Genetic Background of Fetal Growth Restriction

Nowakowska, Beata; Pankiewicz, Katarzyna; Nowacka, Urszula; Niemiec, Magdalena; Kozłowski, Szymon; Issat, Tadeusz

doi:10.3390/ijms23010036

Cited by 15 publications

(3 citation statements)

References 105 publications

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“…Fetal growth restriction (FGR) is mainly due to the low invasive ability of trophoblast cells and poor remodeling of the uterine spiral artery, which leads to placental ischemia and hypoxia, which afects fetal development [6,7]. Preeclampsia combined with FGR is relatively common, the onset of gestational age is generally earlier, the functional development of fetal organs is immature, and the incidence of adverse pregnancy outcomes is high [8,9]. Until now, the diagnosis and treatment of patients with preeclampsia complicated by fetal growth restriction has always been the focus of clinical attention.…”

Section: Introductionmentioning

confidence: 99%

Clinical Value of Serum SIRT1 Combined with Uterine Hemodynamics in Predicting Disease Severity and Fetal Growth Restriction in Preeclampsia

Kong

2023

Evidence-Based Complementary and Alternative Medicine

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Objective. The sirtuin regulator 1-related enzyme (SIRT1) has been shown to play an important role in various pathophysiological processes. Our aim was to investigate the effect and correlation of serum SIRT1 combined with uterine hemodynamic parameters on disease severity and fetal uterine growth restriction in the progression of preeclampsia and to evaluate its clinical value as a potential marker. Methods. A total of 100 patients with preeclampsia who were hospitalized in Qufu Normal University Hospital from June 2017 to June 2021 were selected as the research objects. According to the severity, they were divided into the mild (62 cases) and severe groups (38 cases), and according to whether the fetal growth restriction was combined or not, they were divided into the combined fetal growth restriction group (56 cases) and the uncomplicated fetal growth restriction group (44 cases). Serum SIRT1 expression and uterine artery hemodynamic parameters were detected, and Spearman analysis was used to evaluate the association of serum SIRT1 expression and uterine artery hemodynamic parameters (the peak-to-trough ratio of arterial blood velocity, the pulsatility index, and the resistance index) with disease severity (systolic blood pressure, diastolic blood pressure, and random urinary protein levels) and fetal growth restriction (femoral length, biparietal diameter, head circumference, and neonatal weight); unsupervised principal component analysis (PCA), supervised partial least-squares discrimination analysis (PLS-DA), cluster heat map analysis, the receiver operating characteristic (ROC) curve, and the area under curve (AUC) were used to evaluate the diagnostic value of serum SIRT1 expression combined with uterine artery hemodynamic parameters in the severity of disease and fetal growth restriction in patients with preeclampsia. Results. Compared with patients with mild preeclampsia, serum SIRT1 expression was lower in patients with severe preeclampsia ( p < 0.0001 ), the arterial blood flow velocity peak-to-trough ratio, pulsatility index, and resistance index were higher ( p < 0.001 ; p < 0.0001 ); and serum SIRT1 expression and uterine artery hemodynamic parameters were closely related to disease severity ( p < 0.001 ; p < 0.0001 ). In addition, the expression of serum SIRT1 in patients with preeclampsia combined with fetal growth restriction was lower than patients without preeclampsia ( p < 0.0001 ); the peak-to-trough ratio of arterial blood flow velocity, the pulsatility index, and the resistance index were higher ( p < 0.0001 ); and serum SIRT1 expression and uterine artery hemodynamics were closely related to fetal growth restriction ( p < 0.0001 ). Unsupervised PCA analysis and supervised PLS-DA analysis showed that patients with different severity of disease and patients with or without fetal growth restriction were similar within the groups, and there were significant differences between the groups; cluster heat map analysis showed that the mild and severe groups were stratified clustering, and the combined fetal growth restriction group and the uncombined group were hierarchically clustered; ROC curve showed that the AUC of serum SIRT1 expression combined with uterine artery hemodynamic parameters was 0.776 in identifying the severity of preeclampsia and 0.956 in identifying the preeclampsia complicated by fetal growth restriction. Conclusion. Serum SIRT1 combined with uterine hemodynamic parameters in preeclampsia is closely related to disease severity and fetal growth restriction and is expected to become a potential biomarker for early clinical intervention in patients.

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Section: Introductionmentioning

confidence: 99%

Clinical Value of Serum SIRT1 Combined with Uterine Hemodynamics in Predicting Disease Severity and Fetal Growth Restriction in Preeclampsia

Kong

2023

Evidence-Based Complementary and Alternative Medicine

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“…The etiology of FGR is multifactorial, and can include impaired placental development and function, pre-eclampsia and maternal hypertension, and poor maternal cardiovascular adaptation to pregnancy, multiple gestation, maternal diabetes, maternal environment (e.g. high altitude, asthma, and stress) and lifestyle factors such as smoking, drug-use, malnutrition, and placental and fetal abnormalities (genetic or otherwise) (Sharma et al, 2016;Burton and Jauniaux, 2018;Damhuis et al, 2021;Nowakowska et al, 2021). Infections such as cytomegalovirus, syphilis and hepatitis C can also be associated with FGR (Longo et al, 2014).…”

Section: Etiologymentioning

confidence: 99%

Fetal growth restriction and stillbirth: Biomarkers for identifying at risk fetuses

et al. 2022

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Fetal growth restriction (FGR) is a major cause of stillbirth, prematurity and impaired neurodevelopment. Its etiology is multifactorial, but many cases are related to impaired placental development and dysfunction, with reduced nutrient and oxygen supply. The fetus has a remarkable ability to respond to hypoxic challenges and mounts protective adaptations to match growth to reduced nutrient availability. However, with progressive placental dysfunction, chronic hypoxia may progress to a level where fetus can no longer adapt, or there may be superimposed acute hypoxic events. Improving detection and effective monitoring of progression is critical for the management of complicated pregnancies to balance the risk of worsening fetal oxygen deprivation in utero, against the consequences of iatrogenic preterm birth. Current surveillance modalities include frequent fetal Doppler ultrasound, and fetal heart rate monitoring. However, nearly half of FGR cases are not detected in utero, and conventional surveillance does not prevent a high proportion of stillbirths. We review diagnostic challenges and limitations in current screening and monitoring practices and discuss potential ways to better identify FGR, and, critically, to identify the “tipping point” when a chronically hypoxic fetus is at risk of progressive acidosis and stillbirth.

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“…However, studies on the genetic burden in fetuses with FGR are lacking. The monogenic disorders associated with fetal growth impairment include Cornelia de Lange syndrome (CdLS), Smith‐Lemli‐Opitz syndrome, and Meier‐Gorlin syndrome 8 . However, most of the studies on genetic causes use the gene panel or specific gene detection approaches instead of exome sequencing (ES), implying that the utility of ES in fetuses with FGR has not been fully verified and elaborated.…”

Section: Introductionmentioning

confidence: 99%

Genetic causes of isolated and severe fetal growth restriction in normal chromosomal microarray analysis

Zhou

Wang

et al. 2023

Intl J Gynecology & Obste

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Objective To investigate the genetic burden in fetuses with isolated and severe fetal growth restriction (FGR) using Trio whole‐exome sequencing (WES) with a normal chromosomal microarray. Method This retrospective study analyzed WES results of singleton fetuses with isolated and severe FGR, whose estimated fetal weight (EFW) was less than the third percentile by Hadlock formula, in a tertiary center between March 2016 and March 2022. Cases with abnormal chromosomal microarray analysis (CMA) and TORCH results were excluded. Results Fifty‐one fetuses with isolated and severe FGR and negative CMA results underwent Trio‐WES. Of all patients, eight (15.7%) were diagnosed with FGR at its early onset (<32 weeks) and showed pathogenic or likely pathogenic variants involving Nipped‐B‐like protein gene (NIPBL) (n = 3), fibroblast growth factor receptor 3 (n = 1), pyruvate dehydrogenase E1 subunit alpha 1 (n = 1), collagen, type I, alpha 1 (n = 1), superkiller viralicidic activity 2‐like (n = 1), and chloride voltage‐gated channel (CLCN5) (n = 1). De novo–generated variants were identified in five fetuses, of which two were novel, including c.6983C>A (p. Thr2328Lys) in NIPBL and c.934‐1G>T in CLCN5. Genetic disorders involved Cornelia de Lange syndrome and metabolic and skeletal genetic diseases. Conclusion The present study indicates that Trio‐WES can improve effectivity of prenatal diagnoses for isolated and severe FGR in cases with normal CMA results, aiding prenatal genetic counseling and pregnancy management for FGR fetuses.

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Genetic Background of Fetal Growth Restriction

Cited by 15 publications

References 105 publications

Clinical Value of Serum SIRT1 Combined with Uterine Hemodynamics in Predicting Disease Severity and Fetal Growth Restriction in Preeclampsia

Clinical Value of Serum SIRT1 Combined with Uterine Hemodynamics in Predicting Disease Severity and Fetal Growth Restriction in Preeclampsia

Fetal growth restriction and stillbirth: Biomarkers for identifying at risk fetuses

Genetic causes of isolated and severe fetal growth restriction in normal chromosomal microarray analysis

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