The placenta is a vital, multi-functional organ that acts as an interface between maternal and fetal circulation during pregnancy. Nutritional deficiencies during pregnancy alter placental development and function, leading to adverse pregnancy outcomes, such as pre-eclampsia, infants with small for gestational age and low birthweight, preterm birth, stillbirths and maternal mortality. Maternal nutritional supplementation may help to mitigate the risks, but the evidence base is difficult to navigate. The primary purpose of this umbrella review is to map the evidence on the effects of maternal nutritional supplements and dietary interventions on pregnancy outcomes related to placental disorders and maternal mortality. A systematic search was performed on seven electronic databases, the PROSPERO register and references lists of identified papers. The results were screened in a three-stage process based on title, abstract and full-text by two independent reviewers. Randomized controlled trial meta-analyses on the efficacy of maternal nutritional supplements or dietary interventions were included. There were 91 meta-analyses included, covering 23 types of supplements and three types of dietary interventions. We found evidence that supports supplementary vitamin D and/or calcium, omega-3, multiple micronutrients, lipid-based nutrients, and balanced protein energy in reducing the risks of adverse maternal and fetal health outcomes. However, these findings are limited by poor quality of evidence. Nutrient combinations show promise and support a paradigm shift to maternal dietary balance, rather than single micronutrient deficiencies, to improve maternal and fetal health. The review is registered at PROSPERO (CRD42020160887).
Healthy maternal diets can lower the odds of developing pre-eclampsia, a direct and second leading cause of maternal death, globally. However, there is a research gap in low- and middle-income countries (LMIC), which bear a disproportionate burden of these deaths. The objectives of this systematic review were to: 1) evaluate the association between dietary patterns in pregnancy and hypertensive disorders, including pre-eclampsia for pregnant and postpartum women in LMIC, and 2) compile barriers and facilitators to an adequate maternal diet. A systematic search was performed on MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health, Web of Science, Cochrane Central Register of Controlled Trials, African Journals Online, the WHO Regional Databases, 2 trial registries, Google Scholar, and reference lists. Included in the analysis were primary research studies of dietary patterns during pregnancy, with pregnancy hypertension outcome(s), and conducted in LMIC. Included studies were assessed using ROBINS-I risk of bias. Thirteen studies were included, of which 5 studies were included in a meta-analysis (Review Manager 5). Lower odds of pre-eclampsia were associated with adequate (compared with no or low) consumption of vegetables (OR: 0.38; 95% CI: 0.18, 0.80; I2 = 85%; P = 0.01) and adequate (compared with no or low) consumption of fruit (OR: 0.42; 95% CI: 0.24, 0.71; I2 = 79%; P = 0.008). No firm conclusions could be drawn about the impact on pre-eclampsia odds of any of the following during pregnancy: high consumption of meat or grains; a “Western” diet; or alcohol consumption. More LMIC-based research is needed to explore whether the apparent beneficial effects of fruits and vegetables on pre-eclampsia incidence might be enhanced when maternal malnutrition is prevalent, and/or whether other sociodemographic factors might contribute.
Background Pre-eclampsia is a leading cause of maternal mortality and morbidity that involves pregnancy-related stressors on the maternal cardiovascular and metabolic systems. As nutrition is important to support optimal development of the placenta and for the developing fetus, maternal diets may play a role in preventing pre-eclampsia. The purpose of this scoping review is to map the maternal nutritional deficiencies and imbalances associated with pre-eclampsia incidence and discuss evidence consistency and linkages with current understandings of the etiology of pre-eclampsia. Methods A narrative scoping review was conducted to provide a descriptive account of available research, summarize research findings and identify gaps in the evidence base. Relevant observational studies and reviews of observational studies were identified in an iterative two-stage process first involving electronic database searches then more sensitive searches as familiarity with the literature increased. Results were considered in terms of their consistency of evidence, effect sizes and biological plausibility. Results The review found evidence for associations between nutritional inadequacies and a greater risk of pre-eclampsia. These associations were most likely mediated through oxidative stress, inflammation, maternal endothelial dysfunction and blood pressure in the pathophysiology of pre-eclampsia. Maternal nutritional risk factors for pre-eclampsia incidence with the strongest consistency, effect and biological plausibility include vitamin C and its potential relationship with iron status, vitamin D (both on its own and combined with calcium and magnesium), and healthy dietary patterns featuring high consumption of fruits, vegetables, whole grains, fish, seafood and monounsaturated vegetable oils. Foods high in added sugar, such as sugary drinks, were associated with increased risk of pre-eclampsia incidence. Conclusion A growing body of literature highlights the involvement of maternal dietary factors in the development of pre-eclampsia. Our review findings support the need for further investigation into potential interactions between dietary factors and consideration of nutritional homeostasis and healthy dietary patterns. Further research is recommended to explore gestational age, potential non-linear relationships, dietary diversity and social, cultural contexts of food and meals.
Objectives Pregnancy is a metabolically active life stage. Formate plays a major role in one-carbon metabolism, a biosynthetic pathway critical for cellular growth and function. Because formate can be synthesized from amino acid precursors serine, glycine, tryptophan and methionine, it suggests that urinary formate concentration may be low in response to low protein intakes. Additionally, sulfate is the excretory endpoint for the breakdown of indispensable, sulfur containing amino acids methionine and cysteine. Our objectives were to determine if urinary excretion of formate/sulfate can be utilized as non-invasive biomarkers in pregnancy, when protein intakes range from deficient to adequate. Methods Urinary samples (n = 81) from pregnant women (11–20- and 30–38-weeks’ gestation) were collected when consuming graded protein intakes (0.2–2.56 g/kg/d) and were analyzed for sulfate and formate concentrations. For sulfate, spectrophotometric absorbance was measured and compared to a standard curve, and formate was analyzed using an enzymatic assay. Concentrations of the catabolites were normalized using creatinine concentrations and plotted against protein intakes. Regression models were used to examine potential relationships. Sulfate excretion was also compared to the estimated total sulfur amino acid intake (TSAA, methionine + cysteine). Results With increasing protein intakes, formate excretion remained constant. Urinary sulfate concentrations increased in response to increasing protein. A bi-phase linear regression model revealed there was an observable breakpoint in increased sulfate excretion in early gestation at 33–36 mg/kg/d of estimated TSAA intake, and at 30–39 mg/kg/d for late gestation. Conclusions There was no observable relationship to suggest urinary formate could be used as a biomarker for protein/amino acid status during pregnancy. Urinary sulfate concentrations may be a viable indicator for measuring total sulfur amino acid (methionine, cysteine) status. Further studies on TSAA requirements in pregnancy using more state-of-the-art stable isotope techniques are needed to confirm these findings from non-invasive urinary biomarkers. Funding Sources Canadian Institutes of Health Research.
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