Gut Microbiota, Obesity, Maternal, Pregnancy Complications
Conditions
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.
Interventions
OTHERBlood withdrawal
venous punction with blood withdrawal Vaginal and rectal swab, done by patient itself
Sponsors
Erasmus Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gut and vaginal microbiota | Preconceptional (up to 1 year before pregnancy) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maternal immune response | Preconceptional (up to 1 year before pregnancy) | 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. |
| Maternal metabolic response | Preconceptional (up to 1 year before pregnancy) | Markers of the one-carbon metabolism; folate, measured in micromol/l, obtained by blood withdrawal and measured in the lab. |
| 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). |
| Gut virome | Preconceptional (up to 1 year before pregnancy) | Composition of gut virome, obtained by a rectal swab |
| 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. |
| Fetal growth | First trimester (Between 7-7+6 days of gestational age) | Fetal growth trajectories, Crown-Rump-Length (CRL) obtained by using ultrasound imaging. |
| 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. |
| 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. |
Countries
Netherlands
Contacts
Primary ContactNicole Schenkelaars, MD
Outcome results
None listed