Preeclampsia is one of the most common obstetrical complications worldwide. The pathomechanism of this disease begins with abnormal placentation in early pregnancy, which is associated with inappropriate decidualization, vasculogenesis, angiogenesis, and spiral artery remodeling, leading to endothelial dysfunction. In these processes, appropriate cellular deaths have been proposed to play a pivotal role, including apoptosis and autophagy. The proper functioning of these physiological cell deaths for placentation depends on the wellbeing of the trophoblasts, affected by the structural and functional integrity of each cellular component including the cell membrane, mitochondria, endoplasmic reticulum, genetics, and epigenetics. This cellular wellness, which includes optimal cellular integrity and function, is heavily influenced by nutritional adequacy. In contrast, nutritional deficiencies may result in the alteration of plasma membrane, mitochondrial dysfunction, endoplasmic reticulum stress, and changes in gene expression, DNA methylation, and miRNA expression, as well as weakened defense against environmental contaminants, hence inducing a series of inappropriate cellular deaths such as abnormal apoptosis and necrosis, and autophagy dysfunction and resulting in abnormal trophoblast invasion. Despite their inherent connection, the currently available studies examined the functions of each organelle, the cellular death mechanisms and the nutrition involved, both physiologically in the placenta and in preeclampsia, separately. Therefore, this review aims to comprehensively discuss the relationship between each organelle in maintaining the physiological cell death mechanisms and the nutrition involved, and the interconnection between the disruptions in the cellular organelles and inappropriate cell death mechanisms, resulting in poor trophoblast invasion and differentiation, as seen in preeclampsia.
Introduction: Cesarean section is one of the most common obstetrical interventions that has been performed at an increasing rate globally, due to both medical and non-medical reasons. This study aims to develop a prediction tool for pregnant women potentially needing c-section, such that necessary preparations from the mothers, families, and health providers can be made. Methods: A total of 603 pregnant women were recruited in the first phase of c-section prediction tool development. The association between the maternal and fetal factors on the risk of c-section were analyzed, followed by a stepwise multivariate regression analysis. In the next phase, 61 pregnant women were enrolled for external validation. Discrimination was assessed using area under the curve. The calibration plot was then made and assessed using the Hosmer–Lemeshow test. Results: There were 251 (41.6%) cases of vaginal delivery and 352 (58.4%) of c-section assessed. Multivariate analysis showed that gestational age < 37 wg (OR: 1.66, 95% CI: 1.10–2.51), pre-pregnancy body mass index (underweight) (OR: 0.40, 95% CI: 0.22–0.76), no history of vaginal delivery (OR: 2.66, 95% CI: 1.76–4.02), history of uterine surgery (OR: 8.34, 95% CI: 4.54–15.30), obstetrical complications (OR: 5.61, 95% CI: 3.53–8.90), birthweight ⩾ 3500 g (OR: 4.28, 95% CI: 2.16–8.47), and non-cephalic presentation (OR: 2.74, 95% CI: 1.53–4.89) were independently associated with c-section delivery. Those parameters were included in a 7-item scoring tool, with consecutive predictive scores of 1,–1,2,3,3,2,2,1. The area under the curve result was 0.813 (95% CI: 0.779–0.847), indicating a good predictive ability. The external validation showed AUC: 0.806, 95% CI: 0.694–0.917, Hosmer–Lemeshow test p = 0.666 and calibration plot coefficient of r = 0.939. Conclusion: A total of 7 maternal-fetal factors were found to be strongly associated with c-section delivery, including gestational age < 37, maternal underweight body mass index, previous uterine surgery, obstetrical complications, birthweight ⩾ 3500, history of vaginal delivery, and non-cephalic presentation. Using these factors, a prediction tool was developed and validated with good quality.
Introduction: Although vitamin D is widely known as an essential micronutrient during pregnancy, the exact supplementation dose to prevent maternal–fetal outcomes remains a question. This study aims to provide a systematic review and a meta-analysis of data from randomized controlled trial on > 2000 IU/day vitamin D supplementation compared to ⩽ 2000 IU/day; and ⩽ 2000 IU/day compared to placebo, on their effects on the incidence of preeclampsia, gestational diabetes mellitus, preterm birth, and differences on birth weight. Methods: A systematic literature search on PubMed, EBSCO-MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases was carried out to evaluate randomized controlled trial studies on the effects of oral vitamin D > 2000 IU/day versus ⩽ 2000 IU/day; and ⩽ 2000 IU/day versus placebo, on preeclampsia, gestational diabetes mellitus, preterm birth and birth weight. Risk ratio, mean difference, and 95% confidence interval were calculated. Results: There were a total of 27 randomized controlled trials selected. Maternal vitamin D supplementation > 2000 IU/day had a positive effect only on gestational diabetes mellitus (seven randomized controlled trials; risk ratio = 0.70, 95% confidence interval: 0.51–0.95, I2 = 0). Vitamin D supplementation ⩽ 2000 IU/day has reduced the risk of preeclampsia (three randomized controlled trials; risk ratio = 0.29, 95% confidence interval: 0.09–0.95, I2 = 0), with no significant difference when compared to > 2000 IU/day (eight randomized controlled trials; risk ratio = 0.80, 95% confidence interval: 0.51–1.24, I2 = 31). No difference in preterm birth risk and birth weight after vitamin D supplementation. The quality of evidence varies from moderate to very low certainty. The risk of preeclampsia and gestational diabetes mellitus after high-dose versus low-dose vitamin D supplementation was the ones with moderate certainty. Conclusion: Vitamin D supplementation > 2000 IU/day might be important to reduce the risk of gestational diabetes mellitus. Lower dose vitamin D supplementation (⩽ 2000 IU/day) seemed adequate to reduce the risk of preeclampsia, with no significant difference compared to the higher dose.
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