BACKGROUND: Pregnant veterans with post-traumatic stress disorder (PTSD) are at increased risk for spontaneous preterm birth, yet the underlying reasons are unclear. We examined factors associated with spontaneous preterm birth among pregnant veterans with active PTSD. METHODS: This was an observational study of births from administrative databases reimbursed by the Veterans Health Association (VA) between 2005 and 2015. Singleton livebirths among veterans with active PTSD within 12 months prior to childbirth were included. The primary outcome was spontaneous preterm birth. Maternal demographics, psychiatric history, and pregnancy complications were evaluated as exposures. Covariates significant on bivariate analysis, as well as age and race/ethnicity as a social construct, were included in multivariable logistic regression to identify factors associated with spontaneous preterm birth. Additional analyses stratified significant covariates by the presence of active concurrent depression and explored interactions between antidepressant use and preeclampsia. RESULTS: Of 3,242 eligible births to veterans with active PTSD, 249 (7.7%) were spontaneous preterm births. The majority of veterans with active PTSD (79.1%) received some type of mental health treatment, and active concurrent depression was prevalent (61.4%). Preeclampsia/eclampsia (adjusted odds ratio [aOR] 3.30, 95% confidence interval [CI] 1.67-6.54) and ≥6 antidepressant medication dispensations within 12 months prior to childbirth (aOR 1.89, 95% CI 1.29-2.77) were associated with spontaneous preterm birth. No evidence of interaction was seen between antidepressant use and preeclampsia on spontaneous preterm birth (p=0.39). Findings were similar when stratified by active concurrent depression. CONCLUSION: Among veterans with active PTSD, preeclampsia/eclampsia and ≥6 antidepressant dispensations were associated with spontaneous preterm birth. While the results do not imply that people should discontinue needed antidepressants during pregnancy in veterans with PTSD, research into these factors might inform preterm birth prevention strategies for this high-risk population.

Development of effective prevention and treatment strategies for pre-eclampsia is limited by the lack of accurate methods for identification of at-risk pregnancies. We performed small RNA sequencing (RNA-seq) of maternal serum extracellular RNAs (exRNAs) to discover and verify microRNAs (miRNAs) differentially expressed in patients who later developed pre-eclampsia. Sera collected from 73 pre-eclampsia cases and 139 controls between 17 and 28 weeks gestational age (GA), divided into separate discovery and verification cohorts, are analyzed by small RNA-seq. Discovery and verification of univariate and bivariate miRNA biomarkers reveal that bivariate biomarkers verify at a markedly higher rate than univariate biomarkers. The majority of verified biomarkers contain miR-155-5p, which has been reported to mediate the pre-eclampsia-associated repression of endothelial nitric oxide synthase (eNOS) by tumor necrosis factor alpha (TNF-α). Deconvolution analysis reveals that several verified miRNA biomarkers come from the placenta and are likely carried by placenta-specific extracellular vesicles.