Newborn DNA sequencing finds actionable disease risks in nearly 10% of enrolled babies

BabySeq study sequenced the DNA of 159 newborns
(PHOTO: AdobeStock)

Current newborn screening tests a baby’s blood for several dozen known, treatable conditions. Can full-on DNA sequencing at birth add more benefit? Interpreting sequencing results is complex: having a genetic variant doesn’t always mean having the disease, and many of the conditions identified may not currently be treatable.

To explore what DNA sequencing might turn up, the BabySeq study, an NIH-funded project, was in launched in 2015. A team led by Ozge Ceyhan-Birsoy, PhD of Partners HealthCare and Alan H. Beggs, PhD, now reports the comprehensive results of whole-exome sequencing in 159 infants. Their analysis is published in the American Journal of Human Genetics.

Overall, 7 percent of the families initially approached enrolled an infant in BabySeq. Their 315 infants included 65 in newborn intensive care units (NICUs) at Boston Children’s, Brigham and Women’s Hospital and Massachusetts General Hospital, and 251 healthy babies in the Brigham and Women’s well-baby nursery.

Half of the babies were randomly assigned to standard newborn screening alone. The other 159 (127 healthy babies and 32 in NICUs) also underwent whole-exome sequencing.

Newborn sequencing results

Fifteen babies (9.4 percent) had genetic variants that conferred a high likelihood of a childhood-onset disease — or a moderate likelihood of a disease for which early intervention and monitoring could help. Conditions included cardiomyopathy, biotinidase deficiency, congenital adrenal hyperplasia, venous malformations, cystinuria and hearing loss.

Only time will tell how the costs — both financial and in terms of extra medical testing and family stress — balance out against the benefits. That’s what we’re really trying to find out.

“None of these findings were predicted based on known clinical or family histories of the newborns,” notes Ceyhan-Birsoy, first author on the paper.

Of note, three newborns who “passed” routine newborn screening were identified to be at risk for conditions included in newborn screening. They had either extremely mild disease that wasn’t clinically evident, or had forms not expected to manifest until later in life.

Interestingly, only one of the 32 NICU babies had a likely genetic cause identified for their illness, although five (16 percent) had variants whose significance was uncertain. Beggs notes that many babies in the NICU have non-genetic problems, like prematurity or respiratory distress. Also, parents who wanted sequencing to investigate their baby’s illness may have decided not to roll the dice with a randomized study. This could have left behind a group of babies less likely to have a genetic cause.

Carrier status

Most newborns — 88 percent — were found to be carriers, meaning they at least one genetic variant associated with disease. While the babies had just one copy of the variant and were not at risk for disease themselves, they could potentially pass the variant on to their own children.

Risk for adult-onset conditions

Families of 85 babies also agreed to receive results indicating a risk for adult-onset conditions, provided they were actionable. (Diseases with no treatment, such as Alzheimer’s disease, were excluded.) Three babies (3.5 percent) had such genetic risk factors. Two babies had a variant linked to breast cancer, and one had a variant linked to colon and endometrial cancer. Each gene was also found in a parent, who was referred for counseling and potential cancer surveillance.


Eight (5 percent) of the sequenced babies had a “pharmacogenomic” variant, one that predicts an adverse effect, lack of response or altered dose requirement for particular medications. (In four cases, this was a cancer chemotherapy drug; in the rest, an immunosuppressive medication). These babies would need to have their prescription or dosage adjusted should they need these medications in the future.

Next steps for BabySeq

The BabySeq investigators will follow the sequenced babies over time. Forthcoming papers will report what actions families take based on the genetic findings, what tests they lead to, their cost and how knowledge of the genetic findings affects family dynamics.

“Sequencing results have potential to raise questions that may be upsetting for parents, but could also lead to helpful or even lifesaving interventions,” says Beggs, the paper’s senior author. “Only time will tell how the costs — both financial and in terms of extra medical testing and family stress — balance out against the benefits. That’s what we’re really trying to find out.”

The overall BabySeq study is led by Beggs and Robert C. Green, MD, MPH, of Brigham and Women’s, with Amy L. McGuire, JD, PhD and collaborators at the Baylor College of Medicine. The current study was funded by the National Institute of Child Health and Human Development and the National Human Genome Research Institute of the NIH.

More coverage of the BabySeq findings:

WBUR: Baby DNA: Boston Researchers Find Childhood Genetic Risks In 9 Percent Of Newborns

STAT: A deep dive into newborns’ DNA can reveal potential disease risks — but is the testing worth it?

Washington Post: Baby DNA tests raise as many questions as answers

The Scientist: Babies’ Genomes Identify Risks Overlooked by Newborn Screens