Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Protective Mechanisms in Preeclampsia.

Depression and preeclampsia share risk factors and are bi-directionally associated with increased risk for each other. Despite epidemiological evidence linking selective serotonin reuptake inhibitors (SSRIs) in pregnancy to preeclampsia, serotonin (5-HT) and vasopressin (AVP) secretion mechanisms suggest that SSRIs may attenuate preeclampsia risk. However, there is a need to clarify the relationship between SSRIs and preeclampsia in humans to determine therapeutic potential. This retrospective cohort study included clinical data from 9558 SSRI-untreated and 9046 SSRI-treated pregnancies. In a subcohort of 233 pregnancies, early pregnancy (< 20 weeks) maternal plasma copeptin, an inert and stable AVP prosegment secreted 1:1 with AVP, was measured by enzyme-linked immunosorbent assay. Diagnoses and depression symptoms (Patient Health Questionnaire-9 [PHQ-9]) were identified via medical records review. Descriptive, univariate, and multivariate regression analyses were conducted (α = 0.05). SSRI use was associated with decreased preeclampsia after controlling for clinical confounders (depression severity, chronic hypertension, diabetes, body mass index, age) (OR = 0.9 [0.7-1.0], p = 0.05). Moderate-to-severe depression symptoms were associated with significantly higher copeptin secretion than mild-to-no depression symptoms (240 ± 29 vs. 142 ± 10 ng/mL, p < 0.001). SSRIs significantly attenuated first trimester plasma copeptin (78 ± 22 users vs. 240 ± 29 ng/ml non-users, p < 0.001). In preeclampsia, SSRI treatment was associated with significantly lower copeptin levels (657 ± 164 vs. 175 ± 134 ng/mL, p = 0.04). Interaction between SSRI treatment and preeclampsia was also significant (p = 0.04). SSRIs may modulate preeclampsia risk and mechanisms, although further studies are needed to investigate the relationships between 5-HT and AVP in depression and preeclampsia.

Barriers and solutions to developing and maintaining research networks during a pandemic: An example from the iELEVATE perinatal network.

Introduction: To improve maternal health outcomes, increased diversity is needed among pregnant people in research studies and community surveillance. To expand the pool, we sought to develop a network encompassing academic and community obstetrics clinics. Typical challenges in developing a network include site identification, contracting, onboarding sites, staff engagement, participant recruitment, funding, and institutional review board approvals. While not insurmountable, these challenges became magnified as we built a research network during a global pandemic. Our objective is to describe the framework utilized to resolve pandemic-related issues. Methods: We developed a framework for site-specific adaptation of the generalized study protocol. Twice monthly video meetings were held between the lead academic sites to identify local challenges and to generate ideas for solutions. We identified site and participant recruitment challenges and then implemented solutions tailored to the local workflow. These solutions included the use of an electronic consent and videoconferences with local clinic leadership and staff. The processes for network development and maintenance changed to address issues related to the COVID-19 pandemic. However, aspects of the sample processing/storage and data collection elements were held constant between sites. Results: Adapting our consenting approach enabled maintaining study enrollment during the pandemic. The pandemic amplified issues related to contracting, onboarding, and IRB approval. Maintaining continuity in sample management and clinical data collection allowed for pooling of information between sites. Conclusions: Adaptability is key to maintaining network sites. Rapidly changing guidelines for beginning and continuing research during the pandemic required frequent intra- and inter-institutional communication to navigate.

Postpartum ambulatory and home blood pressure monitoring in women with history of preeclampsia: Diagnostic agreement and detection of masked hypertension.

Women with a history of preeclampsia (hxPE) are at a four-fold higher risk for chronic hypertension after pregnancy compared with healthy pregnancy, but 'masked' hypertension cases are missed by clinical assessment alone. Twenty-four hour ambulatory blood pressure monitoring (ABPM) is the reference-standard for confirmation of hypertension diagnoses or detection of masked hypertension outside of clinical settings, whereas home blood pressure monitoring (HBPM) may represent a well-tolerated and practical alternative to ABPM in the postpartum period. The objectives of this study were to 1) assess concordance between ABPM and HBPM postpartum in women with a hxPE compared with healthy pregnancy controls and 2) evaluate HBPM in the detection of masked postpartum hypertension. Young women with a hxPE (N = 26) and controls (N = 36) underwent in-office, 24-h ABPM and 7-day HBPM 1-4 years postpartum. Chronic hypertension was more prevalent among women with a hxPE by all three blood pressure measures, but the prevalence of masked postpartum hypertension did not differ (36% vs 37%, P = 0.97). HBPM showed excellent agreement with ABPM (systolic: r = 0.78, intraclass coefficient [ICC] = 0.83; diastolic: r = 0.82, ICC = 0.88) and moderate concordance in classification of hypertension (κ = 0.54, P < 0.001). HBPM identified 21% of masked postpartum hypertension cases without false-positive cases, and HBPM measures among those with normotensive in-office readings could detect ABPM-defined masked hypertension (area under the curve [AUC] = 0.88 ± 0.06, P < 0.0001). The findings of the present study indicate that HBPM may be a useful screening modality prior or complementary to ABPM in the detection and management of postpartum hypertension.

Umbilical Cord Blood Leptin and IL-6 in the Presence of Maternal Diabetes or Chorioamnionitis.

Diabetes during pregnancy is associated with elevated maternal insulin, leptin and IL-6. Within the placenta, IL-6 can further stimulate leptin production. Despite structural similarities and shared roles in inflammation, leptin and IL-6 have contrasting effects on neurodevelopment, and the relative importance of maternal diabetes or chorioamnionitis on fetal hormone exposure has not been defined. We hypothesized that there would be a positive correlation between IL-6 and leptin with progressively increased levels in pregnancies complicated by maternal diabetes and chorioamnionitis. To test this hypothesis, cord blood samples were obtained from 104 term infants, including 47 exposed to maternal diabetes. Leptin, insulin, and IL-6 were quantified by multiplex assay. Factors independently associated with hormone levels were identified by univariate and multivariate linear regression. Unlike IL-6, leptin and insulin were significantly increased by maternal diabetes. Maternal BMI and birth weight were independent predictors of leptin and insulin with birth weight the strongest predictor of leptin. Clinically diagnosed chorioamnionitis and neonatal sepsis were associated with increased IL-6 but not leptin. Among appropriate for gestational age infants without sepsis, IL-6 and leptin were strongly correlated (R=0.6, P<0.001). In summary, maternal diabetes and birth weight are associated with leptin while chorioamnionitis is associated with IL-6. The constraint of the positive association between leptin and IL-6 to infants without sepsis suggests that the term infant and placenta may have a limited capacity to increase cord blood levels of the neuroprotective hormone leptin in the presence of increased cord blood levels of the potential neurotoxin IL-6.

Effect of positioning on blood pressure measurement in pregnancy.

Blood pressure is the key vital sign to detecting hypertensive disorders in pregnancy. The importance of taking blood pressure properly was recently underscored by the publication of updated ACC/AHA guidelines for measuring blood pressure in patients. However, the recommended position of seating with arms and back supported is not always feasible to achieve clinically, especially for inpatient women who are pregnant. Therefore, it is clinically important to understand the effects of alternative patient positioning on blood pressure measurements. We conducted a review of studies which considered patient position on the effect of blood pressure in pregnancy. This review demonstrates that clinically significant differences may occur based on patient positioning. Despite the small number of primary studies that include pregnant women, notable reductions in blood pressure measurements have been observed in the left lateral recumbent position, a common position during labor or during monitoring, in comparison to measurements taken in the supported seated position. Ultimately, these differences could affect the clinical management of patients and care should be taken to document and consider the position in which the reading was taken.

Group B Streptococcus Screening and Treatment Adherence in Pregnancy: A Retrospective Cohort Study and Opportunities for Improvement.

Introduction: Pregnancy is a time of increased healthcare screening, and past adherence to evolving guidelines informs best practices. Although studies of Group B Streptococcus guideline adherence have focused primarily on treatment of Group B Streptococcus carriers, this study broadly evaluated long-term adherence to both Group B Streptococcus screening and treatment guidelines. Adherence was evaluated across provider types (obstetrics and gynecology, certified nurse midwives, and family medicine). Methods: We conducted a retrospective cohort study. Demographic and clinical information were extracted from all prenatal care and delivery patients at a single institution in a single year. Vancomycin prescriptions in pregnancy were tracked for 10 years to determine long-term adherence. Adherence was defined as no deviation from 2010 Group B Streptococcus screening and treatment guidelines. Results: Adherence occurred in 89% (1,610/1,810) of patients. Reasons for deviations from guidelines could not always be determined. There was no significant difference in maternal age, race, prenatal provider type, provider type at delivery, gestational age at delivery, delivery mode, or whether antibiotic sensitivities were performed between compliant and noncompliant groups. Significant differences in adherence were found between obstetric clinics (high-risk obstetrics clinic, maternal‒fetal medicine fellows clinic, continuity of care clinic, and faculty private clinic) (p<0.0001) and between the faculty family medicine clinic and resident family medicine clinic (p=0.001). Vancomycin prescription practice did not change significantly over the10-year period. Conclusions: High rates of adherence to Group B Streptococcus screening and treatment guidelines in pregnancy have positive implications for reducing antibiotic resistance. Given evolving guidelines, there is a need to periodically evaluate adherence and to re-educate providers about standard practices and best documentation practices.

Twenty-Four-Hour Blood Pressure Variability Is Associated With Lower Cognitive Performance in Young Women With a Recent History of Preeclampsia.

BACKGROUND: Women with a history of preeclampsia (hxPE) exhibit sustained arterial stiffness and elevated blood pressure postpartum. Aortic stiffness and 24-hour blood pressure variability (BPV) are associated with age-related cognitive decline. Although hxPE is related to altered cognitive function, the association between aortic stiffness and BPV with cognitive performance in young women with hxPE has not been investigated. The objectives of this study were to (i) test whether cognitive performance is lower in young women with hxPE and (ii) determine whether aortic stiffness and BPV are associated with cognitive performance independent of 24-hour average blood pressure. METHODS: Women with hxPE (N = 23) and healthy pregnancy controls (N = 38) were enrolled 1-3 years postpartum. Cognitive performance was assessed in domains of memory, processing speed, and executive function. Twenty-four-hour ambulatory blood pressure monitoring and carotid-femoral pulse wave velocity (cfPWV) were used to measure BPV and aortic stiffness, respectively. RESULTS: Women with hxPE had slower processing speed (-0.56 ± 0.17 vs. 0.34 ± 0.11 Z-score, P < 0.001) and lower executive function (-0.43 ± 0.14 vs. 0.31 ± 0.10 Z-score, P = 0.004) compared with controls independent of education, whereas memory did not differ. BPV and cfPWV (adjusted for blood pressure) did not differ between women with hxPE and controls. Greater diastolic BPV was associated with lower executive function independent of 24-hour average blood pressure and education in women with hxPE (r = -0.48, P = 0.03) but not controls (r = 0.15, P = 0.38). CONCLUSIONS: Select cognitive functions are reduced postpartum in young women with a recent hxPE and linked with elevated 24-hour diastolic BPV.

Development and Pilot of a REDCap Electronic Informed Consent Form for Research: An Example from the ROPE Study.

A study that describes the development of an electronic informed consent, using the REDCap platform, and the results of a pilot study to assess participants' understanding and acceptance of that electronic informed consent for use in a research study.

Single-arm, neoadjuvant, phase II trial of pertuzumab and trastuzumab administered concomitantly with weekly paclitaxel followed by 5-fluoruracil, epirubicin, and cyclophosphamide (FEC) for stage I-III HER2-positive breast cancer.

PURPOSE: The purpose of this two-cohort Phase II trial was to estimate the pathologic complete response (pCR: ypT0/is ypN0) rate when trastuzumab plus pertuzumab are administered concurrently during both the taxane and anthracycline phases of paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide (FEC) neoadjuvant chemotherapy. METHODS: The pCR rates were assessed separately in hormone receptor (HR) positive and negative cases following Simon's two-stage design, aiming to detect a 20% absolute improvement in pCR rates from 50 to 70 and 70 to 90% in the HR-positive and HR-`negative cohorts, respectively. RESULTS: The HR-negative cohort completed full accrual of 26 patients; pCR rate was 80% (95% CI 60-91%). The HR+ cohort was closed early after 24 patients due to lower than expected pCR rate of 26% (95% CI 13-46%) at interim analysis. Overall, 44% of patients (n = 22/50) experienced grade 3/4 adverse events. The most common were neutropenia (n = 10) and diarrhea (n = 7). There was no symptomatic heart failure, but 28% (n = 14) had ≥ 10% asymptomatic decrease in LVEF; in one patient, LVEF decreased to < 50%. Cardiac functions returned to baseline by the next assessment in 57% (8/14) of cases. CONCLUSIONS: Eighty percent of HR-negative, HER2-positive breast cancers achieve pCR with paclitaxel/FEC neoadjuvant chemotherapy administered concomitantly with pertuzumab and trastuzumab. These results are similar to pCR rates seen in trials using HER2-targeted therapy during the taxane phase only of sequential taxane-anthracycline regimens and suggest that we have reached a therapeutic plateau with HER2-targeted therapies combined with chemotherapy in the neoadjuvant setting.

A closer look at the recommended criteria for disclosing genetic results: perspectives of medical genetic specialists, genomic researchers, and institutional review board chairs.

Next generation sequencing offers benefit of improved health through knowledge, but comes with challenges, such as inevitable incidental findings (IFs). The applicability of recommended criteria for disclosure of individual results when applied to disclosure of IFs is not well known. The purpose of this study was to examine how medical genetic specialists, genomic researchers, and Institutional Review Board (IRB) chairs perceive the importance of recommended criteria when applied to genetic/genomic IFs. We conducted telephone interviews with medical genetic specialists (genetic counselors, genetic nurses, medical geneticists, laboratory professionals), genomic researchers, and IRB chairs (N = 103). Respondents rated and discussed the importance of nine recommended criteria regarding disclosure of genetic/genomic IFs. Stakeholders agreed the most important criteria for disclosure were: (1) the IF points to a life-threatening condition; (2) there is a treatment; (3) individuals indicate in writing they wanted to be informed of IFs. Criteria rated less important were: analytic validity, high penetrance, association with a young age of onset and relative risk more than 2.0. Respondents indicated that some technical criteria were confusing, and in need of context. Our findings suggest that development of guidelines regarding management of IF include multiple stakeholders' perspectives and be based on a common language.

Understanding Goals of Care Statements and Preferences among Patients and Their Surrogates in the Medical ICU.

BACKGROUND: Treatment decisions should be based on patients' goals of care to provide an ethical, patient-centered framework for decision-making. OBJECTIVES: The purpose of this study is to improve our understanding about how patients' and surrogates' goals of care are communicated and interpreted in an MICU. METHODS: One hundred patients admitted to an MICU, or their surrogates, responded to an open-ended question about goals of care for their hospitalization followed by a closed-ended question regarding their most important goal of care. Investigators interpreted participants' open-ended responses and compared these interpretations with participants' closed-ended, most-important-goal selections. RESULTS: Investigators' interpretations of participants' open-ended goals of care responses matched participants' closed-ended most important goal of care in only 28 of 100 cases. However, there was good inter-rater reliability between investigators in their interpretation of participants' open-ended responses, with agreement in 78 of 100 cases. CONCLUSIONS: Clinicians should be cautious in interpreting patients' or surrogates' responses to open-ended questions about goals of care. A shared understanding of goals of care may be facilitated by alternating open-ended and closed-ended questions to clarify patients' or surrogates' responses.

A CTSA-sponsored program for clinical research coordination: networking, education, and mentoring.

Upon receipt of the National Institutes of Health Clinical and Translational Science Award, the University of Iowa's Institute for Clinical and Translational Science committed to develop an infrastructure for research professionals. Three goals were established: (1) identification of research professionals within the University of Iowa, (2) development of an educational series, including orientation and continuing education, and (3) development of a mentoring system. The purpose of this paper is to describe the process of development, initiation, and outcomes of a successful networking, educational, and mentoring system crafted for research professionals at the University of Iowa.

Pregnant women have increased incidence of IgE autoantibodies reactive with the skin and placental antigen BP180 (type XVII collagen).

BP180 (type XVII collagen) is a transmembrane protein expressed in a variety of cell types. It is also the target of autoantibodies in cutaneous autoimmune disease including bullous pemphigoid and pemphigoid gestationis, a disease unique to pregnancy. The purpose of this study was to determine the prevalence and specificity of cutaneous autoantibodies in a cohort of pregnant women. De-identified sera were collected from pregnant women (n=299) and from non-pregnant controls (n=134). Sera were analyzed by ELISA for the presence of IgG and IgE autoantibodies directed against several cutaneous autoantigens. IgE antibodies against the NC16A domain of BP180 were detected in 7.7% of pregnant women, compared to 2.2% of healthy controls (p=0.01). No increase in total or cutaneous autoantigen specific IgG was seen. Total serum IgE was within the normal range. Full-length BP180 was detected by western immunoblot in epidermal, keratinocyte, placental and cytotrophoblast (CTB) cell lysates. Furthermore, flow cytometry and indirect immunofluorescence confirmed the expression of BP180 on the surface of cultured CTBs. Finally, it was demonstrated that IgE antibodies in the pregnancy sera labeled not only cultured CTBs, but also the placental amnion and cutaneous basement membrane zone using indirect immunofluorescence. We conclude that some pregnant women develop antibodies specific for BP180, and that these autoantibodies are capable of binding both CTB and the placental amnion, potentially affecting placental function.