Develop in utero fetal therapy to prevent or treat disease
A WRH Research Group operates within our department's Maternal & Fetal Health theme and is lead by Prof Usha Kini (RDM) and Dr Christina Aye (NDWRH)
OxFIT (Oxford Fetal In Utero Therapy) research group
Why this project is important?
Several severe rare disorders have no cure as most of the damage is already done during fetal development and is irreversible. This project aims to identify disorders that may benefit from early in-utero treatment and develop and deliver therapies for such disorders to actively prevent the development of symptoms.
Recent advances in genomics technology have led to early diagnosis of rare disorders. Prenatal testing has increased the in-utero diagnosis rate for rare genetic disorders significantly. Postnatally, newborn screening, in the form of whole genome sequencing, is being carried out to identify genetic disorders that may benefit from early treatment. Additionally, bespoke (n=1) advanced molecular therapies are being developed to treat severe disorders with poor prognosis.
Potential treatments
Most current molecular therapy (e.g., gene therapy, nucleic acid therapies, small molecules) is delivered postnatally. However, other treatments such as enzyme replacement for rare lysosomal storage disorders have been administered successfully in-utero.
The use of in utero therapy for other conditions such as HDFN (Haemolytic Disease of the Fetus and Newborn) and FNAIT (Fetal and Neonatal Autoimmune Thrombocytopaenia) are being explored through clinical trials. It's clear that for many rare disorders the earlier the therapy, the better the outcome.
How this project will help
Our collaborative network of a multi-disciplinary team (MDT) of experts will develop pathways for delivering therapy as early as possible (in utero) for rare disorders to improve the clinical outcomes and prognosis in affected individuals.
The core MDT will seek stake-holder opinion and take into account ethical considerations to develop a framework that facilitates the appropriate selection of disorders and patient groups to receive fetal therapy.
We will develop clinical trials to test the safety and efficacy of such bespoke therapies.
Our project aims
- Establishment of a multi-disciplinary team of experts
- Public and Patient Involvement/ Engagement
- Development of a generic framework to select appropriate disorders and patients for therapy
- Establishing a list of standardised measurable clinical outcomes
- Development of strong links with Pharmaceutical Industry
- Annual symposium to share knowledge and practices with national and international experts
To develop and deliver therapies, we will
- Develop cost-effective screening tools to make an early diagnosis
- Conduct studies to understand the in-utero natural history of rare diseases to allow us to identify the optimal time for treatment
- Identify the best disorders that lend themselves to treatment
- Identify reliable objective biomarkers to monito outcome of therapy
- Work with groups across the University and with biopharma industries to carry out clinical trials
- Deliver clinical trials for appropriate disorders
- Monitor long-term outcomes of participants in Clinical Trials
From Trials to Treatment
Our team are actively recruiting to the AZALEA and FREESIA-3 studies which are randomised controlled trials studying the use of Nipocalimab in HDFN Haemolytic disease of the Fetus and Newborn) and FNAIT (Fetal and Neonatal Alloimmune Thrombocytopaenia). We have successfully enrolled the second and third worldwide recruits for FREESIA-3.
We are also actively pursuing prenatal therapy for SMA (Spinal Muscular Atrophy) where maternal oral Risdiplam is given in the third trimester to prevent symptoms of SMA at birth.
Useful links
Clinical Trial
A Study of Nipocalimab in Pregnancies at Risk for Severe Hemolytic Disease of the Fetus and Newborn (HDFN) (AZALEA)
Clinical Trial
A Study of Nipocalimab or Intravenous Immunoglobulin (IVIG) in Pregnancies At Risk of Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT) (FREESIA-3)
Maternal and Fetal Health theme
Learn more about our other research projects within Maternal & Fetal Health
Latest publications
- Risk factors for mortality and severe morbidity in fetuses with normal late third-trimester scan: population-based cohort study. D'Alberti E, Dockree S, Garbagnati M, Granieri C, Cavallaro A, Impey L.Ultrasound Obstet Gynecol. 2025 Jul;66(1):56-64. doi: 10.1002/uog.29256. Epub 2025 Jun 16.PMID: 40519155
- The impact of late pregnancy dating on the detection of fetal growth restriction at term. Mathewlynn S, Kitmiridou D, Impey L, Ioannou C.Acta Obstet Gynecol Scand. 2024 May;103(5):938-945. doi: 10.1111/aogs.14769. Epub 2024 Jan 19.PMID: 38240293
- Adverse perinatal outcomes are strongly associated with degree of abnormality in uterine artery Doppler pulsatility index. Dockree S, Aye C, Ioannou C, Cavallaro A, Black R, Impey L; Oxford Growth Restriction Identification Programme Group (OxGRIP).Ultrasound Obstet Gynecol. 2024 Oct;64(4):504-512. doi: 10.1002/uog.27668. Epub 2024 Sep 5.PMID: 38669595
- Early antenatal risk factors for births before arrival: An unmatched case-control study. Hubble TR, Nair M, Aye CYL, Mathewlynn S, Greenwood C, Impey L.Acta Obstet Gynecol Scand. 2024 Feb;103(2):294-303. doi: 10.1111/aogs.14720. Epub 2023 Nov 15.PMID: 37965812
- Perinatal outcome of fetuses predicted to be large-for-gestational age on universal third-trimester ultrasound in non-diabetic pregnancy. Robertson K, Vieira M, Impey L.Ultrasound Obstet Gynecol. 2024 Jan;63(1):98-104. doi: 10.1002/uog.26305.PMID: 37428957
- The impact of a universal late third-trimester scan for fetal growth restriction on perinatal outcomes in term singleton births: A prospective cohort study. Aderoba AK, Ioannou C, Kurinczuk JJ, Quigley MA, Cavallaro A, Impey L; Oxford Growth Restriction Identification Programme (OxGRIP) Group.BJOG. 2023 Jun;130(7):791-802. doi: 10.1111/1471-0528.17395. Epub 2023 Feb 13.PMID: 36660877
- Ultrasound predictors of adverse outcome in pregnancy complicated by pre-existing and gestational diabetes. Garbagnati M, Aye CYL, Cavallaro A, Mathewlynn S, Ioannou C, Impey L.Acta Obstet Gynecol Scand. 2022 Jul;101(7):787-793. doi: 10.1111/aogs.14361. Epub 2022 Apr 20.PMID: 35441701
- Prenatal and Postnatal Cardiac Development in Offspring of Hypertensive Pregnancies. Aye CYL, Lewandowski AJ, Lamata P, Upton R, Davis E, Ohuma EO, Kenworthy Y, Boardman H, Frost AL, Adwani S, McCormick K, Leeson P.J Am Heart Assoc. 2020 May 5;9(9):e014586. doi: 10.1161/JAHA.119.014586. Epub 2020 Apr 30.PMID: 32349586
Impact of rapid genomic testing on clinical outcomes of acutely unwell children presenting with severe epilepsy. Eur J Hum Genet. 2025 Oct;33(10):1324-1332. doi: 10.1038/s41431-025-01870-5. Epub 2025 May 21. PMID: 40399560; PMCID: PMC12479891.
Identifying the Impacts, Obstacles and Information Barriers for Parents of Children Living With Genetic Neurodevelopmental Disorders: A Qualitative Study. Health Expect. 2025 Aug;28(4):e70340. doi: 10.1111/hex.70340. PMID: 40607502; PMCID: PMC12223786.
Avoiding Premature Diagnostic Closure: Lessons from Two Children with Neurotransmitter Disorders Associated with Dual Pathology. Mov Disord Clin Pract. 2024 Sep;11(9):1149-1152. doi: 10.1002/mdc3.14164. Epub 2024 Jul 31. PMID: 39082248; PMCID: PMC11452789.
Blepharophimosis with intellectual disability and Helsmoortel-Van Der Aa Syndrome share episignature and phenotype. Am J Med Genet C Semin Med Genet. 2024 Dec;196(4):e32089. doi: 10.1002/ajmg.c.32089. Epub 2024 Jun 17. PMID: 38884529
PSMC5 insufficiency and P320R mutation impair proteasome function. Hum Mol Genet. 2024 Aug 18;33(17):1506-1523. doi: 10.1093/hmg/ddae085. PMID: 38776958; PMCID: PMC11336065.
The phenotype of MEGF8-related Carpenter syndrome (CRPT2) is refined through the identification of eight new patients. Eur J Hum Genet. 2024 Jul;32(7):864-870. doi: 10.1038/s41431-024-01624-9. Epub 2024 May 17. PMID: 38760421; PMCID: PMC11220001.
Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases. Genome Med. 2023 Nov 9;15(1):94. doi: 10.1186/s13073-023-01240-0. PMID: 37946251; PMCID: PMC10636885.
Neurodevelopmental dimensional assessment of young children at high genomic risk of neuropsychiatric conditions. JCPP Adv. 2023 May 4;3(2):e12162. doi: 10.1002/jcv2.12162. PMID: 37753151; PMCID: PMC10519742.
Senior team members
Dr Christina Aye
Honorary Senior Clinical Lecturer and Consultant in Obstetrics and Fetal Medicine at the Nuffield Department of Women’s & Reproductive Health. Christina is Fetal Monitoring Lead for OUH and Academic Training Representative for HETV. Her research focuses on the long-term cardiovascular effects of pregnancy complications on both mother and child and early interventional therapies to treat or prevent diseases in the fetus or newborn.
Prof Usha Kini
Associate Professor of Genomic Medicine and Consultant Clinical Geneticist. Usha leads research at the Oxford Centre for Genomic Medicine and holds key roles across clinical and academic programmes. Her work focuses on improving diagnostics and understanding the genetic basis of rare disease to benefit patients.
Prof Elizabeth Ormondroyd
Associate Professor at the Radcliffe Department of Medicine, University of Oxford. Elizabeth’s research explores how rapid advances in genetics and genomics are shaping outcomes for patients, their families, and society.
Other core team members
Prof Lawrence Impey (NDWRH)
Dr Christos Ioannou (NDWRH)
Prof Anneke Lucassen (Nuffield Department of Medicine)
Dr Maria Ivan (OUH)
Dr Mike Shea (OUH)
Dr Miranda Rogers (RDM)
Dr Lyndell Sarkies (RDM)
Prof Stephan Sanders (Department of Paediatrics)
How can you help?
If you wish to learn more or support our work please visit our contact us page or email Dr Christina Aye