Association of Peripartum Lactate Levels With Infection Outcomes.

OBJECTIVE: To determine whether lactate levels were associated with maternal infection and infection-related outcomes in the antepartum, intrapartum, and early postpartum periods. DESIGN: Retrospective, observational cohort. SETTING: Eleven hospitals from a single health system. PARTICIPANTS: Women (N = 783) with at least one lactate and blood culture test for obstetric sepsis screening in the antepartum period (n = 154), intrapartum period (n = 348), and early postpartum period (n = 281) from January 2, 2018, to October 21, 2020. METHODS: We reported the proportion of participants with adverse outcomes by lactate cut points (≤2.0 and >2.0 mmol/L). We used logistic regression to model the association of infection-related outcomes with lactate levels and calculated receiver operating characteristic curves. RESULTS: Lactate was associated with bacteremia among participants in the antepartum period (odds ratio [OR] = 1.60, 95% confidence interval [CI] [1.00, 2.56]) but not among participants in the intrapartum and early postpartum periods. Higher lactate levels were significantly associated with a composite measure of infection-related outcomes (OR = 1.41, 95% CI [1.14, 1.81]), with no differential association by antepartum, intrapartum, or early postpartum periods. Lactate levels were positively associated with intraamniotic infection in the antepartum period (OR = 1.57, 95% CI [1.06, 1.81]) but not in the intrapartum period. The receiver operating characteristic curve indicated that the lactate threshold of 2.0 mmol/L has poor sensitivity. Overall, participants in the antepartum period had lower lactate values than participants in the intrapartum and early postpartum periods. CONCLUSION: Lactate levels were not consistently associated with infection-related measures across all periods. We suggest caution when interpreting lactate levels when sepsis is suspected.

Implementation and Outcomes of a Model of Care for Placenta Accreta Spectrum in a Community-Based Private Practice.

OBJECTIVE: The aim of the study is to describe a model of care and outcomes for placenta accreta spectrum (PAS) implemented in the context of a community based non-academic health system. STUDY DESIGN: The program for management of PAS includes a multidisciplinary team approach with protocols for ultrasound assessment, diagnosis, and surgery. The program was implemented in the two largest private hospitals in the Twin Cities, Minnesota, United States. Maternal and fetal outcomes as well as cost were compared for histopathologic confirmed PAS cases before (2007-2014, n = 41) and after (2015-2017, n = 26) implementation of the PAS program. RESULTS: Implementation of the PAS program was associated with ICU admission reductions from 53.7 to 19.2%, p = 0.005; a decrease of 1,682 mL in mean estimated blood loss (EBL) (p = 0.061); a decrease in transfusion from 85.4 to 53.9% (p = 0.005). The PAS program also resulted in a (non-significant) decrease in both surgical complications from 48.8 to 38.5% (p = 0.408) and postoperative complications from 61.0 to 42.3% (p = 0.135). The total cost of care for PAS cases in the 3 years after implementation of the program decreased by 33%. CONCLUSION: The implementation of a model of care for PAS led by a perinatology practice at a large regional non-academic referral center resulted in reductions of ICU admissions, operating time, transfusion, selected surgical complications, overall postoperative complications, and cost. KEY POINTS: · Implementation of a PAS care model resulted in reduced ICU admissions from 53.7% to 19.2%.. · Patient safety increased by reducing blood loss, transfusions and postoperative complications.. · This model decreased operating time, as well as total cost of care by 33%..

Effect of maternal cystic fibrosis genotype on diabetes in pregnancy.

OBJECTIVE: To evaluate the association between the cystic fibrosis (CF) genotype and the rate of diabetes complicating pregnancy. METHODS: We conducted a retrospective cohort analysis of all pregnant patients with CF from 1972-2011 at a single institution. Patients who were homozygous for the ΔF508 mutation were compared with patients who were heterozygous for the ΔF508 mutation. Primary outcomes measured were incidence of CF-related diabetes and gestational diabetes mellitus (GDM) stratified by CF genotype. Secondary outcomes measured included pancreatic insufficiency, preterm premature rupture of membranes, preterm delivery, mode of delivery, gestational age at delivery, and maternal mortality. RESULTS: We identified 54 pregnancies among 36 women who met inclusion criteria. Of these pregnancies, 28 (51.9%) were carried by women who were homozygous for the ΔF508 mutation. Homozygous women had a significantly greater incidence of pancreatic insufficiency (89.3% compared with 61.5%, P=.03) and diabetes complicating pregnancy (60.7% compared with 23.1%, P<.01) compared with heterozygous women. In addition, there was some evidence of an increased incidence of GDM specifically among homozygous women (35.7% compared with 15.4%, P=.12). Regarding neonatal outcome, there was a lower mean birthweight (2,881 g compared with 3,203 g, P=.04) among the women who were homozygous for the ΔF508 mutation. There was no statistical difference in preterm deliveries, mode of delivery, gestational age at delivery, rate of preterm premature rupture of membranes, or incidence of maternal mortality between the two groups. CONCLUSION: Women with CF who are homozygous for the ΔF508 mutation have an increased risk of having a pregnancy complicated by diabetes.

Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection.

Typhoid fever is a persistent infection caused by host-adapted Salmonella strains adept at circumventing immune-mediated host defences. Given the importance of T cells in protection, the culling of activated CD4+ T cells after primary infection has been proposed as a potential immune evasion strategy used by this pathogen. We demonstrate that the purging of activated antigen-specific CD4+ T cells after virulent Salmonella infection requires SPI-2 encoded virulence determinants, and is not restricted only to cells with specificity to Salmonella-expressed antigens, but extends to CD4+ T cells primed to expand by co-infection with recombinant Listeria monocytogenes. Unexpectedly, however, the loss of activated CD4+ T cells during Salmonella infection demonstrated using a monoclonal population of adoptively transferred CD4+ T cells was not reproduced among the endogenous repertoire of antigen-specific CD4+ T cells identified with MHC class II tetramer. Analysis of T-cell receptor variable segment usage revealed the selective loss and reciprocal enrichment of defined CD4+ T-cell subsets after Salmonella co-infection that is associated with the purging of antigen-specific cells with the highest intensity of tetramer staining. Hence, virulent Salmonella triggers the selective culling of high avidity activated CD4+ T-cell subsets, which re-shapes the repertoire of antigen-specific T cells that persist later after infection.

Foxp3+ regulatory T cells impede the priming of protective CD8+ T cells.

T cell activation is controlled by incompletely defined opposing stimulation and suppression signals that together sustain the balance between optimal host defense against infection and peripheral tolerance. In this article, we explore the impacts of Foxp3(+) regulatory T cell (Treg) suppression in priming Ag-specific T cell activation under conditions of noninfection and infection. We find the transient ablation of Foxp3(+) Tregs unleashes the robust expansion and activation of peptide-stimulated CD8(+) T cells that provide protection against Listeria monocytogenes infection in an Ag-specific fashion. By contrast, Treg ablation had nonsignificant impacts on the CD8(+) T cell response primed by infection with recombinant L. monocytogenes. Similarly, nonrecombinant L. monocytogenes administered with peptide stimulated the expansion and activation of CD8(+) T cells that paralleled the response primed by Treg ablation. Interestingly, these adjuvant properties of L. monocytogenes did not require CD8(+) T cell stimulation by IL-12 produced in response to infection, but instead were associated with sharp reductions in Foxp3(+) Treg suppressive potency. Therefore, Foxp3(+) Tregs impose critical barriers that, when overcome naturally during infection or artificially with ablation, allow the priming of protective Ag-specific CD8(+) T cells.

Foxp3(+) regulatory T cell expansion required for sustaining pregnancy compromises host defense against prenatal bacterial pathogens.

Although pregnancy confers unique susceptibility to infection, the pregnancy-associated immune defects that erode host defense remain largely undefined. Herein, we demonstrate that expansion of immune-suppressive Foxp3(+) regulatory T cells (Tregs) which occurs physiologically during pregnancy or when experimentally induced in transgenic mice caused enhanced susceptibility to prenatal pathogens including Listeria and Salmonella species. Reciprocally, infection susceptibility was uniformly reduced with Treg ablation. Importantly however, the sustained expansion of maternal Tregs was essential for maintaining immune tolerance to the developing fetus because even partial transient ablation of Foxp3-expressing cells fractured maternal tolerance to fetal antigen and triggered fetal resorption. Interestingly, Foxp3 cell-intrinsic defects in the immune-suppressive cytokine IL-10 alone were sufficient to override Treg-mediated infection susceptibility, while IL-10 was nonessential for sustaining pregnancy. Thus, maternal Treg expansion required for sustaining pregnancy creates naturally occurring holes in host defense that confer prenatal infection susceptibility.