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Placentas from COVID-19-positive pregnant women show injury

The type of injury seen in the placentas shows abnormal blood flow between the mothers and their babies in utero, pointing to a new complication of COVID-19.

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The placentas from 16 women who tested positive for COVID-19 while pregnant showed evidence of injury, according to pathological exams completed directly following birth, reports a new Northwestern Medicine study.

The type of injury seen in the placentas shows abnormal blood flow between the mothers and their babies in utero, pointing to a new complication of COVID-19. The findings, though early, could help inform how pregnant women should be clinically monitored during the pandemic.

The study was published today (May 22) in the journal American Journal of Clinical Pathology. It is the largest study to examine the health of placentas in women who tested positive for COVID-19.

“Most of these babies were delivered full-term after otherwise normal pregnancies, so you wouldn’t expect to find anything wrong with the placentas, but this virus appears to be inducing some injury in the placenta,” said senior author Dr. Jeffrey Goldstein, assistant professor of pathology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine pathologist. “It doesn’t appear to be inducing negative outcomes in live-born infants, based on our limited data, but it does validate the idea that women with COVID should be monitored more closely.”

This increased monitoring might come in the form of non-stress tests, which examine how well the placenta is delivering oxygen, or growth ultrasounds, which measure if the baby is growing at a healthy rate, said co-author Dr. Emily Miller, assistant professor of obstetrics and gynecology at Feinberg and a Northwestern Medicine obstetrician.

“Not to paint a scary picture, but these findings worry me,” Miller said. “I don’t want to draw sweeping conclusions from a small study, but this preliminary glimpse into how COVID-19 might cause changes in the placenta carries some pretty significant implications for the health of a pregnancy. We must discuss whether we should change how we monitor pregnant women right now.”

Previous research has found that children who were in utero during the 1918-19 flu pandemic, which is often compared to the current COVID-19 pandemic, have lifelong lower incomes and higher rates of cardiovascular disease. Flu doesn’t cross the placenta, Goldstein said, so whatever is causing life-long problems in those people is most likely due to immune activity and injury to the placenta.

“Our study, and other studies like it, are trying to get on the ground floor for this exposure so we can think about what research questions we should be asking in these kids and what can or should we do now to mitigate these same types of outcomes,” Goldstein said.

Fifteen patients delivered live infants in the third trimester, however one patient had a miscarriage in the second trimester. “That patient was asymptomatic, so we don’t know whether the virus caused the miscarriage or it was unrelated,” Goldstein said, “We are aware of four other cases of miscarriage with COVID. The other reported patients had symptoms and three of four had severe inflammation in the placenta. I’d like to see more before drawing any conclusions.”

The placenta is the first organ to form in fetal development. It acts as the fetus’ lungs, gut, kidneys and liver, taking oxygen and nutrients from the mother’s blood stream and exchanging waste. The placenta also is responsible for many of the hormonal changes within the mother’s body. Examining a woman’s placenta allows a pathologist to follow a retroactive roadmap of a woman’s pregnancy to learn what happened to the baby in utero or what could happen to both the mother and the infant after birth.

“The placenta acts like a ventilator for the fetus, and if it gets damaged, there can be dire outcomes,” Miller said. “In this very limited study, these findings provide some signs that the ventilator might not work as well for as long as we’d like it to if the mother tests positive for SARS-CoV2.”

The placentas in these patients had two common abnormalities: insufficient blood flow from the mother to the fetus with abnormal blood vessels called maternal vascular malperfusion (MVM) and blood clots in the placenta, called intervillous thrombi.

In normal cases of MVM, the mother’s blood pressure is higher than normal. This condition is typically seen in women with preeclampsia or hypertension. Interestingly, only one of the 15 patients in this study had preeclampsia or hypertension.

“There is an emerging consensus that there are problems with coagulation and blood vessel injury in COVID-19 patients,” Goldstein said. “Our finding support that there might be something clot-forming about coronavirus, and it’s happening in the placenta.”

The 16 women in the study delivered their babies at Northwestern Medicine Prentice Women’s Hospital. All tested positive for COVID-19. Four patients came in with flu-like symptoms three to five weeks before delivery and tested positive for the virus. The remaining patients all tested positive when they came in to deliver. Five patients never developed symptoms, others were symptomatic at delivery.

Between 30 and 40 patients deliver at Prentice daily. The team began testing placentas of COVID-19-positive mothers in early April. Fourteen of the live-born infants in the study were born full term and with normal weights and Apgar scores. One live-born infant was premature.

“They were healthy, full-term, beautifully normal babies, but our findings indicate a lot of the blood flow was blocked off and many of the placentas were smaller than they should have been,” Miller said. “Placentas get built with an enormous amount of redundancy. Even with only half of it working, babies are often completely fine. Still, while most babies will be fine, there’s a risk that some pregnancies could be compromised.”

In February, before the pandemic was known to have reached Chicago, Goldstein assembled his research team.

“If you get the flu and you’re pregnant, we know nothing about what that looks like in your placenta, so I began thinking how we’d study this flu-like epidemic if it came through Chicago,” Goldstein said. “We started setting things up and then lo and behold, the epidemic came here, so we were ready.”

Other Northwestern co-authors include Elisheva D. Shanes, Leena B. Mithal and Hooman A. Azad.

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Heart disease risk may start in the womb, study finds

Young adults whose mothers had high blood pressure during pregnancy — either pregnancy-associated hypertension, pre-eclampsia or eclampsia — had more signs of early arterial injury, higher blood pressure, higher body mass index and higher blood sugar than peers.

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A child’s future heart health may be partially shaped before they are born, reports a new Northwestern Medicine study that found pregnancy complications are linked to poorer cardiovascular health in offspring more than 20 years later.

The study found that young adults whose mothers had high blood pressure during pregnancy — either pregnancy-associated hypertension, pre-eclampsia or eclampsia — had more signs of early arterial injury, higher blood pressure, higher body mass index and higher blood sugar than peers.

The authors said the study adds to growing evidence that cardiovascular risk may be transmitted across generations through a combination of biological, environmental and behavioral factors.

“That means we must make sure people maintain good health from childhood into young adulthood, so that if or when someone becomes a parent, they pass on the best opportunity for good health to their children,” said study senior author Dr. Nilay Shah, assistant professor of medicine in the division of cardiology at Northwestern University Feinberg School of Medicine.

How the study was conducted

Shah and colleagues evaluated nearly 1,350 mother-child pairs from the Future of Families and Child Well-Being Study, which enrolled mothers and children at birth between 1998 and 2000 across 20 U.S. cities. The children were then followed into adulthood.

Using delivery hospitalization records, the Northwestern scientists first identified whether mothers experienced pregnancy complications, including high blood pressure during pregnancy, gestational diabetes (high blood sugar during pregnancy) or preterm birth (before 37 weeks of pregnancy).

The three pregnancy complications are on the rise, and affect almost one in four pregnancies in the U.S.

The research team then analyzed cardiovascular health of offspring at age 22, using blood pressure measurements, blood testing, body mass index assessments and carotid artery ultrasounds to look for signs of artery injury.

Finally, the scientists compared participants with and without exposure to each pregnancy complication and adjusted for factors like income, education, difference in birth weight and smoking during pregnancy.

Key findings

At around age 22, participants whose mothers had high blood pressure during pregnancy had:

  • Higher body mass index (+2.8 BMI points)
  • Higher diastolic blood pressure (+2.3 mm Hg)
  • Higher blood sugar levels (+0.2% HbA1c)
  • Thicker artery walls (~0.02 mm)

While the difference in artery wall thickness may seem small, the study authors said it corresponds to roughly three to five years of additional vascular aging. That means arteries looked older and less healthy than expected, which raises the risk of future heart disease.

Other pregnancy complications also showed some long-term effect:

  • Exposure to gestational diabetes was linked to worse blood pressure and some evidence of artery thickening
  • Being born preterm was associated with higher blood sugar levels

‘Most heart disease is preventable’

With pregnancy complications on the rise in the U.S., Shah said the study provides compelling evidence that improving health before and during pregnancy could help reduce heart disease risk in the next generation.

“There is evidence that both parents’ health at the time of conception and during pregnancy influences a child’s health,” he said. “So, promoting health from an early age, like exercising regularly, eating healthfully, never smoking and getting enough sleep, is not just meant for an individual, but doing so may help future generations be healthier, too.”

Shah also emphasizes that risk is not destiny.

“The good news is that most heart disease is preventable,” he said. “If you experienced high blood pressure or high blood sugar during pregnancy, or your child was born early, it does not absolutely mean that your child will have worse health as adults. But I would encourage you to pay attention now to your child’s health behaviors.

“What children learn in childhood sets the stage for their health across their lives. If you are wondering whether your children’s behaviors are healthy, or are considering making a change, please speak with your child’s pediatrician for advice and guidance.”

Other Northwestern co-authors include Emily Lam, Abigail Gauen, Dr. Sadiya Khan, Alexa Freedman and Norrina Allen.

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Viagra could hold key to halting Peyronie’s disease

Combining two widely prescribed drug classes could provide the first effective treatment for early-stage Peyronie’s disease.

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Combining two widely prescribed drug classes could provide the first effective treatment for early-stage Peyronie’s disease, according to a study published in The Journal of Sexual Medicine.

Peyronie’s disease (PD) is caused by the development of fibrotic scar tissue within the penis, leading to pain, curvature, sexual dysfunction and, in many cases, significant psychological distress. It affects an estimated 10 per cent of men during their lifetime, but despite its prevalence, treatment options are limited, particularly in the early phase of the condition.

The study, carried out by Anglia Ruskin University (ARU) and University College London Hospital (UCLH), found that combining phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil (Viagra) and tadalafil (Cialis) with selective oestrogen receptor modulators (SERMs), including tamoxifen, may slow or even stop disease progression when given early.

The clinical study, carried out by Professor David Ralph of UCLH, evaluated outcomes in 133 men diagnosed with acute Peyronie’s disease who were treated with the drug combination for three months. Their results were compared with a smaller group of patients receiving standard care, which included giving vitamin E or no treatment at all. Standard care did not include surgery.

The study found 43 per cent of patients on the combination experienced an improvement in penile curvature, almost three times higher than in the standard‑care group (15 per cent).

At the start of treatment, 65 per cent of patients in the combination group reported pain during erections. After three months, that figure had fallen to just 1.5 per cent. By comparison, pain prevalence in the standard‑care group fell from 50 per cent to 27 per cent.

The clinical findings build on earlier laboratory work led by Professor Selim Cellek at ARU’s Fibrosis Research Group. Over the course of several years, Professor Cellek’s team screened 1,953 FDA‑approved drugs to identify compounds capable of blocking the transformation of fibroblasts into myofibroblasts, the key cells responsible for fibrosis. PDE5 inhibitors and SERMs emerged as particularly effective, and when used together demonstrated an effect greater than either drug alone.

Currently, there are no approved oral therapies proven to prevent early disease progression, forcing patients in the acute phase to wait until the condition stabilises before they can be offered treatments including injections or surgery.

Professor Cellek said: “Positive findings from this pilot clinical study validate our drug‑screening approach in the lab. It shows how repurposing well‑known medicines can accelerate progress in areas of unmet clinical need.

“Because both PDE5 inhibitors and SERMs are already widely used in clinical practice and have established safety profiles, the approach could be readily adoptable if confirmed in larger studies.

“These results suggest that early intervention targeting fibrosis could change how we treat Peyronie’s disease. Repurposing existing drugs may allow us to move from managing symptoms to modifying the disease itself.”

Professor David Ralph, Professor of Urology at UCLH, said: “This paper confirms the basic science research with regards to halting the progression of Peyronie’s disease. In previous papers we have noted that tamoxifen and PDE5 inhibitors inhibit the transformation of fibroblasts into myofibroblasts and therefore contraction of the plaque.

“This has now been put into clinical practice where this paper shows that when tamoxifen and a PDE5 inhibitor are combined, there is statistically less progression of the disease and improvement in curvature compared to the control arm. This is where from bench to clinical practice prevails and hopefully now a prospective clinical trial can be initiated.”

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Healthier brains may be more resilient to early Alzheimer’s disease

Maintaining good overall brain health may help reduce the impact of Alzheimer’s‑related changes on cognitive function.

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A healthy brain may help protect thinking and memory skills from the early effects of Alzheimer’s disease, a new study has found.

Dementia is currently the leading cause of death in Australia and Alzheimer’s disease is its most common form — accounting for more than 70% of cases.

Alzheimer’s is a progressive brain disease in which cognitive abilities gradually decline, leading to impaired memory and thinking skills.

However, some people maintain high levels of cognitive function even though their brains show early signs of the disease. Specifically, some older adults have Alzheimer’s‑related brain pathology, but no noticeable cognitive problems.

The study, Cognitive and Brain Reserve as Modifiers of Early Alzheimer Disease–Related Cognitive Vulnerability, was a collaboration between Murdoch University and AdventHealth, and investigated why some people remain cognitively healthy despite early Alzheimer’s‑related brain changes.

“Our study looked at why some brains were more resilient than others, and whether factors such as peoples’ education, socioeconomic status and health of their brain made a difference,” said lead author Dr Kelsey Sewell, from Murdoch University’s School of Allied Health.

“Understanding these protective factors could help us develop earlier and more targeted strategies to minimise the effects of the disease on memory and thinking skills,” she said.

The research team analysed data from more than 600 older adults in the United States aged 65 to 80, who were living independently and had no signs of dementia or memory impairment.

They used blood tests and MRI scans to assess early Alzheimer’s‑related changes and overall brain health, examined life and social factors such as years of education, income, savings and financial security, and conducted cognitive tests measuring memory, attention, processing speed, working memory and executive function.

“Our main finding was that maintaining good overall brain health may help reduce the impact of Alzheimer’s‑related changes on cognitive function,” Dr Sewell said.

“We also observed early evidence that people with a higher socioeconomic status may be less affected by Alzheimer’s-related changes when it comes to memory, although more research is needed to confirm this relationship.”

Dr Sewell said the main takeaway for the public was to do everything you can to maintain a healthy brain.

“Things like exercise, maintaining a healthy diet, sleeping well, and finding new cognitive challenges can help to maintain a healthy brain. It is never too late, or too early to start,” she said .

“These results underscore the need for coordinated action across research, policy, and industry to design environments that support healthier choices and promote brain health at a population level.”

The data collection for this study was led by researchers at AdventHealth in Orlando, Florida.

The paper, Cognitive and Brain Reserve as Modifiers of Early Alzheimer Disease–Related Cognitive Vulnerability, was published in the journal Neurology.

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