PRISM Follow-up: Child health review following progesterone in pregnancy
| ISRCTN | ISRCTN10651813 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10651813 |
| IRAS number | 333342 |
| Secondary identifying numbers | RG_23-147 |
- Submission date
- 30/09/2025
- Registration date
- 08/10/2025
- Last edited
- 06/10/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Background and study aims
The PRISM trial (https://www.isrctn.com/ISRCTN14163439) was the largest ever study that tested whether vaginal progesterone treatment can prevent miscarriage in women with early pregnancy bleeding. The trial found that vaginal progesterone increased the live birth rate by 5% in comparison to placebo for women with early pregnancy bleeding and a history of one or more previous miscarriages.
The UK NICE Committee for the guideline ‘Ectopic pregnancy and miscarriage: diagnosis and initial management (NG126)’ reviewed this evidence and updated their guidance in November 2021 to recommend the use of vaginal micronised progesterone to treat women with the dual risk factors of a history of one or more previous miscarriages and early pregnancy bleeding.
Vaginal progesterone treatment has been routinely used in early pregnancy for women undergoing fertility treatment and early pregnancy bleeding complications over the last 40 years. However, data on long-term health outcomes of children born following early pregnancy progesterone treatment have not been routinely collected. For clinical trials conducted in pregnancy, it is good standard practice to check the health and development of children who were born during the trial. This information will give us assurances about the use of vaginal progesterone treatment during early pregnancy. The large cohort of children born in the PRISM trial provides a unique opportunity to conduct a follow-up study to assess the long-term health of children who were born to women with and without progesterone treatment. This study aims to compare the health outcomes of children born to women who took progesterone during early pregnancy with those who received a placebo.
Who can participate?
Adult women who previously participated in the PRISM trial and the children who were born. The women will complete information about their child. The central team will make all efforts, including verification using the NHS Spine, to ensure only appropriate participants are contacted.
What does the study involve?
The relevant participants will be contacted to:
1. Describe the PRISM Follow-up study
2. Provide a participant information sheet and, if willing, complete a consent form and a health questionnaire on behalf of their child(ren).
To maximise the validity of this study, Confidentiality Advisory Group (CAG) approval will be used to check the electronic health record. This permission will support the existing ethically approved PRISM consent to follow up and trace the participants through the NHS database and GP records. The electronic health record will be used to check the mortality status of the woman and her child(ren) and to confirm their current contact information. If a participant does not reply, where available, some of the health data may be retrieved from the electronic health care record. This is a legal provision to temporarily release confidential patient information (CPI) without the need for “explicit” consent in line with section 251 of the National Health Service Act 2006. Section 251 allows the common law duty of confidentiality to be temporarily lifted for medical purposes and in the public interest.
What are the possible benefits and risks of participating?
Current evidence indicates that early pregnancy exposure to vaginal progesterone does not have long-term harmful effects during childhood. Data from this study may inform the evidence base and future practice.
Where is the study run from?
University of Birmingham, UK
When is the study starting and how long is it expected to run for?
August 2025 to December 2026
Who is funding the study?
NIHR Research for Patient Benefit (RfPB), UK
Who is the main contact?
prism@trials.bham.ac.uk
Contact information
Public, Scientific, Principal investigator
Research Fellow, Tommy’s National Centre for Miscarriage Research (Birmingham)
WHO Collaborating Centre for Global Women’s Health
Department of Metabolism and Systems Science
School of Medical Sciences
College of Medicine and Health
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
 ORCID ID |
0000-0002-0070-2294 |
|---|---|
| l.priest.1@bham.ac.uk |
Public, Scientific, Principal investigator
Associate Professor of Maternal Health Clinical Trials
University of Birmingham
Edgbaston
Birmingham
B15 2TH
United Kingdom
| ORCID ID |
0000-0001-5632-079X |
|---|---|
| a.j.devall@bham.ac.uk |
Study information
| Study design | Prospective observational cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Home, Medical and other records |
| Study type | Quality of life |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Long-term health assessment of children following first trimester progesterone treatment in the PRISM trial (PRISM Follow-up) |
| Study acronym | PRISM FU |
| Study objectives | • To compare the Health Utilities Index (HUI3) score between the progesterone and placebo groups. • To compare the EQ-5D-y3L score between the progesterone and placebo groups. • To compare the incidence of Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), dyslexia, dysgraphia, dyspraxia, dyscalculia, Obsessive-Compulsive Disorder (OCD), anxiety, and depression between the progesterone and placebo groups. |
| Ethics approval(s) |
Approved 18/08/2025, Seasonal REC (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 104 8241; seasonal.rec@hra.nhs.uk), ref: 25/LO/0587 |
| Health condition(s) or problem(s) studied | A prospective observational study to follow up children born to women following first-trimester progesterone treatment who participated in the PRISM trial. |
| Intervention | This is a prospective observational study to follow up children born to women who participated in the PRISM trial (https://www.isrctn.com/ISRCTN14163439). Health Utilities Index (HUI3) score of the children – a rating scale used to measure general health status and health-related quality of life (HRQoL). The Health Utilities Index 3 (HUI3) is a generic, preference-based, comprehensive system for measuring health status and health-related quality of life. HUI3 was developed to apply to both clinical and general population studies, and to have structural independence among the attributes. Each HUI attribute (dimension) has 3–6 levels of classification and is very responsive to changes in health caused by treatment therapies or other influences. The questionnaire is validated and commonly used as an outcome measure in clinical studies and population health surveys. The HUI3 classification system is comprised of 8 attributes – (i) Vision, (ii) Hearing, (iii) Speech, (iv) Ambulation, (v) Dexterity, (vi) Emotion, (vii) Cognition and (viii) Pain, each measuring 5 or 6 levels of ability (including low ability and disability). EQ-5D-Y-3L score of the children: The EQ-5D-Y-3L descriptive system comprises the five dimensions: (i) mobility, (ii) self-care, (iii) usual activities, (iv) pain/discomfort and (v) anxiety and depression. Within this validated questionnaire, each dimension has three levels: no problems, some problems, and extreme problems. The participant is asked to indicate their child(ren)’s health state by ticking the box next to the most appropriate statement in each of the five dimensions. Additional secondary outcomes for the children: 1. Autism spectrum disorder (ASD) – a neurodevelopmental disorder characterised by deficits in social communication and the presence of restricted interests and repetitive behaviours. 2. Attention deficit hyperactivity disorder (ADHD) – an ongoing pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development. 3. Dyslexia – a learning difficulty that primarily affects the skills involved in accurate and fluent word reading and spelling. 4. Dysgraphia – a disorder of writing ability, including problems with letter formation/legibility, letter spacing, spelling, fine motor coordination, rate of writing, grammar, and composition. 5. Dyspraxia – a developmental co-ordination disorder (DCD) that affects movement and co-ordination. 6. Dyscalculia – a specific and persistent difficulty in understanding numbers, which can lead to a diverse range of difficulties with mathematics. 7. Obsessive-compulsive disorder (OCD) – a mental health condition where a person has obsessive thoughts and compulsive behaviours. 8. Anxiety – an emotion characterised by feelings of tension, worried thoughts, and associated physiological changes. 9. Depression – a mood disorder that causes a persistent feeling of sadness and loss of interest These health conditions must have been formally diagnosed by a doctor or a relevant specialist. Most commonly, this will involve the child being referred for a formal assessment. |
| Intervention type | Other |
| Primary outcome measure | General health status and health-related quality of life (HRQoL) measured using the Health Utilities Index (HUI3) at one time point |
| Secondary outcome measures | 1. Health-related quality of life measured using the EuroQol EQ-5D-Y-3L quality-of-life tool at one time point 2. Incidence of childhood health conditions (formally diagnosed by a doctor or relevant specialist) measured using University of Birmingham questions at one time point. The conditions investigated are autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), dyslexia, dysgraphia, dyspraxia, dyscalculia, obsessive-compulsive disorder (OCD), anxiety and depression. |
| Overall study start date | 18/08/2025 |
| Completion date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target number of participants | 2502 |
| Key inclusion criteria | 1. Participation in the PRISM Trial and had a live birth 2. Previously gave informed consent as part of the PRISM trial to be contacted about future follow-up studies 3. Willing and able to give informed consent for this study 4. Ability to confirm they wish to complete the parental follow-up questionnaire |
| Key exclusion criteria | Not meeting the key inclusion criteria |
| Date of first enrolment | 01/11/2025 |
| Date of final enrolment | 31/05/2026 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
-
-
United Kingdom
Sponsor information
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| researchgovernance@contacts.bham.ac.uk | |
| Website | http://www.birmingham.ac.uk/index.aspx |
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/01/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from prism@trials.bham.ac.uk. The type of data that will be shared: Appropriate data-sharing requests will be considered by the study management group and the Tommy’s National Centre for Miscarriage Research, based at the University of Birmingham. Any data shared will be anonymous. Data will be stored securely in a redcap database on servers at the University of Birmingham. Personal data recorded on all documents will be regarded as strictly confidential and will be handled and stored in accordance with the General Data Protection Regulation, 2018. |
Editorial Notes
01/10/2025: Study's existence confirmed by Health Research Authority (HRA) (UK)
