Vaccine Completion and Timeliness Among Children in the Military Health System: 2010-2019.

OBJECTIVE: Few studies have evaluated pediatric vaccination coverage in the Military Health System, although some evidence suggests lower than ideal coverage. This study assessed vaccine completion and timeliness among military dependents through age 24 months. METHODS: Children born at military hospitals from 2010 through 2019 were identified using Department of Defense Birth and Infant Health Research program data. Vaccine completion and timeliness were assessed for diphtheria, tetanus, and pertussis; polio; measles, mumps, and rubella; hepatitis B; Haemophilus influenzae type b; varicella; and pneumococcal conjugate individually and as a combined 7-vaccine series; rotavirus was assessed separately. Modified Poisson regression models were used to calculate risk ratios (RRs) and 95% confidence intervals (CIs) for noncompletion and delays, adjusting for demographic characteristics. RESULTS: Of 275 967 children, 74.4% completed the combined 7-vaccine series, and 36.2% of those who completed the series had delays. Completion peaked at 78.7% among children born in 2016 and 2017. Among all vaccines, completion was lowest for rotavirus (77.5%), diphtheria, tetanus, and pertussis (83.1%), Haemophilus influenzae type b (86.6%), and pneumococcal conjugate (88.4%). Risk for noncompletion was higher among children born to younger pregnant parents (adjusted RR = 1.33; 95% CI = 1.27-1.40) and with a well-child care location change (adjusted RR = 1.10; 95% CI = 1.09-1.12). Risk for delays paralleled that for noncompletion. CONCLUSIONS: Vaccine completion and timeliness generally improved among military children, but greater noncompletion of vaccine series with more versus fewer doses and disparities for younger and mobile service members suggest system barriers remain.

Disease activity-guided dose optimisation including discontinuation of TNF-inhibitors in rheumatoid arthritis is effective for up to 10 years: an observational follow-up of the DRESS study.

OBJECTIVES: To investigate safety and effectiveness of disease activity-guided dose optimisation of TNF-inhibitors in rheumatoid arthritis over 10 years. METHODS: Observational long-term extension of a randomised study of participants who completed the 3-year extension of the DRESS-study. After the randomised phase (month 0-18), disease activity-guided dose optimisation was allowed for all. Main outcomes were mean time-weighted DAS28-CRP; biological and targeted synthetic anti-rheumatic drug (b/tsDMARD) use per year as proportion of daily defined dose; proportion of patients reaching discontinuation; durability, effectiveness of subsequent dose reduction attempts; and radiographic progression between 3 and 10 years using the Sharp-van der Heijde score. RESULTS: 170 patients were included of whom 127 completed 10-year follow-up. The mean disease activity remained low (DAS28-CRP 2.13, 95% confidence interval 2.10-2.16), whilst the b/tsDMARD dose reduced from 97% at baseline (95%CI 96% to 99%, n = 170)% to56% at year 10 (49% to 63%, n = 127). 119 of 161 participants (74%) with an optimisation attempt reached discontinuation, with a median duration of 7 months (interquartile range 3-33 months), and 25 participants never had to restart their b/tsDMARD (21%, 14% to 29%). The mean dose reduction after dose optimisation was 48% (n = 159) for the first optimisation attempt and 33% for subsequent attempt (n = 86). 48% (41/86) of participants had radiographic progression exceeding the smallest detectable change (5.7 units), and progression was associated with disease activity, not b/tsDMARD use. CONCLUSION: Long-term disease activity-guided dose optimisation of TNF-inhibitors in rheumatoid arthritis, including discontinuation and multiple tapering attempts, remains safe and effective.

Was COVID-19 a heyday for education? Lessons learned from a COVID-19 "pop-up" simulation developed overnight.

Introduction: To adjust for the COVID-19 pandemic's rapidly changing guidelines and clinical needs, educators turned to simulation to create realistic yet safe environments for drilling and innovating various care strategies. Individually, institutions faced creating a pathway for deploying new behaviors and techniques widely across their populace. Methods: In response to this need, we rapidly developed an interprofessional teaching curriculum for safe intubation techniques and donning/doffing of personal protection equipment to anesthesiology clinicians and technicians. Participants were taught using Roussin's Zone 1 simulation techniques including coaching from interprofessional facilitators. Survey data were collected from participants. Results: Participants' confidence levels increased, with coaching and the use of simulation cited as the most useful elements of the training. Conclusions: We believe COVID-19 catalyzed many educational initiatives, and though teams drew their own roadmaps to create programs, sharing the learning from these endeavors may inform future similar situations. Lessons of stakeholder buy-in, use of multidisciplinary teams, and building a psychologically safe space can promote rapid uptake of new techniques and technologies.

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.

Cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas stratified for patients with organ transplantation and hematologic malignancies: A nationwide cohort study.

BACKGROUND: There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC. OBJECTIVE: To investigate the cumulative incidence and timing of subsequent cSCCs. METHODS: Patients with a first cSCC in 2007/2008 from the Netherlands Cancer Registry were linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry. Cumulative incidence function curves were calculated for subsequent cSCCs and stratified for immune status. RESULTS: Among the 12,345 patients, second to sixth cSCC occurred in 4325, 2010, 1138, 739, and 501 patients, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years after the previous cSCC, respectively. The cumulative incidence of a subsequent cSCC at 5 years increased from 28% to 67% for the second to sixth cSCC. For solid organ transplant recipients, the cumulative incidences increased from 74% to 92% and from 41% to 64% for patients with hematologic malignancy. LIMITATIONS: Only histopathologically confirmed cSCCs were included. CONCLUSION: The risk of a subsequent cSCC steeply rises with the number of prior cSCCs and immune status, while the time interval decreases. This can support more informed decisions about follow-up management.

Stem cell-derived brain organoids for controlled studies of transcranial neuromodulation.

Transcranial neuromodulation methods have the potential to diagnose and treat brain disorders at their neural source in a personalized manner. However, it has been difficult to investigate the direct effects of transcranial neuromodulation on neurons in human brain tissue. Here, we show that human brain organoids provide a detailed and artifact-free window into neuromodulation-evoked electrophysiological effects. We derived human cortical organoids from induced pluripotent stem cells and implanted 32-channel electrode arrays. Each organoid was positioned in the center of the human skull and subjected to low-intensity transcranial focused ultrasound. We found that ultrasonic stimuli modulated network activity in the gamma and delta ranges of the frequency spectrum. The effects on the neural networks were a function of the ultrasound stimulation frequency. High gamma activity remained elevated for at least 20 minutes following stimulation offset. This approach is expected to provide controlled studies of the effects of ultrasound and other transcranial neuromodulation modalities on human brain tissue.

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.

Points to consider for cost-effective use of biological and targeted synthetic DMARDs in inflammatory rheumatic diseases: results from an umbrella review and international Delphi study.

OBJECTIVES: To develop evidence-based points to consider for cost-effective use of biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in the treatment of inflammatory rheumatic diseases, specifically rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis. METHODS: Following EULAR procedures, an international task force was formed, consisting of 13 experts in rheumatology, epidemiology and pharmacology from seven European countries. Twelve strategies for cost-effective use of b/tsDMARDs were identified through individual and group discussion. For each strategy, PubMed and Embase were systematically searched for relevant English-language systematic reviews and, for six strategies, additionally for randomised controlled trials (RCTs). Thirty systematic reviews and 21 RCTs were included. Based on the evidence, a set of overarching principles and points to consider was formulated by the task force using a Delphi procedure. Level of evidence (1a-5) and grade (A-D) were determined for each point to consider. Individual voting on the level of agreement (LoA; between 0 (completely disagree) and 10 (completely agree)) was performed anonymously. RESULTS: The task force agreed on five overarching principles. For 10 of 12 strategies, the evidence was sufficient to formulate one or more points to consider, leading to 20 in total, regarding response prediction, drug formulary use, biosimilars, loading doses, low-dose initial therapy, concomitant conventional synthetic DMARD use, route of administration, medication adherence, disease activity-guided dose optimisation and non-medical drug switching. Ten points to consider (50%) were supported by level 1 or 2 evidence. The mean LoA (SD) varied between 7.9 (1.2) and 9.8 (0.4). CONCLUSION: These points to consider can be used in rheumatology practices and complement inflammatory rheumatic disease treatment guidelines to incorporate cost-effectiveness in b/tsDMARD treatment.

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.

Seroconversion after a third COVID-19 vaccine is affected by rituximab dose but persistence is not in patients with rheumatoid arthritis.

OBJECTIVES: In patients with RA treated with (ultra-)low-dose rituximab (RTX), we investigated the association of dosing and timing of RTX on seroconversion after a third coronavirus disease 2019 (COVID-19) vaccination and the persistence of humoral response after a two-dose vaccination. MATERIAL AND METHODS: In this monocentre observational study, patients from the COVAC cohort were included in the third vaccine analysis if humoral response was obtained 2-6 weeks after a third vaccination in previous non-responders and in the persistence analysis if a follow-up humoral response was obtained before a third vaccination in previous responders. Dichotomization between positive and negative response was based on the assay cut-off. The association between the latest RTX dose before first vaccination, timing between the latest RTX dose and vaccination and response was analysed with univariable logistic regression. RESULTS: Of the 196 patients in the cohort, 98 were included in the third vaccine analysis and 23 in the persistence analysis. Third vaccination response was 19/98 (19%) and was higher for 200 mg RTX users [5/13 (38%)] than for 500 and 1000 mg users [7/37 (19%) and 7/48 (15%), respectively]. Non-significant trends were seen for higher response with lower dosing [200 vs 1000 mg: odds ratio (OR) 3.66 (95% CI 0.93, 14.0)] and later timing [per month since infusion: OR 1.16 (95% CI 0.97, 1.35)]. Humoral response persisted in 96% (22/23) and 89% (8/9) of patients who received RTX between the two measurements. CONCLUSIONS: Repeated vaccination as late as possible after the lowest RTX dose possible seems the best vaccination strategy. A once positive humoral response after COVID-19 vaccination persists irrespective of intercurrent RTX infusion. Study registration. Netherlands Trial Registry (https://www.trialregister.nl/), NL9342.

Pharmacokinetic boosting to enable a once-daily reduced dose of tofacitinib in patients with rheumatoid arthritis and psoriatic arthritis (the PRACTICAL study).

Background: Tofacitinib is a Janus Kinase (JAK) inhibitor used for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), dosed as 5 mg twice daily (BID). It is primarily metabolized by the cytochrome P-3A (CYP3A) enzyme, and therefore, the manufacturer recommends to halve the dose when using CYP3A-inhibiting co-medication. Combining half-dose tofacitinib with a registered CYP3A inhibitor (cobicistat) could reduce costs and improve patient experience. Objectives: Primary: bioequivalence of tofacitinib 5 mg combined with cobicistat once daily (QD; intervention) to tofacitinib 5 mg BID (control). Secondary: safety, patient preference (7-point Likert scale at study end) and predicted differences in disease activity (DAS28-CRP and probability of ACR20 response) using a validated exposure-response model. Design: Open-label, cross-over pharmacokinetic study. Methods: We included patients with RA or PsA, treated with tofacitinib 5 mg BID for ⩾14 days without co-medication affected by CYP3A inhibition. Pharmacokinetic sampling was performed at baseline and after 2-6 weeks of intervention treatment. Bioequivalence was defined as 90% CI of the average tofacitinib concentration (Cavg,ss; intervention to control) falling between 80% and 125%, assessed by non-linear mixed-effects modelling. Results: Between 16 September 2019 and 15 January 2021, 30 patients were included, of whom 25 completed both PK measurements. The tofacitinib Cavg,ss was 85% (90% CI: 75-96%). No serious adverse events occurred. Patient preference was 56% for intervention versus 18% for control. No relevant differences in median predicted disease activity were found (DAS28-CRP: 0.03, 95% CI: -0.16 to 0.22; ACR20: -0.01, -0.07 to 0.05). Conclusion: Due to slightly lower tofacitinib concentrations during intervention treatment, pharmacokinetic bioequivalence could not formally be established. However, pharmacokinetic boosting may be an attractive strategy for cost reduction of tofacitinib because of its safety, similar predicted pharmacodynamics and patient preference. Registration: This study was registered on 29 May 2019 in the Netherlands Trial Register (register number: NL7766).

Modeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes.

Human telencephalon is an evolutionarily advanced brain structure associated with many uniquely human behaviors and disorders. However, cell lineages and molecular pathways implicated in human telencephalic development remain largely unknown. We produce human telencephalic organoids from stem cell-derived single neural rosettes and investigate telencephalic development under normal and pathological conditions. We show that single neural rosette-derived organoids contain pallial and subpallial neural progenitors, excitatory and inhibitory neurons, as well as macroglial and periendothelial cells, and exhibit predictable organization and cytoarchitecture. We comprehensively characterize the properties of neurons in SNR-derived organoids and identify transcriptional programs associated with the specification of excitatory and inhibitory neural lineages from a common pool of NPs early in telencephalic development. We also demonstrate that neurons in organoids with a hemizygous deletion of an autism- and intellectual disability-associated gene SHANK3 exhibit intrinsic and excitatory synaptic deficits and impaired expression of several clustered protocadherins. Collectively, this study validates SNR-derived organoids as a reliable model for studying human telencephalic cortico-striatal development and identifies intrinsic, synaptic, and clustered protocadherin expression deficits in human telencephalic tissue with SHANK3 hemizygosity.

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.

Humoral response to coronavirus disease-19 vaccines is dependent on dosage and timing of rituximab in patients with rheumatoid arthritis.

OBJECTIVES: Humoral response to vaccines in RA patients treated with rituximab (RTX) in standard dosages (≥1000 mg) is decreased. Ultra-low dosages (500 or 200 mg) may have better response. Also, timing after latest RTX infusion may be an important variable. We aimed to investigate the influence of RTX dosage and timing on response to COVID-19 vaccination in RA patients. METHODS: A single-centre observational study (n = 196) investigated the humoral response, measured by total Ig anti-COVID-19 assay (positive response ≥1.1), 2-6 weeks after complete COVID-19 vaccination. A multivariable logistic regression model was built to study the effect of RTX dosage and time between latest rituximab and vaccination on response, adjusting for age and methotrexate use. RESULTS: After two-dose vaccination, the response rate was significantly better for patients receiving 200 mg (n = 31, 45%) rituximab compared with 1000 mg (n = 98, 26%; odds ratio 3.07, 95% CI 1.14-8.27) and for each additional month between latest rituximab and vaccination (OR 1.67, 1.39-2.01). CONCLUSION: Both increased time between latest rituximab infusion and complete vaccination, and 200 mg as latest dose were associated with a better response to COVID-19 vaccination and should be considered when trying to increase vaccine response after rituximab in RA patients. TRIAL REGISTRATION: Netherlands Trial Register, https://www.trialregister.nl/, NL9342.

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.