Characteristics of preterm births during COVID-19 mitigation measures.

BACKGROUND: During the COVID-19 pandemic, mitigation measures were associated with a reduction in preterm birth rates; while not clearly proven, this observation has sparked significant interest. AIM: To understand the cause of this reduction by exploring the characteristics of preterm birth cohorts. MATERIAL AND METHODS: We performed a retrospective cohort study where we compared women who delivered preterm in three Melbourne maternity hospitals and conceived between November 2019 and February 2020 (mitigation measures-exposed cohort) to women who delivered preterm and conceived between November 2018 and February 2019 (non-exposed cohort). We compared maternal characteristics, pregnancy complications, antenatal interventions, intrapartum care, and indications for delivery. RESULTS: In the exposed cohort, 252/3129 women delivered preterm (8.1%), vs 298/3154 (9.4%) in the non-exposed cohort (odds ratio (OR) 0.84, 95% CI 0.70-1.00, P = 0.051). The baseline characteristic of two cohorts were comparable. Rates of spontaneous preterm labour (sPTL) without preterm pre-labour rupture of membranes (PPROM) were lower in the exposed cohort (13.1% vs 24.2%, OR 0.47, P = 0.001) while PPROM occurred more often (48.0% vs 35.6%, OR 1.67, P = 0.003). With a non-statistically significant prolongation of pregnancy in the cohort exposed to mitigation measures for both sPTL without PPROM (35.4 vs 34.9 weeks, P = 0.703) and PPROM (35.6 vs 34.9 weeks, P = 0.184). The rate of spontaneous labour after PPROM was higher in the exposed cohort compared to the non-exposed cohort (40.1% vs 24.1%, OR 2.09, P < 0.001). CONCLUSION: The reduction in preterm delivery during mitigation measures may have been driven by a reduction in spontaneous labour without PPROM, which seemed to result in more PPROM later in pregnancy.

Randomised controlled trials in women's health in the last two decades: A meta-review.

OBJECTIVES: Obstetric and gynaecological conditions represent a significant burden of disease, requiring clinical research. We aimed to study trends in the publication of randomised controlled trials (RCTs) in women's health over the last two decades. The primary objective was to describe longitudinal trends in the geographical distribution of RCTs in obstetrics and gynaecology. We also described trends in trial funding, publication sources and separately published trial protocols. STUDY DESIGN: RCTs were identified by searching the Web of Science alone, due to the large number of results and descriptive nature of analyses. Using the filter tool, only studies labelled as "Clinical trial" or "Article" were included; all other document types were excluded. Trial protocols were identified and analysed separately. Indexing data were extracted using the Web of Science selection tools. As we aimed simply to describe research trends using a single platform, we did not check for duplicates. No process for data pooling was necessary. Correlation of GDP, funding and number of RCTs was calculated using Pearson's r test. RESULTS: We identified 39,071 RCTs. The number of annual publications globally increased from 1,406 in 2001 to 1,979 in 2020. The US (n = 12,479) and the UK (n = 3,745) were responsible for the most RCTs, followed by Italy (n = 2,676) and China (n = 2,338). The largest percentage increase in annual publications was seen in Iran (n = 5 to n = 113, +2,160 %) and the Western Pacific Region (n = 16 to n = 171, +968.8 %). GDP was significantly correlated with the number of published RCTs in 2019 for the 25 most prolific countries (p < 0.001), but not with the proportion of RCTs funded. CONCLUSIONS: Despite growing contributions from the Western Pacific and Eastern Mediterranean regions, most RCTs are still produced in a small nucleus of high-income countries. Increased international collaboration may benefit both high- and low-income countries.

Insights into the role of maladaptive hexosamine biosynthesis and O-GlcNAcylation in development of diabetic cardiac complications.

Diabetes mellitus significantly increases the risk of heart failure, independent of coronary artery disease. The mechanisms implicated in the development of diabetic heart disease, commonly termed diabetic cardiomyopathy, are complex, but much of the impact of diabetes on the heart can be attributed to impaired glucose handling. It has been shown that the maladaptive nutrient-sensing hexosamine biosynthesis pathway (HBP) contributes to diabetic complications in many non-cardiac tissues. Glucose metabolism by the HBP leads to enzymatically-regulated, O-linked attachment of a sugar moiety molecule, ß-N-acetylglucosamine (O-GlcNAc), to proteins, affecting their biological activity (similar to phosphorylation). In normal physiology, transient activation of HBP/O-GlcNAc mechanisms is an adaptive, protective means to enhance cell survival; interventions that acutely suppress this pathway decrease tolerance to stress. Conversely, chronic dysregulation of HBP/O-GlcNAc mechanisms has been shown to be detrimental in certain pathological settings, including diabetes and cancer. Most of our understanding of the impact of sustained maladaptive HBP and O-GlcNAc protein modifications has been derived from adipose tissue, skeletal muscle and other non-cardiac tissues, as a contributing mechanism to insulin resistance and progression of diabetic complications. However, the long-term consequences of persistent activation of cardiac HBP and O-GlcNAc are not well-understood; therefore, the goal of this timely review is to highlight current understanding of the role of the HBP pathway in development of diabetic cardiomyopathy.