analysis of pregnancies in women with takayasu arteritis: complication of takayasu arteritis...
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Analysis of pregnancies in women with Takayasuarteritis: Complication of Takayasu arteritis involvingobstetric or cardiovascular events
Hiroaki Tanaka, Kayo Tanaka, Chizuko Kamiya, Naoko Iwanaga and Jun YoshimatsuDepartment of Perinatology, National Cerebral and Cardiovascular Center, Osaka, Japan
Abstract
Aims: The incidence of Takayasu arteritis during child-bearing years is relatively high. The management ofpregnancies in patients with this disease is of great importance in clinical obstetrics. Here we analyzedpregnancies of women with Takayasu arteritis with and without complications.Material and Methods: We retrospectively identified 27 pregnancies in 20 women with Takayasu arteritis seenbetween 1983 and 2005 at the National Cardiovascular Center, in Osaka, Japan. The incidences of obstetricevents, steroid dose increase in pregnancy, and cardiovascular events were compared between group I (nocomplications), group II (one complication), and group III (two or more complications).Results: None of the pregnancies showed Takayasu arteritis activity. The obstetric events were pre-eclampsiain four pregnancies (15%), fetal growth restriction in one (4%), and abruption in one (4%). Three pregnanciesinvolved a steroids dose increase. There were no cardiovascular events. Eighty percent of the pregnancies thatincluded an obstetric event also involved the mother’s chronic hypertension.Conclusions: Pregnant women without active Takayasu arteritis have a low risk of developing a cardiovas-cular event. For women with chronic hypertension, it might be important to note the development of pre-eclampsia, fetal growth restriction and abruption.Key words: fetal growth restriction, hypertension, pre-eclampsia, pregnancy, Takayasu arteritis.
Introduction
Takayasu arteritis is a rare idiopathic chronic inflam-matory disease. The cause is not known.1 The incidenceof Takayasu arteritis is 2–3 per million persons per yearwith a female : male ratio of 9:1. It is estimated that inJapan there are approximately 5000 individuals withTakayasu arteritis.2 The disease preferentially involvesarteries, including the aorta, major branches, vertebral,subclavian, carotid, brachiocephalic, iliac, and renal.Because the incidence of Takayasu arteritis duringchild-bearing years is relatively high, the management
of pregnancy with this disease is of great importance inclinical obstetrics. Some pregnancies accompanied byTakayasu arteritis are not problematic. Takayasu arteri-tis is not influenced by pregnancy. Nevertheless,during the course of a pregnancy of a woman withTakayasu arteritis, maternal complications, such as sus-tained hypertension, superimposed pre-eclampsia,congestive heart failure and progression of renalinvolvement, should be anticipated.3 The increasedseverity of Takayasu arteritis may be associated with anincreased likelihood of low-birthweight babies.4
Although Takayasu arteritis is a potentially severe
Received: November 1 2013.Accepted: March 3 2014.Reprint request to: Dr Hiroaki Tanaka, Department of Perinatology, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka565-8565, Japan. Email: [email protected]
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doi:10.1111/jog.12443 J. Obstet. Gynaecol. Res. Vol. 40, No. 9: 2031–2036, September 2014
© 2014 The Authors 2031Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
condition during pregnancy, successful pregnancy out-comes are possible if extreme caution is taken.5 Bloodpressure control is important in obtaining successfuloutcomes.6
A case of pregnancy involving Takayasu arteritis wasrecently reported.5 However, risk factors associatedwith obstetrical complications and cardiovascularevents in such cases are not clear. The relation of vas-cular involvement is also unclear. Our goal was toclarify risk factors involving obstetrical complicationsand cardiovascular events. We analyzed Takayasu arte-ritis cases with and without complications.
Methods
We retrospectively identified 27 pregnancies in 20women with Takayasu arteritis seen between 1983 and2005 at the Department of Perinatology, National Car-diovascular Center, Osaka, Japan. Historical data onprevious pregnancies and the course of the presentpregnancy were abstracted from maternal medicalrecords.
Takayasu arteritis was defined as non-specificinflammatory disease of uncertain cause causing stric-ture, blockage or enhanced changes to the aorta, themajor branch, the pulmonary artery, or coronary artery.The definitive diagnosis was made based on diagnosticimaging (i.e., digital subtraction angiography [DSA],computed tomography [CT], magnetic resonance angi-ography [MRI]). Takayasu arteritis was diagnosedaccording to criteria cited by Ishikawa and Matsuura:7
one obligatory criterion (age < 40 years); two major cri-teria (left and right mid-subclavian artery lesion); andnine minor criteria (high erythrocyte sedimentationrate, carotid artery tenderness, hypertension, aorticartery regurgitation or annuloaortic ectasia, pulmonaryartery lesion, left mid-common carotid artery lesion,distal brachiocephalic trunk lesion, descending tho-racic aorta lesion and abdominal aorta lesion). In addi-tion to the obligatory criterion, the presence of twomajor criteria, or one major and two minor criteria orfour or more minor criteria suggests the presence ofTakayasu arteritis.
The maternal characteristics examined were age,parity, age at diagnosis of Takayasu arteritis, complica-tions of Takayasu arteritis (retinopathy, chronic hyper-tension, aortic regurgitation and aortic or arterialaneurysm and pulmonary arterial involvement), ste-roids use, antiplatelet treatment, and antihypertensivedrug use. Maternal outcomes that are assumed to be anobstetric event included abruption, pre-eclampsia,
fetal growth restriction (FGR), steroids dose increase inpregnancy, and cardiovascular events. Neonatal out-comes were assessed by gestational week, birthweight,Apgar score at 5 min, and pH of the umbilical artery(UA).
We categorized the patients into three groups accord-ing to the Ishikawa criteria.8 Group I had no complica-tions. Group II had one of the following complications:retinopathy, chronic hypertension, aortic regurgitationand aortic or arterial aneurysm. Group III had two ormore of those complications.9 We compared thegroups’ obstetric events, steroids dose increase in preg-nancy, and cardiovascular events.
The univariate analysis by χ2-test was used for thestatistical analysis. P-values < 0.05 were consideredsignificant.
Results
Our analysis examined a total of 27 pregnancies in 20women. All patients continued the pregnancy anddelivered. All pregnancies showed no manifestationsof Takayasu arteritis. The maternal background data forthe pregnancies and patients are shown in Table 1. Themedian age was 30 years (range 22–35 years). Themother was nulliparous in 19 pregnancies (70%) andmultiparous in eight (30%). The median age at the diag-nosis of Takayasu arteritis was 21 years (16–33 years).
The maternal complications for Takayasu arteritiswere chronic hypertension in five pregnancies (18%)and aortic regurgitation in five (18%), renal obstructionin none (0%), aortic and arterial aneurysm in three(11%), and pulmonary arterial involvement in none(0%). Steroid use was present in 15 pregnancies (55%),but there were no cases in which Takayasu arteritisshowed activity. Antiplatelet treatment was used infour pregnancies (15%). Three pregnancies (11%)involved antihypertensive drug use, and an antihyper-tensive drug was administered for anti-arrhythmia incase 27.
Obstetric events included pre-eclampsia in fourpregnancies (15%), FGR in one (4%), and abruption inone (4%). Three pregnancies involved a steroids doseincrease. There were no cardiovascular events. Themode of delivery was cesarean section in nine pregnan-cies (33%). The indications for cesarean section amongthese patients were pre-eclampsia (four pregnancies),fetal disorder (one), abruption (one), and previouscesarean section (three). The gestational ages at deliv-ery included preterm birth in three pregnancies (11%).Low birthweight infants occurred in three pregnancies
H. Tanaka et al.
2032 © 2014 The AuthorsJournal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Tab
le1
Mat
erna
lbac
kgro
und
Cas
eA
geat
dia
gnos
isA
geat
del
iver
yPa
rity
Com
plic
atio
nsof
Taka
yasu
arte
riti
sSt
eroi
ds
use
Ant
ipla
tele
ttr
eatm
ent
Ant
ihyp
erte
nsiv
ed
rug
use
Ret
inop
athy
Chr
onic
hype
rten
sion
Aor
tic
regu
rgita
tion
Ren
alob
stru
ctio
nA
orti
can
dar
teri
alan
eury
sm
Pulm
onar
yar
teri
al
118
220
No
Yes
No
No
No
No
No
No
No
227
340
No
Yes
No
No
No
No
No
No
Yes
321
240
No
Yes
Yes
No
No
No
No
No
No
421
301
No
Yes
Yes
No
No
No
No
No
No
521
320
No
Yes
No
No
No
No
Yes
No
Yes
627
300
No
No
No
No
No
No
Yes
Yes
No
729
330
No
No
No
Yes
No
No
Yes
No
No
829
351
No
No
No
No
No
No
Yes
No
No
927
300
No
No
No
No
No
No
No
No
No
1028
280
No
No
No
No
Yes
No
No
No
No
1117
240
No
No
No
No
No
No
No
No
No
1217
281
No
No
No
No
No
No
No
No
No
1320
230
No
No
No
No
Yes
No
No
No
No
1433
331
No
No
No
No
No
No
No
No
No
1521
300
No
No
No
No
No
No
Yes
No
No
1624
310
No
No
No
No
No
No
Yes
No
No
1724
331
No
No
No
No
No
No
Yes
No
No
1824
290
No
No
No
No
No
No
Yes
No
No
1924
311
No
No
No
No
No
No
No
No
No
2019
290
No
No
No
No
Yes
No
Yes
No
No
2122
320
No
No
No
No
No
No
Yes
No
No
2222
331
No
No
No
No
No
No
Yes
No
No
2316
290
No
No
Yes
No
No
No
No
No
No
2421
290
No
No
No
No
No
No
Yes
Yes
No
2521
301
No
No
No
No
No
No
Yes
Yes
No
2621
330
No
No
Yes
No
No
No
Yes
No
No
2717
320
No
No
Yes
No
No
No
Yes
Yes
Yes
Pregnancy and Takayasu arteritis
© 2014 The Authors 2033Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
(11%). Apgar score (5-min) and pH of the UA wereexcellent, except in case 1 (involving abruption), inwhich both the Apgar score and the pH of the UA werelow (Table 2).
Table 3 shows the correlations among obstetricevents, steroid dose increase in pregnancy, cardiovas-cular events and complication of Takayasu arteritis.Group I included 16 pregnancies (59%). Group IIincluded nine pregnancies (33%), with chronic hyper-tension in three pregnancies (11%), aortic regurgitationin three (11%), and aortic and arterial aneurysm inthree (11%). Group III included chronic hypertensionand aortic regurgitation in two pregnancies (7%).Obstetric events occurred in five pregnancies, and 80%of the pregnancies that included an obstetric event alsoinvolved the mother’s chronic hypertension. Therewere significantly more obstetric events among thechronic hypertension patients of group II compared togroup I (P = 0.04). Three pregnancies involved a ste-roids dose increase, with no significant differencebetween group I and groups II or III regarding thisparameter. Cardiovascular events did not occur in anyof the 27 pregnancies.
The arterial involvement is summarized in Table 4.Various arteries were involved, but no cardiovascularevents occurred, as mentioned above. Moreover, fourof the five cases with renal arterial involvement (80%)also showed chronic hypertension.
Cases involving the exacerbation of heart functionand aortic regurgitation with Takayasu arteritis thatwere investigated at 1 month postpartum, were notincluded in this study.
Discussion
We conclude that in some pregnancies, Takayasu arte-ritis does not affect the outcome. Moreover, Takayasuarteritis is not influenced by pregnancy. The rates ofpre-eclampsia and FGR are increased among womenwith Takayasu arteritis.4,9,10 Blood pressure controlduring pregnancy is important to achieving successfuloutcomes.6 In the present study, our goal was to clarifyrisk factors involving obstetrical complications and car-diovascular events.
Obstetric events developed in six of the 27 presentpregnancies with Takayasu arteritis (22%), as pre-eclampsia (n = 4), FGR (n = 1) and abruption (n = 1).This result corresponds to those of previous reports.4,9,10
The neonatal outcome was excellent when there was noobstetric event. When we began our investigation ofthe complications of Takayasu arteritis, we suspected
that chronic hypertension was related to obstetricevents. Although blood pressure control during preg-nancy is important,5 we suspected that it was a riskfactor not only for blood pressure control but also forthe existence of chronic hypertension, and importantobstetrics events. We found that 80% of the pregnanciesinvolving chronic hypertension had a stricture of therenal artery. In a word, there were many cases of renalhypertension.
A prior study reported that renal artery stenosis isrelated to FGR, and that renal artery stenosis isdescended in association with chronic hypertension.3
This is related not only to FGR but also pre-eclampsiaand abruption. The rate of increases in steroid doseduring pregnancy in the present study was 11%, butTakayasu arteritis does not progress with increased ste-roids alone. Our result agrees with that of a past reportshowing that Takayasu arteritis is not influenced bypregnancy.5 However, it must be borne in mind that all27 of the present study’s pregnancies were not activeTakayasu arteritis cases. The post-partum heart func-tion and aortic regurgitation values were unchanged.Takayasu arteritis presents as a stricture and bloodvessels enhanced due to inflammation. At the sametime, the compliance of the blood vessel is decreasedby the inflammatory change. The post load increases tothe change in circulating blood volume by the preg-nancy compared with a normal pregnancy andincreases the strain on the heart. However, it is impor-tant to be able to achieve no exacerbation of the heartfunction and aortic regurgitation during the postpar-tum period.
In the present patient population, a cardiovascularevent did not occur. We expected to observe deteriora-tion of the aortic regurgitation and/or the exacerbationof chronic hypertension because the circulating bloodvolume doubles during pregnancy. The results did notmeet this expectation.
We cannot be certain of the rationale underlying thedecision, because this study was performed as a retro-spective analysis. However, pregnancy with Takayasuarteritis without activity is predicted to have a lowpossibility of cardiovascular events, and no deteriora-tion of arteritis.
Considering obstetrics events, the presence ofchronic hypertension might be an important factor inthe complications of Takayasu arteritis. The obstetri-cian of a woman with Takayasu aortitis should confirmthat there is no Takayasu aortitis activity and carefullymonitor the pregnancy. Women without Takayasu arte-ritis activity who are pregnant have a low risk of the
H. Tanaka et al.
2034 © 2014 The AuthorsJournal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Tab
le2
Mat
erna
land
neon
atal
outc
omes
Cas
eM
ater
nalo
utco
me
Neo
nata
lout
com
eO
bste
tric
even
tSt
eroi
dd
ose
incr
ease
inpr
egna
ncy
Car
dio
vasc
ular
even
tD
eliv
ery
mod
eG
esta
tion
alag
eat
del
iver
y(w
eeks
)
Bir
thw
eigh
t(g
)A
pgar
scor
e(5
-min
)
pHof
UA
1A
brup
tion
No
No
CS
36+2
2140
27.
162
FGR
No
No
CS
33+2
1554
87.
253
Pre-
ecla
mps
iaYe
sN
oC
S39
+235
229
7.21
4Pr
e-ec
lam
psia
No
No
CS
38+1
3044
97.
315
Pre-
ecla
mps
iaN
oN
oC
S28
+297
5g9
7.31
6Pr
e-ec
lam
psia
No
No
CS
39+4
3490
97.
247
No
No
No
VD
38+6
2788
97.
218
No
No
No
VD
38+1
3196
97.
349
No
No
No
VD
40+3
3558
97.
2510
No
No
No
CS
39+3
2654
87.
3211
No
No
No
VD
39+4
2860
107.
3212
No
No
No
VD
38+6
2744
97.
2913
No
No
No
VD
40+1
3614
107.
2714
No
No
No
VD
37+0
3006
97.
3415
No
No
No
VD
39+2
3074
97.
3216
No
No
No
CS
40+1
2988
67.
1417
No
No
No
CS
38+4
2842
97.
2718
No
No
No
VD
39+6
3062
97.
2319
No
Yes
No
VD
39+2
2856
97.
3620
No
No
No
VD
39+4
2632
97.
3421
No
No
No
VD
38+1
3053
97.
3822
No
No
No
VD
38+0
2636
107.
1523
No
No
No
VD
39+0
2758
97.
3324
No
No
No
VD
38+5
2474
97.
2525
No
No
No
VD
38+6
2600
97.
2726
No
No
No
VD
38+6
2790
87.
2627
No
Yes
No
VD
39+0
2640
87.
32
CS,
cesa
rean
sect
ion;
FGR
,fet
algr
owth
rest
rict
ion;
UA
,um
bilic
alar
tery
;VD
,vag
inal
del
iver
y.
Pregnancy and Takayasu arteritis
© 2014 The Authors 2035Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
development of a cardiovascular event. For pregnantwomen with chronic hypertension, it might be impor-tant to check for the development of pre-eclampsia,FGR, and abruption.
Disclosure
The sponsor of the study had no role in the studydesign, conduct of the study, data collection, data inter-pretation or preparation of the report.
References
1. Ishikawa K. Diagnosis approach, proposed criteria for theclinical diagnosis of Takayasu arteriopathy. J Am Coll Cardiol1988; 12: 964–972.
2. Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH.The American College of Rheumatology 1990 criteria for theclassification of Takayasu arteritis. Arthritis Rheum 1990; 33:1129–1134.
3. Papantoniou N, Katsoulis I, Papageorgiou I, Antsaklis A.Takayasu arteritis in pregnancy: Safe management options inantenatal care. Fetal Diagn Ther 2007; 22: 449–451.
4. Gasch O, Vidaller A, Pujol R. Takayasu arteritis and preg-nancy from the point of view of the internist. J Rheumatol2009; 36: 1554–1555.
5. Hidaka N, Yamanaka Y, Fujita Y, Fukushima K, Wake N.Clinical manifestations of pregnancy in patients withTakayasu arteritis: Experience from a single tertiary center.Arch Gynecol Obstet 2012; 285: 377–385.
6. Mandal D, Mandal S, Dattaray C et al. Takayasu arteritis inpregnancy: An analysis from eastern India. Arch GynecolObstet 2012; 285: 567–571.
7. Ishikawa K, Matsuura S. Occlusive thromboaortopathy(Takayasu’s disease) and pregnancy. Clinical course and man-agement of 33 pregnancies and deliveries. Am J Cardiol 1982;50: 1293–1300.
8. Abdul-Karim R, Assalin S. Pressor response to angiotonin inpregnant and nonpregnant women. Am J Obstet Gynecol 1961;82: 246–251.
9. Matsumura R, Moriwaki R, Numano F. Pregnancy inTakayasu arteritis from the view of internal medicine. HeartVessels Suppl 1992; 7: 120–124.
10. Wong VC, Wang RY, Tse TF. Pregnancy and Takayasu’s arte-ritis. Am J Med 1983; 75: 597–601.
Table 3 Correlations among obstetric events, steroid dose increase in pregnancy, cardiovascular events and complications
Group I Group II Group IIINone Chronic
hypertensionAorticregurgitation
Aortic orarterialaneurysm
Chronic hypertensionand aorticregurgitation
n = 16 n = 3 n = 3 n = 3 n = 2
Obstetric event 1 (6%) 2 (66%)* 0 (0%) 0 (0%) 2 (100%)Steroids dose increase in pregnancy 1 (6%) 0 (0%) 1 (33%) 0 (0%) 1 (50%)Cardiovascular event 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
*P = 0.04.
Table 4 Arterial involvement among patients withTakayasu arteritis
n = 20
Ascending aorta 3 (11%)Arch of aorta 3 (11%)Common carotid artery 11 (53%)Brachiocephalic artery 2 (11%)Internal carotid artery 1 (4%)External carotid artery 1 (4%)Subclavian artery 13 (70%)Vertebral artery 9 (44%)Abdominal aorta 4 (18%)Renal artery 5 (26%)
H. Tanaka et al.
2036 © 2014 The AuthorsJournal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology