Term and preterm (&lt;34 and &lt;37 weeks gestation) placental pathologies associated with fetal growth restriction

Apel‐Sarid, Liat; Levy, Amalia; Holcberg, Gershon; Sheiner, Eyal

doi:10.1007/s00404-009-1255-1

Cited by 43 publications

(26 citation statements)

References 13 publications

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“…However, in IUGR placentas, SNAT2 staining intensity seemed to be lower in the syncytiotrophoblast. As expected, IUGR placentas presented (27), and it may reflect conditions of cellular distress (28). Hypoxia frequently affects IUGR babies, and it could increase the formation of syncytial knots (28) and decrease the expression of SNAT2 (19), as was found in our study population.…”

Section: Discussionsupporting

confidence: 83%

SNAT2 expression and regulation in human growth-restricted placentas

et al. 2013

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Background: Amino acid placental delivery is reduced in human intrauterine growth-restricted (IUGR) fetuses, and the activity of placental amino transporters has been consistently shown to be decreased in in vitro studies. We hypothesized lower placental expression and localization of sodium-coupled neutral amino acid transporter 2 (SNAT2 (also known as SLC38A2)), altered levels of intron-1 methylation, and altered distribution of single-nucleotide polymorphisms in human IUGR vs. normal pregnancies. Methods: We studied 88 IUGR and 84 control placentas from singleton pregnancies at elective caesarean section. SNAT2 expression was investigated by real-time PCR and immunohistochemistry. Intron-1 methylation levels were analyzed by pyrosequencing, and single-nucleotide polymorphism distribution was analyzed by allelic discrimination. results: mRNA levels were significantly decreased in IUGR placentas with reduced umbilical blood flows. Syncytiotrophoblast immunostaining was lower in IUGR placentas than in control placentas. Methylation levels were steadily low in both IUGR and control placentas. SNP genotype and allele frequencies did not differ between the two groups. conclusion: This is the first study investigating SNAT2 expression and regulation mechanisms in human IUGR placentas. We confirm previous results obtained in rats and cell cultures that support the fundamental role of SNAT2 in fetal growth and well-being, as well as a possible role of oxygen levels in regulating SNAT2 expression, indicating the relevance of hypoxia in IUGR.

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Section: Discussionsupporting

confidence: 83%

SNAT2 expression and regulation in human growth-restricted placentas

et al. 2013

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“…Our results are consistent with evidence suggesting different histologic features related to placental disease in early versus late gestations [43, 65, 184, 185]. The results of this study also support the view that angiogenic markers reflect pathways to preterm delivery that do and do not relate to preeclampsia [186].…”

Section: Commentsupporting

confidence: 91%

Maternal plasma angiogenic index-1 (placental growth factor/soluble vascular endothelial growth factor receptor-1) is a biomarker for the burden of placental lesions consistent with uteroplacental underperfusion: a longitudinal case-cohort study

Korzeniewski

Romero

Chaiworapongsa

et al. 2016

American Journal of Obstetrics and Gynecology

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Background Placental lesions consistent with maternal vascular underperfusion (MVU) are thought to be pathogenically linked to preeclampsia, small-for-gestational-age newborns, fetal death, and spontaneous preterm labor and delivery; yet, these lesions cannot be diagnosed antenatally. We previously reported that patients with such conditions and lesions have an abnormal profile of the angiogenic placental growth factor (PlGF) and anti-angiogenic factors [e.g., soluble vascular endothelial growth factor receptor-1 (sVEGFR-1)]. Objectives The objectives of this study were to: 1) examine the relationship between the maternal plasma PlGF/sVEGFR-1concentration ratio (referred to herein as angiogenic index-1) and the burden of histologic placental features consistent with MVU; and 2) test the hypothesis that angiogenic index-1 can identify patients in the midtrimester who are destined to deliver before 34 weeks of gestation with multiple (i.e., 3 or more) histologic placental features consistent with MVU. Study Design A two-stage case-cohort sampling strategy was used to select participants from among 4,006 women with a singleton gestation enrolled from 2006 through 2010 in a longitudinal study. Maternal plasma angiogenic index-1 ratios were determined using enzyme-linked immunosorbent assays. Placentas underwent histologic examination according to standardized protocols by experienced pediatric pathologists who were blinded to clinical diagnoses and pregnancy outcomes. The diagnosis of lesions consistent with MVU was made using criteria proposed by the Perinatal Section of the Society for Pediatric Pathology. Weighted analyses were performed to reflect the parent cohort, ‘n*’ is used to reflect weighted frequencies. Results 1) Angiogenic index-1 (PlGF/sVEGFR-1) concentration ratios were determined in 7,560 plasma samples collected from 1,499 study participants; 2) the prevalence of lesions consistent with MVU was 21% (n* = 833.9/3,904) and 27% (n* = 11.4/42.7) of women with 3 or more MVU lesions delivered before 34 weeks of gestation; 3) a low angiogenic index-1 (<2.5th quantile for gestational age) in maternal plasma samples obtained within 48 hours of delivery had a sensitivity of 73% [n* = 8.3/11.4; 95% confidence interval (CI), 47%–98%], a specificity of 94% (n* = 3130.9/3316.2; 95% CI, 94%–95%), a positive likelihood ratio (LR+) of 12.2, and a negative likelihood ratio (LR-) of 0.29 in the identification of patients who delivered placentas with 3 or more MVU lesions at <34 weeks; 4) prospectively, at 20–23 weeks of gestation, a maternal plasma concentration of angiogenic index-1 below the 2.5th quantile identified 70% (n* = 7.2/10.3; 95% CI, 42%–98%) of patients who delivered placentas with 3 or more MVU lesions before 34 weeks [specificity, 97% (n* = 2831.3/2918; 95% CI, 96%–98%); LR+, 23; LR−, 0.31]; and 5) among women without obstetrical complications who delivered at term, angiogenic index-1 was lower in women with compared to those without placental lesions consistent with MVU (p < 0.05). Conclusio...

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“…In keeping with the findings discussed above for PET, whilst placentas from FGR fetuses delivered at term have significantly increased frequencies of uteroplacental vascular lesions (especially infarcts) compared to normal controls, the incidence of such lesions is much lower than in preterm FGR, and many cases are histologically unremarkable [11,39,101]. Furthermore, it has been reported that compared to normal term pregnancies, placentas from FGR at term may have an increased incidence of other villous lesions including fibrosis, hypovascularity and avascularity, suggestive of fetal thrombotic events [102], although these changes had not been described in previous studies.…”

Section: Placental Pathology Of Fgr At Term (‘Late-onset' Fgr)mentioning

confidence: 69%

Placental Pathology in Early-Onset and Late-Onset Fetal Growth Restriction

2014

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Several histopathological features are found more frequently in placentas from pregnancies complicated by fetal growth restriction (FGR), including villous infarction, maternal vascular changes and villous morphological alterations, although around one quarter of placentas associated with FGR lack any morphological abnormality on routine examination. Since similar changes may also affect clinically uncomplicated pregnancies, the positive predictive value of such findings for pathological FGR in an unselected case remains low. However, the pattern of placental pathologies varies with clinical subgroup. The combination of placental bed and parenchymal lesions in FGR with abnormal uterine artery Doppler velocimetry is essentially identical to preterm pre-eclampsia (PET), and there is an association between FGR with abnormal umbilical artery Doppler findings and lesions of fetal stem arteries and terminal villous hypovascularity. Conversely, placentas from pregnancies complicated by PET or FGR presenting at or near term have a significantly lower frequency of histological abnormalities compared to early-onset disease and absence of a distinctive biochemical profile. The histological placental findings in FGR are therefore varied, from morphologically unremarkable through to severe uteroplacental vasculopathy, with no single pathological feature associated with high sensitivity or specificity. Severe early-onset FGR, overlapping with severe early-onset PET, is mainly associated with features of impaired maternal uteroplacental perfusion secondary to defective extravillous trophoblast invasion, and its consequences. Late-onset FGR probably represents a more heterogeneous group with less characteristic histological changes. Future research using histopathological assessment of aggregated data from multiple studies into larger datasets with centralised pathology review will allow delineation of distinctive clinicopathological associations and further understanding of pathophysiology.

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Term and preterm (<34 and <37 weeks gestation) placental pathologies associated with fetal growth restriction

Cited by 43 publications

References 13 publications

SNAT2 expression and regulation in human growth-restricted placentas

SNAT2 expression and regulation in human growth-restricted placentas

Maternal plasma angiogenic index-1 (placental growth factor/soluble vascular endothelial growth factor receptor-1) is a biomarker for the burden of placental lesions consistent with uteroplacental underperfusion: a longitudinal case-cohort study

Placental Pathology in Early-Onset and Late-Onset Fetal Growth Restriction

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