The Impact of Infection in Pregnancy on Placental Vascular Development and Adverse Birth Outcomes

Abstract

Healthy fetal development is dependent on nutrient and oxygen transfer via the placenta. Optimal growth and function of placental vasculature is therefore essential to support in utero development. Vasculogenesis, the de novo formation of blood vessels, and angiogenesis, the branching and remodeling of existing vasculature, mediate the development and maturation of placental villi, which form the materno-fetal interface. Several lines of evidence indicate that systemic maternal infection and consequent inflammation can disrupt placental vasculogenesis and angiogenesis. The resulting alterations in placental hemodynamics impact fetal growth and contribute to poor birth outcomes including preterm delivery, small-for-gestational age (SGA), stillbirth, and low birth weight (LBW). Furthermore, pathways involved in maternal immune activation and placental vascularization parallel those involved in normal fetal development, notably neurovascular development. Therefore, immune-mediated disruption of angiogenic pathways at the materno-fetal interface may also have long-term neurological consequences for offspring. Here, we review current literature evaluating the influence of maternal infection and immune activation at the materno-fetal interface and the subsequent impact on placental vascular function and birth outcome. Immunomodulatory pathways, including chemokines and cytokines released in response to maternal infection, interact closely with the principal pathways regulating placental vascular development, including the angiopoietin-Tie-2, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) pathways. A detailed mechanistic understanding of how maternal infections impact placental and fetal development is critical to the design of effective interventions to promote placental growth and function and thereby reduce adverse birth outcomes.

Relation of High Maternal Body Mass Index to Perinatal and Maternal Outcome

“…We found a significantly rising incidence of low birth weight babies among BMI more than or equal to 35mothers 83.3%. which is similar to Takai et al, 2017 [15] results which may be due to dysregulation of proinflammatory cytokines as well as increased risk of infection in obese and overweight individuals as they will lead to reduced placental surface area and also their vasculature with consequent uteroplacental insufficiency [16] In our study, we found more incidence of IUGR and NICU admissions in the BMI group more than or equal to 35, which is like Shah PM et al 2018 results [17] .…”

Recent insights on indirect mechanisms in developmental toxicity of nanomaterials

“…Early in pregnancy, the uterine spiral arteries are structurally converted from small diameter arteries into low-resistance large diameter vessels by interaction with the fetal placental extravillous trophoblasts that invade the myometrium and the spiral arteries [159]. Some chemicals have been shown to interfere with vascular remodeling and development of the placenta, thereby impairing oxygen and nutrient delivery to the fetus and ultimately increasing the risk for adverse pregnancy outcomes (reviewed in [160,161]). Several epidemiological studies have found that components of air pollution, including PM with 2.5 μm or less in diameter (PM 2.5 ) , were associated with increased risk of pregnancy-induced hypertensive disorders [2].…”

Exploring the Role of Fusobacterium nucleatum in Preterm Birth: A Narrative Review

“…Whether the impact from periodontal infection influences or explicates a direct effect is uncertain but suggests a potentially damaging interaction between periodontitis and preterm delivery (PTD) [23]. From the empirical findings, a clear interest focused on the placental inflammation has emerged [1], [4], [25], [26], [27], [28], [29]. Central relationship between the periodontal disease and preterm birth (PTB) is due to an inflammatory response system responding to signal from bacterial invasion [30], [31].…”

“…Interestingly, a similarity between placental and oral microbiome was found to be essential to describe as coherent a hypothesis of relationship between oral dysbiosis and pregnancy poor outcomes [32], [33], [34], [35], [36], [37]. This hypothesis is referred to an activate inflammatory signaling pathways stimulated by periodontal damage, or direct dissemination of periodontal pathogens through hematogenous spread from the oral cavity [18], [21], [27], [35], but they do not fully explain such behaviors, suggesting that other mechanisms and factors might play a key role in determining the link [22], [23], [24], [25]. Fusobacterium nucleatum (FN) is an opportunistic commensal Gram-negative anaerobe microorganism ubiquitous to the oral cavity, one of the most abundant pathogens implicated in severe periodontal disease [18], [38], [39], [40], [41], [42], [43], [44], [45], [46].…”

“…Specifically, it has been investigated the role of the Gram-negative periodontal pathogen FN, an opportunistic pathogen agent having a specific role in the pathogenesis of different periodontal conditions, and it is increasingly recognized as an important agent of PTB [42], [50]. FN is credited with the distinction of being the most crucial pathogen implicated in the pathogenesis of periodontitis [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], counting its systemic effects on immune system [59], [60]. The localized infection and inflammation of the mouse placenta mediated by oral FN colonization have been described previously by several researchers who suggested that the hematogenous transmission of this bacterium had a detrimental effect on pregnancy, producing intrauterine inflammatory response [51].…”