Researchers at the UCD Centre for Human Reproduction have published the results of a large longitudinal observational study examining changes in body mass index (BMI) of mothers between successive pregnancies. The study, published recently in the journal of the Obesity Society, found that one in five women who were overweight at the start of their first pregnancy were classified as obese by the time of their second pregnancy. Moreover, 88% of women who started in the obesity category at the start of their first pregnancy remained in this BMI category at the start of their second pregnancy.
The study was conducted in the Coombe Women & Infants University Hospital where routine, accurate and standardised measurement of both the height and weight of mothers was performed by trained midwives at the first prenatal visit since 1st January 2009. During the period 2009 to 2017, a total of 76,470 first prenatal appointments were recorded in the hospitals electronic health records. Of these, 9,724 women attended hospital for both their first and second deliveries of infants weighing ≥500 g and had their weight measured before 15 weeks of gestation. Women who had their weight first measured after 15 weeks of gestation in either pregnancy were excluded.
Among the cohort examined, the incidence of obesity increased from 11.6% in the first pregnancy to 16.0% in the second pregnancy. The mean inter-pregnancy interval was 32.5 months ± 15.7 months. The mean Body Mass Index change was +0.6 kg/m2 (interquartile range 2.2, P<0.001). Overall 10.3% developed overweight and 5.9% developed obesity by the second pregnancy. 20.6% of the first time mothers in the overweight category entered the obesity category in their second pregnancy.
Maternal obesity is known to present significant challenges in obstetrics and is associated with an increase in pregnancy complications, such as gestational diabetes, preeclampsia and venous thromboembolism. Maternal obesity also leads to increases in interventions during delivery through induction of labour and caesarean section. There are lifelong cardiometabolic consequences for both mother and her baby and increased societal healthcare costs.
The prevalence of obesity is increasing among high-income countries and although much research has gone into examining weight gain during pregnancy, the impact of weight gain between pregnancies and the associated risk factors is less well studied. Most studies of inter-pregnancy weight gain focus on pregnancy outcomes rather than the factors contributing to inter-pregnancy weight gain. Studies of maternal obesity have invariably been cross-sectional with self-reported maternal weight and height leading to less accurate BMI classification.
The study reported by Prof Michael Turner’s group was a longitudinal observational study with well characterised maternal BMI’s and examined both BMI and maternal weight changes in early pregnancy of nulliparas who returned to the Coombe Women & Infants University Hospital within a decade to deliver a second baby. The also examined characteristics and lifestyle factors associated with developing overweight or obesity in the inter-pregnancy period.
The prevalence of obesity increased in all groups of women studies in the second pregnancy. However, certain subgroups were identified as more likely to develop obesity. For example, women not in professional/managerial employment, women who were not exclusively breastfeeding at the time of hospital discharge, women taking antidepressants or anxiolytics, women who had postnatal depression after their first baby, and women who had an interval of 3 years or more between pregnancies had higher odds of developing obesity by the start of their second pregnancy.
Longitudinal Study of Maternal BMI in Successive Pregnancies
Ciara M. E. Reynolds, Brendan Egan, Eimer G. O’Malley, Léan McMahon, Sharon R. Sheehan,
and Michael J. Turner
Obesity 2020 Feb;28(2):460-467 [link]
Researchers at Systems Biology Ireland (SBI) at University College Dublin have identified what they believe to be a streamlined method of tracking and predicting how mutations in KRAS genes change protein interactions in colorectal cancer cells.
In a paper titled “Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D,” SBI scientists, together with an international consortium from Australia, Europe and Canada, explain the intracellular network they have studied which will hopefully lead to new, more targeted cancer treatments. The paper was published on 24th January 2020 in the scientific journal, Nature Communications.
“We know that gene mutations cause cancer, but we don't know what these mutations are actually doing and how they change cells so that they become cancer cells,”
said Prof. Walter Kolch, Director of Systems Biology Ireland (SBI) and corresponding author on the paper.
“This study lifts the curtain on how mutations in one of the most frequently altered culprits in human cancer, the KRAS gene, change protein interaction networks in colorectal cancer cells. The results are mindboggling. A single mutation in KRAS is associated with widespread protein interaction changes which rewires about one third of all connections. The result is a very profound change in information flow through this network which reprograms gene expression turning the cell into a cancer cell. Understanding these fundamental mechanisms how mutations actually impact cellular functions is the first and prerequisite step towards developing better and more efficacious cancer drugs.”
Using quantitative mass spectrometry, the researchers analysed more than 1,000 protein complexes and mapped more than 6,000 protein interactions along the epidermal growth factor receptor (EGFR) network.
“The EGFR network is the key cellular pathway that controls how cancer cells survive and grow in colorectal cancer,”
said Prof. David Lynn, an EMBL Australia Group Leader at SAHMRI and Flinders University and corresponding author.
“Like flight maps or social networks, these cellular networks involve a complex series of interactions generating an enormous number of potential pathways,” he said.
“Interactions define the interplay of proteins within a cell and thereby how signalling networks are organized. In a comparative analysis of networks and by integrating multiple data types, we demonstrate how oncogenic mutation highjack these networks by extensive rewiring,”
said Dr. Karsten Boldt, corresponding author from the Institute for Ophthalmic Research at the Eberhard-Karls University of Tuebingen.
“I think that our unique approach can, in future, be applied to further networks and will help to understand the molecular basis of various diseases,” he said.
Other SBI authors include SBI authors include Susan Kennedy ('17), Cinzia Raso ('16), Theodosia Charitou ('17), Carlos Herrera-Montavez ('16), Aleksandar Krstic, David Gomez Matallanas, Christina Kiel, Nora Rauch, Oleksii Rukhlenko, Boris Kholodenko, Luis Iglesias-Martinez, Colm Ryan and Ruth Pilkington.
The ultimate hope of the researchers in this study is to garner a better understanding of RAS signalling and mutations, which, when paired with computational network modelling strategies in the screening process, will lead to eventual increased drug success and cancer treatment.
Kolch also revealed that Nature Communications will also be publishing a blog piece corresponding with the research article. The blog, titled "The ripple effects of a RAS mutation," was written by Walter Kolch and David Lynn and gives additional perspective on the study and its history.
“Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D” ; Nature Communications 2020 The article will be available on the journal website.
Nature Communications is an open access journal that publishes high-quality research from all areas of the natural sciences. Papers published by the journal represent important advances of significance to specialists within each field.
An international research consortium which included the Irish Critical Care Trials Group has published a major study comparing two strategies of stress ulcer prophylaxis (SUP) in mechanically ventilated adults. The international, randomised, open-label, cluster cross-over study (PEPTIC) was one of four major studies presented at Critical Care Reviews 2020 meeting in Belfast and was published simultaneously in the Journal of the American Medical Association.
With almost 27,000 patients in 50 hospitals across 5 countries, the trial represents one of the largest studies ever conducted in intensive care units. The study aimed to compare the effects of proton pump inhibitors (PPIs) against histamine-2-receptor blockers (H2RBs) on 90-day mortality among patients requiring invasive mechanical ventilation. Cross-over randomisation was performed at the level of ICU unit rather individual patient (Clustered Cross-over). The study included patient data from existing registries and the open label nature of the trial allowing the study to be completed with a budget of less than US$500,000.
The primary outcome of the study was in-hospital all-cause mortality up to 90 days with secondary outcomes including clinically significant upper gastro-intestinal bleeding, Clostridioides difficile infection, ICU and hospital lengths of stay.
A total of 18.3% of patients admitted to ICU when PPIs were the default stress ulcer prophylaxis treatment and 17.5% of patients admitted when H2RBs were used, died in hospital by 90-days. Rates of C.difficile infection and both ICU and hospital stays were similar for both treatment groups. The difference in mortality rates did not reach statistical significant and interpretation of the study may be limited by cross-over in the assigned medication.
Nevertheless, the interpretation of this large, complex trial does have implications for routine clinical practice, a fact highlighted in the discussion of the study results at the presentation in the Titanic Centre in Belfast.
Clinically significant upper GI bleeds occurred less frequently in the PPI patient groups. Study first author, Dr Paul Young (Wellington Hospital ICU) noted that
‘For every 1,000 mechanically ventilated patients admitted when PPI was the default SUP treatment, five fewer patients had an upper GI bleed compared to when H2RB was the default prophylaxis.
While such bleeds may not result in patient death, they can significantly complicate critical care management. PPIs are effective at reducing upper GI bleeds but for some subgroups of patients, notably patients who have had cardiac surgery (approximately 6,500 patients in this study), the observed risk of death was statistically higher in the PPI group (2.5%) compared with the H2RB group (1.9%) for no improvement in SUP benefit. While the observed increase mortality for this subgroup with the PPI treatment may be a chance finding, there is little to be lost by adopting a H2RB default treatment in cases where upper GI bleeds are rare.
Also, the PEPTIC trial results (which had the narrowest treatment effect estimates ever seen in an ICU trial) were consistent with a treatment difference that ranges from no effect to a 10% relative risk increase in mortality using the PPI strategy. So while the PPI treatment strategy is unlikely to reduce mortality by a clinically significant degree, the possibility of increased mortality cannot be excluded based on the results of the PEPTIC trial. With over 2.5 million people per annum mechanically ventilated worldwide, this size effect could account for around 25,000 ICU deaths per year in developed countries alone.
“Although there is still uncertainty about whether PPIs actually increase mortality risk, I think most patients would rather not have a therapy that might kill them in order to have a 1 in 200 chance of being prevented from having an upper GI bleed that probably will not. Remember though, PPIs are highly effective at treating upper GI bleeding. If a patient has an upper GI bleed, you should give a PPI.”
noted Dr Young.
Lead Irish investigator and principal investigator of the Irish Critical Care Trials Network, Prof Alistair Nichol, UCD Professor of Critical Care Medicine at St Vincent’s University Hospital, predicts that routine clinical practice worldwide will change as a result of these findings. Several commentators at the study results presentation indicated that this trial will cause them to question their treatment strategies for particular patient groups.
This is an important study for two reasons. Firstly, the risk balance for clinicians will change. There seems little evidence to support a default PPI strategy as compared to a default H2RB strategy. This will likely lead to a change in current practice in most Irish ICUs. Secondly, we have demonstrated this novel trial design allowed us to recruit large numbers of ICU patients and relatively low cost. This novel design can be used to test other ubiquitous interventions in the critically ill.
The Irish participation in this study was part funded by the Health Research Board’s funding of the Irish Critical Care Trials Network and supported by the UCD Clinical Research Centre. Prof Peter Doran, Director of UCD Clinical Research Centre and Associate Dean for Research, Innovation & Impact noted,
Being a leader of major international clinical trials such as PEPTIC is an important objective for the UCD School of Medicine. By providing facilities and expertise at the UCD Clinical Research Centre we are enabling groups, like the ICCCTG to conduct important, impactful trials that are leading to better healthcare.
Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation | The PEPTIC Randomized Clinical Trial
The PEPTIC Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Alberta Health Services Critical Care Strategic Clinical Network, and the Irish Critical Care Trials Group Young PJ, Bagshaw SM, Forbes AB, Nichol AD, Wright SE, Bailey M, Bellomo R, Beasley R, Brickell K, Eastwood GM, Gattas DJ, van Haren F, Litton E, Mackle DM, McArthur CJ, McGuinness SP, Mouncey PR, Navarra L, Opgenorth D, Pilcher D, Saxena MK, Webb SA, Wiley D, Rowan KM. JAMA. 2020 Jan 17. doi: 10.1001/jama.2019.22190.
JAMA. 2020 Jan 17
A video presentation of the PEPTIC study results and a companion editorial review is available here.
The School is delighted to announce the appointment of two new full professors with the appointment of Professor Yvonne O’Meara as UCD Full Professor of Medicine and Therapeutics at the Mater Misericordiae University Hospital and Professor Helen Heneghan as UCD Full Professor of Surgery at St Vincent’s University Hospital.
Both women were appointed following competitive recruitment campaigns in 2019 and formally took up their appointments at the end of last semester. They are the first female appointees to both these senior leadership roles at the School and are, no doubt, role models for younger female doctors and medical students. We wish both women well on their appointments and look forward to working with them as they implement their visions for Medicine and Surgery in the School.
Professor Yvonne O’Meara, previously interim Professor of Medicine was appointed Full Professor of Medicine and Therapeutics following a competitive recruitment process. A consultant nephrologist at the Mater Misericordiae University Hospital since 1997 when she was appointed as Senior Lecturer at the UCD School Medicine.
Prof O’Meara graduated from University College Cork in 1982 and after initial clinical training in Ireland she moved to Boston University (BU) in 1998 to take up a clinical and research fellowship in Nephrology. She joined the faculty at BU in 1992 and ultimately was Director of Clinical Nephrology and Director of the BU Renal Fellowship Programme.
Professor O’Meara returned to the Mater Misericordiae University hospital and UCD as Consultant Nephrologist / Senior Lecturer in Medicine in 1997. Her research interests include mechanisms of glomerular injury in experimental glomerulonephritis, diabetic nephropathy and quality of life in end stage kidney disease. She has a keen interest in Medical Education and has been the Academic Lead for both the undergraduate and graduate entry teaching programmes in Clinical Medicine at the Mater since 2007. She has served on a range of national committees and roles, including the Irish Postgraduate Medical and Dental Board, Irish Committee on Higher Medical Training, National Specialty Director in Nephrology, and President of the Irish Nephrology Society. She was appointed as Subject Head in Medicine in September 2018 and as Section Head of Medicine and Medical Specialties in November 2018.
Professor Helen Heneghan has been appointed as UCD Full Professor of Surgery at St Vincent’s University Hospital, also following a competitive recruitment process. Prof Heneghan has been consultant bariatric surgeon since 2017 and established a National Bariatric Surgery Centre with units at St Columcille’s, St Michael’s and St Vincent’s University Hospitals. This initiative led to a ten-fold increase in bariatric surgeries with over 100 cases per year, each recorded in the National Bariatric Surgery Registry.
Prof Heneghan graduated from the National University of Ireland, Galway in 2005 and completed a PhD in the molecular expression of breast cancer and obesity at the same University. She completed her basic medical training and subsequently her RCSI higher specialist training in general surgery at Galway University Hospital in 2016. Following completion of her specialist surgical training, Prof Heneghan undertook over two years of bariatric-specific training at the Bariatric Metabolic Institute in Cleveland, Ohio and completed a bariatric fellowship in the UK. Prof Heneghan’s research interests include evaluating the mechanisms of diabetes remission after bariatric surgery and evaluating the effect of significant weight loss on cancer, specifically female cancers such as breast and uterine cancer. She is also interested in studying the effect of bariatric surgery on fatty liver disease, specifically non-alcoholic steatohepatitis (NASH). She is an active researcher within the UCD Diabetes Complications Research Centre and has published extensively.
Although both women are experienced clinicians in their own right, their appointment to the most senior academic rank within the School is particularly welcomed given the low number of female staff at this level. Both Professors are role models for our medical students, particularly our female students. The appointments have been warmly welcomed by the UCD Medical Society and the UCD Surgical Society. Both Prof O’Meara and Prof Heneghan have been strong supporters of medical education within the School and at their respective hospitals and they are actively engaged in our teaching programmes.
The School is delighted to announce the appointment of nine new academic fellows as part of the University’s Ad Astra strategic initiative to recruit high-potential early-stage academic staff. The appointments were made following a highly competitive UCD-wide recruitment process which sees up to 65 new faculty join the University. We extend a warm welcome to all our new colleagues and look forward to working with them. Among the UCD Ad Astra Fellows appointed in 2019/2020 are:-
In welcoming the new appointees, Dean of Medicine and Head of School, Professor Michael Keane said:
I am delighted to welcome our new Ad Astra Fellows to the School and congratulate existing staff who have been appointed to these prestigious new roles. I am confident that each of the Fellows will help us realise our ambition to be a leading research-active Medical School and their research expertise will enhance our teaching programmes.
Prof Peter Doran, Associate Dean for Research, Innovation & Impact echoed the School’s welcome saying,
The appointment of these nine academic fellows to the School of Medicine is a clear signal of the school’s commitment to teaching and research across the clinical and translational sciences. The School boasts some of the leading researchers in the University, and some of the leaders worldwide within their research domains, as recognised by prestigious awards, citation metrics and other esteem indicators.
These new fellows add further substantial breadth and depth to the school’s research footprint and I look forward to welcoming and supporting them as they develop their research endeavour at the School.
The School looks forward to introducing many of our new fellows to the School on Wednesday 8th January 2020 and to showcase their research interests through a series of seminars during the academic year.
Launched in 2018/2019, the UCD Ad Astra Fellows initiative is designed to recruit 65 new academic staff at Lecturer/Assistant level each year to advance our ambition to be a research-intensive, global university with purpose, drive and ambition. This expansion of our academic faculty will reduce our student : staff ratio and allow us to introduce exciting new pedagogical approaches to our education and training.