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62 Journal of The Association of Physicians of India ■ Vol.

64 ■ August 2016

Update Article

Management of Pregnancy in Lupus Patients


Renu Saigal1, Laxmikant Goyal2, ML Tank3, Suresh Saigal4
5. Historyofseverepre-
Abstract eclampsia or HELLP syndrome
(haemolysis, elevated liver
Systemic lupus erythematosus (SLE) mostly affects young women of
enzymes and low platelets
reproductive age group. SLE patients may conceive as any normal
syndrome) despite therapy.
woman but complication may occur in these patients if the disease is
active. Pregnancy in SLE may lead to 1. Aggravation of SLE (Lupus Pregnancy should be deferred if
flare) 2. Pre-term delivery, intrauterine growth retardation and foetal there is 1) severe disease flare within
past 6 months, 2) recent stroke
loss (in presence of antiphospholipid antibodies) 3. Neonatal lupus
within past six weeks and 3) active
especially in presence of Anti-Ro / La antibody. For a successful
lupus nephritis.1
pregnancy, both from maternal and foetal aspects, disease should be
quiescent for at least six months before the conception. Before planning for pregnancy,
estimations of certain antibodies are
Lupus patients with pregnancy require specific management to improve
helpful1 (Table 1).
the maternal and fetal outcomes. Many safe drugs are available for the
When the patient conceives,
management of pregnancy in SLE.
antenatal monitoring for disease
activity and pregnancy related
complications are essential part of
Introduction nephritis (LN), active disease during management (Table 2).1
the past six months before
S LE mostly affects young women of
conception and discontinuation of
hydroxychloroquine (HCQ). For a
Complications of
Pregnancy in SLE
reproductive age group and fertility is
not affected by SLE. Pregnancy in SLE better outcome, drugs safe in
may lead to 1. Aggravation of SLE pregnancy must be started Maternal and fetal risks are h i g h
(Lupus flare) preconception so that the disease e r i n l u p u s p a t i e n t s a s
2. Pre-term delivery, intrauterine remains under control. compared to the healthy women.
growth retardation and foetal loss Pr egnancysh oul db e LN was associated with preterm
especially in presence of contraindicated in following as birth and maternal hypertensive
antiphospholipid antibodies (APL) maternal risk is considerably disorders in women with active,
3. Neonatal lupus especially in increased in these conditions:1 compared with quiescent disease.2
presence of Anti-Ro/ La antibody. Disease Flares
1. Renal insufficiency (serum
For a successful pregnancy, both
creatinine level >2.8 mg%) If SLE is active at the time of
from maternal and foetal aspects,
2. Severe pulmonary hypertension conception then frequency of flare
disease should be quiescent for at
(systemic pulmonary artery was found to be higher (61-67 %)
least six months before the
pressure>50mmHgor during pregnancy as compared to
conception.
symptomatic) those who were in remission for six
Planning for Pregnancy months (7- 33%).3 Patients with LN
3. Severe restrictive lung disease
may have renal flare during
(forced vital capacity <1 L)
Lupus flare during pregnancy pregnancy.4
occurs more in patients with lupus 4. Severe cardiac disease leading to
Flares may occur with equal
heart failure
Table 1: Preconception antibody frequency in any of the trimester
profile estimation
Journal of The Association of
An 1Consultant Physicians of India ■ Vol. 64 ■ August
tic Rheumatologist and 2016
ar
di
Senior Physician,
Apex Hospital Pvt.
63
oli Table 2: Ante-
Ltd., Ex-Professor
pi and Head, natal
n Upgraded monitori Table 3: Lupus nephritis (LN) versus pre-
ant Department of ng by a eclampsia in pregnant lupus patient
ibo Medicine, Former rheumat
die In-Charge ologist Lupus nephritis (LN) Pre-eclamp
s Rheumatology and Urine Proteinuria with active Only protein
an Services, SMS obstetrician sediment
d Medical College and (every 4-6 Complement Low Normal or l
lu Hospital, Jaipur, Anti ds DNA† Increased levels Absent
weeks and
pu Rajasthan; Other organ involvement Present Biomarkers‡
s 2Assistant
more
frequently if Hypertension At any time during pregnancy After 20 wee
ant Professor,
ico Department of the disease Other features May persist even in post- More comm
is active)2 (Thrombocytopenia, elevated partum period after deliver
ag Medicine,
liver enzymes, hyperuricemia
ula Consultant
Blood pressure (>5.5 mg%), decreased 24hrs
nt Rheumatology
monitoring (more urinary excretion of calcium
Ant Services, SMS
frequent if there is (<195 mg%)
i-Ro Medical College,
history of hypertension, Renal biopsy (Avoided Confirm LN
Jaipur, Rajasthan;
and nephritis or pre- usually)
3Associate
anti eclampsia)
Professor, †Anti dsDNA antibodies may potentiate pregnancy loss
-La Complete blood by cross reacting with laminin, molecule important for
Department of
anti counts, Serum uric placental implantation.6 ‡In pre-eclampsia biomarkers
Medicine, 4Assistant
bod acid, serum urea, with low sensitivity viz placenta growth factor (PlGF),
Professor,
ies serum creatinine, vascular endothelial growth factor (VEGF), soluble fms-
Department of
liver function test like tyrosine kinase-1 (sFLT1) and soluble endoglin
Ant Surgery, MG
Complement C3, anti- (sENG), may be present.7-8
i Medical College,
dsDNA and urine
dsD Jaipur, Rajasthan
examination, spot
NA Received:
urine
and 11.02.2015;
Revised: protein/creatinine ratio,
C3
22.06.2015; Lupus anticoagulant
(to Accepted:
asse (LA), anticardiolipin
03.07.2015
ss antibody (aCL)
dise USG monitoring for foetal
ase growth and well being
acti (between 16-20 weeks of
vity gestation)
) Fetal monitoring from
S. week 26
Free AntiRo Antibody if positive
– Fetal echocardiography
T3, weekly from week 16-26,
T4 then biweekly till day, falling thrombosis may be
and delivery complement levels seen with former.1
TS and rising anti ds- Maternal Morbidity
Preeclampsia–Uterine
H artery Doppler (at week DNA levels, may be
20 and then 4 weekly),
Pre-eclampsia,
present. For these
fetal umbilical artery hypertension,
flares, patient may
Doppler velocimetry
be given bleeding, serious
and in postpartum corticosteroid (CS) infections, preterm
period. In SLE flare, in lowest dose or delivery, unplanned
photosensitive rash, short courses of cesarean delivery,
oral or nasal ulcers, high dose of CS and maternal venous
inflammatory azathioprine or thromboembolism
arthritis, fever, calcineurin occur with higher
lymphadenopathy, inhibitors . Intra frequency in
pleuritis, leucopenia, venous pregnant SLE
lymphopenia, Immunoglobulins patients.5
immune haemolytic (IVIg) and
anaemia, plasmapheresis LN and pre -
thrombocytopaenia, may be other eclampsia may
active urinary options but fluid closely resemble as
sediment, overload and risk of both may p r e s e n t
proteinuria >300 mg/ withproteinur
i a , diffe growth done if IUGR is lupus rash CHB. Since CHB is
hypert renti restricti suspected. manifests between irreversible and
ension ate on Neonatal Lupus 4– 6 weeks after mortality is high
thromb betw (IUGR) Syndrome (NLS) birth and may be therefore all patients
ocytop een and Those lupus seen up to 25% of with increased PR
enia a these neonat patients who have newborns.13 These interval should be
ndde two al anti - Ro and anti - manifestations promptly diagnosed
terio cond lupus La subtypes of ANA disappear 6-8 and treated.19
ratio ition syndro targeting 52 kD or 60 months after birth Fluorinated
ninre s as mes kD SSA /Ro and 48 and coincide with corticosteroids ( d e x
n a l enu are few kD SSB/La proteins, the disappearance amethasonean
functio mera of the respectively, cross of the maternal d
n . 1 ted compli the placenta and antibodies.
Some in cations produce neonatal l u Congenital Heart
feature Table which pussyndrome Block (CHB)
s can 3.1,6-8 may be ( N L S ) , a passively CHBaffects
Preec seen in acquired a b o u t 2 % o f
lamp foetuse autoimmune children born to
sia is s born syndrome. NLS is primigravid women
a to SLE characterized b y r a with anti-Ro
frequ mother sh(photosensi antibodies.14 Risk of
ent s. t i v e ) , recurrence is high
com Active haematologic in anti Ro positive
plica lupus, (thrombocytopenia mothers with
tion presen and neutropenia) myxedema and risk
of ce of and hepatic a b n o r also increases in
lupu nephrit malitiesorcar subsequent
s is, d i a c complications pregnancies.15 Fetal
preg presen (Congenital heart genetic
nanc ce o f A block, endocardio- polymorphisms,
y PL,gl fibroelastosis, involving the Fc -
and u c o c structural gamma receptors
occu ortic abnormalities and and transforming
rs o i d u cardiomyopathy) . 12 growth factor-β,
more s e , Neonatal and hypoxia have
frequ hypert been suggested to
ently ension, have a role in CHB
in preecla in NLS.16
LN. mpsia
and CHB mostly
Fetal develops between
Morb thromb
18-24 weeks of
idity ocytop
gestation. Foetal
and enia
echocardiography
Mort increas
ality should be
e the
performed from 16-
Hi foetal
26 weeks of
gher compli
gestation and then
rates cations.
9-11 biweekly . F o e t a l
of
Umbili kinetocardio
fetal
cal gramandtrans
loss,
artery abdominalfoe
prete
Dopple t a l
rm
r electrocardiogram
birth
ultraso can diagnose these
(befo
nograp abnormalities.17-18
re 37
hy Increased PR
week
should interval (first degree
s),
be heart block)
intra
forewarns the
-
subsequent
uteri
development of
ne
64 Journal of The Association of Physicians of India ■ Vol. 64 ■ August 2016
Preg activity, Aceta Glu foetal be dbe
nanc risk of minophe cocorti heart for f o r
betamet CHB and n: It is coids: (Prednis blocks. e e
y
hasone) neonatal safe These olone < Calciu co preg
cross in lupus during must b 10 m nc nanc
placenta SLE activity. pregnan e us e mg/day) supplem ep
y as
and Flare cy. d a t t that ents, in
Ma tio
reach may h e l o controls Vitamin Ritu
Hepa n
foetal nagem occur on we s t disease D should xima
rin: It as
circulati ent of discontin dose activity. be given b
does not all
on and pregna uation of High to plac
cross p l ar
may ncy in HCQ.24 dose patients ental
a c e n t
normaliz SLE may be e trans
Azath a andi who are
e the patient ioprine: associate on ter fer
ssafed
increase requir d with corticost at may
This is u r i n g
d PR es co- diabetes eroids og occu
safe pregnan
interval efforts mellitus, and en ran
during cy. Ease
but not of hyperten heparin ic. dfo
pregnan of
in all as rheum sion, as both rBe
cy in administ
the effect atologi preeclam these 2. Rit lim
dose of ration,
is not st and psia and drugs ux u m
2mg/kg/ higher
consiste obstetr prematu can im abd
day. anti-
ntly ician. re ab a t a
thrombo cause
observed Tacrol rupture (B rega
Dru tic to osteopor
, so role imus of cel rdin
gs for anti- osis.
of CS is and membra l g
SLE Cyclosp coagulan Drugs
controve nes.29 For de safet
Manag orine: S i t ratio which
rsial.20-21 disease pl y are
ement nce,bo and are
Pacemak flares eti lacki
Durin thares predicta contra
ers may short ng ng.30
g afe du ble b i o indica
be courses an
Pregna r i n g availa 3. Ticlo
required of high ted: tib
ncy: bility pidi
in the pregnan dose of od
makes 1. Cyc ne,
majority D r cy and CS or y)
l o w - lop Clop
for better ugsw during intraven an
molecula hos idog
survival h i c h breast ous d
r weight pha rel:
rates. To a r e S feeding, pulse Be
heparin m i All
reduce afein these therapy li
(LMWH) d e , anti
risk of Pregna may be may be m
the anti- Myc plate
CHB in ncy used for used. If u
coagulan ophe lets
subsequ are: suppress patient m
t of nola exce
ent HC ing has been ab
choice.27- pt
pregnan Q: It is disease on te (B
28 Aspi
cies, safe activity.2 prolonge mof A
Anti- rin
HCQ is for
5-26
d CS etil FF
Anti- platelets: shou
effective. fetus therapy and in
hyperten Aspirin ld be
22 Role of stress hi
and s Met stop
IVIg in sive is the dose of
houl hotr bit
preventi drugs: only CS at the ped
dbec exat or
ng this Drugs anti- time of befo
o n t i e: ):
recurren safe in platelet delivery re
nued Bo
ce has pregnan may be Thes preg
d u r i drug th
not been cy are required. e nanc
n g safe in sh
found to Methyld Betamet shou y.
pregna pregnan ou
be opa, hasone ld be ld 4. Warf
ncy as cy and
consiste Labetalol and disc be arin:
it leads may be
nt. 23 , dexamet onti d i It is
to continue
Nifedipi hasone nue s c terat
Manag reduce d if
ne, cross the d 3 o ogen
d indicate
ement Hydrala placenta mon n t ic
diseas d.
of zine. and is ths i n whe
e
given in ue n
used ne plac us and is 10. Be in
in on ental e seco give ta SLE.
earl at perf disc aft nd n for bl Pre
y al usio onti er trim elev oc gna
preg art n. nue 32 ester en ke ncy
nanc eri Bisp d 6- w of days with
7. rs:
y. al hosp 12 ee preg and Anti
Al
Warf hy mon ks nanc level
hona l β pho
arin po ths of y.33 of sph
tes bl
may te prio ge Lefl leflu olipi
shou sta
9.
nom oc
cros ns r to uno d
ld be tio ide ke
s the io preg mid Anti
plac n, n e: in rs
nanc bodi
enta re y. ca This seru ca
es
and na n drug m n
8. N S (AP
caus l lea shou shou ca
A I L)
e fai d ld be ld be us
Ds: APLs
fetal lur to disc < e
F i r are
hae e, pr onti 0.02 IU
s t t present
mor an e nue mg/ G
rim in 25-
rhag d m d 2 L on R
e s t 50%
e so ev at year two an
e r patients
it is en ur s occa d
use of SLE
bette de e befo sion br
may but less
r to at clo re s 14 ad
be than h a l
avoi h.3 su conc days yc
asso fofthe
d 1 re epti apar ar
ciate sepati
oral 6. Di of on t di
d e n t s h
anti- ur du as it befo a
with a ve
coag eti ct has re in
high antiphos
ulan cs: us a conc ne
er pholipid
ts. Th art long epti on
risk syndrom
es eri half- on is ate
5. ACE of e (APS).
e os life cont an
inhi cong APS may
m us. or a emp d
bitor enit manifest
ay
32
was lated ca
s al H clinically
ca h ). n
and malf o as
us out How lea
ARB orm w thrombo
e proc ever, d
s: atio ev tic or
m edur ther to
Thes ns. er obstetric
at e e are ag
e If th complica
er mus stud gr
shou used er tion
na t be ies a
ld after e along
l und that va
be 20 ar with one
vo erta inad t i
avoi wee e serologic
lu ken vert o
ded ks of re al test L
m with ent n
in gest po upusa
e chol expo o f
preg atio rts nticoa
de estyr sure R
nanc n th gulant
pl ami to ay
y as foet at ( L A
eti ne leflu n
ther al N C ) ,
on (or nom a
e is rena S anticardi
an activ ide u
risk l AI olipin
d ated did d
of imp Ds antibodi
re char not ph
ACE airm ar es (ACL)
du coal, lead
- ent e en or Anti
ce 8 g to
inhi may saf o beta 2
d thre terat
bitor occu e m glycopro
ut e ogen
feto r in en tein 1,
er time icity.
path whil fir 34
on positive
o- e st s a
y, in
day
medium
to high
titer on
two
occasion
s 12
weeks
apart.
APL
positive
patients
present
with 3 or
more
early
pregnan
cy losses
(<10
weeks)
or one
pregnan
cy loss
>10
weeks or
one
prematu
re birth
due to
severe
pre-
eclampsi
a or
placental
insufficie
ncy.35
APLs
increase
the risk
of pre-
eclampsi
a,
HELLP
Journal of The Association of Physicians of India ■ Vol. 64 ■ August 2016 65
d to Heparin that anti- mg/ kg impairm APS, I n A
58% dose coagulati every ent is HELL PSpati
syndrom with should on may 12 100 present.4 P entsse
e, aspirin be be hours units/kg 0
syndro vereth
placental monot monitore reversed or 1.5 SC every Patien me rombo
insufficie herapy d by at the mg/kg 12 hours t and c y t o p
ncy, .37 measuri time of /day of or refractor pre- enia(<
IUGR Hepari ng delivery. enoxa 200 y to low eclamp 50,000
and pre- n in activity parin units/kg/ dose sia. / mm3)
APS
term additio of anti- without or day may Aspirin Late requires
delivery. n to its factor Xa prior 10,000 be used. (LDA) onset IVIg,
LAC is a anticoa as thrombo to 39 Target
and throm control
better gulant prolonge sis: 12,000 anti– heparin bocyto of
predicto effect d Prophyla units factor Xa may be penia hyperten
r of and activated ctic UFH 4 hours given occurs sion and
adverse preven partial doses, SC after the corticost in early
pregnan tion of thrombo such as every last dose eroids, pregna delivery.
cy placen plastin 0.5 12 for a IVIg, nt 27

outcome tal t h r time mg/kg/d hours level of and patient


as o m b (aPTT) may plasmap s with Breas
of 0.5 to 1.1
compare osis, may be LMWH be U/ml heresis APS t
d to a l s o seen in (enoxapa used.39 (with though and Feedi
other b l o c these rin) or Altern data are there is
k s t h patients
twice-
limited an
ng
APL.11 5000 u atively daily
The e because twice Daltep dosing), regardin increas Shor
manage activat of LAC. daily of arin or 1.0 to g ed risk t-acti
ment of ion of Treatme UFH 2.0 U/ml efficacy of fetal n g N S
APL in compl nt of subcutan (with of these injury. AIDs,
pregnan ement APS with eously once- drugs Hepari antimala
targete Pregnan and n
cy cy (SC) plus daily rials,
d to low-dose modaliti therap low-dose
requires dosing).4
decidu Use of (81 mg) es.41-43 y may predniso
use of 0
al LMWH aspirin is Treat Warfarin lead to
low dose ne (less
tissues except recomm ment is hepari
aspirin than 15
. for its ended.39 begins at contrain n
and to 20
Hepari cost, is Once or concepti dicated induce
heparin. mg/day),
n a l s preferre twice on and in d warfarin
Inob opre d over pregnan throm
during continue and
stetri s e r ve unfractio cy bocyto
treatmen s for 6 to heparin
cAPSg s t r o nated because penia (
t, anti– 12 weeks are safe
r o u p phob heparin of HIT)
factor Xa postpart for the
aspirin lasti (UFH) teratoge butu
activity um if the infant, as
and c because nic nless
should patient little or
heparin functio of their a n t i
be has no effects. no active
significa n, efficacy, b od i
checked, history T h r drug is
ntly reduce less e s
4 hours of omboc secreted
reduced s chances specifi
after the thrombo ytope in breast
the risk genera of bleed cally
last dose sis, and n i a milk.44
of tion of and associa
for a indefinit Complic
pregnan inflam heparin ted
level of ely if the ating Sum
cy loss mator induced with
0.2 to 0.6 patient Lupus mary
by 54%.36 y thrombo HIT
U/mL.40 has a Pregnan
With mediat cytopeni are
APS history cy: Pregn
combina ors a and demon
with of Thromb ancy in
tion and osteopor strable,
prior thrombo ocytopen SLE is a
treatmen preven osis . 27 hepari
thrombo sis. ia may high risk
t live ts LMWH n
sis: Full Dosing be situation.
births of obstetr is should
anticoag will need caused Active
74% ic replaced not be
ulant to be by active disease
were compli by UFH discont
doses, reduced SLE, at
achieved cations near inued.
such as 1 if renal maternal concepti
compare .38 term so on is
associate e Pract ns al oblast 119

d with quiescen ice in and attach :77


and pre mater ment 8–
worse Pregna t. Rese gn nal and 787
maternal ncy Mater arch ant comp migrat .
and fetal should nal Clinic wo licatio ion:
outcome be complica al me ns. J implic
s. planne tions like
Rheu n Rheu ations
matol wit matol for
d disease ogy h 2010; recurr
when flares, 2013; sys 37:75 ent
the pre - 27:43 te 4– pregn
diseas eclampsi 5– mi 758. ancy
e is a, and
447. c 5. Clows loss
quiesc 2. Smyt lup e ME, in
foetal us SLE
ent for complica
h A, Jamis
patien
Olivei ery on M,
six tions i . e the ts.
ra Myers
month . GHM, ma E, Am J
s. prematu Lahr tos Jame Repr
Effecti rity, BD, us. s AH. od
A Immu
ve IUGR
Bailey A
m nol
contra and
KR,
J
nation
2000;
Norby al
ceptio NLSs ( i Ki 44:13
SM, study
n ncludi Garov dn of the
6.
should n g C H ic VD. ey compl 7. Kleinr
be A Dis ouwel
B) sh o icatio
19
adopte uldbe
syste
91;
ns of er C,
matic lupus et al.
d if the diagnose 17:
revie in Accur
diseas d and w and 12 acy of
pregn
e is treated meta- 3.
ancy. circula
active. early. analy 4. Gl Am J ting
sis of ad placen
P r Many
Obste
pregn ma t tal
econ safe ancy n growt
Gyne
cepti drug outco DD col h
onas options mes , 2008; factor,
s e s s are
in Ta 199:1 vascul
patien nd
ment available
27 ar
ts on endot
should which with A,
e1–
e6. helial
be should syste Iba growt
done ne 6. Qures
be mic h
hi F,
regard started
lupus z factor,
D, Yang
ing to
eryth
Y,
solubl
emat Ur
renal improve owi Jaque
e fms-
osus like
status, maternal and tz s SM,
tyrosin
organ and lupus MB Johns
e
on
involv foetal nephr .
kinase
Th MP,
ement, outcome
itis.
Napar
1 and
Clin J e
APL s. eff stek solubl
Am e
and Soc ect Y,
endog
anti Ro Refer Neph of Ulma
lin in
nsky
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the
us R,
dy and 2010;
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5:206 ne
treatm 1. Latee phr ger L. tion of
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ent f, M.
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an cross-
vely patie al. cy reacti review
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ed to durin nal co with meta-
g and analys
make pregn fetal
me lamini
an n is.
the ancy. comp BJOG
d inhibit
diseas Best licatio fet troph 2012;
66 Journal of The Association of Physicians of India ■ Vol. 64 ■ August 2016
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