Category: Obstetrics & Gynaecology

Categories : Mental Health Obstetrics & GynaecologyTags :

Depression and Psychosis Risk Increases After Childbirth – but Suicide Risk Decreases

On By ModernMedia
Photo by Alina Matveycheva

Depression and psychosis are more common in women after childbirth than before, but the risk of suicide attempts decreases. This is shown by two new studies from Karolinska Institutet. The results suggest that national guidelines for screening can help women get help earlier.

Mental ill health in connection with pregnancy and childbirth can have long-term consequences for women’s health. During this period, major biological and psychosocial changes occur that can increase vulnerability to depression, anxiety, and other psychiatric conditions. Despite previous research, knowledge has been limited, especially regarding how different psychiatric diagnoses develop before, during, and after pregnancy.

In a new study, researchers have used data from Swedish registers covering all women who gave birth in Sweden between 2003 and 2019 – a total of nearly 1.8 million pregnancies.

The study, published in the journal Molecular Psychiatry, shows that mental ill health has increased over time during this period, especially before pregnancy. During pregnancy itself, the number of new diagnoses decreases, but after childbirth, the risk increases again, especially for depression and psychosis.

“We can see that the risk of depression is about 20 percent higher during weeks 5 to 15 after childbirth, compared to the year before pregnancy. For psychosis, the risk is up to seven times higher during the first 20 weeks after childbirth,” says the study’s first author Emma Bränn, researcher, Institute of Environmental Medicine, Karolinska Institutet.

When Swedish national guidelines for screening pregnant women for depression were introduced in 2010, it opened up the possibility of detecting mental illness earlier. By comparing women who gave birth before and after 2010, the researchers saw that the peak of depression diagnoses occurred earlier after childbirth in women who gave birth after the guidelines were introduced.

“We don’t see that more people are being diagnosed, but screening could mean that women are identified earlier and don’t have to suffer as long before they can get the support and help they need,” says Emma Bränn. 

Lower risk for other psychiatric diagnoses

The study also shows that the risk of other psychiatric diagnoses, such as anxiety, stress-related conditions, and substance abuse, is lower during pregnancy and after childbirth compared to before. The researchers believe that this may be due to biological changes, lifestyle changes, and increased contact with healthcare during pregnancy.

Another study from the same research group has investigated the risk of suicide in connection with pregnancy and childbirth. In the study, published in Nature Human Behaviour, researchers found that mothers were less likely to attempt suicide during and after pregnancy compared to fathers. This is the opposite of what researchers usually observe in the general population, where women tend to have higher rates of suicide attempts than men. For fathers, the risk decreased in the first ten weeks after childbirth, only to increase again.

“Our results suggest that both mothers and fathers are less likely to attempt suicide immediately after having a child, especially mothers,” says first author Yihui Yang, PhD student at the same department. She continues:

“Although suicide attempts during and after pregnancy are rare, they can have devastating consequences and are often preventable. It is therefore important that healthcare providers conduct regular check-ups during and after pregnancy to identify parents who are struggling and offer support to prevent suicide.”

Source: Karolinska Institutet

Categories : Environmental Effects Obstetrics & GynaecologyTags :

Artificial Light Changes Menstrual Synchronisation with the Moon

On By ModernMedia

There is no question that the moon has a significant influence on Earth. Its gravitational pull affects the planet and moves water masses in the daily rhythm of ebb and flow (tides) – this point is undisputed. More difficult to answer is the question of whether the same gravitational force also affects life on Earth, especially the human organism. And the discussion becomes even more complicated when it comes to how the fluctuating brightness of the Earth’s satellite between full and new moon affects humans.

A research team led by Julius-Maximilians-Universität Würzburg (JMU) has now presented new findings on this topic. Its conclusion: “We show that synchronisation with the moon has decreased significantly since the introduction of LEDs and the increasing use of smartphones and screens of all kinds,” explains Charlotte Förster. The Würzburg chronobiologist recently headed the Department of Neurobiology and Genetics; she now conducts research there as a senior professor.

Comparing Records from two Centuries

For their study, now published in the journal Science Advances, Förster and her team analysed long-term menstrual records of women from the past 50 years. “The results showed that the menstrual cycles of women whose records were made before the introduction of light-emitting diodes in 2010 and the widespread use of smartphones were significantly synchronised with the cycle of the full and new moon,” says Förster, describing the key finding. After 2010, the cycles were mostly only synchronized in January, when the gravitational forces between the moon, sun, and Earth are at their highest.

The scientists therefore hypothesize that humans have an internal moon clock that can be synchronised to the lunar cycle by natural night light and gravitational forces. However, the coupling of the moon clock to the lunar cycle in humans is impaired by increasing nighttime illumination from artificial light.

Other Studies Support the Moon Clock Hypothesis

“Moon clocks are widespread in marine organisms, but have not yet been proven in humans,” explains Charlotte Förster. In fact, many species synchronize their reproductive behaviour with a specific phase of the lunar cycle in order to increase reproductive success. The human menstrual cycle also has a similar duration to the lunar cycle, at approximately 29.5 days, and recent studies also suggest at least temporary synchronicity between the menstrual and lunar cycles.

The influence of the moon on the female cycle remains controversial. “It is completely unclear how such a lunar clock can be synchronised by the small cyclical changes in gravity between the Earth and the moon,” says Förster. The findings now published are consistent with results from sleep research and psychiatry.

For example, studies by two chronobiologists, Basel researcher Christian Cajochen and Washington biologist Horacio de la Iglesia, show that people sleep significantly less around the full and new moon than at other times. “Interestingly, this also applies to city dwellers, where nighttime city lighting is much brighter than the light of the full moon,” says the chronobiologist. And US psychiatrist Thomas Wehr has concluded that people with bipolar disorder are more likely to switch between mania and depression around the full and new moon.

Artificial Light Disrupts Synchronisation

Taken together, these findings suggest that humans can respond not only to moonlight, but also to the gravitational cycles caused by the moon, according to the Würzburg research team. “However, our study shows that increased exposure to artificial light severely impairs the synchrony between the menstrual cycle and the lunar cycle,” explains Charlotte Förster.

According to this, artificial light at night not only “outshines” the natural moonlight cycles, but also shortens the length of the menstrual cycle. However, since continuous synchronization is only possible if the length of the cycle is close to the lunar cycle, this shortening in turn reduces the likelihood of synchronization.

A High Proportion of Blue Light Increases the Effect

Anyone wondering why the introduction of LEDs and the increasing use of smartphones have this effect – after all, artificial lighting has been around for a long time, from gas lanterns to incandescent light bulbs – will find an explanation in Charlotte Förster’s words: “LEDs have much higher energy than gas lanterns and light bulbs. In addition, they have a high proportion of blue light, to which our photoreceptors in the eye are particularly sensitive.” That is why LED light has a much stronger effect on humans than previous light sources.

And even though Charlotte Förster and her team were able to clearly demonstrate that the synchronization of the female menstrual cycle with the moon is weakened by LEDs, smartphones, and screens of all kinds, there is one small caveat when interpreting these results: “Our findings show a correlation between these two phenomena. We were unable to establish a causal link,” says the scientist.

In principle, the study now published is basic research. Nevertheless, a potential benefit emerges from the evaluation of the data: “Since period length appears to be a possible age-dependent marker for female fertility, our findings could be relevant not only for human physiology and behaviour, but also for fertility and contraception,” says Charlotte Förster.

Source: University of Würzburg

Categories : Cancer Obstetrics & GynaecologyTags :

New Study Reveals a Hidden Risk After Cervical Cancer

On By ModernMedia
Cervical cancer. Credit: Scientific Animations CC4.0

For women who’ve overcome cervical cancer, new research from MUSC Hollings Cancer Center points to another health risk that may not be on their radar: anal cancer.

Led by Hollings researchers Haluk Damgacioglu, Ph.D., and Ashish Deshmukh, PhD, co-leader of the Cancer Prevention and Control Research Program, the study sheds light on an under-recognised risk facing women with a history of cervical cancer – and highlights the need for updated screening guidelines. The paper was published in JAMA Network Open.

While cervical cancer is one of the most preventable cancers, with a survival rate of over 90% when found early, clinical guidelines have not addressed what comes next for these patients, who may be at high risk for a related type of cancer.

“We’ve known for a long time that both cervical and anal cancers are caused by HPV, the human papillomavirus,” Deshmukh said. “But what hasn’t been well-understood is how that shared risk might connect the two diseases over a woman’s lifetime.”

Currently, anal cancer screening is recommended for certain high-risk groups, such as people living with HIV, organ transplant recipients and women with a history of vulvar cancer. But there are no clear screening guidelines for women with cervical cancer.

One problem has been a lack of long-term data on their risk and how that risk changes with age and over time. This study helps to fill that gap using high-quality, population-based data.

The researchers turned to the National Cancer Institute’s SEER (Surveillance, Epidemiology and End Results) program – a comprehensive set of registries that tracks cancer diagnoses across the US. They analysed data from more than 85 000 women diagnosed with cervical cancer, tracking them over two decades to see how many went on to develop anal cancer and when those diagnoses occurred.

What they found was striking. Compared with the general population, women with a history of cervical cancer had nearly twice the risk of developing anal cancer.

Anal cancer rates increased with age and over time, with the most diagnoses found in women ages 65 to 74 who were more than 15 years out from their original diagnosis. For women in this age group, the rate of anal cancer diagnoses surpassed a widely accepted threshold for recommending routine screening.

“Our study shows that the risk doesn’t go away – it actually increases with age and over time,” Damgacioglu said.

Why the delay? HPV-related cancers often take years, sometimes decades, to develop. In some cases, the virus may linger undetected or have spread from another part of the body.

“It’s a slow process,” Deshmukh said, “and that’s part of why it’s been so hard to detect. By the time symptoms show up, the cancer is often advanced.”

While anal cancer screening is not as routine as screening for other cancers, reliable methods do exist, including anal cytology (a kind of Pap screen) and anoscopy. Unfortunately, access to specialised screening remains limited. In South Carolina, for example, there is currently only one provider trained to perform high-resolution anoscopy.

That is why it is so important to identify and prioritise the highest-risk groups.

“These results tell us that women who had cervical cancer years ago should be considered for routine anal cancer screening,” Damgacioglu said. “Right now, that’s not happening.”

Deshmukh and his team are now working on a project to determine when and how often screening should happen.

Source: Medical University of South Carolina

Categories : Mental Health Obstetrics & GynaecologyTags :

Placenta Acts to Shield Foetus from Serotonin

On By ModernMedia
Image by Scientific Animations CC4.0

The placenta has long been thought to produce serotonin during pregnancy. But in a new study, Yale researchers shatter the deep-rooted hypothesis – and show that the placenta doesn’t produce serotonin but instead regulates its delivery to the embryo and foetus. They found that serotonin comes from the pregnant parent, with the placenta acting as a “serotonin shield” that controls how much reaches the embryo and foetus. 

The findings, published in the journal Endocrinology, could offer critical insights into how a parent’s serotonin levels might affect the development of their baby’s body and brain, the researchers say. 

“The placenta is in essence the ‘serotonin shield’ that regulates how much serotonin is ultimately delivered to the embryo and foetus, not the source of serotonin,” said Harvey Kliman, a research scientist in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Yale School of Medicine and corresponding author of the study. “Why does this matter? Because now we correctly know where this delivery is regulated.”

Often called a “happiness hormone,” serotonin regulates mood, so it’s often associated with the brain. In reality, less than 5% of serotonin is made in the brain, with 95% of it made in the gut. But serotonin does more than just regulate mood. It’s also a growth hormone. In the gut, it gets taken up by platelets and is delivered to parts of the body that need to grow, including in wound healing. 

During pregnancy, serotonin also helps with growth: It travels into the placenta through a special protein known as the serotonin transporter (SERT) where it plays a critical role in the development of the embryo and foetus. 

Serotonin from the mother is taken up by the foetal placenta, which then produces a myriad of hormones, growth factors, and regulators that are delivered to the foetus.

For the new study, researchers sought to better understand these relationships by using a pure source of placenta cells, unlike in previous studies that looked at either whole animals or isolated mouse placentas. To do so, they first purified human cytotrophoblasts, which are the stem cells that make all the cells of the placenta. They then added serotonin to those cells to see where it would go and discovered it concentrated in the nucleus. Next, they used a selective serotonin reuptake inhibitor (SSRI) that blocked SERT, escitalopram, to show that the normal growth, function, and differentiation of these cells was completely blocked. 

They also used another inhibitor called cystamine to block serotonylation, or the process by which serotonin is added to proteins like histone 3, which turns genes “on” and “off.” Again, that completely blocked the normal growth of the cells. 

Blocking either SERT or serotonylation led to significant changes in gene expression of RNAs in the cytotrophoblasts, they found. Some genes, including ones involved in making, moving, and growing cells, became downregulated, or less active, when serotonin couldn’t enter the cell. Other gene, including ones that help cells stay alive and protect them, became upregulated, or more active. According to the researchers, these findings show that serotonin is critical for the growth of the cytotrophoblasts, the placenta, and by extension, the foetus. 

Additionally, researchers discovered that the cytotrophoblasts don’t contain tryptophan hydroxylase (TPH-1), or the enzyme that makes serotonin, indicating the cells within the placenta can’t produce serotonin on their own. 

“This suggests that factors that either inhibit serotonin transport through the placenta, or increase it, may have a significant impact on the placenta, embryo, foetus, and ultimately, the newborn and its brain,” Kliman said.

For example, Kliman says this explains why taking SSRIs, which decrease the levels of serotonin into the placenta, leads to smaller babies, and why, conversely, increased levels of serotonin may lead to bigger babies, with bigger brains, who may be at increased risk for developmental disabilities like autism.

Kliman and his lab have long investigated the link between placentas and children with autism, specifically the number of trophoblast inclusions (TIs) in the placenta. TIs are like wrinkles or folds in the placenta, caused by cells multiplying more than they should, typically only seen in pregnancies where there are genetic problems with the foetus. 

This new study is the culmination of research first published in 2006 that found significantly more TIs in the placentas from children with autism, and later in 2021, that the genetics of the foetus, and not the parent’s uterine environment, determine how many TIs are in the placenta. 

“This puts a big nail into the theory that vaccines cause autism,” suggested Kliman. “Autism, in essence, starts in the womb, not after delivery, and is most likely due to the genetics of the placenta and to a lesser extent, the maternal environment the placenta finds itself in.”

Source: Yale News

Categories : Neurology Obstetrics & GynaecologyTags :

Mother’s Microbes Play Role in Neonatal Brain Development

On By ModernMedia
Photo by Christian Bowen on Unsplash

New research from Michigan State University finds that microbes play an important role in shaping early brain development, specifically in a key brain region that controls stress, social behaviour, and vital body functions.

The study, published in Hormones and Behavior, used a mouse model to highlight how natural microbial exposure not only impacts brain structure immediately after birth but may even begin influencing development while still in the womb. A mouse model was chosen because mice share significant biological and behavioural similarities with humans and there are no other alternatives to study the role of microbes on brain development.

This work is of significance because modern obstetric practices, like peripartum antibiotic use and Cesarean delivery, disrupt maternal microbes. In the United States alone, 40% of women receive antibiotics around childbirth and one-third of all births occur via Cesarean section.

“At birth, a newborn body is colonised by microbes as it travels through the birth canal. Birth also coincides with important developmental events that shape the brain. We wanted to further explore how the arrival of these microbes may affect brain development,” said Alexandra Castillo Ruiz, lead author of the study and assistant professor in the MSU Department of Psychology.

The research team focused on a brain region called the paraventricular nucleus of the hypothalamus (PVN), which plays a central role in regulating stress, blood pressure, water balance, and even social behaviour. Their previous work had shown that mice raised without microbes, or germ-free mice, had more dying neurons in the PVN during early development. The new study set out to determine whether this increased cell death translated to changes in neuron number in the long run, and if any effects could be caused by the arrival of microbes at birth or if they began in the womb via signals from maternal microbes.

To find out, the researchers used a cross-fostering approach. Germ-free newborn mice were placed with mothers that had microbes and compared them to control groups. When the brains of these mice were examined just three days after birth, results were striking: All mice gestated by germ-free mothers had fewer neurons in the PVN, regardless of whether they received microbes after birth. They also found that germ-free adult mice had fewer neurons in the PVN.

“Our study shows that microbes play an important role in sculpting a brain region that is paramount for body functions and social behaviour. In addition, our study indicates that microbial effects start in the womb via signaling from maternal microbes,” said Castillo-Ruiz.

Rather than shunning our microbes, we should recognise them as partners in early life development,” said Castillo-Ruiz. “They’re helping build our brains from the very beginning.”

Source: Michigan State University

Categories : Cancer Obstetrics & GynaecologyTags :

Groundbreaking Ovarian Cancer Research Targets Cells that Fuel Tumour Growth

On By ModernMedia
Female reproductive system. Credit: Scientific Animations CC4.0 BY-SA

In a recent paper published in Nature, researchers at the University of Chicago discovered how to block nicotinamide N-methyl transferase (NNMT), an enzyme that is involved in the progression of high-grade serous ovarian cancer. The team showed that NNMT promotes cancer growth by helping the tumour evade the immune system, and they also developed a potent NNMT inhibitor that could help overcome therapy resistance, providing a new and effective strategy for treating ovarian cancer.

A common yet deadly form of ovarian cancer

High-grade serous ovarian cancer is the most common and deadly form of ovarian cancer. It is often diagnosed at advanced stages and is notoriously challenging to treat. Although surgery and chemotherapy initially provide substantial benefits, the cancer frequently recurs, leading to low survival rates. Immunotherapy, a breakthrough treatment for many cancers, has failed in ovarian cancer, largely because activity of surrounding cells has been programmed by the tumour to suppress the immune response. These cells, known as cancer-associated fibroblasts (CAFs), differ from normal fibroblasts, which play a vital role in supporting tissue integrity and facilitating wound healing. Instead, CAFs surround the tumor, offer protection, and release signals that weaken immune responses and promote metastasis.

“Most therapies focus on the cancer cells, but we are interested in the fibroblasts in the surrounding stroma. These cells don’t mutate like cancer cells, which makes them more stable and, we think, more targetable,” said Ernst Lengyel, MD, PhD, Professor and Chair of Obstetrics and Gynecology at UChicago and lead author of the paper. “We have pinpointed the mechanism behind CAF activation and found a drug that can halt it in its tracks.”

NNMT: A master regulator

In a landmark 2019 Nature study, Lengyel’s team showed that NNMT, a metabolic enzyme, is highly expressed in CAFs and converts normal fibroblasts into tumour-promoting fibroblasts by changing epigenetic and metabolic programming. The new Nature study demonstrates how NNMT promotes immune evasion and how to stop it. The UChicago team discovered that NNMT-expressing CAFs secrete complementary proteins, which convert monocytes (a type of white blood cells) into myeloid-derived suppressor cells (MDSCs).

“The enzyme NNMT induces widespread epigenetic changes in fibroblasts that promote tumour growth. Inhibiting NNMT has the potential to reverse these changes and reduce the tumour-supportive role of fibroblasts,” says Janna Heide, MD, a postdoctoral researcher in the Lengyel Lab and first author of the study.

Better results with combined NNMT inhibitor and immunotherapy

To translate these findings into treatment, the team collaborated with scientists at the National Center for Advancing Translational Sciences (NCATS) and the National Cancer Institute (NCI) Experimental Therapeutics (NExT) program, which supports early-stage drug development with high translational potential. After screening over 150 000 compounds, they identified a highly targeted NNMT inhibitor. In preclinical animal models of ovarian cancer, the NNMT inhibitor decreased tumour burden and restored immune activity. Most importantly, when the inhibitor was combined with immune checkpoint inhibitors, it halted tumour growth.

Historically, drug development has focused almost entirely on cancer cells. This study demonstrates that non-cancerous cells in the tumour microenvironment can also play a crucial role in disease progression and treatment resistance. Targeting CAFs through NNMT inhibition offers a new therapeutic approach to overcome these barriers.

“Immunotherapy hasn’t worked in ovarian cancer, but the combination therapy of an NNMT inhibitor with immunotherapy worked remarkably well in our preclinical models,” Lengyel said. “It was exciting to show that tumor growth can be controlled without even touching the cancer cells, just by reprogramming the supporting cells around them.”

Lengyel said this research was only possible through the partnership with the National Center for Advancing Translational Sciences and the collaborative spirit at the UChicago, particularly with Ralph Weichselbaum, MD, Chair of the Department of Radiation Oncology, an expert in immune regulation, and his team, including postdoctoral researcher András Piffkó, MD. This work is part of Lengyel’s broader efforts to transform ovarian cancer treatment, supported by an NCI Outstanding Investigator Award (R35), which funds long-term, high-impact research with the potential to change clinical practices.

“Without NIH funding, we simply couldn’t have accomplished this,” Lengyel said. “It allowed us to take risks, innovate, and ultimately develop something that might help patients.”

Source: University of Chicago Medicine

Categories : Obstetrics & GynaecologyTags :

Prenatal Paracetamol Use May Be Linked to Increased Risk of Autism and ADHD

On By ModernMedia
Photo by SHVETS production

Researchers at the Icahn School of Medicine at Mount Sinai have found that prenatal exposure to paracetamol may increase the risk of neurodevelopmental disorders, including autism spectrum disorder and attention-deficit/hyperactivity disorder (ADHD), in children. The study, published in BMC Environmental Health, is the first to apply the rigorous Navigation Guide methodology to systematically evaluate the rigour and quality of the scientific literature.

Paracetamol (known as acetaminophen in the US and Canada) is the most commonly used over-the-counter pain and fever medication during pregnancy and is used by more than half of pregnant women worldwide. Until now, acetaminophen has been considered the safest option for managing headache, fever, and other pain. Analysis by the Mount Sinai-led team of 46 studies incorporating data from more than 100 000 participants across multiple countries challenges this perception and underscores the need for both caution and further study.

The Navigation Guide Systematic Review methodology is a gold-standard framework for synthesising and evaluating environmental health data. This approach allows researchers to assess and rate each study’s risk of bias, such as selective reporting of the outcomes or incomplete data, as well as the strength of the evidence and the quality of the studies individually and collectively.

“Our findings show that higher-quality studies are more likely to show a link between prenatal acetaminophen exposure and increased risks of autism and ADHD,” said Diddier Prada, MD, PhD, Assistant Professor of Population Health Science and Policy, and Environmental Medicine and Climate Science, at the Icahn School of Medicine at Mount Sinai. “Given the widespread use of this medication, even a small increase in risk could have major public health implications.”

The paper also explores biological mechanisms that could explain the association between acetaminophen use and these disorders. Paracetamol is known to cross the placental barrier and may trigger oxidative stress, disrupt hormones, and cause epigenetic changes that interfere with foetal brain development.

While the study does not show that paracetamol directly causes neurodevelopmental disorders, the research team’s findings strengthen the evidence for a connection and raise concerns about current clinical practices.

The researchers call for cautious, time-limited use of paracetamol during pregnancy under medical supervision; updated clinical guidelines to better balance the benefits and risks; and further research to confirm these findings and identify safer alternatives for managing pain and fever in expectant mothers.

“Pregnant women should not stop taking medication without consulting their doctors,” Dr Prada emphasised. “Untreated pain or fever can also harm the baby. Our study highlights the importance of discussing the safest approach with health care providers and considering non-drug options whenever possible.”

With diagnoses of autism and ADHD increasing worldwide, these findings have significant implications for public health policy, clinical guidelines, and patient education. The study also highlights the urgent need for pharmaceutical innovation to provide safer alternatives for pregnant women.

Source: Mount Sinai

Categories : Obstetrics & GynaecologyTags :

Big Data Begins to Crack the Puzzle of Endometriosis

On By ModernMedia
Photo by Sora Shimazaki on Pexels

Scientists at UC San Francisco have found that endometriosis, a painful chronic disease that often goes undiagnosed yet is estimated to affect as many as 200 million women worldwide, frequently occurs alongside conditions like cancer, Crohn’s disease, and migraine.

The research could improve diagnosis and, ultimately, treatments for endometriosis, preventing women from having to go on long diagnostic journeys in which they are told that nothing is wrong with them.

The study, which appeared in Cell Reports Medicine on July 31, used computational methods developed at UCSF to analyse anonymised patient records collected at the University of California’s six health centres.

“We now have both the tools and the data to make a difference for the huge population that suffers from endometriosis,” said Marina Sirota, PhD, the interim director of the UCSF Bakar Computational Health Sciences Institute (BCHSI), professor of pediatrics, and senior author of the paper. “We hope this can spur a sea change in how we approach this disorder.”

“The impact on patients’ lives is huge”

Endometriosis, often called ‘endo,’ occurs when the endometrium, the blood-rich tissue that grows in the uterus before being expelled each month during menstruation, spreads to other nearby organs. It causes chronic pain and infertility. It is estimated that nearly 10% of women worldwide suffer from it.

“Endo is extremely debilitating,” said Linda Giudice, MD, PhD, MSc, a physician-scientist in the Department of Obstetrics, Gynecology and Reproductive Sciences at UCSF and co-author of the paper. “The impact on patients’ lives is huge, from their interpersonal relationships to being able to hold a job, have a family, and maintain psychological wellbeing.”

The gold standard to diagnose endometriosis is surgery to find endometrial tissue outside of the uterus, and it is mainly treated with hormones to suppress the menstrual cycle, or surgery to remove the excess tissue.

But not everyone responds to hormonal therapy, which can have debilitating side effects. Even after surgery, the condition can flare up. Removal of the uterus is a last-ditch measure that is usually reserved for older women; but some women continue to experience pain even after a hysterectomy.

Giudice partnered with Sirota to leverage the UC health system’s anonymised patient data against endo, which can vary dramatically across patients. Both Giudice and Sirota are principal investigators at the UCSF-Stanford Endometriosis Center for Discovery, Innovation, Training and Community Engagement (ENACT).

“This data is messy; it was not collected for research purposes but for the real, human purpose of helping women who need care,” Sirota said. “We had the rare chance to rigorously assess how endometriosis presents across UCSF’s patient population and then ask whether these observations held true with patients seen at the other UC health centers.”

Data connects the dots for understanding endometriosis

Using algorithms developed for the task, Umair Khan, a bioinformatics graduate student in Sirota’s lab and first author of the paper, hunted for connections linking endometriosis with the rest of each patient’s health history.

He compared endo patients with patients who did not have it, and categorised the patients with endo into groups based on shared health histories. He mapped his findings from the UCSF data against the rest of the UC’s health data to see if they held up across California.

“We found over 600 correlations between endometriosis and other conditions,” Khan said. “These ranged from what we already knew or suspected, like infertility, autoimmune disease, and acid-reflux, to the unexpected, like certain cancers, asthma, and eye-related diseases.”

Some patients had migraines, bolstering previous studies suggesting that migraine drugs might help treat endometriosis.

“In the past, studies like this would have been nearly impossible,” said Tomiko Oskotsky, MD, an investigator at ENACT, associate professor in UCSF BCHSI, and co-author of the paper. “It was only 12 years ago that de-identified electronic health records became available at this scale.”

The study supports the growing understanding of endometriosis as a “multi-system” disorder – a disease arising from dysfunction throughout the body.

“This is the kind of data we need to move the needle, which hasn’t moved in decades,” Giudice said. “We’re finally getting closer to faster diagnosis and, eventually, we hope, tailored treatment for the millions of women who suffer from endometriosis.”

Source: University of California – San Francisco

Categories : Mental Health Obstetrics & GynaecologyTags :

Surrogates Have an Increased Risk of a Mental Illness Diagnosis

On By ModernMedia
Source: Pixabay CC0

People who are gestational carriers (or “surrogates”) appear more likely to be diagnosed with a new mental illness during and after pregnancy, according to new research from ICES, McGill University, and the Research Institute of the McGill University Health Centre. 

As the number of births by surrogacy increases, this is the first large study using Ontario-based health data to explore the mental health challenges faced by some surrogates. 

Despite guidelines requiring mental health screening, the researchers found that nearly 1 in 5 gestational carriers had a prior mental illness diagnosis before pregnancy—including some with serious conditions that may have made them ineligible to carry a pregnancy for someone else. 

“Our findings underscore the importance of adequate screening and counselling of potential gestational carriers before pregnancy about the possibility of a new-onset mental illness, or exacerbation of a prior mental-illness during or after pregnancy,” says lead author Dr. Maria Velez, an adjunct scientist at ICES, associate professor at McGill University, and scientist at the Research Institute of the McGill University Health Centre. 

The study, published in JAMA Network Open, included 767 406 births at more than 20 week’s gestation in Ontario, Canada between 2012 and 2021 among women without known mental illness before pregnancy. Comparison groups included 97.6% (748,732) who were conceived without assistance, 2.3% (17,916) by IVF and 0.1% (758) using gestational carriers. 

Gestational carriers were more likely to have previously given birth, resided in a lower-income area, and had higher rates of obesity and chronic hypertension. 

Adequate mental health support needed 

The incidence rate per 100 person-years of new-onset mental illness was 5.2 among non-gestational carriers with unassisted conception, 5.0 among non-gestational carriers who conceived by IVF, and 6.9 among gestational carriers. 

The findings were even more pronounced for mental illness that was newly diagnosed through an emergency department encounter or a hospitalisation, compared to an outpatient mental illness diagnosis. 

“Unfortunately, fewer than half of those who visit the emergency room for mental health concerns after childbirth receive timely follow-up care which leaves many, especially gestational carriers, at risk during a vulnerable period,” says Velez. 

The authors say that they hope this study will inform future guidelines that ensure adequate mental health support for gestational carriers during and after pregnancy. 

Source: ICES

Categories : Metabolic Disorders Obstetrics & GynaecologyTags :

How Obesity also Affects the Next Generation

On By ModernMedia

Study reveals why children of obese mothers are more likely to develop metabolic disorders

Metabolites – from the mother permanently reprogram Kupffer cells. This changes their function, causes liver cells (hepatocytes) to accumulate fat and ultimately leads to a fatty liver. The graphic was created with BioRender.com (http://BioRender.com). © Image: AG Mass/University of Bonn

Children born to obese mothers are at higher risk of developing metabolic disorders, even if they follow a healthy diet themselves. A new study from the University of Bonn published in the journal Nature offers an explanation for this phenomenon. In obese mice, certain cells in the embryo’s liver are reprogrammed during pregnancy. This leads to long-term changes in the offspring’s metabolism. The researchers believe that these findings could also be relevant for humans.

The team focused on the so-called Kupffer cells. These are macrophages that help protect the body as part of the innate immune system. During embryonic development, they migrate into the liver, where they take up permanent residence. There, they fight off pathogens and break down ageing or damaged cells.

“But these Kupffer cells also act as conductors,” explains Prof Dr Elvira Mass from the LIMES Institute at the University of Bonn. “They instruct the surrounding liver cells on what to do. In this way, they help ensure that the liver, as a central metabolic organ, performs its many tasks correctly.”

Changing the tune: From Beethoven to Vivaldi

It appears, however, that it is this conducting function that is changed by obesity. This is what mouse experiments carried out by Mass in cooperation with other research groups at the University of Bonn suggest. “We were able to show that the offspring of obese mothers frequently developed a fatty liver shortly after birth,” says Dr Hao Huang from Mass’s lab. “And this happened even when the young animals were fed a completely normal diet.”

The cause of this disorder seems to be a kind of “reprogramming” of the Kupffer cells in the offspring. As a result, they send out molecular signals that instruct the liver cells to take up more fat. Figuratively speaking, they no longer conduct one of Beethoven’s symphonies but rather a piece by Vivaldi.

This shift already seems to occur during embryonic development and is triggered by metabolic products from the mother. These activate a kind of metabolic switch in the Kupffer cells and change the way these cells direct liver cells in the long term. “This switch is a so-called transcription factor,” says Mass. “It controls which genes are active in Kupffer cells.”

No fatty liver without the molecular switch

When the researchers genetically removed this switch in the Kupffer cells during pregnancy, the offspring did not develop a fatty liver. Whether this mechanism could also be targeted with medication is still unclear. The teams now plan to investigate this in follow-up studies.

If new treatment approaches emerge from this, it would be good news. The altered behaviour of the Kupffer cells likely has many negative consequences. Fat accumulation in the liver, for example, is accompanied by strong inflammatory responses. These can cause increasing numbers of hepatocytes to die and be replaced with scar tissue, resulting in fibrosis. At the same time, the risk that hepatocytes degenerate and become cancerous increases.

“It is becoming ever more evident that many diseases in humans already begin at a very early developmental stage,” says Mass, who is also spokesperson for the transdisciplinary research area “Life & Health” and a board member of the “ImmunoSensation2” Cluster of Excellence at the University of Bonn. “Our study is one of the few to explain in detail how this early programming can happen.”

Source: University of Bonn