Publication: The Journal of Clinical Endocrinology & Metabolism
19 November 2021
Large size at birth is associated with complications in the mother and the baby. Alongside work in fetal growth restriction (FGR), researchers analysed their previously developed metabolite ratio in relation to large for gestational age (LGA) infants born at term.
They found that the metabolite ratio predictive of FGR was inversely associated with both LGA and birth weight z score as a continuous trait. These findings, obtained from the Pregnancy Outcome Prediction study, were externally validated in the Born in Bradford study.View publication
Nancy McBride, Paul Yousefi, Ulla Sovio, Kurt Taylor, Yassaman Vafai, Tiffany Yang, Bo Hou, Matthew Suderman, Caroline Relton, Gordon C. S. Smith, Deborah A. Lawlor
10 August 2021
Many women who experience gestational diabetes (GDM), gestational hypertension (GHT), pre-eclampsia (PE), have a spontaneous preterm birth (sPTB) or have an offspring born small/large for gestational age (SGA/LGA) do not meet the criteria for high-risk pregnancies based upon certain maternal risk factors. The aim of this study was to assess the predictive ability of an untargeted platform of over 700 metabolites to predict the above pregnancy-related disorders in two cohorts.View publication
Publication: Nature Communications
Sungsam Gong, Francesca Gaccioli, Justyna Dopierala, Ulla Sovio, Emma Cook, Pieter-Jan Volders, Lennart Martens, Paul D. W. Kirk, Sylvia Richardson, Gordon C. S. Smith & D. Stephen Charnock-Jones
11 May 2021
The placenta is understudied and is commonly omitted from large-scale “-omic” analyses, this study enables tissue-wide comparison of transcriptome analyses, looking at identification placentally-related adverse pregnancy outcomes such as fetal growth restriction (FGR) and preeclimisia (PE).View publication
Publication: American Journal of Obstetrics and Gynecology
Ulla Sovio, Francesca Gaccioli, Emma Cook, Stephen Charnock-Jones, .Gordon C.S,
24 April 2021
Slowing of fetal growth and elevated maternal serum are associated with early term spontaneous laborView publication
Publication: The Lancet
Kathryn Beardsall, Lynn Thomson, Catherine Guy, Isabel Iglesias-Platas, Prof Mirjam M van Weissenbruch, Simon Bond, et al
9 February 2021
Hyperglycaemia and hypoglycaemia are common in preterm infants and have been associated with increased risk of mortality and morbidity. Interventions to reduce risk associated with these exposures are particularly challenging due to the infrequent measurement of blood glucose concentrations, with the potential of causing more harm instead of improving outcomes for these infants.
Continuous glucose monitoring (CGM) is widely used in adults and children with diabetes to improve glucose control, but has not been approved for use in neonates. The REACT trial aimed to evaluate the efficacy and safety of CGM in preterm infants requiring intensive care.
This international, open-label, randomised controlled trial was done in 13 neonatal intensive care units in the UK, Spain, and the Netherlands. Infants were randomly assigned (1:1) to real-time CGM or standard care (with masked CGM for comparison). The primary efficacy outcome was the proportion of time sensor glucose concentration was 2·6–10 mmol/L for the first week of life. Safety outcomes related to hypoglycaemia (glucose concentrations <2·6 mmol/L) in the first 7 days of life.
Between July 4, 2016, and Jan 27, 2019, 182 infants were enrolled, 180 of whom were randomly assigned (85 to real-time CGM, 95 to standard care). 70 infants in the real-time CGM intervention group and 85 in the standard care group had CGM data and were included in the primary analysis.
Compared with infants in the standard care group, infants managed using CGM had more time in the 2·6–10 mmol/L glucose concentration target range. More infants in the standard care group were exposed to at least one episode of sensor glucose concentration of less than 2·6 mmol/L for more than 1 h than those in the intervention group. There were no serious adverse events related to the use of the device or episodes of infection.
Real-time CGM can reduce exposure to prolonged or severe hyperglycaemia and hypoglycaemia. Further studies using CGM are required to determine optimal glucose targets, strategies to obtain them, and the potential effect on long-term health outcomes.View publication
Tim H. H. Coorens, Thomas R. W. Oliver, Rashesh Sanghvi, Ulla Sovio, Emma Cook, Roser Vento-Tormo, Muzlifah Haniffa, Matthew D. Young, Raheleh Rahbari, Neil Sebire, Peter J. Campbell, D. Stephen Charnock-Jones, Gordon C. S. Smith & Sam Behjati
10 March 2020
Researchers found evidence to support the theory of the placenta as a ‘dumping ground’ for genetic defects, whereas the fetus corrects or avoids these errors. The findings provide a clear rationale for studying the association between genetic aberrations and birth outcomes, in order to better understand problems such as premature birth and stillbirth. Read the full story.View publication
Publication: PLOS Medicine
Alexandros A. Moraitis, Norman Shreeve, Ulla Sovio, Peter Brocklehurst, Alexander E. P. Heazell, Jim G. Thornton, Stephen C. Robson, Aris Papageorghiou, Gordon C. Smith
13 October 2020
Delivering a large baby (usually defined as above 4Kg or 90th birth weight centile) has been associated with complications such shoulder dystocia – after the vaginal delivery of the head, the baby’s shoulder gets stuck behind the mother’s pubic bone. This could lead to the baby with fractured bones and lack of oxygen during the delivery. There may be then a potential need for emergency caesarean section and neonatal unit admission.
Predicting the delivery of a large baby can be difficult and there is currently no standard screening programme to predict these complications.
Screening more than 100,000 patients, Cambridge researchers found that offering a scan to all women at 36 weeks could increase the detection of delivering a large baby and the prediction was more effective for very large babies (above 4.5Kg). However, the screening could not identify shoulder dystocia to the same effect or enough evidence to predict which babies could have other complications.
More evidence is needed on the benefit of introducing another ultrasound for all women, to help identify any potential problems before labour as well as predict large babies.View publication
Publication: Cell Reports
Michael C. Lee, Michael S. Nahorski, James R.F. Hockley, Frank Reimann, Ewan St. John Smith, C. Geoffrey Woods
21 July 2020; DOI: 10.1016/j.celrep.2020.107941
Women who don’t need pain relief during childbirth may have a key genetic variant that acts as a natural epidural. Supported by the NIHR Cambridge BRC, researchers investigated why some women experience different levels of pain during childbirth.
Women who did not require any pain relief during the birth of their first child took part in a study to understand their pain threshold. This included applying heat and pressure to their arms and putting their hands in icy water. They were then measured against a control group of women were who were given pain relief during childbirth.
They found the group the women who didn’t need any pain relief had a high pain threshold than those of the control group. Their genetic cold was then sequenced and found these women had a higher-than-expected prevalence of a rare variant of the gene KCNG4. This gene acts as a gate, controlling the electric signal that flows along our nerve cells. This could be the reason why these women did not require pain relief during childbirth. Read the full news articleView publication
Publication: Nature Microbiology
Francesca Gaccioli, Susanne Lager, Marcus C. de Goffau, Ulla Sovio, Justyna Dopierala, Sungsam Gong, Emma Cook, Andrew Sharkey, Ashley Moffett, Wai Kwong Lee, Christian Delles, Cristina Venturini, Judith Breuer, Julian Parkhill, Sharon J. Peacock, D. Stephen Charnock-Jones & Gordon C. S. Smith
4 May 2020
The placenta is the interface between the mum and the fetus and supports the growth of the baby in the womb. Abnormal function of the placenta is associated with poor pregnancy outcome, including maternal and infant diseases and deaths. In turn, placental dysfunction could be due to viral infections, which are known to cause organ failure. We investigated whether viral infection of the placenta is associated with diseases of human pregnancy related to poor placental function, such as pre-eclampsia (hypertensive disorder in the mother) and fetal growth restriction (impaired growth of the fetus during pregnancy).
Using samples from more than 5,000 pregnancies and data available in the literature, we demonstrated that the presence of inherited human herpesvirus 6 (HHV-6) DNA in the feto-placental unit is associated with an increased risk of the mother to develop pre-eclampsia. The virus can be passed to the fetus and the placenta from both the mother and the father. Importantly, our study did not identify any other viral associations with the 2 studied conditions. HHV-6 was the only clear viral signal observed in a large number of placental samples from pathological and normal pregnancies.
Pre-eclampsia is a condition characterized by high maternal blood pressure and protein levels in the urine in the second half of pregnancy. It represents a major determinant of the global burden of disease. Although pre-eclamspia is known to be associated with poor development and function of the placenta, the causes of placental insufficiency are not fully understood. Identifying those will help us to understand and treat this condition, which affects 5-8% of all pregnant women and is responsible for over 75,000 maternal deaths and 500,000 fetal deaths worldwide every year. Our work demonstates that viral infection of the placenta is not a major cause of pre-eclampsia and that a small proportion of cases is likely to be due to the presence of HHV-6 in the feto-placental unit.View publication
Luiza Moore, Daniel Leongamornlert, Tim H. H. Coorens, Mathijs A. Sanders, Peter Ellis, Stefan Dentro, Kevin Dawson, Tim Butler, Raheleh Rahbari, Thomas J Mitchell, Francesco Maura, Jyoti Nangalia, Patrick S. Tarpey, Simon F. Brunner, Henry Lee-Six, Yvette Hooks, Sarah Moody, Krishnaa Mahbubani, Mercedes Jimenez-Linan, Jan J. Brosens, Christine A. Iacobuzio-Donahue, Inigo Martincorena, Kourosh Saeb-Parsy, Peter J. Campbell, Michael R. Stratton
22 April 2020
This paper looks at somatic mutation (changes in the DNA) in healthy human tissue in the endometrium (womb lining) and provides insights into the earliest stages of uterine cancer development, which is the fourth most common cancer in women in the UK.
Many cells in the inner lining of the uterus carry ‘cancer-driving’ mutations that frequently arise early in life. Using whole-genome sequencing to better understand the genetic changes in healthy endometrial tissue, the researchers found that a high proportion of cells carry driver mutations, even though they appear completely normal under the microscope. Furthermore the team found that many of these driver mutations appear to have arisen early in life, in many cases during childhood.View publication
Publication: Nature Medicine
Ulla Sovio, Neil Goulding, Nancy McBride, Emma Cook, Francesca Gaccioli, D. Stephen Charnock-Jones, Debbie A. Lawlor & Gordon C. S. Smith
11 March 2020
Fetal growth restriction (FGR) means that the fetus fails to grow according to its growth potential. The condition is a major cause of stillbirth, neonatal illness and death. Maternal risk factors and ultrasound measurements alone are not effective in screening for fetal growth restriction. Biomarkers in the pregnant woman’s blood could possibly improve screening for FGR.
Using serial maternal serum samples from the Pregnancy Outcome Prediction (POP) study, the research team identified metabolites that were predictive of FGR at term. These were used to calculate a ratio that clearly improves the prediction of FGR over currently known risk factors. They successfully validated the finding in plasma samples from a demographically different Born in Bradford (BiB) study.
Together with ultrasound measurements, the metabolite ratio could possibly be used to improve late pregnancy screening for fetal growth restriction. Screen-positive women could be offered enhanced monitoring and targeted induction of labour to prevent adverse effects associated with FGR.View publication
Margherita Y. Turco, Lucy Gardner, Richard G. Kay, Russell S. Hamilton, Malwina Prater, Michael S. Hollinshead, Alasdair McWhinnie, Laura Esposito, Ridma Fernando, Helen Skelton, Frank Reimann, Fiona M. Gribble, Andrew Sharkey, Steven G. E. Marsh, Stephen O’Rahilly, Myriam Hemberger, Graham J. Burton & Ashley Moffett
28 November 2018
During pregnancy a complex interaction between the mother and the embryo/fetus takes part to secure placental provision of nutrients to the fetus. Human models of this interaction, involving so called trophoblast invasion, had not been established, making it difficult to study this process, that results in life threatening diseases when it goes wrong.
The laboratory of Aschley Moffett, who led this research, established a new organoid model for human trophoblast/placenta development. Our contribution was LC-MS/MS showing that this model faithfully produced pregnancy related hormones.
This organoid model will be transformative for studying human placental development and for investigating trophoblast interactions with the local and systemic maternal environment.View publication
Tim H. H. Coorens, Taryn D. Treger, Reem Al-Saadi, Luiza Moore, Maxine G. B., Thomas J. Mitchell, Suzanne Tugnait, Christine Thevanesan, Matthew D. Young, Thomas R. W. Oliver, Minou Oostveen, Grace Collord, Patrick S. Tarpey, Alex Cagan, Yvette Hooks, Mark Brougham, Ben C. Reynolds, Giuseppe Barone, John Anderson, Mette Jorgensen, G. A. Amos Burke, Johannes Visser, James C. Nicholson, Naima Smeulders, Imran Mushtaq, Grant D. Stewart, Peter J. Campbell, David C. Wedge, Iñigo Martincorena, Dyanne Rampling, Liz Hook, Anne Y. Warren, Nicholas Coleman, Tanzina Chowdhury, Neil Sebire, Jarno Drost, Kourosh Saeb-Parsy, Michael R. Stratton, Karin Straathof, Kathy Pritchard-Jones, Sam Behjati
6 December 2019
Wilms tumour is the most common type of kidney cancer in childhood but it was not previously known how it arose in children’s kidneys. This research found out that both pediatric and adult kidney cancer arise in a similar way, from premalignant clonal expansions.View publication
Publication: Pediatric Nephrology
Jack L. Martin, Anja V. Gruszczyk, Timothy E. Beach, Michael P. Murphy, Kourosh Saeb-Parsy
2 June 2018
Acute kidney injury (AKI) is a major problem in critically unwell children, including ischaemic reperfusion (IR) injury involving mitochondria. This research proposes a variety of novel therapeutic targets as potential treaments of AKI.View publication
Publication: PLOS Medicine
David Wastlund, Alexandros A. Moraitis, Alison Dacey, Ulla Sovio, Edward C. F. Wilson, Gordon C. S. Smith
16 April 2019
Despite the relative ease with which breech presentation can be identified through ultrasound screening, the assessment of foetal presentation at term is often based on clinical examination only. Due to limitations in this approach, many women present in labour with an undiagnosed breech presentation, with increased risk of foetal morbidity and mortality. This study sought to determine the cost effectiveness of universal ultrasound scanning for breech presentation near term (36 weeks of gestational age [wkGA]) in nulliparous women.View publication
Publication: European Heart Journal
Chiesa ST, Charakida M, McLoughlin E, Nguyen HC, Georgiopoulos G, Motran L, Elia Y, Marcovecchio ML, Dunger DB, Dalton RN, Daneman D, Sochett E, Mahmud FH, Deanfield JE.
12 March 2019View publication
Publication: Diabetes Care
Lowe WL Jr, Scholtens DM, Kuang A, Linder B, Lawrence JM, Lebenthal Y, McCance D, Hamilton J, Nodzenski M, Talbot O, Brickman WJ, Clayton P, Ma RC, Tam WH, Dyer AR, Catalano PM, Lowe LP, Metzger BE;
17 January 2019View publication
Publication: The Journal of Clinical Endocrinology & Metabolism
Jayasuriya NA, Hughes AE, Sovio U, Cook E, Charnock-Jones DS, Smith GCS. J Clin Endocrinol Metab.
15 February 2019View publication
Publication: Pediatric Diabetes
Ruan Y, Willemsen RH, Wilinska ME, Tauschmann M, Dunger DB, Hovorka R. .
16 January 2019View publication
Publication: Diabetes Care
Scholtens DM, Kuang A, Lowe LP, Hamilton J, Lawrence JM, Lebenthal Y, Brickman WJ, Clayton P, Ma RC, McCance D, Tam WH, Catalano PM, Linder B, Dyer AR, Lowe WL Jr, Metzger BE; HAPO Follow-Up Study Cooperative Research Group.
7 January 2019View publication
Publication: LancetThe Lancet Child & Adolescent Health
Gaccioli F, Sovio U, Cook E, Hund M, Charnock-Jones DS, Smith GCS.
August 2018View publication
Publication: Diabetic Medicine
Thabit H, Hovorka R.
21 December 2017View publication
Sovio U, Smith G.
22 February 2019View publication
Publication: Best Practice & Research Clinical Obstetrics & Gynaecology
Smith GCS. Best Pract Res Clin Obstet Gynaecol.
May 2018View publication
Publication: The Lancet
Tauschmann M, Thabit H, Bally L, Allen JM, Hartnell S, Wilinska ME, Ruan Y, Sibayan J, Kollman C, Cheng P, Beck RW, Acerini CL, Evans ML, Dunger DB, Elleri D, Campbell F, Bergenstal RM, Criego A, Shah VN, Leelarathna L, Hovorka R; APCam11 Consortium.
3 October 2018View publication
Norah M. E. Fogarty, Afshan McCarthy, Kirsten E. Snijders, Benjamin E. Powell, Nada Kubikova, Paul Blakeley, Rebecca Lea, Kay Elder, Sissy E. Wamaitha, Daesik Kim, Valdone Maciulyte, Jens Kleinjung, Jin-Soo Kim, Dagan Wells, Ludovic Vallier, Alessandro Bertero10, James M. A. Turner & Kathy K. Niakan
20 September 2017View publication
Publication: N Engl J Med
Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, Vanhole C, Palmer CR, van Weissenbruch M, Midgley P, Thompson M, Thio M, Cornette L, Ossuetta I, Theyskens C, de Jong M, Ahluwalia JS, de Zegher F, Dunger DB.
30 October 2008View publication
Publication: N Engl J Med
Thabit H, Tauschmann M, Allen JM, Leelarathna L, Hartnell S, Wilinska ME, Acerini CL, Dellweg S, Benesch C, Heinemann L, Mader JK, Holzer M, Kojzar H, Exall J, Yong J, Pichierri J, Barnard KD, Kollman C, Cheng P, Hindmarsh PC, Campbell FM, Arnolds S, Pieber TR, Evans ML, Dunger DB, Hovorka R.
26 November 2015View publication
Thabit H, Elleri D, Leelarathna L, Allen J, Lubina-Solomon A, Stadler M, Walkinshaw E, Iqbal A, Choudhary P, Wilinska M, Barnard K, Heller S, Amiel S, Evans M, Dunger D, Hovorka R.
26 February 2015View publication
Paredes MF, James D, Gil-Perotin S, Kim H, Cotter JA, Ng C, Sandoval K, Rowitch DH, Xu D, McQuillen PS, Garcia-Verdugo JM, Huang EJ, Alvarez-Buylla A.
7 October 2016View publication
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung WS, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, Stevens B, Barres BA.
18 January 2017View publication
Salavati N, Sovio U, Mayo RP, Charnock-Jones DS, Smith GC.
February 2016View publication
Publication: Diabetes Care
Sovio U, Murphy HR, Smith GC.
24 May 2016View publication
Publication: Am J Epidemiol
Partap U, Sovio U, Smith GC.
15 July 2016View publication
Publication: Nat Genet
Cleaton MA, Dent CL, Howard M, Corish JA, Gutteridge I, Sovio U, Gaccioli F, Takahashi N, Bauer SR, Charnock-Jones DS, Powell TL, Smith GC, Ferguson-Smith AC, Charalambous M.
24 October 2016View publication
Gaccioli F, Lager S, Sovio U, Charnock-Jones DS, Smith GCS.
28 October 2016View publication