Lupus (2016) 25, 343345

http://lup.sagepub.com

VIEWPOINT

Pregnancies in women with systemic lupus erythematosus

and antiphospholipid antibodies
K Schreiber1,2
1
Guys and St Thomas NHS Foundation Trust, London, UK; and 2Copenhagen University Hospital Department
of Rheumatology, Copenhagen, Denmark

Systemic lupus erythematosus (SLE) has preponderance in women in their childbearing years;
consequently pregnancy has always been an important issue of concern for the patient and the
treating physician. Based upon numerous reports on successful pregnancy outcomes in the
past decades, the initial advice against pregnancy in the 1950s has been replaced by a common
understanding that women with SLE often have successful pregnancy outcomes, and clinicians
therefore advise on pregnancy planning, including possible drug adjustments, timing and close
surveillance. The recently published Predictors of Pregnancy Outcome: Biomarkers in
Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus (PROMISSE)
study, so far the largest multicentre cohort study of pregnant women with underlying stable
SLE, has given some important answers to long-discussed questions. Future studies on data
collected from the PROMISSE cohort will hopefully identify serological biomarkers, possibly
genes, and in addition, give valuable information about underlying disease
mechanisms. Lupus (2016) 25, 343345.

Key words: Systemic lupus erythematosus; pregnancy; antiphospholipid syndrome; anticardio-

lipin antibodies; lupus anticoagulant

The pregnancy outcome in women with systemic diverse ethnic and socio-economic background
lupus erythematosus (SLE) has unquestionably recruited from nine centres in total (eight centres
improved with a signicant decrease in pregnancy across the United States and one in Canada) who
morbidity over the last ve decades, from 40% in were followed prospectively during pregnancy.
the early 1960s to less than 15% in recent years.1 Outcome measures were adverse pregnancy out-
Indeed, pregnancy was discouraged in women with comes dened as fetal or neonatal death, birth
SLE until fairly recently. The twenty-rst century before 36 weeks due to placental insuciency,
brought renewed interest in research focusing on hypertension or pre-eclampsia and small-for-gesta-
pregnancy outcomes in women with SLE, with tional-age (SGA) neonate (birth weight less than
new concepts challenging previously assumed the fth percentile). Disease activity was assessed
theories. with the Systemic Lupus Erythematosus
Buyon et al. joined this fascinating debate in a Pregnancy Disease Activity Index (SLEPDAI)
recent issue of Annals of Internal Medicine in June and the Physicians Global Assessment (PGA).
2015, publishing the results of the Predictors The aim of the study was to identify risk factors
of Pregnancy Outcome: Biomarkers in for adverse pregnancy outcomes due to SLE or/and
Antiphospholipid Antibody Syndrome and the presence of antiphospholipid antibodies (aPL).
Systemic Lupus Erythematosus (PROMISSE) It is well-known that SLE has a preponderance
study; PROMISSE is so far the largest multicentre in women in their childbearing years; consequently
cohort study of pregnant women with underlying pregnancy has always been an important issue of
stable SLE.2 The study included 385 women with a concern for the patient and the treating physician.
Based upon numerous reports on successful preg-
Correspondence to: Karen Schreiber, Centre for Thrombosis and nancy outcomes in the past decades, the initial
Haemostasis, Guys and St Thomas NHS Foundation Trust, advice against pregnancy in the 1950s3 has been
Westminster Bridge Road, London SE1 7EH, UK. replaced by a common understanding that women
Email: karen.schreiber@gstt.nhs.uk
with SLE often have successful pregnancy out-
Received 15 August 2015; accepted 21 December 2015 comes, and clinicians therefore advise on pregnancy
! The Author(s), 2016. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav 10.1177/0961203315627201
 Pregnancies in women with SLE and antiphospholipid antibodies
K Schreiber
344
planning, including possible drug adjustments,
timing and close surveillance.4,5
The PROMISSE study is a unique study that has
given answers to some long-discussed questions
based on previously available studies within this
eld. However, it is important to note that the
PROMISSE cohort included patients with quies-
cent SLE embarking on pregnancy. Patients with
a urine proteincreatinine ratio >1000 mg/g, a cre-
atinine level greater than 1.2 mg/dL and prednisone
use greater than 20 mg/d and twin pregnancies were
therefore excluded from participation.
The are rate of SLE patients during pregnancy,
for example, has been a subject of much debate. In
the PROMISSE cohort are rates in the second and
third trimester were 2.5% and 3%, respectively,
which is much lower than other studies have
reported previously. This emphasises the import-
ance of, and reassures, common clinical practice,
namely the recommendation of pre-pregnancy
counselling and conceiving during a disease quies-
cent phase. This in turn highlights the importance of
specialist clinics and pregnancy counselling,5 and
once again draws attention to the condential
enquiry into maternal deaths in the United
Kingdom, which recommends that pregnancy coun-
selling should be provided for women with under-
lying pre-existing medical illnesses. This was in
response to the identication of maternal mortality
in women who had not received pre-pregnancy
advice.6 In 81% of the study participants Buyon
et al.2 found women to have a successful pregnancy
outcome, in other words, the child was born alive,
delivered after 36 weeks of gestation and was in at
least the fth percentile for birth weight.
The PROMISSE study also highlights the
remarkable dierence in pregnancy outcomes
across ethnic groups. Attributes of women with
successful pregnancy outcomes were: non-
Hispanic white origin, negative for lupus anti-
coagulant, not treated for hypertension at study
entry, no or low disease activity and a platelet
count of at least 100  109 cells/L. In comparison,
women who were not of non-Hispanic white origin
had more than double the risk of developing one or
more adverse pregnancy outcomes; in women of
African (N 78) and Hispanic (N 58) decent,
poor fetal outcomes were found in 27.4% and
20.6%, respectively.
Other predictors of poor pregnancy performance
were antihypertensive use at baseline, the presence
of lupus anticoagulant, severe clinical are of SLE
during pregnancy, mild or moderate clinical are,
moderate clinical disease activity at baseline and
Lupus
thrombocytopenia. Interestingly, commonly-used
serologic variables to anticipate clinical outcomes,
such as complement levels and anti-dsDNA posi-
tivity, were not associated with adverse pregnancy
outcomes. However, anti-dsDNA was analysed as a
dichotomized variable, whereas the clinical use
mainly is based in the titre tendency. Complement
levels in turn are dicult to interpret in pregnancy
due to the inuence of oestrogen in particular, and
in the PROMISSE cohort, low complement levels
at baseline were more often seen in patients with
adverse pregnancy outcomes.
Data from the PROMISSE cohort will hopefully
in the future identify serological biomarkers,
possibly genes, and in addition give valuable infor-
mation about underlying disease mechanisms.
These data will also need external validation.
Moreover, due to study design, the issue of rst-
trimester loss was not addressed in the PROMISSE
study, and the multicentre nature of the study did
not allow adjustment for the individual treatment
received, thus preventing the identication of
causal links between adverse pregnancy outcomes
and treatment.
In conclusion, this unique study provides reassur-
ance for women with stable disease, and their respon-
sible clinicians, that pregnancy outcomes are
favourable. It also highlights the importance of
pre-pregnancy counselling. Several groups world-
wide are focussing on the improvement of the man-
agement of these women: in the United Kingdom an
upcoming systematic review supported by the British
Society of Rheumatology provides clear comprehen-
sive guidance with regards to drug safety for clin-
icians treating pregnant and lactating women with
underlying rheumatic disease.7,8 Moreover, a work-
ing group under the umbrella of the European
League against Rheumatism (EULAR) has very
recently presented its initial work on recommenda-
tions on the management of women with a diagnosis
of SLE and/or antiphospholipid syndrome in preg-
nancy, covering additional important elds such as
assisted reproduction and menopause, and under the
umbrella of EULAR and the American College of
Rheumatology (ACR) have published the summary
of the Reproductive Health Summit on the manage-
ment of fertility, pregnancy and lactation in women
with autoimmune diseases.10
Declaration of Conflicting Interests
The author(s) declared no potential conicts of
interest with respect to the research, authorship,
and/or publication of this article.

Funding
The author(s) disclosed receipt of the following
nancial support for the research, authorship,
and/or publication of this article: Received educ-
tional support from Daichii Sankyo
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