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PARA study Rotterdam: >10 years of research on RA and pregnancy

The annual 2-day conference of the Dutch Rheumatology Association (NVR) took place last week. One of the invited speakers was Dr RJEM Dolhain (photo) from Erasmus University Medical Center, Rotterdam, the Netherlands. Dr Dolhain provided the audience with a nice overview of what over a decade of research (in the so-called PARA study 2002-2015) in rheumatoid arthritis and pregnancy has yielded so far. The Rotterdam PARA study can be considered as the world’s largest (and ongoing) study of pregnancy related topics in rheumatoid arthritis (follow-up of n=300 of which 250 women have become pregnant). The highlights (i.e. from my own notes during his excellent talk) are listed in this blogpost.

Fertility in women with rheumdtoid arthritis
***The time-to-pregnancy on average is longer in women with rheumatoid arthritis as compared to the general population.
***The time-to-pregnancy in women with rheumatoid arthritis is furthermroe related to age, use of NSAIDs, use of corticosteroids and disease activity (DAS28 score) (ref)
***About 40% of women with rheumatoid arthritis become pregnant within one year (as compared to approximately 70% in general ppulation)
***However when their rheumatoid arthritis is in remission (stable low DAS28) women with rheumatoid arthritis have a comparable chance to become pregnant within one year as in the general population (i.e. 70%)
***Upon referral to an obstetrician/gynaecologist for additional subfertility evaluation in the majority of women with rheumatoid arthritis no specific (other) cause of subfertility can be identfied, so subferitility (per exlucionem) in these women is hypothesised to be at least partially related to (disease activity of) rheumatoid arthritis itself

The influence of pregnancy on disease activity of rheumatoid arthritis
***in contrast to the old paradigm that once pregnant the disease activity of rheumatoid arthritis in general reduces (even the PARA study is named after this paradign ‘Pregnancy-induced Amelioration of Rheumatoid Arthritis’) in the last decade fluctuations in disease activity of rheumatoid arthritis during pregnancy (either better or worse) have been less prominent then assumed before
***especially in ACPA-postive rheumatoid arthritis patients amelioration of diseae activty whilst pregnant occurs less often then in ACPA-negative patients (ref), and keeping rheumatoid arthritis in remission in ACPA-positive rheumatoid arthritis patients can be challenging
***although the disease activity fluctuation of rheumatoid arthritis during pregnancy is less then previously assumed, functionality goes downwards (i.e. the HaQ scores increase) in the vast majority of rheumatoid arthritis patients during pregnancy. In other words, pregnancy is related with higher HAQ scores in most women with rheumatoid arthritis and disease activity is one thing bit overall functioning requires a broader view of the physician.

The outcome of pregnancy in rheumatoid arthritis
***the risk of pregnancy complications in rheumatoid arthritis is slightly elevated, but far lower then the significantly increased and well-known risk in women with systelmic luus erthymetaosus (SLE)
***the birthweight of the newborn is inversely correlated to the disease activity of rheumatoid arthritis during pregnancy, i.e. higher disease activity scores correlate woth a lower birthweight of the newborn (ref)
***higher disease activity scores are also related to an increased frequency of partus via sectio caesaria
***corticosteroids (as opposed to sulfasalazin which does not) shorten the duration of pregnancy
***a lower birthweight is associated with an increased risk of developing metabolic syndrome / cardiovascular disease at adult age, this is a general relation (not specific for newborns from mothers with rheumatoid arthritis)
***if the birthweight is low (and the rheumatoid arthritis diease activity was high), but the newborn “catches-up” and reaches a normal weight within 3 months, there is also an increased risk for developing cardiovascular disease, popular spoken a fat baby becomes a fat toddler, becomes a fat child, becaomes a fat adolescent and ultimately a fat adult.

Current and ongoing research
Since a number of the above mentioned findings of the PARA studies in the last decade indicate the importance of keeping disease activity low in rheumatoid arthritis in patients wishing to become pregnant or whilst pregnant, not only for the known joint-protective effect but also for the protective effects on both mother and newborn (ref) current ongoing research in Rotterdam is now focused on whether the Treat-to-Target approach in rheumatoid arthritis also leads to better pregnancy outcomes.

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