Hypotonic-hyporesponsive episodes reported to the Vaccine Adverse Event Reporting System (VAERS), 1996-1998

Background. A hypotonic-hyporesponsive episode (HHE) is the sudden onset of hypotonia, hyporesponsiveness, and pallor or cyanosis that occurs within 4 8 hours after childhood immunizations. This syndrome has been primarily ass ociated with pertussis-containing vaccines administered to children <2 year s of age, and has been estimated to occur once every 1750 diphtheria-tetanu s-pertussis (DTwP) vaccinations. Previous studies of HHE were limited by sm all numbers of cases and, sometimes, by limited details of the event. Objectives. To characterize a large number of HHE cases reported to the Vac cine Adverse Event Reporting System (VAERS), to assist clinicians in identi fying HHE, and to assist researchers in investigating the risk factors, cau se, and pathogenesis of this syndrome. Methods. More than 40 000 VAERS reports received between 1996 and 1998 were screened for HHE by a computer algorithm and reviewed, and a telephone fol low-up questionnaire was administered to the witness of HHE. Results. There were 215 HHE cases, all nonfatal. The median age of onset of HHE was 4.0 months (range: 1.1-107 months). Over half of the reports (53%) concerned females. The median birth weight was 3.36 kg (range: 1.27-4.96 k g); 4.7% had a birth weight <2500 g. The median interval between vaccinatio n and HHE was 210 minutes (range: 1 minute-2 days). Among children with HHE who were <24 months of age, the episode occurred within 5 minutes in only 8.5%, compared with 66.7% of children with HHE >24 months of age. There wer e no relevant findings regarding family medical history or the mothers' ges tational history. Nearly all of the children (98.6%) returned to their prevaccination state a ccording to the telephone questionnaire; median time to return was 6 hours (range: 1 minute-4 months). The 3 children reported as not returning to the ir prevaccination state all had VAERS reports submitted after they develope d conditions (autism, complex partial epilepsy, and developmental delays wi th infantile spasms) that are not known to be causally associated with immu nization. The vast majority of children (93%) with HHE received a pertussis-containin g vaccine, either diphtheria-tetanus-acellular pertussis (DTaP, 28%), DTwP (11%), or diphtheria-tetanus-pertussis-Haemophilus influenzae type b (DTwP- HIB, 61%). During the HHE episode, 90.1% of the children had pallor and 49% had cyanosis. Because of the HHE event, 6.8% of children had had all vacci nes withheld as of the date of the interview. Of the remainder, 66.5% of ch ildren have had 1 or more subsequent vaccinations or vaccine components wit hheld, and 26.7% have not had any subsequent vaccinations withheld. Only 1 child was reported to have had a repeat episode of HHE, occurring after hep atitis B vaccination. From 1996 to 1998, the number of HHE reports decrease d from 99 to 38, when the predominant pertussis vaccine administered to inf ants changed from whole-cell to acellular. Conclusion. This study represents the largest published case series of chil dren with HHE and supports the generally benign, self-limited, nonrecurrent nature of this syndrome. Although HHE has been less frequently reported to VAERS after increased use of DTaP, HHE does occur after the administration of DTaP and other nonpertussis-containing vaccines. Although most parents and pediatricians withheld the pertussis component of subsequent vaccinatio ns, many did not, with no reported adverse events occurring in the children after the subsequent immunizations. Restricting the definition of HHE to a more narrow age range (eg, <2 years of age) is also proposed because most of the older children probably experienced vasovagal syncope rather than HH E within 5 minutes of immunization.