Pregnancy is a physiological state of continuous adaptation to changing maternal and fetal nutritional needs, including a reduction of maternal insulin sensitivity allowing for appropriately enhanced glucose availability to the fetus. However, excessive insulin resistance in conjunction with insufficient insulin secretion results in gestational diabetes mellitus (GDM), greatly increasing the risk for pregnancy complications and predisposing both mothers and offspring to future metabolic disease. Here, we report a signaling pathway connecting pregnancy-associated plasma protein A (PAPPA) with adipose tissue expansion in pregnancy. Adipose tissue plays a central role in the regulation of insulin sensitivity, and we show that, in both mice and humans, pregnancy caused remodeling of adipose tissue evidenced by altered adipocyte size, vascularization, and in vitro expansion capacity. PAPPA is known to be a metalloprotease secreted by human placenta that modulates insulin-like growth factor (IGF) bioavailability through prolteolysis of IGF binding proteins (IGFBPs) 2, 4, and 5. We demonstrate that recombinant PAPPA can stimulate ex vivo human adipose tissue expansion in an IGFBP-5– and IGF-1–dependent manner. Moreover, mice lacking PAPPA displayed impaired adipose tissue remodeling, pregnancy-induced insulin resistance, and hepatic steatosis, recapitulating multiple aspects of human GDM. In a cohort of 6361 pregnant women, concentrations of circulating PAPPA are inversely correlated with glycemia and odds of developing GDM. These data identify PAPPA and the IGF signaling pathway as necessary for the regulation of maternal adipose tissue physiology and systemic glucose homeostasis, with consequences for long-term metabolic risk and potential for therapeutic use.

Objective To examine rates of attempted and successful vacuum-assisted vaginal delivery by pre-pregnancy body mass index (BMI). Methods We conducted a retrospective cohort study of 2,084 women with singleton gestations needing operative delivery assistance and vacuum-eligible (fully dilated, ≥ +2 station, ≥34 weeks) using 2006–2014 in-patient records. Pre-pregnancy BMI was categorized as underweight (<18.5kg/m2), normal weight (18.5kg/m2≤BMI<25kg/m2), overweight (25kg/m2≤ BMI<30kg/m2), or obese (≥30kg/m2). Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of attempted and successful vacuum-assisted vaginal delivery by pre-pregnancy BMI adjusted for age, race, marital status, parity, diabetes, labor induction–augmentation, episiotomy, gestational age, and infant birth weight. Results Thirty-nine percent of women requiring delivery assistance and eligible for a vacuum were overweight or obese, 79% had vacuum attempts, and 95.3% of attempted vacuum-assisted vaginal deliveries were successful. Compared to women who were normal weight pre-pregnancy (82.8%), women who were overweight or obese were less likely to have vacuum attempted (75.8%, OR=0.71, 95% CI 0.53–0.96 and 71.2%, OR=0.53, 95% CI 0.39–0.74, respectively). Among women with attempted vacuum-assisted vaginal delivery, successful delivery did not differ by pre-pregnancy BMI (92.6%, OR=0.54, 95% CI 0.21–1.37 for underweight; 94.5%, OR=1.07, 95% CI 0.57–2.00 for overweight; 96.3%, OR=1.09, 95% CI 0.51–2.33 for obese, versus 95.6% among normal weight women). Conclusions Among women in need of operative delivery assistance, pre-pregnancy obesity was associated with lower likelihood of attempted vacuum-assisted vaginal delivery, but if attempted, success rates were similar to rates among normal weight women. With significant morbidity of second stage cesarean delivery in obese women, research should examine whether vacuum-assisted vaginal delivery may be appropriate for additional obese patients.