Monday, November 27, 2023

Proof of concept of new material for long lasting relief from dry mouth conditions

UNIVERSITY OF LEEDS

Synthetic saliva using a dairy protein — IMAGE:
LACTOFERRIN WHICH IS A PROTEIN FOUND IN MILK - COLOURED DARK BLUE - FORMS THE MESH-LIKE ARCHITECTURE OF THE HYDRATED MICROGEL, PARTIALLY COATED BY A HYDROGEL MADE BY A POLYSACCHARIDE Κ-CARRAGEENAN, COLOURED LIGHT BLUE.
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CREDIT: PLEASE CREDIT: DR ANNA TANCZOS, WWW.SCICOMMSTUDIOS.CO.UK

A novel aqueous lubricant technology designed to help people who suffer from a dry mouth is between four and five times more effective than existing commercially available products, according to laboratory tests.

Developed by scientists at the University of Leeds, the saliva substitute is described as comparable to natural saliva in the way it hydrates the mouth and acts as a lubricant when food is chewed.

Under a powerful microscope, the molecules in the substance - known as a microgel - appear as a lattice-like network or sponge which bind onto the surface of the mouth. Surrounding the microgel is a polysaccharide-based hydrogel which traps water. This dual function will keep the mouth feeling hydrated for longer.

Professor Anwesha Sarkar, who has led the development of the saliva substitute, said: “Our laboratory benchmarking reveals that this substance will have a longer-lasting effect.

“The problem with many of the existing commercial products is they are only effective for short periods because they do not bind to the surface of the mouth, with people having to frequently reapply the substance, sometimes while they are talking or as they eat.

“That affects people’s quality of life.”

Results from the laboratory evaluation - “Benchmarking of a microgel-reinforced hydrogel-based aqueous lubricant against commercial saliva substitutes” - are reported today (Monday, November 20) in the journal Scientific Reports.

The performance of the newly developed substance in comparison to existing products is due to a process called adsorption. Adsorption is the ability of a molecule to bind to something, in this case the surface of the inside of the mouth.

Benchmark results

The novel microgel comes in two forms: one made with a dairy protein and the other a vegan version using a potato protein.

The new substance was benchmarked against eight commercially available saliva substitutes including Boots own brand product - Biotene; Oralieve; Saliveze; and Glandosane. All the benchmarking was done in a laboratory on an artificial tongue-like surface and did not involve human subjects.

The testing revealed the Leeds product had a lower level of desorption - the opposite of adsorption - which is how much lubricant was lost from the surface of the synthetic tongue.

With the commercially available products, between 23% to 58% percent of the lubricant was lost. With the saliva substitute developed at Leeds, the figure was just 7%. The dairy version slightly outperformed the vegan version.

Dr Olivia Pabois, a Research Fellow at Leeds and first author in the paper, said: “The test results provide a robust proof of concept that that our material is likely to be more effective under real-world conditions and could offer relief up to five times longer than the existing products.

“The results of the benchmarking show favourable results in three key area. Our microgel provides high moisturisation, it binds strongly with the surfaces of the mouth and is an effective lubricant, making it more comfortable for people to eat and talk.”

The substances used in the production of the saliva substitute - diary and plant proteins and carbohydrates - are non-toxic to humans and non-caloric.

Although testing of the new product has involved just laboratory analysis, the scientific team believe the results will be replicated in human trials.

The authors of the study are looking to translate the lubricant technology into commercially available products, to improve the quality of life of people who experience debilitating dry mouth conditions.

Xerostomia – healthcare burden

A dry mouth or xerostomia, to give it its medical name, is a common condition which affects around one in ten of the population, and is prevalent among older people and people who have had cancer treatment or need to take a mix of medicines.

In severe cases, a dry mouth results in people having discomfort swallowing and leads to malnutrition and dental problems, all of which increase the burden on healthcare systems.

The paper - “Benchmarking of a microgel-reinforced hydrogel-based aqueous lubricant against commercial saliva substitutes” - can be downloaded from the Scientific Reports website when the embargo lifts - https://doi.org/10.1038/s41598-023-46108-w. The authors are Olivia Pabois, Alejandro Avila-Sierra, Marco Ramaioli, Mingduo Mu, Yasmin Message, Kwan-Mo You, Evangelos Liamas, Ben Kew, Kalpana Durga, Lisa Doherty and Anwesha Sarkar.

END

A potato protein - coloured dark green - forms the mesh-like architecture of the hydrated microgel, partially coated by a hydrogel made by a polysaccharide xanthan gum, shown in light green.

CREDIT

Dr Anna Tanczos, www.SciCommStudios.co.uk

JOURNAL

Scientific Reports

DOI

10.1038/s41598-023-46108-w

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Benchmarking of a microgel-reinforced hydrogel-based aqueous lubricant against commercial saliva substitutes

Dwarf galaxies use 10-million-year quiet period to churn out stars

Peer-Reviewed Publication

UNIVERSITY OF MICHIGAN

Images

ANN ARBOR—If you look at massive galaxies teeming with stars, you might be forgiven in thinking they are star factories, churning out brilliant balls of gas. But actually, less evolved dwarf galaxies have bigger regions of star factories, with higher rates of star formation.

Now, University of Michigan researchers have discovered the reason underlying this: These galaxies enjoy a 10-million-year delay in blowing out the gas cluttering up their environments. Star-forming regions are able to hang on to their gas and dust, allowing more stars to coalesce and evolve.

In these relatively pristine dwarf galaxies, massive stars—stars about 20 to 200 times the mass of our sun—collapse into black holes instead of exploding as supernovae. But in more evolved, polluted galaxies, like our Milky Way, they are more likely to explode, thereby generating a collective superwind. Gas and dust get blasted out of the galaxy, and star formation quickly stops.

Their findings are published in the Astrophysical Journal.

"As stars go supernova, they pollute their environment by producing and releasing metals," said Michelle Jecmen, study first author and an undergraduate researcher. "We argue that at low metallicity—galaxy environments that are relatively unpolluted—there is a 10-million-year delay in the start of strong superwinds, which, in turn, results in higher star formation.”

The U-M researchers point to what's called the Hubble tuning fork, a diagram that depicts the way astronomer Edwin Hubble classified galaxies. In the handle of the tuning fork are the largest galaxies. Huge, round and brimming with stars, these galaxies have already turned all of their gas into stars. Along the tines of the tuning fork are spiral galaxies that do have gas and star-forming regions along their compact arms. At the end of the tuning fork's tines are the least evolved, smallest galaxies.

"But these dwarf galaxies have just these really mondo star-forming regions," said U-M astronomer Sally Oey, senior author of the study. "There have been some ideas around why that is, but Michelle's finding offers a very nice explanation: These galaxies have trouble stopping their star formation because they don't blow away their gas."

Additionally, this 10-million-year period of quiet offers astronomers the opportunity to peer at scenarios similar to the cosmic dawn, a period of time just after the Big Bang, Jecmen said. In pristine dwarf galaxies, gas clumps together and forms gaps through which radiation can escape. This previously known phenomenon is called the "picket fence" model, with UV radiation escaping between slats in the fence. The delay explains why gas would have had time to clump together.

Ultraviolet radiation is important because it ionizes hydrogen—a process that also occurred right after the Big Bang, causing the universe to go from opaque to transparent.

"And so looking at low-metallicity dwarf galaxies with lots of UV radiation is somewhat similar to looking all the way back to the cosmic dawn," Jecmen said. "Understanding the time near the Big Bang is so interesting. It's foundational to our knowledge. It's something that happened so long ago—it's so fascinating that we can see sort of similar situations in galaxies that exist today."

A second study, published in the Astrophysical Journal Letters and led by Oey, used the Hubble Space Telescope to look at Mrk 71, a region in a nearby dwarf galaxy about 10 million light years away. In Mrk 71, the team found observational evidence of Jecmen's scenario. Using a new technique with the Hubble Space Telescope, the team employed a filter set that looks at the light of triply ionized carbon.

In more evolved galaxies with lots of supernova explosions, those explosions heat gas in a star cluster to very high temperatures—to millions of degrees Kelvin, Oey said. As this hot superwind expands, it blasts the rest of the gas out of the star clusters. But in low metallicity environments such as Mrk 71, where stars aren't blowing up, energy within the region is radiated away. It doesn't have the chance to form a superwind.

The team's filters picked up a diffuse glow of the ionized carbon throughout Mrk 71, demonstrating that the energy is radiating away. Therefore, there is no hot superwind, instead allowing dense gas to remain throughout the environment.

Oey and Jecmen say there are many implications for their work.

"Our findings may also be important in explaining the properties of galaxies that are being seen at cosmic dawn by the James Webb Space Telescope right now," Oey said. "I think we're still in the process of understanding the consequences."

Studies:

Delayed massive-star mechanical feedback at low metallicity

Nebular C IV 1550 imaging of the metal-poor starburst Mrk 71: Direct evidence of catastrophic cooling

JOURNAL

The Astrophysical Journal

DOI

10.3847/1538-4357/ad0460

METHOD OF RESEARCH

Computational simulation/modeling

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Delayed Massive-star Mechanical Feedback at Low Metallicity

AI recognizes the tempo and stages of embryonic development

How can we reliably and objectively characterize the speed and various stages of embryonic development? With the help of artificial intelligence! Researchers at the University of Konstanz present an automated method.

Peer-Reviewed Publication

UNIVERSITY OF KONSTANZ

Animal embryos go through a series of characteristic developmental stages on their journey from a fertilized egg cell to a functional organism. This biological process is largely genetically controlled and follows a similar pattern across different animal species. Yet, there are differences in the details – between individual species and even among embryos of the same species. For example, the tempo at which individual embryonic stages are passed through can vary. Such variations in embryonic development are considered an important driver of evolution, as they can lead to new characteristics, thus promoting evolutionary adaptations and biodiversity.

Studying the embryonic development of animals is therefore of great importance to better understand evolutionary mechanisms. But how can differences in embryonic development, such as the timing of developmental stages, be recorded objectively and efficiently? Researchers at the University of Konstanz led by systems biologist Patrick Müller are developing and using methods based on artificial intelligence (AI). In their current article in Nature Methods, they describe a novel approach that automatically captures the tempo of development processes and recognizes characteristic stages without human input – standardized and across species boundaries.

Every embryo is a little different
Our current knowledge of animal embryogenesis and individual developmental stages is based on studies in which embryos of different ages were observed under the microscope and described in detail. Thanks to this painstaking manual work, reference books with idealized depictions of individual embryonic stages are available for many animal species today. "However, embryos often do not look exactly the same under the microscope as they do in the schematic drawings. And the transitions between individual stages are not abrupt, but more gradual," explains Müller. Manually assigning an embryo to the various stages of development is therefore not trivial even for experts and a bit subjective.

What makes it even more difficult: Embryonic development does not always follow the expected timetable. "Various factors can influence the timing of embryonic development, such as temperature," explains Müller. The AI-supported method he and his colleagues developed is a substantial step forward. For a first application example, the researchers trained their Twin Network with more than 3 million images of zebrafish embryos that were developing healthily. They then used the resulting AI model to automatically determine the developmental age of other zebrafish embryos.

Objective, accurate and generalizable
The researchers were able to demonstrate that the AI is capable of identifying key steps in zebrafish embryogenesis and detecting individual stages of development fully automatically and without human input. In their study, the researchers used the AI system to compare the developmental stage of embryos and describe the temperature dependence of embryonic development in zebrafish. Although the AI was trained with images of normally developing embryos, it was also able to identify malformations that can occur spontaneously in a certain percentage of embryos or that may be triggered by environmental toxins.

In a final step, the researchers transferred the method to other animal species, such as sticklebacks or the worm Caenorhabditis elegans, which is evolutionarily quite distant from zebrafish. "Once the necessary image material is available, our Twin Network-based method can be used to analyze the embryonic development of various animal species in terms of time and stages. Even if no comparative data for the animal species exists, our system works in an objective, standardized way", Müller explains. The method therefore holds great potential for studying the development and evolution of previously uncharacterized animal species.

Key facts:

EMBARGOED UNTIL THURSDAY, 23 NOVEMBER 2023, 17:00 CET (16:00 LONDON TIME, 11:00 U.S. EASTERN TIME)
Original publication: N. Toulany, H. Morales-Navarrete, D. Čapek, J. Grathwohl, M. Ünalan & P. Müller (2023) Uncovering developmental time and tempo using deep learning. Nature Methods; doi: 10.1038/s41592-023-02083-8
Konstanz researchers develop AI model that objectively records characteristic stages and tempo of embryonic development in animals without human input
Open science: The authors have made the Twin-Network open source code and their research data available for free on GitHub and KonDATA.
Funding: European Research Council (ERC), German Research Foundation (DFG), Max Planck Society (MPG), European Molecular Biology Organization (EMBO), Interdisciplinary Graduate School of Medicine (IZKF) University of Tübingen, Blue Sky funding programme of the University of Konstanz

Note to editors:
You can download an image here:

Link: https://www.uni-konstanz.de/fileadmin/pi/fileserver/2023/embryonalentwicklung.jpg

Caption: Zebrafish embryos go through characteristic developmental stages, but even sibling embryos differ in the speed of these stages. Artificial intelligence can be used to calculate differences between embryos in terms of development tempo, characteristic developmental stages and structural differences.

Image: © Patrick Müller, Nikan Toulany

JOURNAL

Nature Methods

DOI

10.1038/s41592-023-02083-8

ARTICLE TITLE

Uncovering developmental time and tempo using deep learning

ARTICLE PUBLICATION DATE

23-Nov-2023

Researchers obtain promising results against capacity loss in vanadium batteries

A computational study conducted in Brazil could help extend the working lives of these batteries, which are widely used by utilities and manufacturers.

Peer-Reviewed Publication

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO

Researchers obtain promising results against capacity loss in vanadium batteries — IMAGE:
THE STUDY INVOLVED COMPUTER SIMULATIONS DESIGNED TO FIND OUT HOW ION LEAKAGE BETWEEN THE ANOLYTE AND CATHOLYTE, CALLED TRANSPORT LOSS, LEADS TO BATTERY DEACTIVATION
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CREDIT: CDMF

An article by researchers at the Center for Development of Functional Materials (CDMF) in Brazil describes a successful strategy to mitigate charge capacity loss in vanadium redox flow batteries, which are used by electric power utilities among other industries and can accumulate large amounts of energy. The article is published in the Chemical Engineering Journal.

CDMF is a Research, Innovation and Dissemination Center (RIDC) funded by FAPESP and hosted by the Federal University of São Carlos (UFSCar) in São Paulo state.

The study involved computer simulations designed to find out how ion leakage between the anolyte and catholyte, called transport loss, leads to battery deactivation, and how to mitigate this loss so as to keep ion concentration constant over time. Initially, the researchers estimated the effects of current density, active species concentration and volumetric flow on capacity loss. The second stage sought optimal conditions to minimize capacity loss based on the flow between electrolyte tanks in the opposite direction to cross-contamination (transport of electroactive species through the membrane).

The results showed current density and active species concentration to be the main variables affecting capacity loss. According to the researchers, their approach successfully mitigated cross-contamination in different combinations of the two variables, providing an optimal flow between electrolyte tanks under different operating conditions.

Ernesto Pereira, last author of the article and a professor at UFSCar, noted that the main advantage of redox flow batteries is lack of electrode aging as the electroactive components are dissolved in solutions instead of being coated onto electrodes.

Commercial vanadium redox flow batteries are expected to have a longer lifetime than other types, although the study was conducted on a small scale. “Energy efficiency loss due to aging is minimal, given the slow pace of aging,” he said.

The researchers explained that they are exploring and analyzing flow batteries computationally, with commercial batteries as a model, as part of a broader strategy that includes the development of novel organic substances for this type of battery.

About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

JOURNAL

Chemical Engineering Journal

DOI

10.1016/j.cej.2023.145336

ARTICLE TITLE

Mitigating the capacity loss by crossover transport in vanadium redox flow battery: A chemometric efficient strategy proposed using finite element method simulation

Review article shows key role of Brazil in research on sugarcane for bioenergy

The study by researchers at the University of São Paulo also shows that genetic engineering techniques need to be improved in order to increase ethanol production without expanding crop acreage, a strategy considered crucial to cope with climate change

Peer-Reviewed Publication

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO

The key role of Brazil in research on sugarcane for bioenergy — IMAGE:
THE STUDY WAS CONDUCTED AT THE UNIVERSITY OF SÃO PAULO’S LABORATORY OF PLANT PHYSIOLOGICAL ECOLOGY
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CREDIT: MARCOS BUCKERIDGE

Publications on sugarcane have increased exponentially since 2006 worldwide, and Brazil has had more articles published on the topic than any other country in the period, according to a review in BioEnergy Research.

The number of articles on the subject averaged about five per year between 1999 and 2006 but had reached 327 by 2021. Brazil has twice as many articles on sugarcane as the United States, which ranks first in the world for scientific publications in general. Brazil is also ahead of Australia, China and India, which are also major sugarcane growers.

According to the authors of the review, who are affiliated with the Laboratory of Plant Physiological Ecology (LAFIECO) at the University of São Paulo’s Institute of Biosciences (IB-USP), these statistics highlight Brazil’s importance to global sustainability efforts.

“Sugarcane is one of Brazil’s main tools for coping with climate change as ethanol from sugarcane is one of the most important renewable biofuels that can replace fossil fuels. However, there isn’t enough ethanol in the world. More needs to be produced, and this requires genetic improvement of sugarcane,” said Marcos Buckeridge, last author of the review and head of LAFIECO.

The study was funded by FAPESP via three projects (19/13936-0, 22/05524-7 and 22/00441-6).

The review also discusses the history of sugarcane genetic improvement in Brazil from the arrival of the Portuguese to the currently available varieties. “Despite all the improvement, the genetic engineering strategies applied to sugarcane need to advance further compared to other crops. Moreover, we’ve reached a limit in genetic terms: we’ll have to increase the number of cells or their size for the plant to store more sugar, and this requires sophisticated techniques. Big data, advanced analytical methods, bioinformatics and substantial computational resources, among others, are needed to help improve sugarcane’s physiological performance and yield without expanding crop acreage,” Buckeridge explained.

Challenges ahead

Scientists all over the world who aim to control the behavior of sugarcane with precision and leverage its potential to help cope with the extreme droughts and floods that are part of climate change face two challenges. The first is the need for better genome sequencing. In Brazil, this effort is being led by Diego Pachon, a researcher at the University of São Paulo’s Center for Nuclear Energy in Agriculture (CENA-USP).

Once precise whole genome sequencing of sugarcane is successfully obtained, the next step will be to develop techniques capable of making specific modifications in the genome. The main hope for most scientists resides in CRISPR-Cas9 gene editing, currently being tested by Marcelo Menossi, a researcher at the State University of Campinas’s Institute of Biology (IB-UNICAMP).

Progress has also been achieved in the field in recent years in other major sugarcane production and research centers, such as the United States, India and Australia.

The review of the literature conducted by LAFIECO was supported by INCT Bioethanol, one of the National Institutes of Science and Technology (known as INCTs, the Portuguese-language acronym) in São Paulo state funded by FAPESP and the National Scientific and Technological Development Council (CNPq) – and the Research Center for Greenhouse Gas Innovation (RCGI), an Engineering Research Center (ERC) established by FAPESP and Shell at the University of São Paulo’s Engineering School (POLI-USP).

About São Paulo Research Foundation (FAPESP)

JOURNAL

BioEnergy Research

DOI

10.1007/s12155-023-10649-9

ARTICLE TITLE

Biotechnologies to Improve Sugarcane Productivity in a Climate Change Scenario

Maternal vaccination against COVID-19 lowered risk of preterm births, Stanford study finds

Peer-Reviewed Publication

STANFORD UNIVERSITY

During the first two years of the pandemic, a COVID-19 infection during pregnancy increased the risk of preterm birth and NICU hospitalizations. However, by 2022, when COVID-19 vaccines were readily available in the United States, this effect disappeared – suggesting that vaccination against the coronavirus may have prevented thousands of preterm births, according to a new study led by Stanford sociologist Florencia Torche.

The study’s findings, published Nov. 27 in the journal Proceedings of the National Academy of Sciences, show how vaccination against COVID-19 may have helped a generation of U.S. children avoid the long-term health issues and costs associated with premature delivery. As previous studies have shown, children who are born prematurely are more likely to encounter educational and economic setbacks later in life.

“The effects of COVID-19 on infant health may be among the most enduring legacies of the pandemic,” said Torche, the Dunlevie Family Professor in the School of Humanities and Sciences. “I hope the study provides strong evidence supporting the benefits of vaccination for the health of the next generation.”

Studying the effects of COVID-19 infection

Torche, along with Jenna Nobles at the University of Wisconsin-Madison, based their study on natality data for California, a diverse and populous state that accounts for 12% of all U.S. births.

In June 2020, California began recording confirmed or presumed cases of COVID-19 infection for all mothers giving birth. This is also when the researchers began their analysis, focusing on facilities with documented, universal testing.

The researchers identified infants with siblings in the California birth records, which allowed them to compare “treated” infants exposed to COVID-19 infection in utero with their “untreated” siblings who did not experience a COVID infection.

The researchers also took into consideration the zip code of the mother’s residence to compare areas that had low and high uptakes of vaccination against COVID-19.

Some of Torche and Nobles’ key findings include:

Maternal COVID-19 infection increases the probability of preterm delivery, defined as a birth that occurs before 37 weeks of gestation, by 1.2 percentage points, from 7.1 to 8.3%. “This effect is roughly equivalent to in utero exposure to a 9 percentage point increase in the area-level unemployment rate – or to high-intensity wildfire smoke for 20 days – an enormous impact,” the researchers write.
Maternal COVID-19 infection also led to higher rates of premature delivery before 32 weeks of gestation, resulting in infants facing the highest risk of mortality, morbidity, and developmental difficulties later in life.
By January 2022, the impacts of COVID-19 on preterm births dropped to zero, but zip codes that had high vaccination rates saw the harmful effects disappear a year earlier than areas with a slower vaccination uptake.

How COVID-19 may exacerbate inequality

Torche and Nobles’ study is one of the first to offer a causal estimate of the impact of maternal COVID-19 infection on neonatal health.

With vaccine rates for the most recent booster hovering at about 7% of U.S. adults, Torche hopes the study emphasizes the importance of staying protected against the virus.

“Unfortunately, even if the adverse impact of COVID-19 infection on preterm birth has plummeted to zero, this adverse impact is likely to emerge again as the virus continues to evolve and mutate, and as vaccine-driven immunity wanes,” Torche said.

The study builds on Torche and Nobles’ previous work that looked at the socioeconomic disparities of the COVID-19 pandemic and its impacts on inequality in the U.S. – an issue Torche is concerned about here, too.

“Barriers to vaccination are higher in disadvantaged and racialized populations, including people with less education and those living in rural areas, i.e. populations that experience much worse infant health even in absence of COVID-19,” Torche said. “This suggests COVID-19 will further exacerbate disparities in infant health in the United States.”

This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and by the National Science Foundation (NSF).

DOI

10.1073/pnas.2311573120

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Vaccination, immunity, and the changing impact of COVID-19 on infant health

ARTICLE PUBLICATION DATE

27-Nov-2023

Study: Spike in premature births caused by COVID, halted by vaccines

Peer-Reviewed Publication

UNIVERSITY OF WISCONSIN-MADISON

MADISON, Wis. — COVID-19 caused an alarming surge in premature births, but vaccines were key to returning the early birth rate to pre-pandemic levels, according to a new analysis of California birth records.

“The effect of maternal COVID infection from the onset of the pandemic into 2023 is large, increasing the risk of preterm births over that time by 1.2 percentage points,” says Jenna Nobles, a University of Wisconsin–Madison sociology professor. “To move the needle on preterm birth that much is akin to a disastrous environmental exposure, like weeks of breathing intense wildfire smoke.”

But the first two years of the pandemic alone were far worse for many pregnancies, according to findings Nobles and co-author Florencia Torche, a Stanford University sociology professor, published today in the Proceedings of the National Academy of Sciences.

The virus that causes COVID-19 endangers pregnancies by causing immune and inflammation responses, and via deterioration of the placenta. One consequence is early interruption of the pregnancy and birth well in advance of the end of the expected 39- to 40-week gestation.

As the virus spread from July to November of 2020, the likelihood that a mother with COVID-19 in California would give birth more than three weeks before the due date was 5.4 percentage points higher than anticipated — 12.3% instead of 6.9% — according to the new study.

The researchers measured the impact of the pandemic with the help of birth records for California’s nearly 40 million people, using information on birth timing and the comparison of sibling births to help control for the pandemic’s disparate impacts on different demographic groups. They found the excess risk of preterm birth fell slightly in early 2021 before dropping steeply in 2022, at which point maternal COVID-19 infection in pregnancy caused no excess risk of preterm birth for infants.

Vaccines contributed to that decrease, the researchers say, an effect that jumps out when the birth records are divided up geographically.

“In ZIP codes with the highest vaccination rates, the excess risk of preterm birth declines much faster. By summer 2021, having COVID-19 in pregnancy had no effect on preterm birth risk in these communities. It takes almost a year longer for that to happen in the ZIP codes with the lowest vaccine uptake,” Nobles says. “That highlights how protective COVID vaccines have been. By increasing immunity faster, early vaccination uptake likely prevented thousands of preterm births in the U.S.”

Preterm birth is associated with a host of short- and long-term health problems and deficiencies for the children and their families. It’s the leading contributor to infant mortality, and cutting short development in the womb can require additional medical attention that costs, on average, more than $80,000 per child. Preterm birth by even just a few weeks reduces expected educational attainment, health and earnings as an adult.

“And we found similar increases, of about 38%, in the risk of very preterm birth — that is pre-32 weeks — when a child is likely to need neonatal intensive care, with the possibility of developmental delays and serious implications for their families as well,” Nobles said.

The evidence showing the positive effects of vaccination in preventing premature births could help allay some of the most prominent concerns voiced as COVID-19 vaccines became available to pregnant patients.

“One big contributor to vaccine hesitancy is that people are worried about safety for the fetus and about the ability to get pregnant,” Nobles says. “We already know there is very little evidence of adverse effects of vaccination on fetal development. The results here are compelling evidence that what will actually harm the fetus is not getting vaccinated. That’s a message practitioners can share with concerned patients.”

The results should be a compelling argument in favor of getting vaccinations and boosters, according to the researchers, even after COVID-related premature birth risk ebbed in California.

“This is still an evolving epidemic, and the rate of vaccine boosters among pregnant people right now is very low,” Nobles says. “The question is, how many more iterations of viral evolution does this need to escape the immunity that we have? It’s miraculous and incredible that we're now down to essentially zero additional preterm births, but it does not indicate that it’s going to be that way in perpetuity.”

This research was supported in part by grants from the National Science Foundation (NSF2049529) and the National Institutes of Health (R21 HD105361-01).

###

— Chris Barncard, barncard@wisc.edu

JOURNAL

Proceedings of the National Academy of Sciences

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

Fractional COVID-19 booster vaccines produce similar immune response as full-doses

Peer-Reviewed Publication

MURDOCH CHILDRENS RESEARCH INSTITUTE

Reducing the dose of a widely used COVID-19 booster vaccine produces a similar immune response in adults to a full-dose with fewer side effects, according to a new study.

The research, led by Murdoch Children's Research Institute (MCRI) and the National Centre for Communicable Diseases in Mongolia, found that a half dose of a Pfizer COVID-19 booster vaccine elicited a non-inferior immune response to a full dose in Mongolian adults who previously had AstraZeneca or Sinopharm COVID-19 shots. But it found half-dose boosting may be less effective in adults primed with the Sputnik V COVID-19 vaccine.

The research is part of an international clinical trial, which also includes Australia and Indonesia, that’s investigating the different COVID-19 booster shot approaches to help guide future vaccination strategies. The Coalition for Epidemic Preparedness Innovations (CEPI) is funding the trial that is being overseen by MCRI.

The first batch of findings, published in The Lancet Regional Health - Western Pacific, and involving 601 participants over 18 years old from Mongolia, reports on the initial responses seen 28-days after vaccination. The study is the first of its kind to assess and compare COVID-19 vaccines widely used in low- and middle-income countries.

MCRI Professor Kim Mulholland, who also sits on the WHO SAGE committee, said the study found that fractional doses elicited an immune response that was non-inferior to a full dose with fewer side effects and was less costly.

“Fractional dosing may improve COVID-19 booster acceptability and uptake and reduce the per-dose cost of COVID-19 booster programs,” he said. Policymakers and immunisation advisory committees can draw upon this data to make flexible boosting schedules decisions.”

The study found half-dose boosted participants reported fewer local reactions than those receiving full doses (60 per cent versus 72 per cent) including less pain and tenderness. They also reported fewer systemic reactions (25 per cent versus 32 per cent) including less fevers, vomiting, diarrhoea and headaches.

The cohort will be followed up at six and 12 months with the data to answer key questions on other aspects of the immune response including the rate of waning and breakthrough infections.

Dr Melanie Saville, Executive Director of R&D at CEPI said; “This CEPI-funded study has generated valuable data about combinations of vaccines that have been widely distributed through COVAX, which will help to inform future booster strategies in countries in the global south. Fractional dosing can contribute to equitable access by making vaccination more acceptable and less costly.”

Researchers from Onoshmed Laboratory, Sukhbaatar District Health Centre, General Laboratory of Clinical Pathology, the University of Melbourne, Mongolian National University of Medical Sciences, Bayangol District Health Centre, Mongolia Ministry of Health and the National Centre for Public Health in Mongolia also contributed to the findings.

Publication: Tsetsegsaikhan Batmunkh, Kerryn A Moore, Helen Thomson, Bolor Altangerel, Otgonjargal Amraa, Naranbaatar Avaa , Lkhagvagaram Batbayar, Khishigjargal Batsukh, Kathryn Bright, Tsogjargal Burentogtokh, Lien Anh Ha Do, Gantuya Dorj, John D Hart, Khulan Javkhlantugs, Sarantsetseg Jigjidsuren, Frances Justice, Shuo Li, Paul V Licciardi, Khaliunaa Mashbaatar, Nadia Mazarakis, Eleanor F G Neal, Cattram Duong Nguyen, Batbayar Ochirbat, Bilegtsaikhan Tsolmon, Alimaa Tuya, Unursaikhan Surenjav, Claire von Mollendorf and Kim Mulholland. ‘Immunogenicity, safety, and reactogenicity of a half-versus full-dose BNT162b2 (Pfizer-BioNTech) booster following a two-dose ChAdOx1 nCoV-19, BBIBP-CorV, or Gam-COVID-Vac priming schedule in Mongolia: a randomised, controlled, non-inferiority trial,’ The Lancet Regional Health - Western Pacific. DOI: 10.1016/j.lanwpc.2023.100953

*The content of this communication is the sole responsibility of the MCRI and does not reflect the views of the NHMRC.

Available for interview:

Professor Kim Mulholland, MCRI Group Leader, New Vaccines

JOURNAL

The Lancet Regional Health - Western Pacific

DOI

10.1016/j.lanwpc.2023.100953

METHOD OF RESEARCH

Randomized controlled/clinical trial

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Immunogenicity, safety, and reactogenicity of a half-versus full-dose BNT162b2 (Pfizer-BioNTech) booster following a two-dose ChAdOx1 nCoV-19, BBIBP-CorV, or Gam-COVID-Vac priming schedule in Mongolia: a randomised, controlled, non-inferiority trial