Report A0380289A describes the occurrence of autism in a male child *less than 2 yra of age* who was vaccinated with hepatitis B vaccine recombinant for prophylaxis. This report was received as part of litigation proceedings. Medical history, concurrent conditions, and concurrent medications were not provided. The child is one of four *fraternal 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, preclampsia, and urinary tract infection. The subject's mother was on bed rest for 4 mts and was hospitalized for 6 wks prior to delivery. She was treated w/terbutaline, magnesium, betamethasone to help induce fetal lung maturity, and "other medications". Complications of labor and delivery included toxamia, pulmonary edema, and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Birth weight was 1200 g. The subject's Aspar scores were 8 and 9 at one and five minutes, respecitvely. He experienced "mild transitional respiratory distress" and was taken to a special care unit nursery. He was treated w/oxygen via nasal connula. He also experienced mixed apnea and bradycardia of prematurity, thrombocytopenia, anemia of prematurity, jaundice (max total bilirubin concentration, 7.4 mg/dL), slow feeding, nonspecific feeding intolerance, gastroesophageal reflux, and a "small" right hydrocale. Neurobehavioral assessments were appropriate for age throughout hospitalization. He was treated w/cisapride, caffeine, multivitamins w/iron, and packed red blood cell transfusion. A cranial ultrasound was performed at 2 wks of age. This revealed no hemorrhage or hydrocephalus. The subject was discharged to home 6 wks after birth w/an apnea monitor due to his history of apnea and bradycardia. Subsequently, an inguinal bernia was noted. The subject experienced otitis media at 9 mts of age, pharyngitis at 10 mts of age, avulsed primary incisors and a mild gum inceration at 12 mts of age, and a viral infection at 13 mts of age. Developmental history revealed that "Motor milestones appear to have been not w/in normal limits." Specifically, the subject sat w/out support at 8 mts (6 mts adjusted for prematurity), walked by 12 mts (10 mts adjusted), and "started saying a few single words at around age 17 mts" (15 mts adjusted).* The subject received an injection of Engerix B *on 1/24/99, 2/15/99, and 6/30/99. He also received diphtheria and tetanus toxoids and acellular pertussis vax absorbed (2/15/99, 4/28/99, 6/30/99, and 3/10/00), Haemophilus influenzas type b conjugate vax, oral poliomyelitis virus vax, inactivated poliomyelitis virus vax, MMRII, varicella virus vax, and rotavirus vax. He also received polivirumab. In the spring of 2000,* the subject "suffered neurologic damage as a result of exposure to thimerosol and mercury contained in the various vaccine which were administered, the subject to a reasonable degree of medical certainty has suffered injury and is autistic." Treatment and outcome were not specified. *The mother alleged that "the infants who were administered the vax earlier in life were more profoundly affected w/autism." **Continuation of F/UP report on 11/5/02: Info received from medical records: The subject was treated by pediatrician from 2/15/99 thru at least 1/9/01. During this time, the MD noted the subject's mother stated that she was "concerned w/hearing" at 6 mts of age and responded that the subject was "not talking yet" at 9 mts of age. At 15? mts of age, the MD noted that the subject was "Flat footed, especially on left." On 5/18/99, the subject was evaluated by a neunatologist in a developmental clinic. He was 5 mts of age (adjusted age, 3.5 mts). The results of the evaluation was "Fine motor: 4.5-5 mts, Gross motor: 5 mts, Social: 4-5 mts, Feeding: 3-4 mts, Language: 3.5 mts." The neunatologist wrote, "[The subject] is doing well developmentally." The subject returned to this MD on 12/14/99: he was 12 mts of age (adjusted age 10 mts). The results of the evaluation were "Fine motor: 10 mts. Gross motor: 11 mts, Social: 11-12 mts, Feeding: 10-11 mts, Language: 8 mts." The neonatologist stated, "[The subject] is catching up developmentally 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. [He] does have some tibial torsion in his right foot which is not a prob at this time." 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 were "Fine motor: 28 mts, Gross motor: 20 mts, Social: 18-20 mts, Feeding: 20 mts, Language: expressive: 13-15 mts, receptive: 13-15 mts." The neonatologist stated, "at this time I have no major concers about [the subject's] development. [He] has not quite caught up in his speech, but I see no signs of a cognitive problem at this time. The delay cound be environmental in nature." The neonatologist recommended speech screening in the next 4-6 mts. The subject was evaluated by an early interventionist using the Carolina Curricululm, 2nd Edition on 9/19/00. He was "referred by his mother because of developmental delays. [The mother] feels that [the subject] is doing well except that he does not eat foods well, and also his lack of speech. She is also concerned about his aggressive behaviors and socialization skills." The evaluator summarized the assessments as follows: "[The subject] scored approximately at a 13 month level in cognition, w/some scores up to 18 mts in visual perception. He scored less than a 12 mt level in communication. [The subject] scored approximately a 15 mt level in social adaptation w/scattered scores less than 12 mts up to 22 mts. [He] scored approximately at a 15 to 18 mt level in fine motor w/scattered scores in all areas. With his gross motor, [he] scored approximately at age equivalent. Speech therapy is recommended to address communication needs. Possible day care is recommended to help [his] speech and social skills. Behavior modifications are recommended to help work on getting [him] to decrease some aggressive behaviors. 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 his lack of speech and his socialization skills, including some aggressive behavior." At that time, his mother reported that the subject "loves to play: he likes puzzles, a shape sorter, books, and containers into which he puts various items. Per the intake paperwork, [he] displays frustration by screaming if he tris to get something for himself or make something work and is unsucessful." The subject's speech was "characterizes by grunting and screaming w/occasional single words to get his needs met or to remark/point out." Using the Preschool Language Scale, the subject's auditory comprehension was assessed at 15 mts, expressive communication at 15 mts, and total language at 15 mts. The evaluator's assessments wrote "1) Mild delay in receptive language skills, 2) Mild delay in expressive language skills." He added, "Prognosis for improved communication skills is excellent w/initiation of intervention and involvement of parents in carryover suggestions... speech therapy on a regular basis is strongly recommended to provide extra stimulation of [the subject's] communication skills." The subject was evaluated by a psychologist on 10/9/00 "to determine strengths and weaknesses related to early intervention needs." The psychologist noted that the subject "responded well to social interaction... [He] can repeat some single words. He was referred by his mother because of possible developmental delay. [She] feels that [the subject] is doing well except for his eating skills. She is concerned about his lack of speech, aggressive behavior, and socialization skills." Assessments used included Bayley Scales of Infant Development 2nd Edition and Vineland Adaptive Behavior Scaled Interview Edition. Using Baylay Scales of Infant Development 2nd Edition, the subject exhibited a mental developmental age of 15 mts, a psychomotor developmental age of 16 mts, a cognitive developmental age of 18 mts, a language developmental age of 12 mts w/"scattered successes up to the 19 month level", a social developmental age of 10 mts, and a motor developmental age of 16 mts. Using the Vineland Adaptive Behavior Scale, communication was graded on a 10 mt level, daily living skills at a 12 mt level, socialization at a 10 mt level, and motor skills at a 12 mt level. The psychologist's Dx was "Mixed Reception/Expressive Language Disorder". He recommended speech therapy and special instruction focusing on cognitive, language, and social stimulation. The subject was evaluated by a 2nd psychologist on 1/4/01 at the "autism resource center" of a tertiary care center. At that time, it was reported that "His parents becamse concerned about his development at around 18 mts, because his language appeared delayed." The subject was evaluated "to determine if [his] behavior and development are due to a Pervasive Developmental Disorder." The subject was evaluated w/the Autism Diagnostic Interview - Revised. Autism Diagnostic Observation Schedule Nodule I, Childhood Autism Rating Scale, and Vineland Adaptive Behavior Scales. The psychologist noted, "[The subject's] parents described him as being initially timid around other children, but then overbearing once he is familiar w/the environment. They reported that he is slow to warm up and does not seem aware of that to do around other children. However, he watches other children, plays w/his brothers somewhat at home, and shows enjoyment during interactions. If a toy he is playing with is taken away, he will persist in his efforts to get the toy back. His parents reported he has a good range of facial expression... He responded to his name and to efforts to share interest, and initiated sharing his own interests w/the examiner several times. His parents reported that he smiles when he is proud, and runs to greet his father upon his arrival home." The parents reported that they were concerned "that some of the good social behaviors he has demonstrated in the past (initiating joint attention, using gestures) no longer happen w/the same frequency at home. They have also been concerned that his interest in playing w/other children has decreased. They reported that when other people are hurt or up9set he seems to want to make some comforting response, but the response is limited. During the evaluation, [he] engaged in limited verbalizations, but he did not use some compensatory strategies such as eye contact and reaching while making a vocalization. He used some single word and word approximations ("car", "choo choo", "wasis" for "what's that"). His parents reported that he can also say "hi dada", "bye bye" and will repeat "sit down" when told to sit down, but does not use more flexible phrase speech and rarely used speech w/out being prompted to do so. During the evaluation he showed objects to other people or gave them (w/eye contact) when he needed help. He pointed at objects on occasion, but often had to be prompted to do so. [He] demonstrated some unusual receptive language difficulties. He often responded to directions as if he had heard them incorrectly... His parents reported that he often demonstrates this type of confusion at home as well, appearing to listen closely to directions but then responding in a way that shows he did not understand... [He] demonstrated some beginning pretend play skills during the evaluation... He imitated some simple games and used some objects as placeholders w/a demonstration. His parents reported that he used to play this way w/one of his brothers, but that this type of play has decreased significantly in the past several wks. [His] parents reported that at home he enjoys looking at books and will point to some of the pictures when prompted. He also likes puzzles and sorting activities... Shortly after the evaluation they contacted the center concerned that he had very recently begun demonstrating some behaviors that he was not showing previously, such as lining up toys and objects (e.g., blocks, chairs in the waiting rooms, etc, instead of playing more appropriately like he used to." His level of adaptive behavior was assessed as being in the "Borderline Impaired range relative to other children his age." His domain scores were as follows: Communication: 15 mts, Daily living skills: 15 mts, Socialization: 14 mts, Motor skills: 22 mts. The psychologist concluded, "According to the info. gathered in this and previous evaluations, [the subject] meets criteria for a DSH-IV diagnosis of Mixed Expressive Receptive Language Disorder... a Pervasive Developmental Disorder could not be ruled out w/the present evaluation." The psychologist recommended "Intensive Intervention", speech therapy, structured interactions w/"typical peers", and parent training. The psychologist stated, "[The subject] may be currently experiencing a developmental regression. It is recommended that he be re-evaluated w/in the next 6 mts to further monitor his development and determine if he has a Pervasive Developmental Disorder." The subject was evaluated by an occupational therapist on 1/15/01. His mother reported that "Like his brothers, [the subject] had pneumonia this past summer and repeated ear infections. It was about this time that the parents report seeing changes in their developmental progress and became concerned." Assessments included chart review, parent interview/questionnaire, clinical observations, the Peabody Developmental Fine Motor Scales (PDMS), and the self-care portion of the Pediatric Evaluation Disabilities Inventory (PEDI). The occupational therapist concluded that the subject "appears to be exhibiting mild delays in fine motor development. According to the PDMS he is functioning at the 20-month level for fine motor skills. The results of the self-care portion of the PEDI suggest that skills in this area are slightly below average range. Response to Sensory Input guide along w/observations and parent report suggests that [the subject] may be having some difficulties regarding and processing some sensory info. Defensiveness in the tactile system in particular could be limiting pleasure associated w/learning about himself and his world through this sensory system." Occupational therapy was recommended. The subject was evaluated by an autism trainer on 2/13/01. He was assessed using the Autism Treatment Evaluation Checklist. At that time, his mother reported that the subject had "developed normally for the first 21-23 mts of life. Between 21-23 mts, [he] began to develop Sx's of developmental delay and autism. Sx's included: excessive shyness, difficulty w/speech, lining up toys, and he used language repetitively. He recently began to receive speech therapy and special instruction. [He] was Dx'd w/autism recently by the [autism resource center mentioned above]." Using the Autism Treatment Evaluation Checklist, the subject was rated in the "moderate" autism catetory. The evaluator concluded, "[The subject] shows mild to severe developmental delays in all areas and will require intensive early intervention to overcome these dalays. His Sx's of autism, while mild, still interfere w/his ability to learn." He recommended intensive early intervention using applied behavioral analysis, and continued speech and occupational therapy. Following the reported onset of autism, the subject experienced pneumonia, reactive airway disease, left otitis media, 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.* The outcome of the mercury toxicity was not provided.* The most recent information received on 26Feb04 indicated that he autism persisted as of 15July02. This report of autism is considered medically serious by the manufacturer. (OMIC)