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