Report A0380032A 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 as part of litigation proceedings. Medical history and concurrent condition were not provided. *Concurrent medications included multiple vitamins w/iron, caffeine, and clotricarole. *F/UP report on 11/5/02: The subject was the 3rd of 4 fraternal quadruplets delivered by cesarean section at 31.5 wks gestation to a 33 y.o., gravida III, pare I, abertus I, mother following a pregnancy complicated by multiple gestation, preterm labor, preeclempsia, and URI. 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 treated w/tarbutaline, magnesium, betamethasone to help induce fetal lung maturity, and "other complications". Complications of lable and delivery included toxemia, pulmonary edema, and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Birth weight was 1210 g. The subject's Apgar scorer were 8 and 9 at 1 and 5 mins, respectively. Due to prematurity and low birth weight, the subject was taken to a special care unit nursery. He was soon noted to have mild retractions associated w/mild decrease in air movement and "borderline" oxygen saturation. Continuous positive airway pressure (CPAP) was initiated and maintained for 24 hrs. He was then weaned and maintained on oxygen via nasal caneula. The subject initially had mild decrease in tone associated w/a magnesium level of 5.2 mg/dL. His tone and activity subsequently pormalized and he exhibited appropriate neurological behavior. He also experienced mixed apnes and bradycardia of prematurity, thrombocytopenia "2ndary to maternal condition", anemia of prematurity, jaundice (maximum bilirubin concentration, 9.1 mg/dL), slow feeding, gastroesophageal reflux, and "very minimal" hypospadias. He was Tx'd w/claspride, caffeine, multivitamins w/iron, clotrimatole (Lotrimin), and phototherapy. 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. Right inguinal hernia was noted at 2 mts of age. At 5 mts of age, his mother reported "choking spells". He had a viral infection at 16 mts of age. Developmental history revealed that "Motor milestones appear to have been met w/in normal limits." Specifically, the subject smiled in response to adult or his voice, exhibited eye and head control, and handled toys w/his hands at 3 mts (1 mt adjusted for prematurity); made sounds at 5 mts (3 mts adjusted); sat w/out support and crawled at 9 mts (7 mts adjusted); pulled up to a standing position at 10 mts (8 mts adjusted), and stood w/out support, walked, and finger fed himself by 12 mts (10 mts adjusted). The subject reportedly never pointed at objects. Around 14 mts, the subject "very loosely" said simple and 2 syllables such as "da", "ba", "da-da" and "ba-ba". Around 18 mts, the subject tried to say the alphabet. His mother reported that he communicated via screaming. 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.** The subject received injections of Engerix on 1/18/99, 2/15/99, and 6/30/99. He also received diphtheria and tetanus toxoids and acellular pertussis vax absorbed, Haemophilus influenzae type b conjugate vax, oral poliomyelitis virus vax, inactivated poliomyelitis virus vax, MMRII, varicella virus vax, and rotavirus vax. He also received palivizumab. In the spring 2000,* the subject "suffered neurologic damage as a result of exposure to thimerosol and mercury contained in the various vaccines which were administrered, 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." The most recent info. received was on 10/4/02. The autism persisted as of 9/30/02. The otucome of the mercury toxicity was not provided.* **The following info was received from medical records. The subject was Tx'd by his pediatrician from 2/15/99 thru at least 1/21/01. During this time, the MD noted the subject's mother complained the subject was not sitting up yet at 9 mts of age. Uring peptide analysis was performed on 1/2/01. Please see Lab Data section. The lab made a Dx of gluten sensitivity. The lab recommended a "gluten/casein free" diet and/or "peptidase supplementation". The lab also suggested supplementation w/acidophilus, folic acid, reduced glutathione, and ascorbic acid. 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: 4.5 - 5 mts, Gross motor: 4.5-5 mts, Social: 5 mts, Feeding, 3-4 mts, Language: 3.5 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 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 participate 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 were, "Fine motor: 20 mts, Gross motor: 20 mts, Social: 18-20 mts, Feeding: 20 mts, Language: expressive 10-11 mts, receptive: 12 mts." The neonatologist recommended a full speech evaluation. The subject was evaluated by an early intraventionist using the Carolina Curriculum, 2nd edition on 9/20/00. He was "referred by his mother because of developmental delays... [The mother] reports that [the subject] has been slower to sit up, pulling up, and other gross motor skills." The evaluator summarized the assessments as follows. "[The subject] scored approx at a 12 to 15 mt level in cognition. He scored less than a 12-month level in communication. [The subject[ scored approx a 15 month level in social adaptation w/scattered scores less than 12 mts up to 20 mts. [He] scored approx at a 15-month level in fine motor w/scattered scores in all areas. W/his gross motor skills, [he] scored approx at age equivalent. 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 that the subject "enoys books, especially reading alone, and tends to 'jabber' as if reading the words." The subject's speech was "characterized by grunting and screaming w/some consonant sounds, but no words, to get his needs met or to remark/point out." Using the Preschool Language Scale, the subject's auditory comprehension was assessed at 11 mts, expressive communication at 12 mts, and total language at 12 mts. The evaluator's assessments were "1) Moderate delay in receptive language skills, 2) Moderate 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 neurologist on 12/8/00 "for possible autism". At that time, his mother reports that the subject was "a bit slower" than his 3 brothers. The mother reported that the subject "screams much of the time. He does not point to objects. He does not bring objects to his parents. He also exhibits a lot of flapping maneuvers, and allso tip toes in his gait... He does not participate w/the other three [siblings] in various play activities. He makes poor eye contact. He physicallyl avoids being touched by others." The neurologist noted, "Physical exam shows a very active child... The child made poor eye contact. I heard no speech. He avoided being touched during the exam. General physical exam did not show any abnormalities... Sensory exam was probably normal, but it was difficult to be sure. Coordination was somewhat poor for age." The neurologist's impression was, "On the basis of the history and exam, this child may have pervasive developmental delay or autism". 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 because he was not yet speaking." 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 Module I, Childhood Autism Rating Scale, and Vineland Adaptive Behavior Scales. The psychologist noted, "[The subject] displays very limited social skills, marked by little use of nonverbal communication, little effort to initiate or maintain intersections, and little social or emotional reciprocity. [He] has a very difficult time making eye contact or responding to his name when called. He generally has a limited range of facial expressions, but will smile at certain objects. The few words he uses are said in a guttural, effortful tone of voice. He rarely initiates to other people, including his brothers... He typically appears unaware of other people's feelings and he does not offer comfort... He sometimes displays inappropriate affect and laughs for no apparent reason... [The subject's] verbalizations are limited to babbling, saying most of the alphabet, and using less than 5 other words or word approximations. He typically does not use gestures such as pointing, shaking his head, or reaching to compensate for his difficulty using words. His parents reported that he used to engage in simple social play such as peekaboo or a cartoon character's name, used to wave goodbye, and used to do a mealtime game that involved touching his finger to his mother's. However, he stopped engaging in these play routines about 6 mts ago. During the evaluation he did not demonstrate any pretend play, even w/assistance and promts... [The subject] enjoys looking at books and using pencils to draw. He does some simple functional play such as banging musical instruments or working cause-and-effect toys... [He] demonstrates some repetitive use of objects, stereotypes mannerisms, and sensory interests. His parents reported that he likes to line up toys, spin wheels on cars, and gather toys together. He is drawn to the number "7" and the letter "J" and will pick up things w/a 7 or J on them, or other long skinny things that have a similar shape. He stands on toys or books frequently. He flaps his arms or tenses his body when excited. During the evaluation he demonstrated several sensory interests, including visually inspecting objects in his peripheral vision and gently crumbling food. His parents reported that he walks on his toes, and that this behavior has increased in the last few mts. They have also noticed an increased amount of drooling. Finally, they have been concerned that no wakes at night screaming as if he might be in pain." His level of adaptive behavior was assessed as being in the "Impaired range relative to other children his age." His domain scores were as follows: Communication: 6 mts, Daily living skills: 13 mts, Socialization: 8 mts, Motor skills: 22 mts. The psychologist concluded, "According to the info gathered in this evaluation [the subject] meets criteria for a DSM-IV Dx of Autistic Disorder." The psychologist recommended "intensive intervention", speech therapy, occupational therapy, "structured interactions w/typical pears", and parent training. The psychologist noted that "Because [the subject] presents the most severe communication delays of any of his brothers, it will be important to ensure that his language instruction is extremely intensive and systematic." The psychologist also recommended that the subject "be examined by a neurologist to assess reports of starting spells and recent significant increase in drooling." The subject was evaluated by an occupational therapist on 1/11/01. His mother was concerned he was not learning self-help skills or feeding himself at an age appropriate level. Assessments included chart review, parent interview, clinical observations, the Sensorimotor History Questionnaire completed by the mother, and the Peabody Developmental Fine Motor Scales (PDMS). The occupational therapist concluded that the subject "appears to be functioning at the 15 mt level in fine motor skills according to the PDMS. Testing scores also indicate atypical processing of a variety of sensory inputs and delays in self-help, social and play skills. [The subject] has some strengths in grasping skills and his somewhat precocious interest in numbers and letters. He could benefit from occupational therapy to provide opportunities for enhanced sensory input and more normalized sensory processing, as well as addressing developmental delays and providing support and assistance for [the subject's] family in maximizing skills." 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, Psychoeducational Profile Revised, 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. Btwn 18 and 21 mts, [he] began to develop SXs of developmental delay and autism. SXs included: tantrums, preferring to be alone, unresponsive, lining up toys, preferring odd toys and avoiding eye contact. He began to receive speech therapy and special instruction at age 21 mts." Using Bayley Scales of Infant Development 2nd Edition, the subject exhibited a mental developmental age of 18 mts, a motor developmental age of 22 mts, and a behavior rating "w/in normal limits". Using the psychoeducational Profile Revised, he exhibited an overall developmental age of 19 mts. Imitation skills were on an 18 mt level, perception skills were on a 31 mt level, fine motor skills were on a 30 mt level, gross motor skills were on a 20 mt level, eye-hand interaction skills were on a 23 mt level, cognitive performance skills were on a 10 mt level, and cognitive verbal skills were on a 9 mt level. Using the Vineland Adaptive Behavior Scale, communication was graded on an 8 mt level, daily living skills at 13 mts, socialization at 12 mts, and motor skills at 21 mts. The subject's score on the childhood autism rating scale was 35, corresponding to a rating of "Mildly to moderately autistic". Using the Autism Tx evaluation checklist, the subject was rated in the "severe" autism category. The evaluator concluded, "Based upon the assessment results, [the subject's] strongest areas include: perception skills, fine motor skills, and eye-hand integration skills. Based upon the assessment results, [the subject's] weakest areas include: cognitive performance skills, cognitive verbal skills, receptive intervention using applied behavioral analysis, and speech and occupational therapy. Following the reported onset of autism, the subject experienced pneumonia, ear infections, gluten sensitivity, and underwent a hernia repair in March 99 and a re-repair in June 00. These events were not reported by 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 10/15/01 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. Following the reported onset of autism, the subject experienced pneumonia, ear infrections, gluten sensitivity, viral infections, chronic upper airway obstruction due to adenoid hyperplasia, dark circles under eyes, gastrointestinal symptoms including diarrhea, milk intolerance, chronic rhinitis and sinusitis, and underwent a hernia repair in March 1999 and a re-repair in June 2000. These events were not reported as adverse events due to vacination administration, but were found during the course of reveiw of the subject's medical records. 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).