Anti-RhD antibody therapy modulates human natural killer cell function.

Anti-RhD antibodies are widely used in clinical practice to prevent immunization against RhD, principally in hemolytic disease of the fetus and newborn. Intriguingly, this disease is induced by production of the very same antibodies when an RhD negative woman is pregnant with an RhD positive fetus. Despite over five decades of use, the mechanism of this treatment is, surprisingly, still unclear. Here we show that anti-RhD antibodies induce human natural killer (NK) cell degranulation. Mechanistically, we demonstrate that NK cell degranulation is mediated by binding of the Fc segment of anti-RhD antibodies to CD16, the main Fcγ receptor expressed on NK cells. We found that this CD16 activation is dependent upon glycosylation of the anti-RhD antibodies. Furthermore, we show that anti-RhD antibodies induce NK cell degranulation in vivo in patients who receive this treatment prophylactically. Finally, we demonstrate that the anti-RhD drug KamRho enhances the killing of dendritic cells. We suggest that this killing leads to reduced activation of adaptive immunity and may therefore affect the production of anti-RhD antibodies.

Neonatal subgaleal hemorrhage unrelated to assisted vaginal delivery: clinical course and outcomes.

PURPOSE: The purpose of the study was to evaluate the occurrence of subgaleal hemorrhage (SGH) following non-assisted vaginal delivery (normal vaginal delivery or cesarean delivery), and to characterize associated factors, clinical course, and outcomes, compared to attempted assisted vaginal delivery (AVD)-associated SGH METHODS: A retrospective cohort study was conducted. All cases of SGH encountered following delivery of a singleton neonate at Hadassah, Hebrew University Medical Center during 2011-2018 were included. Maternal, fetal, intrapartum, and neonatal characteristics and outcomes were compared between AVD-related and non-AVD-related SGH groups. RESULTS: The overall incidence of SGH was 4.5/1000 (369/82,256) singleton deliveries. The incidences of AVD- and non-AVD-related SGH were 44.6/1000 (350/7852) and 0.3/1000 (19/74,404) singleton deliveries, respectively. Ten (53%) of the 19 non-AVD-related SGH were diagnosed after vaginal delivery and 9 (47%) after an urgent cesarean section. SGH severity was mild, moderate, and severe in 68%, 16%, and 16% of the cases, respectively. SGH severity did not differ between the attempted AVD group and the non-AVD-related SGH group. A higher proportion of neonates with non-AVD SGH required phototherapy treatment than did those diagnosed with AVD-related SGH (56% vs. 24%, P = 0.003). Other neonatal outcomes, including Apgar scores, maximal bilirubin level, length of stay, and the rate of composite adverse outcomes, did not differ between the groups. CONCLUSIONS: SGH, although rare, may be diagnosed after unassisted vaginal or cesarean delivery in the absence of an AVD attempt. We advocate continuing education for all medical staff who participate in peripartum and neonatal care, regarding the possible occurrence of non-AVD-related SGH.

Immune-Mediated Fetal Complete Atrioventricular Block: Can Dexamethasone Therapy Revert the Process?

BACKGROUND: Fetal complete atrioventricular block (CAVB) is usually autoimmune mediated. The risk of developing CAVB is 2% to 3% in anti-Ro/SS-A seropositive pregnancies and it increases 10 times after previous CAVB in siblings. Despite being a rare complication, CAVB carries a 20% mortality rate and substantial morbidity, as about 65% of newborns will eventually need life-long pacing. Once found, fetal CAVB is almost always irreversible, despite aggressive immunotherapy. This poor outcome prompted some research groups to address this situation. All groups followed anti-Ro/SS-A seropositive pregnancies on a weekly basis during the second trimester of pregnancy and tried to detect first degree atrioventricular block (AVB) using accurate echocardiographic tools, assuming they may characterize the initiation of the immune damage to the A-V conduction system, at which point the process might still be reversible. Some of the groups treated fetuses with first degree AVB with maternal oral fluorinated steroids. We summarized the results of all groups, including our group. We describe a case of a fetus that developed CAVB 6 days after normal sinus rhythm (NSR), who under aggressive dexamethasone therapy gradually reverted to NSR. This fetus had a previous sibling with CAVB. We assumed the immune damage to the conduction system in this small group of fetuses with a previous CAVB sibling may have occurred more quickly than usual. We therefore recommend a twice-weekly follow-up with these fetuses.

Risk factors associated with subgaleal hemorrhage in neonates exposed to vacuum extraction.

INTRODUCTION: Subgaleal hemorrhage (SGH) is a life-threatening neonatal condition that is strongly associated with vacuum assisted delivery (VAD). The factors associated with the development of SGH following VAD are not well-established. We aimed to evaluate the factors associated with the development of SGH following attempted VAD. MATERIAL AND METHODS: A retrospective case-control study of women who delivered at a tertiary university-affiliated medical center in Jerusalem, Israel, during 2009-2018. Cases comprised all parturients with singleton pregnancies for whom attempted VAD resulted in neonatal SGH. A control group of VAD attempts was established by matching one-to-one according to gestational age at delivery, parity and year of delivery. Fetal, intrapartum and vacuum procedure characteristics were compared between the groups. RESULTS: In all, 313 (89.5%) of the 350 attempted VAD were nulliparous. Baseline maternal and fetal characteristics were similar between the groups except for higher neonatal birthweight in the SGH group. In multivariate logistic regression analysis, only six independent risk factors were significantly associated with the development of SGH: second-stage duration (for each 30-minute increase, adjusted odds ratio [OR] 1.13; 95% confidence intervals [CI] 1.04-1.25; P = .006), presence of meconium-stained amniotic fluid (adjusted OR 2.61; 95% CI 1.52-4.48; P = .001), presence of caput succedaneum (adjusted OR 1.79; 95% CI 1.11-2.88; P = .01), duration of VAD (for each 3-minute increase, adjusted OR 2.04; 95% CI 1.72, 2.38; P < .001), number of dislodgments (adjusted OR 2.38; 95% CI 1.66-3.44; P < .001), and fetal head station (adjusted OR 3.57; 95% CI 1.42-8.33; P = .006). Receiver operating characteristic curves showed that VAD duration of ≥15 minutes had a 96.7% sensitivity and 75.0% specificity in predicting SGH formation, with an area under the curve equal to .849. CONCLUSIONS: Vacuum duration, the number of dislodgments, the duration of second stage of delivery, fetal head station, the presence of caput succedaneum and the presence of meconium were found to be independently associated with SGH formation.

Breast Implant Q Fever as a Source of In-Hospital Transmission.

Herein, we describe the first case of mammary implant infection caused by Coxiella burnetii, resulting in delayed diagnosis and treatment and an in-hospital cross-transmission of Q fever to medical personnel.

Nerve growth factor plays a role in the neurotherapeutic effect of a CD45+ pan-hematopoietic subpopulation derived from human umbilical cord blood in a traumatic brain injury model.

BACKGROUND AIMS: Human umbilical cord blood (HUCB) is an important source of stem cells for therapy of hematopoietic disorders and is a potential therapy for various neurological disorders, including traumatic brain injury (TBI). The expression of nerve growth factor (NGF) and its receptors TrkA, p75NTR and α9ß1 integrin on an HUCB CD45+ pan-hematopoietic subpopulation was investigated in the context of its neurotherapeutic potential after TBI. METHODS: NGF and its receptors were detected on CD45+ cells by reverse transcriptase polymerase chain reaction, flow cytometry analysis and confocal microscopy. CD45+ cells were stimulated by TBI brain extracts, and NGF levels were measured by enzyme-linked immunosorbent assay. TBI mice were divided into six groups for xenogeneic intravenous transplantation, 1 day post-trauma, with 1 × 106 CD45+ cells untreated or treated with the anti-NGF neutralizing antibody K252a, a TrkA antagonist; VLO5, an α9ß1 disintegrin; or negative (vehicle) and positive (NGF) controls. RESULTS: The HUCB CD45+ subpopulation constitutively expresses NGF and its receptors, mainly TrkA and p75NTR and minor levels of α9ß1. In vitro experiments provided evidence that trauma-related mediators from brain extracts of TBI mice induced release of NGF from HUCB CD45+ cell cultures. HUCB CD45+ cells induced a neurotherapeutic effect in TBI mice, abrogated by cell treatment with either anti-NGF antibody or K252a, but not VLO5. CONCLUSIONS: These findings strengthen the role of NGF and its TrkA receptor in the HUCB CD45+ subpopulation's neurotherapeutic effect. The presence of neurotrophin receptors in the HUCB CD45+ pan-hematopoietic subpopulation may explain the neuroprotective effect of cord blood in therapy of a variety of neurological disorders.

Antiphospholipid antibody profile-based outcome of purely vascular and purely obstetric antiphospholipid syndrome.

Antiphospholipid syndrome (APLS) is caused by antiphospholipid autoantibodies, and manifests with vascular and/or obstetric complications. The factors associated with initial disease presentation and course are unknown. We assessed the antibody profile associated with disease presentation and with the development of vascular and obstetric complications in women with initially vascular or initially obstetric APLS. A review of records of APLS women at childbearing age followed at one center during 2006-2015. Of 126 women, median age at diagnosis 29 [23-37] years, 62 were initially diagnosed with purely obstetric APLS and 64 with purely vascular APLS. Baseline characteristics and antibody profile did not differ according to the initial diagnosis. At a mean follow-up duration of 61 ± 23 months, 19 (30.6%) with initially obstetric disease, and 20 (31.3%) with initially vascular disease, developed vascular and obstetric complications, respectively (P = 1.0). Among those with triple positivity [lupus anticoagulant (LAC)+, anticardiolipin (ACL)+, anti beta2-glycoprotein I (AB2GPI)+], a higher proportion developed both obstetric and vascular complications, compared to those with single or double positivity (42.3 vs. 16.4%, P = 0.002). In multivariate analysis, the presence of LAC (P = 0.008), ACL IgG (P = 0.009) or AB2GPI IgG (P = 0.01) was the only independent predictor of the development of both obstetric and vascular complications. Almost one-third of women with initially vascular or initially obstetric APLS developed mixed disease. The antibody profile was the only prognostic marker for disease course. The association found between LAC, ACL IgG or AB2GPI IgG, and patient outcomes could contribute to risk stratification and individualized patient management.

Patterns of use and optimal timing of antenatal corticosteroids in twin compared with singleton pregnancies.

INTRODUCTION: Previous reports have shown that suboptimal antenatal corticosteroids administration occurs in most cases. However, as multifetal gestations were either excluded or constituted a small proportion of the participants in these studies, little is known about the patterns of use of antenatal corticosteroids in twin pregnancies. MATERIAL AND METHODS: We reviewed the records of women who received antenatal corticosteroids and delivered between 240/7 and 346/7 weeks of gestation during 2015-2017 at 2 university hospitals. Optimal antenatal corticosteroids timing was defined as delivery ≥24 hours ≤7 days from the previous antenatal corticosteroids course. RESULTS: Of 424 pregnancies, 307 (72.4%) were singleton and 117 were (27.6%) twin. For twin compared with singleton pregnancies, gestational age at initial antenatal corticosteroids administration was lower (P = 0.02), the proportion of deliveries within the optimal window of the initial antenatal corticosteroids course was lower (19.7% vs 33.2%, P = 0.001), and the proportion of women eligible for a rescue antenatal corticosteroids course was higher (58.1% vs 32.9%, P < 0.0001). However, despite similar rates of rescue antenatal corticosteroids administration (P = 0.64), the overall rate of delivery within any optimal window (either initial or rescue course) was lower in twin than singleton pregnancies (26.5% vs 42.3%, P = 0.004), and the antenatal corticosteroids-to-delivery interval was longer (median 6.9 vs 4.2 days, P = 0.0009). In multivariate analysis, optimal antenatal corticosteroids administration was negatively associated with twin pregnancy (P = 0.04) and preterm labor (P = 0.05), and positively associated with the presence of gestational hypertensive disorders (P = 0.03). CONCLUSIONS: Twin pregnancy is an independent risk factor for suboptimal antenatal corticosteroids administration. Directed efforts should be made to improve the utilization of antenatal corticosteroids in this vulnerable group of women.

Using medical specialty and selection criteria clusters to study specialty selection by Israeli medical students.

BACKGROUND: During their final year of medical school, Israeli students must consider which specialty to choose for residency. Based on the vocational counseling literature we presumed that choices are made by selecting from a cluster of related specialties while considering professional and socio-economic issues. METHODS: Questionnaires distributed to final-year medical students at two Israeli medical schools ascertained inclinations toward various medical specialties and the importance of various selection criteria. Analysis focused on seven specialties where >20% of students reported they had positive inclinations. For each such specialty, the specialty and selection criteria query were compared using unpaired two-tailed Student's t-tests to determine differences between students with positive inclinations toward the specialty with those not so inclined. These data were placed in tables, with the significant differences highlighted to facilitate visual recognition of cluster patterns. RESULTS: Completed questionnaires were obtained from 317 of 455 students. Students often had positive inclinations toward more than one specialty (specialty clusters) associated with a group of selection criteria (selection criteria clusters). For example, interest in internal medicine was clustered with interest in internal medicine subspecialties, cardiology and research. Furthermore, there was a "reciprocal" aspect to some specialty cluster patterns. For example, those interested in internal medicine had little interest in surgical specialties. Selection criteria clusters revealed occupational interests and socio-environmental factors associated with the specialty clusters. For example, family medicine, which clustered with pediatrics and psychiatry, had a sub-cluster of: Bedside specialty with family orientation affording long-term patient care. Another sub-cluster was time for childrearing and family, only daytime work and outpatient care. Clusters also revealed students' perceptions that differed from expected: Cardiology is changing from a cognitive to a procedure-oriented subspecialty, clustering not only with internal medicine and its subspecialties but also with emergency medicine, surgical subspecialties and anesthesiology. CONCLUSIONS: The concept that career choice involves selecting from a cluster of related specialties provides information about the specialties students might be considering. Moreover, students are not only looking for individual aspects of a specialty, but for a package including clusters of socio-economic and occupational features. Practically, examining clusters can help in career counseling of medical students and assist residency program directors in marketing their specialties.

Pharmacomechanical catheter-directed thrombolysis for pregnancy-related iliofemoral deep vein thrombosis.

PURPOSE: Pharmacomechanical catheter-directed thrombolysis (PCDT) is relatively contraindicated during pregnancy and postpartum. The purpose of this study was to evaluate outcomes of PCDT in this population. MATERIALS AND METHODS: Data for 11 consecutive patients (aged 21-35 y) undergoing PCDT at a tertiary center for symptomatic pregnancy-related iliofemoral deep vein thrombosis (DVT) were retrospectively reviewed. Details regarding patient presentation, location and extent of thrombus, the PCDT procedure, outcomes, frequency of postthrombotic syndrome (PTS), and subsequent pregnancies were recorded. Two patients who presented in the first trimester terminated their pregnancies after PCDT, 2 patients who presented in the third trimester delayed PCDT until after delivery, and 7 patients who presented with postpartum DVT underwent immediate PCDT. RESULTS: Thrombus extended into the inferior vena cava in 5 patients (45%) and into popliteal/tibial veins in 7 (64%). Four patients (36%) had synchronous pulmonary embolism and three had May-Thurner compression. Median interval from diagnosis to PCDT was 5 days (range, 2-68 d); median duration of urokinase infusion was 27 hours (range, 16-72 h). Greater than 90% clot lysis was achieved in 9 of 11 patients (82%). Metal stents were placed in 8 of 11 patients (73%). A self-limiting popliteal hematoma developed in 1 patient, and 2 had early recurrent thrombosis requiring repeat PCDT. At median 20-month follow-up, nonocclusive thrombus was seen in 5 patients. No patient developed PTS. Three patients, all with stents, had uneventful pregnancies after PCDT. CONCLUSIONS: Pharmacomechanical catheter-directed thrombolysis achieved encouraging initial outcomes in this series. Validation in prospective trials with larger enrollment and longer follow-up is needed.

Induction of labor at term following external cephalic version in nulliparous women is associated with an increased risk of cesarean delivery.

PURPOSE: To determine whether induction of labor (IOL) after successful external cephalic version (ECV) is associated with an increased risk of cesarean delivery (CD) compared with IOL with spontaneous cephalic presentation. METHODS: Retrospective case-control study. All women having IOL after successful ECV were eligible. Each woman in the study group was matched for parity, age and indication for induction with two consecutive controls having IOL and spontaneous cephalic presentation. The primary outcome measure was CD. Secondary outcomes measures were operative vaginal delivery, perineal tear/episiotomy and post-partum hemorrhage. RESULTS: 79 women enrolled in the study group were matched with 158 controls. The overall incidence of CD was significantly higher in the study group compared with the control group (20.3 vs. 10.1 %; OR 2.25, 95 % CI 1.06-4.79, P = 0.03). After dividing the groups according to parity, the difference in the CD rate remained statistically significant for nulliparous women (36.7 vs. 15 %; OR 3.28, 95 % CI 1.17-9.16, P = 0.02), but not for multiparous women (10.2 vs. 7.1 %; OR 1.48, 95 % CI 0.44-4.92, P = 0.53). There was no significant difference in adjusted odds ratios for secondary outcomes. CONCLUSION: Induction of labor after successful ECV in nulliparous women increased the risk of CD compared with IOL with spontaneous cephalic presentation.

The association of maternal intrapartum subfebrile temperature and adverse obstetric and neonatal outcomes.

BACKGROUND: Subfebrile intrapartum maternal temperature is very common, yet there is sparse evidence regarding its causes or its effects on perinatal outcomes. We examined whether mild temperature elevation during labour is a risk marker for adverse obstetric and neonatal outcomes. METHODS: A retrospective cohort analysis including 42 601 term, singleton live-births in two medical centres between 2003 and 2010 was performed. This study compared women who experienced a maximal intrapartum temperature of ≤37°C with women who experienced subfebrile intrapartum temperature (37.1-37.9°C). Adjusted risks for adverse obstetric and neonatal outcomes were calculated by using multivariable logistic regression models. RESULTS: Compared with maternal temperature ≤ 37°C, subfebrile temperature was associated with higher rates of primary caesarean deliveries {adjusted odds ratios [aOR] = 1.36 [95% confidence interval (CI) 1.25, 1.49])} and assisted vaginal deliveries (aOR = 1.20 [95% CI 1.11, 1.30]), as well as with greater risks of early neonatal sepsis (aOR = 2.66 [95% CI 1.88, 3.77]), neonatal intensive care unit admissions (aOR = 1.40 [95% CI 1.08, 1.83]), and neonatal asphyxia or seizures (aOR = 3.18 [95% CI 1.51, 6.70]). Mildly elevated maternal intrapartum temperature (37.1-37.5°C) was also associated with adverse outcomes. CONCLUSIONS: Maternal intrapartum subfebrile temperature may be an indicator of operative delivery and neonatal morbidity. Further research is needed to confirm these findings and to reveal underlying mechanisms.

Using marketing research concepts to investigate specialty selection by medical students.

OBJECTIVES: This study was intended to examine whether a marketing research approach improves understanding of medical specialty selection by medical students. This approach likens students to consumers who are deciding whether or not to purchase a product (specialty). This approach proposes that when consumers' criteria match their perceptions of a product's features, the likelihood that they will purchase it (select the specialty) increases. This study examines whether exploring students' selection criteria and perceptions of various specialties provides additional insights into the selection process. METHODS: Using a consumer behaviour model as a framework, a questionnaire was designed and administered to Year 6 (final-year) students in 2008 and 2009 to elicit information on their knowledge about and interests in various specialties, the criteria they used in specialty selection, and their perceptions of six specialties. RESULTS: A total of 132 (67%) questionnaires were returned. In many instances, consistency between selection criteria and perceptions of a specialty was accompanied by interest in pursuing the specialty. Exceptions were noted and pointed to areas requiring additional research. For example, although > 70% of female students replied that the affordance of a controllable lifestyle was an important selection criterion, many were interested in obstetrics and gynaecology despite the fact that it was not perceived as providing a controllable lifestyle. Minimal overlap among students reporting interest in primary specialties that possess similar characteristics (e.g. paediatrics and family medicine) demonstrated the need to target marketing (recruitment) efforts for each specialty individually. CONCLUSIONS: Using marketing research concepts to examine medical specialty selection may precipitate a conceptual shift among health care leaders which acknowledges that, to attract students, specialties must meet students' selection criteria. Moreover, if consumers (students) deem a product (specialty) unattractive, it may need to be examined further to improve its appeal.

Factors associated with postcesarean blood transfusion: a case control study.

OBJECTIVE: Cesarean delivery (CD) is a known risk factor for postpartum hemorrhage. However, the characteristics associated with post-CD transfusion are not well-established. We aimed to assess blood transfusion rates and associated factors following CD. METHODS: A retrospective case-control study of women who underwent CD at a university hospital. The study group comprised all women who received blood transfusion following surgery. A control group of women who did not receive postoperative blood transfusion was assigned in a two-to-one ratio. RESULTS: During study period, the overall post-CD blood transfusion rate was 4.7%. The study group comprised 170 women, and the control group 340. Maternal age (aOR [95% CI]: 1.07 (1.03, 1.11), p = .001), parity (aOR [95% CI]: 1.26 (1.09, 1.47), p = .002), gestational hypertensive disorders (aOR [95% CI]: 4.07 (1.52, 10.91), p = .005), maternal comorbidities (aOR [95% CI]: 4.16 (1.88, 9.1), p < .001), lower predelivery hemoglobin level (aOR [95% CI]: 0.43 (0.34, 0.54), p < .001), and major placental abnormalities (aOR [95% CI]: 2.74 (1.04, 7.18), p = .04) were independently associated with blood transfusion requirement. Intrapartum characteristics associated with blood transfusion requirement included nonelective procedure (aOR [95% CI]: 3.21 (1.72, 5.99), p < .001), prolonged second stage of labor (aOR [95% CI]: 5.50 (2.57, 11.78), p < .001), longer duration of surgery (aOR [95% CI]: 1.03 (1.02, 1.04), p < .001), general anesthesia (aOR [95% CI]: 2.11 (1.14, 3.91), p = .02), and greater estimated operative blood loss (aOR [95% CI]: 5.72 (3.15, 10.36), p < .001). CONCLUSIONS: Among women who underwent CD, we identified 11 factors associated with blood transfusion following surgery. Prospective studies are warranted to assess the implementations of prophylactic interventions to reduce transfusion rates among those deemed at high risk for CD-related bleeding.

Risk factors for uterine incision extension during cesarean delivery.

BACKGROUND: Unintentional extension of uterine incision is a known complication during cesarean delivery estimated to occur in 4-8% of cesarean deliveries. The aim of this study was to examine risk factors associated with unintentional uterine incision extension and to assess which of them are independent risk factors for this condition. STUDY DESIGN: We conducted a retrospective cohort study at a large public university tertiary referral center between 2003 and 2017. Included were women who underwent cesarean delivery during this time period. Demographic, medical, obstetrical and surgical data were collected. The primary outcome was the presence of uterine incision extension during cesarean delivery. Secondary outcomes included detection of risk factors associated with uterine incision extension. A multivariate analysis was additionally performed to identify general and labor related risk factors for unintentional extension of uterine incision among patients that underwent cesarean delivery during second stage of labor. RESULTS: During the study period, 25,879 cesarean deliveries performed in our medical center were assessed. Out of them, 731 (2.8%) cases of unintended uterine incision extension were identified. Women in this group had high rates of full cervical dilatation and increased maternal hemorrhage. Assessment of incision extension direction revealed that two-thirds of extensions were lateral, mostly unilateral. Median size of the extension was 2.7 ± 1.2 cm.Independent parameters associated with unintended uterine incision extension included nulliparity, vertex presentation, epidural anesthesia and cesarean section indication. Further analysis including cesarean deliveries performed during the second stage of labor revealed 397 (15.3%) cesarean deliveries in which incision extension was noted and 2205 (84.7%) cesarean deliveries without incision extension. Following multivariate analysis performed in women who underwent cesarean delivery during second stage of labor, two independent parameters associated with unintended uterine incision extension remained significant - past cesarean delivery and failed vacuum attempt. CONCLUSIONS: Vacuum extraction attempt and previous cesarean delivery are independent risk factors for uterine incision extension in women undergoing cesarean delivery during the second stage of labor. We also showed the majority of these extensions to be lateral.

Missed opportunities for optimal antenatal corticosteroid timing in medically indicated preterm births.

OBJECTIVE: Although delivery timing is physician dictated in indicated preterm births, suboptimal antenatal corticosteroids (ACS) administration occurs in most cases. We aimed to characterize the patterns of use of ACS in indicated preterm births and identify missed opportunities of optimal ACS administration. METHODS: We reviewed the records of women who received ACS and were delivered due to maternal or fetal indications at 24-34 weeks of gestation during 2015-2017 at a university hospital. Optimal ACS timing was defined as delivery ≥24 h ≤7 d from the previous ACS course. RESULTS: Overall, 188 pregnancies were included. The median gestational age at delivery was 32 weeks. Considering only the initial ACS course, the rate of optimal timing was 32.4%. Of 105 (55.8%) women eligible (delivery >7 d since the initial ACS course), only a third (n = 38) received a rescue ACS course. Among women who did not receive rescue ACS course despite their eligibility (n = 67), the decision-to-delivery was ≥3 h in 36 (53.7%), and ≥24 h in 20 (29.9%), representing 19.1 and 10.6% of the entire cohort, respectively. The urgency of the decision to deliver (i.e. in the upcoming 24 h and later) and allowing a trial of labor, were both positively associated with decision-to-delivery interval ≥3 h and ≥24 h. The rate of delivery within any optimal window (either initial or rescue course) was 40.4%, with gestational hypertensive disorders (OR [95% CI]: 2.40 (1.23, 4.72), p = .01) and decision to deliver made at first hospitalization (OR [95% CI]: 2.27 (1.04, 4.76), p = .04) as independent positive predictors of optimal ACS timing. The rate of composite adverse neonatal outcome was significantly lower in those with optimal ACS administration as compared to those with suboptimal timing (32.9 versus 50.9%, OR [95% CI]: 0.47 (0.26, 0.87), p = .02). CONCLUSIONS: Suboptimal ACS administration occurred in most indicated preterm births. Underutilization of rescue ACS course and a substantial rate of missed opportunities for optimal ACS administration were identified as potentially modifiable contributors to improve ACS timing.

Pharmacomechanical catheter thrombolysis for pregnancy-related proximal deep venous thrombosis: prevention of post-thrombotic syndrome.

OBJECTIVE: The efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) in preventing post thrombotic syndrome (PTS) for pregnancy related deep vein thrombosis (DVT) is unknown. STUDY DESIGN: An observational cross section study of women with pregnancy related proximal (femoral/iliofemoral) DVT who underwent PCDT followed by anticoagulation (study group), and women who were treated with anticoagulation alone (control group). Women were evaluated for PTS using the Villalta scale (primary outcome) and VEINES-QOL/Sym questionnaires. RESULTS: Eleven women with iliofemoral DVT underwent PCDT, two during their first trimester and nine postpartum; 18 women were treated with anticoagulation only. There were no significant differences in age, number of previous pregnancies, and duration of anticoagulation or thrombophilia between the groups. The time between DVT diagnosis and study inclusion was longer in the study group [median 50.5 (range 16-120) months] compared to the control group [median 27 (range 11-64) months], p = .4. None of the women in the PCDT group developed PTS, compared to six (33.3%, p = .03) in the control group, four of whom developed severe PTS. One patient in each group developed recurrent DVT, and one patient in the study group developed a calf hematoma. A reduced frequency of lower extremity symptoms was observed in the PCDT group (VEINES-Sym questionnaire), but no differences in quality of life (VEINES-QOL questionnaire) were reported. CONCLUSION: This study suggests that PCDT may reduce the incidence of PTS in women with pregnancy related proximal DVT.Bullet pointsDVT involving the iliofemoral veins and development of post thrombotic syndrome is frequent among pregnant or postpartum womenStudies of pharmacomechanical catheter-directed thrombolysis (PCDT) for deep vein thrombosis did not include pregnant or postpartum womenIn our observational cross section study women who underwent PCDT (mainly in the postpartum period) had reduced frequency of post-thrombotic syndrome compared to women who received anticoagulation onlyLarger studies are required to confirm the use of PCDT for prevention of PTS in this population.

Chronic hypoxia in pregnant mice impairs the placental and fetal vascular response to acute hypercapnia in BOLD-MRI hemodynamic response imaging.

INTRODUCTION: Brief hypercapnic challenge causes acute placental hypoperfusion with fetal brain sparing on BOLD-MRI. We hypothesize that this non-invasive imaging strategy can distinguish between normal pregnancy and chronic placental hypoperfusion (using the maternal hypoxia model). METHODS: Eighteen pregnant female ICR mice were randomized to three groups: normoxia, late-onset hypoxia (12%O2;E13.5-17.5) and early-onset hypoxia (12%O2;E10.5-17.5). On E17.5, animals were imaged in a 4.7-T Bruker-Biospec MRI scanner. Fast coronal True-FISP was performed to identify organs of interest (placenta and fetal heart, liver and brain). BOLD-MRI was performed at baseline and during a 4-min hypercapnic challenge (5%CO2). %-change in placental and fetal signal was analyzed from T2*-weighted gradient echo MR images. Following MRI, fetuses and placentas were harvested, weighed and immuno-stained. RESULTS: In normoxic mice, hypercapnia caused reduction in BOLD-MRI signal in placenta (-44% ± 7%; p < 0.0001), fetal liver (-32% ± 7%; p < 0.0001) and fetal heart (-54% ± 12%; p < 0.002), with relative fetal brain sparing (-12% ± 5%; p < 0.0001). These changes were markedly attenuated in both hypoxia groups. Baseline fetal brain/placenta SI ratio was highest in normoxic mice (1.14 ± 0.017) and reduced with increasing duration of hypoxia (late-onset hypoxia: 1.00 ± 0.026; early-onset hypoxia: 0.91 ± 0.016; p = 0.02). Both hypoxic groups exhibited fetal growth restriction with prominent placental glycogen-containing cells, particularly in early-onset hypoxia. There was increased fetal neuro- and intestinal-apoptosis in early-onset hypoxia only. CONCLUSIONS: BOLD-MRI with brief hypercapnic challenge distinguished between normoxia and both hypoxia groups, while fetal neuroapoptosis was only observed after early-onset hypoxia. This suggests that BOLD-MRI with hypercapnic challenge can identify chronic fetal asphyxia before the onset of irreversible brain injury.