S100B Protein as a Biomarker for Fetal Hypoxia in Late Growth Restriction: Study Protocol

Introduction

This study protocol aims to evaluate the role of S100B protein concentration in umbilical cord blood as a potential biomarker indicating fetal hypoxia associated with late fetal growth restriction (FGR). The significance of S100B lies in its association with central nervous system (CNS) injury following hypoxic-ischemic events. Measuring S100B levels soon after birth may provide a noninvasive method for identifying newborns at risk due to perinatal hypoxia resulting from FGR. Early detection is crucial to enhance surveillance, enable timely diagnostic evaluations, and prompt interventions that could improve long-term neurodevelopmental outcomes.

Methods and Analysis

The study will involve two groups of full-term pregnant women: a case group with prenatally diagnosed late FGR and a control group having normal fetal growth parameters. After delivery, cord blood samples will be collected for analysis of S100B protein levels along with assessments of pH, base excess (BE), and lactate levels. Additionally, fetal blood flow metrics will be evaluated in the umbilical artery (UA), uterine arteries (UtA), ductus venosus (DV), and middle cerebral artery (MCA) via ultrasound conducted within 48 hours prior to delivery. The primary objectives are to compare S100B protein concentrations between the groups and evaluate possible correlations with fetal Doppler findings as well as blood gas parameters.

Objectives

The study's objectives are threefold:

1. To determine whether S100B protein concentrations in cord blood are statistically higher in neonates with diagnosed late FGR compared to healthy controls.
2. To assess the correlation of these S100B levels with fetal blood flow parameters measured via ultrasound in the UA, UtA, DV, and MCA.
3. To evaluate the effectiveness of S100B concentration in relation to other perinatal markers of hypoxic stress, such as pH, BE, and lactate levels in umbilical blood.

Trial Design

This prospective cohort study is designed to clarify the utility of S100B protein levels as an early biomarker for identifying perinatal hypoxia in neonates with FGR versus a control cohort without growth limitations. It is structured to comply with STROBE guidelines for observational research studies.

Study Setting

The research is being conducted at the Institute of Mother and Child in Warsaw, within both the Department of Obstetrics and Gynecology and the Department of Neonatology and Neonatal Intensive Care. These departments are recognized as tertiary referral units and manage a considerable number of full-term FGR cases each year. Recruitment began in June 2024 and is set to last for approximately 18 months, concluding around December 2025. The authors anticipate initial results to be available by June 2026, though delays may arise depending on recruitment success.

Definitions

The criteria for diagnosing late FGR follows certain guidelines established by the Polish Society of Gynecologists and Obstetricians for conditions arising after the 32nd week of gestation.

Late FGR is confirmed based on the following ultrasound criteria:

• Abdominal circumference (AC) below the 3rd percentile for gestational age.
• Estimated fetal weight (EFW) below the 3rd percentile for gestational age.
• Or, EFW or AC below the 10th percentile along with at least one of: significant growth retardation, a low cerebroplacental index (CPR), or elevated UA pulsatility index (PI).

Eligibility Criteria

Study Group – Inclusion Criteria

• Full-term, singleton pregnancies (≥37 weeks).
• Diagnosis of late-onset FGR based on the established criteria.

Study Group – Exclusion Criteria

• Maternal conditions affecting placental blood flow, such as smoking or other drug use.
• Maternal depression requiring treatment with SSRIs.
• Signs of intrauterine infection or complications such as prolonged labor during delivery.

Assessing S100B protein levels in cord blood could facilitate the early identification of infants likely to develop complications related to fetal hypoxia, ensuring timely intervention and tailored care from birth to improve overall neurodevelopmental outcomes.