Clinical trial NCT05754645: The Microbiome in (Non-) Obese Pregnancy and Pregnancy Outcomes
Official title: The PROMOTE Study, a Pilot: The Characterization of the Microbiome in Pregnancy and Prediction of Pregnancy Outcomes
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Obesity, Maternal
Pregnancy Complications
Gut Microbiota
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2023-03-06
Enrollment: 110
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This pilot study is embedded in the Rotterdam Periconceptional Cohort study (Predict study). The Predict study population includes preconceptional or pregnant women \> 18 years and \< 45 years old visiting the Erasmus MC and that are willing to participate. We will select the participants, that meet our undermentioned inclusion criteria, for our study from this cohort: 50 women with a BMI \> 30 kg/m2 (cases) and 50 women with a BMI ranging 18-25 kg/m2 (controls) and their neonates.

We will longitudinally sample first/2nd/3rd/postpartum, 100 women, in addition we will include 10 preconceptional women with BMI \> 30 kg/m2 and 10 preconceptional women with BMI 18-25 kg/m2, these participants do not necessarily have to conceive a pregnancy in order to remain in the study (these women are part of the preconceptional Predict population).

Brief summary: This research aims to elucidate an underlying mechanism of maternal obesity induced pregnancy and longterm health complications for mothers and their offspring.

Detailed description: With the increasing global prevalence of obesity, pregnancy problems related to maternal obesity are increasingly occurring. Microbial gut symbiosis plays an important role in health, with dysbiosis being associated with diseases such as obesity. Of interest are pregnancy, dietary patterns and pre- or probiotics that affect the composition of the gut microbiome. The microbiome itself can influence many physiological processes, such as immune responses (production of microbial products) and the nutrient-dependent one-carbon metabolism. It is hypothesized that gut dysbiosis, due to maternal obesity, during pregnancy can be considered an endogenous chronic stressor causing impaired immune response and carbon metabolism. Both processes result in excessive oxidative stress, detrimental to cell replication, differentiation and epigenetic programming of maternal and infant tissues. Together, these biological disturbances contribute to placental and vascular dysfunction, leading to an increased risk of preeclampsia or gestational diabetes mellitus. Vertical (during pregnancy) and horizontal (during delivery) transmission of gut dysbiosis from mother to newborn and epigenetic placental and foetal changes may ultimately lead to macrosomia and obesity in children. Therefore, the differences between the gut and vaginal microbiome, maternal and fetal immune responses and one-carbon metabolism in obese versus normal-weight pregnant women will be analysed.

Eligibility criteria: Inclusion Criteria:

* Participation in Predict study
* Preconceptional women who wish to become pregnant or pregnancy \<13 weeks of gestational age.
* BMI \> 30 kg/m2 or 18-25 kg/m2
* Understanding of Dutch in speaking and reading
* Willingness to give written informed consent

Exclusion Criteria:

* Age \< 18 years and \> 45 years.
* ≥13 weeks of gestational age
* Multiple pregnancy
* Smoking
* Gastro-intestinal diseases, heart diseases, liver, pancreas and kidney diseases.
* Use of antibiotics \< 2 weeks before sampling
* Pre-existent diabetes mellitus

Primary outcomes:
measure: Gut and vaginal microbiota
timeFrame: Preconceptional (up to 1 year before pregnancy)
measure: Gut and vaginal microbiota
timeFrame: First trimester (between 7-12 weeks gestational age)
measure: Gut and vaginal microbiota
timeFrame: Second trimester (between 22-25 weeks gestational age)
measure: Gut and vaginal microbiota
timeFrame: Third trimester (between 30-32 weeks gestational age)
measure: Gut and vaginal microbiota
timeFrame: Antepartum (during delivery)
measure: Gut and vaginal microbiota
timeFrame: Postpartum (6-8 weeks post delivery)
Secondary outcomes:
measure: Gut virome
timeFrame: Preconceptional (up to 1 year before pregnancy)
measure: Gut virome
timeFrame: First trimester (between 7-12 weeks gestational age)
measure: Gut virome
timeFrame: Second trimester (between 22-24 weeks gestational age)
measure: Gut virome
timeFrame: Third trimester (between 30-32 weeks gestational age)
measure: Gut virome
timeFrame: Antepartum (during delivery)
measure: Gut virome
timeFrame: Postpartum (6-8 weeks post delivery)
measure: Maternal immune response
timeFrame: Preconceptional (up to 1 year before pregnancy)
measure: Maternal immune response
timeFrame: First trimester (between 7-12 weeks gestational age)
measure: Maternal immune response
timeFrame: Second trimester (between 22-24 weeks gestational age)
measure: Maternal immune response
timeFrame: Third trimester (between 30-32 weeks gestational age)
measure: Maternal immune response
timeFrame: Antepartum (during delivery)
measure: Maternal immune response
timeFrame: Postpartum (6-8 weeks post delivery)
measure: Maternal immune response
timeFrame: Preconceptional (up to 1 year before pregnancy)
measure: Maternal immune response
timeFrame: First trimester (between 7-12 weeks gestational age)
measure: Maternal immune response
timeFrame: Second trimester (between 22-24 weeks gestational age)
measure: Maternal immune response
timeFrame: Third trimester (between 30-32 weeks gestational age)
measure: Maternal immune response
timeFrame: Antepartum (during delivery)
measure: Maternal immune response
timeFrame: Postpartum (6-8 weeks post delivery)
measure: Maternal immune response
timeFrame: Preconceptional (up to 1 year before pregnancy)
measure: Maternal immune response
timeFrame: First trimester (between 7-12 weeks gestational age)
measure: Maternal immune response
timeFrame: Second trimester (between 22-24 weeks gestational age)
measure: Maternal immune response
timeFrame: Third trimester (between 30-32 weeks gestational age)
measure: Maternal immune response
timeFrame: Antepartum (during delivery)
measure: Maternal immune response
timeFrame: Postpartum (6-8 weeks post delivery)
measure: Maternal immune response
timeFrame: Preconceptional (up to 1 year before pregnancy)
measure: Maternal immune response
timeFrame: First trimester (between 7-12 weeks gestational age)
measure: Maternal immune response
timeFrame: Second trimester (between 22-24 weeks gestational age)
measure: Maternal immune response
timeFrame: Third trimester (between 30-32 weeks gestational age)
measure: Maternal immune response
timeFrame: Antepartum (during delivery)
measure: Maternal immune response
timeFrame: Postpartum (6-8 weeks post delivery)
measure: Maternal metabolic response
timeFrame: Preconceptional (up to 1 year before pregnancy)
measure: Maternal metabolic response
timeFrame: First trimester (between 7-12 weeks gestational age)
measure: Maternal metabolic response
timeFrame: Second trimester (between 22-24 weeks gestational age)
measure: Maternal metabolic response
timeFrame: Third trimester (between 30-32 weeks gestational age)
measure: Maternal metabolic response
timeFrame: Antepartum (during delivery)
measure: Maternal metabolic response
timeFrame: Postpartum (6-8 weeks post delivery)
measure: Maternal metabolic response
timeFrame: Preconceptional (up to 1 year before pregnancy)
measure: Maternal metabolic response
timeFrame: First trimester (between 7-12 weeks gestational age)
measure: Maternal metabolic response
timeFrame: Second trimester (between 22-24 weeks gestational age)
measure: Maternal metabolic response
timeFrame: Third trimester (between 30-32 weeks gestational age)
measure: Maternal metabolic response
timeFrame: Antepartum (during delivery)
measure: Maternal metabolic response
timeFrame: Postpartum (6-8 weeks post delivery)
measure: Maternal metabolic response
timeFrame: Preconceptional (up to 1 year before pregnancy)
measure: Maternal metabolic response
timeFrame: First trimester (between 7-12 weeks gestational age)
measure: Maternal metabolic response
timeFrame: Second trimester (between 22-24 weeks gestational age)
measure: Maternal metabolic response
timeFrame: Third trimester (between 30-32 weeks gestational age)
measure: Maternal metabolic response
timeFrame: Antepartum (during delivery)
measure: Maternal metabolic response
timeFrame: Postpartum (6-8 weeks post delivery)
measure: Clinical maternal outcome: gestational age
timeFrame: Durante partum
measure: Clinical maternal outcome: pre-eclampsia
timeFrame: from 20 weeks of gestation to <8 weeks postpartum
measure: Clinical maternal outcome: hypertension
timeFrame: from 20 weeks of gestation to <8 weeks postpartum
measure: Clinical maternal outcome: gestational diabetes
timeFrame: From the first positive pregnancy test to delivery
measure: Fetal growth
timeFrame: First trimester (Between 7-7+6 days of gestational age)
measure: Fetal growth
timeFrame: First trimester (Between 9-9+6 days of gestational age)
measure: Fetal growth
timeFrame: First trimester (Between 11-11+6 days of gestational age)
measure: Fetal growth
timeFrame: Second trimester (Between AD 22-25 weeks of gestational age)
measure: Fetal growth
timeFrame: Third trimester (Between 30-33 weeks of gestational age)
measure: Histological placental function
timeFrame: Postpartum (<2 days postpartum)
measure: Placental weight
timeFrame: Postpartum (<2 days postpartum)
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-Holland
Study officials:
References:
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