Pregnancy
Newborn screening by genome sequencing shown to be safe and effective
Two studies show the potential for genomic screening in newborns to address high rates of infant hospitalisation and mortality.
Presently, hundreds of genetic diseases are either preventable or treatable but currently are detected only after a child falls ill and endures a years-long “diagnostic odyssey,” often receiving diagnoses too late to achieve the best outcomes.
The first study described a novel platform with scalability and performance that will allow millions of babies to be screened and treated by genome sequencing and artificial intelligence within two weeks from birth.
Previously, medical genome sequencing was much too expensive for newborn screening. Plus, a high rate of false positive results – genome findings that falsely suggest a newborn to have a genetic disease – have been of great concern when genomes are examined without clinical context.
Previously, no method existed to translate genome results into treatment guidance in a way that most physicians could understand and put into practice.
The novel platform, BeginNGS (pronounced beginnings) solves this. It makes use of the latest genome sequencing technology to provide an affordable genome.
BeginNGS uses a combination of human and artificial intelligence tools to automate the complex process of interpreting disease risk based on genome information alone, which is critical for scaling to the 3.7 million babies born in the U.S. each year.
The study reported a 97 per cent reduction in false positives based on a method derived from human evolution. The genome variations that cause severe childhood diseases are subject to extreme natural selection called purifying hyperselection.
As a result, DNA variants that truly cause severe childhood disease are not found in genomes of elderly persons. By studying the genomes of almost half a million middle aged and elderly subjects, from the UK Biobank and Mexico City Prospective Study, researchers were able to discover those false positive DNA differences and reduce their occurrence to less than 1 in 50 subjects tested.
The computational methodology uses query federation, a method to analyse genomes remotely without data being moved or shared, which is enabled by TileDB, a database technology partner for BeginNGS.
Remarkably, after removing these DNA variants, BeginNGS retained greater than 99 percent sensitivity when compared with the gold standard method of rapid diagnostic genome sequencing.
BeginNGS used a custom-built clinical guidance system called Genome to Treatment (GTRx) to communicate a potential course of action for babies who screen positive. Many of these disorders are so rare the typical physician will rarely see them in practice.
GTRx provides practical guidance for physicians in a manner that is easy to understand. Testing of over 3,000 children with suspected genetic diseases revealed that 1 in 14 would have benefited from BeginNGS by receiving a time-to-diagnosis of 121 days earlier than compared with gold standard testing after those children developed symptoms.
In addition, testing revealed that BeginNGS would have benefited one in 13 babies who died in infancy.
“The future of newborn genetic screening lies in global collaboration and shared data resources,” says Stavros Papadopoulos, CEO and founder of TileDB.
“By connecting genetic information across international databases, we significantly enhance our ability to identify and understand rare diseases — an endeavour that transcends individual projects and geographical boundaries.
“Through TileDB’s expansion of the BeginNGS consortium and our federated query capabilities, we’re enabling more comprehensive analysis of variant datasets. For RCIGM and the families they serve, this translates directly into faster, more reliable answers during those critical early days of life.”
The second study evaluated whether BeginNGS was ready for broader expansion. In this trail, 120 babies in the neonatal intensive care unit at Rady Children’s Hospital – San Diego, received the BeginNGS screening.
Results were compared with traditional, federally mandated newborn screening and t\rapid diagnostic genome sequencing which evaluated all ~10,000 genetic diseases.
“The amazing, unexpected result of this BeginNGS trial was that nearly 30 percent of NICU babies who weren’t considered to need genome sequencing actually had genetic diseases — this is similar to the rate of diagnosis in babies who are suspected of having genetic diseases,” said Stephen Kingsmore, president and CEO of Rady Children’s Institute for Genomic Medicine
“This suggests that the health benefits of rapid whole genome sequencing apply to every baby admitted to a Level IV NICU, not just those who are currently being tested.”
Only babies who were not suspected of having genetic diseases were eligible for enrolment in the clinical trial since the trial wished to mimic screening of healthy newborns.
BeginNGS genome-based newborn screening was shown to be safe and effective. One in 24 babies tested had positive results that were likely to impact their care.
BeginNGS had no false positives, showing that the purifying hyperselection methods indeed worked in the real world. Eighty four percent of parents in the trial reported that their child’s genomic sequencing results were useful, and 80 per cent felt that participation did their child a lot of good. When compared with state newborn screening, BeginNGS had a higher true positive rate and lower false positive rate.
“Genome-based newborn screening has the potential to transform health outcomes for children with certain rare diseases by accelerating their time to diagnosis and proper care,” said Tom DeFay, vice chair of BeginNGS and deputy head of diagnostics at Alexion, AstraZeneca Rare Disease.
“As a founding member of the BeginNGS Consortium, Alexion is encouraged by these Phase 2 results and remains committed to advancing health equity by helping improve diagnostics for families impacted by rare genetic and often life-threatening conditions.”
These studies pave the way for a much larger, multicentere clinical trial to formally compare BeginNGS with standard newborn screening.
That trial has started and to date is replicating the findings of the pilot study. In addition, now that computational methods exist for removal of false positives, BeginNGS is poised to expand from 412 severe childhood genetic diseases to the more than 2,000 disorders that have been suggested to be actionable early onset rare disorders for newborn screening.
Now that the feasibility of federated queries has been successfully demonstrated it will be possible to expand these to many genome biobanks worldwide to examine the incidence and prevalence of genetic diseases across the globe, allowing BeginNGS be tailored to screen each population.
Fertility
Most NHS regions in England limit IVF to single cycle, research finds
Nearly 70 per cent of NHS regions in England fund only one IVF cycle for women under 40, breaking national guidelines, new research has found.
Twenty-nine of the 42 integrated care boards, which control local NHS budgets, now offer only one round of treatment, after four reduced access in the past year.
National Institute for Health and Care Excellence (Nice) guidelines recommend three full cycles for women under 40 who have been unable to conceive for two years.
Only two of England’s 42 integrated care boards have policies consistent with these guidelines, which they are not legally obliged to follow.
The research was conducted by the Progress Educational Trust, a fertility charity.
Sarah Norcross, the director of PET, said the impact was “devastating” for couples struggling with infertility.
She said: “Infertility is already incredibly stressful for people, and it puts them under even more pressure, because there is so much riding on whether that one NHS-funded cycle is going to work.
“And for some people, that will be their only chance, because private fertility treatment is so expensive.”
The data showed regional variations, with the whole of the north-west offering just one cycle.
“It’s a postcode lottery, and we’re seeing a race to the bottom,” said Norcross.
Of the 29 integrated care boards that offer a single cycle, 19 provide only a partial cycle, where not all viable embryos created are transferred.
There was just one recent example of improved services, from NHS South East London, which in July 2024 went from one partial to two full cycles.
The NHS estimates that about one in seven couples may have difficulty achieving a pregnancy. One cycle of IVF can cost from £5,000 at a private clinic.
Fertility rates in England and Wales have fallen since 2010 to 1.41 children per woman in 2024, the lowest on record and below the replacement level of 2.1 at which a population is stable without immigration.
Health minister Karin Smyth said in a written parliamentary answer last month that it was “unacceptable” that access to NHS-funded fertility services varied across the country.
Revised Nice fertility guidelines are due this spring, but Norcross said changing them seemed pointless.
She said: “Fertility treatment has always been a Cinderella service. It’s always been the one they’ve chosen to cut or to ignore.
“Nice has recommended three full NHS-funded cycles, for women under 40, for more than 20 years. This has never been implemented across England, unlike in Scotland.”
Norcross advocated centralised commissioning and replicating Scotland’s approach, which included financial modelling and a phased implementation starting with two cycles to avoid long waits, moving up to three once capacity was achieved.
“It is a tried and tested plan that England could follow,” Norcross added.
A Department of Health and Social Care spokesperson said: “We recognise access to fertility treatment varies across the country and we are working with the NHS to improve consistency.
“Nice provides clear clinical guidelines, and we expect integrated care boards to commission treatment in line with these.
“Updated Nice fertility guidelines are expected this spring and we will continue to support NHS England to make sure the guidance is fully considered in local commissioning decisions.”
An NHS England spokesperson said: “These clinical services are commissioned by integrated care boards for their area based on the needs of the local population and prioritisation of resources available.
“All ICBs have a responsibility to ensure services are provided fairly and are accessible by different population groups.”
Fertility
France urges 29-year-olds to start families now
France is urging 29-year-olds to have children as part of a 16-point plan to boost fertility and raise birth rates.
Health officials say the aim is to prevent men and women facing fertility problems later in life and thinking “if only I had known”.
The strategy comes as the country, like many western nations including the UK, faces tumbling birth rates.
The trend is creating concerns about how governments can fund pensions and healthcare for ageing populations with fewer younger working people paying taxes.
But policies to raise fertility rates globally have produced limited results, and critics of the scheme suggest better housing and maternity provision could be more effective.
The government will send out “targeted, balanced, and scientifically sound information” to young people on issues including sexual health and contraception.
The material “will also reiterate that fertility is a shared responsibility between women and men,” the country’s health ministry said.
The plan includes efforts to increase the number of egg-freezing centres from 40 to 70. The process involves extracting and storing a woman’s eggs for potential future use.
The country’s health system already provides free egg-freezing for people aged 29 to 37, a service that costs about £5,000 per round in the UK.
The country’s fertility rate of 1.56 children per woman is below the 2.1 needed to maintain a stable population.
However, it is higher than rates in China, Japan and South Korea, and the UK, where the latest figures show it dropped to a record low of 1.41 in England and Wales by 2024.
Professor François Gemenne, who specialises in sustainability and migration at HEC Paris Business School, told Sky News: “This is something that demographers had known for a long time, but the fact that there were more deaths than births in France last year created a shock effect.”
He said the country’s “demographic worry” is exacerbated by the design of its pensions system and its “obsession with immigration and the fear of being ‘replaced'”.
The plan also includes a new national communication campaign, a “My Fertility” website advising on the effects of smoking, weight and lifestyle, and school lessons for children about reproductive health.
The health ministry has acknowledged its maternal and infant mortality rates are higher than neighbouring countries and is beginning a review of perinatal care to address the “concerning” situation.
Channa Jayasena, professor in reproductive endocrinology at Imperial College London, told Sky News: “On the female side, societal changes leading to older age of motherhood are certainly important.
He said obesity was also a problem as it increased women’s risk of polycystic ovary syndrome and endometriosis.
Allan Pacey, professor of andrology (male reproductive health) at Manchester University, said for most people globally, deciding to have children was “down to [non-medical] factors such as better access to education, career opportunities, taxation, housing, mortgages, finance, etc.”
“Medicine can’t help with those things,” Pacey added.
Ageing
Pregnancy and breastfeeding linked to higher cognitive ability in postmenopausal women
Pregnancy and breastfeeding are linked to stronger cognition in postmenopausal women, a long-term study suggests.
Greater cumulative time spent pregnant and time spent breastfeeding correlated with higher overall scores in the study, including verbal and visual memory, in later life.
Researchers analysed annual assessments of more than 7,000 women aged about 70 for up to 13 years using data from the Women’s Health Initiative Memory Study and the Women’s Health Initiative Study of Cognitive Aging.
On average, those who were pregnant for around 30.5 months were expected to have a 0.31 per cent higher global cognition score than those who had never been pregnant.
A lifetime average of 11.6 months of breastfeeding was linked to a 0.12 per cent higher global score.
Each additional month spent pregnant was associated with a 0.01-point rise in overall ability.
Each extra month of breastfeeding showed the same increase, and a 0.02-point gain in verbal and visual memory. Although small, these effects are similar to known protective factors such as not smoking and high physical activity.
The work was led by Molly Fox, an anthropology professor at the University of California, Los Angeles.
Fox said: “Any ways in which we can focus public health outreach or clinical interventions towards higher-risk populations leads to more effective and efficient efforts.”
Participants who had ever been pregnant scored, on average, 0.60 points higher than those who had never been pregnant.
Those who had breastfed scored 0.19 points higher overall and 0.27 points higher for verbal memory than those who had never breastfed.
Women are disproportionately affected by Alzheimer’s disease, a progressive condition that impairs memory and thinking skills, and this is not fully explained by life expectancy differences.
The authors say biology and social factors may both play roles.
They noted that more adult children could contribute to cognitive health by buffering stress, supporting wellbeing or encouraging healthy behaviour.
“If we can figure out, as a next step, why those reproductive patterns lead to better cognitive outcomes in old age, then we can work towards figuring out how to craft therapies, for example, new drugs, repurposed drugs or social programmes, that mimic the naturally occurring effect we observed,” said Fox.
The study team is now working to identify the mechanisms that link reproductive histories to cognitive resilience.
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