Integrated Review of Cytokines in Maternal, Cord, and Newborn Blood: Part II— Associations With Early Infection and Increased Risk of Neurologic Damage in Preterm Infants

Abstract

A growing body of literature supports the relationship of maternal inflammation with preterm birth and adverse neonatal outcomes, including infection and central nervous system (CNS) dysfunction. Mediators of inflammation, most notably proinflammatory cytokines, have been implicated as having an association with and perhaps playing a causal role in the pathogenesis, leading to adverse neonatal outcomes. Even though the association of cytokines with early adverse neonatal outcomes has been actively pursued as a line of research, there has been little integration of diverse findings across studies. Therefore, the purpose of this systematic review was to appraise and classify empirical evidence from human studies for the association of cytokine levels in blood (serum, plasma, or cells; maternal, cord, or neonatal) with two adverse early outcomes in preterm infants: early infection and increased risk of neurologic damage. The review revealed that the proinflammatory cytokines most frequently linked with sepsis are in the interleukin (IL) 1 family as well as tumor necrosis factor alpha (TNF-alpha) and IL-6. The proinflammatory cytokines most frequently linked to neurologic insult in the reviewed studies were IL-1beta, IL-6, and IL-8. In all cases where IL-1beta was studied, the levels were increased when there was neurologic insult. A better understanding of the relationship of these inflammatory substances with these adverse conditions is needed for the future development of maternal and neonatal biobehavioral nursing research.

Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder

“…Prenatal immune activation can impact many aspects of fetal development and is associated with adverse outcomes including preterm birth, cerebral palsy, and miscarriage. (63-66) More subtly, maternal atopic disorders such as asthma and allergy as well as increased IL-4 and IFN-γ during pregnancy have been shown to be associated with an increased risk of ASD. (10, 67, 68) While many studies have examined the maternal gestational immune profile, newborn blood spots are primarily reflective of the infant’s immune status.…”

DHA supplementation: Current implications in pregnancy and childhood

“…The cytokines TNFα and IL-1β are implicated in most inflammatory conditions associated with pregnancy, birth, and childhood [57,59,60]. However, these molecules also play essential signaling roles in neurogenesis [57].…”

The Placenta as a Research Biospecimen

“…In addition, maternal cytokines may cross the placenta and affect the fetus directly (e.g., IL‐6), or they may affect the fetus indirectly via interactions with placental cells and alteration of the placental environment. A growing body of literature suggests proinflammatory cytokines may be predictive of adverse birth outcomes, such as preterm birth, neonatal infection, and neurologic insults in the newborn (Bowen, Chamley, Keelan, et al., 2002; Pickler et al., ). Notably, the proinflammatory cytokines IL‐1β, IL‐6, IL‐8, and tumor necrosis factor (TNF‐α) were found to be increased in umbilical cord blood of preterm infants diagnosed with white matter lesions shortly after birth, suggesting that infants who produce an immune response in utero may be at higher risk of neurologic insult (Pickler et al.).…”

“…One class of molecular biomarkers are cytokines, small proteins that regulate and mediate molecular processes involved in immunity, inflammation, and blood cell formation (Lyon et al, 2010). Cytokines can be found in maternal, neonatal, and umbilical cord blood as well as in the placenta and amniotic fluid (Pickler et al, 2010).…”