Archive for the ‘CHILDREN’ Category

IVF baby born using the latest revolutionary genetic-screening process

Saturday, May 28th, 2016

Next-generation sequencing could enable IVF clinics to determine the chances of diseases developing in children

David-Levy-and-Marybeth-S-010 with dna selection image

Baby Connor Levy with his parents David Levy and Marybeth Scheidts

The first IVF baby to be screened using a procedure that can read every letter of the human genome has been born in the US.

Connor Levy was born on 18 May after a Philadelphia couple had cells from their IVF embryos sent to specialists in Oxford, who checked them for genetic abnormalities. The process helped doctors at the couple’s fertility clinic in the US select embryos with the right number of chromosomes. These have a much higher chance of leading to a healthy baby.

The birth demonstrates how next-generation sequencing (NGS), which was developed to read whole genomes quickly and cheaply, is poised to transform the selection of embryos in IVF clinics. Though scientists only looked at chromosomes – the structures that hold genes – on this occasion, the falling cost of whole genome sequencing means doctors could soon read all the DNA of IVF embryos before choosing which to implant in the mother.

If doctors had a readout of an embryo’s whole genome, they could judge the chances of the child developing certain diseases, such as cancer, heart disease or Alzheimer’s.

Marybeth Scheidts, 36, and David Levy, 41, had tried another fertility treatment, called intrauterine insemination (IUI), three times without success before they signed up for IVF at Main Line Fertility clinic in Pennsylvania.

As part of an international study with Dagan Wells, a fertility specialist at Oxford University, the couple were offered NGS to check their IVF embryos for abnormal chromosomes. Abnormal chromosomes account for half of all miscarriages.

The chances of an embryo having the wrong number of chromosomes rises with the mother’s age, and potentially with the father’s. For women in their 20s, one in 10 embryos may have the wrong number of chromosomes, but for women in their 40s, more than 75% can be faulty.

Most of the time, embryos with abnormal chromosomes fail to implant in the womb. Those that do are usually miscarried. The portion that survive to full term are born with genetic disorders, such as Down’s syndrome and Turner syndrome.

After standard treatment at the US clinic, the couple had 13 IVF embryos to choose from. The doctors cultured the embryos for five days, took a few cells from each and sent them to Wells in Oxford for genetic screening. Tests showed that while most of the embryos looked healthy, only three had the right number of chromosomes.

“It can’t make embryos better than they were in the beginning, but it can guide us to the best ones,” said Wells.

Based on the screening results, the US doctors transferred one of the healthy embryos into Scheidts and left the rest in cold storage. The single embryo implanted, and nine months later Connor was born. Details of the study will be given at the European Society of Human Reproduction and Embryology (Eshre) meeting in London on Monday.

“I think it saved us a lot of heartache,” Scheidts told the Guardian. “My insurance covered me for three cycles of IVF. We might have gone through all three without the doctors picking the right embryos. I would not have a baby now.”

A second baby who had the same genetic screening is due to be born next month, after a US couple had IVF at New York University fertility centre.

Doctors can already screen embryos for abnormal chromosomes using a technique called Array CGH, but the procedure adds more than £2,000 to the cost of IVF. Wells said NGS could bring the cost down by a third. To check the number of chromosomes is much simpler than reading all of the DNA accurately.

“It is hard to overstate how revolutionary this is,” said Michael Glassner, who treated the couple at the Main Line Fertility clinic. “This increases pregnancy rates by 50% across the board and reduces miscarriages by a similar margin. It will be much less expensive. In five years, this will be state of the art and everyone who comes for IVF will have it.”

In Britain, doctors are banned from selecting embryos for anything other than the most serious medical reasons. But as scientists learn more about genetic causes of disease, the urge to choose embryos to avoid cancer and other diseases later in life will intensify.

“You can start to have a very scary picture painted if you talk about height and hair colour and so on,” said Glassner. “We have to make sure this is used judiciously.”

The prospect of “designer babies” is remote for now, even if it were made legal. IVF produces only a dozen or so embryos at best, so the odds that one has all the traits a couple desires are very low. “IVF is still expensive and uncomfortable with no guarantee of a baby at the end. I can’t imagine many people wanting to go through the strains of IVF for something trivial,” said Wells.

The Oxford team now plans a large trial of the screening procedure to assess how much it boosts pregnancy rates, and which age groups it benefits the most.

Scheidts still has two screened embryos in cold storage, but has not yet decided whether to use them. “We haven’t even thought about that. We’ll see how the first year goes.”


Henry Sapiecha

How Can Viruses Like Zika Cause Birth Defects?

Monday, February 8th, 2016
While the link between Zika and microcephaly is uncertain, similar diseases show how the virus might be affecting infants

Thousands of infants born in Brazil have been reported to show signs of microcephaly,-image

Thousands of infants born in Brazil have been reported to show signs of microcephaly, like Alice pictured here being comforted by her father. (Rafael Fabres/dpa/Corbis)

In adults, the symptoms of the Zika virus are relatively mild—rashes, fever, joint pain, malaise. Most who are infected may not even know it. But as this seemingly routine disease spreads across the Americas, so do cases of a much more severe problem: infants born with microcephaly.

This birth defect comes from malformation of the brain, leaving those inflicted with varying degrees of shrunken heads and in many cases a slew of neurologic problems. These include hearing troubles, developmental delays and intellectual impairment.

Brazil usually sees a couple hundred cases of microcephaly per year—a number that some suggest is unusually low due to underreporting. Diseases from parasites like malaria or toxoplasmosis, genetic mutations and even excessive alcohol consumption during early pregnancy can all cause microcephaly. But since October 2015, well over 3,500 infants have been reported with telltale signs of the deformation, coinciding with the explosive spread of the Zika virus in the region.

The spotty information from this outbreak is not enough to definitively say whether Zika causes microcephaly. But the link is plausible, and medical experts are looking to other viruses known to cause developmental defects to try to figure out Zika’s potential pathway to destruction.

“Certain viruses really love the brain,” says Kristina Adams Waldorf, an obstetrics and gynecology doctor who studies how infection induces preterm labor. Cytomegalovirus and rubella have relatively mild impacts on healthy adults but can cause debilitating birth defects. And varicella-zoster virus (which causes chicken pox) can cause a host of complications, including problems in the brain.

Many mosquito-borne viruses, like West Nile, also cause forms of brain injury in adults. “So it’s not a big stretch for us to make the connection between a mosquito-born virus [and] microcephaly,” she says.

Spread mainly by the Aedes aegypti mosquito, Zika was first identified in Uganda in 1947 in rhesus monkeys. Notable outbreaks struck humans on the tiny island of Yap in 2007 and in French Polynesia in 2013. But few people in the Americas had likely heard of Zika until the recent outbreak exploded in Brazil.

No one knows how the virus got there, but many have suggested that it arrived in 2014, carried in the blood of someone among the hordes of people flocking to the World Cup. Since then Zika has spread to more than 20 countries and territories. The possible link to microcephaly has sparked travel warnings for pregnant women and prompted the World Health Organization to declare Zika a global health emergency.

It’s no medical surprise that a virus like Zika can have relatively mild impacts on adults but potentially catastrophic effects on developing fetuses.

Viruses reproduce by hijacking their host’s cells, using their natural processes to make copies of themselves. These copies then strike out on their own to infect more cells. When a virus interferes, the cells can’t function normally—the virus either kills the cells or prevents them from functioning well enough to report for duty. That makes viral infections especially dangerous for developing babies.

“When the fetus is developing its brains, there are a lot of sensitive cells there that have to get to the right places at the right times,” says virologist Kristen Bernard at the University of Wisconsin, Madison. That’s a serious problem in fetuses, which don’t yet have robust ways to fight off microbial invaders.

“You’re talking about a fetus that has a minimal immune system, whereas an adult has, hopefully, a fully functioning immune system,” explains pediatrician and immunologist Sallie Permar of the Duke University School of Medicine.

This cellular vulnerability is the basis of developmental issues linked to cytomegalovirus, or CMV, says Permar. CMV is in the Herpes family of viruses and is the most common infection passed from mother to child in the United States. Between 50 and 80 percent of people in the U.S. will be infected with the virus by the age of 40, according to the Centers for Disease Control and Prevention. Similar to Zika, few of these people will ever show symptoms of the infection.


We don’t have a great understanding of how CMV-infected cell impairment results in specific neurologic defects in babies, Permar says, but there are clues. “It seems that where the virus is replicating is where you end up with some neurologic impairments.”

For example, hearing loss is a major problem for infants born with CMV. In such cases, the virus can be found in both the part of the brain that helps with hearing as well as a portion of the inner ear called the cochlea, Permar says.

Similarly, some genetic cases of microcephaly have previously been linked to the dysfunction of a particular structure in cells called a centrosome, says Adams Waldorf. This structure is where the “scaffolding system” of the cell organizes and is involved in cell replication, she explains. When the centrosome is damaged, the brains don’t develop properly.

It’s possible Zika is staging an attack on infant brain cells that mirrors the genetic condition. In December, the Brazil Ministry of Health announced identification of Zika virus in multiple tissues of an infant with microcephaly, including the brain. But it’s still too early to make a direct link.

It’s also unclear how Zika can penetrate the natural barrier between mom’s bloodstream and her placenta—although there’s already evidence that it can happen. In the same report, the Brazil Ministry of Health also confirmed two instances of Zika in the amniotic fluid of developing fetuses with microcephaly.

No matter the virus, if mom gets a severe illness during pregnancy, additional damage can be caused by the so-called “bystander effect,” says placental biologist Ted Golos of the University of Madison-Wisconsin.

When the body detects something foreign, like a virus or parasite, it triggers inflammation in an attempt to get rid of the intruder. Despite these positive intentions, “the cascade of events that happen in response to a pathogen can [poorly impact the fetus] in a collateral damage kind of way,” he says. Inflammation of the placenta, for instance, can cause miscarriages and other complications.

There’s added concern that if the link between Zika and birth defects is confirmed, many of the longer term impacts of this disease won’t be identified for years. “Microcephaly is a tragic outcome,” says Golos. “But it could very well be the tip of the iceberg. Or it might not … we simply don’t know.”

The hope now is that researchers can develop a Zika vaccine, so if the virus is causing birth defects, we can stamp out their cause.

“We have the tools to eliminate one very severe congenital infection, and that’s been rubella virus,” says Permar. “So there is a success story with a maternal vaccine.”



Henry Sapiecha


Friday, January 30th, 2015

The front view X-ray that shocked Dr Ghofran Ageely.

An unexpected sighting of SpongeBob SquarePants gave a radiologist in Saudi Arabia quite a shock.

Dr Ghofran Ageely at King Abdulaziz University Hospital had X-rayed a 16-month-old boy who had been taken to hospital after it was thought he’d swallowed something.

Ageely told Live Science the first X-ray she saw was the side view, which showed a thin object in the toddler’s throat which she thought was a pin or hair slide.

The side view, which made Dr Ageely think the foreign object was a pin.

She then checked the front view X-ray and got a shock to see SpongeBob staring right back at her.


“I screamed! I was amazed by the visible details. You can see his freckles, shoes and fingers…AMAZING,” said Ageely.

The SpongeBob figure turned out to be a necklace pendant that belonged to the boy’s sister, and doctors managed to remove it from his esophagus without any complications.

Ageely then shared the images on, so they could be discussed by other medical professionals and students.

Managing editor of Radiopaedia, Dr Andrew Dixon, says while they get a lot of interesting X-rays on the sight, the SpongeBob one is unique.

“We see a lot of amazing X-rays on our site, but this one is particularly amazing,” said Dixon.

He told Live Science the features in SpongeBob’s face are distinctive because they are made from raised lines of metal rather than just paint.

While the SpongeBob pendant is out of the ordinary, Dixon said young children often swallow or inhale foreign objects.

“As a father, I know kids put things in their mouth all the time. But as a radiologist, we see this not infrequently,” said Dixon.

While coins, bobby pins, and marbles, are some of the many things children put in their mouths, some things they swallow can be dangerous.

In 2012, parents were issued warnings after a grade 2 student from Sydney swallowed magnets the children were using as fake piercings.

The tiny magnets stuck together on either side of Joel Smith’s stomach wall, and doctors performed a five-hour surgery to remove them before they ruptured his bowel.

His mother Melinda Smith said the surgeons at Wesmead Children’s Hospital were fantastic, but it was a horrible experience.

“They showed me the X-ray showing how quickly and aggressively the magnets had joined up and said he would have been a very, very sick little boy. They said they were an hour to an hour and a half from perforating the bowel and if that happened it would have been touch and go.”

Similar magnets, which are sold as adult stress management toys, killed a toddler in Queensland the year before.


Henry Sapiecha


Monday, August 25th, 2014

family shadow symbol image

It’s a good question. The simple answer is threefold:

  • We don’t know what causes brain cancer
  • Current treatments are not good enough
  • We don’t have enough money for research to change this

But in addition, there are specific issues to deal with in paediatric or childhood cases.

Let’s start with the cause: the fact is we don’t know what causes children to develop brain cancer, or adults for that matter. There are various theories, from genetic mutations to epigenetic or environmental factors to viral infections, and research is continually making new discoveries which improve our understanding of the disease. But the more we discover about brain cancer, the more we realise there is still so much more to find out. Take medulloblastoma, for example, which is a common paediatric brain tumour. Because of research and a greater understanding of how brain cancer operates on a molecular level, what was previously thought of as one type of brain cancer is now known to have at least four genetic sub-types, which all require different treatments. As we discover more about the disease, we discover there are even more questions to answer regarding how to treat it.

As well as genetic mutations there are epigenetic factors to consider. A recent Australian study found that fathers working in jobs where they are regularly exposed to benzene in the year before their child is conceived are more than twice as likely to have that child develop a brain tumour. Women working in occupations that expose them chlorinated solvents – found in degreasers, cleaning solutions, paint thinners, pesticides and resins – at any time in their lives also have a much higher risk of their child developing a brain tumour. The researchers stressed that it’s still too early to say whether solvent exposure causes brain tumours. But it is an example of research pointing to epigenetic factors in the development of brain tumours, and specifically the vulnerability of children to brain cancer even before they are born. What we suspect at this stage is that it is likely to be a combination of genetic and environmental factors that lead to increased risk.

The next thing to consider is how effective treatments for children with brain cancer are. The answer: not effective enough. In fact, the internationally recognised expert in childhood brain cancer, Dr Nick Gottardo, describes current treatments as “woefully ineffective”.

Brain cancer is different in children than in adults. There are forms which more commonly affect kids, such as medulloblastoma. But even when typically adult tumours such as high grade gliomas do occur in children, they present very differently on a molecular level.


“They look the same under the microscope, but molecularly they are very distinct diseases….Having more information on these tumours can only benefit us in being able to choose more rational therapies in the near future.”

– Dr. Nick Gottardo

Again, we don’t know why children manifest their own versions of this disease. And some paediatric brain tumours, such as DIPG (Diffuse Intrinsic Pontine Glioma) are brain-stem based and therefore usually inoperable; with the limited treatments available, without surgery, the prognosis is very bleak.

Plus, children’s brains are still developing so the standard treatments for brain cancer, which include surgery, radiotherapy and chemotherapy, can result in more substantial and permanent side effects than they would for an adult. This is a massive problem with childhood cases; applying treatment is harder than in the case of adults. Hence a major consideration when developing new treatments for paediatric brain cancer is how to provide quality of life as well as increasing survival.

“We’re all aiming for 100%, that’s our goal – to cure all children. But we also want to cure them, leaving them with a good quality of life in the long term.”

– Dr. Nick Gottardo

Research funded by The Brain Tumour Charity in the UK has been investigating ways to improve quality of life for children diagnosed with a brain tumour. The team at the University of Southampton collected data on children surviving a brain tumour, including looking at the use of an alternative radiotherapy technique called hyperfractionated radiotherapy, which involves dividing the total dose of radiation into a larger number of smaller doses or fractions, to decrease the effect of the radiation on other tissues, such as the brain. The clinical trial was run by the European International Society for Paediatric Oncology and found that hyperfractionated radiotherapy had less of an impact on children’s memory, planning and organisational skills than conventional radiotherapy. The team says this is an example of how adjusting radiation dose can help reduce side effects while still treating the tumour. In a separate study the researchers looked into different tumour types and observed that different tumours have an impact on quality of life. Furthermore, tumour sub-type is important, with children with medulloblastoma tumours containing the ‘sonic hedgehog’ gene experiencing a better quality of life after treatment than those with other medulloblastoma sub-types. This is the first time that tumour biology has been related to quality of life in medulloblastoma sub-types.

“What we want to do is find new therapies that will be more specific against the tumour and with fewer side effects, so that the children are cured and also cured with excellent quality of life in the future”.

– Dr. Nick Gottardo

The next problem is not insignificant, but nor is it insurmountable: funding. Survival rates for brain cancer have hardly changed in 30 years and remain far too low, with only 2 in 10 people surviving for 5 years. The reason for this – and by association, the reason why brain cancer kills more children than any other disease in Australia – is largely that not enough money has been invested in research. Cure Brain Cancer is doing things differently to improve outcomes for patients and one of things that makes us different is our approach and outlook. Our question is not ‘why?’ but ‘why not?’ and – more importantly – ‘how can we?’ Perhaps this is the more pertinent question here; not why brain cancer kills these children, but how are we going to change this

Research into paediatric brain tumours has come a long way already. Yes, there is a long way to go; survival rates for brain cancer have hardly improved for 30 years. But that’s not because nothing has been done. However, the number of clinical trials for children and access to these trials is limited; with a disease of such low incidence, the clinical research has historically tended to follow what has been done in adult trials, but this is changing.

Professor Stewart Kellie, a paediatric neuro-oncologist & oncologist at The Children’s Hospital at Westmead, says there have already been huge advances, but says global collaboration is key to success when it comes to paediatric clinical trials and research. By pooling resources, answers can be arrived at more quickly.

“I think the biggest change that I’ve seen in my professional career has been the incorporation of research – and particularly clinical trials – into the frontline treatment of children”.

– Prof. Stewart Kellie

Back in April, four international studies made breakthroughs simultaneously in a fatal form of brain cancer, Diffuse Intrinsic Pontine Glioma (DIPG). All of them focused on mutations in the ACVR1 gene. (We published an article at the time looking in more detail at these studies.) Discovering these links between ACRV1 and DIPG opens up many more questions, but that’s not necessarily a bad thing, because it also opens up many more possibilities. One of those studies, led by scientists at the Institute of Cancer Research in London, identified recurrent activating mutations in the ACVR1 gene in DIPG, but also found that those mutations are identical to ones found in people with the congenital childhood developmental disorder fibrodysplasia ossificans progressiva (FOP). What this means is that they can start to investigate whether drugs that have already been developed for FOP could be repurposed to treat DIPG. By discovering common gene mutations between paediatric brain cancer and other diseases or cancers, new treatment options present themselves. This discovery was made possible in part because of international collaboration.

Access to children’s tissue samples to facilitate research is also vital, not just because it can provide insights into that particular patient’s tumour, but because developing tissue banks enables researchers to compare and cross reference data from across brain tumours and across other cancers and diseases. In a recent blog for Cure Brain Cancer, Barrie Littlefield, whose own daughter died from glioblastoma in 2011, said he thinks quick and accurate tumour pathology and up-to-date genetic testing should happen regardless of whether there are clear clinical implications, as the information may be useful at a later stage if not immediately. Tissue banks are invaluable resources when it comes to developing new therapies and understanding the molecular biology of brain tumours. Just last week, a study using data from The Cancer Genome Atlas (a large scale genomic sequencing project) suggested that 1 in 10 cancers could be diagnosed more accurately based on genetic makeup, rather than where they occur in the body. The researchers genetically profiled and compared 3,500 samples of tumor tissue and identified 12 sub-types of cancer, only five of which correlated with their tissue-of-origin classifications. The other seven were newly identified genetic subtypes of cancer which affect more than one type of tissue. They say it ultimately provides the biologic foundation for a new era of personalized cancer treatment, in which cancers are diagnosed based on genetics rather than tissue of origin.

As you can see, many questions remain regarding childhood brain tumours. We don’t know why brain cancer occurs. But crucially we need to answer the question ‘how?’ How do we treat this disease? How do we improve survival, as investment in research has done for other diseases such as leukaemia and breast cancer? How do we give children diagnosed with brain cancer a more hopeful prognosis? The urgency and focus is on finding new treatments but epidemiological advances (which have been hampered by low incidence in children thus far) could ultimately be critical, and this too could be unlocked through further research investment and collaboration. Research will answer these big questions. All that’s required is funding.

Don’t let kids fight brain cancer alone
Henry Sapiecha


Monday, June 30th, 2014

nicu-hospital sign image

One baby has died and 14 others are fighting for their lives after being poisoned in neonatal care units in the UK.

A public health alert was issued by health chiefs last night after it emerged that all the newborns’ infections were caused by a contaminated batch of nutrition drip.

The children were affected at neonatal intensive care units at six different hospitals, but the infected drip is believed to have been used in 22 hospitals across the country.

Officials said that one newborn baby has died. Another 14 remain ill with blood poisoning, but were last night responding to antibiotics.

The newborns, most of whom were premature, were being fed through a tube into their bloodstream because they were too poorly to be mouth fed.

Medical regulators are investigating an incident

which occured last Thursday at a London manufacturing plant owned by ITH Pharma Ltd, affecting the liquid feed produced that day.

The contamination is believed to have been accidental rather than any act of sabotage, with the illness caused by a common bacterium known as Bacillus cereus.

All of the feeds which could be contaminated have since been recalled. Regulators said because the blood poisoning develops quickly they were not anticipating further cases,

although this could not be ruled out.

Last night paediatric doctors said the contamination was “every parent’s worst nightmare” and that urgent action must be taken to improve the safety of processes to produce such nutrition.

Adam Finn, professor of paediatrics, University of Bristol, said: “When a medicine makes patients sick, it is everyone’s worst nightmare. This contamination incident seems to have been detected quickly but, tragically, not quickly enough to save a life lost.

“Having stopped the outbreak, the next priority will be to understand how it came to happen and ensure it cannot recur.”

The first case appeared at Chelsea and Westminster hospital on Saturday and then other London hospitals began to see cases over the weekend. It was thought to have been caused by infected bedding or similar products used locally until cases began appearing elsewhere on Monday and Tuesday.

The final cases at Luton were diagnosed early yesterday and investigations soon identified the feed as the likely cause, a spokesman for Public Health England said.

Bacillus cereus is a bacteria found widely in the environment in dust, soil and vegetation. Most surfaces would be likely to test positive for its presence. Dr Susan Hill, a consultant paediatric gastroenterologist, said, “This is a life-saving treatment for babies who are born very prematurely or with a severe gut problem. Any challenge to their immune system can be life-threatening.”

The Daily Telegraph

Henry Sapiecha