Pathologists and clinical laboratories have an opportunity to help create newborn rWGS programs in their parent hospitals and health systems
Diagnosing disease in infants is particularly difficult using typical clinical laboratory testing and modalities. Thus, the use of rapid Whole Genome Sequencing (rWGS) is gaining acceptance when such a procedure is deemed “medically appropriate” based on the child’s symptoms.
In “Whole Genome Sequencing for Newborns Gains Favor,” Robert Michel, Editor-in-Chief of Dark Daily’s sister publication The Dark Report wrote, “Evidence is swiftly accumulating that use of rapid Whole Genome Sequencing for certain children in NICUs can enable diagnostic insights that guide effective interventions. Further, these pilot rWGS programs in children’s hospitals are showing a solid return on investment because of improved care. It is predicted that more hospitals may soon offer rWGS.”
Conducted at Tufts Medical Center in Boston, the researchers found that “Whole genome tests are nearly twice as good as narrower tests at unearthing genetic abnormalities that can cause disease in infants—the study found 49% of abnormalities, compared to 27% with more commonly used tests targeting particular types of genetic diseases,” the Associate Press reported.
The AP story follows the medical journey of a now 4-year-old who was diagnosed with a rare bleeding disorder. The nearly fatal condition was only caught because broad genetic testing found she suffered from factor XIII deficiency, a blood disorder characterized by the inability to clot properly.
“I’ve been doing clinical trials of babies for over 40 years,” neonatologist Jonathan Davis, MD (above), Chief, Division of Newborn Medicine at Tufts Children’s Hospital at Tufts Medical Center and Professor of Pediatrics, Tufts University School of Medicine, told the AP. “It’s not often that you can do something that you feel is going to really change the world and change clinical practice for everyone.” Clinical laboratories that work with oncologists to treat children suffering from cancer will understand Davis’ enthusiasm. (Photo copyright: Tufts Medicine.)
Incorporating Rapid Whole Genome Sequencing into Infant Care
Genetic diseases are responsible for 41% of infant deaths, according to a Rady Children’s Institute press release, which goes on to say the usage of rWGS may significantly improve the odds for infants born with genetic disorders.
“Broad use of genomic sequencing during the first year of life could have a much greater impact on infant mortality than was recognized hitherto,” said Stephen Kingsmore MD, President/CEO, Rady Children’s Institute for Genomic Medicine, which was one of the additional study sites for the Tufts Medicine researchers.
Genetic testing is already used to predict infant health outcomes, but the Tufts study highlights further developments that could improve the process. Prenatal genetic testing can be utilized both through carrier testing to determine any potential genetic red flags in the parents, and during prenatal screening and diagnostic testing of the fetus.
When an infant presents symptoms after birth, rWGS can then be implemented to cast a broad net to determine the best course of treatment.
According to ScienceDaily, the Tufts study found rWGS “to be nearly twice as effective as a targeted gene sequencing test at identifying abnormalities responsible for genetic disorders in newborns and infants.”
However, the rWGS tests took an average of six days to come back, whereas the targeted tests took only four days, ScienceDaily reported. Also, there is not full consensus on whether a certain gene abnormality is actually the cause of a specific genetic disorder.
“Many neonatologists and geneticists use genome sequencing panels, but it’s clear there are a variety of different approaches and a lack of consensus among geneticists on the causes of a specific patient’s medical disorder,” Jill Maron, MD, Vice Chair of Pediatric Research, Tufts Medical Center, and a co-principal investigator of the Tufts study, told Science Daily.
rWGS Costs versus Return on Investment
Some also question the upfront cost of genetic testing. It can be high, but it’s coming down and Maron stresses the importance of the tests.
“Genome sequencing can be costly, but in this targeted, at-risk population, it proves to be highly informative. We are supportive of ongoing efforts to see these tests covered by insurance,” she told ScienceDaily.
Each of the doctors associated with the Tufts study emphasized the importance of this testing and the good that can be done for this vulnerable group. The potential value to the children, they say, far outweighs the drawbacks of the testing.
“This study provides further evidence that genetic disorders are common among newborns and infants,” Kingsmore told ScienceDaily, “The findings strengthen support for early diagnosis by rapid genomic sequencing, allowing for the use of precision medicine to better care for this vulnerable patient population.”
For clinical laboratories, there is also good news about reimbursement for rWGS. In a story published last fall KFF Health News wrote, “Since 2021, eight state Medicaid programs have added rapid whole-genome sequencing to their coverage or will soon cover it, according to GeneDX, a provider of the test. That includes Florida … The test is also under consideration for coverage in Georgia, Massachusetts, New York, and North Carolina, according to the nonprofit Rady Children’s Institute for Genomic Medicine, another major provider of the test.”
“Collectively, these developments are encouraging children’s hospitals, academic centers, and tertiary care centers to look at establishing their own rWGS programs,” wrote Michel in The Dark Report. “In settings where this is appropriate, hospital and health system-based clinical laboratories have an opportunity to take an active role in helping jump start a newborn rWGS program in their institutions.”
Pathologists should continue to monitor rWGS, as well as prenatal and carrier testing, to have a full awareness of its growing use in infant and young child cancer screening.
New USPSTF guidelines suggest reducing the volume of Vitamin D deficiency testing in the general population, which could reduce revenue for clinical laboratories
From 2005 to 2011, the volume of clinical laboratory tests for Vitamin D soared nationally as more doctors tested more patients for Vitamin D deficiency. This became a major source of revenue growth for many clinical laboratories performing those tests. But at least a portion of lab revenue associated with Vitamin D testing may be in jeopardy.
In a recommendation statement published in JAMA Network, titled, “Screening for Vitamin D Deficiency in Adults,” the United States Preventive Services Task Force (USPSTF)—following up on its 2014 recommendations—stated “that the current evidence is insufficient to assess the balance of benefits and harms of screening for Vitamin D deficiency in asymptomatic adults.”
The USPSTF’s new recommendations concerning Vitamin D testing came after the federal task force performed an extensive review of the benefits and potential harm of screening for Vitamin D deficiencies in non-pregnant adults who displayed no symptoms of a deficiency. Symptoms of a Vitamin D deficiency include fatigue and tiredness, bone and back pain, depression, impaired would healing, bone loss, hair loss, and muscle pain.
After completing its research, the USPSTF concluded “the overall evidence on the benefits of screening for Vitamin D deficiency is lacking. Therefore, the balance of benefits and harms of screening for Vitamin D deficiency in asymptomatic adults cannot be determined.”
Are USPSTF Conclusions Contrary to Current Deficiency Testing Practices?
“Among asymptomatic, community-dwelling populations with low Vitamin D levels, the evidence suggests that treatment with Vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events,” the JAMA Network article states.
Other studies have linked low Vitamin D levels with some health conditions and risks, however, the USPSTF review found no studies that directly evaluated any perks associated with Vitamin D screening in otherwise healthy individuals.
Everyday Health listed 10 illnesses linked to low Vitamin D deficiency. They include:
“We see a lot of associations between Vitamin D deficiency and poor health outcomes,” Mary Byrn, PhD, RN, an associate professor at Loyola University in Chicago who studies Vitamin D, told Everyday Health. “Although these are relationships and we are unable to conclude cause and effect, taking Vitamin D supplements or exposing yourself to the sun in a safe manner to increase Vitamin D naturally are easy ways to improve your health and try to reduce your risk of multiple diseases,” she said. (Photo copyright: Midwest Nursing Research Society.)
Can Vitamin D Supplementation Be Harmful?
The USPSTF study also stated that Vitamin D supplementation appears to be safe and that toxicity from too much Vitamin D would be rare. One of the USPSTF’s key concerns of screening for Vitamin D in asymptomatic individuals was the potential for misclassification and inaccurate diagnoses.
The study also revealed that more research is needed to determine what serum levels are optimal when diagnosing a Vitamin D deficiency, and whether those levels vary by subgroups, such as race, ethnicity, or gender.
The JAMA Network article states that “the evidence is inconclusive about the effect of treatment on physical functioning and infection.”
The amount of Vitamin D individuals need each day depends upon their age. The National Institutes of Health (NIH) recommends that adults between the ages of 19 and 70 get 15 micrograms or 600 International Units (IU) of Vitamin D daily.
According to an NIH fact sheet, people can receive Vitamin D through sun exposure, supplements, and some food, such as fatty fish, mushrooms, beef liver, cheese, and egg yolks, plus foods that are fortified with Vitamin D, such as some milk products and breakfast cereals.
Vitamin D and COVID-19
It has been widely reported that approximately 42% of Americans are Vitamin D deficient. And Vitamin D deficiency has been linked to an increased risk of contracting the SARS-CoV-2 coronavirus and how well patients recover after COVID-19 treatment.
A study published in the Journal of Clinical Endocrinology and Metabolism that examined 216 COVID-19 hospitalized patients in Spain found that over 80% of those individuals were deficient in Vitamin D. The study also found that COVID-19 patients who had lower Vitamin D levels also had a higher number of inflammatory markers that have been associated with poorer COVID-19 outcomes. The results of this study were in March.
For several decades, experts have recommended avoiding sun exposure and using sunscreen to avoid skin cancers. This may have caused people to get less Vitamin D from sun exposure. It may also have contributed to an increase in the number of Vitamin D deficiencies and increased COVID-19 infections.
Pathologists and clinical laboratory managers should keep in mind that the USPSTF recommended less testing for Vitamin D deficiencies in asymptomatic individuals. This proposal may affect test volume in clinical laboratories, as Vitamin D testing has been a common and lucrative assay for many years.
Researchers observe that over-utilization of lipid tests by many physicians represents a waste of healthcare resources
Up to one-third of coronary heart disease (CHD) patients undergo lipid testing that may be unnecessary. This is one finding from a credible study involving 28,000 patients that could focus more attention on the overuse of lipid tests and similar medical laboratory tests by physicians.
Most pathologists and clinical laboratory managers will welcome the findings of this study. It is widely recognized within the laboratory medicine profession that many physicians regularly order inappropriate medical tests. This has been a problem for decades and is the source of much wasteful spending.
The lipid testing study is significant because of the large volume of lipid tests performed annually in the United States. Any attention to this problem can help improve utilization of this important test and result in substantial savings to the healthcare system. (more…)
