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

Pregnancy Complications Clinical Trial

— PROMOTE  

Official title:

The PROMOTE Study, a Pilot: The Characterization of the Microbiome in Pregnancy and Prediction of Pregnancy Outcomes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05754645
• Other study ID #: NL80155.078.22/OZBS72.21318
• Status: Recruiting
• Start date: July 21, 2022
• Est. completion date: July 21, 2026

Study information

• Verified date: February 2023
• Source: Erasmus Medical Center
• Contact: Nicole Schenkelaars, MD
• Phone: +31627530793
• Email: n.schenkelaars[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: July 21, 2026
• Est. primary completion date: July 21, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Gut Microbiota
• Pregnancy Complications

Intervention

Other:
• Blood withdrawal
venous punction with blood withdrawal Vaginal and rectal swab, done by patient itself

Locations

Country	Name	City	State
Netherlands	Erasmus MC	Rotterdam	Zuid-Holland

Sponsors (1)

Lead Sponsor	Collaborator
Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (10)

Elderman M, Hugenholtz F, Belzer C, Boekschoten M, de Haan B, de Vos P, Faas M. Changes in intestinal gene expression and microbiota composition during late pregnancy are mouse strain dependent. Sci Rep. 2018 Jul 3;8(1):10001. doi: 10.1038/s41598-018-28292-2. — View Citation

Gaillard R, Durmus B, Hofman A, Mackenbach JP, Steegers EA, Jaddoe VW. Risk factors and outcomes of maternal obesity and excessive weight gain during pregnancy. Obesity (Silver Spring). 2013 May;21(5):1046-55. doi: 10.1002/oby.20088. — View Citation

Kuhle S, Muir A, Woolcott CG, Brown MM, McDonald SD, Abdolell M, Dodds L. Maternal pre-pregnancy obesity and health care utilization and costs in the offspring. Int J Obes (Lond). 2019 Apr;43(4):735-743. doi: 10.1038/s41366-018-0149-3. Epub 2018 Jul 13. — View Citation

Mission JF, Marshall NE, Caughey AB. Pregnancy risks associated with obesity. Obstet Gynecol Clin North Am. 2015 Jun;42(2):335-53. doi: 10.1016/j.ogc.2015.01.008. — View Citation

Morgan KL, Rahman MA, Macey S, Atkinson MD, Hill RA, Khanom A, Paranjothy S, Husain MJ, Brophy ST. Obesity in pregnancy: a retrospective prevalence-based study on health service utilisation and costs on the NHS. BMJ Open. 2014 Feb 27;4(2):e003983. doi: 10.1136/bmjopen-2013-003983. — View Citation

Rousian M, Schoenmakers S, Eggink AJ, Gootjes DV, Koning AHJ, Koster MPH, Mulders AGMGJ, Baart EB, Reiss IKM, Laven JSE, Steegers EAP, Steegers-Theunissen RPM. Cohort Profile Update: the Rotterdam Periconceptional Cohort and embryonic and fetal measurements using 3D ultrasound and virtual reality techniques. Int J Epidemiol. 2021 Nov 10;50(5):1426-1427l. doi: 10.1093/ije/dyab030. No abstract available. — View Citation

Schoenmakers S, Steegers-Theunissen R, Faas M. The matter of the reproductive microbiome. Obstet Med. 2019 Sep;12(3):107-115. doi: 10.1177/1753495X18775899. Epub 2018 May 17. — View Citation

Singh AS, Mulder C, Twisk JW, van Mechelen W, Chinapaw MJ. Tracking of childhood overweight into adulthood: a systematic review of the literature. Obes Rev. 2008 Sep;9(5):474-88. doi: 10.1111/j.1467-789X.2008.00475.x. Epub 2008 Mar 5. — View Citation

Tanvig M. Offspring body size and metabolic profile - effects of lifestyle intervention in obese pregnant women. Dan Med J. 2014 Jul;61(7):B4893. — View Citation

Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI. A core gut microbiome in obese and lean twins. Nature. 2009 Jan 22;457(7228):480-4. doi: 10.1038/nature07540. Epub 2008 Nov 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gut and vaginal microbiota	Composition of gut and vaginal microbiota derived by swab sampling, bacteriome profiles will be assessed by 16S ribosomal ribonucleic acid (16SrRNA) gene amplification sequencing (V6-V8). Sequences will be assigned to operational taxonomic units (OTUs).	Preconceptional (up to 1 year before pregnancy)
Primary	Gut and vaginal microbiota	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.	First trimester (between 7-12 weeks gestational age)
Primary	Gut and vaginal microbiota	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.	Second trimester (between 22-25 weeks gestational age)
Primary	Gut and vaginal microbiota	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.	Third trimester (between 30-32 weeks gestational age)
Primary	Gut and vaginal microbiota	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.	Antepartum (during delivery)
Primary	Gut and vaginal microbiota	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.	Postpartum (6-8 weeks post delivery)
Secondary	Gut virome	Composition of gut virome, obtained by a rectal swab	Preconceptional (up to 1 year before pregnancy)
Secondary	Gut virome	Composition of gut virome, obtained by a rectal swab	First trimester (between 7-12 weeks gestational age)
Secondary	Gut virome	Composition of gut virome, obtained by a rectal swab	Second trimester (between 22-24 weeks gestational age)
Secondary	Gut virome	Composition of gut virome, obtained by a rectal swab	Third trimester (between 30-32 weeks gestational age)
Secondary	Gut virome	Composition of gut virome, obtained by a rectal swab	Antepartum (during delivery)
Secondary	Gut virome	Composition of gut virome, obtained by a rectal swab	Postpartum (6-8 weeks post delivery)
Secondary	Maternal immune response	Responses of maternal immune system advanced oxidation protein products (AOPP)) measured in chloramine units per gram of protein (micromol/g) obtained by blood withdrawal and measured in the lab.	Preconceptional (up to 1 year before pregnancy)
Secondary	Maternal immune response	Responses of maternal immune system advanced oxidation protein products (AOPP)) measured in chloramine units per gram of protein (micromol/g) obtained by blood withdrawal and measured in the lab.	First trimester (between 7-12 weeks gestational age)
Secondary	Maternal immune response	Responses of maternal immune system advanced oxidation protein products (AOPP)) measured in chloramine units per gram of protein (micromol/g) obtained by blood withdrawal and measured in the lab.	Second trimester (between 22-24 weeks gestational age)
Secondary	Maternal immune response	Responses of maternal immune system advanced oxidation protein products (AOPP)) measured in chloramine units per gram of protein (micromol/g) obtained by blood withdrawal and measured in the lab.	Third trimester (between 30-32 weeks gestational age)
Secondary	Maternal immune response	Responses of maternal immune system advanced oxidation protein products (AOPP)) measured in chloramine units per gram of protein (micromol/g) obtained by blood withdrawal and measured in the lab.	Antepartum (during delivery)
Secondary	Maternal immune response	Responses of maternal immune system advanced oxidation protein products (AOPP)) measured in chloramine units per gram of protein (micromol/g) obtained by blood withdrawal and measured in the lab.	Postpartum (6-8 weeks post delivery)
Secondary	Maternal immune response	Tumor necrosis factor-alpha (TNF-alpha) measured in picograms per milliliter, obtained by blood withdrawal and measured in the lab.	Preconceptional (up to 1 year before pregnancy)
Secondary	Maternal immune response	Tumor necrosis factor-alpha (TNF-alpha) measured in picograms per milliliter, obtained by blood withdrawal and measured in the lab.	First trimester (between 7-12 weeks gestational age)
Secondary	Maternal immune response	Tumor necrosis factor-alpha (TNF-alpha) measured in picograms per milliliter, obtained by blood withdrawal and measured in the lab.	Second trimester (between 22-24 weeks gestational age)
Secondary	Maternal immune response	Tumor necrosis factor-alpha (TNF-alpha) measured in picograms per milliliter, obtained by blood withdrawal and measured in the lab.	Third trimester (between 30-32 weeks gestational age)
Secondary	Maternal immune response	Tumor necrosis factor-alpha (TNF-alpha) measured in picograms per milliliter, obtained by blood withdrawal and measured in the lab.	Antepartum (during delivery)
Secondary	Maternal immune response	Tumor necrosis factor-alpha (TNF-alpha) measured in picograms per milliliter, obtained by blood withdrawal and measured in the lab.	Postpartum (6-8 weeks post delivery)
Secondary	Maternal immune response	Interleukin-6 (IL-6), measured in picograms per milliliter, obtained by blood withdrawal and measured in the lab.	Preconceptional (up to 1 year before pregnancy)
Secondary	Maternal immune response	Interleukin-6 (IL-6), measured in picograms per milliliter, obtained by blood withdrawal and measured in the lab.	First trimester (between 7-12 weeks gestational age)
Secondary	Maternal immune response	Interleukin-6 (IL-6), measured in picograms per milliliter, obtained by blood withdrawal and measured in the lab.	Second trimester (between 22-24 weeks gestational age)
Secondary	Maternal immune response	Interleukin-6 (IL-6), measured in picograms per milliliter, obtained by blood withdrawal and measured in the lab.	Third trimester (between 30-32 weeks gestational age)
Secondary	Maternal immune response	Interleukin-6 (IL-6), measured in picograms per milliliter, obtained by blood withdrawal and measured in the lab.	Antepartum (during delivery)
Secondary	Maternal immune response	Interleukin-6 (IL-6), measured in picograms per milliliter, obtained by blood withdrawal and measured in the lab.	Postpartum (6-8 weeks post delivery)
Secondary	Maternal immune response	high sensitive C-reactive protein(hsCRP), measured in mg/L, obtained by blood withdrawal and measured in the lab.	Preconceptional (up to 1 year before pregnancy)
Secondary	Maternal immune response	high sensitive C-reactive protein(hsCRP), measured in mg/L, obtained by blood withdrawal and measured in the lab.	First trimester (between 7-12 weeks gestational age)
Secondary	Maternal immune response	high sensitive C-reactive protein(hsCRP), measured in mg/L, obtained by blood withdrawal and measured in the lab.	Second trimester (between 22-24 weeks gestational age)
Secondary	Maternal immune response	high sensitive C-reactive protein(hsCRP), measured in mg/L, obtained by blood withdrawal and measured in the lab.	Third trimester (between 30-32 weeks gestational age)
Secondary	Maternal immune response	high sensitive C-reactive protein(hsCRP), measured in mg/L, obtained by blood withdrawal and measured in the lab.	Antepartum (during delivery)
Secondary	Maternal immune response	high sensitive C-reactive protein(hsCRP), measured in mg/L, obtained by blood withdrawal and measured in the lab.	Postpartum (6-8 weeks post delivery)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; folate, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Preconceptional (up to 1 year before pregnancy)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; folate, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	First trimester (between 7-12 weeks gestational age)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; folate, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Second trimester (between 22-24 weeks gestational age)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; folate, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Third trimester (between 30-32 weeks gestational age)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; folate, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Antepartum (during delivery)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; folate, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Postpartum (6-8 weeks post delivery)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; Homocysteine, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Preconceptional (up to 1 year before pregnancy)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; Homocysteine, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	First trimester (between 7-12 weeks gestational age)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; Homocysteine, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Second trimester (between 22-24 weeks gestational age)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; Homocysteine, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Third trimester (between 30-32 weeks gestational age)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; Homocysteine, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Antepartum (during delivery)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; Homocysteine, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Postpartum (6-8 weeks post delivery)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; B-vitamin 12, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Preconceptional (up to 1 year before pregnancy)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; B-vitamin 12, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	First trimester (between 7-12 weeks gestational age)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; B-vitamin 12, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Second trimester (between 22-24 weeks gestational age)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; B-vitamin 12, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Third trimester (between 30-32 weeks gestational age)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; B-vitamin 12, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Antepartum (during delivery)
Secondary	Maternal metabolic response	Markers of the one-carbon metabolism; B-vitamin 12, measured in micromol/l, obtained by blood withdrawal and measured in the lab.	Postpartum (6-8 weeks post delivery)
Secondary	Clinical maternal outcome: gestational age	Gestational age (amenorrhea duration) at delivery.	Durante partum
Secondary	Clinical maternal outcome: pre-eclampsia	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).	from 20 weeks of gestation to <8 weeks postpartum
Secondary	Clinical maternal outcome: hypertension	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.	from 20 weeks of gestation to <8 weeks postpartum
Secondary	Clinical maternal outcome: gestational diabetes	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.	From the first positive pregnancy test to delivery
Secondary	Fetal growth	Fetal growth trajectories, Crown-Rump-Length (CRL) obtained by using ultrasound imaging.	First trimester (Between 7-7+6 days of gestational age)
Secondary	Fetal growth	Fetal growth trajectories, Crown-Rump-Length (CRL) obtained by using ultrasound imaging.	First trimester (Between 9-9+6 days of gestational age)
Secondary	Fetal growth	Fetal growth trajectories, Crown-Rump-Length (CRL) obtained by using ultrasound imaging.	First trimester (Between 11-11+6 days of gestational age)
Secondary	Fetal growth	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.	Second trimester (Between AD 22-25 weeks of gestational age)
Secondary	Fetal growth	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.	Third trimester (Between 30-33 weeks of gestational age)
Secondary	Histological placental function	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	Postpartum (<2 days postpartum)
Secondary	Placental weight	Placental weight measured (in grams), weighed on the scale.	Postpartum (<2 days postpartum)

External Links

•   Link of recruiting page for participants in Erasmus MC