A 3D map of the islet density routes throughout the healthy human pancreas. Source: Wikimedia CC0
Scientists have long known that pancreatic β cells increase during pregnancy and promptly return to their original number following birth. But the underlying mechanisms that cause the cells to go back to their original number are still not well understood.
In a significant breakthrough, a research group using mouse models, has discovered that macrophages ‘eat’ (phagocytose) the pancreatic β cells, thereby revealing the process behind their return to previous levels after pregnancy.
The research group, which was led by Associate Professor Junta Imai, Assistant Professor Akira Endo, and Professor Hideki Katagiri from Tohoku University’s Graduate School of Medicine, published the results in the journal Development Cell.
Initially, the group examined the number of pancreatic β cells in the islets of Langerhans in a mouse model of pregnancy.
They confirmed the cell number was double at the end of the pregnancy when compared to non-pregnant mice, but that it then gradually decreased, returning to the original amount after delivery.
“After we observed the islets of Langerhans before and after delivery, we noticed an increase in macrophages, which protect the body from infections by engulfing bacteria, foreign substances and dead cells, after delivery,” says Imai.
“When we applied treatment to inhibit this process, the blood glucose levels became too low (hypoglycaemia).”
Additional microscopic observation of the islets of Langerhans after birth revealed β cells to be phagocytosed by macrophages.
This mechanism appeared to keep the mother’s blood glucose levels from decreasing excessively after delivery by rapidly reducing pancreatic β cells to their normal pre-pregnancy number.
Next, the group identified the protein responsible for attracting the macrophages into the islets of Langerhans: cytokine CXCL10.
Accordingly, the inhibition of CXCL10 function suppressed the decrease in pancreatic β cells after birth.
“We hope our results will contribute to clarifying the means by which normal blood glucose levels are maintained as well as the development of methods to prevent and treat diabetes,” adds Imai.
Some individuals with anti-Ro/SSA antibodies (anti–Sjögren’s-syndrome–related antigen A autoantibodies, also called anti-Ro antibodies) have autoimmune diseases such as lupus or Sjögren’s syndrome, but many have no symptoms. A clinical trial published in Arthritis & Rheumatology found that high levels of these antibodies in pregnant women are associated with foetal atrioventricular block (AVB), which occurs when inflammation and subsequent scarring prevent electric signals from the heart’s atria from reaching the ventricles. The disease is associated with life-long pacing and can be fatal.
In the trial, called Surveillance ToPrevent AV Block Likely to Occur Quickly (STOP BLOQ), the incidence of AVB increased with higher levels of anti-Ro/SSA antibodies, reaching 7.7% for those in the top quartile, which increased to 27.3% in those with a previous child who had AVB, although participant numbers in that category were small. Antibody titres did not change over time. The trial also revealed that home-based foetal heart rate monitoring reliably detected conduction abnormalities, which may reduce the need for serial echocardiograms.
“Examining the levels of anti-Ro/SSA antibodies is an important advance since for women with low titres, monitoring is probably not necessary and for those with high titres the increased risk supports surveillance,” said corresponding author Jill Buyon, MD, of NYU Langone Health. She added that this study also indicated that titres of antibodies do not change and that additional factors besides antibodies contribute to risk.
“That home monitoring can rapidly and accurately identify early foetal conduction disease is a major step forward that may significantly decrease the need for echocardiograms and hopefully facilitate reversibility,” added senior author and research professor Bettina Cuneo MD, of the University of Arizona-Tucson College of Medicine.
A meta-analysis of studies published over the past 40 years on cannabis use during pregnancy has found an association between foetal exposure to cannabis in the womb and preterm delivery, low birth weight and the need for neonatal intensive care admission (NICU). The study was published today in the journal Addiction.
Previous research has indicated that THC, the main psychoactive component in cannabis, can cross the placenta to the foetus during pregnancy and bind to receptors in the foetal brain.
The meta-analysis examined the results of 57 studies around the world that included almost 13 million infants in total. Based on either self-reports from pregnant women, or blood and saliva testing depending on the study, just over 100 000 infants were found to be exposed to cannabis in the womb. While none of the studies found a direct causal relationship between cannabis use during pregnancy and adverse birth outcomes, the combined results indicated that newborns exposed to cannabis during pregnancy were twice as likely to require NICU admission, twice as likely to have a low birth rate and one and a half times more likely to be born early.
While there has been little research on cannabis use during pregnancy since cannabis was legalised in Canada five years ago, an American study has indicated an increase in cannabis use during pregnancy in states where it has been legalised and the perceived risk of harm from cannabis has decreased. The study states that overall cannabis use in pregnancy has doubled in the past 20 years, with approximately 10% of pregnancies associated with cannabis exposure. Some studies indicated it was being used to alleviate symptoms of nausea, poor appetite, insomnia or anxiety during pregnancy.
“This research emphasizes the importance of healthcare providers making an effort to create a safe space talking to pregnant women and women planning to be pregnant about their cannabis use and their motivations for using it to educate them about the potential risks and empower them to make informed decisions for their child,” says lead author Maryam Sorkhou, a PHD student within the addictions division at CAMH as well as the University of Toronto. Ms Sorkhou is overseen at CAMH by Senior Scientist and paper co-author Dr Tony George.
A treatment to move blood from the umbilical cord into an infant’s body may provide a safe option for preterm infants born after 28 weeks who need rapid support, suggests a study supported by the National Institutes of Health. The procedure, called umbilical cord milking, involves gently squeezing the cord between the thumb and forefinger and pushing the blood into the newborn’s abdomen.
The new findings suggest that concerns raised by a 2019 study of infants born before 28 weeks (which concluded that umbilical cord milking might increase the risk of bleeding inside the brain) do not apply to preterm infants born after 28 weeks. The current study appears in Pediatrics.
The standard procedure, delaying cord clamping while blood naturally flows into the infant’s body, takes 30 to 180 seconds. However, cord milking, takes about 20 seconds, reducing delay for infants who need immediate assistance, such as respiratory support. Both procedures allow for umbilical cord blood to reach the infant’s body before clamping, reducing the risk of anaemia and other complications seen among infants receiving immediate cord clamping and cutting.
The study was conducted by Anup Katheria, M.D., of the Sharp Mary Birch Hospital for Women & Newborns in San Diego, and colleagues in the United States, Canada and Europe. It was supported by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.
More than 1000 infants were randomly assigned either to umbilical cord milking or delayed cord clamping. Rates of severe intraventricular haemorrhage and/or death did not differ significantly between the two groups (just over 1%). Moreover, the rates of overall intraventricular haemorrhage were also similar between the groups (approximately 12%). The researchers will follow all the infants in the study for two years to observe longer term outcomes.
Research on adding a long-acting nonsteroidal anti-inflammatory drug (NSAID) to an oral emergency contraceptive pill (also known as the morning-after pill) showed that it increases the effectiveness of pregnancy prevention. The study findings were recently published in The Lancet.
Emergency contraception is a contraceptive method that can be used to prevent an unintended pregnancy when a regular contraceptive method fails or is not used. It can be in the form of an oral emergency contraceptive pill or the insertion of a copper intrauterine contraceptive device (Cu-IUD). The oral levonorgestrel emergency contraceptive pill is one of the most popular choices of emergency contraception and is widely used in most countries. It was pioneered by a clinical trial in Hong Kong led by HKUMed’s Professor Ho Pak-chung, published in 1993. However, all contraceptive methods have a failure rate. Hence, the research team is continuing its efforts to explore more effective options.
Prostaglandins mediate a number of biological processes, including inflammatory responses. In the reproductive system, prostaglandin is an important mediator of processes like ovulation, fertilisation and embryo implantation. The research team postulated that adding a medication that blocks prostaglandin synthesis may have an additional complementary effect in achieving contraception.
The collaborative research team, including members of LKS Faculty of Medicine of the University of Hong Kong (HKUMed), as well as The Family Planning Association of Hong Kong (FPAHK) and Sweden’s Karolinska Institutet, conducted the world’s first randomised, placebo-controlled trial on the use of piroxicam, an NSAID used to treat arthritis pain, which blocks prostaglandin production in the body, in combination with the levonorgestrel emergency contraceptive pill. The findings revealed that with the new combination regimen, only one out of 418 women became pregnant, while seven out of another 418 women receiving levonorgestrel and a placebo became pregnant. The results showed that the percentage of pregnancies prevented by piroxicam-levonorgestrel co-treatment (94.7%) was significantly higher than that of the levonorgestrel emergency contraceptive pill alone (63.4%). There was no significant difference in the occurrence of adverse effects, including changes to the menstrual bleeding pattern and stomach ache following intake of the two regimens.
Significance of the study
Chief-investigator Dr Raymond Li Hang-wun, from HKUMed, said, “Our study is the first to find that piroxicam, a readily available medication, taken at the same time as the levonorgestrel pill can prevent more pregnancies than levonorgestrel alone. We hope these findings will lead to further research and ultimately changes in clinical guidelines to enable women around the world to access more effective emergency contraception.”
Co-investigator Dr Sue Lo Seen-tsing, from FPAHK, said, “The levonorgestrel pill was registered in Hong Kong in 2002 and has been used safely since then. Locally, emergency contraceptives must be prescribed by healthcare providers, who assess which emergency contraceptive method is the most suitable in each case. Contraceptive counselling should be provided to help women seeking emergency contraception understand that it cannot replace regular contraceptives and to motivate them to use the latter. Since there is still a small failure rate, a follow-up visit is important. The levonorgestrel emergency contraception pill should be taken within 72 hours after unprotected sex; the earlier it is taken, the more effective it is.”
A new study published in the journal BMC Pregnancy and Childbirth has found considerable variability in the ways pregnancy affects women’s perceptions of their own body, including experiences of negative body image.
Negative body image during pregnancy is known to have serious adverse effects on both the mother and baby. Overall, average levels of body image dissatisfaction were found to be similar for pregnant women compared to the general female population, but on an individual basis, the research discovered large differences, both positive and negative.
The study is thought to be the first meta-analysis comparing pregnant and non-pregnant women, and was led by academics from Anglia Ruskin University (ARU) and the University of York.
The researchers initially screened 2017 separate academic studies, before focusing on 17 studies that provided comparable data. In total, the research included 5200 responses from women who were pregnant and 4172 responses from women who were not pregnant.
By synthesising results from multiple studies, the new research found women’s body image dissatisfaction overall was not statistically different during pregnancy compared with when not pregnant. However, when looking at the separate studies that formed part of the meta-analysis, there are significant variations on an individual level.
Body image dissatisfaction in pregnancy is made up of a combination of complex factors related to the positive and negative experiences of each woman, the researchers believe. For some, body image satisfaction will worsen during pregnancy because of ‘feeling fat’, while others describe feeling that their body is out of their control because they are aware their body will change but cannot stop it. Unrealistic portrayals of pregnant women in the media, often edited to remove uneven skin tone and stretch marks, are also believed to contribute to body image dissatisfaction.
Other pregnant women report having improved body positivity compared to when not pregnant, as they no longer compare their body to the ‘thin ideal’. Some say the improvement is because they place less attention on how their body looks and more on its functionality, focusing on the foetus’s health and their maternal role.
Understanding the causes of body image dissatisfaction in pregnant women is important since it can have physical and mental consequences for mother and baby. Many women who display body image dissatisfaction during pregnancy also exhibit depression and anxiety, both postnatally and longer term. This can lead to negative emotional, cognitive, and behavioural outcomes for the child, as well as poor quality mother-infant interactions.
In addition, body image dissatisfaction has been linked with physical illness as the expectant mother may engage in practices such as unhealthy eating, dieting, purging, and fasting. This can have unwanted negative effects on the foetus, such as low birth weight and premature birth.
Lead author Anna Crossland, University of York, said: “Due to the impact that body dissatisfaction can have on the expectant mother and foetus, it is vital to understand how body image dissatisfaction may change on an individual basis when women are pregnant. What our study has found is there is no universal experience during pregnancy, and so we shouldn’t assume how people feel. Pressures about how we look are still felt by some people during pregnancy and it is much more helpful to ask how someone is, rather than commenting on their appearance.”
Co-author Dr Elizabeth Kirk, Senior Lecturer in Psychology at Anglia Ruskin University, said: “Our earlier work found that women who didn’t feel good about their changing bodies in pregnancy reported lower feelings of bonding with their unborn baby. Therefore, it is crucial that we better understand and support women’s body image during pregnancy, to help women on an individual basis.”
Last month, she won the Mandela Rhodes Foundation’s award for social impact in Africa for a device that can help save the lives of women who suffer excessive bleeding after child birth. PHOTO: Nasief Manie/Spotlight
By Biénne Huisman for Spotlight
As a child growing up in the Ugandan capital of Kampala, Maureen Etuket used a screwdriver to dismantle electronic appliances and toy trucks. “I was around eight, nine years old,” she says. “I guess it just excited me.”
Slightly over a decade later, this curiosity is driving her quest to find solutions to public healthcare challenges.
Last month, Etuket’s Smart PVD device [Postpartum Haemorrhage Volumetric Drape] won the Mandela Rhodes Foundation’s award for social impact in Africa – the 2023 Äänit Prize – with a cash grant of $38 000. At the awards ceremony in Cape Town, judges described the device as “a brilliantly practical intervention that can immediately and directly improve outcomes for patients”.
Inside the Anatomy Building on the University of Cape Town (UCT)’s Health Sciences campus, Etuket explains that she and her team devised a prototype after spending three months in maternity wards at Kawempe National Referral Hospital in Kampala.
“We went almost every day. We had day shifts and night shifts,” she recalls. “I started asking the question to nurses and midwives, how do you know that a woman is likely to get to PPH?” PPH or post-partum haemorrhage is excessive bleeding after a baby’s birth, which could cause a severe drop in blood pressure leading to shock and death if not treated.
“Like, how do you tell? What criteria do you use? And the nurses told me that they had been doing this for a long time. They said they just observe and know. And I thought to myself, if that was working, we would have [fewer] women dying from PPH.”
How does the Smart PVD device work?
“There’s something already on the market – an under-buttock drape bag attached to the bed while a woman is giving birth, which measures amount of blood loss,” says Etuket. “[It’s] basically a bag where the blood flows into. We then created an electronic module that has a probe and a buzzer, which we put inside this bag, and it gives a beeping sound when the blood has reached a certain level. This alarm alerts a midwife to recognise the need to attend to a particular case. So the blood collection module is disposable. And the electronic module, which has the probe and the buzzer, is reusable.”
Etuket declines to share pictures, citing intellectual property rights.
“I really think that this is one of the simplest innovations,” she says. “We’ve been pitching it and talking about it, and everyone that listens is just like it’s common sense, right?” Apart from the Äänit Prize, they have received $16 000 from the Makerere University’s research and innovations fund and $55 000 from the science and technology secretariat in Uganda.
Moving to Cape Town
Etuket moved to Cape Town in 2021, courtesy of a Mandela Rhodes Foundation scholarship. “I applied for a Masters in health innovation at UCT under the Mandela Rhodes Foundation. So, I’m Christian. I believe in the hand of God in everything I do. I made just that one application. Like, there were options to put three universities, three courses, all that. I just wanted health innovation at UCT, and I got it.”
Her Masters supervisor was Professor Sudesh Sivarasu, internationally renowned for medical device innovation and head of UCT’s MedTech laboratory.
“There were so many questions we had at Pumzi Devices about how to transition an innovation to the market and no one really had the answers because it’s a new space. At a certain point, some of us had to travel to Scotland just to sit with experts to guide us through a protocol design process. No one in Uganda really had a clear picture of [this] so that’s what prompted me to do the Masters in health innovation,” says Etuket.
Find your purpose
Presently, she is pursuing a PhD in industrial engineering at Stellenbosch University under the supervision of Professor Sara Grobbelaar and Dr Faatiema Salie. Yet she spends most of her time at UCT, where Sivarasu is her external co-supervisor. Etuket’s PhD’s working title is “Exploring the development of a localisation roadmap for medical devices in South Africa using an Innovation Systems Framework”. She explains that this line of study – systems engineering – is drawing her thinking wider to understand the systems around biomedical design and innovation.
Going forward, Etuket will continue to lecture students back home in Uganda – online – while being open to further her learning and practice where it is apt or required around the world.
At 28 years old, Etuket’s drive and achievements make her a role model for many. However, she is reluctant to wear the label of “a pioneering young black woman,” voicing caution over mantels based on race and gender. “I notice that when we start to have those mindsets, we may end up trampling on people, on men. We have to work together. There is room for all of us,” she says.
The first born of four siblings, Etuket’s father was a computer engineer and her mother an accountant and businesswoman. Elaborating on leadership, she says, “I think it’s important to pray for people. That’s where we get guidance on how to lead. I tell people, not everyone should do a PhD, maybe not everyone should do a Masters, but find your purpose and fulfil it.”
A significant step forward has been taken in the management of gestational diabetes mellitus after a clinical trial involving pregnant women provided new hope for expectant mothers suffering the condition. The findings from the trial are published in the Journal of American Medical Association.
Gestational diabetes affects almost 3 million pregnant women worldwide every year. It is a condition characterised by elevated blood sugar levels during pregnancy, posing increased health risks for both mothers and their babies.
The EMERGE, randomised, placebo-controlled trial, was conducted by the University of Galway and involved more than 500 pregnant women.
The trial results showed that:
Women assigned to metformin were 25% less likely to need insulin, and when insulin was necessary, it was started later in the pregnancy.
Fasting and post-meal glycaemic values in the mother were significantly lower in the metformin exposed group at weeks 32 and 38.
Women receiving metformin gained less weight throughout the trial and maintained this weight difference at the 12-week post-delivery visit.
Importantly, delivery occurred at the same mean gestational age (39.1 weeks) in both groups. There was no evidence of any increase in preterm birth (defined as birth before 37 weeks) among those who received metformin.
Infants born to mothers who received metformin weighed, on average, 113g less at birth, with significantly fewer infants classified as large at birth, or weighing over 4kg.
While there was a slight reduction in infant length (0.7cm), there were no other significant differences in baby measurements.
There were slightly more babies who were small at birth but this did not reach statistical significance.
The study also revealed no differences in adverse neonatal outcomes, including the need for intensive care treatment for new-borns, respiratory support, jaundice, congenital anomalies, birth injuries or low sugar levels.
Additionally there were no variations in rates of labour induction, caesarean delivery, maternal haemorrhage, infection or blood pressure issues during or after birth.
Professor Fidelma Dunne managed the trial, and presented the results at the 59th Annual Meeting of the European Association for the Study of Diabetes in Hamburg, Germany.
Professor Dunne said, “While there is convincing evidence that improved sugar control is associated with improved pregnancy outcomes, there was uncertainty about the optimal management approach following a diagnosis of gestational diabetes.
“In our pursuit of a safe and effective treatment option we explored an alternative approach – administering the drug metformin. A previous trial compared metformin to insulin and found it to be effective, yet concerns remained, especially regarding preterm birth and infant size.”
To address concerns comprehensively, the team at University of Galway conducted a ground-breaking placebo-controlled-trial, filling a critical gap in the gestational diabetes treatment landscape.
535 pregnant women took part, with 268 receiving metformin and 267 a placebo.
98% of women remained in the trial until delivery, with 88% completing the 12-week post-delivery follow up assessment.
Only 4.9% of women discontinued medication due to side effects, highlighting the safety of the interventions.
Professor Dunne said, “Traditionally, gestational diabetes has been managed initially through dietary advice and exercise, with insulin introduced if sugar levels remain sub optimal. While effective in reducing poor pregnancy outcomes, insulin use is associated with challenges, including low sugars in both the mother and infant which may require neonatal intensive care, excess weight gain for mothers, and higher caesarean birth rates.” Professor Dunne added: “The results from the EMERGE study are a significant step forward for women with gestational diabetes. Metformin has emerged as an effective alternative for managing gestational diabetes, offering new hope for expectant mothers and healthcare providers worldwide.”
It has long been known that hot flashes are linked to a number of adverse health effects. Emerging data suggests an association between them and cardiovascular disease. A new study is the first to link physiologically assessed hot flashes with heightened systemic inflammation – a risk factor for cardiac disease. Study results will be presented during the 2023 Annual Meeting of The Menopause Society in Philadelphia September 27-30.
Vasomotor symptoms, more often referred to as hot flashes, are one of the most common symptoms identified during the menopause transition, with roughly 70% of midlife women reporting them. Not only do they interfere with a woman’s quality of life, but they have also been related to physical health risks, such as cardiovascular disease.
Previous research linking hot flashes with heightened systemic inflammation has relied on self-reporting to document the frequency and severity of the hot flashes. These self-reports of hot flashes are limited as they ask women to recall hot flashes over weeks or longer and may be subject to memory or reporting biases. A new study that included 276 participants from the MsHeart study, however, utilised sternal skin conductance to physiologically assess hot flashes and tested whether more frequent physiologically assessed hot flashes are associated with heightened system inflammation.
While large increases in inflammatory markers indicate acute infection or clinical disease, small and sustained increases of markers of inflammation that are in the physiologically normal range are predictive of later disease risk. For example, small and/or sustained increases in inflammatory biomarkers (conceptualised as heightened levels of systemic inflammation) have been related to plaque development and atherosclerotic cardiovascular disease.
Based on the results, the researchers concluded that physiologically assessed hot flashes during wake were associated with higher levels of a high-sensitivity C-reactive protein, even after adjusting for potential explanatory factors such as age, education, race/ethnicity, body mass index, and oestradiol.
The results will be presented during the Annual Meeting of The Menopause Society as part of the presentation entitled “Physiologically measured vasomotor symptoms and systemic inflammation among midlife women.”
“This is the first study to examine physiologically measured hot flashes in relation to inflammation and adds evidence to a growing body of literature suggesting that hot flashes may signify underlying vascular risk and indicate women who warrant focused cardiovascular disease prevention efforts,” says Mary Carson, MS, lead author from the Department of Psychology at the University of Pittsburgh.
“Since heart disease is the leading cause of death for women in the US, studies like these are especially valuable,” adds Dr Stephanie Faubion, medical director of The Menopause Society. “Healthcare professionals need to ask their patients about their hot flash experiences as they not only interfere with their quality of life but may also indicate other risk factors.”
New research from Queen Mary University of London, published in iScience, shows an increased risk of blood clots in women who have any combination of Factor V Leiden gene mutation, oestrogen use, or common medical conditions – specifically: obesity, high blood pressure, high cholesterol, and kidney disease.
Women with the Factor V Leiden (FVL) gene mutation who had been prescribed oestrogen had more than double the risk of blood clotting compared to women who did not have this mutation. And almost 20% of the women who carry FVL, were prescribed oestrogen and had two medical conditions suffered a blood clot. The presence of the FVL gene made a substantial difference to risk, with only around 5% of women taking oestrogen and having two conditions suffering a clotting event.
The study also found that a woman with obesity, hypertension, high cholesterol, and kidney disease (not uncommon in a clinical setting) had an 8 times greater chance of blood clotting compared to a woman with none of these conditions. This amounted to roughly one in every six women with the four conditions in the study suffering a blood clot. Three medical conditions meant a five times greater chance of blood clotting, and two medical conditions meant a two times greater chance.
One in three women who had the FVL gene mutation and three of the medical conditions examined also suffered a blood clotting event.
The researchers examined the health data of 20 048 British-Bangladeshi and British-Pakistani women from the Genes & Health project, a large community-based genetics study. While oestrogen use, FVL, and common medical conditions are all known risk factors of blood clots, studies have not looked at the combined risk of these factors together on blood clot prevalence.
Women are commonly prescribed oestrogen, both through oral contraception containing the hormone and as part of post-menopausal hormone replacement therapy.
Professor Sir Mark Caulfield, from Queen Mary University of London, said: “Our study gives a more complete picture of blood clotting in Bangladeshi and Pakistani communities who have previously been underrepresented in research.
“Genetic testing of the FVL gene mutation could give a clearer sense of someone’s personalised risk of this potentially fatal complication if they were prescribed oestrogen.”
