Successful management of maternal anti-PP1Pk alloimmunization in pregnancy with therapeutic plasma exchange and intravenous immunoglobulin.

Anti-PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti-PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti-PP1PK alloimmunization in a 23-year-old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti-PP1Pk titers. Twice-weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery-peak systolic velocities (MCA-PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen-negative, ABO-compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA-PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice-weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti-PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti-PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan.

Severe Maternal Morbidity in Twins.

OBJECTIVE: While twin gestations are at increased risk of severe maternal morbidity (SMM), there is limited information about timing and causes of SMM in twins. Furthermore, existing data rely on screening definitions of SMM because a gold standard approach requires chart review. We sought to determine the timing and cause of SMM in twins using a gold standard definition outlined by the American College of Obstetricians and Gynecologists (ACOG). STUDY DESIGN: We used a perinatal database to identify all twin deliveries from 1998 to 2013 at a single academic medical center (n = 2,367). Deliveries were classified as screen positive for SMM if they met any of the following criteria: (1) one of the Centers for Disease Control and Prevention (CDC) International Classification of Diseases Ninth Revision diagnosis and procedure codes for SMM; (2) a prolonged postpartum length of stay (>3 standard deviations beyond mean length of stay by mode of delivery); or (3) maternal intensive care unit admission. We identified true cases of SMM through medical record review of all screen-positive deliveries using the definition of SMM outlined in the ACOG Obstetric Care Consensus. We also determined cause and timing of SMM. RESULTS: A total of 165 (7%) of twin deliveries screened positive for SMM. After chart review of all screen-positive cases, 2.4% (n = 56) were classified as a true case of SMM using the ACOG definition for a positive predictive value of 34%. The majority of SMM occurred postpartum (65%). Hemorrhage was the most common cause of SMM, followed by hypertensive and pulmonary etiologies. CONCLUSION: Commonly used approaches to screen for SMM perform poorly in twins. This has important implications for quality initiatives and epidemiologic studies that rely on screening definitions of maternal morbidity. Our study demonstrates that the immediate postpartum period is a critical time for maternal health among women with twin pregnancies. KEY POINTS: · Screening approaches for SMM have low positive predictive value in twins.. · Hemorrhage, hypertensive, and pulmonary complications were the most common morbidities.. · SMM was most common postpartum..

Racial Differences in Postpartum Blood Pressure Trajectories Among Women After a Hypertensive Disorder of Pregnancy.

Importance: Maternal morbidity and mortality are increasing in the United States, most of which occur post partum, with significant racial disparities, particularly associated with hypertensive disorders of pregnancy. Blood pressure trajectory after a hypertensive disorder of pregnancy has not been previously described. Objectives: To describe the blood pressure trajectory in the first 6 weeks post partum after a hypertensive disorder of pregnancy and to evaluate whether blood pressure trajectories differ by self-reported race. Design, Setting, and Participants: This prospective cohort study included deliveries between January 1, 2018, and December 31, 2019. Women with a clinical diagnosis of a hypertensive disorder of pregnancy were enrolled in a postpartum remote blood pressure monitoring program at the time of delivery and were followed up for 6 weeks. Statistical analysis was performed from April 6 to 17, 2020. Main Outcomes and Measures: Mixed-effects regression models were used to display blood pressure trajectories in the first 6 weeks post partum. Results: A total of 1077 women were included (mean [SD] age, 30.2 [5.6] years; 804 of 1017 White [79.1%] and 213 of 1017 Black [20.9%]). Systolic and diastolic blood pressures were found to decrease rapidly in the first 3 weeks post partum, with subsequent stabilization (at 6 days post partum: mean [SD] peak systolic blood pressure, 146 [13] mm Hg; mean [SD] peak diastolic blood pressure, 95 [10] mm Hg; and at 3 weeks post partum: mean [SD] peak systolic blood pressure, 130 [12] mm Hg; mean [SD] peak diastolic blood pressure, 85 [9] mm Hg). A significant difference was seen in blood pressure trajectory by race, with both systolic and diastolic blood pressure decreasing more slowly among Black women compared with White women (mean [SD] peak systolic blood pressure at 1 week post partum: White women, 143 [14] mm Hg vs Black women, 146 [13] mm Hg; P = .01; mean [SD] peak diastolic blood pressure at 1 week post partum: White women, 92 [9] mm Hg vs Black women, 94 [9] mm Hg; P = .02; and mean [SD] peak systolic blood pressure at 3 weeks post partum: White women, 129 [11] mm Hg vs Black women, 136 [15] mm Hg; P < .001; mean [SD] peak diastolic blood pressure at 3 weeks post partum: White women, 84 [8] mm Hg vs Black women, 91 [13] mm Hg; P < .001). At the conclusion of the program, 126 of 185 Black women (68.1%) compared with 393 of 764 White women (51.4%) met the criteria for stage 1 or stage 2 hypertension (P < .001). Conclusions and Relevance: This study found that, in the postpartum period, blood pressure decreased rapidly in the first 3 weeks and subsequently stabilized. The study also found that, compared with White women, Black women had a less rapid decrease in blood pressure, resulting in higher blood pressure by the end of a 6-week program. Given the number of women with persistent hypertension at the conclusion of the program, these findings also appear to support the importance of ongoing postpartum care beyond the first 6 weeks after delivery.

A Postpartum Remote Hypertension Monitoring Protocol Implemented at the Hospital Level.

OBJECTIVE: To evaluate the feasibility, acceptability, and compliance of a remote blood pressure monitoring protocol implemented as a quality improvement measure at the hospital level for management of hypertension in postpartum women after hospital discharge. METHODS: This is an ongoing quality improvement project that included women admitted to the postpartum unit of a single tertiary care hospital. We designed nursing call center-driven blood pressure management and treatment algorithms, which were initiated after hospital discharge until 6 weeks postpartum. Women are eligible to participate if they have a diagnosis of chronic hypertension, superimposed preeclampsia, gestational hypertension, preeclampsia, or postpartum hypertension and have access to a text messaging-enabled smartphone device. After identification by an obstetric care provider, women are enrolled into the program, which is automatically indicated in the electronic medical record. Maternal, obstetric, and sociodemographic data were obtained from the electronic medical record. RESULTS: Between February 2018 and January 2019, we enrolled 499 patients. Here we report on the first 409 enrolled patients. Participants include 168 (41%) with gestational hypertension, 179 (44%) with preeclampsia with no history of chronic hypertension, 49 (12%) with chronic hypertension with superimposed preeclampsia, and 13 (3%) with postpartum preeclampsia. One hundred seventy-one (42%) participants had antihypertensives initiated or titrated through the program. Three hundred forty women (83%) continued the program beyond 3 weeks postpartum, and 360 (88%) attended an in-person 6-week postpartum visit. Two hundred thirty-five out of 250 women who completed a postprogram survey (94%) reported satisfaction with the program. CONCLUSION: In this study, we detail results from an ongoing remote blood pressure monitoring program. We demonstrate high compliance, retention, and patient satisfaction with the program. This is a feasible, scalable remote monitoring program connected to the electronic medical record.

Maternal Mirror Syndrome Masquerading as Congestive Heart Failure: A Case Report.

Mirror syndrome is a rare pregnancy complication, life-threatening to mother and fetus. Increasing survival rates of congenital heart disease into reproductive age mean that complications like Mirror syndrome in this population may be more challenging to diagnose, given overlapping signs of edema in cases of heart failure exacerbation. We report a case of a pregnant woman with a history of unspecified congenital heart disease, presenting with swelling and distension, with diagnostic findings not consistent with preeclampsia. Her course was complicated by dyspnea, oliguria, and fetal hydrops. A cesarean delivery under neuraxial anesthesia was performed. We review the clinical manifestations of Mirror syndrome and discuss anesthetic and obstetric management considerations for this condition.

The expression level of C19MC miRNAs in early pregnancy and in response to viral infection.

INTRODUCTION: We have previously shown that miRNAs produced from the Chromosome 19 MiRNA Cluster (C19MC), which are expressed almost exclusively in primate trophoblasts and are released into the maternal circulation, reduce viral replication in non-placental cells and can modulate migratory behavior of extravillous trophoblast. We sought to define the expression pattern of C19MC miRNA in early pregnancy and in response to viral infection in vitro and in vivo. METHODS: We prospectively followed women undergoing in vitro fertilization (IVF) and determined their blood level of C19MC miRNA using RT-qPCR. To examine the effect of viral exposure on C19MC miRNAs expression, we used three systems: (1) a transgenic mouse overexpressing the C19MC cluster and exposed to Togaviridae during pregnancy, (2) cultured primary human trophoblasts exposed to Vesicular Stomatitis Virus in vitro, and (3) amniotic fluid from women exposed to cytomegalovirus during pregnancy. RESULTS: In 27 IVF pregnancies, C19MC miRNAs were detected as early as 2 weeks after implantation, and their levels increased thereafter. There was no change in C19MC miRNA expression levels in the mouse placenta in response to viral exposure. Similarly, Vesicular Stomatitis Virus infection of primary human trophoblast did not selectively increase C19MC miRNA expression. C19MC miRNA expression in the amniotic fluid was not affected by vertical transmission of cytomegalovirus. DISCUSSION: The expression of C19MC miRNAs in maternal circulation very early in pregnancy suggests a role in the establishment of the maternal-fetal interface. The levels of C19MC miRNA are not influenced by diverse types of viral infection.

Pharmacokinetics of cefazolin prophylaxis in obese gravidae at time of cesarean delivery.

OBJECTIVE: The objective of the study was to compare the pharmacokinetics of 2 g and 3 g doses of cefazolin when used for perioperative prophylaxis in obese gravidae undergoing cesarean delivery. STUDY DESIGN: We performed a double-blinded, randomized controlled trial from August 2013 to April 2014. Twenty-six obese women were randomized to receive either 2 or 3 g intravenous cefazolin within 30 minutes of a skin incision. Serial maternal plasma samples were obtained at specific time points up to 8 hours after drug administration. Umbilical cord blood was obtained after placental delivery. Maternal adipose samples were obtained prior to fascial entry, after closure of the hysterotomy, and subsequent to fascial closure. Pharmacokinetic parameters were determined via noncompartmental analysis. RESULTS: The median area under the plasma concentration vs time curve was significantly greater in the 3 g group than in the 2 g group (27204 µg/mL per minute vs 14058 µg/mL per minute; P = .001). Maternal plasma concentrations had an impact by body mass index. For every 1 kg/m(2) increase in body mass index at the time of the cesarean delivery, there was an associated 13.77 µg/mL lower plasma concentration of cefazolin across all time points (P = .01). By the completion of cesarean delivery, cefazolin concentrations in maternal adipose were consistently above the minimal inhibitory concentration for both Gram-positive and Gram-negative bacteria with both the 2 g and 3 g doses. The median umbilical cord blood concentrations were significantly higher in the 3 g vs the 2 g group (34.5 µg/mL and 21.4 µg/mL; P = .003). CONCLUSION: Cefazolin concentrations in maternal adipose both at time of hysterotomy closure and fascial closure were above the minimal inhibitory concentration for both Gram-positive and Gram-negative bacteria when either 2 g or 3 g cefazolin was administered as perioperative surgical prophylaxis. Maternal cefazolin concentrations in plasma and maternal adipose tissue are related to both dose and body mass index.

Predictors of palliative care consultation on an inpatient gynecologic oncology service: are we following ASCO recommendations?

OBJECTIVE: Determine predictors of inpatient palliative care (PC) consultation and characterize PC referral patterns with respect to recommendations from the American Society of Clinical Oncology (ASCO). METHODS: Women with a gynecologic malignancy admitted to the gynecologic oncology service 3/2012-8/2012 were identified. Demographic information, disease and treatment details and date of death were abstracted from medical records. Student's t-test, Fischer's exact test or χ(2)-test was used for univariate analysis. Binomial logistic regression was used for multivariate analysis. RESULTS: Of 340 patients analyzed, 82 (24%) had PC consultation. Univariate predictors of PC consultation included race, cancer type and stage, recurrent disease, admission frequency, admission for symptom management or malignant bowel obstruction (MBO), discharge to skilled nursing facility (SNF) and number of lines of chemotherapy. On multivariate analysis, significant predictors of PC consultation were recurrent disease (OR 2.4, 95% CI 1.1-5.3), number of admissions (≥ 3, OR 10.9, 95% CI 3.4-34.9), admission for symptom management (OR 19.4, 95% CI 7.5-50.1), discharge to SNF (OR 5, 95% CI 1.9-13.5) and death within 6 months (OR 16.5, 95% CI 6.9-39.5). Of patients considered to meet ASCO guidelines, 53% (63/118) had PC referral. Of patients referred to PC, 51.2% (42/82) died within 6 months of last admission. CONCLUSIONS: Patients referred to inpatient PC have high disease and symptom burden and poor prognosis. High-risk patients, including those meeting ASCO recommendations, are not captured comprehensively. We continue to use PC referrals primarily for patients near the end of life, rather than utilizing early integration as recommended by ASCO.

Recurrent breast carcinoma presenting as postmenopausal vaginal bleeding: A case report.

•We discuss the recurrence of breast carcinoma presenting as postmenopausal vaginal bleeding in a patient on Tamoxifen therapy.•Case report illustrates widespread genital tract manifestation of recurrent disease at time of presentation and rapid disease progression.•Discusses the importance of maintaining broad differential in diagnosis of postmenopausal vaginal bleeding.

Perceived comfort level of medical students and residents in handling clinical ethics issues.

BACKGROUND: Studies have shown that medical students and residents believe that their ethics preparation has been inadequate for handling ethical conflicts. The objective of this study was to determine the self-perceived comfort level of medical students and residents in confronting clinical ethics issues. METHODS: Clinical medical students and residents at the University of Maryland School of Medicine completed a web-based survey between September 2009 and February 2010. The survey consisted of a demographic section, questions regarding the respondents' sense of comfort in handling a variety of clinical ethics issues, and a set of knowledge-type questions in ethics. RESULTS: Survey respondents included 129 medical students (response rate of 40.7%) and 207 residents (response rate of 52.7%). There were only a few clinical ethics issues with which more than 70% of the respondents felt comfortable in addressing. Only a slight majority (60.8%) felt prepared, in general, to handle clinical situations involving ethics issues, and only 44.1% and 53.2% agreed that medical school and residency training, respectively, helped prepare them to handle such issues. Prior ethics training was not associated with these responses, but there was an association between the level of training (medical students vs residents) and the comfort level with many of the clinical ethics issues. CONCLUSIONS: Medical educators should include ethics educational methods within the context of real-time exposure to medical ethics dilemmas experienced by physicians-in-training.

Androgen deficiency: association with increased anxiety and depression symptom severity in anorexia nervosa.

OBJECTIVE: Anorexia nervosa is associated with a high prevalence of psychiatric comorbidities, including anxiety and depression, and with endocrine dysfunction, including relative androgen deficiency compared with healthy young women. Because androgens are known to affect mood and behavior, we hypothesized that low endogenous androgen production in anorexia nervosa would predict anxiety and depression severity. METHOD: Serum androgen levels and severity of depression (Hamilton Rating Scale for Depression) and anxiety (Hamilton Rating Scale for Anxiety) were measured in 43 community-dwelling women with DSM-IV-defined anorexia nervosa from May 2004 to July 2006. RESULTS: Strong inverse associations were observed between both total and free testosterone and anxiety and depression severity, independent of weight. Free testosterone was also inversely associated with 4 eating-disordered thinking and behavior subscales of the Eating Disorder Inventory 2 (EDI-2). Mean free testosterone blood levels were lower in women with clinically significant anxiety and in women with clinically significant depression, compared with those without. In stepwise regression models, free testosterone was an important predictor of anxiety and depression severity. EDI-2 ineffectiveness, perfectionism, interpersonal distress, and social insecurity scores were also inversely associated with androgen levels, independent of weight. CONCLUSIONS: Our data suggest that low androgen levels may contribute to anxiety, depression, and eating-disordered thinking and behavior in women with anorexia nervosa and form the basis for future studies to investigate the effectiveness of androgen replacement therapy. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00089843.

Comorbid anxiety in phenotypes of pediatric bipolar disorder.

OBJECTIVE: There has been limited research on anxiety in pediatric bipolar disorder (BPD). Adult BPD studies suggest comorbid anxiety disorders are common and impact treatment outcome. We explored the association of comorbid anxiety with two phenotypes of pediatric BPD. METHODS: We studied two groups of children. The first group (BPD; N = 31) represents the "narrow phenotype" of pediatric BPD, meeting stringent DSM-IV criteria for mania, including duration and elevated/expansive mood. The second group (ED; N = 32) exhibited chronic, non-episodic irritability without elation or grandiosity ("broad phenotype"). RESULTS: Both samples demonstrate high prevalence of anxiety (BPD 77.4%; ED 46.9%). In the BPD sample, anxiety predates BPD onset, and those with comorbid anxiety have earlier age of onset of BPD than those without. Children with BPD plus anxiety have more hospitalizations than those without anxiety. ED subjects with and without comorbid anxiety did not differ with respect to onset of ED symptoms or number of hospitalizations. CONCLUSIONS: Narrow and broad phenotype BPD children have high rates of comorbid anxiety, although only in the narrow phenotype group is comorbid anxiety associated with greater functional impairment BPD plus comorbid anxiety may represent a particularly severe phenotype of pediatric BPD.