The effect of a neonatal sleep intervention on maternal postpartum hypertension: a randomized trial.

BACKGROUND: In nonpregnant adults, poor sleep is associated with higher blood pressure. Poor sleep is common in the postpartum period and is often attributed to infant caretaking needs. However, its effects on cardiovascular health in individuals with a hypertensive disorder of pregnancy are unknown. OBJECTIVE: This study aimed to determine the effect of a neonatal sleep intervention on maternal postpartum blood pressure in individuals with a hypertensive disorder of pregnancy. STUDY DESIGN: In this single-institution pilot randomized controlled trial from July 2021 to March 2022, 110 individuals with a hypertensive disorder of pregnancy were randomized to receive a neonatal sleep intervention (SNOO responsive bassinet) plus usual care of safe sleep education (n=54) or usual care alone (n=56). Remote follow-up visits were conducted at 1 week, 6 weeks, and 4 months after delivery and involved blood pressure and weights, sleep and mood questionnaires, and self-reported infant and maternal sleep logs. Based on institutional data, the sample size had 80% power to detect a 4.5-mm Hg difference in the primary outcome of mean arterial pressure at 6 weeks after delivery. RESULTS: Baseline characteristics were similar between the arms. At 1 week after delivery, the intervention arm had lower mean arterial pressure and less antihypertensive medication use than the control arm (99±10 vs 103±7 mm Hg [P=.04] and 23% vs 35% [P=.15], respectively). At 6 weeks after delivery, mean arterial pressure was similar between arms (93±8 vs 94±8 mm Hg; P=.54), but there was a lower rate of antihypertensive use in the intervention arm (15% vs 26%; P=.19). Scores from maternal sleep and mood questionnaires at 6 weeks after delivery and self-reported infant and maternal sleep duration at 6 weeks and 4 months after delivery were similar between arms (P>.05). CONCLUSION: The SNOO responsive bassinet as a neonatal sleep intervention did not result in improved mean arterial pressure at 6 weeks after delivery after hypertensive disorders of pregnancy.

Influencing the Tumor Microenvironment: A Phase II Study of Copper Depletion Using Tetrathiomolybdate in Patients with Breast Cancer at High Risk for Recurrence and in Preclinical Models of Lung Metastases.

PURPOSE: Bone marrow-derived progenitor cells, including VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent pathways, model the tumor microenvironment. We hypothesized that copper depletion using tetrathiomolybdate would reduce EPCs in high risk for patients with breast cancer who have relapsed. We investigated the effect of tetrathiomolybdate on the tumor microenvironment in preclinical models. EXPERIMENTAL DESIGN: Patients with stage II triple-negative breast cancer (TNBC), stage III and stage IV without any evidence of disease (NED), received oral tetrathiomolybdate to maintain ceruloplasmin (Cp) between 8 and 17 mg/dL for 2 years or until relapse. Endpoints were effect on EPCs and other biomarkers, safety, event-free (EFS), and overall survival (OS). For laboratory studies, MDA-LM2-luciferase cells were implanted into CB17-SCID mice and treated with tetrathiomolybdate or water. Tumor progression was quantified by bioluminescence imaging (BLI), copper depletion status by Cp oxidase levels, lysyl oxidase (LOX) activity by ELISA, and collagen deposition. RESULTS: Seventy-five patients enrolled; 51 patients completed 2 years (1,396 cycles). Most common grade 3/4 toxicity was neutropenia (3.7%). Lower Cp levels correlated with reduced EPCs (P = 0.002) and LOXL-2 (P < 0.001). Two-year EFS for patients with stage II-III and stage IV NED was 91% and 67%, respectively. For patients with TNBC, EFS was 90% (adjuvant patients) and 69% (stage IV NED patients) at a median follow-up of 6.3 years, respectively. In preclinical models, tetrathiomolybdate decreased metastases to lungs (P = 0.04), LOX activity (P = 0.03), and collagen crosslinking (P = 0.012). CONCLUSIONS: Tetrathiomolybdate is safe, well tolerated, and affects copper-dependent components of the tumor microenvironment. Biomarker-driven clinical trials in high risk for patients with recurrent breast cancer are warranted. Clin Cancer Res; 23(3); 666-76. ©2016 AACR.