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Predicting Neonatal Morbidity and Correlations with Maternal and Neonatal Biomarkers in Connection with Fetal
Diana Iulia Vasilescu1,2, Adriana Mihaela Dan2,3, Ion Dragomir2
1Doctoral School, "Carol Davila" University of Medicine and Pharmacy, 020956 Bucharest, Romania.
Insights
Fetal Inflammatory Response Syndrome (FIRS) in preterm infants is linked to adverse outcomes and increased medical needs. Early identification of intrauterine inflammation is crucial for targeted neonatal monitoring and improved care.
Area of Science:
- Neonatalogy
- Perinatal Medicine
- Immunology
Background:
- Fetal Inflammatory Response Syndrome (FIRS) significantly contributes to neonatal morbidity in premature infants.
- FIRS is a systemic inflammatory process triggered by intrauterine infections, leading to adverse outcomes like preterm birth, sepsis, and neurodevelopmental impairments.
- Elevated fetal plasma Interleukin-6 (IL-6) levels (>11 pg/mL) are a key biomarker for FIRS.
Purpose of the Study:
- To evaluate clinical, laboratory, and therapeutic differences between preterm neonates with and without FIRS.
- To identify associations between FIRS and specific neonatal complications and maternal factors.
Main Methods:
- A prospective cohort study of 125 preterm neonates (23-37 weeks gestation) admitted to NICU.
- Infants were categorized into FIRS and non-FIRS groups based on cord blood IL-6 levels (>11 pg/mL).
- Demographic, biochemical, and therapeutic parameters were compared between groups.
Main Results:
- Preterm neonates with FIRS exhibited lower birth weight, length, head circumference, and Apgar scores.
- FIRS was associated with higher rates of vaginal delivery, meconium-stained fluid, metabolic imbalances, respiratory support, antibiotic use, and blood transfusions.
- Neonatal complications including sepsis (EOS/LOS), respiratory distress, NEC, IVH, and ROP were significantly more frequent in the FIRS group. *Chlamydia trachomatis* was linked to FIRS.
Conclusions:
- FIRS in preterm neonates is associated with perinatal inflammation, adverse short/long-term outcomes, and intensive medical interventions.
- Early identification of intrauterine inflammation is vital for developing targeted neonatal monitoring strategies.
- Further research is needed to investigate long-term outcomes and refine diagnostic and therapeutic protocols for FIRS.
Abstract:
Introduction: Fetal Inflammatory Response Syndrome (FIRS) is widely acknowledged for its contribution to neonatal morbidity in premature infants. Being a systemic inflammatory process triggered by intrauterine infections or other stimuli, FIRS has gained significant attention due to its complex implications for neonatal adverse outcomes: preterm birth, early onset neonatal sepsis, death or long-term neurodevelopmental impairments. Fetal plasma Interleukin-6 (IL-6) levels above 11 pg/mL define FIRS and serve as an essential biomarker, providing insights into the complex mechanisms underlying this response. This study aims to evaluate the clinical, laboratory, and therapeutic differences between preterm neonates with and without FIRS. Methods: A prospective cohort study was conducted, involving 125 preterm neonates with gestational ages between 23 and 37 weeks, who were admitted to the Neonatal Intensive Care Unit (NICU) at the Emergency University Hospital Bucharest between April 2023 and April 2025. Infants were stratified into FIRS and non-FIRS groups based on the measurement of cord blood IL-6 levels greater than 11 pg/mL. Demographic, biochemical, and therapeutic parameters were compared across the two groups. Results: Preterm neonates with FIRS had significantly lower birth weight, length, and head circumference, and lower Apgar scores at 1 and 5 min (p = 0.001). FIRS was associated with a higher incidence of vaginal delivery, meconium-stained amniotic fluid, and neonatal metabolic imbalances, requiring more respiratory support, longer antibiotic treatment periods, and more blood transfusions (p < 0.05). Neonatal complications such as early-onset sepsis (EOS) and late-onset sepsis (LOS), respiratory distress, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP) were significantly more frequent in the FIRS group (p ≤ 0.01). Among maternal cervical screening, Chlamydia trachomatis was the only pathogen significantly associated with FIRS. Conclusions: FIRS in preterm neonates is linked to important perinatal inflammation, adverse short and long-term outcomes, and extensive medical intervention. These findings highlight the value of early identification of intrauterine inflammation and targeted neonatal monitoring strategies. Further studies are needed to explore long-term outcomes and improve diagnostic and therapeutic protocols.
