Universal third-trimester ultrasonic screening using fetal macrosomia in the prediction of adverse perinatal outcome: A systematic review and meta-analysis of diagnostic test accuracy

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


Summary:

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.

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Human labour pain is influenced by the voltage-gated potassium channel Kv6.4 subunit

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


Summary:

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 BRC: Cambridge, 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 article

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Fetal inheritance of chromosomally integrated human herpesvirus 6 predisposes the mother to pre-eclampsia

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


Summary: 

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.

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The mutational landscape of normal human endometrial epithelium

Publication: Nature

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


Summary: 

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.

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A maternal serum metabolite ratio predicts fetal growth restriction at term

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


Summary: 

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.

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Embryonal precursors of Wilms tumor

Publication: Science

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

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Summary:

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.

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Human placenta has no microbiome but can contain potential pathogens

Publication: Nature

Marcus C. de Goffau, Susanne Lager, Ulla Sovio, Francesca Gaccioli, Emma Cook, Sharon J. Peacock, Julian Parkhill, D. Stephen Charnock-Jones & Gordon C. S. Smith
31 July 2019

Summary:

This paper from the Department of Obstetrics and Gynaecology at the University of Cambridge presents three key messages: (1) the placenta does not have a microbiome; (2) bacterial infection of the placenta is not a common cause of adverse pregnancy outcome; and (3) the placenta is however a potential site of perinatal acquisition of Streptococcus agalactiae, a major cause of neonatal sepsis.

Screening for breech presentation using universal late-pregnancy ultrasonography: A prospective cohort study and cost effectiveness analysis

Publication: PLOS Medicine

David Wastlund, Alexandros A. Moraitis, Alison Dacey, Ulla Sovio, Edward C. F. Wilson, Gordon C. S. Smith

16 April 2019


Summary:

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.

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Elevated high-density lipoprotein in adolescents with Type 1 diabetes is associated with endothelial dysfunction in the presence of systemic inflammation

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 2019

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Evaluation of a simple risk score to predict preterm pre-eclampsia using maternal characteristics: a prospective cohort study.

Publication: BJOG

Sovio U, Smith G.

22 February 2019

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