Anna T. Bukowinski

Safety of the pandemic H1N1 influenza vaccine among pregnant U.S. military women and their newborns.

OBJECTIVES: To assess adverse pregnancy outcomes among active-duty U.S. military women who received pandemic H1N1 vaccine during pregnancy as well as adverse health outcomes among the newborns resulting from these pregnancies. METHODS: The primary study population was a retrospective cohort of active-duty U.S. military women vaccinated during pregnancy with either the pandemic H1N1 vaccine between October 2009 and June 2010 or with seasonal influenza vaccine between October 2008 and June 2009. Rates of pregnancy loss, preeclampsia or eclampsia, and preterm labor were compared between pandemic H1N1 vaccine-exposed (n=10,376) and seasonal influenza vaccine-exposed pregnancies (n=7,560). A secondary study population consisted of newborns resulting from these pregnancies. Rates of preterm birth, birth defects, fetal growth problems, and the male-to-female sex ratio were compared between newborns exposed to pandemic H1N1 vaccine and newborns exposed to seasonal influenza vaccine in utero. RESULTS: No significant differences were observed in rates of pregnancy loss (6.4% compared with 6.5%), preeclampsia or eclampsia (5.8% compared with 5.2%), or preterm labor (6.5% compared with 6.2%) between pandemic H1N1 vaccine-exposed and seasonal influenza vaccine-exposed pregnancies. Furthermore, no significant differences were observed in rates of preterm birth (6.2% compared with 6.3%), birth defects (2.1% compared with 2.0%), fetal growth problems (2.6% compared with 2.4%), or the male-to-female sex ratio (1.05 compared with 1.07) between newborns exposed in utero to pandemic H1N1 vaccine compared with seasonal influenza vaccine. Rates of all outcomes were lower or similar to overall general population rates. This study had at least 80% power to detect hazard ratios of 1.18–1.21 or odds ratios of 1.10–1.36, depending on outcome prevalence. CONCLUSION: No adverse pregnancy or newborn health outcomes associated with pandemic H1N1 vaccination during pregnancy were noted among our cohort. These findings should be used to encourage increased vaccine coverage among pregnant women. LEVEL OF EVIDENCE: II

Racial differences in prostate cancer risk remain among US servicemen with equal access to care

Prostate cancer is the most common cancer among US men, however, the etiology remains unclear. Yet, one consistency is that black non‐Hispanic men are at increased risk for prostate cancer compared to white, non‐Hispanic men. The goal of this study was to assess relations between demographic and other potential prostate cancer risk factors in the context of the US military healthcare system, which provides equal access to all US servicemen.

Birth outcomes among military personnel after exposure to documented open-air burn pits before and during pregnancy.

Objective: To examine birth outcomes in military women and men with potential exposure to documented open-air burn pits before and during pregnancy. Methods: Electronic data from the Department of Defense Birth and Infant Health Registry and the Defense Manpower Data Center were used to examine the prevalence of birth defects and preterm birth among infants of active-duty women and men who were deployed within a 3-mile radius of a documented open-air burn pit before or during pregnancy. Results: In general, burn pit exposure at various times in relation to pregnancy and for differing durations was not consistently associated with an increase in birth defects or preterm birth in infants of active-duty military personnel. Conclusions: These analyses offer reassurance to service members that burn pit exposure is not consistently associated with these select adverse infant health outcomes.

Analysis of pregnancy and infant health outcomes among women in the National Smallpox Vaccine in Pregnancy Registry who received Anthrax Vaccine Adsorbed.

The National Smallpox Vaccine in Pregnancy Registry (NSVIPR) actively follows women inadvertently vaccinated with smallpox vaccine during or shortly before pregnancy to evaluate their reproductive health outcomes. Approximately 65% of NSVIPR participants also inadvertently received Anthrax Vaccine Adsorbed (AVA) while pregnant, providing a ready opportunity to evaluate pregnancy and infant health outcomes among these women. AVA-exposed pregnancies were ascertained using NSVIPR and electronic healthcare data. Rates of pregnancy loss and infant health outcomes, including major birth defects, were compared between AVA-exposed and AVA-unexposed pregnancies. Analyses included AVA-exposed and AVA-unexposed pregnant women who also received smallpox vaccine 28 days prior to or during pregnancy. Rates of adverse outcomes among the AVA-exposed group were similar to or lower than expected when compared with published reference rates and the AVA-unexposed population. The findings provide reassurance of the safety of AVA when inadvertently received by a relatively young and healthy population during pregnancy.

Haemangiomas and associated congenital malformations in a large population-based sample of infants

Haemangiomas are common, benign, vascular tumours, observed in 4-12% of infants during the first year of life. Most cases progress without complication, yet a small proportion experience life-threatening complications. Concomitant congenital malformations have been reported in a small but significant proportion of haemangioma patients. This study aimed to describe haemangioma cases and to identify patterns of congenital malformations associated with these diagnoses in a large population. Diagnoses of haemangiomas and 21 congenital malformations were extracted from electronic medical records of 467 295 singleton infants born to US military families from 1998 to 2003. Cluster analysis was used to group cases according to these diagnoses. Multivariable logistic regression was used to further explore the associations of the 21 congenital malformations with the diagnosis of haemangioma and to assess the adjusted relationships between a number of characteristics of interest and diagnosis of haemangioma. Clusters found to be associated with haemangioma were characterised by anomalies of the cervix, vagina, and external female genitalia, anophthalmia or microphthalmia, hydrocephalus without spina bifida, and reduction deformities of the brain. Logistic regression identified three congenital malformations significantly associated with haemangioma diagnosis: spina bifida without anencephalus, hydrocephalus without spina bifida, and anomalies of the cervix, vagina and external female genitalia. Characteristics significantly associated with haemangioma included female gender, preterm birth, white non-Hispanic race/ethnicity and increasing maternal age. This exploratory study identified a number of important associations between haemangiomas and congenital malformations that may provide insight into the pathogenesis of these disorders and have possible implications for clinical care.

Tetanus, diphtheria, and acellular pertussis vaccination during pregnancy and reduced risk of infant acute respiratory infections

BACKGROUND To protect infants from pertussis infection, the Advisory Committee on Immunization Practices (ACIP) recommends women receive the tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) vaccine between 27 and 36weeks of pregnancy. Here, we assessed the association between timing of maternal Tdap vaccination during pregnancy and acute respiratory infection (ARI) in infants <2months of age. METHODS This retrospective cohort study included 99,434 infants born to active duty military women in the Department of Defense Birth and Infant Health Registry from 2006 through 2013. Multivariable log-binomial regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association between maternal Tdap vaccination during pregnancy and infant ARI at <2months of age. RESULTS Infants of mothers who received Tdap vaccination during pregnancy vs those who did not were 9% less likely to be diagnosed with an ARI at <2months of age (RR, 0.91; 95% CI, 0.84-0.99), and the risk was 17% lower if vaccination was received between 27 and 36weeks of pregnancy (RR, 0.83; 95% CI, 0.74-0.93). Similar results were observed when comparing mothers who received Tdap vaccination prior to pregnancy in addition to Tdap vaccination between 27 and 36weeks of pregnancy versus mothers who only received vaccination prior to pregnancy (RR, 0.85; 95% CI, 0.74-0.98). CONCLUSIONS Maternal Tdap vaccination between 27 and 36weeks of pregnancy was consistently protective against infant ARI in the first 2months of life vs no vaccination during pregnancy, regardless of Tdap vaccination prior to pregnancy. Our findings strongly support current ACIP guidelines recommending Tdap vaccination in late pregnancy for every pregnancy.

A follow-up comparative safety analysis of pandemic H1N1 vaccination during pregnancy and risk of infant birth defects among U.S. military mothers

OBJECTIVE To update a previous assessment of birth defects among infants born to active duty U.S. military mothers who received the 2009-2010 pandemic H1N1 vaccine, in comparison to the 2008-2009 seasonal influenza vaccine, during pregnancy. Here, we updated the previous comparative analyses with a more refined definition for birth defects using an additional year of follow-up data from both inpatient and outpatient medical encounters. METHODS The study population included 15,510 live born infants born to active duty mothers vaccinated during pregnancy with either the 2009-2010 pandemic H1N1 vaccine (n = 9033) or the 2008-2009 seasonal influenza vaccine (n = 6477). Birth defect cases were defined as those infants who received a birth defect diagnosis on one inpatient record or two outpatient records on different days within the first year of life. Multivariable logistic regression models were conducted to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between birth defects and maternal vaccination during pregnancy with pandemic H1N1 vaccine versus seasonal influenza vaccine. RESULTS Infants born to mothers vaccinated during pregnancy with the pandemic H1N1 vaccine, versus the seasonal influenza vaccine, were not at increased odds of birth defects in univariable (OR: 1.13, 95% CI: 0.95-1.34) or multivariable (OR: 1.14, 95% CI: 0.96-1.35) models. Findings were not significant when further limited to first trimester exposure. Multivariable models were adjusted for infant sex and plurality; maternal age, race/ethnicity, marital status, service branch, military rank, and occupation; timing of vaccination; and receipt of vaccination(s) not routinely recommended during pregnancy. CONCLUSION Comparable to our previous analyses assessing birth defects diagnosed at birth, no significant association was found between the pandemic H1N1 vaccination during pregnancy and birth defects, versus the seasonal influenza vaccine. These findings are reassuring and provide additional support for H1N1-containing seasonal influenza vaccination during pregnancy.