Cord Blood S100B Protein Concentration in Neonates With Fetal Growth Restriction

Official title

Evaluating the Utility of S100B Protein Concentration for Diagnosing Fetal Central Nervous System Hypoxia-Ischemia in Children With Late Fetal Growth Retardation: A Prospective Cohort Study

Overview

S100B protein is a biomarker that increases following central nervous system (CNS) damage. Measuring this protein's levels may allow for the early identification of infants at high risk for developmental abnormalities, such as fetal growth restriction (FGR), even on the first day of life, in a non-invasive manner. Early detection could enable timely interventions and rehabilitation, potentially improving the child's prognosis and long-term outcomes. This study investigates two groups of full-term pregnancies: a study group with prenatally diagnosed late FGR, and a control group with normal fetal growth. Following delivery, cord blood samples from both groups will be analyzed for S100B protein concentrations, pH, base excess (BE), and lactate levels. Additionally, fetal blood flow parameters in the umbilical artery (UA), uterine arteries (UtA), ductus venosus (DV), and middle cerebral artery (MCA) will be monitored via ultrasound within 48 hours before delivery. This study aims to compare S100B protein concentrations in umbilical cord blood between the two groups and to assess correlations with fetal Doppler parameters, pH, BE, and lactate levels in cord blood gas analysis. Ultimately, we seek to determine the effectiveness of S100B protein concentration as a biomarker for diagnosing fetal CNS hypoxia- ischemia in FGR-affected children, compared to those with normal growth.

Interventions

• Diagnostic test Prenatal ultrasound examination with blood flow analysis
  For all patients who provide informed consent to participate in the study, an ultrasound examination is performed within 48 hours prior to delivery. This assessment includes: 1. Measurement of fetal anthropometric parameters and estimation of fetal weight. 2. Evaluation of blood flow using the pulsatility index (PI) in the UA, UtA, DV, and MCA.
• Diagnostic test Umbilical cord blood gas analysis
  A 0.5 mL blood sample is collected from the clamped section of the umbilical cord and immediately sent to the laboratory for cord blood gas analysis, including the determination of pH, base excess (BE), and lactate levels.
• Diagnostic test Umbilical cord blood S100B protein level
  A 1 mL sample of cord blood is collected in a labeled tube, which includes the mother's name, the child's gender, date of birth, and date of collection. The sample is then sent to the laboratory for centrifugation. The resulting serum samples are frozen, and once approximately 80 samples have been collected, they will be thawed and analyzed for S100B protein concentration. Any remaining material after laboratory processing will be properly disposed of.
• Diagnostic test Neonatal transfontanelle ultrasound assessment
  A transfontanelle ultrasound examination is performed to assess for any abnormalities in the newborn.

Primary outcome measures

• Cord blood S100B protein concentration [Time frame: Within 3 months of enrollment]

Secondary outcome measures (2)

• Correlation of cord blood S100B concentration with pH, BE, and lactate levels in cord blood gas analysis [Time frame: Within 3 months of enrollment]
• Association between cord blood S100B protein concentration and fetal blood flow parameters [Time frame: Within 3 months of enrollment]

Eligibility criteria

Study Group - Inclusion Criteria:

• Women with a full-term pregnancy (≥37 weeks of gestation), singleton.
• Pregnancy complicated by FGR.

Study Group - Exclusion Criteria:

• Antenatal (at recruitment):

• Maternal conditions that may affect the blood flow in placental vessels, including smoking, use of illicit stimulant substances, or pregestational diabetes.
• Maternal depression requiring pharmacological treatment (e.g., SSRIs).
• Intrapartum:

• Factors indicating a possible intrauterine infection, such as amniotic fluid leakage for more than 15 hours, spontaneous preterm labor, diagnosed intrauterine infection, or symptoms of infection in the mother.
• Prolonged labor lasting more than 15 hours.

Control Group - Inclusion Criteria:

• Women with a full-term pregnancy (≥37 weeks of gestation), singleton.
• Pregnancy not complicated by FGR.

Control Group - Exclusion Criteria:

• Antenatal (at recruitment):

• Maternal conditions that may affect placental blood flow, such as smoking, use of illicit stimulant substances, pregestational diabetes, or chronic hypertension.
• Maternal depression requiring pharmacological treatment (e.g., SSRIs).
• Risk factors for intrauterine HI, including abnormal fetal blood flow parameters on ultrasound, abnormal CTG recordings, or the need for intrauterine transfusion.
• Intrapartum:

• Indicators of possible intrauterine infection, such as amniotic fluid leakage for more than 15 hours, spontaneous preterm delivery, diagnosed intrauterine infection, or maternal symptoms of infection.
• Risk factors for perinatal HI.
• Prolonged labor lasting more than 15 hours (counted from the onset of regular uterine contractions).
• Birth weight below the 10th percentile or above the 90th percentile.
• Apgar score less than 8 at the 1st, 3rd, 5th, or 10th minute of life.
• Abnormal umbilical cord blood gas analysis results, defined as pH < 7.15 or BE < -9.3 mmol/l.
• Postnatal:

• Neonatal anemia requiring a top-up transfusion within the first 24 hours of life

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Poland · 1 center

• Institute of Mother and Child — Warsaw

Publications

• Mazarico E, Llurba E, Cumplido R, Valls A, Melchor JC, Iglesias M, Cabero L, Gratacos E, Gomez-Roig MD. Neural injury markers in intrauterine growth restriction and their relation to perinatal outcomes. Pediatr Res. 2017 Sep;82(3):452-457. doi: 10.1038/pr.2017.108. Epub 2017 May 31. PMID 28426650
• Strzalko B, Karowicz-Bilinska A, Wyka K, Krajewski P, Kesiak M, Kociszewska-Najman B. Serum S100B Protein Concentrations in SGA/FGR newborns. Ginekol Pol. 2021 Jun 9. doi: 10.5603/GP.a2021.0119. Online ahead of print. PMID 34105746
• Malhotra A, Ditchfield M, Fahey MC, Castillo-Melendez M, Allison BJ, Polglase GR, Wallace EM, Hodges R, Jenkin G, Miller SL. Detection and assessment of brain injury in the growth-restricted fetus and neonate. Pediatr Res. 2017 Aug;82(2):184-193. doi: 10.1038/pr.2017.37. Epub 2017 May 17. PMID 28234891
• Zaigham M, Lundberg F, Olofsson P. Protein S100B in umbilical cord blood as a potential biomarker of hypoxic-ischemic encephalopathy in asphyxiated newborns. Early Hum Dev. 2017 Sep;112:48-53. doi: 10.1016/j.earlhumdev.2017.07.015. Epub 2017 Jul 27. PMID 28756088
• Bouvier D, Giguere Y, Pereira B, Bernard N, Marc I, Sapin V, Forest JC. Cord blood S100B: reference ranges and interest for early identification of newborns with brain injury. Clin Chem Lab Med. 2020 Jan 28;58(2):285-293. doi: 10.1515/cclm-2019-0737. PMID 31622243
• Velipasaoglu M, Yurdakok M, Ozyuncu O, Portakal O, Deren O. Neural injury markers to predict neonatal complications in intrauterine growth restriction. J Obstet Gynaecol. 2015;35(6):555-60. doi: 10.3109/01443615.2014.978848. Epub 2014 Nov 13. PMID 25392968
• Perrone S, Grassi F, Caporilli C, Boscarino G, Carbone G, Petrolini C, Gambini LM, Di Peri A, Moretti S, Buonocore G, Esposito SMR. Brain Damage in Preterm and Full-Term Neonates: Serum Biomarkers for the Early Diagnosis and Intervention. Antioxidants (Basel). 2023 Jan 29;12(2):309. doi: 10.3390/antiox12020309. PMID 36829868
• Chiang LM, Chen WY, Yang YC, Jeng MJ. Elevation of serum S100 protein concentration as a marker of ischemic brain damage in extremely preterm infants. J Chin Med Assoc. 2015 Oct;78(10):610-6. doi: 10.1016/j.jcma.2015.06.009. Epub 2015 Aug 15. PMID 26285828

Identifiers

NCT: NCT06893926 · S100BFGR

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗