Survival trends from the Prader-Willi Syndrome Association (USA) 40-year mortality survey

Abstract

PurposePrader-Willi syndrome (PWS) is a complex genetic disorder characterized by hyperphagia and morbid obesity with increased cardiopulmonary and hyperphagia-related mortality. Survival trends in PWS were evaluated to assess the impact of modern interventions on mortality risk.MethodsThe Prader-Willi Syndrome Association (USA) 40-year mortality syndrome-specific database of 486 death reports was utilized to examine survival trends in PWS and cohort effects for recent deaths (years 2000-2015, N=331) relative to deaths prior to 2000 (N=94). Cox proportional hazards regression modeling was applied to generate log rank statistics and Kaplan-Meier curves examining sex, cause of death, and cohort.ResultsRisk for all-cause mortality in PWS was 1.5 (95% confidence interval (CI)=1.2-1.9) times higher for the Early than the Recent era cohort reflected in female cardiac failure (hazard ratio (HR)=1.8; 95% CI=1.3-2.6), pulmonary embolism (HR=6.1; 95% CI=1.7-22), and gastrointestinal-related (HR=3.2; 95% CI=1.1-7.4) causes. Accidental deaths in males increased in the Recent era cohort (HR=5.7; 95% CI=1.2-27.1), possibly due to enhanced weight management and mobility. Risk of death from respiratory failure was unchanged.ConclusionWe report measurable increases in survival effecting cardiovascular and gastrointestinal-related causes in PWS most likely attributable to earlier diagnosis and proactive interventions to prevent morbid obesity. More research is needed to address underlying vulnerability to respiratory failure, an unchanged mortality risk in PWS.

Figure 1

Figure 1a. Kaplan-Meier plots of survival probability for deaths due to respiratory failure [Respiratory Failure (1)] relative to all other causes [Respiratory Failure (2)] in Prader-Willi syndrome are shown for females [F] and males [M]. The number of uncensored participants are listed by group at the bottom of each figure. Quartile estimates for age of death and mean age of mortality due to respiratory failure are indicated. Figure 1b. Kaplan-Meier plots of survival probability for accidental deaths [accident (1)] relative to all other causes [accident (2)] in Prader-Willi syndrome for females (F) and males (M). The number of uncensored male and female participants are listed at the bottom of each figure. Quartile estimates for age of death and mean age of mortality are indicated for males and females.

Figure 1

Figure 1a. Kaplan-Meier plots of survival probability for deaths due to respiratory failure [Respiratory Failure (1)] relative to all other causes [Respiratory Failure (2)] in Prader-Willi syndrome are shown for females [F] and males [M]. The number of uncensored participants are listed by group at the bottom of each figure. Quartile estimates for age of death and mean age of mortality due to respiratory failure are indicated. Figure 1b. Kaplan-Meier plots of survival probability for accidental deaths [accident (1)] relative to all other causes [accident (2)] in Prader-Willi syndrome for females (F) and males (M). The number of uncensored male and female participants are listed at the bottom of each figure. Quartile estimates for age of death and mean age of mortality are indicated for males and females.

Figure 2

Kaplan-Meier plot of survival probability for deaths due to all causes for Early era [recent (0)] and Recent era [recent (1)] cohorts with Prader-Willi syndrome are shown for females (F) and males (M). The numbers of uncensored Recent and Early era participants are listed at the bottom of the figure. Quartile estimates for age of death and mean age of mortality are indicated for Recent and Early era groups.

Figure 3

Figure 3a. Kaplan-Meier plot of survival probability for deaths due to pulmonary embolism [Pulmonary_Embolism (1)] relative to all other causes [Pulmonary_Embolism (2)] in Prader-Willi syndrome for Recent era [recent (1)] vs Early era [recent (0)] cohorts are shown. The numbers of uncensored Recent and Early era participants are listed at the bottom of each figure. Quartile estimates for age of death and mean age of mortality are indicated for Recent and Early era groups with pulmonary embolism. Figure 3b. Kaplan-Meier plot of survival probability for deaths due to Gastrointestinal-related problems [Gastrointestinal (1)](top) and accidents [accident (1)](bottom) relative to all other causes [Gastrointestinal (2); accident (2)] in Prader-Willi syndrome for Recent era [recent (1)] vs Early era [recent (0)] are shown. The numbers of uncensored Recent and Early era participants are listed at the bottom of each figure. Quartile estimates for age of death and mean age of mortality are indicated for Recent and Early era groups for gastrointestinal-problems or accidents respectively.

Figure 3

Figure 3a. Kaplan-Meier plot of survival probability for deaths due to pulmonary embolism [Pulmonary_Embolism (1)] relative to all other causes [Pulmonary_Embolism (2)] in Prader-Willi syndrome for Recent era [recent (1)] vs Early era [recent (0)] cohorts are shown. The numbers of uncensored Recent and Early era participants are listed at the bottom of each figure. Quartile estimates for age of death and mean age of mortality are indicated for Recent and Early era groups with pulmonary embolism. Figure 3b. Kaplan-Meier plot of survival probability for deaths due to Gastrointestinal-related problems [Gastrointestinal (1)](top) and accidents [accident (1)](bottom) relative to all other causes [Gastrointestinal (2); accident (2)] in Prader-Willi syndrome for Recent era [recent (1)] vs Early era [recent (0)] are shown. The numbers of uncensored Recent and Early era participants are listed at the bottom of each figure. Quartile estimates for age of death and mean age of mortality are indicated for Recent and Early era groups for gastrointestinal-problems or accidents respectively.