Breath Metabolomics in the Laboring Parturient

Feasibility Study of the Collection of the Breath Metabolome From Healthy Parturients During Labor

This is primarily a feasibility study to determine whether quantitative measurement of volatile organic compounds (VOCs) in the breath of parturients undergoing labor is possible.

Aim A: To determine baseline values of breath metabolites and volatile organic compounds (VOCs) in the breath for term pregnant women.

Aim B: To gather preliminary data to determine breath metabolite and volatile organic compound (VOCs) signature change during labor and delivery.

Aim C: Compare the breath metabolite and volatile organic compound (VOCs) signature women undergoing induction compared to spontaneous vaginal deliveries.

Study Overview

• Status: Terminated
• Conditions: Labor Onset and Length Abnormalities
• Intervention / Treatment: Procedure: Breath Sample

Detailed Description

Breath metabolites, also known as volatile organic compounds (VOC's) are produced during periods of increased stress and as a marker of underlying medical conditions. The goal of this project is to collect VOCs within the breath in the initial stages of delivery in otherwise healthy parturients undergoing induction of labor. In addition to a panel of metabolites, we will obtain information on the 3400 compounds which compose the breath metabolome by gas mass spectrometry technology. This is the first step of a larger planned project to develop specialized panels of breath signatures during labor and delivery in parturients.

We will collect breath samples at bedside and measure metabolites in the laboratory. This is a feasibility study which we will use to determine normal values for a term parturient and changes of VOCs during the course of labor. We will also use this data to construct a power analysis and perform a follow-up study to test whether VOCs are associated with different aspects of pregnancy.

• Study Type: Observational
• Enrollment (Actual): 53

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305-5640
      • Lucile Packard Children Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Women with presenting for labor at Stanford.

Description

Inclusion Criteria:

• Otherwise healthy nulliparous women with singleton term (37-41 weeks) pregnant at least 18 years of age.
• Presenting for labor (induction of labor and spontaneous labor) at LPHC.

Exclusion Criteria:

• Participants unable to or refuse to give informed consent
• Participants that do not understand English or are hearing impaired
• Medical History: Chronic disease (HTN, diabetes, asthma)
• Obstetric History during this pregnancy: gestational diabetes, gestational hypertension, pre-eclampsia, Eclampsia
• Multiple gestation
• Any significant fetal anomalies
• Morbid obesity (BMI>50)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Induction of Labor; Samples collected from women who present for induction of labor. - The parturient will be asked to breathe 2 tidal volume breaths into a single breath collection bag. The breath collection bag will be closed between each breath. The combined 2 tidal volume breaths will count as a single sample. Samples will be collected at the following time points for patients presenting for induction of labor: A) Baseline: At presentation to labor and delivery unit and prior to initiation of augmentation of labor. A total of 1 sample. B) End of 1st stage of labor: At complete cervix dilatation and prior to starting to push. A total of 1 sample will be taken. C) End of 3rd stage of labor: Immediately (within 30 minutes) of delivery of the neonate. A total of 1 sample will be taken.	Procedure: Breath Sample; breathe 2 tidal volume breaths into a single breath collection bag. The breath collection bag will be closed between each breath. The combined 2 tidal volume breaths will count as a single sample.
Spontaneous Labor; Samples will be collected from women who present in spontaneous labor - The parturient will be asked to breathe 2 tidal volume breaths into a single breath collection bag. The breath collection bag will be closed between each breath. The combined 2 tidal volume breaths will count as a single sample. Samples will be taken at the following endpoints: A) End of 1st stage of labor: At completely cervix dilated and prior starting pushing. A total of 1 sample will be taken. B) End of 3rd stage of labor: Immediately (within 30 minutes) of delivery of the neonate. A total of 1 sample will be taken.	Procedure: Breath Sample; breathe 2 tidal volume breaths into a single breath collection bag. The breath collection bag will be closed between each breath. The combined 2 tidal volume breaths will count as a single sample.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Profile of volatile organic compounds of the breath	Mass spectrometry analysis of volatile organic compounds of the breath	Up to 24 hours

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Cedar J Fowler, MD/PhD/MPH, Stanford University; Principal Investigator: Pervez Sultan, MD, Stanford University

Publications and helpful links

General Publications

• Rattray NJ, Hamrang Z, Trivedi DK, Goodacre R, Fowler SJ. Taking your breath away: metabolomics breathes life in to personalized medicine. Trends Biotechnol. 2014 Oct;32(10):538-48. doi: 10.1016/j.tibtech.2014.08.003. Epub 2014 Aug 29.
• Norwitz ER, Bonney EA, Snegovskikh VV, Williams MA, Phillippe M, Park JS, Abrahams VM. Molecular Regulation of Parturition: The Role of the Decidual Clock. Cold Spring Harb Perspect Med. 2015 Apr 27;5(11):a023143. doi: 10.1101/cshperspect.a023143.
• McLoughlin G. Interventions during pregnancy to prevent preterm birth: An overview of Cochrane systematic reviews. Res Nurs Health. 2020 Apr;43(2):206-207. doi: 10.1002/nur.22005. Epub 2019 Dec 20. No abstract available.
• Wallace MAG, Pleil JD. Evolution of clinical and environmental health applications of exhaled breath research: Review of methods and instrumentation for gas-phase, condensate, and aerosols. Anal Chim Acta. 2018 Sep 18;1024:18-38. doi: 10.1016/j.aca.2018.01.069. Epub 2018 Feb 9.
• Sukul P, Schubert JK, Trefz P, Miekisch W. Natural menstrual rhythm and oral contraception diversely affect exhaled breath compositions. Sci Rep. 2018 Jul 18;8(1):10838. doi: 10.1038/s41598-018-29221-z.
• Nakhleh MK, Haick H, Humbert M, Cohen-Kaminsky S. Volatolomics of breath as an emerging frontier in pulmonary arterial hypertension. Eur Respir J. 2017 Feb 23;49(2):1601897. doi: 10.1183/13993003.01897-2016. Print 2017 Feb.
• Cristescu SM, Kiss R, Hekkert St, Dalby M, Harren FJ, Risby TH, Marczin N; Harefield BIOSTRESS study investigators. Real-time monitoring of endogenous lipid peroxidation by exhaled ethylene in patients undergoing cardiac surgery. Am J Physiol Lung Cell Mol Physiol. 2014 Oct 1;307(7):L509-15. doi: 10.1152/ajplung.00168.2014. Epub 2014 Aug 15.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2020
• Primary Completion (Actual): June 6, 2023
• Study Completion (Actual): June 6, 2023

Study Registration Dates

• First Submitted: September 17, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Congenital Abnormalities
• Other Study ID Numbers: 54731

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after publication and deidentification (text, tables, figures, and appendices). The data will be available for individual participant data meta-analysis.
• IPD Sharing Time Frame: Beginning 9 months and ending 24 months following article publication
• IPD Sharing Access Criteria: Proposals may be submitted up to 24 months following article publication. These proposals will be only reviewed if those investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. After 24 months, the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at (Link to be provided later, please contact PI if unable to locate link).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No