Pregnancy Complications - A Probiotic Interventional Study

Study Overview
=================
Brief Summary
-----------------
Investigators hypothesize that a) probiotics decrease the overall inflammatory state in the pregnant woman, especially in women with high risk pregnancies.

Detailed Description
-----------------
The main of the Project is to determine if dietary supplementation intake of probiotics are associated with a decreased inflammatory response in pregnant women, especially those with a history of previous preterm birth or preeclampsia, in a randomized clinical trial. Investigators also want to further investigate the relationship between intake of probiotics and the degree of inflammation in different compartments during pregnancy to see how the probiotic components affect the inflammatory state in the women.

Official Title
-----------------
Pregnancy Complications - A Probiotic Interventional Study

Conditions
-----------------
Preterm Birth, Preeclampsia

Intervention / Treatment
-----------------
* Drug: probiotic
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Maternal age > or = 18 y Singleton pregnancy Nulli or multiparous without maternal intercurrent diseases or pregnant women with a history of spontaneous preterm delivery or pregnant women with a history of preeclampsia. Exclusion Criteria Multiple pregnancy Gestational age > 17+6 weeks at first visit Chronic intermittent diseases (e.g. diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis, Chron disease, ulcerative colitis) Uterus malformations Immunomodulatory medication Hormonal treatment (e.g. crinone, progesterone) Subject disagrees to stop intake of other products containing probiotics during study time. Subject is unable to provide written informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PROBIOTIC in low-risk women<br>In low-risk women, probiotic group will be treated with the Active ingredient containing Lactobacillus rhamnosus (LGG) (> 10x8 CFU) during all pregnancy until delivery. Capsules contain maltodextrin, LGG and vegetal magnesium stearate. | Drug: probiotic<br>* Low-risk women, women with prior preeclampsia and women with a prior preterm birth will be randomized to be treated with LGG during pregnancy. Effect on maternal and perinatal outcome as well as the effect of treatment on immunological and inflammatory biomarkers will be evaluated.<br>* Other names: LGG;|
| Placebo Comparator: PLACEBO in low-risk women<br>In low-risk women, placebo group will be treated with the placebo ingredient during all pregnancy until delivery. The capsules of the placebo Group have similar content but lack the probiotic lactic acid bacteria which has been replaced by maltodextrin to make the mg amount equal. | Drug: placebo<br>* Low-risk women, women with prior preeclampsia and women with a prior preterm birth will be randomized to be treated with placebo during pregnancy. Effect on maternal and perinatal outcome as well as the effect of treatment on immunological and inflammatory biomarkers will be evaluated.<br>|
| Active Comparator: PROBIOTIC in women with a prior PTB<br>In women with a prior preterm birth (PTB), probiotic Group will be treated with the Active ingredient containing Lactobacillus rhamnosus (LGG) (> 10x8 CFU) during all pregnancy until delivery. Capsules contain maltodextrin, LGG and vegetal magnesium stearate. | Drug: probiotic<br>* Low-risk women, women with prior preeclampsia and women with a prior preterm birth will be randomized to be treated with LGG during pregnancy. Effect on maternal and perinatal outcome as well as the effect of treatment on immunological and inflammatory biomarkers will be evaluated.<br>* Other names: LGG;|
| Placebo Comparator: PLACEBO in women with a prior PTB<br>In women with a prior preterm birth (PTB), placebo group will be treated with the placebo ingredient during all pregnancy until delivery. The capsules of the placebo Group have similar content but lack the probiotic lactic acid bacteria which has been replaced by maltodextrin to make the mg amount equal. | Drug: placebo<br>* Low-risk women, women with prior preeclampsia and women with a prior preterm birth will be randomized to be treated with placebo during pregnancy. Effect on maternal and perinatal outcome as well as the effect of treatment on immunological and inflammatory biomarkers will be evaluated.<br>|
| Active Comparator: PROBIOTIC in women with a prior PE<br>In women with a prior preeclampsia (PE), probiotic Group will be treated with the Active ingredient containing Lactobacillus rhamnosus (LGG) (> 10x8 CFU) during all pregnancy until delivery. Capsules contain maltodextrin, LGG and vegetal magnesium stearate. | Drug: probiotic<br>* Low-risk women, women with prior preeclampsia and women with a prior preterm birth will be randomized to be treated with LGG during pregnancy. Effect on maternal and perinatal outcome as well as the effect of treatment on immunological and inflammatory biomarkers will be evaluated.<br>* Other names: LGG;|
| Placebo Comparator: PLACEBO in women with a prior PE<br>In women with a prior preeclampsia (PE), placebo Group will be treated with the placebo ingredient during all pregnancy until delivery. The capsules of the placebo Group have similar content but lack the probiotic lactic acid bacteria which has been replaced by maltodextrin to make the mg amount equal. | Drug: placebo<br>* Low-risk women, women with prior preeclampsia and women with a prior preterm birth will be randomized to be treated with placebo during pregnancy. Effect on maternal and perinatal outcome as well as the effect of treatment on immunological and inflammatory biomarkers will be evaluated.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory modulation of Lactobacillus Rhamnosus in low risk mothers. | Intake of LGG Rhamnosus throughout the pregnancy and its effect on levels of subpopulations of lymphocytes in peripheral blood (T/B/NK-celler), and cytokine production (TNF alfa, IL10, IL12) after stimulation with E. Coli, L. paracasei and P. aerugnousa, measuring change from baseline to 25 and 35 weeks gestation. | at recruitment, week 25, week 35 of gestation | 
| Inflammatory modulation of Lactobacillus Rhamnosus in mothers with previous preterm birth. | Intake of LGG Rhamnosus throughout the pregnancy and its effect on levels of subpopulations of lymphocytes in peripheral blood (T/B/NK-celler), and cytokine production (TNF alfa, IL10, IL12) after stimulation with E. Coli, L. paracasei and P. aerugnousa, measuring change from baseline to 25 and 35 weeks gestation. | at recruitment, week 25, week 35 of gestation | 
| Inflammatory modulation of Lactobacillus Rhamnosus in mothers with previous preeclampsia. | Intake of LGG Rhamnosus throughout the pregnancy and its effect on levels of subpopulations of lymphocytes in peripheral blood (T/B/NK-celler), and cytokine production (TNF alfa, IL10, IL12) after stimulation with E. Coli, L. paracasei and P. aerugnousa, measuring change from baseline to 25 and 35 weeks gestation. | at recruitment, week 25, week 35 of gestation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
preterm birth, preeclampsia, Probiotics, inflammation, immunological response