Exposure to nicotine and tobacco products during pregnancy
| ISRCTN | ISRCTN13835237 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13835237 |
| IRAS number | 269631 |
| Secondary identifying numbers | V4.0; IRAS project ID: 269631 |
- Submission date
- 25/11/2019
- Registration date
- 27/11/2019
- Last edited
- 17/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English Summary
Background and study aims
Health professionals and pregnant women are cautious about recommending or using e-cigarettes (ECs) in pregnancy, due to lack of detailed safety information. The main aim of the study is to measure toxins and cancer causing substances in the urine of women who used to smoke and now just use ECs compared with women who just smoke.
Who can participate?
Pregnant women who are smokers, users of ECs, nicotine replacement therapy, smoke and use ECs, or have never smoked.
What does the study involve?
Pregnant women will be invited to take part when they attend a routine antenatal appointment. If they agree to participate, they will be asked by a researcher to provide a urine sample (or a routinely collected sample will be used if available) and to complete a questionnaire (about themselves and use of nicotine/tobacco products, alcohol, cannabis). They will also be asked to blow into a device that measures exposure to tobacco smoke. They will then be asked to meet with the researcher again at a further routine antenatal visit, in order to repeat the assessments.
What are the possible benefits and risks of participating?
None
Where is the study run from?
1. St George’s University Hospitals NHS Foundation Trust, UK
2. Lancashire teaching Hospitals NHS Foundation Trust, UK
3. Bradford Teaching Hospital NHS Foundation Trust, UK
4. The Newcastle Upon Tyne Hospitals NHS Foundation Trust, UK
5. Gateshead Health NHS Foundation Trust, UK
When is the study starting and how long is it expected to run for?
November 2019 to October 2021
Who is funding the study?
Cancer Research UK
Who is the main contact?
Prof. Michael Ussher
mussher@sgul.ac.uk
Contact information
Scientific
Population Health Research Insititute
St George's University of London
Cranmer Terrace
London
SW17 ORE
United Kingdom
 ORCID ID |
0000-0002-0995-7955 |
|---|---|
| Phone | +44 (0)20 8725 5605 |
| mussher@sgul.ac.uk |
Study information
| Study design | Observational cross-sectional multicentre study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | Maternal exposure to carcinogens, toxicants and nicotine during pregnancy among e-cigarette users, smokers, nicotine replacement therapy users and among those who have never used nicotine or tobacco products |
| Study hypothesis | During pregnancy, we hypothesise that eletronic cigarette (EC) users will have significantly lower levels of urinary acrolein than smokers. As secondary objectives we will explore levels of a range of biomarkers in exclusive EC users compared with exclusive smokers, dual users of cigarettes and ECs, exclusive nicotine replacement therapy (NRT) users; dual users of cigarettes and NRT, and ‘never users of tobacco or nicotine products’. Generally, the hypothesis is that less tobacco smoke exposure will equate to less toxin and carcinogen exposure. |
| Ethics approval(s) | Approved 29/10/2019, London - Brighton & Sussex Research Ethics Committee (Health Research Authority, Skipton House, 80 London Road, London, SE1 6LH; +44(0)207 104 8052; NRESCommittee.SECoast-BrightonandSussex@nhs.net), ref: 19/LO/1599 |
| Condition | Use of nicotine and tobacco products during pregnancy |
| Intervention | Pregnant women will be invited to take part when they attend a routine antenatal appointment. If they agree to participate, they will be asked by a researcher to provide a urine sample (or a routinely collected sample can be used if available) and to complete a questionnaire (about themselves and use of nicotine/tobacco products, alcohol, cannabis). They will also be asked to blow into a device that measures exposure to tobacco smoke. They will then be asked to meet with the researcher again at a further routine antenatal visit, in order to repeat the assessments. Urine samples will be stored in a freezer and at the end of the study will be sent to an external laboratory for testing. The results will provide valuable information for women who are pregnant, for healthcare professionals who care for those women and for regulators, about the potential safety of using ECs during pregnancy. |
| Intervention type | Other |
| Primary outcome measure | Current primary outcome measure as of 13/12/2021: Maternal urinary levels of the volatile organic compound Acrolein (metabolite HPMA) measured using urine test at the time of participation. Acrolein has two metabolites (3HPMA & 2CoEMA); the single primary outcome will be 3HPMA because 3HPMA has a higher ratio in smokers vs non-smokers compared with 2CoEMA. The metabolite 2CoEMA will be analysed as a secondary outcome. Previous primary outcome measure: Maternal urinary levels of the volatile organic compound Acrolein (metabolites HPMA and CEMA) measured using urine test at the time of participation |
| Secondary outcome measures | Current secondary outcome measures as of 13/12/2021: All tested in maternal urine at time of participation: 1. Tobacco exposure will be assessed with a test for minor tobacco alkaloids (anabasine, anatabine), expired carbon monoxide levels 2. Levels of nicotine, cotinine and their metabolites, to derive total nicotine equivalents 3. Nicotine metabolite ratio (NMR) 4. Two tobacco-specific nitrosamines (TSNAs) (i.e., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL) and N-nitrosonornicotine (NNN)), two heavy metals (i.e., cadmium (Cd) and lead (Pb)) and one polycyclic aromatic hydrocarbon (PAH) (i.e., 2-naphthol) 5. 13 volatile organic compounds (VOCs) parent (metabolite): acrolein (2CoEMA), 1,3-butadiene (MHB3), acrylamide (AAMA), acrylonitrile (CYMA), Benzene (PMA), crotonaldehyde (HPMM), cyanide (ATCA), isoprene (IPM3), ethylbenzene (PHGA), propylene oxide (HPM2), styrene (MADA), toluene/benzyl alcohol (BMA), and m,p-xylene (34MH) 6. Human chorionic gonadotropin (hCG) 7. Pregnancy-associated plasma protein A (PAPPA-A) 8. Use of alcohol and cannabinoids Previous secondary outcome measures: All tested in maternal urine at time of participation: 1. Tobacco exposure will be assessed with a test for minor tobacco alkaloids (anabasine, anatabine), expired carbon monoxide levels 2. Levels of nicotine, cotinine and their metabolites, to derive total nicotine equivalents 3. Nicotine metabolite ratio (NMR) 4. Two tobacco-specific nitrosamines (TSNAs) (i.e., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL) and N-nitrosonornicotine (NNN)), two heavy metals (i.e., cadmium (Cd) and lead (Pb)) and one polycyclic aromatic hydrocarbon (PAH) (i.e., 2-naphthol) 5. 12 volatile organic compounds (VOCs) parent (metabolite): 1,3-butadiene (MHB3), acrylamide (AAMA), acrylonitrile (CYMA), Benzene (PMA), crotonaldehyde (HPMM), cyanide (ATCA), isoprene (IPM3), ethylbenzene (PHGA), propylene oxide (HPM2), styrene (MADA), toluene/benzyl alcohol (BMA), and m,p-xylene (34MH) 6. Human chorionic gonadotropin (hCG) 7. Pregnancy-associated plasma protein A (PAPPA-A) 8. Use of alcohol and cannabinoids |
| Overall study start date | 01/09/2019 |
| Overall study end date | 31/10/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Sex | Female |
| Target number of participants | 204 |
| Total final enrolment | 149 |
| Participant inclusion criteria | 1. Pregnant women 2. Aged at least 16 years of age 3. Able to speak and read English 4. Do not report having had an active infection (chest infection, cold or flu, sore throat, or fever) within 24 hours of either of the two assessments 5. Willing and able to give informed consent for participation in the study 6. Meet criteria for one of six groups related to level and type of use of nicotine and tobacco products: 6.1. Group A. ‘Exclusive smokers’: Smoked more than 5 cigarettes every day for more than the last six months and have not vaped or used NRT in the last month 6.2. Group B. ‘ECs only’: Not smoked cigarettes for at least a month and have vaped every day for at least the last two weeks. Also, have not used NRT in the last month 6.3. Group C. ‘NRT only': Not smoked cigarettes for at least a month and have used NRT every day for at least the last two weeks. Also, have not vaped in the last month 6.4. Group D. Dual users of cigarettes and ECs: Smoked cigarettes on most days of the week for more than 6 months. Also, have been using e-cigarettes on most days of the week for at least the last two weeks 6.5. Group E. Dual users of cigarettes and NRT: Smoked cigarettes on most days of the week for more than 6 months. Also, have been using NRT on most days for at least the last two weeks 6.6. Group F. ‘never smokers’: Have never smoked or used any nicotine or tobacco products |
| Participant exclusion criteria | Current participant exclusion criteria as of 20/10/2021: 1. Have used tobacco products other than cigarettes in the last month (e.g., cigars, heat-not-burn) 2. Have used both NRT and ECs in the last month 3. Have used nicotine free e-cigarettes in the last month 4. Report having had an active infection (chest infection, cold or flu, sore throat, or fever) within 24 hours of either of the two assessments 5. Reported as not currently smoking with an expired carbon monoxide reading of >3 parts per million (where an expired carbon monoxide reading has been obtained) Previous participant exclusion criteria: 1. Have used tobacco products other than cigarettes in the last month (e.g., cigars, heat-not-burn) 2. Have used both NRT and ECs in the last month 3. Have used nicotine free e-cigarettes in the last month 4. Report having had an active infection (chest infection, cold or flu, sore throat, or fever) within 24 hours of either of the two assessments |
| Recruitment start date | 14/11/2019 |
| Recruitment end date | 30/04/2020 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
London
SW17 0QT
United Kingdom
Sharoe Green Lane
Preston
PR2 9HT
United Kingdom
Smith Lane
Bradford
BD9 6RJ
United Kingdom
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom
Queen Elizabeth Avenue
Sheriff Hill
Gateshead
NE9 6SX
United Kingdom
Sponsor information
Hospital/treatment centre
Blackshaw Road
London
SW17 0QT
England
United Kingdom
| Phone | +44(0)208 725 0892 |
|---|---|
| sahollin@sgul.ac.uk | |
| Website | https://www.stgeorges.nhs.uk/ |
"ROR" |
https://ror.org/039zedc16 |
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 28/02/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | The findings will be presented at international conferences (e.g., Society for Research on Nicotine and Tobacco) and, towards the end of the study period, will be submitted to a high impact journal (e.g., BMJ). We will also disseminate the findings to policy makers, NGOs and health professionals. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available as consent has not be obtained for this purpose. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Plain English results | 17/01/2025 | No | Yes |
Additional files
Editorial Notes
17/01/2025: Plain English results added.
18/12/2024: The intention to publish date was changed from 31/12/2024 to 28/02/2025.
10/09/2024: The intention to publish date was changed from 30/09/2024 to 31/12/2024.
20/06/2024: The intention to publish date has been changed from 30/06/2024 to 30/09/2024.
04/01/2024: The intention to publish date has been changed from 01/05/2024 to 30/06/2024.
18/12/2023: The intention to publish date has been changed from 30/12/2023 to 01/05/2024.
20/06/2023: The intention to publish date has been changed from 30/06/2023 to 30/12/2023.
15/12/2022: The intention to publish date has been changed from 31/12/2022 to 30/06/2023.
11/08/2022: Total final enrolment added.
21/04/2022: The intention to publish date has been changed from 30/04/2022 to 31/12/2022.
13/12/2021: The following changes have been made:
1. The primary outcome measure has been updated.
2. The secondary outcome measures have been updated.
3. Internal review.
20/10/2021: The participant exclusion criteria have been updated.
20/04/2021: The intention to publish date has been changed from 31/10/2020 to 30/04/2022.
14/10/2020: The following changes were made to the trial record:
1. Recruitment to this study is no longer paused.
2. The recruitment end date was changed from 31/10/2020 to 30/04/2020.
3. The overall trial end date was changed from 30/04/2021 to 31/10/2021.
4. The intention to publish date was changed from 30/04/2019 to 31/10/2020.
5. The protocol number was changed from V2.0 to V4.0.
20/04/2020: Due to current public health guidance, recruitment for this study has been paused.
26/11/2019: Trial’s existence confirmed by Cancer Research UK
