Introduction:
Chronic inflammatory diseases (CIDs) are a group of autoimmune diseases
which affect between 5-7% of the population and include rheumatoid
arthritis (RA), psoriatic arthritis and inflammatory bowel disease
(IBD).1,2 Many CIDs have a female preponderance and
are often associated with activity during reproductive
years.3–5 They share a similar pathophysiology
centring on dysregulation of the systemic immune response mediated by
cytokines including tumour necrosis factor (TNF), interleukin 1 (IL-1),
and interleukin 6 (IL-6) which are known to affect pregnancy and
embryogenesis.6,7 Modulation of these cytokines with
the introduction of biologic agents over two decades ago was a
revolution in the care for these patients and are increasingly used to
manage chronic autoimmune diseases during pregnancy.
CID activity is inherently associated with an increased risk of a range
of adverse pregnancy outcomes.8–10 Women with active
IBD during pregnancy have higher rates of miscarriage, preterm delivery,
low birth weight, congenital anomalies and Caesarean section compared to
a general population.8 Likewise, there is a strong
correlation with activity in RA and adverse outcomes such as
miscarriage, low birth weight, pre-eclampsia and Caesarean
section.9 Disease flares are associated with a greater
magnitude of risk for both women and their pregnancy with balancing the
risk of disease flare with fears regarding adverse effects of biologic
medications.10
Randomised control trials on biologic medications during pregnancy are
lacking and the majority of data regarding safety in pregnancy arises
from case series, population data review and cohort studies. One of the
most recent meta-analysis by Tsao et al11 focused
solely on studies that had a disease matched control group thus limiting
their review to 24 studies including 10 published as abstracts only. The
other most recent meta-analysis by Komaki et al included 13 studies and
compared outcomes in the treatment group to the general population only,
with no disease matched cohort included.12
The primary aim of this systematic review and meta-analysis was to
examine a range of maternal and neonatal adverse pregnancy outcomes in
pregnant women exposed to biologics for the management of underlying CID
compared with disease matched cohorts and women without CID.