Emerging evidence that medical and surgical interventions improve the survival and outcome in the trisomy 13 and 18 syndromes

The trisomy 13 and 18 syndromes represent the second and third most common autosomal trisomy conditions in humans. Their combined total prevalence (elective termination of pregnancies, stillbirths, and livebirths) is approximately 1 in 1,800 total births, which makes the experience of having a fetus or baby with either condition a common event (over 2,000 U.S. families annually, Carey, 2012). Both of these well-established syndromes consist of a recognizable pattern of multiple congenital anomalies with increased neonatal and infant mortality and significant intellectual disability in older children. The early childhood mortality is unique to these conditions among the relatively common syndromes cared for by the neonatologist and medical geneticist. Because of reasons that are not always well characterized in clinical care or in the literature, the conventional approach to management of newborns with the trisomy 13 and 18 syndromes has been a withholding of technological support, including surgery, with the provision of comfort care, which more recently has been under the compassionate guidance of Palliative Care teams (Carey, 2012). Recent series of inpatient hospitalizations of children with these two syndromes have demonstrated a notable number with interventions such as tracheostomy and major surgery (Nelson, Hexem, & Feudtner, 2012; Josephsen et al., 2016). In particular, Janvier, Farlow, and Barrington (2016) summarized the previous series of children with the syndromes who have had cardiac surgery up to that time. Since that important review, four series have been published in the medical literature summarizing experience with cardiac surgery for various indications in infants with these conditions (Cooper et al., 2019; Domingo, Carey, Eckhauser, Wilkes, & Menon, 2018; Kosiv, Gossett, Bai, & Collins, 2017; Peterson, Kochilas, Catton, Moller, & Setty, 2017). These investigations indicate that a substantial and previously unexpected proportion of infants with trisomy 18 (and 13) survive cardiac surgeries and go home from the hospital. Overall, 85% (range about 70–90%) of infants live and are discharged. Long-term follow-up, however, is generally lacking in these series. Two recent investigations into 1and 5-year mortality performed on a scale with higher numbers of infants than in the previously reported population studies were published in the same year (Meyer et al., 2016; Nelson, Rosella, Mahant, & Guttmann, 2016). The population studies from 1985 until that time had shown that about 50% of infants died in the first week of life and 0–8% (average about 6%) survived to their first birthday. The papers by Meyer et al. and Nelson et al. documented a more than a doubling of this 1-year survival for both trisomy 13 and 18 syndromes and that the overwhelming majority of infants who survived to 1 year lived to 5 years. The paper by Goel et al., 2019 published in this issue of the Journal demonstrated a similar 1-year survival in a large-scale international study of collected data. Overall, about 12% of infants with both conditions survived to the first year of life. Of note, in all three of these investigations, the early neonatal mortality in the first week of life and median survival are quite similar to the early population studies summarized by Carey (2012) and Lorenz and Hardart (2014). These 1-week data suggest that there may be population of infants who have quite serious respiratory difficulties (e.g., pulmonary hypoplasia or central apnea) or malformations (e.g., diaphragmatic hernia) and did not survive the early days of life; but once an infant lives into the first few weeks, survival is markedly better. The reason for this is not completely known (and should be studied), but the figures certainly raise an issue mentioned by the authors in all three papers: Increased intervention (as demonstrated by the hospitalization and surgery data cited above) may be accounting for better survival and outcome in a condition that in the past had been incorrectly labeled then as “lethal” and” incompatible with life” (Carey, 2012). The evidence at the time that intervention had improved survival in the syndromes was summarized by Kosho and Carey (2016). Despite these reviews and recent data, the existing evidence that intervention in trisomy 13 and 18 improves outcome demands further study. To this point a paper in the same issue as Meyer et al. (2016), which was addressed in the editorial by Kosho and Carey (2016), suggested that intervention in trisomy 18 did not improve outcome (Subramaniam et al., 2016). I would assert that a comprehensive large-scale longitudinal study over multiple years and in several regions and including patientreported data that investigate all the variables could answer this question. In addition, such a longitudinal study could also explore the question of the impact of caring for a child with trisomy 13 and 18 on the family. The issue of quality of life of the parents and child is consistently raised in clinical care discussions; a state-of-the-art evaluation of health-related quality of life in caregivers of infants with trisomy 13 and 18 would help address this issue. In addition, other impacts on the family, such as depression in mothers and coping skills in parents, could be assessed by standardized instruments. In conclusion, I would suggest that the time has arrived where conventional wisdom and tradition are no longer the appropriate methods to approach routine care of children with trisomy 13 and 18, and, as in the rest of medicine, there is the need for evidence-based approaches. Received: 1 September 2019 Accepted: 6 September 2019