Carter J. Sevick

Birth Defects among Infants Born to Women Who Received Anthrax Vaccine in Pregnancy

In response to bioterrorism threats, anthrax vaccine has been used by the US military and considered for civilian use. Concerns exist about the potential for adverse reproductive health effects among vaccine recipients. This retrospective cohort evaluated birth defects, in relation to maternal anthrax vaccination, among all infants born to US military service women between 1998 and 2004. Department of Defense databases defined maternal vaccination and infant diagnoses; multivariable regression models described potential associations between anthrax vaccination and birth defects in liveborn infants. Among 115,169 infants born to military women during this period, 37,140 were born to women ever vaccinated against anthrax, and 3,465 were born to women vaccinated in the first trimester of pregnancy. Birth defects were slightly more common in first trimester-exposed infants (odds ratio = 1.18, 95% confidence interval: 0.997, 1.41) when compared with infants of women vaccinated outside of the first trimester, but this association was statistically significant only when alternative referent groups were used. Although the small observed association may be unlikely to represent a causal relation between vaccination in early pregnancy and birth defects, this information should be considered when making decisions about administering anthrax vaccine to pregnant women.

Does acute maternal stress in pregnancy affect infant health outcomes? Examination of a large cohort of infants born after the terrorist attacks of September 11, 2001

BackgroundInfants in utero during the terrorist attacks of September 11, 2001 may have been negatively affected by maternal stress. Studies to date have produced contradictory results.MethodsData for this retrospective cohort study were obtained from the Department of Defense Birth and Infant Health Registry and included up to 164,743 infants born to active-duty military families. Infants were considered exposed if they were in utero on September 11, 2001, while the referent group included infants gestating in the same period in the preceding and following year (2000 and 2002). We investigated the association of this acute stress during pregnancy with the infant health outcomes of male:female sex ratio, birth defects, preterm birth, and growth deficiencies in utero and in infancy.ResultsNo difference in sex ratio was observed between infants in utero in the first trimester of pregnancy on September 11, 2001 and infants in the referent population. Examination of the relationship between first-trimester exposure and birth defects also revealed no significant associations. In adjusted multivariable models, neither preterm birth nor growth deficiencies were significantly associated with the maternal exposure to the stress of September 11 during pregnancy.ConclusionThe findings from this large population-based study suggest that women who were pregnant during the terrorist attacks of September 11, 2001 had no increased risk of adverse infant health outcomes.

Evaluation of preterm births and birth defects in liveborn infants of US military women who received smallpox vaccine.

BACKGROUND Women serving in the US military have some unique occupational exposures, including exposure to vaccinations that are rarely required in civilian professions. When vaccinations are inadvertently given during pregnancy, such exposures raise special concerns. These analyses address health outcomes, particularly preterm births and birth defects, among infants who appear to have been exposed to maternal smallpox vaccination in pregnancy. METHODS This retrospective cohort study included 31,420 infants born to active-duty military women during 2003-2004. We used Department of Defense databases to define maternal vaccination and infant health outcomes. Multivariable regression models were developed to describe associations between maternal smallpox vaccination and preterm births and birth defects in liveborn infants. RESULTS There were 7,735 infants identified as born to women ever vaccinated against smallpox, and 672 infants born to women vaccinated in the first trimester of pregnancy. In multivariable modeling, maternal smallpox vaccination in pregnancy was not associated with preterm or extreme preterm delivery. Maternal smallpox vaccination in the first trimester of pregnancy was not significantly associated with overall birth defects (OR 1.40; 95% CI: 0.94, 2.07), or any of seven specific defects individually modeled. CONCLUSIONS Results may be reassuring that smallpox vaccine, when inadvertently administered to pregnant women, is not associated with preterm delivery or birth defects in liveborn infants.

Infant Abusive Head Trauma in a Military Cohort

OBJECTIVE: Evaluate the rate of, and risk factors for, abusive head trauma (AHT) among infants born to military families and compare with civilian population rates. METHODS: Electronic International Classification of Diseases data from the US Department of Defense (DoD) Birth and Infant Health Registry were used to identify infants born to military families from 1998 through 2005 (N = 676 827) who met the study definition for AHT. DoD Family Advocacy Program data were used to identify infants with substantiated reports of abuse. Rates within the military were compared with civilian population rates by applying an alternate AHT case definition used in a civilian study. RESULTS: Applying the study definition, the estimated rate of substantiated military AHT was 34.0 cases in the first year of life per 100 000 live births. Using the alternate case definition, the estimated AHT rate was 25.6 cases per 100 000 live births. Infant risk factors for AHT included male sex, premature birth, and a diagnosed major birth defect. Parental risk factors included young maternal age (<21 years), lower sponsor rank or pay grade, and current maternal military service. CONCLUSIONS: This is the first large database study of AHT with the ability to link investigative results to cases. Overall rates of AHT were consistent with civilian populations when using the same case definition codes. Infants most at risk, warranting special attention from military family support programs, include infants with parents in lower military pay grades, infants with military mothers, and infants born premature or with birth defects.

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.

Health outcomes among infants born to women deployed to United States military operations during pregnancy

BACKGROUND Military professionals who deploy to combat operations may encounter hazards that could adversely affect reproductive health. Pregnant women are generally exempt from deployment to military operations; however, exposures to such environments may inadvertently occur. We investigated whether maternal deployment during pregnancy was associated with adverse health outcomes in infants. METHODS The United States Department of Defense Birth and Infant Health Registry identified infants born to military service women between 2002 and 2005, and defined their health outcomes at birth and in the first year of life. Multivariable modeling was applied to investigate preterm birth and birth defects among infants, based on maternal deployment experience during pregnancy. RESULTS Among 63,056 infants born to military women from 2002 to 2005, 22,596 were born to women with deployment experience in support of the current military operations before, during, or after their pregnancy. These included 2941 infants born to women who appeared to have been deployed some time during their first trimester of pregnancy. Compared to infants born to women who deployed at other times, or never deployed, exposed infants were not more likely to be born preterm, diagnosed with a major birth defect, or diagnosed with a malignancy. CONCLUSIONS In this exploratory analysis, infants born to women who inadvertently deployed to military operations during their pregnancy were not at increased risk of adverse birth or infant health outcomes. Future analyses should examine outcomes related to specific maternal exposures during deployment, and outcomes among the growing number of infants conceived after deployment.

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.

Health-Related Behaviors and Effectiveness of Trivalent Inactivated versus Live Attenuated Influenza Vaccine in Preventing Influenza-Like Illness among Young Adults

Background Vaccination is the preferred preventive strategy against influenza. Though health behaviors are known to affect immunity and vaccine delivery modes utilize different immune processes, data regarding the preferred influenza vaccine type among adults endorsing specific health-related behaviors (alcohol use, tobacco use, and exercise level) are limited. Methods The relative effectiveness of two currently available influenza vaccines were compared for prevention of influenza-like illness during 2 well-matched influenza seasons (2006/2007, 2008/2009) among US military personnel aged 18–49 years. Relative vaccine effectiveness was compared between those self-reporting and not reporting recent smoking history and potential alcohol problem, and by exercise level using Cox proportional hazard modeling adjusted for sociodemographic and military factors, geographic area, and other health behaviors. Results 28,929 vaccination events and 3936 influenza-like illness events over both influenza seasons were studied. Of subjects, 27.5% were smokers, 7.7% had a potential alcohol-related problem, 10.5% reported minimal exercise, and 4.4% reported high exercise levels. Overall, the risk of influenza-like illness did not significantly differ between live attenuated and trivalent inactivated influenza vaccine recipients (hazard ratio, 0.98; 95% confidence interval, 0.90–1.06). In the final adjusted model, the relative effectiveness of the 2 vaccine types did not differ by smoking status (p = 0.10), alcohol status (p = 0.21), or activity level (p = 0.11). Conclusions Live attenuated and trivalent inactivated influenza vaccines were similarly effective in preventing influenza-like illness among young adults and did not differ by health-related behavior status. Influenza vaccine efforts should continue to focus simply on delivering vaccine.

Hypothyroidism among military infants born in countries of varied iodine nutrition status

BackgroundIodine deficiency is a global problem representing the most common preventable cause of mental retardation. Recently, the impact of subtle deficiencies in iodine intake on children and pregnant women has been questioned. This study was designed to compare hypothyroidism among infants born to US military families in countries of varied iodine nutrition status.MethodsA cohort design was used to analyze data from the Department of Defense Birth and Infant Health Registry for infants born in 2000-04 (n = 447,691). Hypothyroidism was defined using ICD-9-CM codes from the first year of life (n = 698). The impact of birth location on hypothyroidism was assessed by comparing rates in Germany, Japan, and US territories with the United States, while controlling for infant gender, plurality, gestational age, maternal age, maternal military status, and military parents race/ethnicity.ResultsHypothyroidism did not vary by birth location with adjusted odds ratios (OR) as follows: Germany (OR 0.82, [95% CI 0.50, 1.35]), Japan (OR 0.67, [95% CI 0.37, 1.22]), and US territories (OR 1.29, [95% CI 0.57, 2.89]). Hypothyroidism was strongly associated with preterm birth (OR 5.44, [95% CI 4.60, 6.42]). Hypothyroidism was also increased among infants with civilian mothers (OR 1.24, [95% CI 1.00, 1.54]), and older mothers, especially ages 40 years and older (OR 2.09, [95% CI 1.33, 3.30]).ConclusionsIn this study, hypothyroidism in military-dependent infants did not vary by birth location, but was associated with other risk factors, including preterm birth, civilian maternal status, and advanced maternal age.

Smallpox Vaccination is Not Associated with Infertility in a Healthy Young Adult Population

Concerns exist regarding reproductive health, including potential infertility, among young adults with military-related occupational exposures. This study evaluated infertility diagnoses in a large population of healthy young adults in relation to prior smallpox vaccination. Using a retrospective cohort design, the population consisted of United States military members eligible for smallpox vaccination in 2003-2004 who had electronic health care utilization records available through at least December 2005. Multivariable logistic regression models were applied to evaluate infertility among male and female populations separately. Among 253,973 men and 44,332 women included in these analyses, the adjusted odds of infertility diagnoses in those with prior smallpox vaccination were 0.94 (95% confidence interval [CI], 0.83-1.06) and 1.10 (95% CI, 0.94-1.28), respectively. Therefore, no association was found between smallpox vaccination and subsequent infertility diagnoses in either men or women. This study represents the first large epidemiologic investigation of infertility after the smallpox vaccine.