The Microbiome in (Non-) Obese Pregnancy and Pregnancy Outcomes

Recruiting

• Conditions: Pregnancy Complications; Obesity, Maternal; Gut Microbiota
• Interventions: Other: Blood withdrawal

• Registration Number: NCT05754645
• Lead Sponsor: Erasmus Medical Center

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.

Study Timeline

• Study Start: 2022-07-21
• Study First Submitted: 2023-01-24
• Status Verified: 2023-02
• Study First Submitted QC: 2023-02-22
• Last Update Submitted: 2023-02-22
• Study First Posted: 2023-03-06
• Last Update Posted: 2023-03-06
• Primary Completion: 2025-07-21
• Study Completion: 2026-07-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 110

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
110 women	Blood withdrawal	60 women with a BMI between 18,5-25 kg/m2, of which 10 preconceptional 60 women with a BMI \> 30 kg/m2, of which 10 preconceptional

Primary Outcome Measures

Name	Time	Method
Gut and vaginal microbiota	Postpartum (6-8 weeks post delivery)	Composition of gut and vaginal microbiota derived by swab sampling, bacteriome profiles will be assessed by 16SrRNA gene amplification sequencing (V6-V8). Sequences will be assigned to OTUs.

Secondary Outcome Measures

Name	Time	Method
Gut virome	Postpartum (6-8 weeks post delivery)	Composition of gut virome, obtained by a rectal swab
Clinical maternal outcome: gestational age	Durante partum	Gestational age (amenorrhea duration) at delivery.
Clinical maternal outcome: pre-eclampsia	from 20 weeks of gestation to <8 weeks postpartum	Pre-eclampsia is defined as the combination of gestational hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg (Korotkoff V) occurring after 20 weeks of gestation gestational age, measured twice, in a woman who previously had normal blood pressure) with proteinuria (≥ 300 mg/24 hours).
Fetal growth	Third trimester (Between 30-33 weeks of gestational age)	Fetal growth trajectories defined as Estimated Fetal Weight (EFW) (in grams) based on the measurements (in mm) of the Head circumference (HC), Biparietal diameter (BPD), Abdominal circumference (AC) and Femur length (FL) to be obtained/measured during the ultrasound.
Maternal immune response	Postpartum (6-8 weeks post delivery)	high sensitive C-reactive protein(hsCRP), measured in mg/L, obtained by blood withdrawal and measured in the lab.
Maternal metabolic response	Postpartum (6-8 weeks post delivery)	Markers of the one-carbon metabolism; B-vitamin 12, measured in micromol/l, obtained by blood withdrawal and measured in the lab.
Clinical maternal outcome: hypertension	from 20 weeks of gestation to <8 weeks postpartum	Hypertension is defined as a systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg (Korotkoff V) occurring after 20 weeks of gestation gestational age, measured twice, in a woman who previously had normal blood pressure.
Clinical maternal outcome: gestational diabetes	From the first positive pregnancy test to delivery	Gestational diabetes defined as any form of hyperglycaemia detected during pregnancy, regardless ofwhether this abnormality disappears after pregnancy. Diagnosed through a 75 gr Oral Glucose Tolerance Test (OGTT) with a fasting venous value \> 7 mmol/l or above 7.8 mmol/l after 2 hours.
Histological placental function	Postpartum (<2 days postpartum)	Histology of placenta: biopsies are taken within 2 days after delivery, these are snapfrozen in -80 degrees Celsius and assessed according to protocol by pathologist
Placental weight	Postpartum (<2 days postpartum)	Placental weight measured (in grams), weighed on the scale.

Trial Locations

Locations (1)

Erasmus MC; 🇳🇱 Rotterdam, Zuid-Holland, Netherlands