Developing methods of simultaneously analysing occurrence of several birth defects to improve identification of teratogenic medications
Lead Research Organisation:
St George's, University of London
Department Name: Institute of Population Health
Abstract
Many pregnant women take prescribed or over-the counter medications in the 1st trimester of their pregnancy. In many cases, the medication is imperative to the health of the woman and cannot be avoided. In some cases, a woman who is taking medication may not know she is pregnant until after organogenesis has begun. Some medications are known to be teratogenic when taken in the 1st trimester of pregnancy, however, the risk to the fetus of most drugs is uncertain. Clinical trials do not assess possible effects of new medications on a fetus as pregnant women are purposefully excluded, and the effects of medications on animal models are not always comparative to humans due to differences in developmental pathways. Identification of teratogenic medications, therefore, requires careful analysis of observational data on congenital anomalies occurring in exposed pregnancies in the clinical setting.
Although around 2-3% of pregnancies are affected by a birth defect, specific birth defects are rare. Therefore, the analysis of very large numbers of exposures is required to identify statistically significant effects for specific birth defects. Previous statistical methods for teratogen identification have focused on identifying increased occurrence of single defects. However, teratogen exposure often results in constellations of defects dependant on timing, dosage, and genetic interactions. Analysis of a group of birth defects may produce a statistically significant result when separate analysis of the single defects did not, implicating the medication as associated to the pattern of defects.
EUROmediCAT has established a unique database containing information on the medications 33,000 mothers were prescribed during the first trimester of pregnancy, and the congenital anomalies the fetus had, from 15 countries in Europe from 1995-2016. This project will build upon the quantitative skills and knowledge developed during the Medical Statistics MSc (MRC-LID funded). Statistical and computational methods will be explored and applied to the EUROmediCAT dataset, in order to produce a methodology with increased ability to identify teratogenic medications, through the analysis of groups of birth defects. This will provide information on potential teratogens and will therefore influence targeted evidence gathering for these medications. This evidence can be used to help women and healthcare providers make better decisions when balancing the risk and benefit of medications taken during pregnancy.
Although around 2-3% of pregnancies are affected by a birth defect, specific birth defects are rare. Therefore, the analysis of very large numbers of exposures is required to identify statistically significant effects for specific birth defects. Previous statistical methods for teratogen identification have focused on identifying increased occurrence of single defects. However, teratogen exposure often results in constellations of defects dependant on timing, dosage, and genetic interactions. Analysis of a group of birth defects may produce a statistically significant result when separate analysis of the single defects did not, implicating the medication as associated to the pattern of defects.
EUROmediCAT has established a unique database containing information on the medications 33,000 mothers were prescribed during the first trimester of pregnancy, and the congenital anomalies the fetus had, from 15 countries in Europe from 1995-2016. This project will build upon the quantitative skills and knowledge developed during the Medical Statistics MSc (MRC-LID funded). Statistical and computational methods will be explored and applied to the EUROmediCAT dataset, in order to produce a methodology with increased ability to identify teratogenic medications, through the analysis of groups of birth defects. This will provide information on potential teratogens and will therefore influence targeted evidence gathering for these medications. This evidence can be used to help women and healthcare providers make better decisions when balancing the risk and benefit of medications taken during pregnancy.
People |
ORCID iD |
Joan Morris (Primary Supervisor) | |
Hannah Johnson (Student) |
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
MR/N013638/1 | 30/09/2016 | 29/09/2025 | |||
2444769 | Studentship | MR/N013638/1 | 30/09/2020 | 29/09/2024 | Hannah Johnson |
Description | International Alliance for PharmacoGenetic Epidemiology Excellence (iAPOGEE) |
Amount | krĀ 54,000 (NOK) |
Organisation | Research Council of Norway |
Sector | Public |
Country | Norway |
Start | 02/2023 |
End | 04/2023 |
Description | Nordic Childhood Cancer Project |
Organisation | University of Oslo |
Country | Norway |
Sector | Academic/University |
PI Contribution | Direct work on the project "Signal detection methods for identifying associations between maternal medication exposure and subsequent childhood cancers", including development of the protocol and analysis. |
Collaborator Contribution | Access to the dataset, advise on protocol and analysis, supervision and support. Scholarship grant to cover housing and transportation expenses during 3-month visit to Oslo. |
Impact | Ongoing. |
Start Year | 2023 |
Description | EUROmediCAT Advisory Group 1st Meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | To present an overview of the project and request input from the advisory panel in the form of future meetings to discuss project related decisions. |
Year(s) Of Engagement Activity | 2022 |
Description | EUROmediCAT Advisory Group 2nd Meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | To present preliminary results from the project and request input on decisions related to analysis. |
Year(s) Of Engagement Activity | 2023 |
Description | Faculty Section Update |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Short presentation to update colleagues on work being undertaken in the faculty. |
Year(s) Of Engagement Activity | 2022 |
Description | ISCB43 Conference Poster and Lightening Talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Poster presentation and lightening talk at the ISCB conference in Newcastle on "Improving Signal Detection in Small Pharmacovigilance Datasets - A New Pipeline Approach". |
Year(s) Of Engagement Activity | 2022 |
Description | Nordic Childhood Cancer Team Meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation on the proposed protocol for work on Signal detection methods for associations between childhood cancer and prenatal exposure to prescription medications - a Nordic registry-based study. |
Year(s) Of Engagement Activity | 2022 |
Description | PharmaSafe faculty meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation on proposed protocol for work on Signal detection methods for associations between childhood cancer and prenatal exposure to prescription medications - a Nordic registry-based study. |
Year(s) Of Engagement Activity | 2023 |
Description | RSS International Conference 2022 Poster Presentation and Rapid Fire Talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Poster presentation and Rapid-Fire talk given at the RSS conference in Aberdeen on "Improvements to 2-dimensional Bayesian hierarchical modelling in pharmacovigilance data". |
Year(s) Of Engagement Activity | 2022 |
Description | SGUL Postgraduate Symposium |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Project overview presented in 5-minute talk to other postgraduate students within the institution. |
Year(s) Of Engagement Activity | 2022 |
Description | Statistics Seminar - Bayesian Hierarchical Models for Pharmacovigilance |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Presentation at faculty statistics seminar describing methods commonly used for signal detection in spontaneous reporting datasets. |
Year(s) Of Engagement Activity | 2022 |
Description | Work In Progress Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Present overview of the project to other PhD students. |
Year(s) Of Engagement Activity | 2021 |