Sex: M
Vaccine: DTAPIPVHIB, HEP, HIBV, RV5, UNK
Symptoms: Hypotonia, Intraosseous access placement, Musculoskeletal stiffness, Pulse absent, Respiratory arrest
Clinical narrative: Seizure; Information was received from an investigator concerning a 6-month-old male subject enrolled in a study.  The subject's concurrent conditions and concomitant therapies were not reported. The subject's medical history included shoulder dystocia. ^^The subject had family history of seizures (2 maternal cousins had seizures when they were toddlers). the infant was born at 38 4/7 weeks gestational age, length 52 cm, weight 3470 grams, head circumference 35 cm. No neonatal problems except shoulder dystocia^^  On 11-JUL-2019, the subject was randomized into the study protocol. On that date, at 15:06, the subject was vaccinated with the first dose of Rotavirus Vaccine, Live, Oral, Pentavalent (ROTATEQ) (dose: 2 mL) orally (PO), and on the same day, at 15:07, he was vaccinated with the first dose of V114 or pneumococcal 13 valent conjugate vaccine (CRM197) (PREVNAR 13) 0.5 mL intramuscularly (IM), 4 doses in visits 1, 2, 3 and 5. He as was also vaccinated at 15:08, with the first dose of diphtheria toxoid (+) Haemophilus b conjugate vaccine (unspecified carrier) (+) pertussis acellular vaccine (unspecified) (+) poliovirus vaccine, inactivated (unspecified) (+) tetanus toxoid (DTAP-IPV HIB) (PENTACEL) vaccine (dose: 0.5 mL) IM, and at 15:09, with Hepatitis B Vaccine (Recombinant) (RECOMBIVAX HB) (dose: 0.5 mL) IM. On an unspecified date, the subject was also vaccinated with Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate) (HIBERIX) (dose details not reported). V114 or pneumococcal 13 valent conjugate vaccine (CRM197) (PREVNAR 13) was administered as prophylaxis for pneumococcal disease; while, all other vaccines were administered as prophylaxis (unspecified).    On 10-SEP-2019 at 10:31, 10:32 and 10:33, the subject received second doses of Rotavirus Vaccine, Live, Oral, Pentavalent (ROTATEQ) and the second dose of V114 or pneumococcal 13 valent conjugate vaccine (CRM197) (PREVNAR 13) (doses and route of administration as previously described) and diphtheria toxoid (+) Haemophilus b conjugate vaccine (unspecified carrier) (+) pertussis acellular vaccine (unspecified) (+) poliovirus vaccine, inactivated (unspecified) (+) tetanus toxoid (DTAP-IPV HIB) (PENTACEL). On 12-NOV-2019 at 14:42, 14:44, 14:45 and 14:46, the subject received third doses of Rotavirus Vaccine, Live, Oral, Pentavalent (ROTATEQ) and the second dose of V114 or pneumococcal 13 valent conjugate vaccine (CRM197) (PREVNAR 13)  (doses and route of administration as previously described), diphtheria toxoid (+) Haemophilus b conjugate vaccine (unspecified carrier) (+) pertussis acellular vaccine (unspecified) (+) poliovirus vaccine, inactivated (unspecified) (+) tetanus toxoid (DTAP-IPV HIB) (PENTACEL) and Hepatitis B Vaccine (Recombinant) (RECOMBIVAX HB).  Since an unspecified date (reported since the subject was 4-month-old), the subject's mother reported that he had episodes of seizures that lasted several seconds; ^^the child did not present with seizures prior to randomization at 2 months age. There were no similar events experienced after the administration of the first and second doses of study vaccines, and there were no signs and/or symptoms prior to the administration of the third dose of study vaccines. No evidence of failure to thrive^^. On 12-NOV-2019, the subject was seen for his 6-month well child check. ^^During the clinic visit, his mother reported that a few weeks ago, the child started having episodes where he would be crying and then he would tighten his arms and his legs. This would only last for a few seconds and then he was fine. She reported that last week, the maternal grandmother noted that he did this, and eyes rolled to the back of his head and he seemed like he was not breathing. She blew in his face and then he started crying again. He was immediately fine after this and not lethargic or drowsy. At the WCC, the child was assessed as 6-month-old male with normal growth and development. The episodes of tightening his arms and legs were considered to be more like temper tantrums but it was discussed with the parent that if that was seizure, he would be needed to be evaluated further.^^ Moreover, the physician asked the mother to record a video of the seizures and they would be referred to a specialist for workup and possible treatment.  On 13-NOV-2019 at 13:15, the subject was in the grandmother's arms when he started crying and screaming for several seconds, his eyes rolled back, and he became limp and stopped breathing. The subject experienced seizure (severe). ^^There were no relevant signs / symptoms, apart from crying already noted, prior or concurrent to previous episodes of possible seizures^^. His grandmother took him to freestanding emergency room (ER) (outside the site facility). At the outside facility, the subject was found to be in asystole and apneic; became bradycardic down to 50's then coded. ^^On that day, his glucose was 246 mg/dl.^^ Cardio pulmonary resurrection (CPR) started with return of spontaneous circulation. He was transferred by ambulance to the site ER but lost the pulse again in route; 6 doses of epinephrine were administered prior to arrival. During transfer pulse less electrical activity noted and asystole on emergency medical services (EMS) monitors, CPR was performed while bagged, EMS attempted to intubate without success in route. An oral airway was placed and bilateral intraosseous lines in lower extremities. They arrived at the site ER with the subject in cardiac arrest and apneic. On arrival to the site, the subject was intubated, epinephrine, atropine, bicarbonate and naloxone (NARCAN) were administered ^^for cardiac arrest^^. An ultrasound for pulse check showed no cardiac activity. ^^It was reported that the subject was hospitalized^^. Core temperature was 94.6 Fahrenheit rectally, CRP continued with no success an at 14:19 (after 1 hour) the subject died due to ^^seizure^^ as per hospital records. ^^An autopsy was performed. No imaging testing to evaluate the seizures was carried out; no medications were given for previous episodes of possible seizures. The subject died in the ER before he could be admitted to the hospital; therefore, admission date, discharge date and discharge diagnosis were not applicable. There was no confirmed diagnosis of seizures prior to the day of death and no further information available regarding onset dates of 'episodes' reported by the mother^^. The action taken with the study therapies was reported as ^^dose not changed^^.  The investigator considered the seizure (severe) to be related to V114 or pneumococcal 13valent conjugate vaccine (CRM197) (PREVNAR 13), Rotavirus Vaccine, Live, Oral, Pentavalent (ROTATEQ), Hepatitis B Vaccine (Recombinant) (RECOMBIVAX HB), to diphtheria toxoid (+) Haemophilus b conjugate vaccine (unspecified carrier) (+) pertussis acellular vaccine (unspecified) (+) poliovirus vaccine inactivated (unspecified) (+) tetanus toxoid (DTAP-IPV HIB) (PENTACEL) vaccine and Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate) (HIBERIX), but not related to the study procedure. ^^The investigator assessed the event related to administration of all vaccines due to temporal relationship and no other definitive cause of death^^. The investigator considered the seizure (severe) to be a life-threatening event.  Updated information received on 15-NOV-2019 from the investigator has been captured in between double caret (^^).  The record for this subject was unblinded on 18-NOV-2019. Company Causality Assessment: Although there is a family history of seizures and co-suspect use RECOMBIVAX HB (known to be associated with non-fatal seizure), based on the clinically relevant information currently available for this individual case, there is a possibility  that the reported serious adverse event of Seizure with a fatal outcome is related to the use of the investigational vaccines (blinded investigational vaccine [V114 or PREVNAR 13] and open-label study vaccine [PENTACEL and HIBERIX). The plausible temporal relationship, the known safety profiles of the blinded comparator (known to be associated with non-fatal seizure and apnea) and open label study vaccines (PENTACEL [known to be associated with non-fatal apnea] and HIBERIX [known to be associated with non-fatal convulsions]) support the possible relationship. Additional information regarding laboratory data due to increased glucose prior to CPR, autopsy report and the history of shoulder dystocia with unknown complications are needed for further assessment. Important missing information includes any record of fever accompanying the event. Febrile seizures have previously been reported in children who have received pneumococcal conjugate vaccines (PREVNAR 13).  An Analysis of Similar Events regarding this follow up report of the adverse reaction of Seizure with the serious criteria of hospitalization, life threatening and death was performed. This case refers to a 6-month-old male subject who experienced Seizure after the third dose of the investigational vaccines (blinded investigational vaccine [V114 or pneumococcal 13 valent conjugate vaccine (CRM197) PREVNAR 13] and open label study vaccines [PENTACEL and HIBERIX]). This is the first reported case of Seizure in association with the investigational vaccines (blinded investigational vaccine [V114 or pneumococcal 13 valent conjugate vaccine (CRM197) PREVNAR 13] and open label study vaccines [PENTACEL and HIBERIX]) submitted to the FDA.     The Suspected Adverse Reactions of Seizure does not alter the existing benefit-risk profile of the product. Merck and Co., Inc., known as MSD outside of certain countries, will continue to monitor this event and other serious adverse events reported in association with V-114 and will communicate any relevant changes to the protocol, Investigator's Brochure and/or Core Safety Information.; Reported Cause(s) of Death: Seizure