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Objective Evidence is inconsistent regarding grand multiparity and its association with adverse obstetric outcomes. Few large American cohorts of grand multiparas have been studied. We assessed if increasing parity among grand multiparas is associated with increased odds of adverse perinatal outcomes. Study Design Multicenter retrospective cohort of patients with parity ≥ 5 who delivered a singleton gestation in New York City from 2011 to 2019. Outcomes included postpartum hemorrhage, preterm delivery, hypertensive disorders of pregnancy, shoulder dystocia, birth weight > 4,000 and <2,500 g, and neonatal intensive care unit (NICU) admission. Parity was analyzed continuously, and multivariate analysis determined if increasing parity and other obstetric variables were associated with each adverse outcome. Results There were 2,496 patients who met inclusion criteria. Increasing parity among grand multiparas was not associated with any of the prespecified adverse outcomes. Odds of postpartum hemorrhage increased with history (adjusted odds ratio [aOR]: 2.65, 95% confidence interval [1.83, 3.84]) and current cesarean delivery (aOR: 4.59 [3.40, 6.18]). Preterm delivery was associated with history (aOR: 12.36 [8.70–17.58]) and non-White race (aOR: 1.90 [1.27, 2.84]). Odds of shoulder dystocia increased with history (aOR: 5.89 [3.22, 10.79]) and birth weight > 4,000 g (aOR: 9.94 [6.32, 15.65]). Birth weight > 4,000 g was associated with maternal obesity (aOR: 2.92 [2.22, 3.84]). Birth weight < 2,500 g was associated with advanced maternal age (aOR: 1.69 [1.15, 2.48]), chronic hypertension (aOR: 2.45 [1.32, 4.53]), and non-White race (aOR: 2.47 [1.66, 3.68]). Odds of hypertensive disorders of pregnancy increased with advanced maternal age (aOR: 1.79 [1.25, 2.56]), history (aOR: 10.09 [6.77–15.04]), and non-White race (aOR: 2.79 [1.95, 4.00]). NICU admission was associated with advanced maternal age (aOR: 1.47 [1.06, 2.02]) and non-White race (aOR: 2.57 [1.84, 3.58]). Conclusion Among grand multiparous patients, the risk factor for adverse maternal, obstetric, and neonatal outcomes appears to be occurrence of those adverse events in a prior pregnancy and not increasing parity itself. Key Points Increasing parity is not associated with adverse obstetric outcomes among grand multiparas. Prior adverse pregnancy outcome is a risk factor for the outcome among grand multiparas. Advanced maternal age is associated with adverse obstetric outcomes among grand multiparas. [ABSTRACT FROM AUTHOR]

Objective This study was aimed to evaluate how the novel coronavirus disease 2019 (COVID-19) pandemic may have negatively impacted birth outcomes in patients who tested negative for the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus. Study Design We conducted a retrospective cohort study using electronic health records of pregnant women admitted to a tertiary medical center in New York City, an epicenter of the pandemic. Women with a singleton gestation admitted for delivery from March 27 to May 31, 2019, and March 27 to May 31, 2020, were included. Women less than 18 years of age, those with a positive SARS-CoV-2 polymerize chain reaction (PCR) test on admission, fetal anomaly, or multiple gestation were excluded. Adverse pregnancy outcomes were compared between groups. Univariable and multivariable logistic regression analyses were used to assess outcomes. The primary outcome was preterm birth. Results Women who delivered during the 2020 study interval had a significantly higher rate of hypertensive disorders of pregnancy (gestational hypertension [GHTN] or preeclampsia; odds ratio [OR] = 1.40, 95% confidence interval [CI]: 1.05–1.85; p = 0.02), postpartum hemorrhage (PPH; OR = 1.77, 95% CI: 1.14–2.73; p = 0.01), and preterm birth (OR = 1.49, 95% CI: 1.10–2.02; p = 0.01). Gestational age at delivery was significantly lower in the 2020 cohort compared with the 2019 cohort (39.3 versus 39.4 weeks, p = 0.03). After adjusting for confounding variables, multivariate analysis confirmed a persistent increase in hypertensive disorders of pregnancy (OR = 1.56, 95% CI: 1.10–2.20, p = 0.01), PPH (OR = 1.74, 95% CI: 1.06–2.86, p = 0.03), and preterm birth (OR = 1.72, 95% CI: 1.20–2.47, p = 0.003) in patients who delivered in 2020 compared with the same period in 2019. Specifically, medically indicated preterm births increased during the pandemic (OR = 3.17, 95% CI: 1.77–5.67, p < 0.0001). Conclusion Those who delivered during the COVID-19 pandemic study interval were more likely to experience hypertensive disorders of pregnancy, medically indicated preterm birth, and PPH even in the absence of SARS-CoV2 infection. Key Points Stressful life events can lead to adverse pregnancy outcomes. Even patients negative for COVID-19 experienced GHTN, preeclampsia, PPH and preterm birth during the pandemic. Pandemic-related stress may adversely affect perinatal outcomes. [ABSTRACT FROM AUTHOR]

The routine use of surgical safety checklists can reduce perioperative complications. Generic surgical safety checklists are insufficient for cesarean delivery because each cesarean delivery involves 2 patients (the mother and the fetus or newborn), each with separate care teams and health and safety considerations. To address the added complexity of care coordination and communication inherent in cesarean delivery, the Society for Maternal-Fetal Medicine presents sample standard surgical safety checklists for cesarean delivery that include elements of care for both the mother and newborn. In addition, we present an alternative checklist for time-critical emergency cesarean deliveries in which there is no time to safely perform the standard checklist and a sample preoperative checklist for use before moving the patient to the operating room. We also recommend steps for implementation of the checklists at individual facilities. [ABSTRACT FROM AUTHOR]

Amniotic fluid embolism is a rare syndrome characterized by sudden cardiorespiratory collapse during labor or soon after delivery. Because of its rarity, many obstetrical providers have no experience in managing amniotic fluid embolism and may therefore benefit from a cognitive aid such as a checklist. We present a sample checklist for the initial management of amniotic fluid embolism based on standard management guidelines. We also suggest steps that each facility can take to implement the checklist effectively. [ABSTRACT FROM AUTHOR]

Optimal management of HIV-positive pregnant individuals involves many specific interventions made by many healthcare professionals at specific time-points before, during, and after pregnancy. Errors of omission are likely unless those professionals use a cognitive aid such as a checklist as a reminder of critical steps. In this document, SMFM presents updated and expanded checklists to help ensure that all relevant elements are considered for every person with HIV during prepregnancy, antepartum, intrapartum, and postpartum periods. The checklists are intended to be used as tools to facilitate the care of individuals with HIV during all phases of pregnancy care. Their use should improve the safety of HIV-positive patients by ensuring that appropriate treatment is given and relevant information is shared with consultative services. Routine use should also facilitate improved documentation, communication, and continuity of care before, during, and after pregnancy. [ABSTRACT FROM AUTHOR]

Introduction  Data regarding transplacental passage of maternal coronavirus disease 2019 (COVID-19) antibodies and potential immunity in the newborn is limited. Case Report  We present a 25-year-old multigravida with known red blood cell isoimmunization, who was found to be COVID-19 positive at 27 weeks of gestation while undergoing serial periumbilical blood sampling and intrauterine transfusions. Maternal COVID-19 antibody was detected 2 weeks after positive molecular testing. Antibodies were never detected on cord blood samples from two intrauterine fetal cord blood samples as well as neonatal cord blood at the time of delivery. Conclusion  This case demonstrates a lack of passive immunity of COVID-19 antibodies from a positive pregnant woman to her fetus, neither in utero nor at the time of birth. Further studies are needed to understand if passage of antibodies can occur and if that can confer passive immunity in the newborn. Key Points Passive immunity should not be assumed in COVID-19 infection in pregnancy. Isoimmunization may impair passive immunity of certain antibodies. Vaccination to or maternal infection of COVID-19 may not be protective for the fetus. [ABSTRACT FROM AUTHOR]

The lymphomas probably represent the most complex and heterogenous set of malignancies known to cancer medicine. Underneath the single term lymphoma exist some of the fastest growing cancers known to science (i.e Burkitt's and lymphoblastic lymphoma), as well as some of the slowest growing (i.e. small lymphocytic lymphoma [SLL] and follicular lymphoma). It is this very biology that can dictate the selection of drugs and treatment approaches for managing these patients, strategies that can range from very aggressive combination chemotherapy administered in an intensive care unit (for example, patients with Burkitt's lymphoma), to watch and wait approaches that may go on for years in patients with SLL. This impressive spectrum of biology emerges from a relatively restricted number of molecular defects. The importance of these different molecular defects is of course greatly influenced by the intrinsic biology that defines the lymphocyte at its different stages of differentiation and maturation. It is precisely this molecular understanding that is beginning to form the basis for a new approach to thinking about lymphoma, and novel approaches to its management. Unfortunately, while our understanding of human lymphoma has blossomed, our ability to generate appropriate animal models reflective of this biology has not. Most pre clinical models of these diseases still rely upon sub-cutaneous xenograft models of only the most aggressive lymphomas like Burkitt's lymphoma. While these models clearly serve an important role in understanding biology, and perhaps more importantly, in identifying promising new drugs for these diseases, they fall short in truly representing the broader, more heterogenous biology found in patients. Clearly, depending upon the questions being posed, or the types of drugs being studied, the best model to employ may vary from situation to situation. In this article, we will review the numerous complexities associated with various animal models of lymphoma, and will try to explore several alternative models which might serve as better in vivo tools for to study these interesting diseases. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether the combination of the proteasome inhibitor bortezomib and the bcl-2 antisense molecule oblimersen can sensitize human lymphoma to cyclophosphamide., Experimental Design: Cytotoxicity assays were conducted to determine if there was any additive or synergistic interaction between the combinations of bortezomib, oblimersen, and cyclophosphamide using a standard trypan blue exclusion assay. Based on these experiments, in vivo experiments in severe combined immunodeficiency beige mice were done using human lymphoma xenografts in which different schedules were explored. Bcl-2 and oblimersen levels were determined in treated tumors, some of which were resected at the end of the in vivo experiment and evaluated pathologically., Results: The results suggest that the combination of bortezomib and oblimersen seem to interact in at least an additive fashion, and that the addition of cyclophosphamide to this drug combination can markedly improve tumor cell kill. In addition, it seems that these drug combinations may be schedule-dependent, with a requirement for oblimersen pretreatment. Animals treated with the triplet drug combination in a schedule-dependent manner experienced pathologic complete regression of disease, which was not observed in other treatment cohorts. The addition of bortezomib also seemed to increase the levels of intracellular oblimersen, which resulted in a marked reduction in Bcl-2. Histologic studies confirmed marked necrosis and caspase-3 activation only in the cohort receiving all three drugs., Conclusion: The use of Bcl-2-directed therapy and a proteasome inhibitor sensitizes human lymphoma cells to cytotoxic drugs like cyclophosphamide. This combination may offer new opportunities for integrating novel targeted therapies with conventional chemotherapy.

Purpose: Methotrexate is known to synergize with cytarabine [1-beta-D-arabinofuranosylcytosine (ara-C)] in a schedule-dependent manner. The purpose of this article is to compare and contrast the activity of pralatrexate (10-propargyl-10-deazaminopterin)/gemcitabine to the standard combination of methotrexate/ara-C and to determine if schedule dependency of this combination is important in lymphoma., Experiment Design: Cytotoxicity assays using the standard trypan blue exclusion assay were used to explore the in vitro activity of pralatrexate and gemcitabine against a panel of lymphoma cell lines. Both severe combined imunodeficient beige and irradiated nonobese diabetic/severe combined imunodeficient mouse xenograft models were used to compare and contrast the in vivo activity of these combinations as a function of schedule. In addition, apoptosis assays were conducted., Results: Compared with methotrexate-containing combinations, pralatrexate plus gemcitabine combinations displayed improved therapeutic activity with some schedule dependency. The combination of pralatrexate and gemcitabine was superior to any methotrexate and ara-C combination in inducing apoptosis and in activating caspase-3. In vivo, the best therapeutic effects were obtained with the sequence of pralatrexate --> gemcitabine. Complete remissions were only appreciated in animals receiving pralatrexate followed by gemcitabine., Conclusions: These data show that the combination of pralatrexate followed by gemcitabine was superior to methotrexate/ara-C in vitro and in vivo, and was far more potent in inducing apoptosis in a large B-cell lymphoma. These data provide strong rationale for further study of this combination in lymphomas where methotrexate and ara-C are used.