The Use of Maternal Serum Unconjugated Estriol for Monitoring the Prevention of Neonatal Respiratory Distress Syndrome

The objective of this project is to evaluate clinical significance of measuring maternal blood estriol levels, after the administration of antenatal corticosteroids to enhance lung maturity. The investigators will test for associations of the change in maternal estriol with the development of respiratory distress syndrome. The investigators are also interested in determining whether salivary estriol is a valid surrogate to estriol blood assays. In addition the investigators will correlate these changes to pharmacokinetic (PK), pharmacodynamics (PD), and pharmacogenetic measures of betamethasone administration and fetal respiratory outcome

Study Overview

• Status: Completed
• Conditions: Neonatal Respiratory Distress Syndrome

Detailed Description

We will obtain serum and saliva for estriol measurement before or within 2 hours of antenatal corticosteroid administration and about 24 hours after each dose is given.

Women who consent to an optional PK portion of the study will have plasma samples obtained pre-dose and then on a schedule of approximately 0.5-2, 4-8, 10-15, 22-24 hours after the first dose and then 6-8, 24, and 48 hours after the 2nd dose. One sample will be collected in each of these times.

A sample of whole blood will be obtained for DNA isolation. At the time of delivery, umbilical cord blood will be collected before being discarded for DNA and plasma. If we are unable to obtain umbilical cord blood, a buccal swab will be collected from the baby for DNA extraction.

• Study Type: Observational
• Enrollment (Actual): 160

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Methodist Hospital
    • Indianapolis, Indiana, United States, 46202
      • Eskenazi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Mothers with preterm labor (23 - 34 weeks) on antenatal corticosteroid for prevention of neonatal respiratory distress syndrome will be recruited

Description

Inclusion Criteria:

• Gestational age between 23-34 weeks with a diagnosis of threatened preterm labor or preterm premature rupture of membranes, or other diagnosis with a high likelihood of preterm delivery where the provider is recommending administering antenatal corticosteroids
• Singleton gestation
• Live fetus at the time of enrollment
• Being administered antenatal corticosteroids to enhance lung maturity
• Ability to provide written informed consent to participate in the study

Exclusion Criteria:

• • Maternal age <18 years old

  • Major congenital anomalies
  • Multiple gestations

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
salivary estriol measurement; Serum Estriol measurement via different assays is complex, expensive, labor intensive, time consuming, and generally performed at specific reference labs. Salivary Estriol level is an ideal potential surrogate for serum Estriol. It is convenient, non-invasive, and expedient. It may not, however, be as sensitive as serum estriol concentrations at detecting the association with glucocorticoid response. This study will collect both samples to determine which one is better suited for clinical use in this condition.
serum estriol measure; we will determine if changes in maternal serum estriol represent a biomarker of response to antenatal corticosteroids as evidenced by neonatal development of RDS
Betamethasone pharmacokinetic; we will determine if pharmacokinetic parameters and neonatal outcomes after antenatal corticosteroid use are associated with genetic polymorphisms in drug metabolizing enzymes, transporters, and steroid pathway genes
betamethasone concentration and genetics; we will determine if maternal betamethasone concentrations and genetics are associated with maternal estriol changes or RDS development

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory distress syndrome	Respiratory Distress Syndrome is diagnosed clinically, by need for mechanical ventilation and oxygen for at least 48 hours, and the presence of radiologic chest findings.	At least 30 days after delivery, the maternal and neonatal charts will be reviewed

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: University of California, Los Angeles
• Investigators: Principal Investigator: David Haas, MD, MSc, Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): November 8, 2016
• Study Completion (Actual): June 30, 2017

Study Registration Dates

• First Submitted: April 9, 2014
• First Submitted That Met QC Criteria: April 11, 2014
• First Posted (Estimate): April 14, 2014

Study Record Updates

• Last Update Posted (Actual): February 28, 2019
• Last Update Submitted That Met QC Criteria: February 27, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Hyaline Membrane Disease
• Other Study ID Numbers: 1108006470

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Will plan to deposit any genetic information into appropriate repository like dbgap. Other data potentially available upon request.
• IPD Sharing Time Frame: after study completion and will be available in dbgap as long as that database is supported
• IPD Sharing Access Criteria: contact study contact or dbgap
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL