Sex: F
Vaccine: HEP
Symptoms: Echocardiogram, Echocardiogram abnormal, Electrocardiogram abnormal, Electrocardiogram ambulatory normal, Foetal exposure during pregnancy
Clinical narrative: Fetal exposure during pregnancy; ebstein's anomaly; This retrospective pregnancy case was reported in a literature article and described the occurrence of ebstein's anomaly in a 3-month-old female infant exposed to Hepatitis B vaccine in utero while the mother was treated for prophylaxis.   The parent's medical history included environmental allergy, overweight, attention deficit/hyperactivity disorder, normal birth (had 2 prior pregnancies), contraceptive (had been using condoms with spermicide for contraception), engerix b adult (1st dose received on 14th August 2014) and engerix b adult (2nd dose received on 11th September 2014).   On 29th January 2015, the 36-year-old mother received the 3rd dose of Hepatitis B vaccine (intramuscular) 20 ug.   The mother's last menstrual period was on 5th February 2015 and estimated date of delivery was 2nd November 2015. The infant was exposed to Hepatitis B vaccine at an unknown time during the pregnancy. 38 weeks and 2 days, the infant was born via vaginal delivery and weighed 3430 grams (7lbs 9oz) at birth. APGAR score was 8. The infant was diagnosed with ebstein's anomaly (serious criteria GSK medically significant and congenital anomaly). On an unknown date, the infant experienced fetal exposure during pregnancy. On an unknown date, the outcome of the ebstein's anomaly and fetal exposure during pregnancy were unknown.   The reporter considered the ebstein's anomaly to be possibly related to Hepatitis B vaccine.   Additional Information: GSK receipt date: 25 Jan 2016 Reporter comment: The study vaccine was confirmed to be Engerix B adult. The patient's mother was 36 years old woman enrolled in study. While enrolled in the study, the mother became pregnant and the baby (patient) was born with Ebstein's anomaly, mild, which was considered a birth defect. The patient's mother did not use benzodiazepines or lithium prior to or during pregnancy, had no dysrhythmia, and no toxic occupational exposure. The investigator did not consider the patent foramen ovale as a separate serious adverse event as it was part of the Ebstein's anomaly and would perinatal take a while to close. Relevant medical history of mother included two prior pregnancies, environmental allergies (1994), being overweight (30th July 2014), and ADHD (attention deficit/hyperactivity disorder). The mother of the patient had been using condoms with spermicide for contraception. The mother had no pregnancy risk factors. Family history was negative for congenital anomalies, sudden death, arrhythmia, dilated cardiomyopathy, hypertrophic cardiomyopathy, and premature coronary artery disease.  The mother held a number of jobs and had been in contract analysis for 15 years, she had no toxic occupational exposure. The mother had no dysrhythmia, and had no exposure to benzodiazepines or lithium prior to or during the pregnancy. The mother was not taking any medications at the time of conception. The mother's last menstrual period (LMP) was on 5th February 2015 and the estimated conception date (ECD) was 11th February 2015. On 29th January 2015, the mother received 3rd dose of Engerix B adult. On 10th April 2015, the mother started taking clindamycin and an unspecified vaginal cream for bacterial vaginosis and Integra Plus for anaemia. On 16th April 2015, the patient had a positive pregnancy test. On 27th April 2015, the patient had a positive serum pregnancy test.  The estimated delivery date (EDD) was 2nd November 2015 (Pregnancy Report MCN 2015US003436). On 20th July 2015, it was reported that the mother's pregnancy was approximately at midterm and that she was doing well with no problems. 275 days after having received the third dose of study vaccine (Engerix B adult), the mother vaginally delivered a live female infant (patient) at 39 weeks gestational age (full term). The infant's (patient) birth weight was 7 pounds 9 ounces, the infant was 20.5 inches in length, head circumference was 14 inches. The Apgar score was 8 (assessed by the investigator as good).  A cardiac murmur was auscultated at the time of birth and an echocardiogram showed moderate tricuspid valve regurgitation and poor mobility of the septal leaflet of the tricuspid valve, suspicious for an Ebsteinod variant of the tricuspid valve with evidence of pulmonary valve stenosis. On an unknown date, the mother and patient were discharged home, and the infant was scheduled for a cardiac consultation. On 6th November 2015, patient was seen by a paediatric cardiologist. The patient had been doing well with no distress since discharge. She had no shortness of breath, diaphoresis, or difficulties with feeding.  Vital signs included respiration 48 breaths per minute, heart rate 146 beats per minute, and oxygen saturation 100 per cent.  The physical examination was notable for no jugular venous distension, clear lungs to auscultation, a cardiovascular exam with regular rate and rhythm, normal brachial and femoral pulses, normal S1 and S2 without S3 or S4, no rub or clicks, and a 3/6 systolic murmur at the left upper sternal border with radiation to the axillae, no significant hepatomegaly, no cyanosis or clubbing . A 12-point review of systems was performed and all were negative except for a murmur. An echocardiogram congenital complete with colour flow Doppler and spectral Doppler showed a small patent foramen ovale with left to right shunting (noted by pediatric cardiologist as hemodynamically insignificant, and not considered a separate SAE or MAE per investigator as it was considered part of the Ebsteinod' s anomaly and would perinatal, (take a while to close.), mild Ebstein's anomaly of the tricuspid valve, upper mild to moderate tricuspid valve regurgitation with a jet that was medially displaced, normal pulmonary valve with no pulmonary valve stenosis, and normal biventricular systolic function.  The great vessels and coronary arteries were unremarkable; there were no pericardial or pleural effusions seen. An electrocardiogram did not show ventricular pre-excitation but did have premature atrial complexes (PACs).  A Holter monitor was placed to assess for ectopic rhythms. The cardiologist concluded that the patient had no cardiac restrictions and needed no medication. The parents were advised to return in one month or sooner if clinically indicated. On 10th November 2015, the site reported that the infant patient was diagnosed with "mild" Ebstein's anomaly. The site reported that the Holter monitor was negative. At the time of reporting, the event was considered not resolved. On 24th November 2015, the investigator noted that an end date would not be available as the Ebstein's anomaly would not go away, but the event was considered hemodynamically and electrophysiologically stable. No action was taken with regard to the study vaccine as the mother had already received all three study vaccines prior to the onset of the pregnancy. The investigator assessed the event of Ebstein's anomaly, mild as serious (congenital anomaly/birth defect), of severity grade 1, and as possibly related to the study vaccine. The investigator attributed the event to an unknown cause. This case has been linked with cases US2016GSK011102, US2016GSK011104 and US2016GSK011105.  Follow-up information received from other healthcare professional via literature article on 20 April- 022 and from author on 5th May 2022. This follow-up was considered significant.  GSK case number US2022GSK069898 was found to be duplicate of case US2016GSK011106. The case US2022GSK069898 will be deleted and all future correspondence will be added to US2016GSK011106 which will be case of record. The patient was the part of retrospective study which aimed to evaluate the safety and immunogenicity of HepB-CpG in women as well as pregnancy outcomes. There was one case of congenital anomaly with event of Ebstein's anomaly reported in a mother in HepB-alum (Engerix-B) arm. Summary of Changes: Case type and reporter details and literature information were updated in case. Parent route of administration and dose was added. Event maternal exposure to pregnancy was updated to fetal exposure during pregnancy.; Sender's Comments:  US-GLAXOSMITHKLINE-US2016GSK011105:Same reporter