Characteristics of Hypotonic–Hyporesponsive Episodes (HHEs) Following Childhood Vaccination: A 13-Year Analysis of Spontaneous Reports to the Dutch Pharmacovigilance Centre Lareb

Background: Hypotonic–hyporesponsive episode (HHE) is a recognised adverse event following immunisation (AEFI) in infants, characterised by sudden hypotonia, hyporesponsiveness, and pallor or cyanosis. Although considered benign, its abrupt and often dramatic presentation often leads to acute medical evaluation. Contemporary data on HHE are limited, and awareness among healthcare professionals needs attention. Methods: We conducted a retrospective analysis of all spontaneous reports of HHE submitted to the national pharmacovigilance centre Lareb between 1 January 2012 and 22 July 2025. Cases were included only when meeting Brighton Collaboration (BC) Level 1 criteria, requiring clear documentation of hypotonia, hyporesponsiveness, and pallor or cyanosis in children younger than 24 months. Demographic and clinical characteristics, vaccine combinations, latency, duration, seriousness, and medical care utilisation were described. Results: A total of 294 Level 1 HHE cases were identified. Most episodes followed combinations of hexavalent vaccines with pneumococcal conjugate vaccines. The median age at onset was 9 weeks, with slightly more reports involving boys. The median latency to onset was 5 h (range 4–8 h), and the median episode duration was 10 min (range 3–30 min), aligning with the historical literature. All children recovered fully, and no long-term sequelae were reported. Although HHE is clinically benign, 27% of cases were classified as serious, primarily due to hospital admission. Among non-serious cases, one third involved medical assessment or emergency services. Healthcare professionals submitted 44% of reports, notably community child health physicians. Conclusions: Contemporary Dutch pharmacovigilance data confirm that the clinical characteristics of HHE remain highly consistent with long-standig evidence. Despite its benign and self-limiting nature, HHE frequently triggers substantial medical care consumption. Improved awareness of the typical presentation, course, and prognosis, supported by the Brighton Collaboration criteria, may help clinicians recognise HHE more readily, reduce unnecessary medical consumption, and provide reassurance to caregivers.