Macrophages and monocytes in uncomplicated pregnancy and fetal growth restriction

Pregnancy is an immunological challenge in which the maternal immune system
must facilitate maternal-fetal tolerance, placental development and
functioning, and adequately defend mother and child against pathogens. Several
immune cell subsets are involved, including natural killer cells, T cells and
macrophages. Inadequate immunological adaptations compromise placental
functioning and are associated with pregnancy complications.

In this study, we will focus on the role of maternal macrophages and monocytes
in uncomplicated pregnancies and fetal growth restriction. Inadequate
adaptations of maternal macrophages can be associated with placental
developmental defect and impaired maternal-fetal tolerance. Macrophage subset
imbalances have earlier been associated with common pregnancy complications
like preeclampsia, preterm birth and recurrent spontaneous pregnancy loss.
However, the role of macrophages in fetal growth restriction is not completely
understood.

Fetal growth restriction is a common pregnancy complication that affects 5-10%
of all pregnancies and that is associated with increased child mortality and
morbidity. Fetal growth restriction is due to placental insufficiency that can
be caused or exacerbated at multiple levels. Most often it results from
placental maldevelopment or placental inflammation and oxidative stress.
Hypothetically, placental macrophages are involved since these cells are known
to have a role in placentation. This study aims to obtain a better
understanding of the role of macrophages and monocytes in healthy pregnancies
and the possible link between altered macrophage functionalities and the
pathogenesis of FGR.

The goal of this study is to obtain insight into possible differences in
macrophage and monocyte populations in uncomplicated pregnancies and
pregnancies complicated by FGR.

This is an observational study in which 24 women with healthy pregnancies and
24 women with a pregnancy complicated by FGR will be included. Macrophages and
monocytes will be derived from placental biopsies, maternal blood and cord
blood and will be analyzed using flowcytometry and RT-PCR. Numbers and
phenotypes and cytokine secretion will be studied and macrophages and monocytes
will be stimulated with pro- and anti-inflammatory triggers to determine their
functional status. Maternal blood will be taking during routine blood sampling
around 30 weeks of pregnancy and at labor. Placental samples and cord blood
will be taken after delivery.

Obtaining placental samples and cord blood takes places after labor and
therefore does not carry any risk nor burden. Maternal blood will if possible
be taken during blood sampling for routine pregnancy check-ups. If necessary,
an additional venapunction will take place, , the additional risk is
negligible. This study will not benefit participating women personally,
however, can on the long term lead to a better understanding and possibly
therapeutic options for immune related pregnancy complications.