Investigation of a transient increase in omphalocele prevalence in a birth cohort of TRICARE beneficiaries.

BACKGROUND: The Department of Defense Birth and Infant Health Research (BIHR) program leverages medical encounter data to conduct birth defect surveillance among infants born to military families. Omphalocele is a major abdominal wall defect with an annual prevalence of ~2 per 10,000 births in BIHR data, but an unexpected increase was observed during 2017-2019, reaching 6.4 per 10,000 births in 2018. To investigate this transient increase in prevalence, this study aimed to validate the omphalocele case algorithm among infants born 2016-2021. METHODS: Omphalocele cases were identified by ICD-10 code Q79.2 (exomphalos) on one inpatient or two outpatient infant encounter records and validated using parental and infant electronic health records. Characteristics of true and false positive cases were assessed using bivariate analyses and compared over time. RESULTS: Of 638,905 live births from 2016 to 2021, 230 met the ICD-10 case definition for omphalocele; 138 (60.0%) cases were eligible for validation, of which 68 (49.3%) were true positives. The geometric mean time from birth to first ICD-10 omphalocele diagnosis was 1.1 (standard error [SE] 0.1) days for true positives and 11.9 (SE 3.1) days for false positives. Among the 70 false positives, 36 (51.4%) were cases of confirmed umbilical hernia; rates of umbilical hernia and delayed omphalocele diagnoses (>30 days after birth) were elevated among false positives during 2017-2019. CONCLUSIONS: Higher misuse of ICD-10 code Q79.2 during 2017-2019 likely influenced the associated increase in omphalocele prevalence. Timing of diagnosis should be considered for omphalocele case definitions using medical encounter data.

Validation of ICD-9-CM codes for major genitourinary birth defects in Military Health System administrative data, 2006-2014.

BACKGROUND: The Department of Defense Birth and Infant Health Research program is dedicated to birth defects research and surveillance among military families. Here, we assess and refine the validity of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for selected genitourinary birth defects in the Military Health System (MHS). We additionally outline methods for the calculation of positive predictive value (PPV) and negative predictive value (NPV), sensitivity, and specificity using a stratified sampling design. METHODS: Among military infants born from 2006 through 2014, a random sample of ICD-9-CM screen-positive cases (for six genitourinary birth defects) and screen-negative cases were selected for chart review. PPV, NPV, sensitivity, and specificity were calculated for individual defects and any included defect (i.e., overall); measures were weighted by the inverse probability of being sampled. RESULTS: Of 461,557 infants, 686 were sampled for chart review. Bladder exstrophy was accurately reported (PPV: >90%), while the accuracy of renal dysplasia, renal agenesis/hypoplasia, and hypospadias was moderate (PPVs: 66%-68%) and congenital hydronephrosis was low (PPV: 20%). Specificity and NPVs always exceeded 98%. The overall PPV was 50%; however, excluding congenital hydronephrosis screen-positive cases and requiring at least two inpatient or outpatient diagnostic codes resulted in a PPV of 85%. CONCLUSIONS: The validity of major genitourinary birth defect codes varied in MHS administrative data. The accuracy of an overall defect measure improved by omitting congenital hydronephrosis and requiring at least two diagnostic codes. Although PPV is generally useful for research, additional calculation of NPV, sensitivity, and specificity better informs the identification of appropriate selection criteria across surveillance and research settings.

Validation of diagnosis codes for chorioamnionitis in medical encounter data, 2013-2018.

PURPOSE: Chorioamnionitis refers to intrauterine infection/inflammation that can be diagnosed clinically or from laboratory testing. This study aimed to validate chorioamnionitis International Classification of Diseases (ICD) codes using reference standards for clinical and histologic cases. METHODS: Department of Defense Birth and Infant Health Research program data identified a cohort of live deliveries at two United States military hospitals from 2013 to 2018. Deliveries were screened for chorioamnionitis using ICD codes from maternal delivery records; a sample of screen positive and negative deliveries was selected for chart review. Primary analyses validated deliveries using a reference standard for clinical chorioamnionitis; secondary analyses employed a reference standard that also included histologic cases, but were limited by temporal differences in availability of laboratory data. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were calculated with 95% confidence intervals (CIs). RESULTS: Overall, 1857 deliveries (465 screen positive, 1392 screen negative) were eligible for analysis and 336 met the reference standard for clinical chorioamnionitis, yielding a PPV of 0.68 (95% CI 0.63, 0.72) and sensitivity of 0.76 (95% CI 0.72, 0.81). In secondary analyses, 390 deliveries met the reference standard for clinical or histologic chorioamnionitis, resulting in an overall PPV of 0.75 (95% CI 0.71, 0.79); in 2018, when more laboratory results were available, the PPV was 0.91 (95% CI 0.84, 0.97). NPV and specificity were ≥0.97 across reference standards. CONCLUSIONS: Chorioamnionitis ICD codes exhibited moderate correlation with clinical disease, suggesting challenges in using medical encounter data to isolate clinical cases from those only identified through laboratory testing.

Health outcomes among offspring of US Coast Guard responders to the Deepwater Horizon oil spill, 2010-2011.

OBJECTIVE: To evaluate the potential for adverse health outcomes among infants born to US Coast Guard (USCG) responders to the Deepwater Horizon (DWH) oil spill disaster. METHODS: Department of Defense Birth and Infant Health Research programme data identified a cohort of singleton infants born 2010-2011 to USCG personnel in the DWH Oil Spill Coast Guard Cohort study. Infants were included if their military parent ('sponsor') responded to the oil spill during a selected reproductive exposure window (ie, 3 months preconception for male sponsors and periconception through pregnancy for female sponsors), or if their sponsor was a non-responder. χ2 tests and multivariable log-binomial regression were used to compare the demographic and health characteristics of infants born to spill responders and non-responders. RESULTS: Overall, 1974 infants with a male sponsor (n=182 responder, n=1792 non-responder) and 628 infants with a female sponsor (n=35 responder, n=593 non-responder) in the DWH Oil Spill Coast Guard Cohort were identified. Health outcomes were similar among the offspring of male responders and non-responders. The frequency of any poor live birth outcome (ie, low birth weight, preterm birth or birth defect) was higher among infants born to female responders (17.1%, n=6) than non-responders (8.9%, n=53); the maternal age-adjusted association was suggestively elevated (risk ratio 1.93, 95% CI 0.89 to 4.16). CONCLUSION: Infant health outcomes were comparable between the offspring of male USCG oil spill responders and non-responders. Findings were limited by the small number of infants identified, particularly among female responders, and should be interpreted with caution.

The association of regional perinatal risk factors and neonatal intensive care capacity for Military Health System-insured newborns.

OBJECTIVE: To characterize hospitals where military-insured newborns received care and test the association of regional perinatal risk with neonatal intensive care unit (NICU) capacity. STUDY DESIGN: We identified birth hospitals for live newborns October 2015-December 2018 (n = 296,568) and assigned newborns to health service areas (HSAs). Perinatal risk factors and the number of neonatal special care beds and neonatologists were calculated at HSA levels. Cross-sectional correlation analyses assessed perinatal risk factors and capacity across HSAs. RESULTS: 27.0% (n = 10) of military birth hospitals had special care beds (intermediate and intensive) compared with 44.3% of civilian hospitals (n = 1224; p < 0.05). The number of special care beds and neonatologists per newborn varied more than twofold across regions and were only weakly associated with the proportion of higher risk newborns (R2 < 0.05). CONCLUSIONS: The lack of meaningful association of regional perinatal risk with NICU capacity poses challenges for effective specialized care among military-associated newborns.

Pregnancy-associated and pregnancy-related deaths in the United States military, 2003-2014.

BACKGROUND: The Centers for Disease Control and Prevention has reported a steady increase in the US pregnancy-related mortality ratio since national surveillance began in 1987, although trends are partially induced by concurrent improvements in the identification of pregnancy-related deaths. No previous work has evaluated pregnancy-associated and pregnancy-related deaths among active-duty service members, a population with comprehensive health coverage and stable employment. OBJECTIVE: This study aimed to assess trends and variations in pregnancy-associated and pregnancy-related deaths in the US military. STUDY DESIGN: Live births to active-duty service members were captured in Department of Defense Birth and Infant Health Research program data from 2003 to 2014. Pregnancy-associated deaths (deaths temporally related to pregnancy from any cause) were identified through 1 year after pregnancy end date using National Death Index Plus data from the Joint Department of Defense and Department of Veterans Affairs Suicide Data Repository. Pregnancy-associated deaths were classified as pregnancy-related (causally related to pregnancy) based on cause-of-death codes in the National Death Index Plus data, administrative medical encounter data, and medical record review. Pregnancy-related deaths were reported including and excluding deaths from suicide and unintentional overdose. Mortality ratios (deaths per 100,000 live births) were reported overall, triennially, and by selected characteristics; the relative contribution of each cause of death to all pregnancy-associated deaths was reported overall and by age, race and ethnicity, and marital status. Timing of death relative to pregnancy end date was assessed by cause of death. RESULTS: A total of 179,252 live births occurred to active-duty service members from 2003 to 2014. Pregnancy-associated and pregnancy-related mortality ratios were 41.3 (95% confidence interval, 32.4-51.8) and 18.4 (95% confidence interval, 12.7-25.9), respectively. Excluding deaths from suicide and unintentional overdose, the pregnancy-related mortality ratio was 11.2 (95% confidence interval, 6.8-17.2). Deaths from suicide and unintentional overdose composed a larger proportion of pregnancy-related deaths over time and accounted for 17.6% of all pregnancy-associated deaths. Deaths from other pregnancy-related causes accounted for a greater share of deaths among older vs younger service members (≥30 years: 41.2%; 18-29 years: 22.8%) and non-Hispanic Black vs White service members (33.3% vs 24.1%). Pregnancy-related deaths, excluding suicide and unintentional overdose, were more likely to occur within 42 days of pregnancy end date; in contrast, deaths from suicide, overdose, assault, and undetermined intent were more likely to occur between 42 days and 1 year after pregnancy. CONCLUSION: Pregnancy-associated and pregnancy-related deaths varied over time and by age and race and ethnicity. Suicide and overdose are major recent causes of pregnancy-related death among active-duty service members.

Pregnancy and posttraumatic stress disorder: associations with infant outcomes and prenatal care utilization.

BACKGROUND: Posttraumatic stress disorder (PTSD) affects 3.6-9.7% of women, and has been associated with adverse outcomes in pregnancy; however, associations with prenatal care (PNC) utilization are not clear. OBJECTIVE: To evaluate associations of PTSD in pregnancy with PNC utilization and adverse infant outcomes in an active-duty military population (a population with universal health insurance). METHODS: This was a retrospective cohort study of pregnant active-duty service members in Department of Defense Birth and Infant Health Research program data from 2007 to 2014. Administrative medical encounter data were used to define PTSD cases and outcomes of interest. Descriptive statistics and multivariable log-binomial regression compared PNC utilization and adverse infant outcomes (preterm birth, small for gestational age [SGA], major birth defects) among service members with current PTSD (defined as PTSD in the year prior to pregnancy or during pregnancy) to those without current PTSD. RESULTS: Of the 103,221 singleton live births identified, 1657 (1.6%) were born to active-duty service members diagnosed with current PTSD. Service members with PTSD were more likely to initiate PNC in the first trimester (93.5% vs. 90.2%) and score adequate plus on the Adequacy of Prenatal Care Utilization Index (63.2% vs. 40.0%) compared to service members without PTSD. PTSD case status was not associated with preterm birth, SGA, or major birth defects, regardless of the adjustment set used (fully adjusted RR 0.96, 95% CI 0.82-1.13; RR 1.08, 95% CI 0.79-1.48; and RR 1.03, 95% CI 0.79-1.34, respectively). CONCLUSION: For pregnant service members with current PTSD, no associations with adverse infant outcomes were noted, and these patients initiated care earlier and had higher PNC utilization scores compared to pregnant service members without current PTSD. Universal health care coverage and utilization of PNC in this population may mitigate adverse pregnancy outcomes observed in civilian populations of patients with PTSD.

Severe Maternal Morbidity among Women in the U. S. Military, 2003-2015.

OBJECTIVE: This study aimed to assess trends and correlates of severe maternal morbidity at delivery among active duty women in the U.S. military, all of whom are guaranteed health care and full employment. STUDY DESIGN: Linked military personnel and medical encounter data from the Department of Defense Birth and Infant Health Research program were used to identify a cohort of delivery hospitalizations among active duty military women from January 2003 through August 2015. Cases of severe maternal morbidity were identified by applying 21- and 20-condition algorithms (with and without blood transfusion) developed by the Centers for Disease Control and Prevention. Rates (per 10,000 delivery hospitalizations) were reported overall and by specific condition. Multivariable Poisson regression models estimated associations with demographic, clinical, and military characteristics. RESULTS: Overall, 187,063 hospitalizations for live births were included for analyses. The overall 21- and 20-condition severe maternal morbidity rates were 111.7 (n = 2089) and 37.4 (n = 699) per 10,000 delivery hospitalizations, respectively. The 21-condition rate increased by 184% from 2003 to 2015; the 20-condition rate increased by 40%. Compared with non-Hispanic White women, the adjusted 21-condition rate of severe maternal morbidity was higher for Hispanic (adjusted rate ratio [aRR] = 1.28, 95% confidence interval [CI]: 1.13-1.46), non-Hispanic Black (aRR = 1.34, 95% CI: 1.21-1.49), Asian/Pacific Islander (aRR = 1.35, 95% CI: 1.13-1.61), and American Indian/Alaska Native (aRR = 1.39, 95% CI: 1.06-1.82) women. Rates also varied by age, clinical factors, and deployment history. CONCLUSION: Active duty U.S. military women experienced an increase in severe maternal morbidity from 2003 to 2015 that followed national trends, despite protective factors such as stable employment and universal health care. Similar to other populations, military women of color were at higher risk for severe maternal morbidity relative to non-Hispanic White military women. Continued surveillance and further investigation into maternal health outcomes are critical for identifying areas of improvement in the Military Health System. KEY POINTS: · Cesarean delivery and multiple birth were the strongest correlates of severe maternal morbidity in this population.. · Racial disparities persisted across indicators of severe maternal morbidity.. · Rates of disseminated intravascular coagulation were higher than those reported nationally..

History of pandemic H1N1-containing influenza vaccination and risk for spontaneous abortion and birth defects.

BACKGROUND: One recent study suggested an association between receipt of pandemic H1N1 (pH1N1)-containing vaccines in consecutive influenza seasons and spontaneous abortion, but corroborating scientific evidence is limited. In the present study, we leveraged a population of vaccine-compliant pregnant military women to examine history of pH1N1-containing influenza vaccination and adverse pregnancy outcomes. Because seasonal influenza vaccination is compulsory for military service, safety concerns regarding repeat vaccination are particularly relevant in this population. METHODS: Pregnancies and live births from Department of Defense Birth and Infant Health Research program data were linked with military personnel immunization records to identify women vaccinated with a pH1N1-containing vaccine in pregnancy prior to 21 6/7 weeks' gestation, October 2009-April 2015. Cox and modified Poisson regression models estimated associations between vaccination with pH1N1- versus non-pH1N1-containing influenza vaccine in the season prior to the index pregnancy, and spontaneous abortion and birth defects, respectively. Cox models were calculated for two periods of follow-up: through (1) 21 6/7 weeks' gestation and (2) 28 days postvaccination. RESULTS: Of 26,264 pregnancies, 21,736 (82.8%) were among women who received a dose of pH1N1-containing vaccine in the prior influenza season and 4,528 (17.2%) were among women who received non-pH1N1-containing vaccine in the prior influenza season. Among 23,121 infants, 19,365 (83.8%) and 3,756 (16.2%) had mothers exposed and unexposed to pH1N1-containing vaccine in the prior influenza season, respectively. The adjusted hazard ratio (aHR) for spontaneous abortion approximated 1.0 across the complete follow-up period (95% confidence interval [CI]: 0.89-1.13) and was slightly elevated when censored at 28 days postvaccination, though the CI was imprecise (aHR: 1.19; 95% CI: 0.97-1.46). No associations with birth defects were observed. CONCLUSION: This work lends additional safety evidence and support for vaccination against pH1N1 in pregnancy, regardless of the vaccine received in the prior influenza season.

Parental occupation and childhood germ cell tumors: a case-control study in Denmark, 1968-2016.

PURPOSE: To examine associations between parental occupation and childhood germ cell tumors (GCTs) in offspring while distinguishing by common histologic subtype (i.e., yolk sac tumor and teratoma). METHODS: This population-based case-control study included childhood GCT cases in Denmark diagnosed 1968-2015 (< 16 years old at diagnosis) and sex and birth year-matched controls. Demographic information and parental employment histories were obtained from Danish registries. Parental occupation was assessed by industry; job-exposure matrices were used to examine specific occupational exposures (i.e., potentially carcinogenic organic solvents and social contact). Conditional multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CIs). RESULTS: Overall, 178 childhood GCT cases (50 yolk sac tumors; 65 teratomas) and 4,355 controls were included for analysis. Maternal employment in education during pregnancy was associated with offspring GCTs (OR 2.45, 95% CI 1.23-4.90), especially yolk sac tumors (OR 5.27, 95% CI 1.94-14.28). High levels of both maternal and paternal occupational social contact were also associated with offspring yolk sac tumors across all exposure periods (ORs 2.30-4.63). No signals were observed for paternal occupational solvent exposure, while imprecise associations were estimated for maternal exposure (e.g., dichloromethane exposure during pregnancy, OR 1.51, 95% CI 0.77-2.95). CONCLUSION: Our findings suggest that parental occupation is associated with offspring GCTs, with most consistent evidence supporting an association between maternal employment in education or other high social contact jobs and offspring yolk sac tumors.

Posttraumatic Stress Disorder in a Cohort of Pregnant Active Duty U.S. Military Servicewomen.

The present study aimed to describe the demographic and occupational characteristics, comorbidities, and psychotropic medication receipt associated with posttraumatic stress disorder (PTSD) diagnosis during pregnancy among a sample of active duty U.S. military servicewomen. Data from the U.S. Department of Defense Birth and Infant Health Research program were used to identify pregnancies in active duty servicewomen from 2007 through 2014. Demographic and occupational data were linked with electronic medical and pharmacy records to capture mental health diagnoses and medication receipt dates. Cases of PTSD were identified by the presence of ICD-9-CM Diagnostic Code 309.81 on maternal records from 1 year before the date of the last menstrual period through the end of pregnancy. Of 134,244 identified pregnancies among active duty servicewomen, 2,240 (1.7%) met the case criteria for PTSD. Women with a PTSD diagnosis compared to those without a PTSD diagnosis were more likely to be White non-Hispanic (51.3% vs. 47.4%), unmarried (33.3% vs. 28.2%), in the Army (49.6% vs. 35.8%) or Marine Corps (10.9% vs. 8.0%), in a service and supply occupation (18.2% vs. 13.6%), and to have a junior enlisted rank (56.3% vs. 50.1%) and have been previously deployed (51.2% vs. 39.6%), RRs = 1.15-1.75. Among PTSD cases, the most common mental health comorbidities were depressive disorder (60.9%), adjustment disorder (43.4%), and anxiety disorder (39.3%). During pregnancy, 44.2% of PTSD cases and 7.2% of noncases received psychotropic medications. Demographic and occupational characteristics, comorbidities, and psychotropic medication use differed substantially among PTSD cases and noncases in this large records-based study.

Safety of yellow fever vaccination in pregnancy: findings from a cohort of active duty US military women.

BACKGROUND: Yellow fever (YF) is a rare viral disease that can be prevented through receipt of a live attenuated vaccine. In the US military, service members must receive the YF vaccine before assignment to endemic areas, putting active duty service women at heightened risk for inadvertent exposure during preconception or pregnancy. Few studies have investigated the safety of YF vaccination in pregnancy to date, and none in a military population. METHODS: Department of Defense Birth and Infant Health Research program data were used to identify pregnancies and infants among active duty US military women, 2003-2014. Multivariable regression models estimated associations with YF vaccine exposure during preconception/pregnancy and adverse outcomes (e.g. spontaneous abortion, birth defects). Sensitivity analyses were performed that excluded pregnancies exposed to other live vaccines. For analyses of birth defects only, a secondary sensitivity analysis was performed that excluded infants diagnosed with chromosomal anomalies. RESULTS: Of the 196 802 pregnancies and 160 706 singleton infants identified, 1347 (0.7%) and 1132 (0.7%), respectively, were exposed to the YF vaccine. No increased risks for adverse pregnancy or infant outcomes were observed in the main analysis. In sensitivity analyses that excluded pregnancies exposed to other live vaccines, preconception YF vaccine exposure was associated with birth defects [adjusted risk ratio (aRR) = 1.71, 95% confidence interval (CI) = 1.08-2.73]; this association was attenuated when further excluding infants with chromosomal anomalies (aRR = 1.59, 95% CI = 0.97-2.62). CONCLUSIONS: Overall, YF vaccine exposure did not appear to be associated with most adverse outcomes among this population of pregnant military women. A tenuous association between preconception YF vaccine exposure and birth defects was observed in sensitivity analyses, which may warrant further investigation.

Maternal and infant outcomes following exposure to quadrivalent human papillomavirus vaccine during pregnancy.

INTRODUCTION: The Department of Defense encourages service members ≤26 years of age to receive the human papillomavirus (HPV) vaccine. Although this vaccine is not recommended in pregnancy, inadvertent vaccination may occur. The objective of this study was to assess whether active duty US military women who received the quadrivalent HPV vaccine (4vHPV) during pregnancy were at increased risk for adverse maternal or infant outcomes. METHODS: The study population included active duty US military women aged 17-28 years with at least one pregnancy between 2007 and 2014, and the infants resulting from those pregnancies. Pregnancies, live births, and outcomes were identified using medical codes in administrative medical records. Exposure to 4vHPV during pregnancy was ascertained from personnel immunization records. Multivariable regression models were used to calculate risk estimates and 95% confidence intervals for the maternal outcomes of spontaneous abortion, preeclampsia/eclampsia and preterm labor, and the infant outcomes of preterm birth, birth defects, growth problems in infancy or in utero, and infant sex. RESULTS: Overall, 90,600 pregnancies and 75,670 singleton infants were identified. Approximately 2% of pregnancies and infants were exposed to 4vHPV during pregnancy. After adjustments, no positive associations were detected between inadvertent exposure to 4vHPV during pregnancy and any adverse pregnancy or infant outcomes. DISCUSSION: Our findings add to an established body of literature demonstrating the safety of 4vHPV when inadvertently administered during pregnancy. Although 4vHPV is no longer administered in the US, its use continues overseas; therefore, safety studies remain important. Furthermore, such studies can provide reassurance to women inadvertently exposed to nonavalent HPV vaccine (9vHPV) in pregnancy, which protects against four of the same antigens as 4vHPV, since safety of 9vHPV has not yet been established in pregnant women.

Racial Disparities in Prenatal Care Utilization and Infant Small for Gestational Age Among Active Duty US Military Women.

OBJECTIVES: To examine racial disparities in prenatal care (PNC) utilization and infant small for gestational age (SGA) among active duty US military women, a population with equal access to health care and known socioeconomic status. METHODS: Department of Defense Birth and Infant Health Research program data identified active duty women with singleton live births from January 2003 through August 2015. Administrative claims data were used to define PNC utilization and infant SGA, and log-binomial regression models estimated associations with race/ethnicity. To examine whether associations between maternal race/ethnicity and infant SGA were subject to effect measure modification, respective analyses were stratified by demographic and health characteristics. RESULTS: Overall, 12.2% of non-Hispanic White women initiated PNC after the first trimester, compared with 14.8% of American Indian/Alaska Native, 15.1% of Asian/Pacific Islander, 14.2% of non-Hispanic Black, and 13.0% of Hispanic women. Infant SGA prevalence was 2.4% and 1.6% among non-Hispanic Black and White women, respectively (aRR 1.52, 95% CI 1.40-1.64). This disparity persisted across stratified analyses, particularly among non-Hispanic Black versus White women with a preeclampsia or hypertension diagnosis in pregnancy (RR 1.96, 95% CI 1.67-2.29) and those aged 35 + years at infant birth (RR 2.04, 95% CI 1.56-2.67). CONCLUSIONS FOR PRACTICE: In multiple assessments of PNC utilization and infant SGA, non-Hispanic Black military women had consistently worse outcomes than their non-Hispanic White counterparts. This suggests that equal access to health care does not eliminate racial disparities in outcomes or utilization; additional research is needed to elucidate the underlying etiology of these disparities.

Japanese encephalitis vaccination in pregnancy among U.S. active duty military women.

INTRODUCTION: Japanese encephalitis (JE) vaccine is an inactivated vaccine that has shown no risks in pregnancy in animal models, but epidemiologic studies are lacking. U.S. military service members located in JE endemic regions are required to be vaccinated; understanding the potential adverse events (AEs), including AEs that may occur in pregnancy, is needed. Here, we assessed pregnancy and infant health outcomes in association with JE vaccination in pregnancy. METHODS: The study population consisted of 192,570 pregnancies to active duty women (2003-2014), captured in the Department of Defense Birth and Infant Health Research program. JE vaccine in pregnancy, vaccine count, formulation, trimester, and whether first career dose coincided with pregnancy were compared with unexposed pregnancies to assess risk of pregnancy and infant health outcomes. Adjusted risk estimates and 95% confidence intervals (CIs) were calculated by multivariable models. RESULTS: Of the 192,570 identifed pregnancies, 513 were exposed to the JE vaccine; 474 exposures occurred in the first trimester. For all outcomes, elevated risk estimates ranging from 1.53 to 1.70, were observed with receipt of >1 JE vaccine in pregnancy, though 95% CIs were wide and encompassed the null. First dose of JE vaccination in pregnancy was associated with a 1.87 (95% CI: 1.12-3.13) times increased risk of low birthweight (LBW) when excluding pregnancies exposed to other non-routinely recommended vaccinations in pregnancy. All other associations were null in both main and subset analyses. CONCLUSIONS: The overall results of these analyses provide reassuring findings for the safety of JE vaccination in pregnancy. Higher counts of JE vaccine received in pregnancy yielded large yet non-statistically significant risk estimates for all outcomes, though likely driven by lack of pregnancy awareness. An association was observed with LBW in subset analyses, but it was limited to women receiving their first JE vaccine and not observed in the larger main analyses.

Infant health outcomes among offspring of male U.S. military divers.

While there are suggestions that the extreme hyperbaric conditions encountered during deep saturation diving may impact male reproductive function, few studies have investigated whether paternal occupational diving influences offspring health outcomes. To examine this, Department of Defense Birth and Infant Health Research program data were used to identify the offspring of male active duty divers and non-divers in the U.S. military, 2001-2016. Log-binomial regression models estimated associations with infant outcomes (e.g., major structural birth defects, low birthweight). Among 1,148,252 identified singleton infants, 3,843 were considered the offspring of male divers; paternal occupational diving was not positively associated with any adverse infant outcome under study. These findings corroborate existing literature and further suggest that male divers in the U.S. military are not occupationally exposed to reproductive hazards that adversely influence offspring infant health outcomes.

Occupational livestock or animal dust exposure and offspring cancer risk in Denmark, 1968-2016.

OBJECTIVE: To examine associations with occupational livestock or other animal dust exposure and offspring cancer risk. METHODS: In this population-based case-control study of Danish children aged < 17 years old, 5078 childhood cancer cases diagnosed 1968-2016 were matched to cancer-free controls by birth year and sex (n = 123,228). Occupational livestock or animal dust exposure was identified using a job-exposure matrix. We employed multivariable conditional logistic regression models to estimate associations with offspring cancer for births 1968-2016 and 1989-2016, with the latter timeframe reflecting a period of presumed higher exposure due to changes in Danish farming practices. Sensitivity analyses considered place of birth (urban areas vs. rural areas and small towns). RESULTS: For births 1968-2016, paternal exposure from offspring birth to cancer diagnosis was associated with central nervous system tumors (adjusted odds ratio [OR] = 1.30, 95% confidence interval [CI] 1.04-1.63) and germ cell tumors (OR = 1.82, 95% CI 1.05-3.27), while maternal pregnancy exposure was associated with astrocytoma (OR = 1.89, 95% CI 1.00-3.57). For births 1989-2016, paternal exposure from offspring birth to cancer diagnosis was negatively associated with acute lymphoid leukemia (OR = 0.58, 95% CI 0.33-1.00). For births in rural areas only, maternal exposure from offspring birth to cancer diagnosis was positively associated with acute myeloid leukemia (OR = 2.16, 95% CI 1.09-4.29). CONCLUSIONS: This study suggests that paternal occupational animal exposure is associated with offspring germ cell tumors, and maternal pregnancy exposure with astrocytomas. Our results are mixed with respect to leukemia subtypes.

Safety of tetanus, diphtheria, and acellular pertussis vaccination among pregnant active duty U.S. military women.

BACKGROUND: The tetanus, diphtheria, and acellular pertussis (Tdap) vaccine was approved for U.S. adults in 2005 and recommended for administration in every pregnancy in 2012, with optimal timing between 27 and 36 weeks' gestation. In the military, however, a current Tdap vaccination status is compulsory for service, and active duty women may be inadvertently exposed in early pregnancy. Safety data in this population are limited. OBJECTIVES: To assess safety of inadvertent (0-13 weeks' gestation) and recommended (27-36 weeks' gestation) exposure to the Tdap vaccine in pregnancy. METHODS: Pregnancies and live births from Department of Defense Birth and Infant Health Research program data were linked with military personnel immunization records to determine pregnancy Tdap vaccine exposure among active duty women, 2006-2014. Multivariable Cox and generalized linear regression models estimated associations between Tdap vaccine exposure and adverse pregnancy or infant outcomes. RESULTS: Of 145,883 pregnancies, 1272 were exposed to the Tdap vaccine in the first trimester and 9438 between 27 and 36 weeks' gestation. Neither inadvertent nor recommended vaccine exposure were associated with spontaneous abortion, preeclampsia, or preterm labor. Among 117,724 live born infants, 984 were exposed to the Tdap vaccine in the first trimester and 9352 between 27 and 36 weeks' gestation. First trimester exposure was not associated with birth defects, growth problems in utero, growth problems in infancy, preterm birth, or low birth weight. Tdap vaccine exposure between 27 and 36 weeks' gestation was not associated with any adverse infant outcome. CONCLUSIONS: Among a population of active duty women in the U.S. military who received the Tdap vaccine during pregnancy, we detected no increased risks for adverse maternal, fetal, or infant outcomes. Our findings corroborate existing literature on the safety of exposure to the Tdap vaccine in pregnancy.

Atovaquone-proguanil exposure in pregnancy and risk for adverse fetal and infant outcomes: A retrospective analysis.

BACKGROUND: Malaria in pregnancy can cause severe maternal and fetal complications. Chloroquine (CQ) and mefloquine (MQ) are recommended for chemoprophylaxis in pregnancy, but are not always suitable. Atovaquone-proguanil (AP) might be a viable option for malaria prevention in pregnancy, but more safety data are needed. METHODS: Data for pregnancies and live births among active duty military women, 2003-2014, from the Department of Defense Birth and Infant Health Research program were linked with pharmacy data to determine antimalarial exposure. Multivariable Cox and logistic regression models were used to assess the relationship of antimalarial exposure with fetal and infant outcomes, respectively. RESULTS: Among 198,164 pregnancies, 50 were exposed to AP, 156 to MQ, and 131 to CQ. Overall, 17.6% of unexposed pregnancies and 28.0%, 16.0%, and 6.1% of pregnancies exposed to AP, MQ, and CQ, respectively, ended in fetal loss (spontaneous abortion or stillbirth) (adjusted hazard ratios [aHR] = 1.46, 95% confidence interval [CI] 0.87-2.46; aHR = 1.06, 95% CI 0.72-1.57; and aHR = 0.47, 95% CI 0.24-0.94, respectively). CONCLUSIONS: The small number of AP exposed pregnancies highlights the difficulty in assessing safety. While definitive conclusions are not possible, these data suggest further research of AP exposure in pregnancy and fetal loss is warranted. TWITTER LINE: More research on fetal loss following atovaquone-proguanil exposure in pregnancy is warranted.