Impact of histological fetal inflammatory response on neonatal outcomes


A recent study reveals associations between concomitant histological fetal inflammatory response and adverse neonatal outcomes, urging further investigation into implications.

Impact of histological fetal inflammatory response on neonatal outcomes | Image Credit: © Bostan Natalia - © Bostan Natalia -

Impact of histological fetal inflammatory response on neonatal outcomes | Image Credit: © Bostan Natalia - © Bostan Natalia -

Concomitant histological fetal inflammatory response (FIR) is associated with early-onset sepsis (EOS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP), according to a recent study published in the American Journal of Obstetrics & Gynecology.1


  1. The study underscores the significance of histological fetal inflammatory response (FIR) in preterm infants born with histological chorioamnionitis (HCA), indicating its association with adverse neonatal outcomes such as early-onset sepsis (EOS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP).
  2. Infants with both HCA and histological FIR exhibited a significantly higher risk of EOS, especially pronounced in those with lower gestational age (GA), emphasizing the importance of understanding FIR's impact on infection susceptibility in preterm infants.
  3. Unlike EOS, rates of late-onset sepsis did not significantly differ between infants with HCA alone and those with both HCA and FIR, suggesting a nuanced relationship between FIR and different types of neonatal infections.
  4. While necrotizing enterocolitis (NEC) rates did not substantially differ between groups, a subgroup analysis revealed lower GA infants with FIR had reduced odds of NEC but increased odds of BPD, highlighting the complexity of FIR's influence on various neonatal morbidities.
  5. Histological FIR was significantly associated with IVH and ROP, indicating its potential role in neurological and ophthalmic complications in preterm infants, necessitating further research for comprehensive understanding and clinical management.

Preterm birth (PTB) occurs in 1 in 10 women worldwide, with intrauterine inflammation reported in approximately half of extremely PTBs. Histological chorioamnionitis (HCA) has been linked to multiple adverse outcomes, including EOS, late-onset sepsis (LOS), BPD, IVH, cerebral white matter damage, and long-term neurodevelopmental sequelae.

Clinical chorioamnionitis impacts 2% to 12% of term deliveries but can be preventing using intrapartum antibiotic prophylaxis among patients with Group B Streptococcus.2 A reduction in clinical chorioamnionitis of 49% has been reported among patients receiving intrapartum antibiotic prophylaxis.

Data has also indicated the presence of FIRs in 50% to 70% of preterm placentas with HCA.1 However, there is little information about the impact of FIR in addition to HCA on maternal and neonatal outcomes.

To determine whether the incidence of adverse neonatal outcomes increased in HCA with concomitant FIR vs HCA without FIR, investigators conducted a systematic review and meta-analysis. Studies were found through searches of the Embase, MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials databases.

Title, abstract, and full-text screening were performed by 3 independent reviews, with disagreements solved through discussion. Eligible studies included cohort and case-control studies and case series with a study population of preterm infants or very low birthweight (VLBW) neonates.

Neonatal outcomes in infants with HCA and FIR were compared to those in preterm infants with HCA alone. Neonatal mortality, EOS, LOS, BPD, and necrotizing enterocolitis (NEC) were the primary outcomes of the analysis. Additional outcomes included IVH, ROP, periventricular leukomalacia, and clinical chorioamnionitis (CCA).

Data abstraction and risk of bias assessment were performed by 2 independent authors. Risk of bias was determined based on Cochrane Prognosis Methods Group recommendations.

There were 50 articles included in the final analysis, 25 of which included chorionic vasculitis when defining FIR. Most studies were observational cohort studies, though 1 retrospective case-control study was included. Vague outcome definitions indicated a high risk of bias.

HCA with histological FIR was reported in 62.4% of infants. The overall odds ratio (OR) for mortality in these infants was 1.18, indicating no significant link between histological intrauterine inflammation and mortality.

A significantly increased OR of 1.84 was reported for EOS among infants with HCA and histological FIR. This association was increased in infants with a lower gestational age (GA), with an OR of 2.23. However, LOS rates did not differ between infants with HCA and FIR vs those with HCA alone.

NEC rates also did not differ between groups, except for a subgroup of patients with a lower GA having significantly reduced odds. The subgroup with a lower GA also had significantly increased odds of BPD, with an OR of 1.30.

FIR presence was also significantly associated with IVH, with an OR of 1.54, but this association was not reported for severe IVH. Additionally, an OR of 2.99 was reported for CCA among preterm infants with FIR. ROP was also significantly associated with the presence of FIR with chorioamnionitis.

These results indicated higher rates of EOS, BPD, IVH, and ROP among infants with HCA and histological FIR. Investigators recommended a meta-analysis comparing HCA alone to histologically negative patients be performed for further understanding.


1. Kovács K, Zsuzsanna Kovács O, Bajzát D, et al. The histologic fetal inflammatory response and neonatal outcomes: systematic review and meta-analysis. American Journal of Obstetrics & Gynecology. 2024;230(5):493-511.E3. doi:10.1016/j.ajog.2023.11.1223

2. Krewson C. Intrapartum antibiotic prophylaxis for Group B Streptococcus reduces risks. Contemporary OB/GYN. December 19, 2023. Accessed May 10, 2024.

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