Prenatal and Neonatal Characteristics of Children with Prader-Willi Syndrome

Objective: Prader-Willi syndrome (PWS) is a rare genetic syndrome with a wide spectrum of clinical features in early life. Late diagnoses are still present. We characterized the perinatal and neonatal features of PWS, compared them with those of healthy newborns and assessed the prenatal and neonatal differences between the genetic subtypes. Design: A cohort study in children with PWS. The prevalence of variables was compared with healthy infants (PLUTO cohort) and to population statistics from literature. Patients: 244 infants with PWS and 365 healthy infants. Measurements: Data on prenatal and neonatal variables in both cohorts. Population statistics were collected through an extensive literature search. Results: A higher prevalence of maternal age >35 years was found in PWS compared to healthy infants and population statistics, and the highest maternal age was found in the mUPD group. Higher prevalence of polyhydramnios, caesarean section, labour induction and breech presentation, and lower birth weight SDS was found in PWS compared to healthy infants. High prevalences of decreased fetal movements (78.5%), hypotonia (100%), cryptorchism (95.9%) and poor sucking/tube feeding (93.9%) were found in PWS. Conclusions: This study presents an overview of prenatal and neonatal variables in infants with PWS compared to healthy infants. Our findings may increase clinical awareness of the early perinatal signs of PWS by obstetricians, neonatologists and all those involved in infant care, enabling early diagnosis and start of multidisciplinary treatment

Assessing the clinical benefit of systemic anti-cancer treatments in the Netherlands:The impact of different thresholds for effectiveness

Background: In the Netherlands, the clinical benefit of systemic anti-cancer treatments (SACTs) is assessed by the Committee for the Evaluation of Oncological Agents (cieBOM). For non-curative SACTs, the assessment is based on the hazard ratio (HR) for progression-free survival and/or overall survival (OS), and the difference in median survival. We evaluated the impact of different thresholds for effectiveness by reassessing the clinical benefit of SACTs. Methods: We reassessed SACTs that were initially assessed by cieBOM between 2015 and 2017. Four scenarios were formulated: replacing an “OR” approach (initial assessment) by an “AND” approach (used in all scenarios), changing the HR threshold from &lt; 0.70 (initial assessment) to &lt; 0.60, changing the threshold for the difference in median survival from &gt; 12 weeks (initial assessment) to &gt; 16 weeks, and including thresholds for OS rates. The outcomes of these scenarios were compared to the outcomes of the initial assessment. Results: Reassessments were conducted for 41 treatments. Replacing the “OR” approach by an “AND” approach substantially decreased the number of positive assessments (from 33 to 22), predominantly affecting immunotherapies. This number further decreased (to 21 and 19, respectively) in case more restrictive thresholds for the HR and difference in median survival were used. Including thresholds for OS rates slightly mitigated the impact of applying an “AND” approach. Conclusions: The scenario-specific thresholds had a substantial impact; the number of negative assessments more than doubled. Since this was not limited to treatments with marginal survival benefits, understanding the potential challenges that may arise from applying more restrictive thresholds is essential.</p