Biomarkers in Obstetrical Complications

Biological Markers for the Prediction of the "Great Obstetrical Syndromes": A Longitudinal Study

Objective: To study the natural history of normal pregnancy and the most frequent pregnancy complications responsible for the excessive rate of perinatal morbidity and mortality, in order to develop models to predict the occurrence of these complications of pregnancy at the earliest possible time. The study focuses on the prediction of preterm labor with intact membranes, preterm prelabor rupture of membranes (PROM), preeclampsia, small for gestational age, gestational diabetes, and fetal death. These complications account for a minimum of $30 billion annually in the US alone.

Study population: A cohort of pregnant women seeking care at the prenatal clinic of the Perinatology Research Branch in Detroit, Michigan.

Design: A prospective observational cohort study of the natural history of women with a normal pregnancy, a history of adverse outcome, or those with a complication in the index pregnancy; therefore, this study will include nulliparous and parous women. Data will be collected at the time of clinic visits and will include interviews, clinical measurements, and ultrasound studies. We will assemble a biorepository of maternal biological fluids (blood, urine, saliva, cervicovaginal fluid, gingival crevicular fluid, swabs to characterize microbiota, amniotic fluid when a clinically indicated amniocentesis is performed). Placentas will be collected at the time of delivery as well as umbilical blood, and swabs to characterize the neonatal microbiota. We will use a retrospective case control and case-cohort design to generate models for the prediction of the most common pregnancy complications. These models will be developed by classifying obstetrical complications according to clinical presentation and histologic placental lesions. Models will be developed and subsequently validated in an independent cohort.

Outcome measures: The goal is to develop sensitive, specific, and parsimonious predictive models to identify the patients at risk for developing complications of pregnancy using a combination of clinical and biological markers (biochemical and biophysical).

Study Overview

• Status: Completed
• Conditions: Pregnancy; Preterm Birth; Preterm Labor; Maternal Fetal Factors

Detailed Description

Objective: To study the natural history of normal pregnancy and the most frequent pregnancy complications responsible for the excessive rate of perinatal morbidity and mortality, in order to develop models to predict the occurrence of these complications of pregnancy at the earliest possible time. The study focuses on the prediction of preterm labor with intact membranes, preterm prelabor rupture of membranes (PROM), preeclampsia, small for gestational age, gestational diabetes, and fetal death. These complications account for a minimum of $30 billion annually in the US alone.

Study population: A cohort of pregnant women seeking care at the prenatal clinic of the Perinatology Research Branch in Detroit, Michigan.

Design: A prospective observational cohort study of the natural history of women with a normal pregnancy, a history of adverse outcome, or those with a complication in the index pregnancy; therefore, this study will include nulliparous and parous women. Data will be collected at the time of clinic visits and will include interviews, clinical measurements, and ultrasound studies. We will assemble a biorepository of maternal biological fluids (blood, urine, saliva, cervicovaginal fluid, gingival crevicular fluid, swabs to characterize microbiota, amniotic fluid when a clinically indicated amniocentesis is performed). Placentas will be collected at the time of delivery as well as umbilical blood, and swabs to characterize the neonatal microbiota. We will use a retrospective case control and case-cohort design to generate models for the prediction of the most common pregnancy complications. These models will be developed by classifying obstetrical complications according to clinical presentation and histologic placental lesions. Models will be developed and subsequently validated in an independent cohort.

Outcome measures: The goal is to develop sensitive, specific, and parsimonious predictive models to identify the patients at risk for developing complications of pregnancy using a combination of clinical and biological markers (biochemical and biophysical).

• Study Type: Observational
• Enrollment (Actual): 746

Contacts and Locations

• Study Contact: Name: Roberto Romero, M.D.; Phone Number: (313) 993-2700; Email: romeror@mail.nih.gov

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University Hutzel Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women attending Detroit Medical Center prenatal clinics in Detroit.

Description

• INCLUSION CRITERIA:

This prospective longitudinal cohort study will recruit consecutive pregnant women aged 18 years or more who are between 6 and 26 6/7 weeks of gestation receiving care at the Detroit Medical Center. Informed consent will be administered prior to any research procedures.

EXCLUSION CRITERIA:

Women who have high order, multiple gestations (greater than or equal to 3 fetuses) or any of the following conditions are ineligible for participation in the study: active vaginal bleeding; serious medical illness (e.g. renal insufficiency, congestive heart disease, and chronic respiratory insufficiency)

EXCLUSION CRITERIA (for MRI examination only):

• Inability to perform MRI scan due to maternal habitus
• Metallic implants that would increase risk to the patient for MRI examination
• Previous occupational exposure to metal
• History of claustrophobia

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Pregnant Women; Pregnant women aged 18 years and older

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To develop sensitive, specific, and parsimonious predictive models to identify the patients at risk for developing complications of pregnancy using a combination of clinical and biological markers (biochemical and biophysical).	The following will be the primary outcome measures analyzed:-Preterm delivery <37, <34, and <32 weeks-Preeclampsia-Small for gestational age neonate-Fetal death-Gestational diabetes	After the study is closed to accrual

Collaborators and Investigators

• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2018
• Primary Completion (Actual): March 21, 2023
• Study Completion (Actual): March 21, 2023

Study Registration Dates

• First Submitted: March 27, 2018
• First Submitted That Met QC Criteria: March 28, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Natural History; Prematurity; Perinatal Mortality; Pregnancy Complications; Prediction of Adverse Pregnancy Outcome; Premature Rupture of Membranes
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Premature Birth; Obstetric Labor, Premature
• Other Study ID Numbers: 999918063; 18-CH-N063

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