Stem cell model offers first glimpse of early human embryonic development

It's one of life's most defining moments -- that crucial step in embryonic development, when an indistinct ball of cells rearranges itself into the orderly three-layered structure that sets the stage for all to come. Known as gastrulation, this crucial process unfolds in the third week of human development. "Gastrulation is the origin of our own individualization, the emergence of our axis," says Rockefeller's Ali Brivanlou. "It is the first moment that separates our heads from our behinds."

Observing the molecular underpinnings of this pivotal event would go a long way toward helping scientists prevent miscarriages and developmental disorders. But studying human gastrulation has proven both technologically difficult and ethically complicated, and thus current approaches have had limited success in expanding our understanding of early human development. Now Brivanlou and colleagues have demonstrated how a stem cell model system known as a blastoid can allow the study of the nuances of human gastrulation in the presence of pre-implantation extra-embryonic cell types. Their study, published in Stem Cell Reports, describes the scientific and clinical potential of this new platform.

"Gastrulation was a tremendous black box. We had never seen ourselves at that stage," Brivanlou says. "This moves us closer to understanding how we begin."

A better blastocyst

Prior to implantation, an embryo is a ball of about 250 cells organized as a blastocyst. This elusive ball of cells was difficult to study directly, so scientists developed blastoids -- stem-cell-based blastocyst models. Blastoids can be cloned, experimentally manipulated, and programmed, allowing scientists to study identical blastoids over and over again.

The question was whether blastoids could gastrulate in vitro. Unlike a blastocyst in vivo, which rolls around in the uterus until it attaches to maternal tissue, blastoids were good at modeling the ball of cells from which life emerges, but it remained unclear whether this in vitro model could model later stages of human development. That is, until Brivanlou developed a platform to allow blastoids to attach in vitro, and thereby progress toward gastrulation.

"We were then able to see epiblast symmetry breaking, marked by BRA expression, for the first time with the high molecular resolution," says Riccardo De Santis, a research associate in the Brivanlou lab and lead author on the study. "This allowed us to start asking more detailed questions about the earliest moments of life."

With this unprecedented clarity, the team directly observed two key moments in gastrulation: the first epiblast symmetry-breaking event and the emergence of the molecular markers of the primitive streak and mesoderm upon in vitro attachment.

The primitive streak is a structure that marks the beginning of gastrulation and lays the foundation for the three primary layers of the embryo. One of those layers, the mesoderm, forms during gastrulation and gives rise to muscles, bones, and the circulatory system. The team discovered that, as early as seven days after attachment, they were already able to use molecular markers to detect the earliest signature of a nascent primitive streak and mesodermal cells.

To confirm their findings, the team also compared the blastoid results with data from in vitro attached human embryos and demonstrated that blastoids express the same genes in vitro that a regular embryo would at that stage in vivo, a strong demonstration of the power of blastoids as models for human embryonic development. Further highlighting the power of the lab's in vitro attached blastoid system, the team then used it to demonstrate that pathways that regulate the rise of the primitive streak and mesoderm in vivo also regulate blastoids symmetry breaking in vitro -- all with nothing but stem-cell-derived blastoid models.

Along the way, the team also demonstrated that gastrulation in vitro can begin at day 12, earlier than once thought. "This will change textbooks," Brivanlou says. "We've contributed to redefining the molecular signature and timing of the onset of gastrulation upon in vitro attachment."

Therapeutic possibilities

The results demonstrate that blastoids, when combined with the Brivanlou lab's unique attachment platform, are now capable of conveying insights into early human development that have long been inaccessible. De Santis envisions a future in which blastoid-based research leads to advancements in diagnosing and treating developmental disorders, or offers insights into potential causes of early miscarriages during gastrulation.

"Many couples can't have babies because the embryo doesn't attach properly, and many miscarriages occur in the first few weeks of pregnancy," De Santis explains. "We now have a model system that can help us understand the molecular mechanism that defines whether a pregnancy will be successful or not." In the near future, De Santis hopes to combine this method with machine learning to help predict pregnancy outcomes and the trajectories of developmental disorders by observing how model blastoids built with particular genetic makeups fare in vitro.

Read more at Science Daily

World's first successful embryo transfer in rhinos paves the way for saving the northern white rhinos from extinction

BioRescue, an international consortium of scientists and conservationists, succeeded in achieving the world's first pregnancy of a rhinoceros after an embryo transfer. The southern white rhino embryo was produced in vitro from collected egg cells and sperm and transferred into a southern white rhino surrogate mother at the Ol Pejeta Conservancy in Kenya on September 24, 2023. The BioRescue team confirmed a pregnancy of 70 days with a well-developed 6.4 cm long male embryo. The successful embryo transfer and pregnancy are a proof of concept and allow to now safely move to the transfer of northern white rhino embryos -- a cornerstone in the mission to save the northern white rhino from extinction.

On September 24, 2023, the BioRescue scientists and veterinarians, led by the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW), transferred two southern white rhino embryos into Curra, a southern white rhinoceros, selected as a surrogate mother at the Ol Pejeta Conservancy in Kenya. The oocytes used in producing the embryos were retrieved from Elenore, a southern white rhinoceros living in the Pairi Daiza Zoo in Belgium. The sperm used for fertilisation originated from the male Athos from the Zoo Salzburg in Hellbrunn, Austria. The oocytes from Elenore were fertilised in vitro by intracytoplasmic sperm injection (ICSI) and developed into blastoscysts at Avantea's laboratories in Cremona, Italy. For the embryo transfer in Kenya, the BioRescue scientists transferred two embryos to increase the chance of a successful outcome.

So far, the BioRescue team has performed 13 embryo transfers in rhinoceroses, three in Kenya and ten in Europe. Previously, an embryo transfer, which is a widely used technique in domestic species, has never been attempted in rhinos. BioRescue scientists developed the necessary techniques, by building on decades of their own research.

Currently, there are only two northern white rhinos left in the world: The female Najin and her daughter Fatu. Additionally, living cells from 12 different northern white rhino individuals are stored in liquid nitrogen. The last two females currently live in Kenya, at Ol Pejeta Conservancy, where they are guarded and cared for day and night. Since 2019, the BioRescue conservation science programme produced and cryopreserved 30 northern white rhino embryos. These are currently stored in liquid nitrogen at minus 196 degrees Celsius in Berlin, Germany, and Cremona, Italy, awaiting embryo transfer into southern white rhino surrogate mothers. The successful transfer of a southern white rhino embryo is a proof of concept that allows to take this crucial step -- an embryo transfer with a northern white rhino embryo -- for the first time.

The embryo transfer in this subspecies is entirely new ground as a veterinary and scientific procedure, and all protocols, methods and pieces of equipment had to be newly developed from scratch. As it is the established routine with all BioRescue procedures, the embryo transfers are accompanied by an ethical assessment conducted by Padua University. This was also the case in September, when all participants of the embryo transfer filled out a questionnaire that proposed any possible scenarios during the procedure, and attendant risks to animals and participants.

The vasectomised, sterile teaser bull Ouwan mated with Curra on September 17 and 18, signalling the ideal timing for the embryo transfer, which took place on September 24. After the procedure until November 2023, Curra was monitored on a daily basis in the enclosure at the Ol Pejeta Conservancy. During this period, Ouwan showed no further interest in Curra, a first sign of a successful embryo transfer resulting in pregnancy. The BioRescue team was scheduled for November 28 to perform a pregnancy check in Curra, but the teaser bull Ouwan was found dead on November 22 and Curra was found dead on November 25. Apparently, extremely heavy rains led to a flooding of the surrogate enclosure and set free dormant clostridianbacteria spores. The dissection of the animals revealed a severe systemic infection by a clostridian bacterial strain and resultant intoxication by the bacterial toxin. It also revealed that Curra was pregnant with a 70 days old male fetus that was 6.4 cm long. Tissue samples of the fetus were collected and transported to the Max Delbrück Centre for Molecular Medicine and the Leibniz-IZW in Berlin, Germany. In January 2024, it was confirmed through the analysis of the fetus DNA that the pregnancy resulted from the embryo transfer.

When the BioRescue team arrived in Kenya on November 28, the preliminary results indicated an intoxication with the clostridian bacterial strains Paraclostridium bifermentans and Paenicolostridium sordellii. Immediately after the incident, the BioRescue team, including Kenya Wildlife Service, Wildlife Training Research Institute, Ol Pejeta Conservancy and Safari Park Dvur Králové formed a crisis team on site and established fast and effective measures to protect all current semi-captive rhinos including the last two northern white rhinos Najin and Fatu. The measures included a vaccination programme, quarantine of affected areas and fencing of new emergency enclosures.

The next steps in the BioRescue research programme included the selection and preparation of a new teaser bull. The bull will allow the scientists to know when a possible surrogate female is ready to receive an embryo implantation. The team also has to select the next surrogate mothers. After these steps, which will take several months, an embryo transfer with a northern white rhino embryo will be attempted.

Read more at Science Daily

Study confirms lead-in-water causes adverse fetal health outcomes

Lehigh University and Bentley University health economics researchers have published the first study to confirm a causal relationship between lead-in-water and adverse fetal health outcomes. Although many studies have found a correlation between lead exposure and health, a causal link had been lacking in the literature -- until now.

The study has recently been published in the Journal of Health Economics in an article titled: Lead in Drinking Water and Birth Outcomes: A Tale of Two Water Treatment Plants.

The researchers,Muzhe Yang, professor of economics at Lehigh University and Dhaval M. Dave of Bentley University, used data on the exact home addresses of pregnant women living in the City of Newark together with information on the spatial boundary separating areas within the city serviced by two water treatment plants. Their study exploits an exogenous, or external, change in the water's pH level that caused lead to leach into the drinking water of one plant's service area, but not the other's, to identify the causal effect of prenatal lead exposure on fetal health.

Yang and his colleague found robust evidence of adverse health impacts. Among the findings: prenatal lead exposure increased the chance of low-birth-weight by 18% and increased the probability of preterm birth by 19%.

"These findings have important policy implications," says Yang, "especially in light of the substantial number of lead water pipes that remain in use as part of the aging infrastructure and the cost-benefit calculus of lead abatement interventions."

Yang notes that the crisis in Newark is not singular, but rather emblematic of the nation's aging water infrastructure.

According to the American Academy of Pediatrics, there is no safe threshold for lead exposure that has been identified for children. Lead collects over time in the human body through repeated exposure and is stored in the bones alongside calcium. In utero exposure is of particular concern as lead in the mother's bones can be mobilized during pregnancy and released as a calcium substitute to aid in the formation of the bones of the fetus, and lead in a mother's blood can also cross the placenta, exposing the fetus to lead poisoning. Prenatal lead exposure has been associated with impaired neural development putting children at risk for cognitive impairment later.

The Environmental Protection Agency (EPA) estimates that drinking water may account for more than 20 percent of total lead exposure for adults and 40 to 60 percent for infants.

In the introduction to their paper, Yang and Dave write: "Drinking water contamination is becoming an increasingly important and widespread source of prenatal exposure to environmental pollution. Between 2018 and 2020, nearly 30 million people received their drinking water from community water systems that were in violation of the EPA's Lead and Copper Rule, which sets maximum enforceable levels of these metals in drinking water…"

Read more at Science Daily

How placentas evolved in mammals

The fossil record tells us about ancient life through the preserved remains of body parts like bones, teeth and turtle shells. But how to study the history of soft tissues and organs, which can decay quickly, leaving little evidence behind?

In a new study, scientists use gene expression patterns, called transcriptomics, to investigate the ancient origins of one organ: the placenta, which is vital to pregnancy.

"In some mammals, like humans, the placenta is really invasive, so it invades all the way through the wall of the uterus, into the maternal tissue. In other mammals, the placenta just touches the wall of the uterus. And then there's everything in between," says senior author Vincent J. Lynch, PhD, associate professor of biological sciences in the University at Buffalo College of Arts and Sciences.

"So what kind of placentas were early placentas?" he says. "We use gene expression patterns to reconstruct the evolution of the placenta and predict what the placenta of the last common ancestor of eutherian mammals looked like. Our data tells us that this placenta was invasive, and that non-invasive placentas evolved multiple times among mammals. This addresses a 150-year-old mystery: People have been debating what kind of placenta the first one was since then."

As Lynch explains, all living mammals other than marsupials and egg-laying monotremes are eutherians, which have long pregnancies in which the developing fetus evokes a strong physiological response in the mother.

The research was published on June 30 in eLife. Lynch led the study with first author Katelyn Mika, PhD, University of Chicago postdoctoral scholar in human genetics and in organismal biology and anatomy. Camilla M. Whittington, PhD, and Bronwyn M. McAllan, PhD, both at the University of Sydney, are also co-authors.

"Our ability to ask how the placenta might have functioned at different points during its evolution by using the gene expression profiles of currently existing animals to reconstruct the ancestors is a really cool approach and provides us more information on how changing gene expression can contribute to the evolution of a new trait," Mika says.

To conduct the analysis, the team compared the genes active in the uterus of various mammals during pregnancy. After finding that these gene expression profiles correlated with the degree of placental invasiveness, the scientists used their data to predict what ancestral mammalian placentas looked like.

The study included about 20 species, such as the egg-laying platypus, pouch-bearing marsupials, and a range of eutherian mammals that give birth to live young.

The small subset is one limitation of the analysis: The authors write in eLife that research on a larger number of species is needed to help determine the strength of the findings.

Nevertheless, the study makes important contributions in understanding how pregnancy evolved, Lynch says. The results could also benefit modern medicine.

Read more at Science Daily

Reducing air pollution can support healthy brain development

A new study finds that having a portable air cleaner in the home can reduce the negative impacts of air pollution on brain development in children.

Simon Fraser University researchers collaborated with U.S. and Mongolian scientists to study the benefits of using air filters to reduce exposure to air pollution during pregnancy, and assessed the impact on children's intelligence.

The researchers note that their randomized controlled trial is the first study of its kind to document the impacts of air pollution reduction on cognition in children.

Beginning in 2014, the team recruited 540 pregnant women in Ulaanbaatar, Mongolia to participate in the Ulaanbaatar Gestation and Air Pollution Research (UGAAR) study. Ulaanbaatar has some of the worst air quality in the world, well exceeding guidelines set by the World Health Organization (WHO).

The women were less than 18 weeks into their pregnancies and non-smokers who had not previously used air filtering devices in their homes. They were randomly assigned to either the control or intervention group. The intervention group was provided with one or two HEPA filter air cleaners and encouraged to run the air cleaners continuously for the duration of their pregnancies. The air cleaners were removed from the home once the child was born.

The researchers later measured the children's full-scale intelligence quotient (FSIQ) at four years of age using the Weschler Preschool and Primary Scale of Intelligence.

They found that the children born to mothers who had used the air cleaners had an average FSIQ that was 2.8-points higher than the group that did not use an air cleaner during pregnancy.

"These results, combined with evidence from previous studies, strongly implicate air pollution as a threat to brain development," says Ryan Allen, professor of environmental health in SFU's Faculty of Health Sciences. "But the good news is that reducing exposure had clear benefits."

Children in the intervention group also had significantly greater average verbal comprehension index scores, which is consistent with results from previous observational studies. The research suggests that a child's verbal skills may be particularly sensitive to air pollution exposure.

More than 90 per cent of the world's population breathes air with particulate matter concentrations above the WHO guidelines. The researchers suggest the population-level impact of air pollution on brain development could be substantive even if the individual-level effects are modest.

Their study results indicate that reducing exposure to air pollution during pregnancy could improve children's cognitive development around the world.

Read more at Science Daily

Researchers identify neuronal mechanisms that control food cravings during pregnancy

Many people have felt the sudden and uncontrollable urge to eat a certain food. These urges -- known as cravings -- are very common, mostly during pregnancy. During this time, the mother's body undergoes a series of physiological and behavioural changes to create a favourable environment for the embryo's development. However, the frequent consumption of tasty and high calorie foods -- derived from the cravings -- contributes to weight gain and obesity in pregnancy, which can have negative effects on the baby's health.

"There are many myths and popular beliefs regarding these cravings, although the neuronal mechanisms that cause them are not widely known," notes March Claret, lecturer at the Faculty of Medicine and Health Sciences of the University of Barcelona and head of the IDIBAPS Neuronal Control of Metabolism Group. Claret leads, together with the researcher Roberta Haddad-Tóvolli, a study published in the journal Nature Metabolism that provides new evidence on the alterations of the neuronal activity that drive cravings in an animal model.

Dopamine and compulsive eating behaviour

According to the results, during pregnancy, the brain of female mice undergoes changes in the functional connections of the brain reward circuits, as well as the taste and sensorimotor centers. Moreover, just like pregnant women, female mice are more sensitive to sweet food, and they develop binge-eating behaviours towards high calorie foods. "The alteration of these structures made us explore the mesolimbic pathway, one of the signal transmission pathways of dopaminergic neurons. Dopamine is a key neurotransmitter in motivational behaviours," notes Claret, member of the Department of Medicine of the UB and the Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM).

The team observed the levels of dopamine -- and the activity of its receptor, D2R -- to increase in the nucleus accumbens, a brain region involved in the reward circuit. "This finding suggests that the pregnancy induces a full reorganization of the mesolimbic neural circuits through the D2R neurons," notes Haddad-Tóvolli. "These neuronal cells -- and their alteration -- would be responsible for the cravings, since food anxiety, typical during pregnancy, disappeared after blocking their activity."

The team led by Claret and Haddad-Tóvolli showed that persistent cravings have consequences for the offspring. They affect the metabolism and development of neural circuits that regulate food intake, which leads to weight gain, anxiety and eating disorders. "These results are shocking, since many of the studies are focused on the analysis of how the mother's permanent habits -- such as obesity, malnutrition, or chronic stress -- affect the health of the baby. However, this study indicates that short but recurrent behaviours, such as cravings, are enough to increase the psychological and metabolic vulnerability of the offspring," concludes Claret.

The conclusions of the study could contribute to the improvement of nutritional guidelines for pregnant women in order to ensure a proper prenatal nutrition and prevent the development of diseases. Among the participants in the study were Guadalupe Soria and Emma Muñoz-Moreno (IDIBAPS), Analía Bortolozzi (IIBB-CSIC-IDIBAPS) and Emmanuel Valjent (INSERM and University of Montpelier).

Read more at Science Daily

'No level of smoke exposure is safe'

Nearly a quarter of pregnant women say they've been around secondhand smoke -- in their homes, at work, around a friend or relative -- which, according to new research, is linked to epigenetic changes -- meaning changes to how genes are regulated rather than changes to the genetic code itself -- in babies that could raise the risk of developmental disorders and cancer.

The study, published today in Environmental Health Perspectives by researchers at Virginia Commonwealth University Massey Cancer Center, is the first to connect secondhand smoke during pregnancy with epigenetic modifications to disease-related genes, measured at birth, which supports the idea that many adult diseases have their origins in environmental exposures -- such as stress, poor nutrition, pollution or tobacco smoke -- during early development.

"What we recommend to mothers in general is that no level of smoke exposure is safe," said study lead author Bernard Fuemmeler, Ph.D., M.P.H., associate director for population science and interim co-leader of the Cancer Prevention and Control program at VCU Massey Cancer Center. "Even low levels of smoke from secondhand exposure affect epigenetic marks in disease-related pathways. That doesn't mean everyone who is exposed will have a child with some disease outcome, but it contributes to a heightened risk."

Fuemmeler and colleagues analyzed data from 79 pregnant women enrolled in the Newborn Epigenetics Study (NEST) between 2005 and 2011. During the first trimester, all had a concentration of cotinine -- a nicotine byproduct -- in their blood consistent with low levels of smoke exposure, ranging from essentially none to levels consistent with secondhand smoke.

After these women gave birth, the researchers sampled the umbilical cord blood, which is the same blood that circulates through the fetus in utero, and performed what's referred to as an epigenome-wide association study (EWAS) to search for correlations between blood cotinine levels of the mothers during pregnancy and epigenetic patterns in the babies at birth.

When cotinine levels were higher, the newborns were more likely to have epigenetic "marks" on genes that control the development of brain function, as well as genes related to diabetes and cancer.

These marks could mean either unusually many or unusually few molecules bound to the DNA strand, which affects how accessible a particular gene is. If a gene is bound up tightly by lots of marks, then it's harder for molecular machinery to access and less likely to be expressed. On the other hand, if a gene is relatively unencumbered, then it might be expressed at higher levels than normal. Tipping the scale in either direction could lead to disease.

To solidify their results, the team repeated the analysis in a separate sample of 115 women and found changes to two of the same disease-related epigenetic regions -- one that regulates genes involved in inflammation and diabetes and another that regulates cardiovascular and nervous system functions -- are correlated with cotinine levels in mothers.

In all cases, the analyses controlled for race, ethnicity, age, prior number of children and maternal education.

Read more at Science Daily

Genetics, not the intrauterine environment, controls abnormal development

Yale researchers have shown that developmental abnormalities, including those that lead to pregnancy loss and autism, are controlled by the genetics of the fetus and placenta -- and not the mother's intrauterine environment.

The findings are reported in the April 28 online edition of the journal Placenta.

One out of every 33 children is diagnosed with a birth defect each year in the United States, according to the Centers for Disease Control and Prevention (CDC). This translates into one baby born every 4 ½ minutes -- or 120,000 per year.

"Mothers often feel that they are responsible for these defects. But it's not their fault," said senior author Dr. Harvey Kliman, a research scientist in the Department of Obstetrics, Gynecology & Reproductive Services at the Yale School of Medicine. "This new research points to the genetics of these children as being the most important cause."

For the study, Kliman's team examined placental data for nearly 50 sets of identical and non-identical twins. The researchers found that abnormal cell growths called trophoblast inclusions (TIs) which are markers for many developmental abnormalities, occurred with similar frequency in identical twins, while non-identical twins showed a markedly different TI count.

Identical twins share the same DNA sequence; non-identical twins share half of their DNA sequence. The researchers found that identical twins often had the same number of TIs or were within one of having the same TI count. Non-identical twins had TI counts that were, on average, different by four or five.

"This work suggests that developmental abnormalities are much more likely to be due to the genetics of the child, and not the mother's fault," Kliman said.

Lead author Julia Katz, a former Yale undergraduate who is now a medical student at Hofstra University, provided the inspiration for the study.

Katz and her brother, Jesse, who was born underweight and with several congenital abnormalities, are non-identical twins. "I had a lot of guilt, growing up, about why my twin had certain conditions that I didn't," Katz said. "I think mothers also tend to blame themselves."

Katz approached Kliman after a Yale lecture and asked him what causes babies to be born undersized. The conversation led to a discussion about developmental abnormalities and Katz's desire to seek out information about her and her twin's genetics -- including looking at her own placental slides from birth.

It also led Kliman, Katz, and co-author Parker Holzer, a graduate student in the Yale Department of Statistics and Data Science, to conduct the new study.

"Julia's need to resolve this burden is what propelled our study," Kliman said. "Hopefully, this finding will help many other people, as well."

Read more at Science Daily

Researchers learn that pregnant women pass along protective COVID antibodies to their babies

 Antibodies that guard against COVID-19 can transfer from mothers to babies while in the womb, according to a new study from Weill Cornell Medicine and NewYork-Presbyterian researchers published in the American Journal of Obstetrics and Gynecology.

This discovery, published Jan. 22, adds to growing evidence that suggests that pregnant women who generate protective antibodies after contracting the coronavirus often convey some of that natural immunity to their fetuses. The findings also lend support to the idea that vaccinating mothers-to-be may also have benefits for their newborns.

"Since we can now say that the antibodies pregnant women make against COVID-19 have been shown to be passed down to their babies, we suspect that there's a good chance they could pass down the antibodies the body makes after being vaccinated as well," said Dr. Yawei Jenny Yang, an assistant professor of pathology and laboratory medicine at Weill Cornell Medicine and the study's senior author.

Dr. Yang and her team analyzed blood samples from 88 women who gave birth at NewYork-Presbyterian/Weill Cornell Medical Center between March and May 2020, a time when New York City was the global epicenter of the pandemic. All of the women had COVID-19 antibodies in their blood, indicating that they had contracted the virus at some point even though 58 percent of those women had no symptoms. Furthermore, while antibodies were detected in both symptomatic and asymptomatic women, the researchers observed that the concentration of antibodies was significantly higher in symptomatic women. They also found that the general pattern of antibody response was similar to the response seen in other patients, confirming that pregnant women have the same kind of immune response to the virus as the larger patient population -- something that hadn't previously been known for sure, since a woman's immune system changes throughout pregnancy.

In addition, the vast majority of the babies born to these women -- 78 percent -- had detectable antibodies in their umbilical cord blood. There was no evidence that any of the infants had been directly infected with the virus and all were COVID negative at the time of birth, further indicating that the antibodies had crossed the placenta -- the organ that provides oxygen and nutrients to a growing baby during pregnancy -- into the fetal bloodstream. Newborns with symptomatic mothers also had higher antibody levels than those whose mothers had no COVID symptoms.

This data implies that pregnant women could pass along vaccine-generated antibodies in the same way, potentially shielding both mother and child from future infection. However it is not yet known exactly how protective these antibodies might be, or how long that protection might last. Dr. Laura Riley, chair of the Department of Obstetrics and Gynecology at Weill Cornell Medicine, obstetrician and gynecologist-in-chief at NewYork-Presbyterian/Weill Cornell and one of the study's co-authors, is still advising pregnant patients who decide to get vaccinated to continue to follow current safety guidelines to prevent the spread of the disease. Dr. Riley, Dr. Yang and their colleagues are leading follow-up investigations that are currently enrolling pregnant women who receive the vaccine, as well as vaccinated mothers who are breastfeeding, to assess the antibody response in those groups after vaccination. That information could help guide maternal vaccination strategies moving forward.

Read more at Science Daily

Vitamin D levels during pregnancy linked with child IQ

 Vitamin D is a critical nutrient and has many important functions in the body. A mother's vitamin D supply is passed to her baby in utero and helps regulate processes including brain development. A study published today in The Journal of Nutrition showed that mothers' vitamin D levels during pregnancy were associated with their children's IQ, suggesting that higher vitamin D levels in pregnancy may lead to greater childhood IQ scores. The study also identified significantly lower levels of vitamin D levels among Black pregnant women.

Melissa Melough, the lead author of the study and research scientist in the Department of Child Health, Behavior, and Development at Seattle Children's Research Institute, says vitamin D deficiency is common among the general population as well as pregnant women, but notes that Black women are at greater risk. Melough says she hopes the study will help health care providers address disparities among women of color and those who are at higher risk for vitamin D deficiency.

"Melanin pigment protects the skin against sun damage, but by blocking UV rays, melanin also reduces vitamin D production in the skin. Because of this, we weren't surprised to see high rates of vitamin D deficiency among Black pregnant women in our study. Even though many pregnant women take a prenatal vitamin, this may not correct an existing vitamin D deficiency," Melough said. "I hope our work brings greater awareness to this problem, shows the long-lasting implications of prenatal vitamin D for the child and their neurocognitive development, and highlights that there are certain groups providers should be paying closer attention to. Wide-spread testing of vitamin D levels is not generally recommended, but I think health care providers should be looking out for those who are at higher risk, including Black women."

Addressing disparities

According to Melough, as many as 80% of Black pregnant women in the U.S. may be deficient in vitamin D. Of the women who participated in the study, approximately 46% of the mothers were deficient in vitamin D during their pregnancy, and vitamin D levels were lower among Black women compared to White women.

Melough and her co-authors used data from a cohort in Tennessee called the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study. CANDLE researchers recruited pregnant women to join the study starting in 2006 and collected information over time about their children's health and development.

After controlling for several other factors related to IQ, higher vitamin D levels in pregnancy were associated with higher IQ in children ages 4 to 6 years old. Although observational studies like this one cannot prove causation, Melough believes her findings have important implications and warrant further research.

Vitamin D deficiency

"Vitamin D deficiency is quite prevalent," Melough said. "The good news is there is a relatively easy solution. It can be difficult to get adequate vitamin D through diet, and not everyone can make up for this gap through sun exposure, so a good solution is to take a supplement."

The recommended daily intake of vitamin D is 600 international units (IU). On average, Americans consume less than 200 IU in their diet, and so if people aren't making up that gap through sun exposure or supplementation, Melough says people will probably become deficient. Foods that contain higher levels of vitamin D include fatty fish, eggs and fortified sources like cow's milk and breakfast cereals. However, Melough notes that vitamin D is one of the most difficult nutrients to get in adequate amounts from our diets.

Additional research is needed to determine the optimal levels of vitamin D in pregnancy, but Melough hopes this study will help to develop nutritional recommendations for pregnant women. Especially among Black women and those at high risk for vitamin D deficiency, nutritional supplementation and screening may be an impactful strategy for reducing health disparities.

Read more at Science Daily

Even natural products can be harmful for the unborn child

Plant products ingested by pregnant women through their diet are broken down by the intestinal microbiota into chemical substances, some of which can cross the placental barrier and reach the fetus. These foreign substances can harm the unborn child, even if they are of "natural origin." Researchers at the Department for BioMedical Research (DBMR) at the University of Bern and Inselspital, University Hospital Bern, therefore warn against underestimating the effects of such substances.

All mammals, including humans are colonized by billions of microbes. These mainly live in our intestines, but which can also be found in the respiratory tract, on the skin and in the urogenital tract. In the gastroenterology research group of the Department for BioMedical Reserarch (DBMR) at the University of Bern and at the University Hospital Bern, Inselspital, Stephanie Ganal-Vonarburg and Andrew Macpherson investigate the interaction of these benign intestinal microbes with the host organism. The positive influence of the intestinal flora on our immune system has been recognized for a long time. Interestingly, even the maternal intestinal microbiota already has an efect on the development of the child's immune system during pregnancy as well as immediately after birth. In a review article published in the journal Science, Stephanie Ganal-Vonarburg and Andrew Macpherson compiled the latest knowledge of the extent to which the maternal intestinal flora is involved in the development of the child's immune system. They also found evidence that the effects of plant-based substances that pregnant women ingest through diet have so far been underestimated in research and may pose a potential risk to the unborn.

The placenta only offers partial protection

Scientists have always assumed that the developing embryo and fetus grow in a completely sterile environment in the womb, i.e. in the absence of colonizing microbes, and that colonization with micorbes only takes place at the time of birth. "However, the fetus is not protected against microbial metabolites that originate from the maternal intestinal flora," says Ganal-Vonarburg. The placenta offers only partial protection and transfer of microbial substances leads to the maturation of the offspring innate immune system already during pregnancy. Previous studies by the group around Ganal-Vonarburg and Macpherson have shown this. "It is common for pregnant women to take medication with great caution and only after consulting their doctor, since many medications can cross the placenta and interfere with the child's development. However, much less is known about which naturally occurring substances present in the diet can pass on to the unborn child and to what extent this can be beneficial or harmful for the development of the child's immune system," explains Ganal-Vonarburg.

Even plant substances need to be handled with caution

Together with Andrew Macpherson, she has now summarized published research results and found evidence that metabolic products from the diet cannot only directly reach the the maternal organism and thus into the developing fetus, but that this often only occurs after metabolism through the intestinal flora. This also applies to the intake of herbal products, such as superfoods that are considered particularly healthy during pregnancy, such as goji berries or chia seeds: "Although plants products are 'natural' substances, they are always so-called xenobiotic substances that are foreign to the body and should be handled very carefully," says Macpherson. "Especially when pregnant women take plant-based products in large quantities."

Ganal-Vonarburg and Macpherson recommend that future studies should investigate which natural substances could have a beneficial or negative effect on the development of the unborn child and what influence differences in the maternal intestinal flora can have on this process.

Read more at Science Daily

Length of pregnancy alters the child's DNA

Researchers from Karolinska Institutet in Sweden have together with an international team mapped the relationship between length of pregnancy and chemical DNA changes in more than 6,000 newborn babies. For each week's longer pregnancy, DNA methylation changes in thousands of genes were detected in the umbilical cord blood. The study is published in Genome Medicine.

Premature birth, that is before 37 consecutive weeks' of pregnancy, is common. Between 5 and 10% of all children in the world are born prematurely. Most children will develop and grow normally, but premature birth is also linked to respiratory and lung disease, eye problems and neurodevelopmental disorders. This is especially true for children who are born very or extremely prematurely. During the fetal period, epigenetic processes, i.e., chemical modification of the DNA, are important for controlling development and growth. One such epigenetic factor is DNA methylation, which in turn affects the degree of gene activation and how much of a particular protein is formed.

"Our new findings indicate that these DNA changes may influence the development of fetal organs," says Simon Kebede Merid, first author of the study and PhD student at Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset.

The majority of observed DNA methylations at birth tended not to persist into childhood, but in 17% the levels were completely stable from birth to adolescence. The levels that you are born with in certain genes thus track with age.

"Now we need to investigate whether the DNA changes are linked to the health problems of those born prematurely," says Professor Erik Melén, at the Department of Clinical Science and Education, Södersjukhuset.

Epigenetics is a hot research topic that links genes, the environment and health. This work was done within the international Pregnancy and Childhood Epigenetics (PACE) consortium. The work represents contributions from 26 studies. Professor Melén's group also contributed to the first PACE paper which showed that mother's smoking during pregnancy changes DNA in newborns and lead two PACE studies showing effects of air pollution. Links to diseases such as asthma, allergy, obesity and even aging have also been shown.

Read more at Science Daily

Moms' obesity in pregnancy is linked to lag in sons' development and IQ

A mother's obesity in pregnancy can affect her child's development years down the road, according to researchers who found lagging motor skills in preschoolers and lower IQ in middle childhood for boys whose mothers were severely overweight while pregnant. A team of epidemiologists, nutritionists and environmental health researchers at Columbia University Mailman School of Public Health and the University of Texas at Austin and found that the differences are comparable to the impact of lead exposure in early childhood. The findings are published in BMC Pediatrics.

The researchers studied 368 mothers and their children, all from similar economic circumstances and neighborhoods, during pregnancy and when the children were 3 and 7 years of age. At age 3, the researchers measured the children's motor skills and found that maternal obesity during pregnancy was strongly associated with lower motor skills in boys. At age 7, they again measured the children and found that the boys whose mothers were overweight or obese in pregnancy had scores 5 or more points lower on full-scale IQ tests, compared to boys whose mothers had been at a normal weight. No effect was found in the girls.

"What's striking is, even using different age-appropriate developmental assessments, we found these associations in both early and middle childhood, meaning these effects persist over time," said Elizabeth Widen, assistant professor of nutritional sciences at UT Austin and a co-author. "These findings aren't meant to shame or scare anyone. We are just beginning to understand some of these interactions between mothers' weight and the health of their babies."

It is not altogether clear why obesity in pregnancy would affect a child later, though previous research has found links between a mother's diet and cognitive development, such as higher IQ scores in kids whose mothers have more of certain fatty acids found in fish. Dietary and behavioral differences may be driving factors, or fetal development may be affected by some of the things that tend to happen in the bodies of people with a lot of extra weight, such as inflammation, metabolic stress, hormonal disruptions and high amounts of insulin and glucose.

The researchers controlled for several factors in their analysis, including race and ethnicity, marital status, the mother's education and IQ, as well as whether the children were born prematurely or exposed to environmental toxic chemicals like air pollution. What the pregnant mothers ate or whether they breastfed were not included in the analysis.

The team also examined and accounted for the nurturing environment in a child's home, looking at how parents interacted with their children and if the child was provided with books and toys. A nurturing home environment was found to lessen the negative effects of obesity.

According to Widen and senior author Andrew Rundle, DrPH, associate professor of Epidemiology at Columbia Mailman School, while the results showed that the effect on IQ was smaller in nurturing home environments, it was still there.

This is not the first study to find that boys appear to be more vulnerable in utero. Earlier research found lower performance IQ in boys but not girls whose mothers were exposed to lead, and a 2019 study suggested boys whose moms had fluoride in pregnancy scored lower on an IQ assessment.

Because childhood IQ is a predictor of education level, socio-economic status and professional success later in life, researchers say there is potential for impacts to last into adulthood.

Read more at Science Daily