The SunBEAm birth cohort: Protocol design.

Background: Food allergy (FA) and atopic dermatitis (AD) are common conditions that often present in the first year of life. Identification of underlying mechanisms and environmental determinants of FA and AD is essential to develop and implement effective prevention and treatment strategies. Objectives: We sought to describe the design of the Systems Biology of Early Atopy (SunBEAm) birth cohort. Methods: Funded by the National Institute of Allergy and Infectious Diseases (NIAID) and administered through the Consortium for Food Allergy Research (CoFAR), SunBEAm is a US population-based, multicenter birth cohort that enrolls pregnant mothers, fathers, and their newborns and follows them to 3 years. Questionnaire and biosampling strategies were developed to apply a systems biology approach to identify environmental, immunologic, and multiomic determinants of AD, FA, and other allergic outcomes. Results: Enrollment is currently underway. On the basis of an estimated FA prevalence of 6%, the enrollment goal is 2500 infants. AD is defined on the basis of questionnaire and assessment, and FA is defined by an algorithm combining history and testing. Although any FA will be recorded, we focus on the diagnosis of egg, milk, and peanut at 5 months, adding wheat, soy, cashew, hazelnut, walnut, codfish, shrimp, and sesame starting at 12 months. Sampling includes blood, hair, stool, dust, water, tape strips, skin swabs, nasal secretions, nasal swabs, saliva, urine, functional aspects of the skin, and maternal breast milk and vaginal swabs. Conclusions: The SunBEAm birth cohort will provide a rich repository of data and specimens to interrogate mechanisms and determinants of early allergic outcomes, with an emphasis on FA, AD, and systems biology.

Reducing Hemorrhage-Related Maternal Morbidity Using Interdisciplinary Simulation Training.

INTRODUCTION: Postpartum hemorrhage (PPH) remains a major cause of preventable maternal morbidity in the United States. Postpartum hemorrhage simulations were developed to improve provider recognition and treatment; however, there exist few studies that investigate their effects on individual outcomes. Our objective is to estimate the effect of a simulation-based educational intervention on PPH-related maternal morbidity outcomes. METHODS: We conducted a retrospective cohort analysis of hemorrhage outcomes at a single institution between March 2012 and January 2016 during the implementation of a high-fidelity PPH simulation. Women with PPH defined as an estimated blood loss greater than 500 mL for vaginal delivery and 1000 mL for cesarean delivery were included. The primary outcome was a composite of hemorrhage-related maternal morbidity (maternal death, hysterectomy, intensive care unit admission, blood transfusion, or unanticipated procedures to treat postpartum bleeding). Multivariable logistic regression adjusted for confounding variables between presimulation and postsimulation outcomes. RESULTS: During the study period, 19,927 deliveries occurred with 4.5% of patients (888) experiencing hemorrhage. Women in the presimulation (n = 278) versus postsimulation groups (n = 610) had similar demographics. Although the PPH rate increased after simulation [2.8% pre vs. 6.1% post, odds ratio (OR), 2.25; 95% confidence interval (CI), 1.95-2.60], composite hemorrhage-related morbidity was lower after simulation training (44% pre vs. 35% post; OR, 0.70; 95% CI, 0.52-0.93). This reduction persisted after adjusting for confounding variables of mode of delivery and time from delivery to first uterotonic use (adjusted OR, 0.66; 95%, CI 0.49-0.89). CONCLUSIONS: Despite an increased PPH rate, simulation education was associated with a reduction in a hemorrhage-related maternal composite morbidity.

EXIT (ex utero Intrapartum Treatment) to Airway Procedure for Twin Fetuses With Oropharyngeal Teratomas: Lessons Learned.

Ex utero intrapartum treatment (EXIT) to airway has been described as a safe method to secure challenging fetal airways while on placental support. Herein, we present a unique case of a monochorionic-diamniotic twin pregnancy where both fetuses presented with oropharyngeal tumors requiring airway securement on placental bypass. A multidisciplinary tabletop simulation was convened to allow for personnel coordination between multiple services, OR equipment allocation, and preparation for a range of possible clinical scenarios. A tabletop simulation was chosen for planning since this is a simulation methodology commonly used for preparation in acute, high intensity multidisciplinary situations such as disaster preparation, and allows for exploration of multiple potential scenarios when outcomes are uncertain. The twins were urgently delivered for decreased fetal movement and decelerations in Twin B at 28 weeks 6 days. Twin A was delivered via EXIT to airway while Twin B had debulking of the tumor on placental support, with subsequent airway securement through a tracheostomy. In conclusion, for complex fetal procedures, detailed pre-operative planning with tabletop simulation may be a useful tool in achieving successful patient outcomes.

Reduced allergenic potency of VR9-1, a mutant of the major shrimp allergen Pen a 1 (tropomyosin).

The major shrimp allergen, tropomyosin, is an excellent model allergen for studying the influence of mutations within the primary structure on the allergenic potency of an allergen; Pen a 1 allows systematic evaluation and comparison of Ab-binding epitopes, because amino acid sequences of both allergenic and nonallergenic tropomyosins are known. Individually recognized IgE Ab-binding epitopes, amino acid positions, and substitutions critical for IgE Ab binding were identified by combinatorial substitution analysis, and 12 positions deemed critical were mutated in the eight major epitopes. The mutant VR9-1 was characterized with regard to allergenic potency by mediator release assays using sera from shrimp-allergic subjects and sera from BALB/c, C57BL/6J, C3H/HeJ, and CBA/J mice sensitized with shrimp extract using alum, cholera toxin, and Bordetella pertussis, as adjuvants. The secondary structure of VR9-1 was not altered; however, the allergenic potency was reduced by 90-98% measuring allergen-specific mediator release from humanized rat basophilic leukemia (RBL) cells, RBL 30/25. Reduced mediator release of RBL-2H3 cells sensitized with sera from mice that were immunized with shrimp extract indicated that mice produced IgE Abs to Pen a 1 and to the same epitopes as humans did. In conclusion, data obtained by mapping sequential epitopes were used to generate a Pen a 1 mutant with significantly reduced allergenic potency. Epitopes that are relevant for human IgE Ab binding are also major binding sites for murine IgE Abs. These results indicate that the murine model might be used to optimize the Pen a 1 mutant for future therapeutic use.

Molecular basis of arthropod cross-reactivity: IgE-binding cross-reactive epitopes of shrimp, house dust mite and cockroach tropomyosins.

BACKGROUND: Shrimp may cross-react with other crustaceans and mollusks and nonedible arthropods such as insects (cockroach and chironomids), arachnids (house dust mites) and even nematodes. Since the muscle protein tropomyosin has been implicated as a possible cross-reacting allergen, this study characterized the IgE-binding epitopes in shrimp tropomyosin, Pen a 1, that cross-react with other allergenic invertebrate tropomyosins in house dust mites (Der p 10, Der f 10) and cockroaches (Per a 7). Pen a 1-reactive sera from shrimp-allergic subjects were used to evaluate the effect on IgE binding of different amino acid substitutions in Pen a 1 epitopes based on homologous sequences in Per a 7 and Der p 10/Der f 10. METHODS: Peptides were synthesized spanning the length of Pen a 1 IgE-binding epitopes and amino acid substitutions were performed based on homologous amino acid sequences from Per a 7 and Der p 10/Der f 10. RESULTS: 7/8 individually recognized Pen a 1 epitopes (2, 3a, 3b, 4, 5a, 5b and 5c) had an identical amino acid sequence with lobster allergen, Hom a 1, 4/8 (3a, 3b, 4 and 5a) with Der p 10 and Der f 10, and 5/8 (2, 3a, 3b, 4 and 5a) with Per a 7. In addition, even homologous regions of other arthropod tropomyosins that differ in one or more amino acids from the sequences of Pen a 1 epitopes are still recognized by shrimp-allergic IgE antibodies. In total, shrimp-allergic sera recognize 6/8 peptides homologous to Pen a 1 epitopes in Per a 7, 7/8 in Der p 10/Der f 10, and 7/8 epitopes in Hom a 1. CONCLUSIONS: The IgE recognition by shrimp-allergic individuals of identified and/or similar amino acid sequences homologous to Pen a 1 epitopes in mite, cockroach and lobster tropomyosins are the basis of the in vitro cross-reactivity among invertebrate species. Based on amino acid sequence similarity and epitope reactivity, lobster tropomyosin has the strongest and cockroach the least cross-reactivity with shrimp. The clinical relevance of these cross-reactivities in developing allergic reactions to different arthropods needs to be determined.