Experiences of children with trisomy 18 referred to pediatric palliative care services on two continents

Abstract Children with trisomy 18 that survive beyond the neonatal period have multiple congenital anomalies, neurodevelopmental disability, and high mortality rates. The experience of children with trisomy 18 who receive pediatric palliative care services is largely unknown. We conducted a retrospective review of children with trisomy 18 receiving pediatric palliative care services at both Boston Children's Hospital, USA and Great Ormond Street Hospital, UK from January 1, 2004 to January 1, 2015. Fifty‐eight children with trisomy 18 were referred to pediatric palliative care, 38 in the United Kingdom, 20 in the United States. Median age at referral was 19 days (2–89) in the United Kingdom, and 25 days (1–463) in the United States. Median length of time being followed by pediatric palliative care was 32 days (1–1,637) in the United Kingdom and 67 days (3–2,442) in the United States. The only significant difference in the two cohorts (p = .001) was in likelihood of receiving cardiac surgical intervention—37% in the United States, 0% the United Kingdom. Children with trisomy 18 receive pediatric palliative care services, with variable age at referral and for a variable length of time. Further research is needed to understand the experience of children with trisomy 18 and their families receiving pediatric palliative care services.


| INTRODUCTION
Trisomy 18 is the second most common autosomal numerical chromosomal disorder, occurring in 15 of every 100,000 live births (Parker et al., 2010) and leads to multi-organ system anomalies, including cardiac malformations and neurological impairment (Merritt et al., 2012).
Population studies have shown that over 50% of children born with trisomy 18 die within weeks of being born, and less than 10% survive beyond 1 year (Irving, Rochmond, Wren, Longster, & Embleton, 2011;Meyer et al., 2015;Rasmussen, Wong, Yang, May, & Friedman, 2003;Vendola et al., 2009). Children that live into early childhood have neurological impairment, with significant cognitive, language, and motor delays (Lorenz & Hardart, 2014;Meyer et al., 2015). However, recent longitudinal studies have shown 5-and 10-year survival rates of Boldt, & Weissman, 2004). A majority of children receiving PPC have a genetic diagnosis and/or congenital malformation, most have some degree of cognitive impairment, and are followed typically by PPC teams for at least 1 year (Feudtner et al., 2011 Children with partial or mosaic trisomy 18 were also included. Children lost to follow up were counted as alive with length of life based on date of last follow up at each hospital. All data were obtained from medical records, information regarding surgical intervention was based on procedure notes. Surgical anomalies, both cardiac and non-cardiac, were defined as any anomaly that would typically require surgical intervention, not whether surgery was indicated or performed. Cardiac surgical intervention was defined as any procedure performed by a cardiac surgeon or interven-

| RESULTS
Fifty-eight children with trisomy 18 were referred to PPC services, 38 at GOSH, 20 at BCH. Eleven of the referrals at GOSH were antenatal, five died prior to being born, and there were no antenatal referrals at BCH. The majority of children referred were female, 79% percent at GOSH, and 75% at BCH (Table 1).
Children with trisomy 18 lived from 0 to 2,505 days. At the time of study, seven were alive at GOSH, five were alive at BCH. No children were lost to follow-up at GOSH, two were lost to follow up at BCH. Survival curves of each cohort are presented in Figure 1. There was no significant difference in survival (p = .095).
A majority of children at both institutions had a congenital heart anomaly, 88% at GOSH, 95% at BCH. Of the children with congenital heart disease, none underwent cardiac surgery at GOSH, while seven (37%) underwent cardiac surgery at BCH (p = .001). A minority of children had a non-cardiac surgical anomaly, 21% at GOSH and 30% at BCH, and of those children, three (38%) at GOSH and five (83%) at BCH underwent a surgical procedure.

| DISCUSSION
We report data from children with trisomy 18 who received PPC services in large tertiary care centers, on two different continents. These  Survival data for children with trisomy 18 who received PPC services mirrors that of larger population studies (Nelson et al., 2016) where the majority die within weeks, but a smaller percentage live for years. The trend toward longer survival at BCH, may be indicative of differing rates of cardiac surgical interventions, which has been shown to be associated with increased survival in cohorts of children with trisomy 18 in Japan (Kaneko et al., 2009;Maeda et al., 2011).  (Bruns & Martinez, 2015;Costello et al., 2015;Donovan, Krigbaum, & Bruns, 2016;Janvier, Farlow, & Barrington, 2016;Kaneko et al., 2008;Kosho et al., 2006;Kosiv, Gossett, Bai, & Collins, 2017;Nakai, Asano, Nomura, Matsumae, & Mishima, 2016;Nelson et al., 2016;Nishi et al., 2013;Peterson, Calamur, Fiore, Huddleston, & Spence, 2018;Peterson, Kochilas, Catton, Moller, & Setty, 2017;Subramanian et al., 2015). decision-making model of care (Boss et al., 2013;Brosco & Feudtner, 2017 conditions, based on experiences of having a diagnosis previously thought to be "incompatible with life" (Janvier, Farlow, & Wilfond, 2012). Important questions include optimal timing of PPC referral, and the role of antenatal PPC consults for children with trisomy 18. As care for children with trisomy 18 expands beyond the delivery room and the neonatal intensive care unit, the role of early PPC involvement in these children's care, as well as family values, preferences, and approaches to decision making also merit exploration.
Given the shifting approach to the care of children with trisomy 18, and the role of PPC in the care of children with chronic and lifelimiting diagnoses, PPC providers will likely be caring for an increasing number of children with trisomy 18. This study provides a glimpse into this patient population, which is anticipated to continue growing, and warrants closer investigation in the years to come.

DATA ACCESSABLITY
Data available on request due to privacy/ethical restrictions.