Predictive Value of Maternal Blood Protein Signatures in Preterm Birth

Accurate prediction of preterm birth is critical for clinical management to improve the neonatal and maternal outcomes. A clinical challenge remains for current predicting biomarkers due to the complexity and multifactorial nature of underlying causes of preterm birth.

This study aims to evaluate the prediction performance of new maternal blood biomarkers (proteomic markers) on the occurrence of preterm birth.

Study Overview

• Status: Completed
• Conditions: Preterm Birth

Detailed Description

Preterm birth (PTB), defined by delivery before 37 weeks of gestational age, represents a substantial public health challenge due to its elevated rates of neonatal morbidity and mortality worldwide. The prevalence of PTB exhibits variation, ranging from approximately 12-13% in the USA to 5-9% in other developed nations, underscoring a complex issue marked by regional disparities.

Emphasizing its significant public health ramifications, PTB is recognized as a primary contributor to mortality among children under five, particularly with 40% of deaths occurring within the first month of life in this demographic. Following PTB, infants face an increased vulnerability to severe complications like respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis, accentuating the acute threats to infant well-being and longevity. Addressing these early-life hurdles requires the formulation of robust strategies for prediction and prevention to alleviate the immediate hazards linked with premature birth.

Preventing PTB crucially depends on accurately identifying women at high risk. Interventions like vaginal progesterone and cervical cerclage are recommended for those with a short cervical length. However, the effectiveness of these strategies is frequently compromised by limitations in current screening methods, which struggle to accurately predict PTB. This underscores a significant gap in effectively identifying all at-risk women, underscoring the necessity for enhanced screening techniques to more precisely pinpoint women who would benefit from preventive interventions.

Current screening methods, primarily based on measuring cervical length and assessing historical risk factors, are inadequate in capturing the multifaceted nature of PTB risk, leading to missed opportunities for intervention and prevention. This inadequacy underscores the importance of developing methods that can more accurately identify women at high risk. Research efforts aimed at addressing these challenges suggest the potential of integrating new biomarkers and maternal characteristics into screening protocols to improve the predictive accuracy of PTB screenings.

Building upon the premise that the placenta plays a pivotal role in fetal health regulation, and that insights into the pathologic mechanisms leading to spontaneous preterm birth can be gleaned from the placental transcriptome, the investigators utilized existing transcriptomic data from the public domain, employing bioinformatics methodologies. This data was further complemented by quantitative proteomics analysis techniques using mass spectrometry. Through this integrated approach, the investigators have developed a novel PTB screening panel comprising three protein biomarkers. The efficacy and prediction performance of this three-protein predictor will be evaluated in this study with independent cohorts.

• Study Type: Observational
• Enrollment (Actual): 18000

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China
      • Department of Obstetrics and Gynecology, the Eighth Affiliated Hospital, Sun Yat-sen University;
    • Shenzhen, Guangdong, China
      • Department of Obstetrics, Shenzhen Maternity and Child Healthcare Hospital
  • Henan
    • Zhengzhou, Henan, China
      • Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University
  • Hunan
    • Changsha, Hunan, China
      • Hunan Provincial Maternal and Child Health Care Hospital
  • Shandong
    • Jinan, Shandong, China
      • Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

General women with pregnancy

Description

Inclusion Criteria:

• Pregnant women between18 and 45 years of age
• Single pregnancy
• Consent to participate in the study

Exclusion Criteria:

• Premature rupture of membranes
• Uterine malformation
• Fetal malformation
• Pregestational Diabetes
• Systemic diseases (chronic kidney disease, autoimmune disease, etc.)
• Serious medical illness (renal insufficiency, congestive heart disease, chronic respiratory insufficiency, etc.).
• Suffering from other disease unfavorable to the trial such as metal illness
• Any maternal or fetal condition that requires termination of pregnancy.
• Active vaginal bleeding.
• Multifetal pregnancy with greater than or equal to 2 fetuses.
• Lack of clinical outcome or incomplete basic information
• Iatrogenic premature delivery or induced labor
• Lack of consent.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Preterm birth; Pregnancy with delivery before 37 weeks of gestational age
Term birth control; Pregnancy with delivery at 37 weeks or later of gestational age

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction of preterm birth	The primary outcome is the prediction of preterm birth, defined as pregnancy duration of less than 37 weeks. Preterm birth prediction score is calculated as sum of the z-score of 3 proteins' multiple of median (MoM) values.	After blood draw during doctor's visit before 37 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity, Specificity, Positive predictive value (PPV), Negative predictive value (NPV)	Sensitivity, Specificity, PPV and NPV was calculate for identification the preterm birth cases using pre-defined threshold of prediction score.	After blood draw during doctor's visit before 37 weeks of gestation

Collaborators and Investigators

• Sponsor: HBI Solutions Inc.
• Collaborators: Shenzhen Maternity & Child Healthcare Hospital
• Investigators: Principal Investigator: Qiong Luo, M.D. Ph.D., Department of Obstetrics, Women's Hospital of Zhejiang University, School of Medicine, Hangzhou, 310006, China

Publications and helpful links

General Publications

• Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science. 2014 Aug 15;345(6198):760-5. doi: 10.1126/science.1251816. Epub 2014 Aug 14.
• Boyle AK, Rinaldi SF, Norman JE, Stock SJ. Preterm birth: Inflammation, fetal injury and treatment strategies. J Reprod Immunol. 2017 Feb;119:62-66. doi: 10.1016/j.jri.2016.11.008. Epub 2016 Dec 2.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: October 28, 2024
• First Submitted That Met QC Criteria: October 28, 2024
• First Posted (Actual): October 29, 2024

Study Record Updates

• Last Update Posted (Estimated): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Preterm birth; Maternal blood; Serological protein
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth
• Other Study ID Numbers: PTB_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No