Safety profile of rubella vaccine administered to pregnant women: A systematic review of pregnancy related adverse events following immunisation,including congenital rubella syndrome and congenital rubella infection in the foetus or infant

BackgroundData on the safety of inadvertent rubella vaccination in pregnancy is important for rubella vaccination programs aimed at preventing congenital rubella syndrome.MethodsThe association between monovalent rubella or combination vaccinations in or shortly before pregnancy and potential harm to the foetus was examined by conducting a systematic review and meta-analysis using fixed effect methods and simulation.ResultsFour cohort studies of inadvertently vaccinated and unvaccinated women were found, 15 cohorts of pregnant women who were rubella susceptible at time of inadvertent vaccination and 9 cohort studies with no information on susceptibility and case series. No case of vaccine associated congenital rubella syndrome (CRS) was identified. Cohort studies with an unvaccinated comparison group were limited in number and size, and based on these only a theoretical additional risk of 6 or more cases of CRS per 1000 vaccinated women (0% observed, upper 95% CI 0.6%) could be excluded. Based on cohorts of vaccinated rubella susceptible pregnant women a maximum theoretical risk of 1 CRS case in 1008 vaccinated women (0% observed, upper 95% CI 0.099%) was estimated. Asymptomatic rubella vaccine virus infection of the neonate was also noted (fixed effects estimate of risk overall 1.74%, 95% CI 1.21, 2.28).ConclusionThere is no evidence that CRS is caused by rubella-containing vaccines but transplacental vaccine virus infection can occur. CRS is effectively prevented by vaccination, thus the risk/benefit balance is unequivocally in favour of vaccination. The data confirm previous recommendations that inadvertent vaccination during pregnancy is not an indication for termination of pregnancy.     

A rubella vaccination program for women entering the U.S. Army

A voluntary rubella vaccination program for female basic trainees was initiated on April 21, 1975, at Fort Jackson, S.C. A total of 29,852 women were tested for rubella titers between April 21, 1975, and December 31, 1977, and 6,167 were found to be nonimmune. An average of 53 percent of the susceptible women were vaccinated. The best results were obtained from August 1 to December 31, 1977, when 67 percent of the susceptible women were vaccinated. During this period, blood specimens for rubella titer and for pregnancy testing were obtained simultaneously. This procedure reduced the number of referrals to the Obstetrics-Gynecology Clinic, as well as the amount of training time lost when pregnancy testing and rubella titer testing were done on separate days. Despite the vaccination program, however, rubella epidemics occurred among female trainees at Fort Jackson in 1975, 1976, and 1977. A significant number of women are still susceptible to rubella. To reduce morbidity and the risk of congenital rubella syndrome, rubella titer testing and immunization of susceptibles should be considered for women-especially where they can be screened, counseled, and vaccinated en masse.     

Inadvertent rubella vaccination of pregnant women: evaluation of possible transplacental infection with rubella vaccine

During mass campaign for measles/rubella vaccination on December 2003 in Iran, many pregnant women have vaccinated mistakenly. These women were grouped to susceptible and immune against rubella before vaccination by the status of IgG avidity response to rubella vaccine, then susceptible women were followed up to delivery time and their neonates were followed up to one year. In five neonates that were born from susceptible women, rubella-specific IgM has detected in cord blood sera, but they have not shown signs compatible to congenital rubella syndrome.     

Seroepidemiological profile of pregnant women after inadvertent rubella vaccination in the state of Rio de Janeiro, Brazil, 2001-2002.

OBJECTIVES: To analyze postvaccination serological status in pregnant women inadvertently vaccinated against rubella in the state of Rio de Janeiro, Brazil. METHODS: This was a cross-sectional study of pregnant women 15 to 29 years old, vaccinated against rubella and measles from November 2001 to March 2002, who were unaware of their pregnancy at the time of vaccination or who became pregnant within 30 days thereafter. They were tested for rubella-specific immunoglobulin M (IgM) and G (IgG) and classified as immune (IgM-negative, IgG-positive, tested within 30 days after vaccination), susceptible (IgM-positive after vaccination) or indeterminate (IgM-negative, IgG-positive, vaccination-serological testing interval greater than 30 days). RESULTS: Of 2 292 women, 288 (12.6%) were susceptible, 316 (13.8%) immune, 1 576 (68.8%) indeterminate, 8 (0.3%) ineligible, and 104 (4.5%) lost to follow-up. IgM seropositivity by vaccination-serological testing interval was 16.1% (相似文献   

Rubella seroprofile of the Italian population: an 8-year comparison

The objective of this study is to evaluate how increasing MMR infant vaccination coverage in recent years has modified the epidemiology of rubella in Italy. A cross-sectional population-based seroprevalence study of rubella antibodies was conducted on 3094 sera, in 2004, and results were compared with data obtained by the same method in 1996. The overall proportion of rubella-seropositive individuals was found to be significantly higher in 2004 with respect to 1996 (84.6% vs. 77.4%). However, an increase in seropositivity was observed only in the 1-19 years age groups. Recent increases in childhood MMR vaccination coverage, therefore, have not had an impact on seroprevalence in women of childbearing age, over 5% of whom remain susceptible to rubella. Preconception screening and postpartum vaccination of susceptible women are fundamental if the WHO target of less than one case of congenital rubella syndrome per 100,000 live births is to be attained.     

Rubella susceptibility in pregnant women and results of a postpartum immunization strategy in Catalonia,Spain

BackgroundElimination of congenital rubella syndrome depends not only on effective childhood immunization but also on the identification and immunization of rubella susceptible women. We assessed rubella susceptibility among pregnant women and evaluated the adherence and response to postpartum immunization with measles, mumps and rubella (MMR) vaccine.MethodsCross-sectional study of women who gave birth at the Hospital Clinic de Barcelona (Spain) between January 2008 and December 2013. Antenatal serological screening for rubella was performed in all women during pregnancy. In rubella-susceptible women, two doses of MMR vaccine were recommended following birth. We evaluated rubella serological response to MMR vaccination in mothers who complied with the recommendations.ResultsA total of 22,681 pregnant women were included in the study. The mean age was 32.3 years (SD 5.6), and 73.6% were primipara. The proportion of immigrants ranged from 43.4% in 2010 to 38.5% in 2012. The proportion of women susceptible to rubella was 5.9% (1328). Susceptibility to rubella declined with increasing maternal age. Immigrant pregnant women were more susceptible to rubella (7.6%) than women born in Spain (4.6%). Multivariate analyses showed that younger age (≤19 years) aOR 1.7 (95% CI 1.1–2.5), primiparas aOR 1.3 (95% CI 1.1–1.5) and immigrant women aOR 1.6 (95% CI 1.4–1.8) were more likely to be susceptible. The second dose of MMR vaccine was received by 57.2% (718/1256) of rubella-susceptible women, with the highest proportion being immigrant women compared with women born in Spain. After vaccination, all women showed rubella immunity.ConclusionsThe higher rubella susceptibility found in the three youngest age groups and in immigrant women highlights the relevance of antenatal screening, in order to ensure identification and postpartum immunization. The postpartum immunization strategy is an opportunity to protect women of childbearing age and consequently prevent occurrence of CRS, and to increase vaccination coverage against rubella and other vaccine-preventable diseases.     

Premarital rubella vaccination program.

A two-year Vermont program identified 494 (7 per cent) of 6,982 premarital female serologies that were seronegative (less than 1:8) to rubella by hemagglutination inhibition (HI) titer. All 494 susceptible patients and their physicians were notified of their results by letter. The State Health Department received reports that a total of 194 (39 per cent) of the susceptible patients had received rubella vaccinations as a result of their notifications. Intensive follow-up of susceptibles appears to be important factor in the success of premarital rubella screening programs.     

Seroepidemiology study of rubella antibodies among pregnant women from seven Asian countries: evaluation of the rubella vaccination program in Taiwan

During 2003-2004, approximately 13% of birth in Taiwan was given by foreign-born females. The aims of this study were to compare the seroprevalence of rubella antibodies between Taiwan-born and foreign-born pregnant women and evaluate the effect of rubella vaccination program in Taiwan. We reviewed the rubella antibody test results of 5007 women during routine pregnancy check-ups at Fooyin University Hospital during 1999-2002. In Taiwan-born women, rubella antibody was undetectable in 29.2%, 7.3%, and 8.3% of the cohorts born before 1971, between 1971 and 1976, and after 1976, respectively. In the cohorts born between 1971 and 1976 and after 1976, pregnant women born in China, Vietnam, Indonesia, and Philippines had significant higher chances of being susceptible. Our results suggested that the voluntary adult vaccination program was not as effective as the school or wipe-out programs. Both Taiwanese women born before 1971 and foreign-born women were more likely to be susceptible to rubella. The introduction of 'catch-up' immunization program and enforcement of the checking of immunization record and/or blood test before pregnancy for these women are necessary in preventing CRS.     

Low postpartum rubella vaccination rates in high-risk women, Miami, Florida, 2001

OBJECTIVE: To evaluate adherence to the Advisory Committee on Immunization Practices' recommendations on postpartum rubella vaccination in hospitals with a high proportion of foreign-born Latina mothers, the highest risk group for congenital rubella syndrome. METHODS: In four large hospitals in Miami-Dade County, maternal medical records for births in 2001 were randomly selected. Using demographic information from birth certificates, vaccination information from medical records, and policy information from a hospital survey, postpartum rubella vaccination rates were characterized among women eligible for vaccination (non-immune and not screened) through univariate and multivariable analyses. Data collection was performed in 2002-2003 and the analysis was completed in 2004-2005. RESULTS: Among 1991 women, 1209 (61%) were foreign born. Overall, 410 (21%) were eligible for vaccination, and of these 44 (11%) were vaccinated. Vaccination rates were not associated with maternal race/ethnicity or the existence of institutional standing-order vaccination policies. A vaccination order was recorded for 59% (240/410), but even in the presence of an order, only 17% (31/240) of those women were vaccinated. CONCLUSIONS: Despite policies and standing orders to vaccinate, postpartum rubella vaccination rates were very low among all racial/ethnic subgroups in a sample of hospitals caring for high-risk, foreign-born women. These findings suggest that additional system-level interventions, such as comprehensive operational guidelines, must accompany standing orders to vaccinate rubella non-immune women postpartum.     

Levels of rubella antibody among vaccinated and unvaccinated Portuguese mothers and their newborns

Maternal and cord sera (231 pairs) were tested to measure rubella IgG levels, using a commercial immunoassay method with final fluorescent detection (ELFA). One hundred and twenty-two women had been vaccinated against rubella. Geometric mean concentrations (GMC) were not associated with time since vaccination. GMC of rubella IgG among vaccinated and unvaccinated mothers were respectively 66.6 and 80.9IU/ml (p=0.29). The corresponding values for cord sera GMC were 140.6 and 140.2IU/ml (p=0.99). These GMC values seem to have been influenced by increased transplacental transport efficiency (TTE) among vaccinated mothers. This was observed if TTE was measured as difference or ratio of cord-maternal concentration of rubella IgG, but was only statistically significantly (p=0.02) for ratio. TTE also seemed to be higher when antibody levels in mothers were below <15IU/ml. There seemed to be some interaction between susceptibility and vaccination status, but these results should be seen with caution. We do not know of a proven biological reason to support differential TTE in vaccinated and unvaccinated mothers. The sensitivity of the lab assay might have influenced the results, such that very low antibody levels in some vaccinated mothers were underestimates of true concentrations. Our finding that 38 mothers had antibody levels considered to be below the threshold for protection highlights the importance of implementing policies to vaccinate susceptible women of childbearing age.     

Prevalence of antibodies against rubella virus in The Netherlands 9 years after changing from selective to mass vaccination

A two-dose mass vaccination programme with a combined vaccine against measles, mumps and rubella (MMR) was adopted in the Netherlands in 1987, replacing the selective schoolgirl vaccination strategy introduced in 1974. To obtain insight into the effect of mass vaccination and the population's immunity, the antibody levels against rubella were studied in the general Dutch population and in religious groups refusing vaccination. In the national sample, we observed a high prevalence (96.5%) for rubella antibodies in vaccinated cohorts as well as in the older unvaccinated cohorts. No indications of rapidly waning immunity after vaccination were found. There are indications of low virus circulation in the last few years. The very high seroprevalence in women at childbearing age is consistent with the few reported cases of congenital rubella syndrome (CRS) at present. However, individuals in the age group of 1-9 years who are not vaccinated for religious or other reasons have a considerably lower seroprevalence and thus there is a potential risk of a CRS outbreak in the future.     

Screening HMO women overdue for both mammograms and pap tests.

BACKGROUND: Regular screening has the potential to reduce breast and cervical cancer mortality, but despite health plan programs to encourage screening, many women remain unscreened. Tailored communications have been identified as a promising approach to promote mammography and Pap test screening. METHODS: The study used a four-group randomized design to compare with Usual Care the separate and combined effects of two tailored, motivational interventions to increase screening-a clinical office In-reach intervention and a sequential letter/telephone Outreach intervention. Subjects were 510 female HMO members ages 52-69 who had had no mammogram in the past 2 years and no Pap smear in the past 3 years. Primary outcomes were the percentage of women in each condition who received a mammogram, a Pap smear, or both screening tests during the 14-month study period. RESULTS: Thirty-two percent of the Combined group, 39% of the Outreach group, and 26% of the In-reach group obtained both services versus 19% of Usual Care participants. Overall, compared with Usual Care, both Outreach (P = 0.006) and Combined (P = 0.05) screened significantly more women. For subjects ages 65-69, Outreach rates were lower than those of Usual Care. CONCLUSION: A tailored letter-telephone Outreach appears to be more effective at screening women ages 52-64 than a tailored office-based intervention, in large part because most In-reach women did not have clinic visits at which to receive the intervention.     

Persistence of antibody induced by rubella vaccine (Wistar RA 27/3 strain) after six years.

A total of 21 rubella seronegative children vaccinated subcutaneously with Wistar RA 27/3 strain live attenuated rubella vaccine in a family study of vaccine virus transmissibility were reviewed after 6 years. Haemagglutinating inhibiting (HAI) antibody titres of sera collected 46 days, 2 years and 6 years after vaccination were compared. Antibody titres in the vaccinated subjects were not significantly influenced by time, infection in susceptible siblings or revaccination.     

Interruption of rubella virus transmission in Australia may require vaccination of adult males: evidence from a Victorian sero-survey.

Prior to the introduction of rubella vaccine to Australia in 1970 rubella was primarily a disease of primary school aged children. Vaccination programs have subsequently altered rubella age and sex susceptibility. Between July 2001 and June 2002, 85 per cent of the 32 laboratory-confirmed cases of rubella ascertained from enhanced surveillance in Victoria were males aged 20-42 years. This study aimed to determine rubella susceptibility by age group and sex in Victoria and to examine the implications of susceptibility for the interruption of circulating rubella virus. Rubella immunoglobulin G concentrations were determined for 934 residual diagnostic sera stored at the Victorian Infectious Diseases Reference Laboratory using a standard commercial enzyme immunoassay. Susceptibility was analysed by age groups defined by previous and current Australian rubella immunisation schedules. Among all subjects aged 1-55 years, males were more susceptible to rubella infection than females (10.2% vs 2.6%, p < 0.0001). Although this sex difference occurred in all age groups, it was unlikely to be explained by sampling variation in sera from subjects aged 23-44 years, for whom rubella vaccine had been recommended only for girls aged 10-14 years and rubella susceptible women post-partum. Australia's past rubella immunisation policies have resulted in a susceptible cohort of adult males. If rubella virus transmission is to be interrupted in Australia, consideration needs to be given to a rubella vaccination program targeting men aged 17-44 years. A campaign, targeting both men and women in a similar age group has recently been successful in Costa Rica.     

Evaluation of Japanese people's perception of risk information for making decisions to receive influenza and rubella vaccinations

BackgroundGenerally, vaccination uptake in Japan lags behind World Health Organization targets.ObjectiveThis study aimed to understand how risk information and advice affect intention to receive vaccinations.MethodsThis study had a within‐subjects design. An online survey based on the Health Belief Model was sent to 2501 Japanese individuals (≧20 years) to assess the intention to be vaccinated for influenza and rubella after receiving minor and severe risk information and hypothetical advice about each vaccine. Regression analysis was used to measure changes in intentions to receive each vaccination after being provided with (1) risk information about each vaccine and (2) hypothetical encouragement and discouragement to be vaccinated.Main OutcomesThe main outcomes included changes in vaccination intentions from baseline.ResultsForty‐one percent (N = 1030) of those sent the survey completed it. At baseline, 43% and 65% of the respondents intended to have influenza and rubella vaccinations, respectively. Being provided with information about severe risks and susceptibility increased the intention to have the influenza vaccination among females in their 40s. Receiving inaccurate and discouraging information from one''s mother significantly decreased the intention to have the rubella vaccination. Women 50 and older were more likely to intend not to have vaccination for rubella. Severe risk information decreased rubella vaccination intention in all age groups, except women in their 30s and 40s (p < .05).ConclusionFor both vaccinations, older individuals demonstrated vaccine hesitancy. This group requires tailored messaging to help them understand their vulnerability (to influenza) and their role in transmission (for rubella) to encourage uptake of essential vaccinations.Patient or Public ContributionMembers of the Japanese public responded to our online questionnaire on vaccination risk.     

Exposure of Ugandan health personnel to measles and rubella: evidence of the need for health worker vaccination

With rubella and, until recently, measles highly endemic in Uganda, health personnel are at risk of these vaccine-preventable diseases and a source of transmission to patients. Measles and rubella serology (IgG) and history of exposure and vaccination were determined among 311 health care workers in a nationwide study. All tested positive for measles IgG, whereas 49.2% reported having been vaccinated. Rubella antibodies were present in 98.1% of personnel; 3.2% of women of child-bearing age were still susceptible. Increasing age and longer duration of service increased the risk of rubella infection. A national policy on health worker protection should include immunisation against vaccine-preventable diseases upon entry to training.     

2005年山东省部分孕期妇女风疹易感性调查

[目的]了解山东省孕期妇女风疹易感性水平,为调整风疹疫苗免疫策略提供依据。[方法]2005年,采集不同地区到医院准备分娩的20~40岁孕妇血清,采用间接酶联免疫吸附定量法检测风疹IgG抗体。[结果]检测标本3 788份,风疹抗体阳性(>20 IU/ml)的2 942人,阴性(<10 IU/ml)的314人,临界值(10~20 IU/ml)的532人,易感(临界值和阴性者)合计846人,易感率为22.33%。几何平均抗体含量(CMT)为34.93 IU/ml。不同地区风疹易感率和CMT的差异均有统计学意义(P<0.01);风疹易感率有随年龄增长而增高的趋势(P<0.01)。[结论]山东省近1/4的孕妇为风疹的易感者,有必要对育龄期妇女开展风疹疫苗接种。     

The relationship of health beliefs and a postcard reminder to influenza vaccination.

The relationship of certain health beliefs to influenza vaccination and the effect of a postcard reminder on vaccination rates was studied among 232 high-risk patients. In agreement with the Health Belief Model tested, the patients vaccinated believed influenza to be more serious, believed they were more susceptible to influenza, and believed the vaccine to be more efficacious than did patients not vaccinated. Those not vaccinated were less satisfied with their medical care and felt the vaccine was more expensive than those vaccinated. A postcard reminding patients of influenza vaccination was an effective way to increase the vaccination rate. Patients receiving the card had a 59.7 percent vaccination rate compared to a 30.0 percent rate among those not receiving the postcard. This study suggests that a reminder postcard is an effective means to promote influenza vaccination and that these beliefs are important determinants of vaccination behavior.