Elsevier

Placenta

Volume 46, October 2016, Pages 72-78
Placenta

Placental histological examination and the relationship with oxidative stress in preterm infants

https://doi.org/10.1016/j.placenta.2016.08.084Get rights and content

Highlights

  • A relationship between placental lesions and cord blood oxidative stress was found.

  • Oxidative stress builds up in response to inflammation or impaired perfusion stimuli.

  • Free iron, lipid and protein oxidation products were the most reliable markers.

  • The risk of placental oxidative injury to newborns should be identify early at birth.

Abstract

Background

Prenatal conditions of enhanced oxidative stress (OS) linked to inflammation or hypoxia have been associated with impaired fetal growth and preterm delivery. Little is known regarding biomarkers of OS in the cord blood of preterm infants and placental histological patterns.

Objectives

To test the hypothesis that placental lesions indicating chorioamnionitis (CA) or vascular underperfusion (VU) are associated with increased OS in the offspring.

Methods

120 neonates born below 29+6 weeks of gestational age (GA) were enrolled. Histological characteristics of placentas from their mothers were classified as normal (CTRL group), histological CA (HCA) and vascular underperfusion (VU). Serum concentrations of isoprostanes (IsoPs), non-protein bound iron (NPBI) and advanced oxidative protein products (AOPP), were determined in cord blood.

Results

IsoPs, NPBI and AOPP were significantly increased in HCA group compared to CTRL group. The multivariable regression model, adjusted for GA, maternal age, parity, maternal diabetes, maternal obesity and presence/absence of fetal growth restriction (FGR), showed a significant association between the presence of HCA and increased OS biomarkers levels in cord blood (IsoPs: p = 0.006; NPBI: p = 0.014; AOPP: p = 0.007). Placental VU lesions were significantly associated with higher umbilical IsoPs, NPBI and AOPP levels (IsoPs: p = 0.008; NPBI: p = 0.002; AOPP: p = 0.040). In the cases of placental VU lesions associations were also found between high AOPP levels and low GA (p = 0.002) and the presence of fetal growth restriction (p = 0.014).

Conclusions

Placental lesions indicating inflammation or impaired perfusion are associated with higher cord blood levels of OS biomarkers explaining the fetal susceptibility to oxidative injury and the need of antioxidant protection.

Introduction

Placenta is a diary of intrauterine life. Many studies support the thesis that placental diseases such as infection or inflammation are responsible of preterm birth in up to 50% of cases [1], [2] even if only a partial correlation was found between clinical and placental finding and gestational age was the main determinant for neonatal outcome [3]. Particularly, prenatal conditions of enhanced oxidative stress (OS) linked to inflammation or hypoxia have been associated with impaired fetal growth and preterm delivery. During hypoxia several pathways involving intracellular calcium release and activation of nitric oxide synthase lead to increased free radicals (FR) generation.

During inflammation the direct activation of inflammatory cells, especially granulocytes, releases a large amount of oxygen radicals and proteases, that contribute to killing bacteria but also enhance OS. OS-induced damage plays an important role in several pathological processes that are involved in fetal-neonatal pathology.

Histological chorioamnionitis (HCA) is responsible for approximately 60–70% of pregnancies complicated by preterm prelabor rupture of membranes (pPROM). In our previous studies we reported that OS was associated with pPROM through the presence of OS markers in the amniotic fluid samples [4], [5]. Higher concentrations of OS markers in umbilical cord blood were also observed in pregnancies that are complicated by preeclampsia, fetal growth restriction (FGR), and subsequent development of necrotizing enterocolitis, maternal obesity and gestational diabetes [4], [6], [7], [8]. Histological analysis of placenta is an useful tool for detecting the etiology and recurrent risk of pregnancy disorders. There is a paucity of information regarding the relationship between placental histological patterns and OS markers in cord blood of preterm infants. Moreover, it still remains unclear whether the presence of HCA or placental vascular underperfusion lesions, the most common risk factors for pPROM and preterm birth, are related to increased OS markers in the umbilical cord.

In this study we tested the hypothesis that placental lesions indicating HCA or vascular underperfusion (VU) are associated with increased levels of OS biomarkers in cord blood.

Section snippets

Samples collection and population

Between November 2012 and December 2014, a prospective cohort study of 120 preterm babies and respective placentas were recruited (for more clinical perinatal details see Table 1, Table 2) at the Department of Molecular and Developmental Medicine, University Hospital of Siena, Italy. The study protocol was approved by the local ethic board. Informed consent was obtained from the babies' parents before the enrollment.

Inclusion criteria were: GA < 32 weeks, inborn and single pregnancies.

Population

Clinical characteristics of mothers and newborns are shown respectively in Table 1, Table 2. Seven mothers in the CTRL group had gestational diabetes but only diet treatment was needed to control glycemia levels. Furthermore, in the CTRL group, nine mothers had cervical incontinence, three had uterine malformations, six presented p-PROM, ten showed low socio-demographic and psychological status. Two of the three mothers in CTRL group and two of the six mothers in the VU group with autoimmune

Discussion

Placenta plays a key role in developmental plasticity. Changing developmental signals or placental adaptation occurred in response to an altered maternal environment may be the general underlying mechanisms that link altered placental function to fetal programming [18]. Fetal programming occurs when the normal pattern of fetal development is disrupted by an abnormal stimulus or insult applied to a critical point in intrauterine life and ultimately leads to chronic metabolic diseases.

Conflict of interest

The Authors state that no conflict of interest exists regarding the described work.

Acknowledgments

Partial Grant from Tuscany Region and Ministry of Health, General Directorate of Scientific and Technological Research for the 2011–2014 Project. RF-2009-1499651.

References (29)

  • S. Perrone et al.

    May oxidative stress biomarkers in cord blood predict the occurrence of necrotizing enterocolitis in preterm infants?

    J. Matern. Fetal Neonatal Med.

    (2012)
  • J. Escobar et al.

    Amniotic fluid oxidative and nitrosative stress biomarkers correlate with fetal chronic hypoxia in diabetic pregnancies

    Neonatology

    (2013)
  • E. Bertino et al.

    Neonatal anthropometric charts

    J. Pediatr. Gastroenterol. Nutr.

    (2010)
  • B. Casetta et al.

    Development of a fast and simple LC-MS/MS method for measuring the F2-isoprostanes in newborns

    J. Matern. Fetal Neonatal Med.

    (2012)
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