An exploratory analysis of factors associated with spontaneous preterm birth among pregnant veterans with post-traumatic stress disorder.

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.

Fasting Compared With Fed and Oral Intake Before the 1-Hour Oral Glucose Tolerance Test: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of fasting compared with eating before the 1-hour oral glucose tolerance test (OGTT) on gestational diabetes mellitus (GDM) screening results. METHODS: In a single-center, prospective randomized trial, participants were randomized to: 1) fasting for 6 or more hours or 2) oral intake ("fed") within 2 hours of the 50-g, 1-hour OGTT. The 1-hour OGTT was administered after 24 weeks of gestation. A positive screen result was defined as a serum glucose level of 140 mg/dL or higher. Protocol adherence was assessed by a survey administered immediately after the OGTT. We planned to enroll 100 participants in each group to detect an absolute difference of 20 percentage points or more on the 1-hour OGTT screen-positive rate using Fisher exact test, assuming an estimated screen-positive rate of 45% in the fasting and 25% in the fed group and 10% attrition, with a two-sided α=0.05, power=0.8. The primary outcome was the 1-hour OGTT screen-positive rate. Secondary outcomes included mean 1-hour OGTT glucose values, GDM diagnosis, maternal and neonatal outcomes, and patient perceptions regarding the 1-hour OGTT. RESULTS: From November 2020 through April 2021, 200 participants were randomized. One hundred ninety-five completed the 1-hour OGTT (97 fasting, 98 fed). Participant surveys confirmed 97.9% (n=95) adherence to the fasting and 91.8% (n=90) adherence to the fed groups. The screen-positive rate was significantly higher in the fasting than the fed group (32.0% vs 13.3%, respectively, P=.002), as was the mean glucose value (127.7 mg/dL vs 113.3 mg/dL, P=.002). The incidence of GDM in the fasting group was 12.4% (n=12) and in the fed group was 5.1% (n=5) (P=.08). There were no significant differences in maternal or neonatal outcomes. CONCLUSION: Fasting for 6 or more hours doubled the incidence of a positive 1-hour OGTT result when compared with eating within 2 hours of the test. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04547023.

Postpartum Readmission for Hypertension After Discharge on Labetalol or Nifedipine.

OBJECTIVE: To assess whether readmission for hypertension by 6 weeks postpartum differed between patients discharged on nifedipine or labetalol. METHODS: This cohort study included patients with delivery admissions from 2006 to 2017 who were discharged from the hospital on nifedipine or labetalol and were included in a large, national adjudicated claims database. We identified patients' discharge medication based on filled outpatient prescriptions. We compared rates of hospital readmission for hypertension between patients discharged postpartum on labetalol alone, nifedipine alone, or combined nifedipine and labetalol. Patients with chronic hypertension without superimposed preeclampsia were excluded. Comparisons based on medication were performed using logistic regression models with adjustment for prespecified confounders. Comparisons were also stratified by hypertensive disorder of pregnancy severity. RESULTS: Among 1,582,335 patients overall, 14,112 (0.89%) were discharged postpartum on labetalol, 9,001 (0.57%) on nifedipine, and 1,364 (0.09%) on both medications. Postpartum readmissions for hypertension were more frequent for patients discharged on labetalol compared with nifedipine (641 patients vs 185 patients, 4.5% vs 2.1%, adjusted odds ratio [aOR] 1.63, 95% CI 1.43-1.85). Readmissions for hypertension were more frequent for patients discharged on labetalol compared with nifedipine for both mild (4.5% vs 2.7%, aOR 1.57, 95% CI 1.29-1.93) and severe hypertensive disorders of pregnancy (261 patients vs 72 patients, 5.7% vs 3.2%, aOR 1.63, 95% CI 1.43-1.85). Readmissions for hypertension were more frequent on combined nifedipine and labetalol compared with nifedipine (3.1% vs 2.1%), but the odds were lower after confounder adjustment (aOR 0.80, 95% CI 0.64-0.99). CONCLUSION: Postpartum discharge on labetalol was associated with increased risk of readmission for hypertension compared with discharge on nifedipine.

Association of Epilepsy and Severe Maternal Morbidity.

OBJECTIVE: To evaluate severe maternal morbidity (SMM) among patients with epilepsy and patients without epilepsy. METHODS: We retrospectively examined SMM using linked birth certificate and maternal hospital discharge records in California between 2007 and 2012. Epilepsy present at delivery admission was the exposure and was subtyped into generalized, focal and other less specified, or unspecified. The outcomes were SMM and nontransfusion SMM from delivery up to 42 days' postpartum, identified using Centers for Disease Control and Prevention indicators. Multivariable logistic regression models were used to adjust for confounders, which were selected a priori. We also estimated the association between epilepsy and SMM independent of comorbidities by using a validated obstetric comorbidity score. Severe maternal morbidity indicators were then compared using the same multivariable logistic regression models. RESULTS: Of 2,668,442 births, 8,145 (0.3%) were to patients with epilepsy; 637 (7.8%) had generalized, 6,250 (76.7%) had focal or other less specified, and 1,258 (15.4%) had unspecified subtypes. Compared with patients without epilepsy, patients with epilepsy had greater odds of SMM (4.3% vs 1.4%, adjusted odds ratio [aOR] 2.91, 95% CI 2.61-3.24) and nontransfusion SMM (2.9% vs 0.7%, aOR 4.16, 95% CI 3.65-4.75). Epilepsy remained significantly associated with increased SMM and nontransfusion SMM after additional adjustment for the obstetric comorbidity score, though the effects were attenuated. When grouped by organ system, all SMM indicators were significantly more common among patients with epilepsy-most notably those related to hemorrhage and transfusion. CONCLUSION: Severe maternal morbidity was significantly increased in patients with epilepsy, and SMM indicators across all organ systems contributed to this.

Discovery and Verification of Extracellular miRNA Biomarkers for Non-invasive Prediction of Pre-eclampsia in Asymptomatic Women.

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.

Positive antenatal Edinburgh Depression Scale: examining behavioral and pharmacological therapy on maternal and neonatal outcomes.

Objective: We hypothesized that women with a positive antenatal Edinburgh Depression Screen (EPDS) (≥10), undergoing behavioral or pharmacologic therapy have improved maternal and neonatal outcomes.Study design: This is a retrospective study of singleton pregnancies at UC, San Diego from 2010 to 2014. Patients with an antenatal EPDS were subdivided based on their intervention: negative score, positive score no treatment, behavioral therapy only, and pharmacologic therapy. The primary outcome was rate of preterm birth with secondary outcomes of maternal and neonatal outcomes.Results: Patients with a positive EPDS had a higher rate of preterm delivery, small-for-gestational age, NICU admission and Apgar score <7. Rates of adverse outcomes were highest among women receiving pharmacologic therapy. Rates of adverse outcomes women were not increased in the behavioral therapy group compared to the negative EPDS group. When adjusting for confounding variables, patient with a positive EPDS were more likely deliver preterm with an adjusted odds ratio of 1.71. Among varying treatment modalities, the odds ratio for preterm delivery was not statistically significant.Conclusion: Adverse pregnancy outcomes were highest among those requiring pharmacotherapy. Behavioral therapy had a positive effect on outcomes. Intervention to reduce these adverse outcomes in these patients needs further study.

Ultrasound Measurements of Frontal Horns and the Cavum Septi Pellucidi in Healthy Fetuses in the Second and Third Trimesters of Pregnancy.

OBJECTIVES: To assess the visualization rate and size of the frontal horns (FHs) and cavum septi pellucidi (CSP) in healthy fetuses throughout pregnancy. METHODS: After Institutional Review Board approval, 522 consecutive uncomplicated singleton pregnancies between 15 and 39 gestational weeks were enrolled in the study. Ultrasound measurements of the anterior horn width (AHW), center from the horn distance (CFHD), distance from the FHs to the CSP, and CSP width were retrospectively performed using axial transventricular or transcerebellar planes. Available maternal body mass indices were recorded. RESULTS: At least 1 FH was seen in 78% of the cases. The mean AHW decreased over the second trimester and plateaued in the third trimester. The CFHD plateaued in the second trimester and increased in the third trimester. Downside FHs were generally larger than upside FHs. More FHs were measured in transventricular (69%) than transcerebellar (31%) planes. Frontal horns were seen with high, low, and no confidence in 57%, 21%, and 22% of cases, respectively. No-confidence rates were 17% in the second trimester and 42% in the third trimester. The CSP was not visualized in 4% of cases; 15 of 19 cases of a nonvisualized CSP were scanned between 18 and 37 weeks. Mean body mass indices ± SDs were 27.6 ± 6.7 kg/m2 for the patients in cases of a visualized CSP and 32.4 ± 9.1 kg/m2 for the patients in cases of a nonvisualized CSP. CONCLUSIONS: Normative data for the fetal FH and CSP width were established. Frontal horns are more frequently seen on transventricular views and are difficult to confidently assess in the late third trimester. This study challenges previously reported data that the CSP is seen in 100% of cases from 18 to 37 weeks.

Recognizing maternal mental health disorders: beyond postpartum depression.

PURPOSE OF REVIEW: Maternal mental health disorders, including anxiety and depression, are one of the most common obstetric complications, presenting in pregnancy and postpartum. RECENT FINDINGS: Maternal mental health disorders are associated with adverse maternal and neonatal outcomes. Screening women in pregnancy and postpartum for mental health disorders is key to early identification and treatment of anxiety and depression in the perinatal population. Although universal screening is now recommended by numerous professional organizations, rates of screening are low and often not performed with a validated screening instrument. Although clinical assessment is important, it is insufficient to identify maternal mental health disorders. As symptoms may change throughout pregnancy, screening for anxiety and depression should be done at multiple time points in pregnancy, including intake and postpartum. In addition, it is important to complete a mental health history on intake to identify women who are either at risk for, or experiencing, anxiety and depression. All screening programmes must be accompanied by a protocol to respond to a positive screen to ensure appropriate follow-up and treatment. SUMMARY: Identification and treatment of maternal mental health disorders has important implications for maternal and child health. Obstetric providers should screen all women using a validated screening instrument and have systems in place to ensure timely diagnosis and treatment.

Anti-coagulation complications in pregnancies with severe pulmonary arterial hypertension.

BACKGROUND: Epoprostenol, a potent vasodilator, is the treatment of choice for severe pulmonary arterial hypertension (PAH) in pregnancy. However, its inhibition of platelet aggregation increases the risk of coagulation complications with conjunctive use of anti-coagulants for thromboprophylaxis. CASES: Case 1 demonstrates a pregnancy complicated by thrombocytopenia. Case 2 describes a pregnancy with newly diagnosed PAH at 35 weeks who delivered by repeat cesarean delivery complicated by a wound hematoma. Case 3 describes a patient who delivered at 32 weeks. She required extracorporeal membrane oxygenation and a heart-lung transplant. Her care was further complicated by severe thrombocytopenia with postpartum hemorrhage refractory to usual conservative measures. CONCLUSIONS: This case series describes three patients with severe PAH in pregnancy and the range of different complications that arose from anticoagulation in the setting of epoprostenol.

Pre-gestational versus gestational diabetes: a population based study on clinical and demographic differences.

AIMS: To assess the clinical and demographic differences in patients with pre-gestational diabetes mellitus (PGDM) compared to those with gestational diabetes (GDM). METHODS: Using the 2001-2007 California Health Discharge Database, we identified 22,331 cases of PGDM and 147,097 cases of GDM via ICD-9-CM codes after excluding cases which were missing race or age data or with extremes of age. Data analyzed included demographics, pre-existing medical conditions, antepartum complications, and intrapartum complications. Logistic regression was used to adjust for potential confounders. RESULTS: Both PGDM and GDM incidences increased during the study period. Advancing age was associated with increased prevalence of both diseases. Although Asians were found to have the highest prevalence of GDM, they, along with Caucasians, were found have the lowest prevalence of PGDM. Conditions with increased frequency in PGDM versus GDM included chronic hypertension, renal disease, thyroid dysfunction, fetal CNS malformation, fetal demise, pyelonephritis, and eclampsia. Subjects with PGDM were more likely than those with GDM to have a shoulder dystocia, failed induction of labor, or undergo cesarean delivery. CONCLUSIONS: We have demonstrated clinical morbidities and demographic factors which differ in patients with PGDM compared to patients with GDM. Our findings suggest PGDM to be associated with significantly higher morbidity when compared to GDM. Our findings also suggest that races with the highest tendency for GDM during pregnancy may not necessarily have the highest tendency for PGDM outside of pregnancy.