The optimal management in monochorionic twins (OMMIT) study

Plain English Summary

Background and study aims
Monochorionic diamniotic (MCDA) twin pregnancy is where a woman is pregnant with twins who share a single placenta. This type of pregnancy is very high-risk, as it can result in fatal complications such as twin-twin transfusion syndrome, TTTS (a condition where blood flows unevenly between the babies). This is thought to happen because inter-twin placental anastomoses (connections between arteries and veins) can form, causing a significant change in the blood pressures of the twins as one twin "donates" a significant proportion of its blood to the other "recipient" twin. The donor twin may then go into kidney failure and produce very little amniotic fluid (fetal urine), and the recipient twin produces too much amniotic fluid and may go into heart failure. Without treatment, 90% of these pregnancies will miscarry before 26 weeks. However, there is an effective treatment for TTTS called fetoscopic laser ablation (FLA) which involves inserting a small camera into the amniotic fluid sac of the recipient twin and burning the vascular anastomoses on the surface of the placenta, to block these connections and attempt to rebalance the blood flow between the twins. In 85% cases treated by FLA at least one twin will survive, in 40% of cases 2 twins will survive. The aim of this study is to develop a model to predict which MC twin pregnancies will develop complications later in pregnancy. The project takes place in two parts, the first part looking back on women who previously had an MCDA pregnancy, and the second part looking at women who are currently experiencing a MCDA pregnancy.

Who can participate?
In the first part of the study, women who had MCDA pregnancies and had samples of blood and information about the result of their pregnancy stored. In the second part of the study, women aged 18-50 who book at Birmingham Women's Hospital with MC twin pregnancies (cohort C) and those who are referred to Birmingham Women's Hospital for assessment of treatment of complications of MC twin pregnancies (cohort S) can participate.

What does the study involve?
In the first part of the study, the researchers look at any chemical indicators (biomarkers) of angiogenesis (new blood vessel formation) and the function of the placenta in previously stored blood samples that were taken in the first 12 weeks of pregnancy. These are then compared to information taken from ultrasound measurements at the same time and then matched to the outcomes (how the pregnancy progressed). In the second part of the study, there are two groups of women being examined: Cohort S and Cohort C. Women in both groups have blood samples taken at 12, 16 and 20 weeks of their pregnancy. In addition, their ultrasound results and information about the outcome of the pregnancy is also collected. For participants in cohort C (women booked to have FLA), a sample of blood and amniotic fluid, and ultrasound measurements are also taken immediately before and after they have the FLA procedure. These blood samples are then looked at in the lab to look for noteworthy biomarkers.

What are the possible benefits and risks of participating?
There are no direct benefits involved with taking part in the study. In the second study, there is a small risk that participants may experience pain, discomfort or bruising during or after blood samples are taken.

Where is the study run from?
Birmingham Women's Hospital (UK)

When is the study starting and how long is it expected to run for?
October 2014 to October 2018

Who is funding the study?
1. The Richard and Jack Wiseman Trust (UK)
2. British Maternal and Fetal Medicine Society (UK)

Who is the main contact?
Dr Fiona Mackie

Study website

Type

Public

Contact name

Dr Fiona Mackie

ORCID ID

http://orcid.org/0000-0001-8248-5811

Contact details

Academic Department O&G
3rd Floor
Birmingham Women's Hospital
Mindelsohn Way
Edgbaston
B15 2TG
United Kingdom

EudraCT/CTIS number

IRAS number

ClinicalTrials.gov number

Protocol/serial number

1

Scientific title

Optimal Management in complicated Monochorionic Twins (OMMIT) Study

Acronym

OMMIT

Study hypothesis

It is possible to predict which monochorionic twin pregnancies will go on to develop complications later in pregnancy based on first-trimester maternal blood samples and ultrasound measurements.

Ethics approval(s)

1. East Midlands - Derby Research Ethics Committee, 09/06/2015, ref: 15/EM/0240 (OMMIT 1)
2. East Midlands - Derby Research Ethics Committee, 01/07/2015, ref: 15/EM/0244 (OMMIT 2)

Study design

Observational single-centre study in two parts: a retrospective study (OMMIT 1) and a prospective study (OMMIT 2)

Primary study design

Observational

Secondary study design

Case-control study

Study setting(s)

Hospital

Study type

Screening

Patient information sheet

Not available in web format, please use contact details to request a patient information sheet

Condition

Complications of monochorionic (MC) twin pregnancies including twin-twin transfusion syndrome (TTTS), twin anaemia-polycythaemia sequence (TAPS), selective intrauterine growth restriction (sIUGR) and single intrauterine fetal demise (sIUFD)

Intervention

There are two parts to this trial: a retrospective study and a prospective study.

In the retrospective study (OMMIT 1), markers of angiogenesis (blood vessel developmental) and placental function in the stored first-trimester blood samples will be analysed, these will then be combined with first-trimester ultrasound measurements and matched to outcome data to attempt to create a model.

In the prospective study (OMMIT 2), there will be 2 cohorts: Cohort S and Cohort C.
Cohort S will have blood samples taken at 12, 16 and 20 weeks gestation, their ultrasound measurements will be recorded and their outcomes collected. Cohort C will have a maternal blood sample pre- FLA and post-FLA. Amniotic fluid samples will be collected immediately pre-FLA and post-FLA, and ultrasound measurements. Researchers will use the results of the retrospective study to decide which biomarkers to investigate in the blood and amniotic fluid samples.
The following will then be compared:
1. "Normal" Cohort S blood samples to Cohort C samples
2. Cohort S samples longitudinally over the 3 time points
3. Cohort C pre-FLA and post-FLA blood and amniotic fluid samples

Intervention type

Other

Primary outcome measure

Complication of MC pregnancy:
1. TTTS
2. Discordant growth
3. Selective IUGR
4. Single twin demise: <24 weeks, >24 weeks
5. Discordant chromosomal or structural anomaly
6. Neonatal mortality (until discharge)

These outcomes will be extracted from the hospital notes using a specially designed data collection form and recognised definitions of conditions where appropriate.

Secondary outcome measures

1. Antenatal complications (e.g. antepartum haemorrhage, small for gestational age, gestational diabetes, pre-eclampsia)
2. Maternal morbidity: (e.g. sepsis, hypertension, platelet or coagulation anomaly)
3. Gestation of delivery (If preterm <37 weeks iatrogenic or spontaneous)
4. Induction (or C/S) and precipitating cause
5. Mode of delivery (and reason)
6. Admission to NICU (and indication)
7. Composite measure of maternal morbidity
8. Composite measure of neonatal morbidity

These outcomes will be extracted from the hospital notes using a specially designed data collection form and recognised definitions of conditions where appropriate.

Overall study start date

01/10/2014

Overall study end date

01/10/2018

Reason abandoned (if study stopped)

Participant inclusion criteria

Retrospective study
Monochorionic diamniotic (MCDA) pregnancies for which trimester blood samples and outcome data have been stored.

Prospective study
Cohort S will be patients:
1. Booking at Birmingham Women's Clinic with an MCDA pregnancy confirmed on first-trimester ultrasound
2. Less than 20+6 weeks gestation at recruitment
3. Provide valid informed consent

Cohort C will be patients:
1. Referred to Birmingham Women's Hospital for treatment of a complication of monochorionic pregnancies
2. Provide valid informed consent

Participant type(s)

Patient

Age group

Adult

Sex

Female

Target number of participants

In the retrospective study the aim is to include approximately 170 participants, in the prospective study the trialists anticipate recruiting 56 recruits to Cohort S and 40-60 recruits to Cohort C

Total final enrolment

177

Participant exclusion criteria

1. Unable to provide consent
2. Unable to confirm chorionicity

Recruitment start date

07/08/2015

Recruitment end date

07/08/2017

Countries of recruitment

England, United Kingdom

Study participating centre

Birmingham Women's Hospital
Mindelsohn Way
Birmingham
B15 2TG
United Kingdom

Organisation

Birmingham Women's NHS Foundation Trust

Sponsor details

Birmingham Women's Hospital
Mindelsohn Way
Edgbaston
B15 2TG
England
United Kingdom

Sponsor type

Hospital/treatment centre

Website

ROR

https://ror.org/056ajev02

Funder type

Charity

Funder name

The Richard and Jack Wiseman Trust

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

British Maternal and Fetal Medicine Society

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

Planned presentation of research at British Maternal & Fetal Medicine Society (BMFMS) and publication in appropriate journals.

Intention to publish date

01/10/2019

Individual participant data (IPD) sharing plan

IPD sharing plan summary

Available on request

Study outputs