A validated model for prediction of survival to 6 months in patients with trisomy 13 and 18.

Congenital heart disease is exceedingly prevalent in trisomy 13 and 18. Improved survival following congenital heart surgery has been reported, however, mortality remains significantly elevated. Utilizing inpatient data on trisomy 13 and 18 from the 2003-2016 Pediatric Health Information System database, a survival model was developed and validated using data from the California Perinatal Quality Care Collaborative and the California Office of Statewide Health Planning and Development. The study cohort included 1,761 infants with trisomy 13 and 18. Two models predicting survival to 6 months of age were developed and tested. The initial model performed excellently, with a c-statistic of 0.87 and a c-statistic of 0.76 in the validation cohort. After excluding procedures performed on the day of death, the revised model's c-statistic was 0.76. Certain variables, including cardiac surgery, gastrostomy, parenteral nutrition, and mechanical ventilation, are predictive of survival to 6 months of age. This study presents a model, which potentially can inform decision-making regarding congenital heart surgery.

The short-term mortality and morbidity of very low birth weight infants with trisomy 18 or trisomy 13 in Japan.

Trisomy 18 (T18) and trisomy 13 (T13) are major concerns in prenatal genetic testing due to their poor prognosis; very low birth weight (VLBW) is also a concern in neonatology. The aim of this study was to investigate the mortality and morbidity of VLBW infants diagnosed with T18/T13 in Japan, compared with those with no birth defects (BD-). Maternal and neonatal data were collected prospectively from infants weighing <1501 g and were admitted to centers of the Neonatal Research Network of Japan during 2003 to 2016. Among 60,136 infants, 563 and 60 was diagnosed with T18 and T13, respectively. Although the age of mothers of infants with T18/T13 was higher, the frequency of maternal complications was lower than those with BD-. With maternal and neonatal characteristic adjustments, T18/T13 had a higher incidence of each morbidity when compared with BD-. Mortality rates in the NICU were 70, 77, and 5.8% for T18, T13, and BD-, respectively, while the survival discharge rates of T18 and T13 were 29.5 and 23.3%, respectively, which was significantly higher than previous reports. This was the first nationwide survey for VLBW infants with T18/T13 in Japan; this novel data will be relevant and useful for prenatal genetic counseling and perinatal management. Although T18/T13 were considered to be fatal in the past, with proper epidemiological information, discussions with affected families, and compassionate patient care, the mortality rate of T18/T13 can be improved.

Outcomes After Extracorporeal Life Support Cannulation in Pediatric Patients With Trisomy 13 and Trisomy 18.

BACKGROUND: Indications for extracorporeal life support (ECLS) have evolved and expanded, yet its use in trisomy 13 (T13) and trisomy 18 (T18) patients remains controversial. We reviewed the experience of the Extracorporeal Life Support Organization with ECLS in these patients to inform practice at our institution. METHODS: The Extracorporeal Life Support Organization registry was queried for all patients younger than 18 y with an International Classification of Diseases, Ninth Edition/Tenth Edition code for T13 or T18 from 2000 to 2018. Basic demographics, ECLS details, and clinical outcomes were recorded. Descriptive statistics were performed. RESULTS: Twenty-eight patients were identified (15 with T13; 13 with T18), representing 0.06% (28 of 46,901) of pediatric ECLS cannulations. The median weight was 3.5 kg (range, 1.4-13), and age at cannulation was 52 d (range, 0 d-6.8 y). Time on ECLS ranged from 13 to 478 h (median, 114). Cardiac defects were diagnosed in 19 (68%) patients, of which 13 (46%) underwent surgical repair. Median oxygenation index pre-ECLS was 45. Venoarterial cannulations accounted for 82% of patients, whereas 14% underwent venovenous cannulation. Overall survival to hospital discharge was 46% with 86% of patients experiencing one or more complications. There were no survivors when cannulation continued past 12 d. CONCLUSIONS: Although complications are frequent, the mortality rate in patients with T13 and T18 remains within the reported range for the general pediatric population. T13 and T18 alone should not be viewed as absolute contraindications to ECLS within the pediatric population but rather considered during the evaluation of a patient's potential candidacy.

Cardiac Surgery in Trisomy 13 and 18: A Guide to Clinical Decision-Making.

There has been substantial controversy regarding treatment of congenital heart defects in infants with trisomies 13 and 18. Most reports have focused on surgical outcomes versus expectant treatment, and rarely there has been an effort to consolidate existing evidence into a more coherent way to help clinicians with decision-making and counseling families. An extensive review of the existing literature on cardiac surgery in patients with these trisomies was conducted from 2004 to 2020. The effects of preoperative and perioperative factors on in-hospital and long-term mortality were analyzed, as well as possible predictors for postoperative chronic care needs such as tracheostomy and gastrostomy. Patients with minimal or no preoperative pulmonary hypertension and mechanical ventilation undergoing corrective surgery at a weight greater than 2.5 kg suffer from lower postoperative mortality. Infants with lower-complexity cardiac defects are likely to benefit the most from surgery, although their expected mortality is higher than that of infants without trisomy. Omphalocele confers an increased mortality risk regardless of cardiac surgery. Gastrointestinal comorbidities increased the risk of gastrostomy tube placement, while those with prolonged mechanical ventilation and respiratory comorbidities are more likely to require tracheostomy. Cardiac surgery is feasible in children with trisomies 13 and 18 and can provide improved long-term results. However, this is a clinically complex population, and both physicians and caretakers should be aware of the long-term challenges these patients face following surgery when discussing treatment options.

Who Is the Next "Baby Doe?" From Trisomy 21 to Trisomy 13 and 18 and Beyond.

The "Baby Doe" case of the early 1980s was marked by considerable controversy, primarily regarding the legal response of the federal government to the case at the time. In the decades that followed, the decision-making for children with trisomy 21, like Baby Doe, has been substantially reevaluated. The data, the assumptions about quality of life that were based on those data, and the ethical principles underpinning the decision-making in the Baby Doe case have all evolved significantly over time. The present strategies for decision-making for children with trisomy 13 and 18 appear to be following a similar pattern. The data, quality-of-life assumptions based on those data, and even the ethical principles underlying the decision-making for these children are currently being reexamined. Children with trisomy 13 and 18 are, in this regard, the next Baby Doe(s).

Obstetric complications in pregnancies with life-limiting malformations.

PURPOSE OF REVIEW: The implementation of palliative care at birth has led to a significant rise in the number of couples who choose to continue with pregnancies complicated by life-limiting malformations (LLMs). Prenatal counselling and appropriate antenatal/perinatal management in these cases are poorly studied and may pose significant challenges. The purpose of this review is to outline specific obstetric risks and to suggest management for mothers who choose to continue with pregnancies with the most common LLMs. RECENT FINDINGS: In pregnancies complicated by LLMs where parents opt for expectant management, clinicians should respect parental wishes, whilst openly sharing potential serious maternal medical risks specific for the identified abnormalities. The focus of both antenatal and perinatal care should be maternal wellbeing rather than foetal survival. Follow-up ultrasound examinations and maternal surveillance should be aimed at achieving timely diagnosis and effective management of obstetric complications. A clear perinatal plan, agreed with the couples by a multi-disciplinary team including a foetal medicine specialist, a neonatologist and a geneticist, is crucial to reduce maternal morbidity. SUMMARY: This review provides a useful framework for clinicians who face the challenges of counselling and managing cases complicated by LLMs where parents opt for pregnancy continuation.

Trisomy 13 and 18-Prevalence and mortality-A multi-registry population based analysis.

The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty-four population- and hospital-based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data-reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3-2.06), and for T18 was 4.08 (95% CI 3.01-5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38-0.72), and for T18 was 1.07 (95% CI 0.77-1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1-year follow-up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions.

The association of Trisomy 13 and 18 and hospital discharge outcomes among neonates in California: A retrospective cohort study.

BACKGROUND: Despite Trisomy 13 and 18 being among the most fatal congenital anomalies, limited information exists about resource utilization and factors associated with length of stay (LOS) and total hospital charges (THC) for these anomalies. METHODS: We studied data sets of the patient discharge data set from the California Office of Statewide Health Planning and Development from 2006 to 2010, to determine differences in resource utilization for survivors and non-survivors and identify the predictors of LOS and total hospital charges. Descriptive statistics were assessed for demographic and clinical characteristics. General linear regression models were used to identify predictors of LOS and THC. RESULTS: Seventy-six Trisomy 13 and 115 Trisomy 18 patients were identified, for whom inpatient mortality was 27.6% and 20.9%, respectively. In patients with Trisomy 13, after adjusting for gender, ethnicity, advanced directive (DNR), insurance and co-morbidities on multivariate analysis, the provision of more than 96 h of mechanical ventilation was associated with significantly increased LOS (standard error, SE) by 18.0 ± 5.3 days and THC (SE) by $399,000 ± $85,000. In terms of insurance type, patients with private coverage had 10.8 ± 4.9 days more than patients with Medicaid. In patients with Trisomy 18, on multivariate analysis, after adjusting for gender, ethnicity, DNR, insurance and co-morbidities, more than 96 h of mechanical ventilation was associated with increased LOS (SE) by 36.8 ± 6.8 days and THC (SE) by $365,000 ± $59,000. CONCLUSION: Understanding predictors that are associated with longer LOS and higher THC may be associated in hospital resource allocation for this vulnerable population of infants.

Mortality and Resource Use Following Cardiac Interventions in Children with Trisomy 13 and Trisomy 18 and Congenital Heart Disease.

We sought to evaluate the mortality, risk factors for mortality, and resource utilization following cardiac interventions in trisomy 13 (T13) and 18 (T18) children. All T13 and T18 children who underwent a cardiac intervention from January 1999 to March 2015 were identified from the Pediatric Health Information System database. Data collected included demographics, type of congenital heart disease (CHD), cardiac interventions, comorbidities, length of stay (LOS), hospital charges, and deaths (within 30 days). Logistic regression analysis was used to determine factors associated with mortality. There were 49 (47% females) T13 and 140 (67% females) T18 subjects. The two cohorts were similar in distribution for race, geographic region, insurance type, and median household income. The most common CHD in both groups was a shunt lesion followed by conotruncal defects. Compared to T18, the T13 cohort had higher mortality (29% vs. 12%), tracheostomies (12% vs. 4%), gastrostomies (18% vs. 6%), and overall resource use (P < 0.05 for all). White race (OR 0.23, 95% CI 0.06-0.81) in T13 and older age (in weeks) at surgery in T18 (OR 0.75, 95% CI 0.64-0.86) were associated with lower mortality. A select group of T13 and T18 CHD patients can undergo successful cardiac interventions, albeit with a higher mortality and resource use. T13 patients have higher mortality and resource use compared to T18. In T13 and T18 patients, interventions for CHD may be an acceptable and ethical option following a careful individualized selection and counseling by a team of experts.

Congenital Heart Surgical Admissions in Patients with Trisomy 13 and 18: Frequency, Morbidity, and Mortality.

Congenital heart defects are common among patients with trisomy 13 and 18; surgical repair has been controversial and rarely studied. We aimed to assess the frequency of cardiac surgery among admissions with trisomy 13 and 18, and evaluate their associations with resource use, complications, and mortality compared to admissions without these diagnoses. We evaluated congenital heart surgery admissions of ages < 18 years in the 1997, 2000, 2003, 2006, and 2009 Kids' Inpatient Database. Bivariate and multivariate analyses examined the adjusted association of trisomy 13 and 18 on resource use, complications, and inpatient death following congenital heart surgery. Among the 73,107 congenital heart surgery admissions, trisomy 13 represented 0.03% (n = 22) and trisomy 18 represented 0.08% (n = 58). Trisomy 13 and 18 admissions were longer; trisomy 13: 27 days vs. 8 days, p = 0.003; trisomy 18: 16 days vs. 8 days, p = 0.001. Hospital charges were higher for trisomy 13 and 18 admissions; trisomy 13: $160,890 vs. $87,007, p = 0.010; trisomy 18: $160,616 vs. $86,999, p < 0.001. Trisomy 18 had a higher complication rate: 52% vs. 34%, p < 0.006. For all cardiac surgery admissions, mortality was 4.5%; trisomy 13: 14% and trisomy 18: 12%. In multivariate analysis, trisomy 18 was an independent predictor of death: OR 4.16, 95% CI 1.35-12.82, p = 0.013. Patients with trisomy 13 and 18 represent 0.11% of pediatric congenital heart surgery admissions. These patients have a 2- to 3.4-fold longer hospital stay and double hospital charges. Patients with trisomy 18 have more complications and four times greater adjusted odds for inpatient death.

Survival and healthcare utilization of infants diagnosed with lethal congenital malformations.

OBJECTIVE: We assessed survival, hospital length of stay (LOS), and costs of medical care for infants with lethal congenital malformations, and also examined the relationship between medical and surgical therapies and survival. STUDY DESIGN: Retrospective cohort study including infants born 1998-2009 with lethal congenital malformations, identified using a longitudinally linked maternal/infant database. RESULTS: The cohort included 786 infants: trisomy 18 (T18, n = 350), trisomy 13 (T13, n = 206), anencephaly (n = 125), bilateral renal agenesis (n = 53), thanatophoric dysplasia/achondrogenesis/lethal osteogenesis imperfecta (n = 38), and infants > 1 of the birth defects (n = 14). Compared to infants without birth defects, infants with T18, T13, bilateral renal agenesis, and skeletal dysplasias had longer survival rates, higher inpatient medical costs, and longer LOS. CONCLUSION: Care practices and survival have changed over time for infants with T18, T13, bilateral renal agenesis, and skeletal dysplasias. This information will be useful for clinicians in counseling families and in shaping goals of care prenatally and postnatally.

Clinical courses of children with trisomy 13 receiving intensive neonatal and pediatric treatment.

Management of children with trisomy 13 (T13) is controversial because of a paucity of evidence of the natural history, especially focusing on efficacy of treatment. There has been no report regarding natural history of children with T13 receiving intensive neonatal and pediatric treatment without cardiac surgery, although several reports have suggested efficacy of cardiac surgery. To describe the detailed and comprehensive natural history of children with T13 receiving intensive neonatal and pediatric treatment without cardiac surgery, we reviewed clinical information of 24 children with full T13 (15 boys, 9 girls) who were admitted to Nagano Children's Hospital from 1994 to 2016. Intensive neonatal and pediatric treatment without cardiac surgery was provided through careful discussion with the parents. We detailed accurate frequencies of complications, survival, underlying factors and the final modes of death, and psychomotor development of survivors. Unpublished complications including aortopulmonary window, pulmonary-ductus-descending aorta-trunk, biliary system abnormalities, eosinophilic enteritis, and neuroblastoma were described. Accurate frequencies of congenital heart defects (92%) and laryngomalacia and/or tracheomalacia (42%) were determined. The median survival time was 451 days and the 1-year survival rate was 54%. The major underlying factor associated with death was congenital heart defects and heart failure (63%) and the major final mode of death was heart failure (50%). Long-term survivors appeared to show slow but constant psychomotor development. Intensive neonatal and pediatric treatment without cardiac surgery for children with T13 is efficient for survival and psychomotor development, and could be a reasonable choice for parents having fetuses or children with T13.

Prenatal counseling and parental decision-making following a fetal diagnosis of trisomy 13 or 18.

OBJECTIVES: To evaluate parental decisions following a prenatal diagnosis of trisomy 13 (T13) or trisomy 18 (T18), prenatal counseling received, and pregnancy outcomes. STUDY DESIGN: Single-center, retrospective cohort study of families with a prenatal diagnosis of T13 or T18 from 2000 to 2016. RESULTS: Out of 152 pregnancies, 55% were terminated. Twenty percent chose induction with palliative care, 20% chose expectant management, 2% chose full interventions, and 3% were lost to follow-up. Counseling was based on initial parental goals, but most women were given options besides termination. Women who chose expectant management had a live birth in 50% of the cases. Women who chose neonatal interventions had a live birth in 100% of the cases, but there were no long-term survivors. CONCLUSIONS: The majority of women who continue their pregnancy after a fetal diagnosis of T13 or T18 desire expectant management with palliative care. A live birth can be expected at least half of the time.

Factors Influencing Outcomes After Cardiac Intervention in Infants with Trisomy 13 and 18.

Cardiac intervention remains controversial in patients with trisomy 13 and 18 and little is known about factors that may affect outcomes. The goal of this study was to evaluate preoperative factors and surgical approach with respect to outcomes in these patients. Patients with congenital heart disease and trisomy 13 or 18 presenting to our institution from 2004 through 2015 were retrospectively reviewed. Patients were grouped into complete intervention, palliated intervention, and non-intervention. Pre-intervention variables, timing and type of intervention, post-intervention outcomes, and survival were recorded and comparisons were made between the groups. Of 34 patients, 18 cardiac interventions were performed. Complete repair was performed in 11(61%) and palliation in 7(39%). Median age for complete repair was 9.2 vs. 1.7 months in palliated patients (p < 0.001) and palliated patients were smaller (median 2.5 vs. 5.2 kg, p < 0.001). All patients who underwent complete repair survived to discharge compared to only 57% of patients that were palliated (p = 0.04). Palliated patients had longer intubation and time to discharge (p < 0.05). Survival at last follow-up was greater in the complete repair group compared with palliated patients and non-intervention patients (72, 14, and 18%, p = 0.009) with a longer median length of survival in the complete repair group (p = 0.002). In our group of trisomy 13 and 18 patients, those able to undergo complete repair had improved outcomes. Patients undergoing complete repair were older and bigger; this suggests that delaying intervention and optimizing the likelihood of complete repair may be beneficial.

Prenatal and Postnatal Follow-up in Trisomies 13 and 18: A 20-Year Experience in a Tertiary Center.

OBJECTIVE: Trisomies 13 and 18 are among the most common autosomal aneuploidies associated with high mortality rates. Conventional management strategies offer to limit interventional support; however, some of the recent studies suggest that intervention does make a difference in terms of survival. STUDY DESIGN: A retrospective cohort study was performed between January 1996 and January 2016, covering all cases with such trisomies. A total of 69 cases were reviewed for clinical aspects, outcome, and management strategies. RESULTS: In almost all pregnancies with follow-up, at least one indication present for invasive testing (54/55). Invasive testing was not performed in 18.5% of such cases. All parents opted for termination in cases with prenatal diagnosis. None of the liveborns had prenatal diagnoses, thus, neonatal resuscitation and intensive care unit admission were not withheld in such infants. Major intervention was done in only one patient with full trisomy 13. Median survival for infants with full trisomies 13 and 18 was 36 and 60 days, respectively. Almost half the patients died within 1 month. CONCLUSION: To which extent the major interventions should be withheld is an issue of debate in managing such infants; however, current approaches are subject to change, given the technological advances.

Factors related to home health-care transition in trisomy 13.

Trisomy 13 (T13) is accompanied by severe complications, and it can be challenging to achieve long-term survival without aggressive treatment. However, recently, some patients with T13 have been receiving home care. We conducted this study to investigate factors related to home health-care transition for patients with T13.We studied 28 patients with T13 born between January 2000 and December 2014. We retrospectively compared nine home care transition patients (the home care group) and 19 patients that died during hospitalization (the discharge at death group). The median gestational age of the patients was 36.6 weeks, with a median birth weight of 2,047 g. Currently, three patients (11%) have survived, and 25 (89%) have died. The home care group exhibited a significantly longer gestational age (38.9 vs. 36.3 weeks, p = 0.039) and significantly larger occipitofrontal circumference Z score (-0.04 vs. -0.09, p = 0.019). Congenital heart defects (CHD) was more frequent in the discharge at death group, with six patients in the home care group and 18 patients in the discharge at death group (67% vs. 95%, p = 0.047), respectively. Survival time was significantly longer in the home care group than in the discharge at death group (171 vs. 19 days, p = 0.012). This study has shown that gestational age, occipitofrontal circumference Z score at birth, and the presence of CHD are helpful prognostic factors for determining treatment strategy in patients with T13.

Treatment Decisions for Babies with Trisomy 13 and 18.

Many babies with trisomy 13 and 18 die in the first year of life. Survivors all have severe cognitive impairment. There has been a debate among both professionals and parents about whether it is appropriate to provide life-sustaining interventions to babies with these serious conditions. On one side of the debate are those who argue that there is no point in providing invasive, painful, and expensive procedures when the only outcomes are either early death or survival with severe cognitive impairment. Others suggest that, although mortality is high and cognitive impairment universal, babies with these conditions have an acceptable quality of life. In this paper, we will discuss both points of view. We will review the ways in which these conditions are portrayed in pediatrics textbooks and on social media sites that offer support to parents. We will then suggest an appropriate way to deal with clinical decisions for babies with these trisomies.

Major anomalies and birth-weight influence NICU interventions and mortality in infants with trisomy 13 or 18.

OBJECTIVE: To describe neonatal intensive care unit (NICU) medical interventions and NICU mortality by birth weight and major anomaly types for infants with trisomy 13 (T13) or 18 (T18). STUDY DESIGN: Retrospective cohort analysis of infants with T13 or T18 from 2005 to 2012 in the Pediatrix Medical Group. We classified infants into three groups by associated anomaly type: neonatal surgical, non-neonatal surgical and minor. Outcomes were NICU medical interventions and mortality. RESULTS: 841 infants were included from 186 NICUs. NICU mortality varied widely by anomaly type and birth weight, from 70% of infants <1500 g with neonatal surgical anomalies to 31% of infants ⩾2500 g with minor anomalies. Infants ⩾1500 g without a neonatal surgical anomaly comprised 66% of infants admitted to the NICU; they had the lowest rates of NICU medical interventions and NICU mortality. CONCLUSIONS: Risk stratification by anomaly type and birth weight may help provide more accurate family counseling for infants with T13 and T18.

Cardiac surgery for children with trisomies 13 and 18: Where are we now?

The objective is to examine whether cardiac surgery should be considered for children with trisomy 13 or 18 (T13 or 18).T13 or 18 were previously referred to as "lethal" conditions due to high mortality rates and severe disability among survivors. In the last decade, investigations have revealed these conditions are heterogeneous, with increasing numbers of studies describing interventions for these children. A number of factors makes the interpretation of reported outcomes after cardiac surgery challenging: (1) dissimilarities in practice lead to a wide variation in reported outcomes after cardiac surgery; (2) cardiac surgery is generally offered to older, healthier children; (3) cardiac surgeries of widely varying risks are often lumped together in individual studies, and (4) cases where cardiac surgery has been withheld are generally not included in publications. It is unclear whether withholding cardiac surgery for some children with a ventricular septal defect will lead to death, or the development of pulmonary hypertension, or if death will occur from other causes. In this article, we describe two children with different clinical situations and examine whether cardiac surgery would benefit them and how to communicate with their families. Cardiac surgery may be beneficial to some children with trisomy 13 or 18, but may harm others. Every child should be approached in an individual fashion and the goals of each family should be addressed. Children who are more likely to benefit from surgery may be older, healthier children without respiratory support. Rigorous and transparent research is needed to identify factors that affect survival in trisomy 13 or 18.