Tag: pregnancy complications

Pre-pregnancy Hypoglycaemia Linked with Higher Risk of Preterm Birth, Other Risks

In study of nearly 5 million Chinese women, these links varied according to body mass index

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An analysis of data from more than 4.7 million Chinese women showed that those who had low blood sugar levels prior to conception were more likely to have certain adverse pregnancy outcomes – such as their baby being born preterm or with low birth weight. Hanbin Wu of the Chinese University of Hong Kong, in collaboration with the National Research Institute for Family Planning, presents these findings on July 29th in the open-access journal PLOS Medicine.

Prior research has shown that women who are hyperglycaemic before or during pregnancy are more likely to face adverse pregnancy outcomes, as are women who are hypoglycaemic during pregnancy.

However, few studies have explored whether hypoglycaemia detected before pregnancy is associated with adverse pregnancy outcomes for women without pre-existing diabetes. To help clarify, Wu and colleagues retrospectively analysed data on 4 866 919 Chinese women from the National Free Preconception Checkup Project, a free health service for women planning to conceive. Using data from 2013 to 2016, they analysed associations between preconception hypoglycaemia and pregnancy outcomes.

A total of 239 128 of the women had preconception hypoglycaemia. Compared to those with normal preconception blood sugar, they had a higher risk of certain adverse pregnancy outcomes, such as preterm birth, low birth weight, or birth defects. Women with hypoglycaemia tended to be younger than those with normal blood sugar levels and were more likely to have BMIs in the “underweight” category.

However, the adverse pregnancy risks associated with preconception hypoglycaemia varied for women with different BMIs. For instance, underweight women had a higher risk of miscarriage, while overweight women had a lower risk of their baby being large for their gestational age.

On the basis of these findings, the researchers suggest that screening for preconception hypoglycemia could be explored for its potential to improve pregnancy outcomes. Further research could also address some limitations of this study, such as by including women from other countries and more information on patients’ gestational complications.

The authors state, “In addition to paying attention to women with preconception hyperglycemia, our findings call for increased concern for women with hypoglycemia in preconception glycemic screening. These findings emphasize the importance of preconception examination in preventing and managing reproductive health risks for all women planning to conceive, and also highlight the necessity of comprehensive screening and coordinated interventions for abnormal FPG (fasting plasma glucose) prior to and during pregnancy, which is crucial for advancing the intervention window and mitigating the risk of adverse pregnancy outcomes.”

Provided by PLOS

Antibiotics Taken During Pregnancy May Reduce Preterm Births

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A study of almost 1000 pregnant women in Zimbabwe found that a daily dose of a commonly used, safe and inexpensive antibiotic may have led to fewer babies being born early. Among women living with HIV, those who received the antibiotic had larger babies who were less likely to be preterm.

One in four live-born infants worldwide is preterm (born at 37 weeks’ gestation or before), is small for gestational age, or has a low birth weight. The mortality rate for these small and vulnerable newborns is high, with prematurity now the leading cause of death among children younger than 5 years of age. Maternal infections and inflammation during pregnancy are linked to adverse birth outcomes, particularly for babies born to mothers living with HIV, who have a greater risk of being born too small or too soon. 

An international group of researchers, led by Professor Andrew Prendergast from Queen Mary University of London, and Bernard Chasekwa from the Zvitambo Institute for Maternal and Child Health Research in Zimbabwe, conducted the Cotrimoxazole for Mothers to Improve Birthweight in Infants (COMBI) randomised controlled trial, to examine whether prescribing pregnant women a daily dose of trimethoprim–sulfamethoxazole (a broad-spectrum antimicrobial agent with anti-inflammatory properties, widely used in sub-Saharan Africa) would result in heavier birth weights, decreased premature births, and better health outcomes for their babies.  

993 pregnant women were recruited from three antenatal clinics in Shurugwi, a district in central Zimbabwe, and received either 960 mg of the drug or a placebo daily. The participants received regular antenatal care during their pregnancies and data regarding their birth outcomes were recorded. 

The study, published in the New England Journal of Medicine, found that although birthweight did not differ significantly between the two groups, the trimethoprim–sulfamethoxazole group showed a 40% reduction in the proportion of preterm births, compared to the placebo group. Overall, 6.9% of mothers receiving the drug had babies born preterm, compared to 11.5% of mothers receiving the placebo, and no women receiving antibiotics had babies born prior to 28 weeks. For babies born to a small group of 131 women with HIV, the reduction in premature births was especially marked, with only 2% of births in the trimethoprim–sulfamethoxazole group preterm, as compared with 14% in the placebo group. Babies exposed to antibiotics during pregnancy also showed a 177 gram increase in their birth weight. 

Bernard Chasekwa, first author, said: “Our trial, conducted within routine antenatal care and enrolling women predominantly from rural areas, showed that trimethoprim-sulfamethoxazole did not improve birthweight, which was our main outcome. However, there was an intriguing suggestion that it may have improved the length of pregnancy and reduced the proportion of preterm births. We now need to repeat this trial in different settings around the world to see whether antibiotics during pregnancy can help reduce the risk of prematurity.”  

Source: Queen Mary University of London

Updated Review Raises Concern About Cannabis Use in Pregnancy

Research team finds moderate risk for preterm birth, low birth weight

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An updated systematic review finds that consuming cannabis while pregnant appears to increase the odds of preterm birth, low birth weight and infant death. This study by researchers at Oregon Health & Science University appears in JAMA Pediatrics.

Study lead author Jamie Lo, MD, MCR, is a physician-scientist who provides prenatal care for high-risk pregnancies at OHSU.

“Patients are coming to me in their prenatal visits saying, ‘I quit smoking and drinking, but is it safe to still use cannabis?’” said Lo, associate professor of obstetrics and gynaecology (maternal-foetal medicine) in the OHSU School of Medicine. “Until direct harms have been proven, they perceive it to be safe to use.”

In fact, cannabis remains one of the most common substances used in pregnancy that’s still illegal under federal law, and, unlike declines in prenatal use of alcohol or nicotine, cannabis use is continuing to increase. Lo said many of her patients are reluctant to give up cannabis during pregnancy because it helps to reduce common prenatal symptoms such as nausea, insomnia and pain.

Researchers updated the systematic review and meta-analysis, drawing on a total of 51 observational studies involving 21.1 million people to examine the potential adverse effects of cannabis use in pregnancy. The researchers found eight new studies since their previous update, raising the certainty of evidence from “very-low-to-low” to “moderate” for increased odds of low birth weight, preterm birth and babies being small for their gestational age.

The updated review also indicated increased odds of newborn mortality, though still with low certainty.

Researchers noted that the new systematic review includes a larger proportion of human observational studies examining people who only use cannabis, but don’t also use nicotine. And even though the evidence is low to moderate for adverse outcomes, Lo noted that the findings are consistent with definitive evidence in nonhuman primate models exposed to THC, the main psychoactive compound in cannabis.

The related research in animal models included standard prenatal ultrasound and MRI imaging that revealed a detrimental effect on the placenta, in terms of blood flow and availability of oxygen in addition to decreased volume of amniotic fluid.

“These findings tell me as an obstetrician that the placenta is not functioning as it normally would in pregnancy,” Lo said. “When the placenta isn’t functioning well, it can affect the baby’s development and growth.”

Even though cannabis remains a Schedule 1 substance under the federal Controlled Substances Act, Oregon is one of several states that have legalised it under state law for medicinal and recreational use. Lo said she recommends a harm-reduction approach to patients. For those who cannot abstain, she advises them to reduce the amount and frequency of use to help reduce the risk of prenatal and infant complications.

“Even using less can mitigate the risk,” she said. “Abstinence is ideal, but it’s not realistic for many patients.”

Source: Oregon Health & Science University

Amniotic Fluid Protects Both Baby and Birthing Parent, Research Finds

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Researchers at Oregon Health & Science University have made new discoveries about amniotic fluid, which is historically not well understood in medical research due to the difficulty in obtaining it during pregnancy, especially across gestation in birthing parents.

In addition to providing much-needed cushion and protection for the foetus, amniotic fluid also aids in development of vital organs – especially the lungs, digestive tract and skin – and stabilises the temperature inside the womb.

The new study, published in the journal Research and Practice in Thrombosis and Haemostasis, found that the addition of amniotic fluid to plasma improves the blood’s ability to thicken and clot, which is a critical and likely a protective function throughout pregnancy and during delivery for both the birthing parent and the baby. It also appears to offer other unexpected functions, such as serving as a ‘pre-milk’ for foetuses.

The mechanism of amniotic fluid’s role in foetal development is not well understood and is understudied: The OHSU study is one of the first to identify how the features and properties of amniotic fluid change over time, especially those properties that play a role in thickening the blood, and how those changes can affect how maternal blood coagulates. If a pregnant person’s blood does not clot properly, it can create life-threatening complications for the foetus and birthing parent, including excessive bleeding during pregnancy and delivery.  

“We have always known that amniotic fluid is very important for foetal development and growth, but we don’t know much about it beyond that,” said the study’s corresponding author Jamie Lo, MD, MCR., associate professor of obstetrics and gynaecology (maternal-foetal medicine) in the OHSU School of Medicine, and Division of Reproductive & Developmental Sciences at the Oregon National Primate Research Center, or ONPRC. “We examined amniotic fluid across the pregnancy and found that indeed the composition and proteins in the amniotic fluid do change to match the growing needs of the developing baby.”

This discovery prompted Lo and her team to work with scientists in the Department of Biomedical Engineering at OHSU to take a deeper dive into the potential protective factors of amniotic fluid, and consider potential regenerative and therapeutic uses that could be developed down the road.

The research involved a multidisciplinary team including Lo, Chih Jen Yang, MD, Lyndsey Shorey-Kendrick, PhD, Joseph Shatzel, MD, MCR, Brian Scottoline, MD, PhD, and Owen McCarty, PhD.

Researchers analysed the properties of amniotic fluid obtained by amniocentesis, a prenatal test that involves sampling a small amount of amniotic fluid to examine the health of the pregnancy, from both human and non-human primates at gestational-age matched timepoints. The findings showed that amniotic fluid increases blood clotting through key fatty acids and proteins that change each trimester and help regulate coagulation.

With the untapped potential for amniotic fluid to aid in diagnosing and treating various prenatal conditions, researchers are now collaborating with Sanjay Malhotra, PhD, professor of cell, developmental and cancer biology in the OHSU School of Medicine, to target disorders of pregnancy – including disorders that affect the blood and blood-forming organs – that could benefit from the protective properties of proteins and other compounds within amniotic fluid.

Researchers are eager to learn more about the potential uses of amniotic fluid components and how they might be harnessed to improve prenatal and maternal health.

“Babies born prematurely miss out on critical weeks developing within amniotic fluid,” said the study’s co-senior author Brian Scottoline, MD, PhD, professor of paediatrics (neonatology), OHSU School of Medicine. “But if we have a better understanding of amniotic fluid, how it develops and what properties are valuable for what functions, that opens up many new possibilities for creating new therapies.”

“Through our research, our team is learning that amniotic fluid may be a critical precursor to breast milk – almost like ‘pre-term’ milk for a foetus in utero. With that analogy, could we eventually develop a formula that’s fit for preterm babies that mimics amniotic fluid, aiding in growth and development and protecting babies from complications of being born prematurely?” Lo added. “This is really the tip of the iceberg for what’s possible.”

Source: Oregon Health & Science University

Study Probes How to Predict Complications from Preeclampsia

Data from 8843 women diagnosed with preeclampsia during pregnancy showed that existing risk prediction models are most accurate only in the days after diagnosis

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The existing prediction models for severe complications of preeclampsia are most accurate only in the two days after hospital admission, with deteriorating performance over time, according to a new study published February 4th in the open-access journal PLOS Medicine by Henk Groen of University of Groningen, the Netherlands, and colleagues.

Preeclampsia is a potentially life-threatening condition that can occur during pregnancy; of women diagnosed with preeclampsia, 5-20% will develop severe complications. Two existing PIERS (Pre-eclampsia Integrated Estimate of RiSk) models, PIERS Machine Learning (PIERS-ML) and the logistic-regression-based fullPIERS, are designed to identify individuals at greatest or least risk of adverse maternal outcomes in the 48 hours following hospital admission for preeclampsia. However, both models are regularly used for ongoing assessment beyond the first 48 hours.

In the new study, researchers used data from 8843 women diagnosed with preeclampsia at a median gestational age of 36 weeks between 2003 and 2016. Data included PIERS-ML and fullPIERS assessments as well as health outcomes.

The study found that neither the PIERS-ML nor fullPIERS model maintained good performance over time for repeated risk stratification in women with preeclampsia. The PIERS-ML remained generally good at identifying the very high-risk and very-low risk groups over time, but performance of the larger high-risk and low-risk groups deteriorated significantly after 48 hours. The fullPIERS model underperformed compared to the PIERS-ML model.

“Since there are no better options, clinicians may still use these two models for ongoing assessments after the first admission with pre-eclampsia, but the predictions should be treated with increasing caution as the pregnancy progresses,” the authors say. More prediction models are needed that perform well over time, they add.

The authors add, “Pregnancy hypertension outcome prediction models were designed and validated for initial assessment of risks for mothers; this study shows that such ‘static’ models if used repeatedly over days yield increasingly inaccurate predictions.”

Provided by PLOS

Pregnancy Complications make Women Less Inclined to Have More Children

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Women who suffer severe complications during their first pregnancy or delivery are less inclined to have more babies, according to a study published in JAMA by researchers at Karolinska Institutet. For Sweden, given its recent steady decline in birth rate, the researchers propose monitoring in antenatal care to address the problem.

“The clinical monitoring of these women is essential, and they need individualised advice on possible future pregnancies,” says the study’s first author Eleni Tsamantioti, doctoral student at the Department of Medicine in Solna, Karolinska Institutet.

Reduced fertility

Birth rates and fertility have both been in steady decline in Sweden over the past years. In this new population-based study, the researchers have studied the association between severe maternal morbidity in first-time mothers and the likelihood of their having a second baby. The study comprised over a million women in Sweden who had their first baby between 1999 and 2021.

“We found that the likelihood of having more children was much lower in women who had experienced severe complications during their first pregnancy, delivery or postnatal period,” says the study’s last author Neda Razaz, associate professor at the same department. “Such events can often have a physical and mental impact on women for a long time to come.”

All in all, 3.5% of the first-time mothers in the study suffered serious complications and were 12% less likely to have a second baby. Most impacted were women who had experienced cardiac complications, a ruptured uterus or severe mental health problems, who were 50% less likely to have another birth than women who had not experienced such complications.

Monitoring in antenatal care

Women who needed respiratory care or who suffered a cerebrovascular accident like stroke or intracranial haemorrhage were 40% less likely to have a second baby. Acute kidney failure, severe preeclampsia and blood clotting were also associated with a lower probability of a second pregnancy. The researchers also compared the women with any sisters they had to control for familial factors. 

“The reasons are hard to speculate on and may result from multiple factors, such as decreased desire for more children, trauma, infertility related to psychiatric medications, or lack of health counselling,” says Tsamantioti. “Proper support and monitoring by antenatal care staff is therefore essential for women who have suffered serious health problems during pregnancy or delivery.”

Source: Karolinska Institutet

Low-dose Aspirin Might Help Prevent Pregnancy Complications Caused by Flu Infections

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A world-first study has found low-dose aspirin may treat flu-induced blood vessel inflammation, creating better blood flow to the placenta during pregnancy. Animal studies examined whether the treatment for preeclampsia could be applied to flu infections – and the results, published in Frontiers in Immunology, were very promising. 

Lead researcher and RMIT Post-Doctoral Research Fellow, Dr Stella Liong, said that flu infections during pregnancy can resemble preeclampsia, a pregnancy complication that causes inflammation to the aorta and blood vessels. Low-dose aspirin is commonly taken to prevent preeclampsia, as it stops the body from creating chemicals that cause inflammation.   

“When the vascular system is inflamed, it leads to poor blood flow and affects the aorta’s function,” she said. “This is especially a problem during pregnancy where good blood flow to the placenta is crucial to the development of the foetus.” 

The research, led by RMIT University in collaboration with Trinity College Dublin, Ireland Professor John O’Leary and University of South Australia Professor Doug Brooks, found foetuses and placenta from mice with influenza A were smaller than those from uninfected mice. 

Markers of low blood oxygenation and poor blood vessel development were also evident in the foetuses. The mice treated daily with low-dose aspirin had less inflammation and improved foetal development and offspring survival. 

While the research was still awaiting human clinical trials, Liong said low-dose aspirin was already recognised as safe to take during pregnancy. The research team however recommended pregnant people seek medical advice before taking new medications.  

Brooks said influenza A infections during pregnancy was a big concern as every pregnancy overlaps with part of a flu season.  

“There are long term implications for both the mother and the foetus, and aspirin might provide a simple solution for preventing this influenza associated pathology,” Brooks said. 

Why flu infection is dangerous during pregnancy 

O’Leary said the research findings had huge implications for pregnancy and seasonal influenza virus infections for pregnant people.

“This study shines a light, for the first time, on the role of vascular inflammation associated with influenza virus and the potential dramatic effect of the disease-modifying drug aspirin, in low dosage, in pregnant women with co-morbid influenza,” O’Leary said.

While there weren’t many studies of the impacts of flu infections during pregnancy, project lead and RMIT Professor Stavros Selemidis said it was clear that pregnancy changed how the body responded to the virus.

Liong and Selemidis’ earlier breakthrough research found the flu virus during pregnancy could trigger a damaging hyperactive immune response, causing the virus to spread around the body from the lungs through the blood vessels.

“We used to think the flu virus just stayed in the lungs, but during pregnancy it escapes from the lungs to the rest of the body,” Selemidis said.

“This infection could set you up for cardiovascular disease later in life, but also set up cardiovascular disease in the offspring later in life.” 

While vaccination was still the considered the best way to prevent flu infection during pregnancy, Selemidis pointed out vaccination rates were generally low in the pregnant population

“Low vaccination rates aside, the flu shot may not generate the perfect immune response, especially if someone is pregnant or has an underlying medical condition,” he said.  

“That’s why it’s useful to have a potential back up in low-dose aspirin to help prevent vascular dysfunction during pregnancy and improve foetal development.”

Source: RMIT University

Low-dose Aspirin Could Help Prevent Pregnancy Complications Caused by Flu Infections

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A world-first study in animals has found low-dose aspirin may treat flu-induced blood vessel inflammation, creating better blood flow to the placenta during pregnancy. The study, published in Frontiers in Immunology, showed that treatment for preeclampsia could be applied to flu infections – and the results, according to the research team, were very promising. 

Lead researcher and RMIT Post-Doctoral Research Fellow, Dr Stella Liong, said flu infections during pregnancy can resemble preeclampsia, a pregnancy complication that causes inflammation to the aorta and blood vessels.  

Low-dose aspirin is commonly taken to prevent preeclampsia, as it stops the body from creating chemicals that cause inflammation.   

“When the vascular system is inflamed, it leads to poor blood flow and affects the aorta’s function,” she said. 

“This is especially a problem during pregnancy where good blood flow to the placenta is crucial to the development of the foetus.” 

The research, led by RMIT University in collaboration with Trinity College Dublin, Ireland Professor John O’Leary and University of South Australia Professor Doug Brooks, found foetuses and placenta from mice with influenza A were smaller than those from uninfected mice. 

Markers of low oxygen to the blood and poor blood vessel development were also evident in the foetuses. 

However, mice treated daily with low-dose aspirin had less inflammation and improved foetal development and offspring survival. 

While the research was still awaiting human clinical trials, Liong said low-dose aspirin was already recognised as safe to take during pregnancy.  

However, the research team recommended pregnant people seek medical advice before taking new medications.  

Brooks said influenza A infections during pregnancy was a big concern as every pregnancy overlaps with part of a flu season.  

“There are long term implications for both the mother and the foetus, and aspirin might provide a simple solution for preventing this influenza associated pathology,” Brooks said. 

Source: RMIT University

Monitoring for Foetal Heart Condition in Pregnant Women with Autoimmune Antibodies

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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 To Prevent 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.

Source: Wiley

Ground-breaking Progress in Identifying the Root Cause of Preeclampsia

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Researchers report in Nature Communications that they have made ground-breaking progress towards identifying the root cause and potential therapy for preeclampsia. They identified a toxic protein, cis P-tau, in the blood and placenta of preeclampsia patients. This protein is also linked to the development of memory loss after brain injury or Alzheimer’s.

The pregnancy complication affects up to 8% of pregnancies globally and is the leading cause of maternal and foetal mortality due to premature delivery, complications with the placenta and lack of oxygen. It also disproportionately affects women of certain races.

According to the study, led by Drs Kun Ping Lu and Xiao Zhen Zhou at the University of Western Ontario, and Drs Surendra Sharma and Sukanta Jash at Brown University, cis P-tau is a central circulating driver of preeclampsia.

“The root cause of preeclampsia has (so far) remained unknown, and without a known cause there has been no cure. Preterm delivery is the only life-saving measure,” said Lu, professor of biochemistry and oncology at Schulich School of Medicine & Dentistry.

“Our study identifies cis P-tau as a crucial culprit and biomarker for preeclampsia. It can be used for early diagnosis of the complication and is a crucial therapeutic target,” said Sharma.

In 2016, Sharma, a leading preeclampsia researcher, and his team had identified that preeclampsia and diseases like Alzheimer’s had similar root causes related to protein issues. This research builds on that finding.

Until now, cis P-tau was mainly associated with neurological disorders like Alzheimer’s disease, traumatic brain injuries (TBI) and stroke. This association was discovered by Lu and Zhou in 2015 as a result of their decades of research on the role of tau protein in cancer and Alzheimer’s.

An antibody developed by Zhou in 2012 to target only the toxic protein while leaving its healthy counterpart unscathed is currently undergoing clinical trials in human patients suffering from TBI and Alzheimer’s Disease. The antibody has shown promising results in animal models and human cell cultures in treating the brain conditions.

The researchers were curious whether the same antibody could work as a potential treatment for preeclampsia. Upon testing the antibody in mouse models they found astonishing results.

“In this study, we found the cis P-tau antibody efficiently depleted the toxic protein in the blood and placenta, and corrected all features associated with preeclampsia in mice. Clinical features of preeclampsia, like elevated blood pressure, excessive protein in urine and foetal growth restriction, among others, were eliminated and pregnancy was normal,” said Sharma.

Sharma and his team at Brown have been working on developing an assay for early detection of preeclampsia and therapies to treat the condition. He believes the findings of this study have brought them closer to their goal.

Preeclampsia, genetics and the brain

Recent research has also thrown light on preeclampsia’s long-term impacts and possible links to brain health.

“Research has shown that women of certain races have genes that could possibly lead to higher than average blood pressure levels, eventually creating conditions for preeclampsia during pregnancy. However, it’s also true that in many low socio-economic countries there’s no registry to record PE cases. So, its link to other environmental factors is still unclear,” said Sharma.

“Preeclampsia presents immediate dangers to both the mother and foetus, but its long-term effects are less understood and still unfolding,” said Sharma. “Research has suggested a heightened risk of dementia later in life for both mothers who have experienced preeclampsia and their children.” However, the causal link between preeclampsia and dementia is not known.

The researchers say this new study has pinpointed a potential underlying cause of the complex relationship between preeclampsia and brain health.

“Our study adds another layer to this complexity. For the first time, we’ve identified significant levels of cis P-tau outside the brain in the placenta and blood of preeclampsia patients. This suggests a deeper connection between preeclampsia and brain-related issues,” said Jash, the lead author of the study.

As researchers delve deeper, how our bodies respond to stress is also emerging as a potential factor in the onset of preeclampsia.

“Although genetics play a role, factors like stress could be an important piece of the puzzle. Understanding how stress and other environmental factors intersect with biological markers like cis P-tau may offer a more complete picture,” said Jash, assistant professor of molecular biology, cell biology and biochemistry (research) and paediatrics (research) at Brown.

A stress-response enzyme called Pin1

In 1996 and 1997, Lu and Zhou made the ground-breaking discovery of Pin1, which turns out to be a stress-response enzyme. This is a specific protein in the cells that becomes active or changes its behaviour in response to stressors, such as environmental challenges, toxins or physiological changes.

“Pin1 plays a pivotal role in keeping proteins, including the tau protein, in the functional shape during stress. When Pin1 becomes inactivated, it leads to the formation of a toxic, misshapen, variant of tau — cis P-tau,” said Zhou, associate professor, pathology and laboratory medicine at Schulich Medicine & Dentistry.

Interestingly, Pin1 is a key player in cancer signalling networks, turning on numerous cancer-causing proteins and turning off many cancer-suppressing ones. Found in high levels in most human cancers, it’s particularly active in cancer stem cells, which are thought to be central to starting and spreading tumours and are hard to target with existing treatments.

“Essentially, when Pin1 is activated, it can lead to cancer. On the other hand, when there’s a decrease or deactivation in Pin1, it results in the formation of the toxic protein cis P-tau, which leads to memory loss in Alzheimer’s and after TBI or stroke. Now, we’ve uncovered its connection to preeclampsia as well,” said Zhou.

“The results have far-reaching implications. This could revolutionise how we understand and treat a range of conditions, from pregnancy-related issues to brain disorders,” said Lu.

Source: University of Western Ontario