Sex: F
Vaccine: HEP
Symptoms: Exposure during pregnancy, Premature delivery
Clinical narrative: This retrospective pregnancy case was reported in a literature article and described the occurrence of premature delivery in a female subject who received Hepatitis B vaccine. The subject's last menstrual period was unknown and estimated date of delivery was unknown. The subject received Hepatitis B vaccine during pregnancy (trimester unknown). On an unknown date, less than a year after receiving Hepatitis B vaccine, the subject developed premature delivery. Serious criteria included other: Serious per author. Additional event(s) included live birth and vaccine exposure during pregnancy. The outcome of premature delivery was unknown. The outcome(s) of the additional event(s) included live birth (unknown) and vaccine exposure during pregnancy (unknown). The pregnancy resulted in a live neonate with no apparent congenital anomaly. The investigator considered that there was a reasonable possibility that the premature delivery may have been caused by Hepatitis B vaccine. Additional information was provided. This retrospective pregnancy case was reported in a literature article and described the occurrence of pre-term delivery (less than 37 weeks) in a pregnant female aged between 14 and 41 years who was vaccinated with unspecified hepatitis B virus  (HBV) vaccine (manufacturer unknown) during pregnancy. The patient was part of the study, aimed to characterize the adverse events (AEs) after hepatitis B vaccination (approved for use in women of reproductive age) or pregnant women reported to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. The authors searched the VAERS for reports of pregnant women vaccinated in a specific country with hepatitis B vaccine from 01 January 1990 through to 30 June 2016. The authors included reports of women vaccinated with hepatitis B vaccine during pregnancy where the primary AE being reported (or the focus of the report) was in the live born infant. The authors excluded the reports wherepon review they determined the subject was not pregnant or that hepatitis B vaccine was administered prior to the last menstrual period. All reports and available medical records were reviewed by physicians from the Food and Drug Administration and the Centers for Disease Control and Prevention to ascertain pregnancy status at time of vaccination, calculated the gestational age, and characterized the AEs. (In this study, VAERS received 192 reports involving hepatitis B vaccination of pregnant women. No maternal deaths were reported. Gestational age at the time of vaccination and at the time of the AE were calculated based on: (1) clinical determination by the health care provider as stated in the report, (2) earliest ultrasound assessment (if the former was not available), or (3) last menstrual period, estimated delivery date, or estimated date of conception (if the first two options were unavailable) in the VAERS report and/or medical records. The authors used the following definition for trimesters: first (0-13 weeks), second (14-27 weeks), and third (greater than and equal to 8 weeks). The patient's last menstrual period was on an unknown date. Estimated date of delivery was on an unknown date. No information on patient's medical or family history or concomitant medication or concurrent condition was provided. On an unspecified date from 01 January 1990 through to 30 June 2016, the patient received unspecified HBV vaccine (administration site and route unspecified; dosages unknown; batch number not provided) during pregnancy at an unknown gestation week. The age of vaccination was not provided. [In this study, 7 maternal cases of pre-term delivery were reported (2 vaccinated in first trimester, 3 in second trimester, 1 in third trimester and the trimester was unknown in 1). Most (191; 99%) reports involved administration of a single antigen Hepatitis B vaccine. In 93 (48.4%) hepatitis B vaccine was given concurrently with other vaccines: 39 (43%) with known age were children and adolescents. The top three vaccines given concurrently with Hepatitis B vaccine were varicella, measles, mumps, rubella, and hepatitis A vaccines, respectively. Hepatitis B vaccines administered included: ENGERIX (93; 46.7%), RECOMBIVAX (85; 42.7%), no brand name (19; 9.6%) and COMVAX (1; 0.5%)]. On an unspecified date from 01 January 1990 through to 30 June 2016, an unknown period after vaccination, the patient pre-term delivery (less than 37 weeks). (In this study, Spontaneous abortion (SAB) was defined as foetal demise less than 20 weeks gestation; stillbirth was defined as foetal demise greater than and equal to 8 weeks 20 weeks gestation and preterm delivery was defined as a live birth less than 37 weeks gestation). This case has been considered serious per author. (In this study, the definition of serious reports based on the Code of Regulations, was a report that includes one of the following: death, life-threatening illness, hospitalization or prolongation of hospitalization, or permanent disability. This definition was based on the reporter's assessment of the condition, and for pregnancy reports, it often is based on conditions in the mother and not necessarily the fetus or live born infant). Treatment was unknown. The pregnancy resulted in live birth. The authors stated 'Strengths of VAERS include its broad national scope and ability to rapidly detect rare AEs and safety signals. However, as a spontaneous reporting system, it has important limitations, including reporting biases (over- or underreporting) and inconsistent quality and completeness of reports. Pregnant women who experience adverse outcomes in their fetuses or infants might be particularly susceptible to recall bias that influences decisions to report. Events that occur close to the time of vaccination and medically serious events are more likely to be reported. In addition, VAERS does not collect data on the number of individuals vaccinated: therefore, it is not possible to calculate the incidence or prevalence of AEs. Due to these limitations, we generally cannot determine from VAERS data alone whether a vaccine caused an AE'. The authors concluded "Our analysis of VAERS reports involving hepatitis B vaccination during pregnancy did not identify any new or unexpected safety concerns. Additional data on the safety of maternal hepatitis B vaccination will be provided by an ongoing study of maternal and fetal adverse events after hepatitis B vaccine in the Vaccine Safety Datalink. Using date in VAERS, our safety review did not find any unusual or unexpected AE reporting patterns associated with hepatitis B vaccination in pregnancy". This is 1 of the 48 valid cases reported in the same literature article.