A proposed bio-panel to predict risk for spontaneous preterm birth among African American women

Abstract

Preterm birth (PTB), or birth prior to 37 weeks gestation, impacts 11.5% of U.S. deliveries. PTB results in significant morbidity and mortality among affected children and imposes a large societal financial burden. Racial disparities in PTB are alarming. African American women are at more than 1.5 times the risk for PTB than white women. Unfortunately, the medical community’s ability to predict who is at risk for PTB is extremely limited. History of a prior PTB remains the strongest predictor during a singleton gestation. Cervical length and fetal fibronectin measurement are helpful tools. However, usefulness is limited, particularly among the 95% of U.S. women currently pregnant and lacking a history of PTB. Therefore, preventive therapies do not reach a great number of women who may benefit from them. This manuscript, in response to the pressing need for predictors of PTB risk and elimination of racial disparities in PTB, presents a proposed bio-panel for use in predicting risk for spontaneous PTB among African American women. This bio-panel, measured each trimester, includes stimulated production of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist (Ra), soluble(s) TNF receptor(R) 1, and sTNFR2, and cortisol responsiveness. We hypothesize that greater IL-1β and TNF-α production, decreased IL-1Ra, sTNFR1, and sTNFR2 production, and decreased cortisol responsiveness at each time point as well as a more expedient alignment with this unfavorable profile over time will be associated with PTB. The choice to focus on inflammatory parameters is supported by data highlighting a crucial role for inflammation in labor. Specific inflammatory mediators have been chosen due to their potential importance in preterm labor among African American women. The bio-panel also focuses on inflammatory regulation (i.e., cytokine production upon ex vivo stimulation), which is hypothesized to provide insight into potential in vivo leukocyte responses and potential for initiation of a preterm inflammatory cascade. Production of receptors antagonists is also considered, as pro-inflammatory mediator effects can be greatly influenced by their balance with respective antagonists. Finally, leukocyte responsiveness to cortisol is included as a measure of cortisol’s ability to convey anti-inflammatory signals. The development of a bio-panel predictive of risk for spontaneous PTB among African American women would represent a significant advancement. Available preventive therapies, namely progesterone supplementation, could be delivered to women deemed at risk. Further, the identification of biological predictors of PTB may uncover novel targets for preventive therapies.

Mothers’ childhood hardship forecasts adverse pregnancy outcomes: Role of inflammatory, lifestyle, and psychosocial pathways

“…Though mediation analyses cannot yield causal inferences in an observational study like this, the results are consistent with a scenario wherein childhood disadvantage predisposes women to express higher IL-6 during pregnancy, which accelerates the gestation and/or instigates labor prematurely. This scenario converges with research showing that childhood hardship instantiates a durable pro-inflammatory phenotype (Miller et al 2009; Loucks et al 2010; Levine et al 2015; Chen et al 2016a; Phillips et al 2009), and with evidence from animal (Romero et al 2014) and human (Gillespie et al 2015) studies linking excessive cytokine activity with PTB. Interestingly, IL-6 is a risk factor for diabetes, metabolic syndrome, coronary heart disease, and premature mortality (Ridker 2016; Wang et al 2013; Alley et al 2007).…”

“…Antecubital blood was drawn at both study visits, and plasma was used to measure a panel of inflammatory biomarkers implicated in adverse pregnancy outcomes (Sykes et al 2012; Gillespie et al 2015). The panel consisted of interferon-γ (IFN-γ), interleukins (IL-) 6, 8, 10, 13, and tumor necrosis factor-α (TNF-α).…”

“…Studies in animals show that high concentrations of inflammatory mediators can restrict fetal growth and speed up parturition (Challis et al 2009). And in some cohorts of pregnant women, higher circulating inflammatory biomarkers forecast preterm delivery and lower birth weight (Sykes et al 2012; Gillespie et al 2015), possibly because they mirror immunologic conditions at the maternal-fetal interface. Based on these observations, our second goal was to determine whether inflammatory biomarkers during gestation link childhood socioeconomic conditions with adverse pregnancy outcomes.…”

Vaginal microbiome in early pregnancy and subsequent risk of spontaneous preterm birth: a case–control study

“…Additionally, a cross‐sectional US study (mainly African Americans) reported no distinct taxa across pregnancy in association with preterm birth . Similarly, no differences in SDI, bacterial taxa and vaginal CSTs were reported between women with early preterm (<34 weeks) versus term deliveries, despite mainly being African Americans, which is an ethnicity associated with higher risk of both BV and preterm birth . These studies suggest that the association between the vaginal microbiome and preterm birth is population‐dependent …”

“…10 Similarly, no differences in SDI, bacterial taxa and vaginal CSTs were reported between women with early preterm (<34 weeks) versus term deliveries, despite mainly being African Americans, 9 which is an ethnicity associated with higher risk of both BV and preterm birth. 6,13 These studies suggest that the association between the vaginal microbiome and preterm birth is population-dependent. 12 Previous studies on the vaginal microbiome and preterm birth had small sample size, 2,[8][9][10] inconsistency in collection of vaginal swabs across pregnancy 8,10 and limited information on spontaneous preterm births.…”