Report A0380288A describes the occurrence of autism in a male child *less than 2 yrs of age* who was vaccinated with hepatitis B vaccine recombinant for prophylaxis. This report was received a spart of litigation proceedings. Medical history and concurrent conditions were not provided. *Concurrent medications included multiple vitamins with iron and caffeine.* **The subject is the first of four quadruplets delivered by cesarean section at 31.5 wks gestation to a 33 y.o., gravida III, para I, abortus I, mother following a pregnancy complicated by multiple gestation, preterm labor, preeclampsia, and urinary tract infection. The subject's mother was on bed rest for 4 mts and was hospitalized for 6 wks prior to delivery. The subject's mother was tx'd w/terbutaline, magnesium, betamethasone to help induce fetal lung maturity, and "other medications". Complications of labor and delivery included toxemia, pulmonary edema, and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Birth weight was 3 lbs 5.8 oz. The subject's Apgar scores were 8 and 9 at 1 and 5 mins, respectively. He was taken to the special care unit for respiratory distress and was initially placed on continuous positive airway pressure (C-PAP) ventilation for transient tachypnea but w/in 24-36 hrs was weaned to nasal cannula with 1L of flow and 25% oxygen. W/in 48 hrs, he was weaned to room air, thereafter, and weaned off of the nasal canuuls w/in the first week of life. During hospitalization, the subject exhibited episodes of apnea of prematurity mainly as hypoventilation and was initially placed on aminophylline, however this was changed to caffeine. The subject also anemia of prematurity and jaundice (max total bilirubin concentration 8.0 mg/dl). He was tx'd w/multivitamins, fluconazole and phototherapy. A cranial ultrasound was performed at 2 wks of age. This revealed no hemorrhage. Initially there was a question of a small cystin lesion, however, follow-up head sonogram was read as normal and there was no evidence for PVL present. The subject was discharged to home 6 wks after birth w/an apnea monitor due to his history of apnea and bradycardia. Right inguinal hernia was noted at 3.5 mts of age. The subject suffered from projectile vomiting btwn his 1st and 4th month of life and had exzema at 9 mts of age. Developmental history revealed that "Motor milestones appear to have been met w/in normal limits." Specifically, the subject sat w/ou support by 8 mts (6 mts adjusted), and walked by 12 mts (10 mts adjusted). At age 16 mts, the subject said single words. At age 2 yrs, he pointed at objects. The subject's parents reported that he used to wave goodbye, seek out his mother, and stack blocks but those activities ceased in July 00.** On 1/18/99, the subject received an injection of Engerix B. *He also received palivizumab on 1/17/99, **IPOL (IPV), and MMR on an unspec'd date.** In the spring of 2000,* the subject "suffered neurologic damage as a result of exposure to thimerosol and mercury contained in the various vaccines which were administered, the subject to a reasonable degree of medical certainty has suffered injury and is autistic." Treatment was not specified. *The mother alleged that "the infants who were administered the vax earlier in life were more profoundly affected w/autism." The most recent info was received on 10/4/02. The autism persisted as of 9/30/02. The outcome of the mercury toxicity was not provided.* **F/UP report on 11/5/02: The following info was received from medical records. The subject was tx'd by his pediatrician from 2/15/99 thru at least 2/26/00. During this time, the MD noted the subject's mother c/o'd the subject was crying a lot. Urine peptide analysis was performed on 1/3/01. Please see Lab Data section. The laboratory recommended a "gluten/casein free" diet and/or "peptidase supplementation". On 5/18/99, the subject was evaluated by a neonatologist in a developmental clinic. He was 5 mts of age (adjusted age 3.5 mts). The results of the evaluation were "Fine motor: 5 mts, Gross motor: 3.5-6 mts, Social: 5 mts, Feeding: 3-4 mts, Language: 4 mts." The neonatologist wrote, "[The subject] is also doing well developmentally." The subject returned to this MD on 12/14/99, he was 12 mts of age (adjusted, 10 mts). The results of the evaluation were "Fine motor: 12-23 mts, Gross motor: 13 mts, Social: 12-13 mts, Feeding: 10-11 mts, Language: 8 mts." The neonatologist stated, "[The subject] is caught up developmentally in all area except for his language development. This language delay is possibly due to prematurity plus his family trying to anticipate his needs along w/his brothers." On 8/22/00, the subject was again evaluated by this MD; he was 20 mts (adjusted age, 18 mts). The results of this evaluation by this MD; he was 20 mts (adjusted age, 18 mts). The results of this evaluation were "Fine motor: 20 mts: Gross motor: 20 mts, Social: 18-20 mts) Feeding: 20 mts, Language: expressive: 13-15 mts, receptive 13-15 mts." The neonatologist noted, "At this time, I have no major concerns about [the subject's] development. [The subject] has not quite caught up in his speech, but I see no signs of a cognitive problem at this time. The delay could be environmental in nature." He also recommended a speech screening. The subject was evaluated by an early interventionist using the Carolina Curriculum, 2nd Edition on 9/19/00. He was "referred by his mother because of developmental delays... [The mother] is concerned because his doctor told her that [the subject's] was speech delayed." The evaluator summarized the assessments as follows. "[The subject] scored approx at a 13-15 mt level in cognition. He scored less than a 12-mt level in communication. [The subject] scored approx a 15-18 mt level in social adaptation w/scattered scores less than 12 mts up to 20 mts. [He] scored approx at a 15-18 mt level in fine motor w/scattered scores in all areas. W/his gross motor skills, [he] scored approx at age equivalence. Speech therapy is recommended to address communication needs. Possible day care is recommended to help [his] speech and social skills. Special instruction is recommended to work on appropriate play skills. The subject was evaluated by a speech pathologist on 9/29/00 "because of some concerns about developmental delay." At that time, his mother reported the subject's speech was "characterized by grunting and screaming w/some occassional single words to get his needs met or remark / point out. He reportedly understood well. Using the Preschool Language Scale, the subject's auditory comprehension was assessed at 11 mts, expressive communication at 1 yr, and total language at 1 yr. The evaluator's assessments were "1) Mild delay in receptive language skills, 2) Mild delay in expressive language skills." He recommended, "speech therapy once or twice wkly." The subject was evaluated by a psychologist on 1/4/01 at the autism resource center of a tertiary care center. At that time, it was reported that "His parents first became concerned about his development at around 18 mts... At that age, he was using some single words but had not developed phrase speech or as much communicative language as other children his age." The parents also reported that his abilities and social behavior had changed significantly in the previous several wks as he had become less social and began waking on his toes. The subject was evaluated "to determine if [his] behavior and development are due to a Pervassive Developmental Disorder." The subject was evaluted w/his Autism Diagnostic Interview - Revised, Autism Diagnostic Observation Schedule Module I, Childhood Autism Rating Scale, and Vineland Adaptive Behavior Scales. The psychologist noted, "[The subject] displayed some good eye contact and shared attention in the first few mins, but then did not display these social behaviors for the remainder of the session. He smiled when pleased w/something an adult did (e.g. during tickling) but did not appear to be responding to the social nature of the situation... [The subect] is able to name at least 30 objects and finish favorite songs or word plays (e.g., saying "to you" at the end of "Happy Birthday"). He uses a few word approximations for requests, but had not developed phrase speech. His use of gestures is limited to occasionally waving... He does not point or use other functional or descriptive gestures to help compensate for his difficulties w/verbal communication, but will cry or bring or show objects to adults when he needs help... His favorite activity is sitting in an adult's lap while being read a book, however [the subject] insists on doing this activity a specific way and to the exclusion of many other types of play or engagement... [The subject] seems to be preoccupied with books and being read in a specific way... During the exam he exhibited some mild hand flapping and body tensing, and his parents reported that he has recently begun walking on his toes. He demonstrates an unusual attachment to stringe and will hold a string for comfort while smoking his thumb... [The subject] used to demonstrate more play skills than he currently does; however, his ability w/puzzles and books are still a relative strength. His good motor skills, initial curiosity about a new environment, and verbal labeling are all strengths for him... His early responsiveness to intervention, and his ability to use some words in a meaningful way, are good prognostic indicators... His level of adaptive behavior was assessed as being in the "Mildly Impaired range relative to other children his age." His domain scores were as follows: Communication: 1 yr, Daily living skills: 1 yr 1 mt, Socialization: 11 mts, Motor skills: 1 yr 10 mts. The psychologist concluded, "According to the info gathered in this evaluation, [the subject] meets criteria for a DMS-IV diagnosis of Autistic Disorder." The psychologist recommended "intensive intervention", speech therapy, occupational therapy, "structured interactions w/typical peers", and parent training. The psychologist noted that "Tontinues to expose [the subject] to new ways of doing things... Replace unusual comfort items. The subject was evaluated by an occupational therapist on 1/8/01. His mother reported developmental milestones were met. Assessments included chart review, parent review, clinical observations, and the Peabody Developmental Fine Motor Skills (PDMS). The occupational therapist concluded that the subject "appears to be functioning at the 20-21 mt according to the PDMS and clinical observation. He is also having some difficulty w/social skills and beginning self-care skills, such as self-feeding." Twice weekly occupational therapy was recommended. The subject was evaluated by an autism trainer on 1/16/01. Assessments used included Bayley Scales of Infant Development 2nd Edition, Vineland Adaptive Behavior Scales Interview Edition Survey Form, Childhood Autism Rating Scale, and Autism Treatment Evaluation Checklist. At that time, his mother reported that the subject had "developed normally for the first 18 mts of life... He had just recently been dx'd w/Pervasive Developmental Disorder... SXs included: some echolalia, fixated on certain toys, holds odd postures, and chews on non-food objects. He had recently begun to receive speech therapy and special instruction. Using Bayley Scales of Infant Development 2nd Edition, the subject exhibited a mnetal developmental age of 25 mts, a motor developmental age of 23 mts, and a behavior using "w/in normal limits". Using the Vineland Adaptive Behavior Scale, communication was graded on a 1 yr, 5 mt level, daily living skills at 1 yr 2 mts, socialization at 1 yr 1 mt, and motor skills at 1 yr 11 mts. The subject's score on the Childhood Autism Rating Scale was 22, corresponding to a rating of "Non-Autistic." The Autism Treatment Evaluation Checklist" (ATEC) were as follows: Total score changed from 52 at baseline to 49 at post-training as well as improvement in all 4 areas: Speech/ Language/ Communication, Sociability, Sensory/ Cognitive Awareness, and Health/ Physical/ Behavior. The evaluator concluded, "There should be consistent use of learning protocol including, making eye-contact on demand, remaining in his seat, sharing w/others, and complying w/directions. Instructions need to be explained to the subject so he will be able to understand. [The subject] should use a picture/written schedule and mark off to bring to a closure to the activity. It is imparative that [the subject] receives instruction in the use of a communication system to help him express his Autism Training Program. By the end of the session, "[the subject] independently said yes or not appropriately... Other recommended training tasks include, copying shapes, tracing shapes, coloring in lines, and saying his full name upon request." Following the reported onset of autism, the subject experienced pneumonia, ear infections, gluten sensitivity, and underwent a hernia repair in March 99. These events were not reported as adverse events due to vax admin, but were found during the course of review of the subject's medical records. Therefore, they are not listed as adverse events. The most recent info received on 10/15/02 did not provide the outcomes of the reported events. Info received on 9/30/02 indicated that the autism persisted on that date.** This report of autism is considered medically serious. This is one of four quaddruplets who experienced autism following receipt of Engerix B. Following the reported onset of autism, the subject experienced pneumonia, ear infections, eye drainage and redness, chronic rhinitis, chronic dark circles under eyes, gluten sensitivity, and underwent a hernia repair in March 1999. These events were not reported as adverse events due to vaccine administration, but were found during the course of reveiw of the subject's medical records. Therefore, they are not listed as adverse events. The most recent information received on 26 February 2004 indicated that the autism persisted as of 15 July 2003. This report of autism is considered by the manufacturer as medically serious. (OMIC).