Deborah A. Bruns, Ph.D. Emily Campbell SOFT Conference July 2013 Providence/Warwick, RI

This session will provide an overview of the Tracking Rare Incidence Syndromes (TRIS) project along with data focusing on long-term survivors with trisomy 18 and 13. Findings describing medical conditions at birth and their resolution will be presented and implications offered for the provision for optimal services and interventions. Annabel, 8 years

The Tracking Rare Incidence Syndromes ( TRIS) project seeks to increase awareness and knowledge for families and professionals touched by rare trisomy conditions and aims to facilitate improved decision making for optimal services and supports for affected children and their families.

TRIS project components  Database development through parent contacts, links with rare trisomy groups and online searches  TRIS Survey (baseline survey) collects information on birth history, medical issues, developmental progress and family support needs. In addition, TRIS Follow-up Survey collects updates annually on key items from the TRIS Survey.  Dissemination of results through presentations and publications  Collaboration with families and experts in field  Outreach for raising awareness and recruitment

Background information  Newborns with trisomy 18 present with distinctive physical characteristics including low-set ears, clenched hands, and rocker bottom feet (Jones, 2006). Common medical conditions include apnea, cardiac anomalies such as ventricular septal defect (VSD), pulmonary hypertension, compromised respiratory functioning that may require mechanical support, kidney malformations and feeding difficulties. Newborns with trisomy 13 exhibit similar physical characteristics and medical conditions.  In the literature, there is an assumption of a limited quality of life for newborns with these conditions. This is used as a rationale for the denial of intensive treatment (Chervenak & McCullough, 2012, Merritt et al., 2012).

Background information continued  The majority of published reports point to a bleak prognosis. For example, a number of population-based studies stress early mortality and life threatening medical conditions (Crider et al., 2008; Rasmussen et al., 2003; Vendola et al., 2010). Most research points to only 5–10% of infants reaching their first birthday (Rasmussen et al., 2003).  A literature base describing survivors over the age one year is emerging with reports of children with t18 reaching their second, third and beyond birthdays (Bruns, 2010; Carey, 2012 ; Imataka et al., 2007).  There is a need to examine medical conditions noted at birth and the immediate perinatal period, along with the presence or absence of the same conditions coupled with medical treatment and outcomes in long-term survivors with trisomy 18 and 13 (full and mosaic types).

TRIS project results Mothers of 21 newborns with full t18 (13 survivors; 8 died prior to mothers' participation in the study). Newborns presented with syndrome-related physical characteristics (e.g., low-set ears, small jaw) and medical conditions (e.g., heart defects). Gestational age was generally older than what is described in the existent literature. In the NICU, newborns were provided with a variety of equipments (e.g., nasal cannula, pulse oximeter) and received treatments including blood transfusions and echocardiograms. Data also indicate longer survival rates (103.3 months for survivors, 37.5 months for non-survivors) than that described in the literature. Data indicate presence of common presenting physical and medical characteristics and varied medical assistance to newborns with full t18. Bruns, D. A. (2010). Neonatal experiences of newborns with full trisomy 18. Advances in Neonatal Care, 10(1),

TRIS project results continued Mothers of 30 long-term survivors with full t13 completed an online survey including maternal and paternal age at conception, physical characteristics, and medical conditions were compared. Data indicate longer mean survival rates (48.4 months for those living at the time of data collection, 40.8 months for those who died prior) than described in the literature. Means for gestations age, birth weight, and length are weeks, 2, g and cm, respectively. Long-term survivors presented with syndrome-related physical characteristics (e.g., low-set ears, cleft lip and palate) and medical conditions (e.g., VSD), feeding difficulties). We conclude that data indicate longer survival and a range in birth information (gestational age, birth weight, and length) along with presence of common presenting physical characteristics and medical conditions of long-term survivors with full t13. Bruns D. (2011). Birth history, physical characteristics, and medical conditions in long-term survivors with full trisomy 13. American Journal of Medical Genetics Part A 155: 2634–2640.

TRIS project database as of July 8, 2013  265 TRIS Full Surveys completed since 2/1/07  Trisomy 18  74 diagnosed with full trisomy 18 (27.9%)  16 diagnosed with trisomy 18 mosaic (6%)  Trisomy 13  39 diagnosed with full trisomy 13 (14.7%)  13 diagnosed with trisomy 13 mosaic (4.9%)  Majority in each group were living at time of survey completion (56/18, 76%, 15/1, 94%, 21/18, 54% and 12/1, 92% respectively)  Age range of survivors varied (3-394 months, months, months and months respectively)

Results: full t18  Analysis began March 2012: 41 surveys represented long-term survivors with full t18 over 12 months of age  Mean age at survey completion was months (range= months)  Gestational age: M=39.26 weeks  Birth weight: M= grams  Birth length: M=44.79 centimeters  33 (80%) were discharged within four week s (M= Mean) Rebekah, 4 years

Results: full t18 continued  ASD= 19/39* (49%) at Birth  4/19 (21%) repaired  PDA= 24/41 (59%) at Birth  5/24 (21%) repaired  VSD= 34/41 (83%) at Birth  7/34 (21%) repaired  Feeding Difficulties  34/41 (83%) at Birth  29/41 (71 %) at Survey  Apnea  21/34* (62%) at Birth  7/34*(21%) at Survey  4/41 (9%) with a tracheotomy ( M=mean) Ava, 6 years

Results: t18 mosaic  Eight surveys represented long-term survivors with t18 mosaic over 12 months of age  Mean age at survey was 61.5 months (range months)  Gestational age: M=38 weeks  Birth weight: M= grams  Birth length: M=34.14 centimeters  All were discharged within 4 weeks (M=Mean) Giuliana, 2 years

Results: t18 mosaic continued  ASD= 4/8 (50%) at Birth  2/4 (50%) repaired  PDA= 2/8 (25%) at Birth  2/2 (100%) repaired  VSD= 3/8 (38%) at Birth  2/3 (67%) repaired  Feeding Difficulties  7/8 (88%) at Birth  2/8 (25%) at Survey  Apnea  3/8 (38%) at Birth  1/8 (13%) at Survey  2/8 (25%) with a tracheotomy Ellie, 8 yearsDominic, 4 years

Results: full t13  14 surveys represented long-term survivors with full t13 over 12 months of age  Mean age at survey was months (range months)  Gestational age: M=38 weeks*  Birth weight: M= grams*  Birth length M=47.41 centimeters*  12 (86%) were discharged within 4 weeks* (*Incomplete data, M=Mean) Arianna, 7 years

Results: full t13 continued  ASD= 6/14 (43%) at Birth  PDA= 2/14 (14%) at Birth  VSD= 3/14 (21%) at Birth  1/14 (7%) healed  Feeding Difficulties  10/14 (71%) at Birth  8/14 (57%) at Survey  Apnea  7/14 (50%) at Birth  2/14 (14%) at Survey  No tracheotomies reported Sofia, 9 years Joey, 6 years

Results: t13 mosaic  10 surveys represented long-term survivors with t13 mosaic over 12 months of age  Mean age at survey was months (range months)  Gestational age: M=36.2 weeks  Birth weight: M= grams (range: 2.8 lbs-11.6lbs)  Birth length: M=46.68 centimeters  Eight (80%) were discharged within 4 weeks (M=Mean) Lillian, 6 years

Results: t13 mosaic continued  ASD= 6/10 (60%) at Birth  1/10 (10%) repaired  PDA= 4/10 (40%) at Birth  1/10 (10%) repaired  VSD= 6/10 (60%) at Birth  2/10 (20%) repaired  Feeding Difficulties  10/10 (100%) at Birth  1/10 (10%) at Survey  Apnea  6/10 (60%) at Birth  2/10 (20%) at Survey  2 children have a tracheotomy Isabel, 2 years

Implications for parents and families  Longer gestation and higher birth weight appear to contribute to long-term survival  Success of “aggressive” medical treatment; parents need to be informed of outcomes as well as benefits and possible complications of treatment  Be familiar with the literature as well as seek out anecdotal information from medical professionals and other parents to assist decision making  Advocate on behalf of your child

Implications for professionals  Results increase awareness of positive outcomes rather than emphasizing mortality  Treatment decisions should be based on “best interest” of the child, parent preferences based on balanced information and, importantly, on individual infant physical characteristics and medical condition(s)  Remain current on the literature; move beyond population studies to small samples and case studies

Conclusion Results provide a new perspective on survivors over the age of one year with t18 and t13. Successful treatment of common medical conditions associated with the syndromes are documented. Data also highlights the need for decision-making, taking into account individual characteristics rather than reliance on general, diagnosis-specific recommendations

For additional information Deborah Bruns, Ph.D. Emily Campbell TRIS project website: