High disease activity and prednisone use during pregnancy; lifelong consequences for children of mothers with rheumatoid arthritis?

To prospectively study the mutual influence of rheumatoid arthritis pregnancy
and pregnancy outcome the PARA-study (Pregnancy induced Amelioration of
Rheumatoid Arthritis) was started in 2002. A main finding of the study is that
both high disease activity (above median) during pregnancy as well as
prednisone use were associated with lower birth weight.
Babies born to women with active disease and prednisone use weighted on average
460 gram less. This is more pronounced then other known factors that influence
the birth weight like that of smoking (100-200gram less) or of the World War II
Dutch famine (100-250 gram less).
Low birth weight has been associated with cardiovascular disease, hypertension,
noninsulin dependent diabetes mellitus (DM) and neuropsychiatric disorders in
adulthood. This association is already present for a lower birth weight within
the normal range. Risk factors for the above mentioned disease associations can
already be demonstrated at a very young age and can be tracked from young age
into adulthood. Whether the lower birth weight of children born to women with
rheumatoid arthritis has similar consequences is not known.
The influence of medication (like prednisone) could depend on the genetic
variation of an individual person (e.g. single nucleotide polymorphisms,
SNP's). The phenomenon that events during early life (pregnancy) may have
lifelong consequences is referred to as the developmental origin of disease.
Epigenetic processes are thought to be one of the mechanisms underlying the
developmental origin of disease. Of these, DNA-methylation has been most
extensively studied. Most pronounced changes occur in early pregnancy. Factors
that have been shown to influence DNA-methylation include maternal disease and
malnutritions, smoking, placental insufficiency, corticosteroids, folate
depletion and cytokines. It is plausible that inflammatory disorders, like
acitve RA may also influence the methylation.

The aim of the current study is to get insight into the in potential lifelong
consequences of active disease and or prednisone use during pregnancy on the
children of women with rheumatoid arthritis. As readout it uses indicators
(risk factors) for future development of cardiovascular disease and non-insulin
dependent diabetes mellitus that are suitable at very young age. Moreover, it
attempts to elucidate potential pathogenic mechanism.

If there are consequences found in the study on the children, another RA
treatment strategy durring the pregnancy can be considered to minimize the
potential lifelong risk factors for the newborn.

Translational epidemiological research study

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