Planned cesarean delivery vs planned vaginal delivery: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: There are over 145 million births worldwide, with over 30 million cesarean deliveries yearly. There are limited data comparing the perinatal and maternal outcomes between planned cesarean delivery and planned vaginal delivery. This study aimed to evaluate perinatal and maternal morbidity and mortality by meta-analysis of randomized controlled trials that randomly assigned patients to either planned cesarean delivery or planned vaginal delivery. DATA SOURCES: Scopus, PubMed, CINAHL, Cochrane Library, and the World Health Organization clinical trial databases were searched from inception through August 2022. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that compared planned cesarean delivery with planned vaginal delivery at any gestational age and for any delivery indication were included. METHODS: Two authors independently extracted data. PRISMA guidelines were used for data extraction and quality assessment. The primary outcome was perinatal mortality. The summary measures were reported as relative risks or as mean differences with 95% confidence intervals. Pooled odds ratios and 95% confidence intervals were calculated using Mantel-Haenszel random-effects models for outcomes. RESULTS: In 15 primary randomized controlled trials, 3265 patients were randomized to planned cesarean delivery and 3353 to planned vaginal delivery. The incidence of perinatal deaths was not different (1.3% vs 1.3%; relative risk, 0.71; 95% confidence interval, 0.33-1.52). Planned cesarean delivery was associated with lower neonatal incidences of low umbilical artery pH (0.3% vs 2.4%; relative risk, 0.18; 95% confidence interval, 0.05-0.67), birth trauma (0.3% vs 0.7%; relative risk, 0.46; 95% confidence interval, 0.22-0.96), tube feeding requirement (2.5% vs 7.1%; relative risk, 0.36; 95% confidence interval, 0.19-0.66), and hypotonia (0.4% vs 3.5%; relative risk, 0.11; 95% confidence interval, 0.03-0.47), compared to planned vaginal delivery. Chorioamnionitis was less frequent in the planned cesarean delivery group (0.3% vs 1.0%; relative risk, 0.27; 95% confidence interval, 0.08-0.98). Wound infection was more common in the planned cesarean delivery group (1.9% vs 1.1%; relative risk, 1.61; 95% confidence interval, 1.04-2.52). Lower rates were observed in the planned cesarean delivery group for urinary incontinence at both ≤3 months (8.7% vs 12.2%; relative risk, 0.71; 95% confidence interval, 0.59-0.85) and 1 to 2 years (16.9% vs 22%; relative risk, 0.77; 95% confidence interval, 0.67-0.88) and for a painful perineum at 2 years (4% vs 6.2%; relative risk, 0.64; 95% confidence interval, 0.47-0.87) compared to planned vaginal delivery. Among singleton pregnancies, planned cesarean delivery was associated with a lower rate of perinatal death (0.69% vs 1.81%; relative risk, 0.45; 95% confident interval, 0.21-0.93). CONCLUSION: Planned cesarean delivery and planned vaginal delivery were associated with similar rates of perinatal and maternal mortality in this meta-analysis of randomized controlled trials. Planned cesarean delivery was associated with significant decreases in adverse neonatal outcomes such as low umbilical artery pH, birth trauma, tube feeding requirement, and hypotonia, and significant decreases in chorioamnionitis, urinary incontinence, and painful perineum. Planned vaginal delivery was associated with significant decreases in need for general anesthesia and wound infection. Further randomized trials are needed to assess the risks and benefits of planned cesarean delivery vs planned vaginal delivery in lower-risk patients and in the general population.

δ-COP modulates Aß peptide formation via retrograde trafficking of APP.

The components involved in cellular trafficking and protein recycling machinery that have been associated with increased Alzheimer's disease (AD) risk belong to the late secretory compartments for the most part. Here, we hypothesize that these late unavoidable events might be the consequence of earlier complications occurring while amyloid precursor protein (APP) is trafficking through the early secretory pathway. We investigated the relevance to AD of coat protein complex I (COPI)-dependent trafficking, an early step in Golgi-to-endoplasmic reticulum (ER) retrograde transport and one of the very first trafficking steps. Using a complex set of imaging technologies, including inverse fluorescence recovery after photobleaching (iFRAP) and photoactivatable probes, coupled to biochemical experiments, we show that COPI subunit δ (δ-COP) affects the biology of APP, including its subcellular localization and cell surface expression, its trafficking, and its metabolism. These findings demonstrate the crucial role of δ-COP in APP metabolism and, consequently, the generation of amyloid-ß (Aß) peptide, providing previously nondescribed mechanistic explanations of the underlying events.

Relevance of the COPI complex for Alzheimer's disease progression in vivo.

Cellular trafficking and recycling machineries belonging to late secretory compartments have been associated with increased Alzheimer's disease (AD) risk. We have shown that coat protein complex I (COPI)-dependent trafficking, an early step in Golgi-to-endoplasmic reticulum retrograde transport, affects amyloid precursor protein subcellular localization, cell-surface expression, as well as its metabolism. We present here a set of experiments demonstrating that, by targeting subunit δ-COP function, the moderation of the COPI-dependent trafficking in vivo leads to a significant decrease in amyloid plaques in the cortex and hippocampus of neurological 17 mice crossed with the 2xTg AD mouse model. Remarkably, an improvement of the memory impairments was also observed. Importantly, human genetic association studies of different AD cohorts led to the identification of 12 SNPs and 24 mutations located in COPI genes linked to an increased AD risk. These findings further demonstrate in vivo the importance of early trafficking steps in AD pathogenesis and open new clinical perspectives.