Decidual Cells Block Inflammation-Mediated Inhibition of 15-Hydroxyprostaglandin Dehydrogenase in Trophoblasts.

Chorioamnionitis generates prostaglandin (PG) E2 and F2α, promoting fetal membrane rupture, cervical ripening, and uterine contractions. 15-Hydroxyprostaglandin dehydrogenase (HPGD) contributes to pregnancy maintenance by inactivating PGs. The role of decidual cells in regulating HPGD expression at the maternal-fetal interface was investigated. HPGD immunostaining was primarily detected in anchoring villi and choriodecidual extravillous trophoblasts (EVTs) in the first, second, and third trimesters. Chorionic EVTs adjacent to decidua parietalis exhibited significantly higher HPDG levels than those adjacent to amnion. HPGD histologic score levels were significantly lower in choriodecidua from chorioamnionitis versus gestational age-matched controls (means ± SEM, 132.6 ± 3.8 versus 31.2 ± 7.9; P < 0.05). Conditioned media supernatant (CMS) from in vitro decidualized term decidual cells (TDCs) up-regulated HPGD levels in EVTs differentiated from human trophoblastic stem cells, primary trophoblasts, and HTR8/SVneo cells. However, CMS from 5 µg/mL lipopolysaccharide or 10 ng/mL IL-1ß pretreated TDC cultures down-regulated HPGD levels in HTR8/SVneo cultures. Similarly, direct treatment of HTR8/SVneo cultures with lipopolysaccharide or IL-1ß significantly reduced HPGD levels versus control (0.57 ± 0.1 or 0.47 ± 0.1 versus 1.03 ± 0.03; P < 0.05) but not in TDC-CMS pretreated HTR8/SVneo cultures. Collectively, the results uncover a novel decidual cell-mediated paracrine mechanism that stimulates levels of trophoblastic HPGD, whose function is to inactivate labor-inducing PGs, thereby promoting uterine quiescence during pregnancy. However, infectious/inflammatory stimuli in decidual cells cause a paracrine inhibition of trophoblastic HPGD expression, increasing PGE2/PGF2α levels, thereby contributing to preterm birth.

Evaluation of Recurrent Pregnancy Loss.

Recurrent pregnancy loss (RPL) affects approximately 5% of couples. Although RPL definitions vary across professional societies, an evaluation after a second clinically recognized first-trimester pregnancy loss is recommended. Good quality evidence links parental chromosomal rearrangements, uterine anomalies, and antiphospholipid syndrome (APS) to RPL. In contrast, the relationship between RPL and other endocrine, hematologic, and immunologic disorders or environmental exposures is less clear. Anticoagulant therapy and low-dose aspirin are recommended for patients with RPL who have also been diagnosed with APS. Vaginal progesterone supplementation may be considered in patients experiencing vaginal bleeding during the first trimester. Surgical correction may be considered for patients with RPL in whom a uterine anomaly is identified. Evaluation and management of additional comorbidities should be guided by the patient's history rather than solely based on the diagnosis of RPL, with the goal of improving overall health to reduce complications in the event of pregnancy. Most people with RPL, including those without identifiable risk factors, are expected to achieve a live birth within 5 years from the initial evaluation. Nevertheless, clinicians should be sensitive to the psychological needs of individuals with this condition and provide compassionate and supportive care across all stages.

Patient-Prosthesis Mismatch in Pregnancy: A Multidisciplinary Approach.

A 24-year-old gravida 3 para 1 woman with history of bioprosthetic aortic valve replacement complicated by patient-prosthesis mismatch presented for prenatal care. Her pregnancy was managed by a multidisciplinary cardio-obstetrics team, resulting in an uncomplicated repeat cesarean section at term.

Resuscitation of traumatic maternal cardiac arrest: A case report and summary of recommendations from Obstetric Life Support™.

Traumatic maternal cardiac arrest (MCA) is a challenging scenario for the healthcare team. Expanding the focused assessment with sonography for trauma (FAST) and modifying cardiopulmonary resuscitation (CPR) is necessary. Critical components in the resuscitation of reproductive-age women with traumatic cardiac arrest are highlighted using recommendations from Obstetric Life Support™. A morbidly obese female presented to the Emergency Department (ED) with ongoing CPR and massive hemorrhage from two gunshot wounds to the chest. Ultrasound used during secondary survey, revealed an intrauterine pregnancy, with uterine fundus palpated above the umbilicus. Four minutes after arrival at the ED, the trauma surgeon initiated a resuscitative cesarean delivery (RCD) by transverse abdominal incision. The on-call obstetrician completed the procedure, and the neonate was resuscitated and transferred to the neonatal intensive care unit (NICU). Multiple agents and surgical techniques were required to control ongoing uterine and abdominal wall hemorrhage during intermittent return of spontaneous circulation (ROSC). Despite ongoing CPR and management of the patient's chest, pelvic and abdominal wounds, eventually, there was no return of cardiac activity, no organized cardiac rhythm, no measurable end-tidal carbon dioxide, and no palpable pulse. Further resuscitation and initiation of extracorporeal cardiopulmonary resuscitation (ECPR) were deemed futile by the multidisciplinary team and stopped at the 60-minute mark. Our case summarizes essential techniques addressing MCA recommended in OBLS™ courses. Including 1) expanding the FAST exam to assess for pregnancy status, 2) estimating gestational age by fundal height or point-of-care ultrasound, 3) performing a RCD via midline vertical incision at 4 min if pregnancy is suspected to be ≥20 weeks' gestation (fundal height at or above the umbilicus, femoral length of ≥30 mm or biparietal diameter of ≥45 mm), and 4) execution of ECPR for refractory cardiac arrest.

Regulation of Proinflammatory Molecules and Tissue Factor by SARS-CoV-2 Spike Protein in Human Placental Cells: Implications for SARS-CoV-2 Pathogenesis in Pregnant Women.

SARS-CoV-2 infects cells via binding to ACE2 and TMPRSS2, which allows the virus to fuse with host cells. The viral RNA is detected in the placenta of SARS-CoV-2-infected pregnant women and infection is associated with adverse pregnancy complications. Therefore, we hypothesize that SARS-CoV-2 infection of placental cells induces pro-inflammatory cytokine release to contribute to placental dysfunction and impaired pregnancy outcomes. First, expression of ACE2 and TMPRSS2 was measured by qPCR in human primary cultured term cytotrophoblasts (CTBs), syncytiotrophoblast (STBs), term and first trimester decidual cells (TDCs and FTDCs, respectively), endometrial stromal cells (HESCs) as well as trophoblast cell lines HTR8, JEG3, placental microvascular endothelial cells (PMVECs) and endometrial endothelial cells (HEECs). Later, cultured HTR8, JEG3, PMVECs and HEECs were treated with 10, 100, 1000 ng/ml of recombinant (rh-) SARS-CoV-2 S-protein ± 10 ng/ml rh-IFNγ. Pro-inflammatory cytokines IL-1ß, 6 and 8, chemokines CCL2, CCL5, CXCL9 and CXCL10 as well as tissue factor (F3), the primary initiator of the extrinsic coagulation cascade, were measured by qPCR as well as secreted IL-6 and IL-8 levels were measured by ELISA. Immunohistochemical staining for SARS-CoV-2 spike protein was performed in placental specimens from SARS-CoV-2-positive and normal pregnancies. ACE2 levels were significantly higher in CTBs and STBs vs. TDCs, FTDCs and HESCs, while TMPRSS2 levels were not detected in TDCs, FTDCs and HESCs. HTR8 and JEG3 express ACE2 and TMPRSS2, while PMVECs and HEECs express only ACE2, but not TMPRSS2. rh-S-protein increased proinflammatory cytokines and chemokines levels in both trophoblast and endothelial cells, whereas rh-S-protein only elevated F3 levels in endothelial cells. rh-IFNγ ± rh-S-protein augments expression of cytokines and chemokines in trophoblast and endothelial cells. Elevated F3 expression by rh-IFNγ ± S-protein was observed only in PMVECs. In placental specimens from SARS-CoV-2-infected mothers, endothelial cells displayed higher immunoreactivity against spike protein. These findings indicated that SARS-CoV-2 infection in placental cells: 1) induces pro-inflammatory cytokine and chemokine release, which may contribute to the cytokine storm observed in severely infected pregnant women and related placental dysfunction; and 2) elevates F3 expression that may trigger systemic or placental thrombosis.

Top 10 Pearls for the Recognition, Evaluation, and Management of Maternal Sepsis.

Maternal sepsis is an obstetric emergency and a leading cause of maternal morbidity and mortality. Early recognition in a pregnant or postpartum patient can be a challenge as the normal physiologic changes of pregnancy may mask the signs and symptoms of sepsis. Bedside assessment tools may aid in the detection of maternal sepsis. Timely and targeted antibiotic therapy and fluid resuscitation are critical for survival in patients with suspected sepsis. Once diagnosed, a search for etiologies and early application of source control measures will further reduce harms. If the patient is in septic shock or not responding to initial treatment, multidisciplinary consultation and escalation of care is necessary. Health care professionals should be aware of the unique complications of sepsis in critically ill pregnant and postpartum patients, and measures to prevent poor outcomes in this population. Adverse pregnancy outcomes may occur in association with sepsis, and should be anticipated and prevented when possible, or managed appropriately when they occur. Using a standardized approach to the patient with suspected sepsis may reduce maternal morbidity and mortality.