Investigating the effects of steroids given in pregnancy on infant stress responses
| ISRCTN | ISRCTN49188855 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN49188855 |
| IRAS number | 309594 |
| Secondary identifying numbers | AC21185, NIHR133388, IRAS 309594, CPMS 52586 |
- Submission date
- 29/04/2022
- Registration date
- 20/07/2022
- Last edited
- 14/01/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English Summary
Background and study aims
The use of ACS in late preterm (35-36 weeks gestation) and early term (37 weeks gestation) is an area of substantial controversy in obstetrics. There is evidence that ACS reduce serious breathing difficulties and neonatal unit admission but there is potential for both short (e.g. low blood sugar levels) and long-term harms (e.g. brain development) in some exposed babies. Practice is highly variable regarding ACS administration at later preterm and early term gestations.
STOPPIT-3 is a multicentre placebo-controlled trial to evaluate the effectiveness of ACS (dexamethasone phosphate) prior to planned birth of twins in an NHS setting. The primary outcome is respiratory support within 72 hours of birth. STOPPIT-M is a linked study to explore the mechanisms underlying ACS effects on the infant’s endogenous HPA axis responses, and resultant effects on neonatal outcomes.
Study aims:
We will use these samples to compare the stress axis in infants with
1. early adverse health (need for respiratory support; low APGAR score; low blood sugar; jaundice), in babies exposed and non-exposed to ACS
2. developmental delay aged 2 years (from the main STOPPIT-3 trial)
A secondary aim is to explore whether these outcomes differ in boys and girls.
Gaining a better understanding of the mechanisms of action of ACS is essential to improve targeted delivery of ACS – ensuring administration to mothers and babies who will benefit from ACS, but avoiding harm in those who will not benefit.
Who can participate?
STOPPIT-M will aim to recruit 543 women pregnant with twins enrolled in the STOPPIT-3 (ISRCTN59959611) trial across 50 sites.
What does the study involve?
Women who have agreed to take part will have the following samples collected at delivery of twins: paired maternal and cord blood samples, amniotic fluid sample and a placenta sample. In a subset of infants in Edinburgh the following samples will be taken: a saliva sample and a hair sample.
What are the possible benefits and risks of participating?
The researchers cannot promise the study will directly help you or your babies. Information the researchers obtain from your participation in the study may help inform on the future healthcare of other patients. Taking part will help create much needed evidence on the use of ACS prior to a planned birth of twins which will help women and babies in future.
Where is the study run from?
University of Edinburgh and NHS Lothian (UK)
When is the study starting and how long is it expected to run for?
November 2021 to May 2025
Who is funding the study?
National Institute for Health and Care Research (NIHR) The Efficacy and Mechanism Evaluation (EME) Programme (UK)
Who is the main contact?
The trial management team at the University of Edinburgh Clinical Trials Unit (ECTU)
STOPPIT.Trial@ed.ac.uk
Contact information
Principal Investigator
Edinburgh Clinical Trials Unit
Usher Building
University of Edinburgh
5-7 Little France Road
Edinburgh BioQuarter – Gate 3
Edinburgh
EH16 4UX
United Kingdom
 ORCID ID |
0000-0001-6226-8270 |
|---|---|
| Phone | +44 131 242 6762 |
| R.Reynolds@ed.ac.uk |
Public
Edinburgh Clinical Trials Unit
Usher Building
University of Edinburgh
5-7 Little France Road
Edinburgh BioQuarter – Gate 3
Edinburgh
EH16 4UX
United Kingdom
| Phone | +44 131 651 9923 |
|---|---|
| STOPPIT.Trial@ed.ac.uk |
Study information
| Study design | Observational/mechanistic study linked to STOPPIT-3 trial (ISRCTN59959611) |
|---|---|
| Primary study design | Observational |
| Secondary study design | Mechanistic |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | 41666 PIS V1.0 22Feb2022.pdf |
| Scientific title | Infant hypothalamic-pituitary-adrenal axis responses following antenatal corticosteroids and perinatal outcomes: a mechanism of action of health intervention study |
| Study acronym | STOPPIT-M |
| Study hypothesis | 1. Late preterm/early term born infants who have respiratory morbidity despite ACS treatment (non-responders); or who have other morbidities (hypoglycaemia; low Apgar score; jaundice; effects on neurodevelopment) have suppressed cord blood cortisol levels and reduction in glucocorticoid signalling 2. In infants who do not receive ACS, immaturity of the HPA axis with low endogenous cortisol levels in cord blood and reduced glucocorticoid signalling is associated with increased rates of morbidity and neonatal care requirements |
| Ethics approval(s) | Approved 28/02/2022, North of Scotland Research Ethics Service (Summerfield House, 2 Eday Road, Aberdeen, AB15 6RE, UK; +44 1224 558458; gram.nosres@nhs.scot), ref: 22/NS/0017 |
| Condition | Effects of antenatal corticosteroids on infant stress responses |
| Intervention | The site clinical team will be asked to take the following samples at delivery of twins: • Paired maternal and cord blood samples (about 10mls) • Amniotic fluid sample • Placenta sample In a subset of infants, in Edinburgh, the following samples will be taken: • a saliva sample • a hair sample |
| Intervention type | Other |
| Primary outcome measure | 1. Measurement of endogenous glucocorticoids, dexamethasone and its metabolites in maternal and cord blood and amniotic fluid in samples collected at birth. 2. Measurement of glucocorticoid receptor in cord blood leukocytes collected at birth. 3. Measurement of placental genes regulating glucocorticoids in placenta samples collected at birth. |
| Secondary outcome measures | 1. Salivary cortisol pre and post heel-prick at 5 days 2. Hair cortisol at 5 days |
| Overall study start date | 01/11/2021 |
| Overall study end date | 01/05/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Female |
| Target number of participants | 543 |
| Total final enrolment | 17 |
| Participant inclusion criteria | 1. Women with a twin pregnancy with a planned caesarean birth scheduled between 35+0 and 38+6 weeks gestation who are enrolled in STOPPIT-3 (ISRCTN59959611) 2. Women aged 16 years or older and able to provide electronic or written consent |
| Participant exclusion criteria | 1. Women taking prescribed corticosteroid medication (orally, injected, inhaled or topical) within the last 3 months. 2. Women with planned vaginal birth. |
| Recruitment start date | 01/05/2022 |
| Recruitment end date | 01/05/2025 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centre
2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom
Sponsor information
University/education
ACCORD
QMRI
47 Little France Crescent
Edinburgh
EH16 4TJ
Scotland
United Kingdom
| Phone | +44 131 242 3330 |
|---|---|
| jo-anne.robertson@ed.ac.uk | |
| Website | https://www.accord.scot/ |
"ROR" |
https://ror.org/01nrxwf90 |
Hospital/treatment centre
Waverley Gate
2-4 Waterloo Place
Edinburgh
EH1 3EG
Scotland
United Kingdom
| Phone | +44 (0)845 424 2424 |
|---|---|
| accord@nhslothian.scot.nhs.uk | |
| Website | https://www.nhslothian.scot/Pages/default.aspx |
|
"ROR" |
https://ror.org/03q82t418 |
Funders
Funder type
Government
No information available
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 | 01/05/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | It is expected that the study findings will be published as soon as possible in a peer-reviewed open access journal. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1.0 | 22/02/2022 | 16/05/2022 | No | Yes |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | version 2.0 | 25/11/2022 | 20/11/2023 | No | Yes |
Additional files
Editorial Notes
02/10/2024: Contact details updated. Total final enrolment added.
20/11/2023: The following changes have been made:
1. An updated participant information sheet (PIS) has been uploaded.
2. The public contact has been changed.
16/05/2022: Trial's existence confirmed by NHS Grampian
