Trisomy 13 and 18: When a lethal condition is no longer lethal

by Jenni Linebarger

What is a “lethal condition” really? How does the definition change as medical advances are made? Several times a year, I meet parents who’ve had providers tell them that their baby has a “lethal diagnosis” (or worse, that the diagnosis is “incompatible with life”) when testing detects trisomy 13 or trisomy 18. Such dire prognostication sets the stage for all future interactions with the health care community. For some, it becomes a rallying cry to prove providers wrong, for others it becomes a sealed fate. For all, it declares a level of certainty that we just do not have.

This summer, a paper published in JAMA by Katherine E. Nelson and colleagues sought to provide “more data about survival in general and after interventions” for families who have children diagnosed with trisomy 13 or trisomy 18. They conducted a retrospective, population-based cohort used linked health administrative databases for all children born in Ontario between 1 April 1991 and 31 March 2012 with a diagnostic code for trisomy 13 or trisomy 18. The data from this cohort confirms that survival is not as uncommon as once thought.

They found:

• Median survival of 12.5 days for children with trisomy 13 , and 9 days for children with trisomy 18
• The rate of deaths slowed around 3 months of age in children with trisomy 13, and 6 months of age in children with trisomy 18
• 1-year survival was 19.8 percent for children with trisomy 13, and 12.6 percent for children with trisomy 18
• 10-year survival was 12.9 percent for children with trisomy 13, and 9.8 percent for children with trisomy 18
• ~50% of all the children had an organ system with a congenital anomaly (most often cardiac)

The researchers also looked at the surgical interventions patients with trisomy 13 or trisomy 18 underwent during their lives. ENT procedures were most common in children with trisomy 13 and procedures to implant medical devices were the most frequent for those with trisomy 18. Median survival after the first surgery was greater than 1 year for all except the children with trisomy 13 who had ophthalmic surgery and children with trisomy 18 who had cardiac surgery. The authors suggest such high survival following surgery “reflects both careful patient selection and procedural benefit.”

While the researchers hope that the survival data presented can help “guide decision making” there are many factors that influence decision making that this study was not designed to delve into. First, the data did not include all prenatal diagnosis, only those surviving to birth. Second, as the authors point out, survival and quality of life are not one in the same. (Although commentator Dr. John Lantos noted, “The concept of quality of life is too vague and subjective to be helpful as a criterion for deciding about the appropriateness of treatment.”) Additionally, the data does not touch upon the decision-making itself – for instance, they did not report the percentage of deaths following decisions to withhold or withdrawal life-sustaining treatments.

So what do I take away from this study on the survival of children with either trisomy 13 or trisomy 18?

1. It is time to change the language around the diagnosis of trisomy 13 and trisomy 18. These diagnoses are not universally “lethal” (since greater than 10% survive greater than 10 years) and all surgical interventions are not futile.
2. Discussing prognosis and survival is still tough and filled with uncertainty. Which babies with trisomy 13 or trisomy 18 will die after a few days and which will live a decade? We still lack useful predictors of long-term survival when facing an individual family in a prenatal meeting.

I also reached out to lead author, and colleague, Dr. Kate Nelson. She agreed with the core take home message, and stated “While the majority of children die within the first few weeks of life, the children who survive can live a decade or more. Since there are few markers associated with long-term survival besides mosaicism, prognostication is difficult. Therefore, care must be individualized, balancing the risks and benefits based on specific clinical situations and families' goals and preferences.” She also noted that readers may link surgical intervention to longer survival, and shared the following: “Children who received surgeries had to live long enough and be healthy enough to undergo procedures, so patient selection likely played a major role in the high post-operative survival rate. More work is needed to understand how surgeries impact survival among children with trisomy 13 and 18.” You can link to the press release from her institution here.

References:
Nelson KE, Rosella, LC, Mahant S, Guttmann A. Survival and Surgical Interventions for Children with Trisomy 13 and 18. JAMA 2016; 316(4):420-429.

Jenni Linebarger, MD, MPH, FAAP is a pediatric palliative care physician at Children's Mercy Hospital in Kansas City, MO.

Photo Credit: Trisomy 13 via Wikimedia Commons