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Background <p>Histopathological placental inflammation provides objective evidence of intrauterine inflammatory exposure in preterm birth, but placental histopathology is not immediately available after delivery. We aimed to determine whether placental inflammatory pathology is associated with cord blood and postnatal inflammatory biomarkers in preterm infants.</p> Methods <p>In this prospective cohort study, 87 preterm infants with birth weight &lt; 2500&#xa0;g were enrolled. Cord blood collected at birth was analyzed for procalcitonin (PCT), presepsin (P-SEP), and high-sensitivity C-reactive protein (hs-CRP). Placentas were categorized as no pathological findings, inflammatory placental pathology, or other placental pathology. Exploratory lesion-specific analyses further classified inflammatory lesions as maternal inflammatory response only (MIR-only) or fetal inflammatory response present (FIR-present). Multiple linear regression models with log-transformed outcomes were used to examine associations between inflammatory placental pathology and cord blood PCT and postnatal CRP after adjustment for perinatal covariates.</p> Results <p>Fifteen infants (17%) had inflammatory placental pathology. Cord blood PCT differed significantly between the primary placental pathology groups and was highest in infants with inflammatory placental pathology (<i>P</i> = 0.001), whereas cord blood P-SEP and hs-CRP did not differ significantly. Postnatal CRP was also higher in infants with inflammatory placental pathology (<i>P</i> = 0.004). In adjusted binary models, inflammatory placental pathology remained associated with higher cord blood PCT (adjusted fold change 2.31, 95% CI 1.50–3.55; <i>P</i> &lt; 0.001) and higher postnatal CRP (adjusted fold change 4.66, 95% CI 2.23–9.76; <i>P</i> &lt; 0.001). Exploratory lesion-specific analyses showed stepwise increases in cord blood PCT and postnatal CRP from no inflammatory lesion to MIR-only and the highest values in FIR-present cases (overall <i>P</i> = 0.003 and <i>P</i> = 0.002, respectively). Culture-confirmed or clinically diagnosed EOS and microbiological positivity were more frequent in infants with inflammatory placental pathology.</p> Conclusions <p>Histopathological placental inflammation in preterm infants was associated with higher umbilical cord PCT and higher postnatal CRP. Cord blood PCT showed the most consistent association with inflammatory placental pathology, including in exploratory analyses of fetal inflammatory response lesions. These findings support the potential clinical relevance of clinically available inflammatory biomarkers in relation to placental inflammatory pathology, but larger studies are needed to confirm lesion-specific associations and clarify their clinical utility.</p>

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Histopathological placental inflammation and umbilical cord blood inflammatory biomarkers in preterm infants: a prospective cohort study

  • 期刊论文

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  • 发表日期：

    2026年6月19日

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  • Krešimir Šantić,
  • Ivana Bogojević,
  • Ines Šahinović,
  • Kristina Kralik,
  • Jasmina Rajc,
  • Silvija Pušeljić,
  • Darjan Kardum

摘要

Background

Histopathological placental inflammation provides objective evidence of intrauterine inflammatory exposure in preterm birth, but placental histopathology is not immediately available after delivery. We aimed to determine whether placental inflammatory pathology is associated with cord blood and postnatal inflammatory biomarkers in preterm infants.

Methods

In this prospective cohort study, 87 preterm infants with birth weight < 2500 g were enrolled. Cord blood collected at birth was analyzed for procalcitonin (PCT), presepsin (P-SEP), and high-sensitivity C-reactive protein (hs-CRP). Placentas were categorized as no pathological findings, inflammatory placental pathology, or other placental pathology. Exploratory lesion-specific analyses further classified inflammatory lesions as maternal inflammatory response only (MIR-only) or fetal inflammatory response present (FIR-present). Multiple linear regression models with log-transformed outcomes were used to examine associations between inflammatory placental pathology and cord blood PCT and postnatal CRP after adjustment for perinatal covariates.

Results

Fifteen infants (17%) had inflammatory placental pathology. Cord blood PCT differed significantly between the primary placental pathology groups and was highest in infants with inflammatory placental pathology (P = 0.001), whereas cord blood P-SEP and hs-CRP did not differ significantly. Postnatal CRP was also higher in infants with inflammatory placental pathology (P = 0.004). In adjusted binary models, inflammatory placental pathology remained associated with higher cord blood PCT (adjusted fold change 2.31, 95% CI 1.50–3.55; P < 0.001) and higher postnatal CRP (adjusted fold change 4.66, 95% CI 2.23–9.76; P < 0.001). Exploratory lesion-specific analyses showed stepwise increases in cord blood PCT and postnatal CRP from no inflammatory lesion to MIR-only and the highest values in FIR-present cases (overall P = 0.003 and P = 0.002, respectively). Culture-confirmed or clinically diagnosed EOS and microbiological positivity were more frequent in infants with inflammatory placental pathology.

Conclusions

Histopathological placental inflammation in preterm infants was associated with higher umbilical cord PCT and higher postnatal CRP. Cord blood PCT showed the most consistent association with inflammatory placental pathology, including in exploratory analyses of fetal inflammatory response lesions. These findings support the potential clinical relevance of clinically available inflammatory biomarkers in relation to placental inflammatory pathology, but larger studies are needed to confirm lesion-specific associations and clarify their clinical utility.