Preeclampsia (PE) is a complication during pregnancy characterized by hypertension, organ damage, and inflammation, without an effective treatment. The underlying mechanisms causing the disease also remain partly unknown. In this double-blind placebo-controlled study, the effects of probiotic dietary supplement GutMagnific during pregnancy will be assessed in pregnancies with a high risk of PE as well as low risk. The hypothesis is that probiotic dietary supplement GutMagnific can prevent or reduce the inflammatory response and clinical manifestations associated with PE through counteracting imbalances in the oral and gut microbiome composition.
PE is a leading cause of maternal and fetal morbidity and mortality worldwide, affecting 3-7% of pregnant women. PE is characterized by hypertension and organ damage manifesting after 20 gestational weeks, and is associated with an increased systemic inflammatory response in the mother. The clinical manifestations may vary greatly and are often more severe in early-onset PE (onset \<34 gestational weeks) than late-onset PE (onset ≥34 gestational weeks). Severe features include blood-pressure ≥160/110 mmHg, severe organ dysfunction, stroke, and eclampsia. Placental failure is central in the pathophysiology of PE, although the underlying mechanisms causing the disease remain partly unknown. Current research, including a previous study conducted by the investigators, suggests that disturbances in the gut microbiome might be involved in the pathogenesis of PE, leading to a dysfunctional immune response and damaged gut barrier functions. The investigators' previous study also indicated that PE is associated with gastrointestinal symptoms. GutMagnific is an evidence-based probiotic dietary supplement, shown to be effective in correcting disturbances in the gut microbiome, reduce inflammation and repair a damaged gut barrier. It was originally developed for treatment of irritable bowel syndrome (IBS). There is an overlap in immunological responses involved in PE and IBS, and women with IBS have a higher risk of developing PE. Therefore, the investigators expect that the product might also have positive effects in pregnant women with a high risk of PE.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
150
Participants will take one stick/10\^9 CFU of probiotic dietary supplement GutMagnific per day from gestational week 12 until gestational week 37
Participants will take one stick/placebo per day from gestational week 12 until partus.
Region Skåne
Lund, Sweden
RECRUITINGChanges in oral and gut microbiota composition
Fecal and salivary samples will be analyzed using next-generation sequencing techniques to monitor possible changes related to probiotic supplement, and possible associations with obstetric outcome (especially PE incidence) will be assessed. Samples taken prior to, during and after probiotic treatment in the same participant will be compared.
Time frame: Around gestational week 12 (baseline), 28, 37, and 6-8 weeks postpartum. In the event of a participant developing PE, samples will be taken at PE diagnosis as well.
Changes in gastrointestinal symptoms
A modified questionnaire for irritable bowel syndrome (IBS) symptoms will be filled in by participants grading different gastrointestinal symptoms from 1-10. Higher score indicates better condition.
Time frame: At the baseline and every two weeks until 6-8 weeks postpartum.
Changes in blood pressure
Blood pressure measurements at standard midwife appointments in antenatal care.
Time frame: At the baseline and continuously every 2-3 weeks from gestational week 24 throughout the pregnancy, and 6-8 weeks postpartum.
Differences in obstetric outcome
Incidence of adverse events during pregnancy, including PE, fetal growth restriction, gestational hypertension, gestational diabetes mellitus, and preterm birth.
Time frame: Data will be collected from the Swedish Pregnancy Register (Graviditetsregistret) and/or medical records through study completion, an average of 6 months for term pregnancies.
Changes in oral glucose tolerance test results
Blood glucose levels before (fasting) and after standard oral glucose tolerance test will be assessed to study possible effects of probiotic supplementation.
Time frame: Gestational week 28
Changes in circulatory Short-chain fatty acids (SCFAs) levels
Analysis of SCFAs levels in blood samples will be assessed to study possible effects of probiotic supplementation.
Time frame: Around gestational week 12 (baseline), 28, 37, and 6-8 weeks postpartum. In the event of a participant developing PE, samples will be taken at PE diagnosis as well.
Changes in circulatory Lipopolysaccharide (LPS) levels
Analysis of LPS levels in blood samples will be assessed to study possible effects of probiotic supplementation.
Time frame: Around gestational week 12 (baseline), 28, 37, and 6-8 weeks postpartum. In the event of a participant developing PE, samples will be taken at PE diagnosis as well.
Changes in metabolic parameters
Analysis of metabolic parameters such as ferritin will be assessed to study possible effects of probiotic supplementation.
Time frame: Around gestational week 12 (baseline), 28, 37, and 6-8 weeks postpartum. In the event of a participant developing PE, samples will be taken at PE diagnosis as well.
Change in systemic cytokine levels
Cytokines relevant in PE including IL6, IL1, IL10, IL17, TNF-alfa and interferon-gamma will be measured in blood samples to monitor possible effects of probiotic supplementation on the maternal inflammatory response.
Time frame: Around gestational week 12 (baseline), 28, 37, and 6-8 weeks postpartum. In the event of a participant developing PE, samples will be taken at PE diagnosis as well.
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