Molecular Signature Pregnancy (MSP)

Molecular Signature of Karen and Burmese Pregnant Women on the Thailand-Myanmar Border

The primary goal of the study is to identify biomarkers from the molecular signature predictive of pre-term birth. This will be achieved through high frequency sampling and profiling throughout pregnancy.

Study Overview

• Status: Completed
• Conditions: Pregnancy

Detailed Description

BACKGROUND Preterm birth occurs before 37 weeks and is a major cause of neonatal mortality and morbidity, and affecting 8% of newborns on the Thailand-Myanmar border. Identifying biochemical markers that are associated with preterm birth can guide in designing the most effective targeted intervention strategies for women at risk.

In order to identify biomarkers signatures predictive of preterm birth the investigators will employ high throughput profiling technologies (aka "a systems approach") that maximize the amount of information that can be obtained and knowledge generated from each participant sample. Preliminary data will also be obtained for infectious complications in order to assess potential for a systems approach such approach in detecting infectious events before onset of clinical symptoms or in absence of clinical symptoms. The rationale behind such approach and its importance for establishing personalized medicine approaches was detailed in a recent opinion article published. In addition parallel studies will be carried out in other countries such as Qatar and the US in order to assess environmental influences on blood and transcriptome signatures.

RESEARCH DESIGN This is a prospective pregnancy cohort from the first trimester until post-partum. The investigators are unable to predict which women will have preterm birth or infection.

STUDY POPULATION 400 Pregnant women with confirmed viable pregnancy of more than 8+0 weeks and less than 14 weeks of pregnancy, who are healthy, intend to deliver at SMRU and can attend for two weekly ANC visits.

METHOD AND TECHNIQUE

• Pregnant women attending SMRU ANC clinics will be invited to participate in the study.

• Study samples will include:

  1. A small blood volume (100 micro litres) will be collected by finger prick sampling via a capillary straw. The sample will be transferred into a microtube containing an RNA stabilizing solution and stored at -80°C. This will be repeated every two weeks, delivery and post-partum.
  2. A stool sample will be collected and stored at -80°C. This will be collected each trimester, delivery and post-partum.
  3. A vaginal swab will be collected from the posterior fornix under direct visualization by the midwife; and stored at -80°C. This will be collected each trimester, delivery and post-partum.

The post-partum visits, will be at 4-6 weeks and at 3months. The investigators estimate 15-18 blood samples, and 6 stool and vaginal swabs will be collected per women if they attend as expected. Fetal growth will be measured by 5-6 weekly ultrasound scans.

The sample set will be repeated if the woman has fever during pregnancy or post-partum (estimated at 5% of the women).

POTENTIAL VALUE Identifying biochemical markers that are associated with preterm can guide in designing the most effective targeted intervention strategies aimed at women at risk for preterm birth.

Funder & grant reference number: Sidra Medical and Research Center (Sidra)/ B9R01250; and supported by Wellcome [220211; assigned to Nicholas Day];

• Study Type: Observational
• Enrollment (Actual): 430

Contacts and Locations

Study Locations

• Thailand
  • Tak
    • Mae Sot, Tak, Thailand, 63110
      • Shoklo Malaria Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Target population: First trimester pregnant women with a viable pregnancy who will be followed for the outcome of interest of preterm births on the Thailand-Myanmar border

Description

Inclusion Criteria:

• Pregnant woman is willing and able to give informed consent for participation in the study.
• Karen or Burmese, age 18-49 years
• Healthy women with viable singleton first trimester (8+0 to < 14 weeks) pregnancy
• Plan to delivery at SMRU clinic
• Able (in the Investigators opinion) and willing to comply with all study requirements.

Exclusion Criteria:

The participant will not enter the study or continue in the study if ANY of the following apply:

• Emergency obstetric care required
• Pregnant woman (in the investigator's opinion) with medical or obstetrics complications which would make it difficult to comply with study requirements

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Characterization of the molecular signature of 30 preterm pregnancies defined by real-time PCR	up to 6 weeks post-partum

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of women who completed two weekly sampling	up to delivery
Proportion of rate of drop-out from sampling	up to delivery
Pain scores of the different samples from pregnant women.	up to 6 weeks post-partum
Molecular signature in relation to infection during pregnancy defined by real-time PCR	up to delivery
Molecular signature across the duration of pregnancy and post-partum time defined by real-time PCR	From enrolment at 8-14 weeks of pregnancy to 4-6 weeks post-partum

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Sidra Medical and Research Center

Publications and helpful links

General Publications

• Brummaier T, Syed Ahamed Kabeer B, Wilaisrisak P, Pimanpanarak M, Win AK, Pukrittayakamee S, Marr AK, Kino T, Al Khodor S, Terranegra A, Carrara VI, Nosten F, Utzinger J, Chaussabel D, Paris DH, McGready R. Cohort profile: molecular signature in pregnancy (MSP): longitudinal high-frequency sampling to characterise cross-omic trajectories in pregnancy in a resource-constrained setting. BMJ Open. 2020 Oct 10;10(10):e041631. doi: 10.1136/bmjopen-2020-041631.
• Brummaier T, Syed Ahamed Kabeer B, Lindow S, Konje JC, Pukrittayaamee S, Utzinger J, Toufiq M, Antoniou A, Marr AK, Suriyakan S, Kino T, Al Khodor S, Terranegra A, Nosten F, Paris DH, McGready R, Chaussabel D. A prospective cohort for the investigation of alteration in temporal transcriptional and microbiome trajectories preceding preterm birth: a study protocol. BMJ Open. 2019 Jan 15;9(1):e023417. doi: 10.1136/bmjopen-2018-023417.

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2016
• Primary Completion (Actual): January 30, 2023
• Study Completion (Actual): January 30, 2023

Study Registration Dates

• First Submitted: May 4, 2016
• First Submitted That Met QC Criteria: June 7, 2016
• First Posted (Estimated): June 13, 2016

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Molecular signature; Thailand-Myanmar border
• Other Study ID Numbers: SMRU1502

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES