Inflammatory Biomarker Profiles in Very Preterm Infants within the Context of Preeclampsia, Chorioamnionitis, and Clinically Diagnosed Postnatal Infection

Abstract

Preterm delivery can be precipitated by preeclampsia or infection, and preterm infants are at heightened risk of postnatal infection. Little is known about the ontogeny of inflammatory biomarkers in extremely preterm infants. We hypothesized that suspected prenatal infection (clinical chorioamnionitis or spontaneous preterm labor) and clinically diagnosed postnatal infection would be associated with unique biomarker signatures, and those patterns would be influenced by the degree of prematurity. Venous blood was collected daily for the first week and weekly for up to 14 additional weeks from 142 neonates born at 22-32 weeks gestation. A custom array was utilized to measure monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). C-reactive protein (CRP) levels were obtained from the electronic medical record. Independent of gestational age, MCP-1 was significantly increased (p < 0.001) in association with maternal preeclampsia, but MCP-1 was decreased (p < 0.01), and CRP was increased (p < 0.01) in the presence of chorioamnionitis with funisitis. IL-6 and CRP were both increased in infants diagnosed with postnatal infection, with peak levels observed on days 2 and 3, respectively. In conclusion, suspected prenatal and postnatal infections and non-infectious complications of pregnancy are associated with unique biomarker profiles, independent of gestational age, including over a 2-fold increase in MCP-1 among newborns of mothers with preeclampsia. Further, in those clinically diagnosed with a postnatal infection in the absence of antenatal infection concerns, IL-6 increases before CRP, emphasizing a potential role for expanded biomarker screening if antibiotics are initially avoided in infants delivered for maternal indications.

Keywords: adipokine; chemokine (C-C motif) ligand 2; interleukin-6; leptin; neonatal; preeclampsia.

Figure 1

Longitudinal values for (a) MCP-1 and (b) IL-6. Values are presented as mean plus or minus the standard error of the mean and are presented with a log scale. The IL-6 level on day 42 was influenced by a value of 10,424 pg/mL obtained from an infant that developed an acute exacerbation of chronic multi-organ failure.

Figure 2

MCP-1, IL-6, and CRP levels from birth to postnatal day 7. (a) Compared to neonates born with suspected prenatal infection (gray bars), neonates delivered without suspected prenatal infection (white bars) had increased plasma MCP-1 on day 2. (b,c) Compared to neonates without postnatal infection (white bars), neonates clinically diagnosed with a postnatal infection (gray bars) had increased plasma IL-6 on days 0 and 1 with increased CRP on days 1 and 2. IL-6 levels are graphed on a log scale. * p < 0.05.

Figure 3

Across the first 7 days after delivery, (a) MCP-1, (b) IL-6, and (c) CRP are contrasted for pregnancies with or without preeclampsia (PET) or clinical chorioamnionitis (Chorio). (a) Postnatal MCP-1 levels were increased in pregnancies complicated by PET, and (c) postnatal CRP levels were increased in pregnancies complicated by Chorio. * p < 0.001 versus no PET or no Chorio.

Figure 4

IL-6 (a) and CRP (b) on postnatal day 1 (blue bars), day 2 (white bars), and day 3 (yellow bars) for infants categorized as having no concern for infection, only prenatal infection, both prenatal and postnatal (perinatal) infection, or only postnatal infection. * p < 0.01 versus the other cohorts.