The mechanisms underpinning maternal metabolic adaptations to a healthy pregnancy and in gestational diabetes mellitus (GDM) remain poorly understood. We hypothesized that small extracellular vesicles (sEVs) isolated from healthy pregnant women promote islet glucose‐stimulated insulin secretion (GSIS) and peripheral insulin resistance in nonpregnant mice and that sEVs from GDM women fail to stimulate insulin secretion and cause exacerbated insulin resistance. Small EVs were isolated from plasma of nonpregnant, healthy pregnant, and GDM women at 24‐28 weeks of gestation. We developed a novel approach in nonpregnant mice involving a mini‐osmotic pump for continuous 4‐day jugular venous infusion of sEVs and determined their effects on glucose tolerance in vivo and islets and skeletal muscle in vitro. Fasting insulin was elevated in mice infused with pregnant sEVs as compared to sEVs from nonpregnant and GDM women. Mice infused with sEVs from GDM women developed glucose intolerance. GSIS was increased in mice infused with healthy pregnancy sEVs compared to mice receiving nonpregnant sEVs. GSIS and muscle basal insulin signaling, and insulin responsiveness were attenuated in mice infused with GDM sEVs. sEVs represent a novel mechanism regulating maternal glucose homeostasis in pregnancy and we speculate that altered sEV content contributes to the development of GDM.

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Tumor volume to fetal weight ratio (TFR) > 0.12 before 24 weeks has been associated with poor perinatal outcomes in fetuses with sacrococcygeal teratoma (SCT) but is not universally accepted. We evaluated the predictive value of TFR in our large cohort of fetuses with SCT. STUDY DESIGN: Retrospective, single-center, cohort review of fetuses evaluated for SCT from 1997-2015. Patients who chose termination of pregnancy (TOP), delivered elsewhere, or had their initial evaluation > 24 weeks were excluded. Outcomes were compared in fetuses with TFR vs > 0.12. Poor outcome was defined as intrauterine fetal demise, neonatal demise, fetal deterioration warranting open fetal surgery, and fetal deterioration warranting delivery prior to 32 weeks. RESULTS: 140 pregnancies were confirmed to have SCT. 28 chose TOP, 13 delivered elsewhere, and 40 had their initial evaluation > 24 weeks. 59 fetuses with TFR at 24 weeks were stratified into two groups based on TFR (table). Fetuses with TFR > 0.12 were more likely to have a poor perinatal outcome compared to those with TFR 0.12 (24/32 vs 3/27; p<0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of TFR > 0.12 in predicting poor outcome was 88.9%, 75.0%, 75.0% and 88.9%, respectively. CONCLUSION: This is the largest single-center study to date and supports the use of TFR > 0.12 at 24 weeks to risk stratify fetuses with SCT. This information is useful in counseling and in forming surveillance programs for these highest risk fetuses.