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.
A recent study developed a new “digital companion” to support the prevention and follow-up of maternal cardiovascular risk in women with pregnancy complications.
Cardiovascular disease, or CVD, is the leading cause of premature death and illness in women, yet sex-specific causes remain understudied and women are underrepresented in research.
Pregnancy complications, including hypertensive disorders of pregnancy, or HDP, and gestational diabetes mellitus, or GDM, are strong predictors of future CVD, with pregnancy itself acting as a natural stress test.
Despite CVD accounting for 35 per cent of female deaths worldwide in 2019, systematic postpartum prevention remains limited in practice and incidence continues to rise.
Myocardial infarction, commonly known as heart attack, and stroke are the main fatal CVD events in women. Up to one-third of women develop hypertension within a decade after HDP, especially as maternal age rises.
Obstetric guidelines have historically lacked clarity on early CVD prevention after HDP and GDM, often relying on expert consensus rather than evidence.
Some cardiology guidelines now recommend personalised approaches, such as periodic hypertension and diabetes screening. Norwegian guidelines recommend cardiovascular risk evaluation at three months and one year postpartum, but adherence in practice is uncertain.
Effective risk reduction requires intervention before middle age. The immediate postpartum period following HDP or GDM is a critical window for early detection and intervention, offering an opportunity to engage women in cardiovascular health management, particularly as pregnancy can encourage long-term lifestyle awareness.
Electronic health, or eHealth, refers to the use of digital technologies and electronic communication tools to support healthcare services, medical information management and related health activities.
Systematic, eHealth-supported postpartum prevention can improve maternal health literacy and long-term cardiovascular outcomes.
However, there is a significant gap in targeted, eHealth-based postpartum interventions for cardiovascular risk management after HDP and GDM, despite strong patient demand and international calls for coordinated digital health strategies.
Home blood pressure monitoring shows promise, but broader digital support remains limited.
A cardiovascular postpartum follow-up programme was created as a mobile app based on Norwegian and international guidelines.
The MumCare app was developed through co-creation involving users, stakeholders and clinical experts. Five qualitative interviews and 10 user testing sessions informed improvements.
This study primarily analysed the iterative co-creation process used to develop the app, rather than evaluating clinical outcomes.
The MumCare project team in Oslo included an IT expert, obstetricians, a midwife, a GP, two sociologists and two cardiologists, all with relevant experience in eHealth and women’s health. A medical student with technological and medical expertise also helped turn ideas into app features for young women.
User representatives from two national patient associations contributed to information, recruitment, design and testing of the MumCare app.
Both associations provided user perspectives and took part in interviews and app testing. Additional users with HDP or GDM at Oslo University Hospital were also involved throughout the co-creation process.
The app’s digital infrastructure prioritises security and privacy, using encryption, de-identification and two-factor authentication.
User data is stored securely on the app and, for research purposes and with consent, on a dedicated University of Oslo server in line with GDPR and Norwegian regulations.
A linear Stage-Gate model structured the co-creation process, dividing it into phases with quality checkpoints reviewed in project meetings.
This approach balanced internal development with external user feedback, helping ensure the app is evidence-based, technically robust and user-centred.
The MumCare app guides postpartum women through tracking blood pressure, weight, physical activity and lab results, and provides personalised feedback to support self-management, mainly during the first postpartum year.
It also includes educational resources such as videos and guideline-based information to support understanding and engagement.
The app is also designed to support the transition from specialist pregnancy care to long-term follow-up with general practitioners.
It is described as a “digital companion” or health coach and does not replace clinical diagnosis or function as a medical device.
The co-creation process followed four phases focused on technical and procedural development.
In phase 1, input from expert organisations and user representatives established the app’s technical foundation.
It also reminds users of the one-year postpartum follow-up with their GP, a key time to assess risk factors and future care needs.
User organisation representatives gave feedback in phase 1, directly guiding content and feature development.
Phase 2 interviews confirmed that users want to monitor cardiovascular risk factors after HDP and GDM.
The analysis highlighted three themes: self-care strategies and uncertainties about hypertension, the need for accessible health information, and a more personalised approach to blood pressure monitoring in the app.
Concerns were also raised that frequent monitoring or app use could increase stress or create a sense of burden.
In phase 3, the app’s design and features were revised in response to feedback to improve usability and make sure they met users’ needs.
These changes led to a more intuitive and supportive interface for women during and after pregnancy.
Phase 4 involved building a prototype based on the updated designs, followed by further refinements after testing by the project team and users. Initial pilot testing with a small number of users suggested the app met its objectives and functioned as intended.
The MumCare app was co-created with input from experts, user organisations and patients over four phases.
Early expert and organisational contributions helped define the app’s goals, while ongoing feedback from patients helped ensure the design and content reflected users’ real needs.
This collaborative approach resulted in an app tailored to support women with pregnancy complications.
The MumCare app is currently being evaluated in a randomised controlled clinical trial that began in June 2024, with results needed to determine whether it improves long-term cardiovascular outcomes.
The first patients have been dosed in a UK miscarriage trial testing a new intravaginal drug delivery platform for threatened miscarriage.
The FREEDOM study is evaluating 400mg progesterone Callavid in patients diagnosed with luteal phase insufficiency, a condition in which progesterone levels may be too low to support early pregnancy, increasing the risk of infertility and recurrent miscarriage.
Callavid uses a patented leak-free, tampon-like design intended to address the limitations of current vaginal treatments, which rely on self-administered pessaries, or vaginal suppositories, that can leak and may move during use.
The device is being developed by London-based Calla Lily Clinical Care, a medical technology company focused on women’s health. The trial is funded by the National Institute for Health and Care Research and run in collaboration with the Trial Management Unit at University Hospitals Coventry and Warwickshire NHS Trust.
According to the company, Callavid is positioned to become the world’s first drug-device combination product to support treatment of threatened miscarriage, as well as luteal phase support as part of assisted reproductive technologies, including in vitro fertilisation, or IVF.
The Government’s Renewed Women’s Health Strategy for England cites estimates ranging from 120,000 to 250,000 cases of miscarriage a year in the UK. Administering 400mg micronised progesterone twice daily is recommended by the National Institute for Health and Care Excellence for women who have suffered a previous miscarriage and experience bleeding during early pregnancy, known clinically as threatened miscarriage.
Current pessary delivery methods can result in uncertain placement and movement during use. These limitations can reduce the efficiency and consistency of drug absorption, potentially compromising delivery of the intended dose, and patients are regularly advised to lie horizontal for extended periods after each administration.
The FREEDOM trial is led by professor Siobhan Quenby MBE, an authority on miscarriage and preterm birth, and an honorary consultant at University Hospitals Coventry and Warwickshire NHS Trust. The study aims to evaluate safety, user acceptability and progesterone absorption, with the goal of providing evidence of improved usability in self-administration.
Quenby commented: “Through my clinical practice, I see the difficulties patients face with existing vaginal progesterone products at an already very stressful time. Callavid offers a promising new solution to ensure delivery of the correct progesterone dosage and give women greater confidence in their treatment. There is genuine excitement among both clinicians and patients at the prospect of Callavid progressing into clinical trials.”
Dr Lara Zibners, co-founder and chair of Calla Lily Clinical Care, added: “As a physician and entrepreneur, I believe we have a responsibility to create more effective, patient-centred solutions in women’s health. Having been through seven rounds of IVF myself, I have experienced how difficult progesterone treatment can be, and I am proud to be advancing an innovation shaped by both medical insight and lived experience.”
Thang Vo-Ta, co-founder and chief executive of Calla Lily Clinical Care, said: “Dosing the first patients in the FREEDOM study marks a critical milestone for Calla Lily Clinical Care. Callavid represents a differentiated delivery modality for a broad range of therapeutics in the pharma pipeline, and will create new opportunities to extend the lifecycle of existing drugs. This trial is a key step in demonstrating Callavid’s massive potential.”
A rare pregnancy complication has led to emergency surgery, including hysterectomies, after staff failed to detect it in affected women.
Scores of women have come forward to tell their stories of how they were affected by placenta accreta spectrum, or PAS, since the launch in February of a campaign to raise awareness among NHS staff and mothers-to-be of the dangers it poses.
One of them lost so much blood while giving birth that she has had to give up working as an NHS operating theatre nurse and suffers from PTSD.
Another lost six litres of blood and blames her daughter’s cerebral palsy on the stroke the child had while hospital staff were battling to save her life after an emergency caesarean section. Others have suffered permanent damage to their bladder or bowels.
Erin Cooper was never assessed for PAS even though she regularly bled heavily from 26 weeks into her pregnancy until she delivered her baby by emergency C-section at 33 weeks in 2024.
She said: “What I didn’t know, what no one had diagnosed, was that my placenta was abnormally and dangerously attached.
“The haemorrhage was catastrophic. I lost 4.5 litres of blood. I needed a massive blood transfusion, 13 units in total, and to save my life they had to perform a hysterectomy.
“It was like a murder scene. I now have PTSD around blood. I was a theatre nurse. I’ve had to change jobs and can no longer work in a patient-facing role.
“I get panicky when I hear sirens. I can’t drive past the hospital without feeling like I’m about to have a panic attack.
“I feel a deep loss of my womanhood. I’m now going into early menopause. Not a day goes by when I don’t think about being infertile at 33.”
PAS is associated with a history of C-section birth, while assisted fertility using in vitro fertilisation also increases the risk.
It occurs when the placenta, which gives the foetus nutrients and oxygen, grows too deeply into the wall of the woman’s uterus and blocks some or all of the cervix.
This makes the usual separation of the placenta from the uterus during birth difficult.
One hundred women who are concerned about how medical teams dealt with their PAS have contacted Amisha and Nik Adhia, who set up the Action for Accreta campaign.
The couple have collated the women’s experiences into a dossier of stories that vividly illustrate how often the condition goes undetected and the appalling physical consequences for those involved.
Seventy-five of the 100 cases are from around the UK and the others from abroad. In other cases, mothers suffered permanent damage to their bladder or bowels.
Six out of 10 of the 100 women say their PAS went undiagnosed, increasing the risk of them bleeding to death.
The 100 cases reveal “a dangerous gap in maternity care” and “systemic failures” that should prompt UK hospitals to do much more to train staff how to spot and treat PAS once it is diagnosed, say campaigners.
Politicians from all the main parties at Westminster are supporting their call for a major overhaul in how the NHS manages the condition.
Chloe Robinson from Burnley was taken to hospital in the middle of the night when she began bleeding heavily at home at 34 weeks pregnant in July 2024.
She said: “In theatre they discovered I had placenta accreta, something no one had suspected.
“They had to get several members of staff who were on call into the hospital because they weren’t prepared. I lost six litres of blood and had a hysterectomy to save my life.
“My daughter had a stroke, which I believe was due to the traumatic birth [and] she now has cerebral palsy.
“If they had found the condition before, none of this may have happened.”
A woman is at higher risk of PAS if she has had a previous birth by caesarean section because the placenta of her new pregnancy can attach itself to the scar of her C-section.
It is unclear exactly why IVF seems to also heighten the risk of the condition.
Doctors believe that the process of transferring and implanting an embryo into the woman during treatment may explain it, though they add that the extra risk posed by IVF is “small”.
Jeremy Hunt, the ex-health secretary who chairs Westminster’s all party parliamentary group on patient safety, urged NHS leaders to learn from the stories.
“Nik and Amisha have highlighted an important and under-recognised issue in maternity care,” she said.
“These stories and the Action for Accreta campaign highlight worrying gaps in how PAS is identified, recorded and managed across the NHS.
“Addressing these will require a more consistent, system-wide approach, including improved data, training and clinical preparedness.”
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