Pregnant women show robust immune response to COVID vaccines, pass antibodies to newborns
March 25, 2021
Science Daily/Massachusetts General Hospital
In the largest study of its kind to date, researchers at Massachusetts General Hospital, Brigham and Women's Hospital and the Ragon Institute of MGH, MIT and Harvard have found the new mRNA COVID-19 vaccines to be highly effective in producing antibodies against the SARS-CoV-2 virus in pregnant and lactating women. They also demonstrated the vaccines confer protective immunity to newborns through breastmilk and the placenta.
The study, published in the American Journal of Obstetrics and Gynecology (AJOG), looked at 131 women of reproductive age (84 pregnant, 31 lactating and 16 non-pregnant), all of whom received one of the two new mRNA vaccines: Pfizer/BioNTech or Moderna. The vaccine-induced titers -- or antibody levels -- were equivalent in all three groups. Reassuringly, side effects after vaccination were rare and comparable across the study participants.
"This news of excellent vaccine efficacy is very encouraging for pregnant and breastfeeding women, who were left out of the initial COVID-19 vaccine trials," says Andrea Edlow, MD, MSc, a maternal-fetal medicine specialist at MGH, director of the Edlow Lab in the Vincent Center for Reproductive Biology and co-senior author of the new study. "Filling in the information gaps with real data is key -- especially for our pregnant patients who are at greater risk for complications from COVID-19. This study also highlights how eager pregnant and lactating individuals are to participate in research."
According to the Centers for Disease Control and Prevention, individuals who are pregnant are more likely to become severely ill with COVID-19, require hospitalization, intensive care or ventilation -- and may be at increased risk for adverse pregnancy outcomes. The team also compared vaccination-induced antibody levels to those induced by natural infection with COVID-19 in pregnancy, and found significantly higher levels of antibodies from vaccination.
Vaccine-generated antibodies were also present in all umbilical cord blood and breastmilk samples taken from the study, showing the transfer of antibodies from mothers to newborns.
"We now have clear evidence the COVID vaccines can induce immunity that will protect infants," says Galit Alter, PhD, core member of the Ragon Institute and co-senior author of the study. "We hope this study will catalyze vaccine developers to recognize the importance of studying pregnant and lactating individuals, and include them in trials. The potential for rational vaccine design to drive improved outcomes for mothers and infants is limitless, but developers must realize that pregnancy is a distinct immunological state, where two lives can be saved simultaneously with a powerful vaccine. We look forward to studying all vaccine platforms in pregnancy as they become available."
The study was also able to provide insight into potential differences between the immune response elicited by the Pfizer vaccine compared to the Moderna vaccine, finding the levels of mucosal (IgA) antibodies were higher after the second dose of Moderna compared to the second dose of Pfizer.
"This finding is important for all individuals, since SARS-CoV-2 is acquired through mucosal surfaces like the nose, mouth and eyes," says Kathryn Gray, MD, PhD, an obstetrician at Brigham and Women's Hospital and a first author of the paper. "But it also holds special importance for pregnant and lactating women because IgA is a key antibody present in breastmilk."
https://www.sciencedaily.com/releases/2021/03/210325150127.htm
Parental burnout hits individualist Western countries hardest
March 18, 2021
Science Daily/Université catholique de Louvain
Does the incidence of parental burnout depend on a country's culture? This question was at the heart of the first international study on the subject for which hundreds of scientists in 42 countries mobilised. In other words, the global scientific community is worried about family stress-induced parental burnout. A high level of stress in the family can lead to parental exhaustion. Such suffering has serious consequences for both parents and children.
'We worked in close collaboration with scientists from all the cultures involved,' UCLouvain researchers and study initiators and coordinators Isabelle Roskam and Moïra Mikolajczak explained in a statement. 'They were the only ones capable of collecting data in their countries, guaranteeing their validity and interpreting them correctly. Such exceptional collaboration deserves to be highlighted.'
The study's findings are categorical: rich, individualistic Western countries, which on average have few children, are the most affected by the phenomenon. Culture, rather than socio-economic and demographic differences between countries, plays a predominant role in parental burnout. 'Prevalence varies greatly from one culture and country to another,' Prof. Roskam explains. 'We could have hypothesised that it would be the same everywhere but that the reasons for exhaustion would be different.' This is not the case.
Published in Affective Science, the study shows that the values of individualism in Western countries can subject parents to higher levels of stress. The results force us to question ourselves in a context where the mantra of "every one for oneself" is spreading all over the world.
'Our individualistic countries cultivate a cult of performance and perfectionism,' says Prof. Roskam, a parental burnout specialist. 'Parenthood in these countries is a very solitary activity, unlike in African countries, for example, where the entire village is involved in raising children.' These poorer countries, which often have many children, are more collectivist. This dimension seems to protect against parental burnout. In addition, Western individualism is exacerbated by the current health crisis: families find themselves isolated and cut off from their social relations.
What measures can be taken to prevent stress in parenting? 'The first would be to revive in our cultures the dimension of sharing and mutual aid among parents within a community,' Prof. Roskam says. 'And abandon the cult of the perfect parent and gain some perspective on all the parenting advice out there in order to choose what works for you.'
Thanks to the study consortium's collective dynamics, their work opens up many avenues for future intercultural investigations. Until now, all studies on parental burnout focused on personal factors. However, parents affected by this syndrome exercise their parenting in a particular cultural context. It is important to take this into account when treating symptoms.
https://www.sciencedaily.com/releases/2021/03/210318085604.htm
In women, higher body fat may protect against heart disease death
March 16, 2021
Science Daily/University of California - Los Angeles Health Sciences
A new UCLA study shows that while men and women who have high muscle mass are less likely to die from heart disease, it also appears that women who have higher levels of body fat -- regardless of their muscle mass -- have a greater degree of protection than women with less fat.
The researchers analyzed national health survey data collected over a 15-year period and found that heart disease-related death in women with high muscle mass and high body fat was 42% lower than in a comparison group of women with low muscle mass and low body fat. However, women who had high muscle mass and low body fat did not appear have a significant advantage over the comparison group.
Among men, on the other hand, while having high muscle mass and high body fat decreased their risk by 26% (compared to those with low muscle mass and low body fat), having high muscle mass and low body fat decreased their risk by 60%.
The American Heart Association estimates that 5 million men and 3 million women have heart attacks annually. Yet despite this wide gender gap and an overall decrease in heart attack-related deaths for both men and women over the past 50 years, an equal number of men and women still die from heart disease.
In addition, mortality among women over those five decades has fallen at a slower rate than for men, and the incidence of heart attacks appears to be increasing among women between the ages of 35 and 54. Recent research has also found that women have significantly higher levels of risk factors associated with adverse heart disease than men.
The researchers analyzed body composition data from the National Health and Nutrition Examination Survey 1999-2004 and cardiovascular disease data from the National Health and Nutrition Examination Survey 1999-2014. They evaluated 11,463 individuals aged 20 and older, who were then divided into four body-composition groups: low muscle mass and low body fat, low muscle and high fat, high muscle and low fat, and high muscle and high fat. Heart disease-related mortality rates where then calculated for each of these groups.
The findings highlight the importance of recognizing physiological differences between women and men when considering body composition and the risk of death from heart disease, particularly when it comes to how differences in body fat may modify that risk.
The research also underscores the need to develop sex-appropriate guidelines with respect to exercise and nutrition as preventive strategies against the development of cardiovascular disease. Even with the current emphasis by health experts on reducing fat to lower disease risk, it may be important for women to focus more on building muscle mass than losing weight, the study authors say.
https://www.sciencedaily.com/releases/2021/03/210316183651.htm
How pregnancy turns the stress response on its head
Researchers seek elusive link between prenatal stress and offspring mental health
March 16, 2021
Science Daily/Ohio State University
The link between psychological stress and physical health problems generally relates to a stress-induced immune response gone wild, with inflammation then causing damage to other systems in the body. It's a predictable cascade -- except in pregnancy, research suggests.
Scientists exploring the negative effects of prenatal stress on offspring mental health set out to find the immune cells and microbes in stressed pregnant mice most likely to trigger inflammation in the fetal brain -- the source for anxiety and other psychological problems identified in previous research.
Instead, the researchers found two simultaneous conditions in response to stress that made them realize just how complex the cross-talk between mom and baby is during gestation: Immune cells in the placenta and uterus were not activated, but significant inflammation was detected in the fetal brain.
They also found that prenatal stress in the mice led to reductions in gut microbial strains and functions, especially those linked to inflammation.
"I thought it was going to be a fairly straightforward tale of maternal inflammation, changes in microbes and fetal inflammation. And while the changes in microbes are there, the inflammation part is more complex than I had anticipated," said Tamar Gur, senior author of the study and assistant professor of psychiatry and behavioral health, neuroscience, and obstetrics and gynecology at The Ohio State University.
"The complex interplay between the stress response and the immune system is dysregulated by stress, which is problematic for the developing fetus. There are key changes during this critical window that can help shape the developing brain, so we want to figure out how we could potentially intervene to help regulate these systems."
The study was published recently in Scientific Reports.
Most attention paid to the negative effects of prenatal stress on offspring mental health focus on disruptive major life events or exposure to disaster, but evidence also suggests that up to 84% of pregnant women experience some sort of stress.
In a previous study, Gur's lab found that prenatal stress's contributions to life-long anxiety and cognitive problems in mouse offspring could be traced to changes in microbial communities in both mom and baby.
Gur focuses on the intrauterine environment in her search for factors that increase the risk for prenatal stress's damaging effects, and this newer study opened her eyes to how complicated that environment is.
"The dogma would be that we're going to see an influx of immune cells to the placenta. The fact that it's suppressed speaks to the powerful anti-inflammatory response of the mom. And that makes sense -- a fetus is basically a foreign object, so in order to maintain pregnancy we need to have some level of immunosuppression," said Gur, also an investigator in Ohio State's Institute for Behavioral Medicine Research and a maternal-fetal psychiatrist at Ohio State Wexner Medical Center.
"We want to figure out what is at the interface between mom and baby that is mediating the immunosuppressive effect on the maternal side and the inflammation on the fetal side. If we can get at that, we'll get really important keys to understanding how best to prevent the negative impact of prenatal stress."
Prevention could come in the form of prebiotics or probiotics designed to boost the presence of beneficial microbes in the GI tract of pregnant women. Maternal microbes affect the brains and immune systems of developing offspring by producing a variety of chemicals the body uses to manage physiological processes.
"I think microbes hold really important clues and keys, making them a tantalizing target for intervention. We can do things about individuals' microbes to benefit both mom and baby," Gur said.
To mimic prenatal stress during the second and early third trimesters, pregnant mice in her lab are subjected to two hours of restraint for seven days to induce stress. Control mice are left undisturbed during gestation.
In this recent study, the researchers found stress in mice activated steroid hormones throughout the body -- the sign of a suppressed immune system -- and resulted in lower-than-expected populations of immune cells in reproductive tissue, suggesting that the uterus was effectively resisting the effects of the stress.
An examination of colon contents showed differences in microbial communities between stressed and non-stressed mice, with one family of microbes that influences immune function markedly decreased in stressed mice. The researchers found that stress showed few signs of gene-level changes in the colon that could let bacteria escape to the bloodstream -- one way that microbes interfere with body processes.
"There are absolutely changes in microbes that might help explain key pathways that are important for health and the immune system, especially when it comes to the placenta and the mom's immune system," Gur said.
In future studies, her lab will examine immune cells in the fetal brain and monitor how gene expression changes in cells in the placenta in response to stress. She is also leading an ongoing observational study in women, tracking microbes, inflammation and stress levels during and after pregnancy.
https://www.sciencedaily.com/releases/2021/03/210316112316.htm
Study reveals process to explain how maternal stress triggers idiopathic preterm birth
March 9, 2021
Science Daily/University of South Florida (USF Health)
Preterm birth is a leading cause of infant deaths and illness in the U.S. -- yet its underlying molecular causes remain largely unclear. About 40 to 50% of preterm births, defined as births before 37 weeks of pregnancy, are estimated to be "idiopathic," meaning they arise from unexplained or spontaneous labor. And, maternal stress linked to depression and post-traumatic stress disorders as well as fetal stress have been strongly implicated in preterm births with no known cause.
Now, for the first time, a University of South Florida Health (USF Health) preclinical study has uncovered a mechanism to help explain how psychological and/or physiological stress in pregnant women triggers idiopathic preterm birth. A research team at the USF Health Morsani College of Medicine Department of Obstetrics and Gynecology shows how cortisol -- the "fight-or-flight" hormone critical for regulating the body's response to stress -- acts through stress-responsive protein FKBP51 binding to progesterone receptors to inhibit progesterone receptor function in the uterus. This reduced progesterone receptor activity stimulates labor.
The findings were reported online first March 8 in Proceedings of the National Academy of Sciences (PNAS).
"This new study fills in some longstanding mechanistic gaps in our understanding of how normal labor begins and how stress causes preterm birth," said the paper's senior author Charles J. Lockwood, MD, senior vice president of USF Health, dean of the USF Health Morsani College of Medicine, and a professor of obstetrics and gynecology specializing in maternal-fetal medicine.
Dr. Lockwood was a co-principal investigator for the study along with the paper's lead author Ozlem Guzeloglu-Kayisli, PhD, a USF Health associate professor of obstetrics and gynecology. Nihan Semerci, MSc, a senior biological scientist, shares the lead authorship with Dr. Guzeloglu-Kayisli.
Progesterone reduces contractions of the uterus and sustained levels are essential to prevent a baby from being born too early. Reduced uterine progesterone receptor expression and signaling stimulates labor. In the brain, elevated FKBP51 expression has been strongly associated with increased risk for stress-related disorders.
Previous work by the USF Health team showed that normal human labor starting at term (between 37 and 42 weeks of pregnancy) was associated with reduced expression of progesterone receptors and increased expression of FKBP51, specifically in maternal decidual cells (specialized cells lining the uterus).
For the current study focused on maternal stress-induced idiopathic preterm birth, the researchers combined experiments in human maternal decidual cells and a mouse model in which FKBP5, the gene that makes FKBP51, had been removed, or "knocked out." Altogether, their results revealed a novel functional progesterone withdrawal mechanism, mediated by maternal stress-induced uterine FKBP51 overexpression and enhanced FKPB51-progesterone receptor binding, that decreased progestational effects and triggered preterm birth. The researchers found that Fkbp5 knockout mice (with depletion of the gene encoding for FKBP51) exhibit prolonged gestation and are completely resistant to maternal stress-induced preterm birth.
Among the USF Health team's key findings:
- FKPB51 levels were greater and FKPB51 binding to progesterone receptors was significantly increased in the decidual cells of women with idiopathic preterm birth, compared to decidual cells of gestational age-matched controls.
- The study reports for the first time that Fkbp5-deficient (knockout) mice are completely resistant to maternal stress-induced preterm birth and exhibit prolonged pregnancies accompanied by slower decline in systemic progesterone levels. This indicates that FKBP51 plays a crucial role in the length of pregnancy and initiation of labor and delivery.
- In contrast, mice with the FKPB5 gene intact and normal levels of FKPB51 protein (wild type mice) delivered earlier when exposed to maternal stress than either non-stressed wild type mice or FKPB5 knockout mice under nonstressed or stressed conditions.
"Collectively, these results suggest that FKBP51 plays a pivotal role both in term labor and stress-associated preterm parturition (birth) and that inhibition of FKBP51 may prove to be a novel therapy to prevent idiopathic preterm birth," the study authors conclude.
Currently, injectable progesterone is the only drug approved to help prevent preterm birth in high-risk women who have had a previous preterm birth. However, its effectiveness was not confirmed by a recent large clinical trial, sparking debate in the health care community. The authors finding that progesterone receptor activity was reduced in idiopathic preterm birth may explain the apparent lack of effectiveness of supplemental progesterone.
Babies born before 37 weeks, particularly those born before 34 weeks, have more health problems and may face long-term health complications, including childhood lung or heart disease and neurodevelopmental delays, Dr. Guzeloglu-Kayisli said. The likelihood of poor outcomes decreases as gestational age (length of the pregnancy) increases.
"Prevention of idiopathic preterm birth by extending gestation even two or three weeks can benefit the newborn, because it provides critical time needed for the fetus's lungs and brain to mature," Dr. Guzeloglu-Kayisli said. "Our research indicates the importance of investigating the potential use of FKBP51 inhibitors as a targeted therapy to reduce the risk of stress-related preterm birth."
The USF Health study was supported in part by The March of Dimes Prematurity Research Center Ohio Collaborative grant.
https://www.sciencedaily.com/releases/2021/03/210309105140.htm
Exercise during pregnancy may save kids from health problems as adults
Parental obesity predisposes children to develop diabetes, metabolic issues
March 15, 2021
Science Daily/University of Virginia Health System
Exercise during pregnancy may let mothers significantly reduce their children's chances of developing diabetes and other metabolic diseases later in life, new research suggests.
A study in lab mice has found that maternal exercise during pregnancy prevented the transmission of metabolic diseases from an obese parent -- either mother or father -- to child. If the finding holds true in humans, it will have "huge implications" for helping pregnant women ensure their children live the healthiest lives possible, the researchers report in a new scientific paper.
This means that one day soon, a woman's first trip to the doctor after conceiving might include a prescription for an exercise program.
"Most of the chronic diseases that we talk about today are known to have a fetal origin. This is to say that the parents' poor health conditions prior to and during pregnancy have negative consequences to the child, potentially through chemical modification of the genes," said researcher Zhen Yan, PhD, a top exercise expert at the University of Virginia School of Medicine. "We were inspired by our previous mouse research implicating that regular aerobic exercise for an obese mother before and during pregnancy can protect the child from early onset of diabetes. In this study, we asked the questions, what if an obese mother exercises only during pregnancy, and what if the father is obese?"
Exercise and Pregnancy
Scientists have known that exercise during pregnancy helps lead to healthy babies, reducing the risk of pregnancy complications and premature delivery. But Yan, the director of the Center for Skeletal Muscle Research at UVA's Robert M. Berne Cardiovascular Research Center, wanted to see if the benefits continued throughout the children's lives. And his work, both previous and new, suggests it does.
To determine that, Yan and his collaborators studied lab mice and their offspring. Some of the adult mice were fed typical mouse chow before and during pregnancy, while other were fed a high-fat, high-calorie diet to simulate obesity. Some receiving the high-fat diet before mating had access to a voluntary running wheel only during pregnancy, where they could run all they liked, while others did not, meaning they remained sedentary.
The results were striking: Both mothers and fathers in the high-fat group could predispose their offspring to metabolic disorders. In particular, male offspring of the sedentary mothers on high-fat diets were much more likely to develop high blood sugar and other metabolic problems in adulthood.
To better understand what was happening, the researchers looked at the adult offspring's metabolism and chemical (epigenetic) modification of DNA. They found there were significant differences in metabolic health and how active certain genes were among the different groups of offspring, suggesting that the negative effects of parental obesity, although different between the father and the mother, last throughout the life of the offspring.
The good news is that maternal exercise only during pregnancy prevented a host of "epigenetic" changes that affect the workings of the offspring's genes, the researchers found. Maternal exercise, they determined, completely blocked the negative effects of either mother's or father's obesity on the offspring.
The results, they say, provide the first evidence that maternal exercise only during pregnancy can prevent the transmission of metabolic diseases from parent to child.
"The take-home message is that it is not too late to start to exercise if a mother finds herself pregnant. Regular exercise will not only benefit the pregnancy and labor but also the health of the baby for the long run," Yan said. "This is more exciting evidence that regular exercise is probably the most promising intervention that will help us deter the pandemic of chronic diseases in the aging world, as it can disrupt the vicious cycle of parents-to-child transmission of diseases."
https://www.sciencedaily.com/releases/2021/03/210315160706.htm
Sounds influence the developing brain earlier than previously thought
February 12, 2021
Science Daily/Johns Hopkins Medicine
Scientists have yet to answer the age-old question of whether or how sound shapes the minds of fetuses in the womb, and expectant mothers often wonder about the benefits of such activities as playing music during pregnancy. Now, in experiments in newborn mice, scientists at Johns Hopkins report that sounds appear to change "wiring" patterns in areas of the brain that process sound earlier than scientists assumed and even before the ear canal opens.
The current experiments involve newborn mice, which have ear canals that open 11 days after birth. In human fetuses, the ear canal opens prenatally, at about 20 weeks gestation.
The findings, published online Feb. 12 in Science Advances, may eventually help scientists identify ways to detect and intervene in abnormal wiring in the brain that may cause hearing or other sensory problems.
"As scientists, we are looking for answers to basic questions about how we become who we are," says Patrick Kanold, Ph.D., professor of biomedical engineering at The Johns Hopkins University and School of Medicine. "Specifically, I am looking at how our sensory environment shapes us and how early in fetal development this starts happening."
Kanold started his career in electrical engineering, working with microprocessors, a natural conduit for his shift to science and studying the circuitry of the brain.
His research focus is the outermost part of the brain, the cortex, which is responsible for many functions, including sensory perception. Below the cortex is the white brain matter that in adults contains connections between neurons.
In development, the white matter also contains so-called subplate neurons, some of the first to develop in the brain -- at about 12 weeks gestation for humans and the second embryonic week in mice. Anatomist Mark Molliver of Johns Hopkins is credited with describing some of the first connections between neurons formed in white matter, and he coined the term subplate neurons in 1973.
These primordial subplate neurons eventually die off during development in mammals, including mice. In humans, this happens shortly before birth through the first few months of life. But before they die off, they make connections between a key gateway in the brain for all sensory information, the thalamus, and the middle layers of the cortex.
"The thalamus is the intermediary of information from the eyes, ears and skin into the cortex," says Kanold. "When things go wrong in the thalamus or its connections with the cortex, neurodevelopmental problems occur." In adults, the neurons in the thalamus stretch out and project long, armlike structures called axons to the middle layers of the cortex, but in fetal development, subplate neurons sit between the thalamus and cortex, acting as a bridge. At the end of the axons is a nexus for communication between neurons called synapses. Working in ferrets and mice, Kanold previously mapped the circuitry of subplate neurons. Kanold also previously found that subplate neurons can receive electrical signals related to sound before any other cortical neurons did.
The current research, which Kanold began at his previous position at the University of Maryland, addresses two questions, he says: When sound signals get to the subplate neurons, does anything happen, and can a change in sound signals change the brain circuits at these young ages?
First, the scientists used genetically engineered mice that lack a protein on hair cells in the inner ear. The protein is integral for transforming sound into an electric pulse that goes to the brain; from there it is translated into our perception of sound. Without the protein, the brain does not get the signal.
In the deaf, 1-week-old mice, the researchers saw about 25% -- 30% more connections among subplate neurons and other cortex neurons, compared with 1-week-old mice with normal hearing and raised in a normal environment. This suggests that sounds can change brain circuits at a very young age, says Kanold.
In addition, say the researchers, these changes in neural connections were happening about a week earlier than typically seen. Scientists had previously assumed that sensory experience can only alter cortical circuits after neurons in the thalamus reach out to and activate the middle layers of the cortex, which in mice is around the time when their ear canals open (at around 11 days).
"When neurons are deprived of input, such as sound, the neurons reach out to find other neurons, possibly to compensate for the lack of sound," says Kanold. "This is happening a week earlier than we thought it would, and tells us that the lack of sound likely reorganizes connections in the immature cortex."
In the same way that lack of sound influences brain connections, the scientists thought it was possible that extra sounds could influence early neuron connections in normal hearing mice, as well.
To test this, the scientists put normal hearing, 2-day-old mouse pups in a quiet enclosure with a speaker that sounds a beep or in a quiet enclosure without a speaker. The scientists found that the mouse pups in the quiet enclosure without the beeping sound had stronger connections between subplate and cortical neurons than in the enclosure with the beeping sound. However, the difference between the mice housed in the beeping and quiet enclosures was not as large as between the deaf mice and ones raised in a normal sound environment.
These mice also had more diversity among the types of neural circuits that developed between the subplate and cortical neurons, compared with normal hearing mouse pups raised in a quiet enclosure with no sound. The normal hearing mice raised in the quiet enclosure also had neuron connectivity in the subplate and cortex regions similar to that of the genetically-engineered deaf mice.
"In these mice we see that the difference in early sound experience leaves a trace in the brain, and this exposure to sound may be important for neurodevelopment," says Kanold.
The research team is planning additional studies to determine how early exposure to sound impacts the brain later in development. Ultimately, they hope to understand how sound exposure in the womb may be important in human development and how to account for these circuit changes when fitting cochlear implants in children born deaf. They also plan to study brain signatures of premature infants and develop biomarkers for problems involving miswiring of subplate neurons.
https://www.sciencedaily.com/releases/2021/02/210212193230.htm
Light pollution linked to preterm birth increase
January 25, 2021
Science Daily/Lehigh University
Scientists conducted the first study to examine the fetal health impact of light pollution based on a direct measure of skyglow, an important aspect of light pollution. Using an empirical regularity discovered in physics, called Walker's Law, a team from Lehigh University, Lafayette College and the University of Colorado Denver in the U.S., found evidence of reduced birth weight, shortened gestational length and preterm births.
Specifically, the likelihood of a preterm birth could increase by approximately 1.48 percentage points (or 12.9%), according to the researchers, as a result of increased nighttime brightness. Nighttime brightness is characterized by being able to see only one-fourth to one-third of the stars that are visible in the natural unpolluted night sky. The findings have been published in an article in Southern Economic Journal called, "Light pollution, sleep deprivation, and infant health at birth."
One possible biological mechanism underlying the findings, based on the existing literature, is light-pollution-induced circadian rhythm disruption, according to Muzhe Yang, a co-author of the study and a professor of economics in Lehigh's College of Business. Yang says circadian rhythm disruption can cause sleep disorders that subsequently lead to adverse birth outcomes.
"While greater use of artificial light at night (ALAN) is often associated with greater economic prosperity, our study highlights an often neglected health benefit of 'darkness,'" says Yang. "We must realize that the biological clock (i.e., the circadian rhythm) of a human body, like all lives on the earth, needs the 'darkness' as part of the light-dark cycle, in order to effectively regulate physiological functions, such as sleep."
While essential to a modern society, ALAN can disrupt a human body's circadian rhythm and therefore become a "pollutant." The societal benefits of ALAN, for example through increased economic activity, may be offset by ALAN's negative externalities such as adverse health effects, say the authors.
The contribution of ALAN to the alteration of natural nocturnal lighting levels is often referred to as light pollution. Light pollution is considered a worldwide ongoing problem
https://www.sciencedaily.com/releases/2021/01/210125191821.htm
Treating moms with postpartum depression helps their babies' brains
Psychiatric help for mothers with postpartum depression results in healthy changes in the brains of their babies
January 21, 2021
Science Daily/McMaster University
For the study 40 infants of women diagnosed with postpartum depression were matched with 40 infants of non-depressed mothers on infant age, gender and socioeconomic status. The mothers with postpartum depression received nine weeks of group CBT. The infants were all tested before the treatment and nine weeks later, including a questionnaire on the infant behaviour completed by the mother and her partner.
New research from McMaster University has found that psychiatric help for mothers with postpartum depression results in healthy changes in the brains of their babies.
The study, published in the journal Depression and Anxiety this week, found treating mothers who had postpartum depression with cognitive behavioural therapy (CBT) not only helped the moms, but resulted in adaptive changes in the brains and behaviour of their infants.
More specifically, after the mothers' treatment, their infants showed healthy changes in their nervous and cardiovascular systems, and they were observed to better regulate their behaviours and emotions by both mothers and fathers.
"In fact, we found that after their moms were treated that their infant's brain activity normalized to the levels seen in our healthy infants," said Ryan Van Lieshout, senior author of the study, a psychiatrist, and associate professor of psychiatry and behavioural neuroscience at McMaster's Michael G. DeGroote School of Medicine.
He added that it is well-known that the children of women with postpartum depression have changes in the functioning of their brains that make it more likely that they will develop emotional and behavioural problems later in life. However, it had not been known before if treating the mother's postpartum depression could reverse these changes.
"We believe that this is the first time that anyone has shown that treating moms' postpartum depression can lead to healthy changes in the physiology of the brains of their infants, a finding that we think provides a lot of good news," he said.
"This study shows that cognitive behavioural therapy, a treatment that is short, cost-effective and preferred by women, could potentially reduce the intergenerational transmission of risk from mother to child."
For the study 40 infants of women diagnosed with postpartum depression were matched with 40 infants of non-depressed mothers on infant age, gender and socioeconomic status. The mothers with postpartum depression received nine weeks of group CBT. The infants were all tested before the treatment and nine weeks later, including a questionnaire on the infant behaviour completed by the mother and her partner.
https://www.sciencedaily.com/releases/2021/01/210121131907.htm
Mouse study finds link between gut disease and brain injury in premature infants
January 6, 2021
Science Daily/Johns Hopkins Medicine
Physicians have long known that necrotizing enterocolitis (NEC), a potentially lethal inflammatory condition that destroys a premature infant's intestinal lining, is often connected to the development of severe brain injury in those infants who survive. However, the means by which the diseased intestine "communicates" its devastation to the newborn brain has remained largely unknown.
Now, working with mice, researchers at Johns Hopkins Medicine and the University of Lausanne in Switzerland have identified that missing link -- an immune system cell that they say travels from the gut to the brain and attacks cells rather than protect them as it normally does.
The team's findings are published Jan. 6, 2021, in the journal Science Translational Medicine.
Seen in as many as 12% of infants weighing less than 3.5 pounds at birth, NEC is a rapidly progressing gastrointestinal emergency in which bacteria invade the wall of the colon and cause inflammation that can ultimately destroy healthy tissue at the site. If enough cells become necrotic (die) so that a hole is created in the intestinal wall, bacteria can enter the bloodstream and cause life-threatening sepsis.
In a 2018 mouse study, researchers at Johns Hopkins Medicine and the Fred Hutchinson Cancer Research Center found that animals with NEC make a protein called toll-like receptor 4 (TLR4) that binds to bacteria in the gut and precipitates the intestinal destruction. They also determined that TLR4 simultaneously activates immune cells in the brain known as microglia, leading to white matter loss, brain injury and diminished cognitive function. What wasn't clear was how the two are connected.
For this latest study, the researchers speculated that CD4+ T lymphocytes -- immune system cells also known as helper T cells -- might be the link. CD4+ T cells get their "helper" nickname because they help another type of immune cell called a B lymphocyte (or B cell) respond to surface proteins -- antigens -- on cells infected by foreign invaders such as bacteria or viruses. Activated by the CD4+ T cells, immature B cells become either plasma cells that produce antibodies to mark the infected cells for disposal from the body or memory cells that "remember" the antigen's biochemistry for a faster response to future invasions.
CD4+ T cells also send out chemical messengers that bring another type of T cell -- known as a killer T cell -- to the area so that the targeted infected cells can be removed. However, if this activity occurs in the wrong place or at the wrong time, the signals may inadvertently direct the killer T cells to attack healthy cells instead.
"We knew from comparing the brains of infants with NEC with ones from infants who died from other causes that the former had accumulations of CD4+ T cells and showed increased microglial activity," says study senior author David Hackam, M.D., Ph.D., surgeon-in-chief at Johns Hopkins Children's Center and professor of surgery at the Johns Hopkins University School of Medicine. "We suspected that these T cells came from the NEC-inflamed regions of the gut and set out to prove it by using neonatal mice as a model of what happens in human infants."
In the first of a series of experiments, the researchers induced NEC in infant mice and then examined their brains. As expected, the tissues showed a significant increase in CD4+ T cells as well as higher levels of a protein associated with increased microglial activity. In a follow up test, the researchers showed that mice with NEC had a weakened blood-brain barrier -- the biological wall that normally prevents bacteria, viruses and other hazardous materials circulating in the bloodstream from reaching the central nervous system. This could, the researchers surmised, explain how CD4+ T cells from the gut could travel to the brain.
Next, the researchers determined that accumulating CD4+ T cells were the cause of the brain injury seen with NEC. They did this first by biologically blocking the movement of the helper T cells into the brain and then in a separate experiment, neutralizing the T cells by binding them to a specially designed antibody. In both cases, microglial activity was subdued and white matter in the brain was preserved.
To further define the role of CD4+ T cells in brain injury, the researchers harvested T cells from the brains of mice with NEC and injected them into the brains of mice bred to lack both T and B lymphocytes. Compared with control mice that did not receive any T cells, the mice that did receive the lymphocytes had higher levels of the chemical signals which attract killer T cells. The researchers also observed activation of the microglia, inflammation of the brain and loss of white matter -- all markers of brain injury.
The researchers then sought to better define how the accumulating CD4+ T cells were destroying white matter -- actually a fat called myelin that covers and protects neurons in the brain, and facilitates communication between them. To do this, they used organoids, mouse brain cells grown in the laboratory to simulate the entire brain. Brain-derived CD4+ T cells from mice with NEC were added to these laboratory "mini-brains" and then examined for several weeks.
Hackam and his colleagues found that a specific chemical signal from the T cells -- a cytokine (inflammatory protein) known as interferon-gamma (IFN-gamma) -- increased in the organoids as the amount of myelin decreased. This activity was not seen in the organoids that received CD4+ T cells from mice without NEC.
After adding IFN-gamma alone to the organoids, the researchers saw the same increased levels of inflammation and reduction of myelin that they had seen in mice with NEC. When they added an IFN-gamma neutralizing antibody, cytokine production was significantly reduced, inflammation was curtailed and white matter was partially restored.
The researchers concluded that IFN-gamma directs the process leading to NEC-related brain injury. Their finding was confirmed when an examination of brain tissues from mice with NEC revealed higher levels of IFN-gamma than in tissues from mice without the disease.
Next, the researchers investigated whether CD4+ T cells could migrate from the gut to the brain of mice with NEC. To do this, they obtained CD4+ T cells from the intestines of infant mice with and without NEC. Both types of cells were injected into the brains of infant mice in two groups -- one set that could produce the protein Rag1 and one that could not. Rag1-deficient mice do not have mature T or B lymphocytes.
The Rag1-deficient mice that received gut-derived helper T cells from mice with NEC showed the same characteristics of brain injury seen in the previous experiments. T cells from both mice with and without NEC did not cause brain injury in mice with Rag1, nor did T cells from mice without NEC in Rag1-deficient mice. This showed that the gut-derived helper T cells from mice with NEC were the only ones that could cause brain injury.
In a second test, gut-derived T cells from mice with and without NEC were injected into the peritoneum -- the membrane lining the abdominal cavity -- of Rag1-deficient mice. Only the intestinal T cells from mice with NEC led to brain injury.
This finding was confirmed by genetically sequencing the same portions from both the brain-derived and gut-derived T lymphocytes from mice with and without NEC. The sequences of the helper T cells from mice with NEC, on average, were 25% genetically similar while the ones from mice without NEC were only 2% alike.
In a final experiment, the researchers blocked IFN-gamma alone. Doing so provided significant protection against the development of brain injury in mice with severe NEC. This suggests, the researchers say, a therapeutic approach that could benefit premature infants with the condition.
"Our research strongly suggests that helper T cells from intestines inflamed by NEC can migrate to the brain and cause damage," says Hackam. "The mouse model in our study was previously shown to closely match what occurs in humans, so we believe that this is the likely mechanism by which NEC-related brain injury develops in premature infants."
Based on these findings, Hackam says measures for preventing this type of brain injury, including therapies to block the action of INF-gamma, may be possible.
https://www.sciencedaily.com/releases/2021/01/210106171334.htm
Gut microbe may promote breast cancers
Short-term exposure to B. fragilis toxin leaves lasting impression in cells, increasing the risk for cancer
January 6, 2021
Science Daily/Johns Hopkins Medicine
A microbe found in the colon and commonly associated with the development of colitis and colon cancer also may play a role in the development of some breast cancers, according to new research from investigators with the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy. Breast tissue cells exposed to this toxin retain a long-term memory, increasing the risk for disease.
In a series of laboratory experiments, researchers discovered that when enterotoxigenic Bacteroides fragilis (ETBF) was introduced to the guts or breast ducts of mice, it always induced growth and metastatic progression of tumor cells. A description of the work is published in the January 6 issue of the journal Cancer Discovery.
While microbes are known to be present in body sites such as the gastrointestinal tract, nasal passages and skin, breast tissue was considered sterile until recently, says senior study author Dipali Sharma, Ph.D., a professor of oncology at Johns Hopkins Medicine.
The study is a first step to show the involvement of ETBF in breast cancer development, Sharma says. Additional studies are needed to clarify how ETBF moves throughout the body, whether ETBF can be a sole driver to directly trigger the transformation of breast cells in humans, and/or if other microbiota also have cancer-causing activity for breast tissue.
"Despite multiple established risk factors for breast cancer, such as age, genetic changes, radiation therapy and family history, a large number of breast cancers arise in women harboring none of these, indicating the need to look beyond," Sharma says. "Our study suggests another risk factor, which is the microbiome. If your microbiome is perturbed, or if you harbor toxigenic microbes with oncogenic function, that could be considered an additional risk factor for breast cancer."
Sharma and colleagues performed several experiments to study the role of ETBF. First, they performed a meta-analysis of clinical data looking at published studies comparing microbial composition among benign and malignant breast tumors and nipple aspirate fluids of breast cancer survivors and healthy volunteers. B. fragilis was consistently detected in all breast tissue samples as well as the nipple fluids of cancer survivors.
In the lab, the team gave the ETBF bacteria by mouth to a group of mice. First, it colonized the gut. Then, within three weeks, the mouse mammary tissue had observable changes usually present in ductal hyperplasia, a precancerous condition. In additional tests, investigators found that hyperplasia-like symptoms also appeared within two to three weeks of injecting ETBF bacteria directly to the teats of mice, and that cells exposed to the toxin always exhibited more rapid tumor progression and developed more aggressive tumors than cells not exposed to the toxin. Breast cells exposed to the toxin for 72 hours retained a memory of the toxin and were able to start cancer development and form metastatic lesions in different mouse models. Investigators also found the Notch1 and beta-catenin cell signaling pathways to be involved in promoting EBFT's role in breast tissue.
In clinical studies, the investigators have started looking for microbiome changes among breast cancer patients to see how this impacts tumor progression and response to therapy. Meanwhile, Sharma says, "we definitely should try to maintain a healthy microbiome, including eating a healthy diet and exercising, and maintaining the correct body mass index."
Down the road, screening for microbiome changes could be as simple as stool sample tests, said lead author Sheetal Parida, a postdoctoral fellow at Johns Hopkins Medicine. "This is just one indicator, and we think there will be multiple," she said. "If we find additional bacteria responsible for cancer development, we can easily look at the stool and check for those. Women at high risk of developing breast cancer might have a high population of some of these."
https://www.sciencedaily.com/releases/2021/01/210106115710.htm
Mothers, but not fathers, with multiple children report more fragmented sleep
Study tracks sleep patterns of first-time and experienced parents
January 12, 2021
Science Daily/McGill University
Mothers with multiple children report more fragmented sleep than mothers of a single child, but the number of children in a family doesn't seem to affect the quality of sleep for fathers, according to a study from McGill University.
A total of 111 parents (54 couples and 3 mothers of single-parent families) participated in the study published in the Journal of Sleep Research led by McGill doctoral student Samantha Kenny under the supervision of Marie-Hélène Pennestri, Assistant Professor in the Department of Educational and Counselling Psychology.
Participants' sleep patterns were studied for two weeks. Mothers with one baby reported having less interrupted and better-quality sleep than mothers with more than one child, although the total amount of sleep did not differ depending on the number of children. No difference was noted in fathers.
"Experienced mothers perceived their sleep to be more fragmented than that of first-time mothers. Tension in the marital relationship may transpire if childcare is one-sided and not discussed collaboratively," says Pennestri, who is also a researcher at the Hôpital en santé mentale Rivière-des-Prairies (CIUSSS-NIM).
According to the researchers, interventions developed by healthcare providers targeting an equal distribution of daytime and nighttime childcare tasks could be helpful. These interventions should be tailored to each family member, depending on their situation.
As next steps, the researchers aim to explain the differences between mothers and fathers, and determine why mothers with more than one child report worse sleep.
https://www.sciencedaily.com/releases/2021/01/210112163627.htm
Can a mother's stress impact children's disease development?
Environmental health researcher says there is a connection between trauma and DNA mutation
January 11, 2021
Science Daily/University of Cincinnati
Stress on an expectant mother could affect her baby's chance of developing disease -- perhaps even over the course of the child's life, UC researchers have found.
Psychosocial factors creating stress -- such as lack of social support, loneliness, marriage status or bereavement -- may be mutating their child's mitochondrial DNA and could be a precursor to a host of diseases, according to a University of Cincinnati study.
"There are a lot of conditions that start in childhood that have ties to mitochondrial dysfunction including asthma, obesity, attention deficit hyperactivity disorder and autism," says Kelly Brunst, PhD, assistant professor of environmental and public health sciences in the UC College of Medicine and lead author of the study.
"The fetal and infant period is a vulnerable time for environmental exposure due to heightened development during these periods," says Brunst. "We don't just wake up one day and have asthma or attention deficit hyperactivity disorder. The programming effects resulting from environmentally induced shifts occur over time and likely start during gestation at the molecular and cellular level. These shifts alter physiological states that likely play a role in who is going to go on and develop adverse health outcomes."
As part of the study, researchers sequenced the mitochondrial genome and identified mutations in 365 placenta samples from birth mothers in Boston and New York City from 2013-18. A multivariable regression model was used to look at maternal lifetime stress in relation to the number of gene mutations in the placenta mitochondrial genome.
Women experiencing increased psychosocial stress -- that can range from sexual assault, domestic violence or serious injury to incarceration, physical or mental illness and family hardship -- over their lifetime exhibited a higher number of placental mitochondrial mutations. The strongest associations were observed among Black women. Higher stress-related DNA mutations in the placenta were seen in Black and white women, but not in Hispanic women.
The study's findings were published in the scholarly journal Biological Psychiatry.
"The idea behind this work is about understanding how our environment, in this case maternal stress and trauma, impact mitochondrial function and ultimately neurobehavioral development," says Brunst. "The hope is to gain insight as to why certain children are vulnerable to developing a range of complex conditions previously linked to environmental exposures such as chronic stress or air pollution."
"We ask about events that might have occurred prior to their pregnancy even during the mother's own childhood as part of our study," says Brunst. "So what this is telling us is that the stress that a woman has experienced even before she is pregnant might have an impact on the fetal mitochondrial genome."
Brunst said there are some diseases for which Black women are more at risk -- obesity, diabetes and certain cancers -- so they might be more affected by stress and subsequently develop these diseases which have also been linked to stress."
"What was interesting about the study was that Hispanics exposed to stress had fewer placental mitochondrial DNA mutations," says Brunst.
She says one explanation could be what researchers call the "Hispanic paradox." It is the epidemiological phenomenon documenting better health and lower mortality relative to non-Hispanic whites despite greater risk and lower socioeconomic status for Hispanics."
"Despite exposure to more stress and trauma, sociocultural dynamics specific to Hispanics may attenuate experiences of stress which in turn has downstream effects on psychophysiological mechanisms and better outcomes," says Brunst. "This is just one possible explanation."
Other co-authors of this study are Xiang Zhang, PhD, and Li Zhang, PhD, both associate professors in the UC College of Medicine, along with Andrea Baccarelli, MD, PhD, and Tessa Bloomquist, both of Columbia University, Mailman School of Public Health, and Rosalind Wright, MD, of the Icahn School of Medicine at Mount Sinai, in New York City.
The study was funded by the National Heart, Lung, and Blood Institute under grants R01HL095606 and R01HL114396; the National Institute of Environmental Health Sciences under grants R00ES024116, P30ES006096 and P30ES023515.
Brunst led a previous research study that looked at the correlation between exposure to traffic-related air pollution and childhood anxiety, by looking at the altered neurochemistry in pre-adolescents. She is also recipient of a recent $2.9 million five-year grant from the National Institutes of Health for the research project, "Epigenetics, air pollution, and childhood mental health."
https://www.sciencedaily.com/releases/2021/01/210111143418.htm
Link between dietary fiber and depression partially explained by gut-brain interactions
New study suggests that higher daily dietary fiber intake is linked to lower risk for depression in premenopausal women
January 6, 2021
Science Daily/The North American Menopause Society (NAMS)
Fiber is a commonly recommended part of a healthy diet. That's because it's good for your health in so many ways -- from weight management to reducing the risk of diabetes, heart disease, and some types of cancer. A new study also finds that it might be linked with a reduced risk of depression, especially in premenopausal women. Study results are published online in Menopause, the journal of The North American Menopause Society (NAMS).
Depression is a common and serious mental health condition that not only affects a person's ability to perform daily activities but can also lead to suicide. It's estimated that more than 264 million people worldwide have depression, with numbers increasing over time. This debilitating condition is much more common in women, and there are a number of theories as to why this is the case. Changes in hormone levels in perimenopausal women have been linked to depression.
Because of the serious consequences and prevalence of depression, numerous studies have been undertaken to evaluate treatment options beyond the use of antidepressants. Lifestyle interventions, including diet, exercise, and mindfulness, may help to reduce the risk for depression. In this new study involving more than 5,800 women of various ages, researchers specifically sought to investigate the relationship between dietary fiber intake and depression in women by menopause status. Dietary fiber is found mainly in fruit, vegetables, whole grains, and legumes.
Previous studies have already suggested the benefits of fiber for mental health, but this is the first known study to categorize the association in premenopausal and postmenopausal women. It also included a broader range of ages in participants and involved women who underwent natural, as well as surgical, menopause.
The study confirmed an inverse association between dietary-fiber intake and depression in premenopausal women after adjusting for other variables, but no significant difference was documented in postmenopausal women. Research has suggested that estrogen depletion may play a role in explaining why postmenopausal women don't benefit as much from increased dietary fiber, because estrogen affects the balance of gut microorganisms found in premenopausal and postmenopausal women. The link between dietary fiber and depression may be partially explained by gut-brain interactions, because it is theorized that changes in gut-microbiota composition may affect neurotransmission. Fiber improves the richness and diversity of gut microbiota.
Results are published in the article "Inverse association between dietary fiber intake and depression in premenopausal women: a nationwide population-based survey."
"This study highlights an important link between dietary fiber intake and depression, but the direction of the association is unclear in this observational study, such that women with better mental health may have had a healthier diet and consumed more fiber, or a higher dietary fiber intake may have contributed to improved brain health by modulating the gut microbiome or some combination. Nonetheless, it has never been more true that 'you are what you eat,' given that what we eat has a profound effect on the gut microbiome which appears to play a key role in health and disease," says Dr. Stephanie Faubion, NAMS medical director.
https://www.sciencedaily.com/releases/2021/01/210106111952.htm
Researchers find 'missing link' between stress and infertility
December 4, 2020
Science Daily/University of Otago
Otago researchers have found the "missing link between stress and infertility."
Published in The Journal of Neuroscience, and led by Professor Greg Anderson of the Centre for Neuroendocrinology, the research has confirmed in laboratory testing that a population of nerve cells near the base of the brain -- the RFRP neurons -- become active in stressful situations and then suppress the reproductive system.
"A revolutionary step forward that has become available to neuroscientists in recent years is the ability to control the activity of selected groups of neurons -- to either silence or ramp up their activity, and then monitor the outcomes," Professor Anderson says.
"We used cutting edge transgenic techniques to show that when the activity of the RFRP cells is increased, reproductive hormones are suppressed -- in a similar manner to what happens during stress, or during exposure to the stress hormone cortisol.
"Amazingly, when we used cortisol to suppress the reproductive hormones but also silenced the RFRP neurons, the reproductive system continued to function as if cortisol wasn't there at all -- proving that the RFRP neurons are a critical piece of the puzzle in stress-induced suppression of reproduction."
The reaction was most evident in females.
Professor Anderson started researching the role of RFRP neurons in controlling fertility in mammals about a decade ago.
"I became interested in whether these neurons might be what causes fertility to be suppressed during chronic stress, after reading that these cells become active during stress. This is a question that has remained stubbornly unanswered over the past decades.
"Although it is known that stress steroids -- like cortisol -- are probably part of the mechanism involved, it is also known that the brain cells that control reproduction are unable to respond to cortisol, so there seemed to be a missing link in the circuit somewhere.
"We have now shown that the RFRP neurons are indeed the missing link between stress and infertility. They become active in stressful situations -- perhaps by sensing the increasing levels of cortisol -- and they then suppress the reproductive system."
It is possible drugs could be used to block the actions of the RFRP neurons, and that will be the focus of further research for Professor Anderson.
"We'd like to see if we can overcome stress-induced infertility using drugs which block the actions of the RFRP neurons.
"For women struggling with infertility, drugs which block the actions of the RFRP neurons may prove to be a novel therapy. From what we know about these neurons, such a drug wouldn't have any side-effects.
"There are such drugs available, but they're not approved for human use and they would likely need refining," he says.
https://www.sciencedaily.com/releases/2020/12/201204110230.htm
Mothers' stress may lead to preterm births, faster aging in children
How stress before and during pregnancy may adversely affect offspring
November 30, 2020
Science Daily/University of California - Los Angeles
Why do some people age faster than others? One potential answer, a new UCLA-led study indicates, is that a mother's stress prior to giving birth may accelerate her child's biological aging.
The researchers found evidence that maternal stress adversely affects the length of a baby's telomeres -- the small pieces of DNA at the ends of chromosomes that act as protective caps, like the plastic tips on shoelaces. Shortened telomeres have been linked to a higher risk of cancers, cardiovascular and other diseases, and earlier death.
The findings are reported this month in the journal Psychoneuroendocrinology.
"Research on aging is beginning to identify some factors that might put a person on an accelerated aging path, potentially leading to diseases of aging such as metabolic disorder and cardiovascular disease much earlier in life than would be expected," said the study's lead author, Judith Carroll, an associate professor of psychiatry and biobehavioral sciences at the Cousins Center for Psychoneuroimmunology, part of the Semel Institute for Neuroscience and Human Behavior at UCLA. "What our research tells us is that we may have early environmental and maternal factors influencing where a person starts in life, which may set them on course to age faster."
While several studies have reported that telomere length is shorter in newborns whose mothers reported high stress during either the first or third trimester of pregnancy, the new study tracked maternal stress prior to conception and followed up in the second and third trimesters. The researchers identified an especially important period in the third trimester -- but not earlier -- during which children are at higher risk for shortened telomeres.
Overall, the study followed 111 mothers and their children from preconception into early childhood. The women were from seven counties in North Carolina, one in Illinois and Washington, D.C. Between the ages of 3 and 5, the children provided cell samples from inside their cheeks, from which the researchers extracted DNA, including telomeres. The team was then able to compare childhood telomere length with the stress measurements they had taken while the children were in utero.
"This allows us to determine the contribution of stress at each of these times on the child's telomere length," Carroll said. "Past studies looked at newborn telomere length, and our findings look years later, when the child is 3 to 5 years old. We see evidence into childhood that telomere length continues to be shorter in those children exposed in utero to maternal stress. We think this finding is quite notable."
How does maternal stress alter cellular aging?
"We have hypotheses," Carroll said. "We know that stress can activate inflammation and metabolic activity, both of which, in high amounts, can contribute to damage to DNA. Telomeres are vulnerable to damage and, if unrepaired before cell division, they can become shortened by this damage. During in utero development, we know there is rapid cell replication, and we suspect there is increased vulnerability to damage during this time."
High maternal stress often leads to preterm births
A second UCLA-led study from the same research group found that women suffering from high stress during the months and even years before conception -- defined as feeling overwhelmed and unable to cope -- had shorter pregnancies than other women. Women who experienced the highest levels of stress gave birth to infants whose time in utero was shorter by one week or more.
"Every day in the womb is important to fetal growth and development," said Christine Dunkel Schetter, a distinguished professor of psychology and psychiatry and senior author of both studies. "Premature infants have higher risk of adverse outcomes at birth and later in life than babies born later, including developmental disabilities and physical health problems."
Dunkel Schetter, who heads the Stress Processes in Pregnancy Lab, which conducted the studies, noted that premature birth rates are unusually high in the U.S., compared to other nations with similar resources, and that low-income and African American women have higher rates of preterm birth. "Preventing preterm birth, with its adverse consequences for mothers and children worldwide and in the U.S., is a top priority," she said.
These results, which appear in the journal Annals of Behavioral Medicine, are based on extensive in-home interviews with 360 mothers from largely low-income, racially diverse areas, many of whom live near or below the poverty level. In addition to collecting data on these women's general stress levels, the interviewers obtained information about various types of environmental stress, including financial worries, job loss, a lack of food, chronic relationship troubles, parenting challenges, interpersonal violence and discrimination.
The researchers found that women who were exposed to the lowest or highest amounts of stress in their environment had the shortest pregnancies, while women who had a moderate level of environmental stress before conception had the longest pregnancies.
"Women exposed to moderate stressors in their environment may have developed coping strategies that serve them well both before and during pregnancy, while exposure to more severe stress challenges even women who normally cope very effectively," said lead author Nicole Mahrer, who conducted the research as a UCLA postdoctoral scholar in health psychology and is now an assistant professor of psychology at the University of La Verne. She is also a co-author of the other study.
A moderate amount of stress in utero may help prepare the developing fetus for the environment to come, Mahrer said, especially if the mother has developed effective coping strategies.
"What we have not known until now," Dunkel Schetter said, "is whether a mother's psychosocial health before conception matters for her birth outcomes. This study is among the first to point out that, yes, it does matter.
"It may even be more influential than prenatal health because some of what is put in motion before conception may be hard to stop during pregnancy," she added. "For example, a mother with dysregulated immune function due to stress may be at risk when she becomes pregnant. The abundance of stress for low-income parents is potent and potentially high risk for them and their children."
These findings, Dunkel Schetter said, support the case for devoting more resources to programs for preconception health and well-being.
Both studies were funded by the National Institutes of Health's Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Mental Health and the National Institute for Nursing Research.
The scientists say their research just scratches the surface of the impact of mothers' preconception health and the fetal environment on biological factors that affect children's health.
"An important takeaway from this work is that prenatal and preconception maternal health and well-being are critically important for the health of the infant," Carroll said. "If we as a society can make changes to help give pregnant women the resources they need and provide them with a safe and supportive environment before and during pregnancy, we may have a significant impact on the health of their children."
https://www.sciencedaily.com/releases/2020/11/201130131427.htm
Stress in pregnancy may influence baby brain development
November 24, 2020
Science Daily/University of Edinburgh
Infants' brains may be shaped by levels of stress their mother experiences during pregnancy, a study has revealed.
Stress levels in mothers -- measured by a hormone linked to anxiety and other health problems -- is related to changes in areas of the infant brain associated with emotional development, the study suggests.
Doctors say the findings highlight the urgent need for women to be better supported with their mental and physical health before and during pregnancy, and could help them spot mums and babies who need help.
The experts add that pregnant women who feel stressed or unwell should seek help from their midwife or consultant and that with support, most health issues can be well managed in pregnancy.
Maternal stress is known to influence the development of the child's behaviour and ability to regulate its emotions as it grows. This is usually measured by questionnaires, which are not always reliable.
The new study is the first time that scientists have used an objective measure -- levels of the hormone cortisol -- in the mother to study links with baby brain development.
Cortisol is involved in the body's response to stress -- with higher levels indicating higher stress -- and also plays a role in fetal growth.
A research team led by the University of Edinburgh showed that levels of cortisol are linked to the development of the baby's amygdala, an area of the brain known to be involved in emotional and social development in childhood.
For the study, scientists took hair samples from 78 pregnant women to determine the women's levels of cortisol in the previous three months.
The women's babies underwent a series of brain scans using Magnetic Resonance Imaging, or MRI, a non-invasive scan that took place whilst the baby slept.
The researchers found that higher levels of cortisol in the mother's hair were linked to structural changes in the infants' amygdala as well as differences in brain connections.
Doctors say this could explain why children whose mothers experienced high levels of stress during pregnancy may be more likely to have emotional issues in later life.
They caution, however, that the study did not assess emotion in children.
The study was funded by the global children's charity, Theirworld, and is published in the journal eLife.
Lead researcher, Professor James Boardman, Director of the Jennifer Brown Research Laboratory at the MRC Centre for Reproductive Health at the University of Edinburgh, said: "Our findings are a call to action to detect and support pregnant women who need extra help during pregnancy as this could be an effective way of promoting healthy brain development in their babies."
Professor Rebecca Reynolds, Personal Chair of Metabolic Medicine at the University of Edinburgh, who co-led the study, said: "Thankfully, psychological treatments are very successful at helping mothers and children and we hope that our findings could guide therapies in future to help spot those who might be most in need of support."
Sarah Brown, Chair of Theirworld, said: "This research highlights how important it is to support women's mental health during pregnancy to ensure that their needs are met and that their babies have the best start in life. Helping mothers cope with stress is an important step to ensure both mum and baby thrive."
https://www.sciencedaily.com/releases/2020/11/201124111105.htm
Predicting preterm births
November 19, 2020
Science Daily/Baylor College of Medicine
Predicting preterm birth can be difficult, especially for women who have not given birth. It has long been known that the best predictor of preterm birth is someone who has had a prior preterm birth; however, this information is helpful only in second and subsequent pregnancies. For women in their first pregnancy, it is a challenge for obstetricians and midwives to advise them on their risks. To address this issue, researchers at Baylor College of Medicine and Texas Children's Hospital studied how family history can predict preterm birth. Their findings were published in the American Journal of Obstetrics & Gynecology.
"This is a retrospective study of prospective data," said Dr. Kjersti Aagaard, professor of obstetrics and gynecology at Baylor and Texas Children's Hospital. "We developed a biobank and data repository called PeriBank where we consistently asked our pregnant patients a set of questions about their familial history. We were able to take that detailed data and determine if that specific woman's family history did or did not predict her delivering preterm."
Once familial information was gathered, the research team was able to answer questions to quantify estimates of risk for preterm birth based on the pregnant patient's family history of preterm birth in herself, her sister(s), her mother, grandmothers and aunts and great-aunts. Their findings showed scenarios for women who have previously given birth (multiparous), as well as women who have never given birth (nulliparous). If a nulliparous woman herself was born preterm, her relative risk for delivering preterm was 1.75-fold higher. If her sister delivered preterm, her relative risk was 2.25-fold higher. If her grandmother or aunt delivered preterm, there was no significant increase of risk. If a multiparous mother with no prior preterm births was born preterm herself, her risk was 1.84-fold higher. However, if her sister, grandmother or aunt delivered preterm, there was no significant increase.
"We've managed over the years to collect data from a very large population of pregnant women that reflect Houston. There was considerable diversity by race, ethnicity, culture and socioeconomic status. This was a key strength of our study. With this breadth and depth of data reflective of the diversity of Houston, we were able to ask some good questions, which gave us really important information about 'heritability' of risk," Aagaard said.
The research team showed that preterm births cannot be fully attributed to genetics, Aagaard said. Family members may share DNA or genetic code, but the same generation of family members are more likely to share social determinants or have experienced systemic racism and bias. This was best demonstrated by their finding that a history of preterm birth in the pregnant woman or her sister was significantly associated with preterm birth, while a grandmother or aunt was not. These same-generation predictors are generally thought to reflect more about common environmental or social exposures (or a combination of limited genetics plus common exposures) than genetic linkages.
"We know that for the majority of women who deliver a baby preterm, we cannot say that the cause of that preterm birth was in whole or in part genetics. Rather, this study provides subtle but important clues that it is more likely the shared familial background and its exposures that render risk," Aagaard said. "We hope others will similarly be mindful of those subtle characteristics when looking at heritability and risk. We remain committed to finding the underlying true causal and driving factors. In the meantime, we provide for the first time some reliable risk estimates for first time moms based on their and their family history of preterm birth."
Other contributors to this work include Amanda Koire and Derrick Chu.
This work was funded by the March of Dimes Preterm Birth Research Initiative (KA) and the NIH (1R01NR014792; KA).
https://www.sciencedaily.com/releases/2020/11/201119165435.htm
Study finds low risk of pregnancy complications from COVID-19
November 19, 2020
Science Daily/UT Southwestern Medical Center
Pregnant women who test positive for COVID-19 and their newborn babies have a low risk of developing severe symptoms, according to a new study from UT Southwestern.
The study, published today in JAMA Network Open, shows that 95 percent of women who tested positive for COVID-19 during pregnancy had no adverse outcomes. Additionally, the study found that the virus was transmitted to the fetus in just 3 percent of the cases.
"Our findings are that approximately 5 percent of all delivered women with COVID-19 infection develop severe or critical illness. Five percent is a major concern when a pandemic is making its way through a population; however, it's lower than previous reports from the Centers for Disease Control and Prevention (CDC)," says Emily Adhikari, M.D., an obstetrician, gynecologist, and first author of the study. "Most women with asymptomatic or mild infection will be relieved to know that their babies are unlikely to be affected by the virus."
The researchers set out to measure how COVID-19 infection impacts pregnancy outcomes, how severely ill a pregnant woman gets, placental pathology, and neonatal infections by studying women at Parkland Health and Hospital System -- a high-volume prenatal clinic system and public hospital affiliated with UT Southwestern. The team followed 3,374 mothers, 252 of whom tested positive for the virus during pregnancy, from March through August. The group was predominantly Hispanic (75 percent), followed by Black (18 percent) and white (4 percent). There were no significant differences between the expectant mothers in age, number of previous births, BMI, or diabetes.
The pandemic has hit the Hispanic population in Dallas particularly hard. "While they make up 75 percent of the population of over 12,000 women delivering annually at our institution, women of Hispanic ethnicity made up over 90 percent of COVID-19-positive women. The higher frequency among Hispanic women in our study is consistent with data on racial and ethnic disparities in COVID-19 cases and deaths reported nationwide," says Adhikari, medical director of perinatal infectious diseases at Parkland Memorial Hospital and an assistant professor of obstetrics and gynecology.
Among the 252 women who tested positive, 239, or 95 percent, were asymptomatic or had mild symptoms at first. Six of those women subsequently developed severe or critical COVID-19 pneumonia. Comparing mothers with and without COVID-19 diagnosed any time during pregnancy, the COVID-19 virus did not increase the risk of adverse outcomes, including preterm birth, preeclampsia with severe features, or cesarean delivery for abnormal fetal heart rate. However, preterm birth was increased among mothers who developed severe or critical illness before reaching 37 weeks in their pregnancy, and it's hard to predict who that will be. The study found that diabetes may be one factor that increases the risk for severe or critical maternal illness.
Pathologists who examined placentas -- the organ that functions as the source of oxygen and nourishment for unborn babies -- found that the majority were unaffected by the virus.
COVID-19 mothers who were outpatients were followed using telemedicine with a scripted evaluation of symptoms and protocol-based management, including instructions for referral to the emergency department for worsening respiratory symptoms or obstetric concerns. Telemedicine has been a vital tool used by many UT Southwestern and Parkland physicians during the pandemic.
Further study is needed to understand whether maternal infection with COVID-19 impacts long-term maternal or infant health.
"Our goal is to develop evidence-based guidelines for the majority of pregnant women who are recovering at home," Adhikari says. "It's difficult to predict who will become severely ill, which is why prevention strategies such as hand-washing, masking, and social distancing are still extremely important."
https://www.sciencedaily.com/releases/2020/11/201119141710.htm
Does air pollution affect mental health later in life?
November 18, 2020
Science Daily/Wiley
In a study of women aged 80 years and older, living in locations with higher exposures to air pollution was associated with increased depressive symptoms. The findings are published in the Journal of the American Geriatrics Society.
When looking at individual air pollutants, a team led by investigators from of the University of Southern California found that long-term exposure to nitrogen dioxide or fine particulate air pollution was associated with increased depressive symptoms, but with only a small effect. Results also suggested that depressive symptoms might play a role in linking long-term air pollution exposure to memory decline more than 10 years after the exposure.
"This is the first study showing how air pollution exposures affect depressive symptoms as well as the interrelationship between the symptoms and subsequent memory decline that had not been found in older people aged less than 80 years," said lead author Andrew Petkus, PhD.
Senior author Jiu-Chiuan Chen, MD, ScD, added, "We know late-life exposures to ambient air pollutants accelerate brain aging and increase the dementia risk, but our new findings suggest the oldest-old populations may respond to air pollution neurotoxicity in a different way that needs to be investigated further."
https://www.sciencedaily.com/releases/2020/11/201118080750.htm