Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women

Fetal growth restriction (FGR) refers to pregnancy complications associated with an increased risk of perinatal morbidity and mortality and is defined in the Russian-language literature as the fetal size and weight retardation in relation to the norm for a given gestational age, and in the English-language literature – as the inability of the fetus to realize its genetically determined growth potential. FGR is the cause of 43% of stillbirths of unspecified etiology, and some cases remain undiagnosed even in high-risk populations due to the lack of universal diagnostic standards for this pathology. The review presents a critical analysis of the existing definitions of FGR, the latest data on risk factors, an assessment of diagnostic methods for its early and late forms, the prospects of using biomarkers and instrumental methods of examination in predicting adverse perinatal outcomes, and an algorithm for the management of pregnancy complicated by FGR. For a more complete coverage of the literature and deeper understanding of the nosology, attention is focused on FGR that is not accompanied by preeclampsia and other hypertensive disorders, which occur in about 30% of cases. Key words: placental insufficiency, fetometry, percentile, pulsatility index, fetal growth restriction For citation: Podzolkova N.M., Denisova Yu.V., Skvortsova M.Yu., Denisova T.V., Shovgenova D.S. Fetal growth restriction: unresolved issues of risk stratification, early diagnosis, and obstetric management. Vopr. ginekol. akus. perinatol. (Gynecology, Obstetrics and Perinatology). 2021; 20(5): 76–86. (In Russian). DOI: 10.20953/1726-1678-2021-5-76-86

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Analysis of placental dysfunction in pregnancies complicated by fetal growth restriction, preeclampsia and HELLP

Geburtshilfe und Frauenheilkunde ◽

10.1055/s-2006-952581 ◽

2006 ◽

Vol 66 (S 01) ◽

Author(s):

MB Langbein ◽

R Strick ◽

PL Strissel ◽

N Vogt ◽

MW Beckmann ◽

...

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Growth Restriction ◽

Placental Dysfunction

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Metabolomics Identifies Placental Dysfunction and Confirms Flt-1 (FMS-Like Tyrosine Kinase Receptor 1) Biomarker Specificity

Hypertension ◽

10.1161/hypertensionaha.119.13184 ◽

2019 ◽

Vol 74 (5) ◽

pp. 1136-1143 ◽

Cited By ~ 1

Author(s):

Marie Austdal ◽

Gabriela Brettas Silva ◽

Sophie Bowe ◽

Liv Cecilie Vestrheim Thomsen ◽

Line Haugstad Tangerås ◽

...

Keyword(s):

Tyrosine Kinase ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Magic Angle Spinning ◽

Maternal Serum ◽

Growth Restriction ◽

Tyrosine Kinase Receptor ◽

Resonance Spectroscopy ◽

Magic Angle ◽

Placental Dysfunction

Clinical end-stage parameters define the pregnancy disorders preeclampsia and fetal growth restriction while classification of the underlying placental dysfunction is missing and urgently needed. Flt-1 (FMS-like tyrosine kinase receptor 1) is the most promising placenta-derived predictive biomarker for preeclampsia. We aimed to classify placental dysfunction in preeclampsia and fetal growth restriction at delivery by metabolic profiling and authenticate the biomarker Flt-1 for placental dysfunction. We studied 143 pregnancies with or without preeclampsia and/or fetal growth restriction delivered by cesarean section. Metabolic placenta profiles were created by high-resolution magic angle spinning nuclear magnetic resonance spectroscopy and the resulting placental phenotypes obtained by hierarchical clustering. Placental Flt-1 expression (membrane-bound and soluble isoforms combined) and maternal serum Flt-1 expression (soluble isoforms) were analyzed by immunohistochemistry and ELISA, respectively. We identified 3 distinct placenta groups by 21 metabolites and diagnostic outcome parameters; normal placentas, moderate placental dysfunction, and severe placental dysfunction. Increased placental Flt-1 was associated with severe placental dysfunction, and increased serum Flt-1 was associated with moderate and severe placental dysfunction. The preeclamptic pregnancies with and without placental dysfunction could be distinguished by 5 metabolites and placental Flt-1. Placental Flt-1 alone could separate normal pregnancies with and without placental dysfunction. In conclusion, metabolomics could classify placental dysfunction and provide information not identified by traditional diagnostics and metabolites with biomarker potential were identified. Flt-1 was confirmed as precision biomarker for placental dysfunction, substantiating its usefulness for identification of high-risk pregnancies for preeclampsia and fetal growth restriction with placental involvement.

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The ability of late pregnancy maternal tests to predict adverse pregnancy outcomes associated with placental dysfunction (specifically fetal growth restriction and pre-eclampsia): a protocol for a systematic review and meta-analysis of prognostic accuracy studies

Systematic Reviews ◽

10.1186/s13643-020-01334-5 ◽

2020 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Melanie Griffin ◽

Alexander E. P. Heazell ◽

Lucy C. Chappell ◽

Jian Zhao ◽

Deborah A. Lawlor

Keyword(s):

Systematic Review ◽

Fetal Growth ◽

Pregnancy Outcomes ◽

Fetal Growth Restriction ◽

Meta Analysis ◽

Late Pregnancy ◽

Growth Restriction ◽

Placental Dysfunction ◽

Prognostic Accuracy ◽

Adverse Pregnancy

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The Role of Proteoglycans in Contributing to Placental Thrombosis and Fetal Growth Restriction

Journal of Pregnancy ◽

10.1155/2011/928381 ◽

2011 ◽

Vol 2011 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Joanne M. Said

Keyword(s):

Fetal Growth ◽

Fetal Growth Restriction ◽

Potential Role ◽

Pregnancy Complication ◽

Growth Restriction ◽

Increased Risk ◽

Fetus And Neonate

Fetal growth restriction is an important pregnancy complication that has major consequences for the fetus and neonate as well as an increased risk of long-term morbidity extending into adulthood. The precise aetiology of most cases of fetal growth restriction is unknown although placental thrombosis is a common feature in many of these cases. This paper will outline the potential role of proteoglycans in contributing to placental thrombosis and fetal growth restriction.

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