The promote study, a pilot: The characterization of the microbiome in pregnancy and prediction of pregnancy outcomes.

Our research aims to elucidate an underlying mechanism of maternal obesity
(MOB)-induced pregnancy and long-term health complications for mothers and
their offspring. With the rising global prevalence of obesity, MOB-related
pregnancy problems are increasingly occurring. Microbial gut symbiosis plays an
important role in health, where dysbiosis is associated with diseases as
obesity. Of interest, pregnancy, dietary patterns and pre- or probiotics 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. We hypothesize that
gut dysbiosis in MOB can be regarded as an endogenous chronic stressor inducing
deranged immune responses and one-carbon metabolism. Both processes result in
excessive oxidative stress, detrimental for cell multiplication,
differentiation and epigenetic programming of maternal and offspring tissues.
Together, these biological derangements contribute to placental and vascular
dysfunction resulting in increased risks of preeclampsia or gestational
diabetes mellitus. Vertical (during pregnancy) and horizontal (during delivery)
transfer of gut dysbiosis from mother to new-born, and epigenetic placental and
fetal changes can ultimately accumulate in macrosomia and childhood obesity.

Research question: Is maternal microbiome dysbiosis in MOB an underlying
mechanism in the pathophysiology of adverse maternal pregnancy and offspring
outcome?

Objectives:
Analyse the differences between the gut and vaginal microbiome, maternal and
fetal immune response and one-carbon metabolism in obese vs normal weight
pregnant women.

A single center prospective longitudinal observational cohort pilot study
embedded in the Rotterdam periconception cohort (Predict study, METC 2004-227)
will be performed periconceptional/early in the first trimester and continue
until the delivery/postpartum at the Erasmus MC.

For all cases, the risks involve primarily the burden of participating in a
study, which usually means additional hospital visits and assessments. There
will be a maximum of 6 hospital visits, which will take approximately 30-45
minutes each. There will be two/three first trimester vaginal ultrasound
examinations, two abdominal ultrasound examinations during the second and third
trimester and 1 postpartum visit (all part of the Predict study, METC
2004-227). At a maximum of 5 of the appointments (periconceptional, in the
first, second, third trimester, postpartum) blood draws and rectal swabs will
be obtained. The first blood draw is combined with the blood draw of the
Predict study, the three/four consecutive blood draws are additional for the
PROMOTE study, as are the rectal swabs. Maternal anthropometrics, including
weight, height and blood pressure will be measured preconceptionally or during
the first trimester (as part of the Predict study). The risks of participation
are considered to be nil and the potential benefit outweighs the risks. From
the above explanations, it is clear that there are no obvious risks associated
with participation in the study. After each visit, the patient will receive a
picture of their fetus obtained by 3D or 2D ultrasound, if it is possible to
generate one. In a subgroup of 20 extra included women we will collect a fecal
(stool) sample, one time, in the third trimester of pregnancy. This subgroup of
20 inclusions will only have one visit for signing the informed consent forms
and receiving the fecal collection package and one visit for handing over the
collected fecal sample to the researchers. They therefore do not follow the
regular PROMOTE study protocol.