Category: Obstetrics & Gynaecology

Categories : Obstetrics & GynaecologyTags :

Lifesaving Post-partum Haemorrhage Intervention is Highly Cost-effective

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A lifesaving package including early detection and bundled treatment for women who have post-partum haemorrhage has been found to incur minimal additional cost according to new analysis from 78 hospitals around the world.

In a paper published in Nature Medicine, a team of researchers working on the E-MOTIVE trial conducted an economic analysis to establish whether a package of interventions to objectively identify and treat post-partum haemorrhage (PPH) was cost effective.

Over 200 000 women from hospitals in Kenya, Nigeria, Tanzania and South Africa were included in the economic analysis of E-MOTIVE, with hospitals being randomly assigned to either the intervention or usual care groups. The intervention resulted in more than 1000 fewer PPH cases compared to the usual care group. The additional cost for E-MOTIVE was estimated to be, on average, an extra $0.30 per patient after adjustments for clinical factors including the proportion of patients with a clinical primary outcome event at each hospital, as well as for cluster and time-period considerations.

The economic analysis explored a range of costs for a key component of the E-MOTIVE package which is a calibrated blood collection drape, used for all women in the intervention group used to objectively measure blood loss. The analysis found that when the cost of the drape is around 1 USD, the average cost per patient could be comparable to usual care.

The cost of delivering the E-MOTIVE intervention could then be, on average, equivalent to usual care, which would represent a significant health benefit for women around the world

Professor Tracy Roberts

Tracy Roberts, Professor of Health Economics at the University of Birmingham and corresponding author of the study said:

“E-MOTIVE is clearly a cost-effective intervention for what is a lifesaving treatment for thousands of women around the world who may experience severe bleeding in childbirth. Our analysis of the E-MOTIVE trial shows that the costs incurred in delivering the package of treatments and the drape are on average minimal and represent really good value for money”.

“The drape forms a key part of the E-MOTIVE package, and should E-MOTIVE be widely adopted and the cost of drapes reduced to below $1, the economic benefits could be even more apparent. The cost of delivering the E-MOTIVE intervention could then be, on average, equivalent to usual care, which would represent a significant health benefit for women around the world.”

60% reduction in heavy bleeding

E-MOTIVE being found cost-effective comes after the publication of a landmark study published that found a 60% reduction in heavy bleeding for women experiencing PPH.

Postpartum haemorrhage (PPH) – defined as the loss of more than 500 mL of blood within 24 hours after birth – is the leading cause of maternal mortality worldwide. It affects an estimated 14 million women each year and results in around 70 000 deaths – mostly in low and middle-income countries – equivalent to 1 death every 6 minutes.

The study found that objectively measuring blood loss using a simple, low-cost collection device called a ‘drape’ and bundling together WHO-recommended treatments – rather than offering them sequentially – resulted in dramatic improvements in outcomes for women. Severe bleeding – when a woman loses more than a litre of blood after birth – was reduced by 60%, and they were less likely to lose their life.

There was also a substantial reduction in the rate of blood transfusions for bleeding, which is of particular importance in low-income countries where blood is a scarce and expensive resource.

Professor Arri Coomarasamy, who led the E-MOTIVE trial and is the Co-Director of the WHO Collaborating Centre on Global Women’s Health at the University of Birmingham said:

“This new approach to treating postpartum haemorrhage could radically improve women’s chances of surviving childbirth globally, helping them get the treatment they need when they need it.

“Time is of the essence when responding to postpartum bleeding, so interventions that eliminate delays in diagnosis or treatment should be gamechangers for maternal health. With this latest study showing that E-MOTIVE is extremely cost effective, and following WHO recommending the treatment bundle we hope that the intervention can quickly become the standard of care that will save many lives around the world.

Source: University of Birmingham

Categories : Obstetrics & GynaecologyTags :

Metabolic Parameters Similar in Children Born via Frozen and Fresh Embryo Transfer

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No differences in blood glucose, insulin, or cholesterol levels seen in children born via frozen versus fresh embryo transfer regardless of age, gender, or method of assisted conception

Children born via frozen embryo transfer have similar metabolic profiles to those born via fresh embryo transfer, according to a study published June 6th in the open-access journal PLOS Medicine by Linlin Cui and Zi-Jiang Chen from Shandong University, China, and colleagues.

Prior studies have shown inconsistent results on the long-term metabolic health impacts of assisted reproductive technology. Some have shown that children born via frozen embryo transfer have a higher risk of metabolic disorders, such as obesity, and unfavorable lipid profiles. Other studies have failed to find any significant metabolic differences between those born via frozen or fresh embryo transfer.

In this study, researchers compared the glucose and lipid profiles of more than 4000 children between 2 and 5 years of age – approximately half had been born via fresh embryo transfer and half had been born via frozen embryo transfer.

Researchers followed the children for an average of 3.6 years and assessed metabolic factors often associated with heart disease and diabetes, such as fasting blood glucose, insulin, cholesterol, and triglycerides.

They found no difference in any of the metabolic factors among children born via fresh embryo transfer and those born via frozen embryo transfer.

Given the relatively large number of participants in this study, the researchers were able to conduct subgroup analyses. After dividing the children into groups based on gender, age, embryo transfer state, and method of conception, there were still no differences in metabolic factors among the frozen and fresh embryo transfer groups.

The study provides more information to women and couples weighing the pros and cons of different techniques offered for assisted reproduction, but the researchers noted the need for additional data on the effect of assisted reproductive technology on long-term metabolic health.

The authors add, “Frozen embryo transfer shows no significant adverse effects on metabolic profiles in early childhood, providing crucial evidence for counseling couples undergoing assisted reproductive technology treatment on its safety.”

Provided by PLOS

Categories : Obstetrics & GynaecologyTags :

New Research Dispels Morning Sickness Myths

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Photo by Andrea Piacquadio

Late last year, geneticist Marlena Fejzo and colleagues made the discovery that morning sickness’s most serious presentation, hyperemesis gravidarum (HG), is caused by the hormone GDF15, not human chorionic gonadotropin as previously thought. In a peer-reviewed opinion article published in the journal Trends in Molecular Medicine, Fejzo dispels common morning sickness myths and discusses potential treatments, including sensitising people to GDF15 prior to pregnancy, similar to the way we treat allergies.

“HG can be life threatening and is associated with adverse outcomes that need to be taken seriously,” says Fejzo of the Keck School of Medicine of the University of Southern California. “Now that we know that GDF15 is the most likely cause of HG, we are on the cusp of having treatments that target this hormonal pathway and end the suffering.”

Myth 1: Severe morning sickness is harmless and normal

Pregnant people with HG are essentially starving, Fejzo says, and an increasing number of studies have demonstrated that this has serious short- and long-term clinical implications for both the parent and child. HG is a top predictor of postnatal depression, and 26% of pregnant people with HG report suicidal ideation while 18% meet the full criteria for post-traumatic stress disorder.

For the child, HG is associated with preterm birth, low birth weight, and later in life, autism spectrum disorder, ADHD, depression, social problems, in addition to an increased risk of childhood cancer and respiratory and cardiovascular disease. Still, pregnant people with the condition are often dismissed by their clinicians and families.

“It really is like a teratogen in pregnancy, a factor which interferes with normal foetal development, but it’s still not taken seriously by a lot of medical professionals,” Fejzo says. “A lot of people are brushed off and told, ‘oh that’s normal, it’s okay, just don’t take your pre-natal vitamins; you don’t need them.'”

At its most extreme, individuals with HG can develop Wernicke encephalopathy, a life-threatening swelling of the brain due to thymine (vitamin B1) deficiency. Since individuals with HG can have trouble even swallowing vitamins, the American College of Obstetricians and Gynecologists currently recommends that they replace broad spectrum prenatal vitamins with folic acid, but Fejzo warns that this is likely insufficient, and that thiamine supplementation is also warranted for individuals with HG.

“I believe all women who have hyperemesis should be given vitamin B1 to avoid this serious brain swelling that can lead to permanent brain damage and often leads to foetal death,” Fejzo says.

Myth 2: Morning sickness is caused by human chorionic gonadotropic hormone (hCG) or is psychosomatic

Though it was long thought that morning sickness is caused by hCG, the recent breakthrough has shown that HG’s main cause is actually the hormone GDF15, which is part of a normal stress response. Usually, GDF15 is expressed only in very small amounts, but during early pregnancy it spikes by a huge amount, then wanes, and finally rises again during the third trimester.

A recent Nature study co-authored by Fejzo showed that individuals who suffer from HG can have genetic variants that causes them to have lower levels of circulating GDF15 prior to pregnancy, which makes them extra sensitive when they become pregnant and are suddenly exposed to high levels. This finding has clinical implications for preventing and treating HG, since preliminary research suggests that it might be safe to manipulate GDF15 during or even prior to pregnancy.

“GDF15 may be safe to manipulate in pregnancy or even prior to pregnancy,” says Fejzo. “If we can increase levels of GDF15 before someone becomes pregnant, that might desensitise them, similar to how we try to desensitize people to allergens who have severe allergies,” says Fejzo. “And during pregnancy, we may be able to minimise or get rid of symptoms by blocking GDF15 or its receptors in the brain stem.”

Myth 3: Only humans experience morning sickness

Nausea and appetite loss during gestation is not a uniquely human trait – these symptoms have been observed throughout the animal kingdom, from monkeys, dogs, and cats, to chickens, vipers, and octopuses.

“I always think it’s interesting that the recommendation for cats is that if they’re unable to eat for a day, you should contact your veterinarian, but we don’t have that recommendation out there for women with hyperemesis,” says Fejzo. “If you call your doctor’s office and say you haven’t eaten for a day, they’ll say, ‘that’s normal’ and won’t do anything. There’s more proactive care for cats than humans.”

In addition to preventing ingestion of harmful foods, Fejzo speculates that pregnancy-induced nausea likely evolved to prevent dangerous foraging trips.

“This condition likely evolved because it was probably beneficial to avoid going out searching for food during pregnancy,” says Fejzo. “That may still be true for animals, but people don’t need this anymore, so let’s end the suffering once and for all if we can.”

Now, Fejzo is working toward developing and testing the proposed GDF15-based treatments. She also plans to investigate other genes and variants of GDF15 that might contribute to HG.

Source: Science Daily

Categories : Obstetrics & GynaecologyTags :

Immune Dysfunction as a Possible Aspect of PCOS Pathology

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The study “Androgens Modulate the Immune Profile in a Mouse Model of Polycystic Ovary Syndrome” sheds light on immune dysfunction as a possible aspect of PCOS pathology, which could constitute a novel target for therapies.

The study shows that hyperandrogenism, a key characteristic of polycystic ovary syndrome (PCOS), affects immune cell populations in reproductive, metabolic, and immunological tissues in a PCOS-like mouse model. These findings are of great importance as it is known that immune dysfunction is an essential part of reproductive complications and metabolic disease, which are very common among women with PCOS. 

However, as the study shows that hyperandrogenism affects different tissues in unique ways, any possible treatments would have to be carefully tailored to target specific tissue dysfunctions. Since concurrent treatment with an androgen receptor antagonist prevented many changes in the mouse model we used in our study, combination therapies that include both anti-androgens and other drugs that target specific altered immune pathways could be explored.

Alteration of immune cells in adipose tissue

One of the most fascinating findings was the clear alterations of immune cells in adipose tissue, despite an unaltered fat mass of the androgen exposed mice. It is well known that immune cells in adipose tissue contribute to insulin resistance in overweight and obese individuals, but here we have an insulin resistant mouse model that mimics normal weight women with PCOS. The impact of androgens on immune cells in adipose tissue is therefore very interesting considering the high prevalence of insulin resistance and type-2 diabetes among normal weight women with PCOS. Another rather surprising finding was the drastic decrease of eosinophils in the uterus, as these don’t express the androgen receptor. This shows that androgens play a broader and more complex role in modulating the immune environment than only through direct androgen receptor activation on immune cells. 

The next step will be to dissect the underlying mechanisms of the immune alterations, and to assess if these do contribute to the reproductive complications and metabolic comorbidities of PCOS. This will include further characterisation of immune cell changes to understand how their function could be affected and link these to reproductive and metabolic mechanisms. We also want to understand how the effect of androgens on eosinophils and mature NK cells is mediated, since neither of them expresses the androgen receptor. 

Source: Karolinska Institutet

Categories : Cancer Obstetrics & GynaecologyTags :

Most Young Breast Cancer Survivors can Still Have Children

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A new study by Dana-Farber Cancer Institute investigators, which tracked nearly 200 young women treated for breast cancer, found that the majority of those who tried to conceive during a median of 11 years after treatment were able to become pregnant and give birth to a child.

The findings, to be presented at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO), are particularly noteworthy because they answer several questions left open by previous studies of pregnancy and live-birth rates among breast cancer survivors, the study authors say.

“Earlier studies were limited because they included select subgroups of patients, followed patients for a relatively short period of time, and didn’t ask participants, during the study period, if they had attempted pregnancy,” says the study’s senior author, Ann Partridge, MD, MPH, the founder and director of the Program for Young Adults with Breast Cancer at Dana-Farber. “This study was designed to address those gaps by tracking pregnancy and live birth rates among a group of breast cancer survivors and patients who indicated they’d attempted to conceive following their cancer diagnosis.”

The patients in the study were participants in the Young Women’s Breast Cancer Study, which is tracking the health of a group of women diagnosed with breast cancer at or under age 40. Of 1213 eligible participants, 197 reported an attempt of pregnancy over a median follow-up period of 11 years. Within this latter group, the median age at the time of diagnosis was 32 years, and most were diagnosed with hormone receptor-positive breast cancer. Participants were periodically surveyed about whether they had tried to become pregnant and whether they had conceived and given birth.

Over the course of the study, 73% of women attempting to conceive achieved a pregnancy and 65% had a live birth, researchers found. Those who opted for fertility preservation by egg/embryo freezing before cancer treatment tended to have a higher live birth rate, while older participants tended to have lower pregnancy and live birth rates

Participants in the study had breast cancers ranging from stage 0, which are non-invasive and confined to the inside of the milk duct, to stage III, in which the cancer has spread to the lymph nodes. There was no statistically significant association with stage of the disease at diagnosis and achieving a pregnancy or live birth.

“For many young women with breast cancer, the ability to have children following treatment is a major concern,” says the study’s first author, Kimia Sorouri, MD, MPH, of Dana-Farber. “The findings of our study can be helpful when counselling patients about fertility issues. The finding that egg/embryo freezing before treatment was associated with a higher live birth rate underscores the need for accessibility to fertility preservation services for this population.”

Source: Dana-Farber Cancer Institute

Categories : Obstetrics & Gynaecology PaediatricsTags :

Health and Economic Benefits of Breastfeeding Quantified

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Among half a million Scottish infants, those exclusively breastfed were less likely to use healthcare services and incurred lower costs to the healthcare system

Photo by Wendy Wei

Breastmilk can promote equitable child health and save healthcare costs by reducing childhood illnesses and healthcare utilisation in the early years, according to a new study published this week in the open-access journal PLOS ONE by Tomi Ajetunmobi of the Glasgow Centre for Population Health, Scotland, and colleagues.

Breastfeeding has previously been found to promote development and prevent disease among infants. In Scotland – as well as other developed countries – low rates of breastfeeding in more economically deprived areas are thought to contribute to inequalities in early childhood health. However, government policies to promote child health have made little progress and more evidence on the effectiveness of interventions may be needed.

In the new study, researchers used administrative datasets on 502,948 babies born in Scotland between 1997 and 2009. Data were available on whether or not infants were breastfed during the first 6-8 weeks, the occurrence of ten common childhood conditions from birth to 27 months, and the details of hospital admissions, primary care consultations and prescriptions.

Among all infants included in the study, 27% were exclusively breastfed, 9% mixed fed and 64% formula fed during the first 6-8 weeks of life. The rates of exclusively breastfed infants ranged from 45% in the least deprived areas to 13% in the most deprived areas.

The researchers found that, within each quintile of deprivation, exclusively breastfed infants used fewer healthcare services and incurred lower costs compared to infants fed any formula milk. On average, breastfed infants had lower average costs of hospital care per admission (£42) compared to formula-fed infants (£79) in the first six months of life and fewer GP consultations (1.72, 95% CI: 1.66 – 1.79) than formula-fed infants (1.92 95% CI: 1.88 – 1.94). At least £10 million of healthcare costs could have been avoided if all formula-fed infants had instead been exclusively breastfed for the first 6-8 weeks of life, the researchers calculated.

The authors conclude that breastfeeding has a significant health and economic benefit and that increasing breastfeeding rates in the most deprived areas could contribute to the narrowing of inequalities in the early years.

Provided by PLOS

Categories : Obstetrics & Gynaecology VaccinesTags :

Birth by C-section More than Doubles Odds of Measles Vaccine Failure

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A study by the University of Cambridge, UK, and Fudan University, China, has found that a single dose of the measles jab is up to 2.6 times more likely to be completely ineffective in children born by C-section, compared to those born naturally.

Failure of the vaccine means that the child’s immune system does not produce antibodies to fight against measles infection, so they remain susceptible to the disease.

A second measles jab was found to induce a robust immunity against measles in C-section children.

Measles is a highly infectious disease, and even low vaccine failure rates can significantly increase the risk of an outbreak.

A potential reason for this effect is linked to the development of the infant’s gut microbiome — the vast collection of microbes that naturally live inside the gut. Other studies have shown that vaginal birth transfers a greater variety of microbes from mother to baby, which can boost the immune system.

“We’ve discovered that the way we’re born – either by C-section or natural birth – has long-term consequences on our immunity to diseases as we grow up,” said Professor Henrik Salje in the University of Cambridge?’s Department of Genetics, joint senior author of the report.

He added: “We know that a lot of children don’t end up having their second measles jab, which is dangerous for them as individuals and for the wider population.

“Infants born by C-section are the ones we really want to be following up to make sure they get their second measles jab, because their first jab is much more likely to fail.”

The results are published today in the journal Nature Microbiology.

At least 95% of the population needs to be fully vaccinated to keep measles under control but the UK is well below this, despite the Measles, Mumps and Rubella (MMR) vaccine being available through the NHS Routine Childhood Immunisation Programme.

An increasing number of women around the world are choosing to give birth by caesarean section: in the UK a third of all births are by C-section, in Brazil and Turkey over half of all children are born this way.

“With a C-section birth, children aren’t exposed to the mother’s microbiome in the same way as with a vaginal birth. We think this means they take longer to catch up in developing their gut microbiome, and with it, the ability of the immune system to be primed by vaccines against diseases including measles,” said Salje.

To get their results, the researchers used data from previous studies of over 1500 children in Hunan, China, which included blood samples taken every few weeks from birth to the age of 12. This allowed them to see how levels of measles antibodies in the blood change over the first few years of life, including following vaccination.

They found that 12% of children born via caesarean section had no immune response to their first measles vaccination, as compared to 5% of children born by vaginal delivery. This means that many of the children born by C-section did still mount an immune response following their first vaccination.

Two doses of the measles jab are needed for the body to mount a long-lasting immune response and protect against measles. According to the World Health Organization, in 2022 only 83% of the world’s children had received one dose of measles vaccine by their first birthday – the lowest since 2008.

Salje said: “Vaccine hesitancy is really problematic, and measles is top of the list of diseases we’re worried about because it’s so infectious.”

Measles is one of the world’s most contagious diseases, spread by coughs and sneezes. It starts with cold-like symptoms and a rash, and can lead to serious complications including blindness, seizures, and death.

Before the measles vaccine was introduced in 1963, there were major measles epidemics every few years causing an estimated 2.6 million deaths each year.

The research was funded by the National Natural Science Foundation of China.

The original text of this story is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Licence.

Source: University of Cambridge

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags :

Infertility Treatment Associated with Double the Risk of Postpartum Cardiovascular Disease

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A study by Rutgers Health experts of more than 31 million hospital records shows that infertility treatment patients were twice as likely as those who conceived naturally to be hospitalised with heart disease in the year after delivery. The results were published in the Journal of Internal Medicine.

Compared to those who conceived naturally, patients who underwent infertility treatment 2.16 times as likely be hospitalised for hypertension.

“Postpartum checkups are necessary for all patients, but this study indicates they are particularly important for patients who undergo infertility treatment to achieve a conception,” said Rei Yamada, an obstetrics and gynaecology resident at Rutgers Robert Wood Johnson Medical School and lead author of the study.

The study authors say their results support standards of care that now call for an initial postpartum checkup three weeks after delivery, standards that some health systems have yet to adopt. Much of the elevated risk came in the first month after delivery, particularly for patients who developed dangerously high blood pressure.

“And these results aren’t the only ones to indicate that follow-up should occur early,” said Cande Ananth, chief of the Division of Epidemiology and Biostatistics in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Rutgers Robert Wood Johnson Medical School and senior author of the study. “We have been involved in a series of studies over the past few years that have found serious risks of heart disease and stroke to various high-risk patient populations within those initial 30 days after delivery – risks that could be mitigated with earlier follow-up care.”

The study analysed the Nationwide Readmissions Database, which contains nationally representative data on about 31 million hospital discharges and readmissions per year. The database contains diagnosis codes, which let researchers find specific populations and identify reasons for readmission.

The researchers used data from more than 31 million patients who were discharged following delivery from 2010 to 2018, including 287 813 patients who had undergone any infertility treatment.

Although infertility treatment predicted a sharply elevated risk of heart disease, the study authors said the relative youth of infertility treatment patients kept their overall risk fairly low. Just 550 of every 100 000 women who received infertility treatment and 355 of every 100 000 who conceived naturally were hospitalized with cardiovascular disease in the year after delivery.

The cause of the elevated risk of heart disease associated with infertility treatment remains unclear. The increase in heart disease could stem from the infertility treatments themselves, the underlying medical issues that made patients infertile or some other cause.

“Looking forward, I’d like to see if different types of infertility treatment and, importantly, medications are associated with different risk levels,” said Yamada. “Our data gave no information about which patients had undergone which treatment. More detailed information might also provide insight into how infertility treatment impacts cardiovascular outcomes.”

Source: Rutgers University

Categories : Genetics Obstetrics & GynaecologyTags :

A Tiny Chromosomal Deletion is Linked to Spina Bifida

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A group of researchers at the University of California San Diego School of Medicine led an investigation that offers new insight into the causes of spina bifida, the most common structural disorder of the human nervous system.

The group’s work reveals the first link between spina bifida and a common chromosomal microdeletion in humans. The study demonstrates that individuals carrying this chromosomal deletion – present in one of 2500 live births – demonstrate a risk of spina bifida more than 10 times greater than the general public.

The study, published in Science, also underscores the potential role of folic acid (aka vitamin B-9) in reducing the risk of spina bifida.

Professor Joseph G. Gleeson at Rady Children’s Institute for Genomic Medicine, is the senior author of the study. He explained that spina bifida, also known as meningomyelocele, affects one in every 3000 newborns. Unfortunately, the causes are mostly unknown. A few mutations were reported but could only explain a tiny fraction of risk, Gleeson added.

To uncover the genetic causes of the disease, Gleeson’s UC lab joined with colleagues around the world to establish the Spina Bifida Sequencing Consortium in 2015. The consortium began focusing on a tiny deletion in chromosome 22. Chromosome microdeletions refer to a condition in which several genes in a chromosome are missing. The group’s target condition, known as 22q11.2del, has been implicated in a number of other disorders. They began looking for 22q11.2del in spinal bifida patients.

“All patients we recruited have the most severe form of spina bifida, and all underwent best-practice comprehensive genomic sequencing,” Gleeson said. “We identified 22q11.2del in 6 out of 715 patients. This may not seem a high percentage, but this is by far the most common single genetic variation that could contribute to spina bifida.”

He went on to say the group identified eight additional spina bifida patients who carried the deletion from a cohort of approximately 1500 individuals recruited because of the presence of the common 22q11.2 deletion, Gleeson said.

The researchers then narrowed the cause among the many genes in the 22q11.2 deletion to a single gene known as CRKL. Gleeson explained that there are nine other genes in this chromosomal region that could have been the cause. He said the team began a process of elimination, “knocking out” each of the mouse genes one-by-one, when they received a fortuitous email from Dolores Lamb from Weil Cornell College of Medicine. Lamb had noted some of the mice in their vivarium that were missing Crkl and showed spina bifida. (Study co-first author Keng Ioi Vong, PhD, explained that researchers use all capital letters to describe the gene in humans, and lower-case for mice.) Lamb’s group heard about the Gleeson lab project through the Spina Bifida Association.

“This finding really got us excited because it meant that CRKL disruption might be sufficient for spina bifida,” said Vong. “We removed the mouse Crkl gene ourselves and confirmed that some of the mice developed neural tube defects, including spina bifida.” Most of the other genes in 22q11.2 deletion were subsequently excluded, he added.

They next turned their attention to how folic acid may modulate CRKL-mediated spina bifida. Vong noted that prior studies in humans demonstrated that folic acid supplementation prior to conception reduces the incidence of spina bifida and other neural tube defects by up to 30-50 %, but the mechanisms are still a mystery.

“When we deprived the Crkl mutant female mice of folic acid in their chow, many more of their offspring had neural tube defects, and the severity increased dramatically,” Vong explained. “This suggests that folic acid taken by pregnant women may not only reduce the risk, but also the severity of neural tube defects in their offspring.”

“We hope our findings can help the research community to better understand causes of neural tube defects, especially the causes attributable to common genetic findings like 22q11.2 deletion,” Gleeson said. “We also hope our findings can contribute to healthy pregnancies, improved women’s health, and improved outcomes for children.”

Source: University of California – San Diego

Categories : Obstetrics & GynaecologyTags :

Genetic Defects – not Hypoxia – Behind 1 in 4 Cerebral Palsy Cases

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The world’s largest study of cerebral palsy (CP) genetics has discovered genetic defects are most likely responsible for more than a quarter of cases in Chinese children, rather than a lack of oxygen at birth as previously thought.

The study, published in Nature Medicine, used modern genomic sequencing and found mutations were significantly higher in CP cases with birth asphyxia, indicating a lack of oxygen could be secondary to the underlying genetic defect. The results are consistent with smaller studies globally.

More than 1500 Chinese children with CP were involved in this collaborative effort between the University of Adelaide and Fudan University Shanghai, Zhengzhou University, Zhengzhou and associates.

The Australian team was led by obstetrician and University of Adelaide’s Emeritus Professor Alastair MacLennan AO and human geneticist, Professor Jozef Gecz.

“24.5 percent of Chinese children in the study had rare genetic variations linked to cerebral palsy. This revelation mirrors our earlier findings in our Australian cerebral palsy cohort, where up to one third of cases have genetic causes,” said Professor Gecz, who is the University of Adelaide’s Head of Neurogenetics at the Adelaide Medical School and the Robinson Research Institute.

“Our research shows at least some babies who experience birth asphyxia and are diagnosed with CP may have improper brain development as a result of the underlying genetic variants rather than a lack of oxygen.

“Crucially, clinically actionable treatments were found in 8.5 percent of cases with a genetic cause. It is exciting to see how genetic pathways to cerebral palsy inform tailored treatments for these individuals.”

Cerebral palsy affects movement and posture and is the most common motor disability in children. The disorder is diagnosed in up to 2 per 1000 children globally and is sometimes in association with epilepsy, autism and intellectual difficulties. Symptoms often emerge during infancy and early childhood and can range from mild to severe.

The research team identified 81 genes with causation mutations in the children with CP. These genes are known to play important roles in neural and embryonic development and may affect the molecular pathways responsible for respiration.

Oxygen deprivation frequently claimed in medical litigation

“A lack of oxygen at birth is often claimed to be the cause of CP in medical litigation following a diagnosis and this has led to the presumption that the condition is preventable with better obstetrics or midwifery. This is simply not the case,” said Professor MacLennan, who has spent the past 30 years advocating that there is little scientific evidence to support the myth that cerebral palsy is due to trauma or lack of oxygen at birth.

Professor MacLennan said frequent litigation has been associated with a high increase in “defensive” caesarean delivery and high insurance premiums for obstetricians.

“These results highlight the need for early genetic testing in children with cerebral palsy, especially those with risk factors like birth asphyxia, to ensure they receive the right medical care and treatment.

“All children with cerebral palsy merit modern genetic screening as early and customised interventions really can make a difference and improve their long-term outcomes,” he said.

Ongoing genetic research is also investigating other types of contributing genetic variation to the cause of CP and, as a result, the researchers expect that the overall genetic diagnosis rate is likely to increase.

Source: University of Adelaide