Abstract
There is no information about whether fetal growth restriction (FGR) is an independent risk factor for low-grade fetal inflammatory response (FIR), and which is more valuable for the prediction of early-onset neonatal sepsis (EONS) between low-grade FIR or fetal inflammatory response syndrome (FIRS) in the context of human early preterm sterile intrauterine environment. We examined FIR (umbilical cord plasma (UCP) CRP concentration at birth) according to the presence or absence of FGR (birth weight < 5th percentile for gestational age (GA)) and EONS in 81 singleton preterm births (GA at delivery: 24.5~33.5 weeks) within 72 h after amniocentesis and with sterile intrauterine environment. A sterile intrauterine environment was defined by the presence of both a sterile amniotic fluid (AF) (AF with both negative culture and MMP-8 < 23 ng/mL) and inflammation-free placenta. Median UCP CRP (ng/mL) was higher in cases with FGR than in those without FGR (63.2 vs. 34.5; p = 0.018), and FGR was an independent risk factor for low-grade FIR (UCP CRP ≥ 52.8 ng/mL) (OR 3.003, 95% CI 1.024–8.812, p = 0.045) after correction for confounders. Notably, low-grade FIR (positive likelihood-ratio (LR) and 95% CI, 2.3969 (1.4141–4.0625); negative-LR and 95% CI, 0.4802 (0.2591–0.8902)), but not FIRS (positive-LR and 95% CI, 2.1071 (0.7526–5.8993); negative-LR and 95% CI, 0.8510 (0.6497–1.1145)), was useful for the identification of EONS. In conclusion, FGR is an independent risk factor for low-grade FIR, and low-grade FIR, but not FIRS, has a value for the identification of EONS in the context of the early preterm sterile intrauterine environment.
Highlights
Fetal Growth Restriction (FGR) frequently develops due to utero-placental insufficiency [1,2], which is associated with chronic hypoxia at the feto–maternal interface [3,4,5]
We used C-reactive protein (CRP) as a marker for Fetal Inflammatory Response (FIR) at the year of 2003 based on the following reasons [24,25,26,27,28,29,30,31]: (1) assay of CRP has the advantage over cytokine determination (i.e., IL-6) in that it is widely available in most clinical laboratories; (2) the sensitivity of umbilical cord plasma (UCP) CRP in the identification of positive amniotic fluid (AF) culture, early-onset neonatal sepsis (EONS) and funisitis was similar to that of IL-6, and the specificity of CRP in the identification of EONS and funisitis was significantly higher than that of IL-6 [21]; and (3) there was a strong correlation between UCP CRP and IL-6 concentrations [21]
Given that chronic hypoxemia-absent bacterial infection results in mildly growth restricted offspring and mild to moderate FIR in animal studies [6,7] and Fetal Inflammatory Response Syndrome (FIRS) is the fetal counterpart of systemic inflammatory response syndrome (SIRS) in adults, there is a good chance that FGR in the sterile intrauterine environment of human preterm gestation is associated with either low-grade FIR or FIRS
Summary
FGR frequently develops due to utero-placental insufficiency [1,2], which is associated with chronic hypoxia at the feto–maternal interface [3,4,5]. Given that chronic hypoxemia-absent bacterial infection results in mildly growth restricted offspring and mild to moderate FIR in animal studies [6,7] and FIRS is the fetal counterpart of SIRS in adults, there is a good chance that FGR in the sterile intrauterine environment of human preterm gestation is associated with either low-grade FIR or FIRS
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