Genomic Sequencing Detects Risks in Seemingly Healthy Newborns

By Marilynn Larkin

January 08, 2019

NEW YORK (Reuters Health) - Newborn genomic sequencing (nGS) can identify risk and carrier status for a wide range of conditions not detectable by currently available newborn screening assays or predicted based on an infant's clinical or family history, researchers say.

GS technologies have the potential to pinpoint risks for disorders in asymptomatic babies; enable rapid diagnosis for ill newborns; inform personalized treatments in childhood and throughout life; and help with reproductive planning, according to two Harvard Medical School researchers, Dr. Robert Green of Brigham and Women's Hospital and Dr. Alan Beggs of Boston Children's Hospital.

Despite these anticipated benefits, Drs. Green and Beggs told Reuters Health in an email, "We are not advocating for it to be standard of care at this time; in fact, this is exactly what the research is designed to illuminate."

"Clinicians should be aware that consumer-facing labs are already preparing to market genomic testing for healthy newborn infants," they noted. "Clinicians will need to understand the strengths and limitations of such information in order to best advise their families."

Drs. Green, Beggs and colleagues studied 159 newborns - 128 healthy and 31 in the neonatal intensive care unit - as part of the ongoing BabySeq Project ( Half of each group were randomized to receive standard care, including heel-prick newborn screening, which tests for about 30 genetic conditions, as well as genetic counseling based on family history; the other half received or whole exome sequencing in addition to standard care and genetic counseling.

Family histories were collected for all participants. Health outcomes and medical, behavioral and economic data were collected at the time of test result disclosure, and three months and 10 months post-disclosure.

As reported online January 3 in the American Journal of Human Genetics, nGS revealed a risk of disease onset during childhood in 9.4% of newborns. Variants were associated with several heart conditions, including dilated or hypertrophic cardiomyopathy in six newborns and supravalvular aortic stenosis in one. None of the disease risks were anticipated based on the infants' known clinical or family histories, according to the authors.

Sequencing also identified actionable adult-onset disease risk, including hereditary breast and ovarian cancer, in three of 85 newborns (3.5%) whose parents elected to receive this information.

Carrier status for recessive diseases and pharmacogenomics variants were reported in 88% and 5% of newborns, respectively.

Indication-based analyses were performed in 91% of NICU newborns and 5% of healthy newborns who subsequently underwent diagnostic analyses. No variants sufficiently explained the reason for the indications; however, suspicious but uncertain results were reported in five newborns.

Further, testing parental samples contributed to the interpretation and reporting of results in (8%) newborns.

"Having a mutation for cancer, heart disease or other conditions does not mean the child or adult will definitely get it, but it does increase the risk," Drs. Green and Beggs acknowledged. "In the rest of medicine, we seem to have come to terms with risk factors, but we have exceptionalized genetics in ways that may not be fully justified."

"One of the questions we are asking in BabySeq," they said, "is whether parents of infants in whom genetic risk factors are discovered become psychologically distressed, or does this influence the relationship between parents and infants in a negative way?"

Although the current study does not address those questions, they noted, "preliminary results presented at the American Society of Human Genetics meeting in October (see abstract by Pereira et al. here: found no additional distress in parents whose infants were so identified, and only a modest (appropriate) amount of concern about the vulnerability of such infants."

Bioethicist Dr. Arthur Caplan, founding director of the Division of Medical Ethics at NYU Langone Health in New York City, told Reuters Health by email, "Expanded newborn genetic screening is undoubtedly going to occur in the future. But it brings huge ethical, financial and practical questions in its wake."

Questions include, he said: "How much risk is worth disclosing? Where will the counseling come from, given limited numbers of genetic counselors to help parents interpret risk? Will children identified as at risk be monitored too aggressively by worried parents and will they find themselves penalized as they seek entry to school, to employment, to marry or to obtain life and other forms of insurance?"

"America has tended to treat genetic testing as a lark - a Christmas gift to find out about ethnicity and genealogy. It is not," he said.

"Newborn genetic testing is a hugely serious matter involving worry, fear, stigma, doubt, high costs and a need for sound advice and trained counseling," Dr. Caplan said. "While testing has, as this study shows, benefits for children, our health system and those in other nations are nowhere near ready to absorb widespread newborn genetic testing for both pediatric and adult onset risks."


Am J Hum Gen 2019.