reduction in birthweight. Many of the morphological changes, principally the intraplacental vascular le...

The Relationship of Intrauterine Growth Restriction with Placental Pathologic Changes in Newborns

World Journal of Peri & Neonatology, 2020

Introduction: Intrauterine growth restriction is a multifaceted problem and is associated with a significant increase in the level of morbidity and perinatal mortality. According to some studies, failure of the placenta is responsible for the most cases of intrauterine growth restriction. The aim of this study was to evaluate the placental pathologic changes in the intrauterine growth restriction (IUGR) samples and compare them with normal cases. Methods: A study population consisted of 60 intrauterine growth restriction neonates and 60 normalized neonates born at Tehran Imam Khomeini Hospital between June 2016 and July 2017. The placenta was weighed, immediately after delivery, and the umbilical cord was separated, then stored in 10% formalin and sent for pathological examination as soon as possible. Data collection was performed according to the following items: the pathologist's report, the results of the infants' examination, and the data in the neonatal cases. Resul...

Fetal growth restriction due to placental disease

Seminars in Perinatology, 2004

Normal fetal growth depends on the genetically predetermined growth potential and its modulation by the health of the fetus, placenta and the mother. Fetuses that are small because of intrauterine growth restriction (IUGR) are at higher risk for poor perinatal and long-term outcome than those who are appropriately grown. Of the many potential underlying processes that may result in IUGR, placental disease is clinically the most relevant. Fetal cardiovascular and behavioral responses to placental insufficiency and the metabolic status are interrelated. The concurrent evaluation of fetal biometry, amniotic fluid volume, heart rate patterns, arterial and venous Doppler, and biophysical variables therefore allow the most comprehensive fetal evaluation in IUGR. In the absence of successful intrauterine therapy, the timing of delivery is perhaps the most critical aspect of the antenatal management. A discussion of the fetal responses to placental insufficiency and a management protocol that accounts for multiple Doppler and biophysical parameters as well as gestational age is provided in this review.

Fetal Growth Restriction (FGR): Review

International Journal of Progressive Sciences and Technologies

In recent years, there has been a growing amount of interest in the possibility that inadequate maternal hemodynamic adaptations to the pregnancy and adverse pregnancy outcomes (APOs) are connected. It has been suggested that "placental syndromes," such as preeclampsia (PE) and fetal growth restriction (FGR), may be linked to later maternal cardiovascular diseases (CVD). The two subtypes of FGR have distinct clinical and pathogenetic characteristics. It is thought that poor trophoblastic invasion of the maternal spiral arteries during placentation is a major factor in the development of early-onset PE and FGR. A pre-existing or subsequent cardiovascular impairment may play a significant role in the pathogenesis of early-onset FGR because placental functioning is dependent on the cardiovascular system of the mother. A primary abnormal placentation in the first trimester does not appear to be the factor that determines late FGR. A primary cardiovascular maladaptation in the...

Microarray analysis of placental tissue in intrauterine growth restriction

Clinical Endocrinology, 2010

Besides foetal or maternal disorders, placental dysfunction is a major cause of intrauterine growth restriction (IUGR). Although numerous macro- and histopathological changes have been described, little is known about the precise aetiology and the contribution of foetal/placental genes in this disorder. Placental tissues of 20 IUGR and control neonates were analysed by microarray technique. Four of the regulated genes with possible relevance in the pathogenesis of IUGR and its consequences were further studied in placentas of 27 IUGR and 35 control newborns. Elevated gene expression of leptin, corticotrophin-releasing hormone (CRH), and IGF-binding protein-1 (IGFBP-1) in IUGR placentas could be confirmed in the larger group by real-time PCR, whereas prolactin showed no significant difference. Accordingly, protein expression of leptin and IGFBP-1 depicted by Western blot was elevated in IUGR, prolactin was not different. Birthweight standard deviation score (SDS) correlated negatively to leptin, IGFBP-1, and CRH, whereas placental weight correlated only to IGFBP-1. Leptin correlated negatively to gestational age of IUGR patients and positively to placental score, a marker of severity of impaired foeto-placental circulation. As confirmed in a large group of IUGR and control samples, the up-regulated factors leptin, IGFBP-1, and CRH may serve as candidate genes for the prediction of subsequent metabolic consequences in IUGR newborns. These three factors may not only influence growth of the foetus, but might also interact with programming of its metabolic functions, which has to be determined in an ongoing study.

The Genetics of fetal growth restriction: Implications for management

Reviews in Gynaecological and Perinatal Practice, 2006

Fetal growth restriction (FGR) is a common clinical problem that has a significant effect on perinatal morbidity and mortality. In addition, it also adversely influences adult health, as it increases the risk of cardiovascular disease and impaired glucose tolerance. There is growing evidence that genes play a role in the pathogenesis. Karyotypic abnormalities, affecting both the fetus and the placenta, are known to be associated with fetal growth restriction. This not only impacts on clinical management but has also aided the understanding of the mechanisms controlling fetal growth. In particular, there is an increasing appreciation of the role of imprinted genes in growth and development. There is good genetic epidemiological evidence that genes also play a role in the more common, multifactorial fetal growth restriction, seen in the presence of a normal karyotype. The number of candidate genes studies is increasing and includes members of the renin angiotensin system and the insulin-like growth factor axis. The most extensively investigated to date are the inherited thrombophilias and meta-analyses seem to support an association with fetal growth restriction. However, larger studies are urgently required to confirm this association. There is currently no evidence to support screening low-risk pregnant women for inherited thrombophilias, and there are no randomised controlled trials to suggest that treatment with anticoagulants improve outcome. At present screening or treatment should occur only within such trials.

An Animal Model of Placental Insufficiency-Induced Intrauterine Growth Restriction

Seminars in Perinatology, 2008

Intrauterine growth restriction (IUGR), often associated with functional placental insufficiency, results in increased perinatal mortality and morbidity. For obvious reasons, many questions regarding the progression of IUGR pregnancies cannot be addressed experimentally in humans, predicating the use of animal models. Although no animal model fully recapitulates human pregnancy, the pregnant sheep has been used extensively to investigate maternal-fetal interactions. In sheep, surgical placement of catheters in both the maternal and fetal vasculature allows repeated sampling from nonanesthetized pregnancies. Considerable insight has been gained on placental oxygen and nutrient transfer and utilization from use of pregnant sheep, often confirmed in the human once appropriate technologies became available. This review will focus on one sheep model, used to examine the impact of placental insufficiency-induced IUGR on oxygen and nutrient transport and utilization.

Maternal predictors of intrauterine growth restriction

Current Opinion in Clinical Nutrition and Metabolic Care, 2013

Purpose of review Intrauterine growth restriction (IUGR) occurs when fetal growth rate falls below the genetic potential and affects a significant number of pregnancies, but still no therapy has been developed for this pregnancy disease. This article reviews the most recent findings concerning maternal characteristics and behaviours predisposing to IUGR as well as maternal early markers of the disease. A comprehensive understanding of factors associated with IUGR will help in providing important tools for preventing and understanding adverse outcomes. Recent findings Maternal nutritional status, diet and exposure to environmental factors are increasingly acknowledged as potential factors affecting fetal growth both by altering nutrient availability to the fetus and by modulating placental gene expression, thus modifying placental function. Summary Assessing nutritional and environmental factors associated with IUGR, and the molecular mechanisms by which they may have a role in the disease onset, is necessary to provide comprehensive and common guidelines for maternal care and recommended behaviours. Moreover, maternal genetic predispositions and early serum markers may allow a better and more specific monitoring of high risk pregnancies, optimizing the timing of delivery.

Intrauterine growth restriction: Recent developments, definitions and future research

Clinical obstetrics, gynecology and reproductive medicine, 2019

The subject of intrauterine growth restriction has and continues to be in confusion because academic journals continue to publish articles that define the outcome of this disease as low birthweight or small for gestational age. This fault has been recently addressed with the recent publication of Fetal-Placental Growth Restriction: a series of 28 articles in 7 sections by 56 recognised authors. But even in this publication no alternative to low birthweight is clearly defined as an alternative to describe the outcome of this disease. As the name of this publication implies, this aberrant fetal growth has its origin in the maldevelopment of a normal, low resistance, uteroplacental circulation. It is therefore not surprising the many these cases have been detected preclinically using in mid-pregnancy uteroplacental Doppler flow studies. Previous studies have shown that an improvement in outcome definition is achieved when it address the asymmetry of growth these infant have. This review concludes that a ratio of birthweight to head circumference would be the simplest and most appropriate definition.

Placental Adaptations in Growth Restriction

Nutrients, 2015

The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR) is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal