Sex: F
Vaccine: FLUX, FLUX(H1N1)
Symptoms: Unevaluable event
Clinical narrative: This literature report (initial receipt 14-Dec-2011) concerns VAERS (Vaccine Adverse Event Reporting System) reports received through 01-Mar-2010, on pregnant women who were vaccinated with the H1N1 during 01-Oct-2009 through 28-Feb-2010. Foreign reports were excluded. The author included reports of AEs (adverse events) in neonates if the report indicated that their mothers had received H1N1 during pregnancy. Risk factors for spontaneous abortions included the following; advanced maternal age equal or >35 years (25 patients), smoking (7 patients), history of intrauterine fetal death (4 patients), hypothyroidism (4 patients), diabetes mellitus type 1 (1 patient), diabetes mellitus  type II (1 patient), history of gestational diabetes (1 patient), alcohol or drug use (2 patients), obesity (1 patient) and other (1 patient). 'Other' risk factors for spontaneous abortions were defined as the following; chlamydia infection with complicated pregnancy. Risk factors for stillbirth included the following; advanced maternal age equal or >35 years (5 patients), smoking (3 patients), history of intrauterine fetal death (2 patients), diabetes mellitus type 1 (1 patient), history of gestational diabetes (1 patient), alcohol or drug use (4 patients), obesity (3 patients) and other (7 patient). 'Other' risk factors for stillbirth included the following; congenital malformations in past pregnancies, uncontrolled diabetes, chronic hypertension, positive Down Syndrome screening and macrocytic hyperchromic anaemia. From 01-Oct-2009 through 28-Feb-2010, VAERS received a total of 10,186 reports after H1N1 vaccination; 422 of these reports involved pregnant women. The author excluded 128 pregnancy reports in which no AE was reported after the administration of inactivated or live H1N1. These pregnant women are being followed up prospectively as part of a separate CDC (Centres for Disease Control and Prevention) study that seeks to assess delivery and infant outcomes. Of the remaining 294 reports, 288 followed inactivated and 6 followed live vaccines. Median maternal age was 30 years (range 15 - 46 years). Median onset interval (adverse event onset date and vaccination date) was 2 days (range 0 - 84 days). Median gestational age at time of vaccination was 13 weeks (range 3 - 39 weeks). The H1N1 was reported as administered mostly during the first (133; 53.8%) and second trimester of pregnancy (67; 27.1%). In 31 reports (10.5%), the H1N1 was administered on the same date as the seasonal influenza vaccine (WAVES 2011030539). Sixty reports (20.4%) were coded as serious, including 2 maternal deaths. Serious reports corresponded to 59 pregnant women who were hospitalized for any reason and 1 to an infant born with a congenital anomaly. The most frequent pregnancy-specific AE reported following H1N1 administration was SAB (spontaneous abortion) in 121 women (41.2% of reports), followed by stillbirth in 19 women (6.5% of reports), preterm delivery of 7 women (one case of preterm delivery where the infant of one mother died approximately 1 month after delivery), threatened abortion in 4 women, preterm labor in 3 women, maternal death in 2 women, preeclampsia in 2 women, intrauterine growth restriction in 2 women, fetal hydronephrosis in 1 woman, fetal tachycardia in 1 woman, cleft lip in 1 woman, neonatal intraparenchymal hemorrhage in 1 woman and intrauterine fetal death in 1 woman. Most SAB reports (n = 62) were received in Nov-2009 but reporting rapidly declined thereafter. All stillbirths were reported during Oct-2009 and Nov-2009 with 10 and 9 reports, respectively. In 42.4% of the SAB reports, the onset interval from the day of vaccination to onset of AE was 0-3 days (61 reports with onset of 0-6 days). In 47.4% of stillbirth reports, the onset interval was 0-6 days. The author did not observe any clustering of SAB or stillbirth cases by geographic location or lot number. Ninety-five SABs (78.5%) and 18 stillbirths (94.7%) were verified by review of medical records. Five fetal adverse outcomes were reported: 2 cases of intrauterine growth restriction and 1 case each of hydronephrosis, tachycardia, and cleft lip. The maternal deaths included 1 patient who experienced hemorrhagic shock because of uterine atony following a cesarean section and 1 patient who experienced a ruptured aortic aneurysm, which resulted in cardiac tamponade and subsequent death. A mild fetal hydronephrosis was detected in the patient during an ultrasound exam at 36 weeks' gestation. However a postnatal ultrasound examination of the infant performed on day 2 of life failed to confirm the presence of hydronephrosis. Cause of death was not reported. Only 1 congenital anomaly was reported to VAERS: a cleft lip in an infant born to a 23 year old woman who was vaccinated at 19 weeks' gestation. The cleft lip was first detected during a prenatal ultrasound examination at 22 weeks' gestation. Cause of death was not reported. Because cleft lip was embryologically determined during the first trimester of pregnancy, it is implausible to consider vaccination at 19 weeks' gestation as a possible causative agent. The most common non pregnancy specific AEs were non anaphylactic allergic reactions (36), constitutional symptoms (28), and local reactions (10). Two hundred thirty-five of the total reports (79.9%) did not require hospitalization. Five cases of Bells' palsy and 1 case of anaphylaxis (meeting Brighton Collaboration case definition) were reported. No cases of Guillain-Barre syndrome were identified. There were 8 cases of paraesthesia's, 5 cases each of syncope and dizziness, 3 cases each of hypoesthesia and headache and 25 cases of 'other' Other events included anxiety, arthralgia, asthenia, asthma, arthritis, blurred vision, chest pain, chronic bronchitis, cough, diarrhoea, dyspnoea, eye swelling, influenza, influenza-like illness, lip injury, nail bleeding, panic attack, shingles, sneezing, tachycardia, tremors, unusual taste, upper respiratory tract and wheezing. One hundred twenty-one cases of SAB after H1N1 vaccination were reported to VAERS (120 after inactivated and 1 after live vaccine), of which 95 were verified. Medical records were not received for 16 reports, and in 10 reports, the available records were not sufficient to confirm the initial diagnosis of SAB. Risk factors for SAB were identified in 47 (49.5%) of the 95 verified reports. Thirty-six women had only 1 risk factor for SAB. The most common risk factor was advanced maternal age (defined as age > or = 35 years) in 25 reports (26.3%). Nineteen stillbirths were reported to VAERS. Of 18 with verified diagnosis, 13 (72.2%) had at least 1 maternal risk factor for stillbirth (eg, obesity) or a pathological finding that may have contributed to the fetal demise. Fourteen of 18 reports had pathology reports. Pathological/placental or other findings were present in 13 of the 14 reports and included chorioamnionitis in 7 reports and 2 reports each of tight nuchal cord, fetal-maternal hemorrhage, and fetal growth restriction. Of note, the 6 adverse event cases involving live H1N1 included 1 case of spontaneous abortion, 2 cases of general/constitutional symptoms, 1 case each of dizziness, headache, and 'other'. The author estimated that during Oct-2009 through Feb-2010, 2,437,113 (95% confidence interval, 1,865,373-3,008,853) pregnant women were vaccinated with H1N1. The overall reporting rate of AEs to VAERS in pregnant women after H1N1 was 118.2 reports per 1 million pregnant women vaccinated. The reporting rates for SABs and stillbirths were 49.2 and 7.8 reports per 1 million pregnant women vaccinated, respectively. The event outcome was not reported. Reporter comments: Review of reports of VAERS following H1N1 vaccination in pregnant women did not identify any concerning patterns of maternal or fetal outcomes.