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.
Pregnancy complications may increase women’s risk of peripheral artery disease later in life, new research suggests.
The study analysed data from more than two million women in Sweden who gave birth to single babies between 1973 and 2015.
Led by Casey Crump, the research examined the long-term risk of peripheral artery disease among women who experienced preterm delivery, pre-eclampsia, gestational diabetes or other adverse pregnancy outcomes.
Crump, professor in the department of family and community medicine at McGovern Medical School at UTHealth Houston, said: “Our prior work has already shown that adverse pregnancy outcomes are associated with long-term risks of heart disease, stroke, and heart failure.
“This study builds on that work by showing that these women have an increased risk of peripheral artery disease, an important but understudied cardiovascular condition.”
Peripheral artery disease is often a precursor to long-term cardiovascular complications, including stroke, ischaemic heart disease and premature death.
The condition affects millions of people worldwide and occurs when narrowed arteries reduce blood flow, most commonly to the legs and feet.
Ischaemic heart disease occurs when the heart does not receive enough blood and oxygen, usually because the arteries have narrowed.
Symptoms of peripheral artery disease can include leg pain, cramps while walking, numbness, cold feet and sores on the feet or legs that are slow to heal.
Crump said women who experience pregnancy complications have an important opportunity after giving birth to make plans with their primary care doctor to monitor long-term risks.
Women who have experienced complicated pregnancies should speak with their doctor about possible future cardiovascular health risks.
Checks for blood pressure, diabetes and cholesterol are important.
While the period after childbirth is an important time for women to monitor their health, Crump said it is never too late to lower the risk of peripheral artery disease.
He said: “Women with a history of adverse pregnancy outcomes who seem to be doing well may still have a higher risk that can emerge later in life.”
Crump also suggested preventive steps such as avoiding smoking, maintaining a healthy weight and following a healthy lifestyle.
He stressed the importance of long-term follow-up care and conversations with healthcare providers to help protect cardiovascular health later in life.
A high-powered ultrasound treatment could help identical twins affected by a rare and serious condition during early pregnancy, an initial study suggests.
Twin-to-twin transfusion syndrome, or TTTS, causes uneven blood flow between identical twins who share a placenta.
The imbalance can leave one baby dangerously small and the other too large, putting both babies’ survival at risk.
Brioney Garrett’s daughters were in danger before doctors used the world-first treatment to seal the blood vessels causing the problem without an operation.
Nancy and Margo were born healthy and, now aged four, are due to start school.
Researchers from Queen Charlotte’s and Chelsea Hospital tested the non-invasive procedure in 10 women from the UK and elsewhere in Europe after scans detected TTTS during early pregnancy.
Five women needed further treatment, while 12 of the 20 babies survived following the procedure.
The researchers described having a treatment that did not require a needle or telescope to be inserted into the mother’s abdomen as “extremely exciting”.
However, they said larger studies involving more pregnant women were needed before the procedure could be offered more widely.
Garrett described her daughters as “my miracle twins”.
She said: “We were in a very dire situation and I don’t forget that.
“It stays with me always how things could have been. Every day I still count my blessings.”
TTTS affects between 10 and 15 per cent of identical twins who share a placenta, representing around 300 to 400 pregnancies in the UK each year.
The uneven blood flow causes excess fluid to build up around the larger recipient baby, while leaving dangerously little fluid around the smaller donor baby.
Treatment usually involves inserting a needle into the womb to drain some of the fluid or using a laser to seal the connecting blood vessels.
Garrett’s procedure took about 20 minutes. She lay flat while a specially designed machine directed high-powered ultrasound waves at small blood vessels in her placenta.
She said: “It was very quick and pretty painless.”
Christoph Lees, head of fetal medicine at Imperial College Healthcare NHS Trust and professor of obstetrics at Imperial College London, described the research as “very promising”.
He said: “If this could work in a fully-fledged study, it could give hope to a lot of women who otherwise might have to have quite invasive treatment.”
Ultrasound is commonly used during medical scans to produce images of the body, but this procedure uses much more focused waves.
Heat generated by the waves can seal blood vessels about 2mm in diameter and located around 5cm to 6cm beneath the skin.
The procedure blocked blood flow in 90 per cent of the vessels treated during the study, with no unwanted side-effects reported.
Twins Trust, which supported the study, said the approach could make a significant difference for families affected by TTTS.
Helen Peck, head of healthcare engagement and research, said: “Any procedure that is non-invasive and can potentially identify TTTS earlier and improve outcomes for our families with this life-threatening condition could be a turning point.”
Scans carried out weeks after Garrett’s procedure showed that blood flow between the babies had been rebalanced, although other problems developed during the pregnancy.
Garrett said Margo, who had too little fluid around her, “was in a much better position” and that “the strain on Nancy’s heart had eased”.
Nancy and Margo were born at nearly 34 weeks, weighing 3lb 7oz and 3lb 3oz respectively.
Garrett said: “They were both healthy, and Margo wasn’t as small as we worried she was going to be.”
The twins are due to start primary school in September.
Garrett said: “They’re funny, smart, energetic little girls that just fit right in with their age group.”
A new reporting tool built specifically for obstetrics and maternal-fetal medicine has launched, aimed at teams managing increasingly complex pregnancies with limited time and resources.
Trice Imaging has released Trice Workspace Reporting, which connects imaging, reporting and longitudinal patient data in a single workflow to support faster clinical decision making.
Birth rates are falling worldwide, but pregnancies are getting more complicated. Advanced maternal age, IVF-assisted pregnancies, rising obesity rates and a higher prevalence of hypertension and diabetes mean more cases now require specialist monitoring, advanced imaging and multidisciplinary care.
At the same time, clinical teams are stretched and facing growing administrative demands.
Trice Workspace Reporting brings together customisable reporting, dynamic pregnancy dating and longitudinal patient history with an AI-ready, EHR-interoperable infrastructure, all inside the company’s Tricefy image management platform.
The company says it aims to accelerate standardised and synchronised report turnaround, support timely clinical decisions and improve operational efficiency for fetal medicine services.
“Maternal fetal medicine teams are managing increasingly complex pregnancies while being asked to do more with limited time and resources,” said Mark A. Samii, chief revenue officer at Trice Imaging.
“Trice Workspace Reporting is designed to remove unnecessary friction from reporting by creating a structured digital foundation that supports today’s need for connected clinical workflows.
“It also provides a digital foundation as practices prepare for tomorrow and the evolution of AI-enabled fetal assessment, anomaly detection and outcome prediction technologies.”
Trice Imaging describes its mission as transforming the women’s health journey by connecting physicians, patients and healthcare systems. From independent practices to large hospital ecosystems, it aims to reach the entire women’s health continuum, spanning IVF and reproductive health, maternal-fetal medicine and OB/GYN, and onwards to lifelong women’s health.
For more than 17 years the firm has worked on cloud-based storage, retrieval, display, organisation and exchange of ultrasound medical images and associated information across health environments.
Its wider platform now extends to dynamic clinical reporting, AI-driven workflow optimisation, data analytics and secure patient engagement.
Trice Imaging holds regulatory and data protection clearances in 40 countries. It has offices in Miami and Stockholm, alongside a growing network of global distributors.
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