This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by DuVernoy, T. S.
Right arrow Articles by the VAERS Working Group,
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by DuVernoy, T. S.
Right arrow Articles by the VAERS Working Group,
Related Collections
Right arrow Infectious Disease & Immunity
Right arrowRelated AAP Red Book topics:
Pertussis (Whooping Cough)
Hepatitis B
Haemophilus influenzae Infections

PEDIATRICS Vol. 106 No. 4 October 2000, p. e52

ELECTRONIC ARTICLE:
Hypotonic-Hyporesponsive Episodes Reported to the Vaccine Adverse Event Reporting System (VAERS), 1996-1998

Received Feb 1, 2000; accepted May 22, 2000.

Tracy S. DuVernoy, M. Miles Braun, and the VAERS Working Group

From the Division of Epidemiology, Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland.

Background.  A hypotonic-hyporesponsive episode (HHE) is the sudden onset of hypotonia, hyporesponsiveness, and pallor or cyanosis that occurs within 48 hours after childhood immunizations. This syndrome has been primarily associated with pertussis-containing vaccines administered to children <2 years of age, and has been estimated to occur once every 1750 diphtheria-tetanus-pertussis (DTwP) vaccinations. Previous studies of HHE were limited by small numbers of cases and, sometimes, by limited details of the event.

Objectives.  To characterize a large number of HHE cases reported to the Vaccine Adverse Event Reporting System (VAERS), to assist clinicians in identifying HHE, and to assist researchers in investigating the risk factors, cause, 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 follow-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 kg); 4.7% had a birth weight <2500 g. The median interval between vaccination 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 were no relevant findings regarding family medical history or the mothers' gestational history. Nearly all of the children (98.6%) returned to their prevaccination state according to the telephone questionnaire; median time to return was 6 hours (range: 1 minute- 4 months). The 3 children reported as not returning to their prevaccination state all had VAERS reports submitted after they developed conditions (autism, complex partial epilepsy, and developmental delays with infantile spasms) that are not known to be causally associated with immunization.The vast majority of children (93%) with HHE received a pertussis-containing 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 vaccines withheld as of the date of the interview. Of the remainder, 66.5% of children have had 1 or more subsequent vaccinations or vaccine components withheld, 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 hepatitis B vaccination. From 1996 to 1998, the number of HHE reports decreased from 99 to 38, when the predominant pertussis vaccine administered to infants changed from whole-cell to acellular.

Conclusion.  This study represents the largest published case series of children 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 vaccinations, 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 HHE within 5 minutes of immunization.  Key words:  hypotonic-hyporesponsive episode, childhood immunization, adverse event, vaccine safety.