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  (MRC DTP) Investigating the impact of Antenatal Corticosteroid Exposure during Pregnancy on Offspring Neurocognitive Outcomes.


   Faculty of Biology, Medicine and Health

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  Dr M Harte, Dr Byron Bitanihirwe  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Current evidence indicates that antenatal corticosteroids (ACS), such as dexamethasone and betamethasone can improve preterm birth outcomes in particular clinical settings [1]. The use of ACS was estimated at 54% among women from 29 low-and middle-income countries (LMICs) [2], and in LMICs there have been concerns of suboptimal clinical practices regarding ACS, including use of low-quality corticosteroids and inadequate assessment of risk for preterm birth, leading to administration of ACS at gestational ages where benefit is controversial [3, 4].  

Concerns exist about potential consequences of ACS and hormonal perturbations on prenatal programming of neurodevelopment that may result in long-term neuropathological and neurocognitive sequelae [5]. In this context, the evidence surrounding neurocognitive functioning in children exposed to ACS in LMICs—especially in sub-Saharan Africa, where the burden of preterm birth is highest, is unclear. 

This project involves will involve an empirical Developmental Origins of Health and Disease (DOHAD)-preclinical study that will investigate the effects of a clinically relevant dosage of dexamethasone administered to pregnant rats at different time points on long-term neuropathological and neurocognitive sequelae of offspring (viz., establish a neurodevelopmental animal model).  

Specifically, effects of dexamethasone treatment on neuroanatomical (e.g., hippocampal and choroid plexus volume), pathological (e.g. synaptic, neuronal and inflammatory markers), epigenetic (e.g., 11β-hydroxysteroid dehydrogenase type 2), and behavioural outcomes (e.g., cognition) will be assessed. Pathological and neurocognitive markers will be probed in offspring at different developmental time-points. 

The proposed research topic has important public health implications, especially in bridging knowledge gaps on the seemingly meagre and conflicting evidence regarding long-term impacts of synthetic glucocorticoids on offspring development.

www.b-neuro.com  

Eligibility

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC DTP website https://www.bmh.manchester.ac.uk/study/research/mrc-dtp/ 

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team [Email Address Removed]

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/

Biological Sciences (4) Medicine (26)

Funding Notes

Studentship funding is for 4 years. This scheme is open to both the UK and international applicants. We are only able to offer a limited number of studentships to applicants outside the UK. Therefore, full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

1. Sahoo T, Aradhya AS, Mukhopadhyay K. Choice of Antenatal Steroids for Prevention of Complications of Prematurity: Betamethasone Versus Dexamethasone. Journal of Neonatology. 2021;35(4):219-25.
2. Vogel JP, Souza JP, Gülmezoglu AM, Mori R, Lumbiganon P, Qureshi Z, et al. Use of antenatal corticosteroids and tocolytic drugs in preterm births in 29 countries: an analysis of the WHO Multicountry Survey on Maternal and Newborn Health. The Lancet. 2014;384(9957):1869-77.
3. Greensides D, Robb-McCord J, Noriega A, Litch JA. Antenatal corticosteroids for women at risk of imminent preterm birth in 7 sub-Saharan African countries: a policy and implementation landscape analysis. Global Health: Science and Practice. 2018;6(4):644-56.
4. Mosoro E, Wilson AN, Homer CS, Vogel JP. Assessing the quality of antenatal corticosteroids in low-and middle-income countries: A systematic review. PloS one. 2020;15(12):e0243034.
5. Gore AC, Martien KM, Gagnidze K, Pfaff D. Implications of prenatal steroid perturbations for neurodevelopment, behavior, and autism. Endocrine Reviews. 2014;35(6):961-91.
6. Walani SR. Global burden of preterm birth. International Journal of Gynecology & Obstetrics. 2020;150(1):31-3.
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