Clinical Presentation and Outcomes of Diabetic Ketoacidosis in Pregnancy.

OBJECTIVE: To examine the presentation, management, and outcomes of pregnancies complicated by diabetic ketoacidosis (DKA) in a contemporary obstetric population. METHODS: This is a case series of all admissions for DKA during pregnancy at a single Midwestern academic medical center over a 10-year period. Diabetic ketoacidosis was defined per the following diagnostic criteria: anion gap more than 12 mEq/L, pH less than 7.30 or bicarbonate less than 15 mEq/L, and elevated serum or urine ketones. Demographic information, clinical characteristics, and maternal and neonatal outcomes were assessed. Patient characteristics and clinical outcomes were compared between individuals with type 1 and those with type 2 diabetes mellitus. RESULTS: Between 2012 and 2021, there were 129 admissions for DKA in 103 pregnancies in 97 individuals. Most individuals (n=75, 77.3%) admitted for DKA during pregnancy had type 1 diabetes. The majority of admissions occurred in the third trimester (median gestational age 29 3/7 weeks). The most common precipitating factors were vomiting or gastrointestinal illness (38.0%), infection (25.6%), and insulin nonadherence (20.9%). Median glucose on admission was 252 mg/dL (interquartile range 181-343 mg/dL), and 21 patients (17.6%) were admitted with euglycemic DKA. Fifteen admissions (11.6%) were to the intensive care unit. Pregnancy loss was diagnosed during admission in six individuals (6.3%, 95% CI, 2.3-13.7%). Among pregnant individuals with at least one admission for DKA, the median gestational age at delivery was 34 6/7 weeks (interquartile range 33 2/7-36 3/7 weeks). Most neonates (85.7%, 95% CI, 76.8-92.2%) were admitted to the neonatal intensive care unit and required treatment for hypoglycemia. The cesarean delivery rate was 71.9%. Despite similar hemoglobin A1C values before pregnancy and at admission, individuals with type 1 diabetes had higher serum glucose (median [interquartile range], 256 mg/dL [181-353 mg/dL] vs 216 mg/dL [136-258 mg/dL], P=.04) and higher serum ketones (3.78 mg/dL [2.13-5.50 mg/dL] vs 2.56 mg/dL [0.81-4.69 mg/dL] mg/dL, P=.03) on admission compared with those with type 2 diabetes. Individuals with type 2 diabetes required intravenous insulin therapy for a longer duration (55 hours [29.5-91.5 hours] vs 27 hours [19-38 hours], P=.004) and were hospitalized longer (5 days [4-9 days] vs 4 days [3-6 days], P=.004). CONCLUSION: Diabetic ketoacidosis occurred predominantly in pregnancies affected by type 1 diabetes. Individuals with type 1 diabetes presented with greater DKA severity but achieved clinical resolution more rapidly than those with type 2 diabetes. These results may provide a starting point for the development of interventions to decrease maternal and neonatal morbidity related to DKA in the modern obstetric population.

Glassy cell carcinoma of the cervix: Findings from a combined National Cancer Database analysis and single institution review of treatment patterns and outcomes.

OBJECTIVES: To describe stage, treatment patterns, and survival for glassy cell carcinoma of the cervix (GCCC), a poorly understood rare tumor. METHODS: Clinical data and survival were compared between GCCC and more common histologic types using the National Cancer Database (NCDB) from 2004 to 2017. A retrospective review of GCCC cases at our institution from 2012 to 2020 was simultaneously performed with staging updated according to 2018 FIGO staging. Descriptive statistics and survival analyses were performed, and outcomes compared to historical references. RESULTS: 143/89,001 (0.16%) NCDB cervical cancer cases were GCCC. Compared to other histologies, GCCC cases were younger, with 74.8% diagnosed before age 50. Stage distribution was similar. Stage I cases were less commonly treated with surgery alone (19/69, 27%). 79.4% of locally advanced (stage II-IVA) cases were treated with definitive chemoradiation. GCCC demonstrated worse OS for early-stage and locally-advanced disease. No survival differences were observed for patients with stage IVB disease. Our institutional review identified 14 GCCC cases. Median age at diagnosis was 34 years. All nine early-stage cases underwent radical hysterectomy. Adjuvant radiation was given for cases meeting Sedlis criteria (4/9, 44%). All five advanced stage cases were stage IIIC and received definitive chemoradiation. Recurrence rate was 0% (0/9) for early-stage and 60% (3/5) for advanced-stage cases. 3-year PFS was 100% for early-stage and 40% for advanced-stage. 3-year OS was 100% for early-stage and 60% for advanced-stage GCCC. CONCLUSIONS: GCCC presents at earlier ages than other cervical cancer histologic types. Although NCDB showed worse OS, our more contemporary institutional review, which incorporates updated staging and newer treatment modalities found outcomes more similar to historical references of more common histologic subtypes.

Unique maternal immune and functional microbial profiles during prenatal stress.

Maternal stress during pregnancy is widespread and is associated with poor offspring outcomes, including long-term mental health issues. Prenatal stress-induced fetal neuroinflammation is thought to underlie aberrant neurodevelopment and to derive from a disruption in intrauterine immune homeostasis, though the exact origins are incompletely defined. We aimed to identify divergent immune and microbial metagenome profiles of stressed gestating mice that may trigger detrimental inflammatory signaling at the maternal-fetal interface. In response to stress, maternal glucocorticoid circuit activation corresponded with indicators of systemic immunosuppression. At the maternal-fetal interface, density of placental mononuclear leukocytes decreased with stress, yet maternal whole blood leukocyte analysis indicated monocytosis and classical M1 phenotypic shifts. Genome-resolved microbial metagenomic analyses revealed reductions in genes, microbial strains, and metabolic pathways in stressed dams that are primarily associated with pro-inflammatory function. In particular, disrupted Parasutterella excrementihominis appears to be integral to inflammatory and metabolic dysregulation during prenatal stress. Overall, these perturbations in maternal immunological and microbial regulation during pregnancy may displace immune equilibrium at the maternal-fetal interface. Notably, the absence of and reduction in overt maternal inflammation during stress indicates that the signaling patterns driving fetal outcomes in this context are more nuanced and complex than originally anticipated.