Pregnancy in systemic sclerosis
Identifieur interne : 001C54 ( Istex/Corpus ); précédent : 001C53; suivant : 001C55Pregnancy in systemic sclerosis
Auteurs : I. Miniati ; S. Guiducci ; F. Mecacci ; G. Mello ; M. Matucci-CerinicSource :
- Rheumatology [ 1462-0324 ] ; 2008.
Abstract
While in the past, pregnant SSc patients were thought to be at high risk for poor fetal and maternal outcome, at present, careful planning, close monitoring and appropriate therapy allows these patients to have a successful pregnancy. Retrospective studies clearly show an increased frequency of pre-term births and small full-term infants but the frequency of miscarriage and neonatal survival rate did not differ from healthy controls. The worst life-threatening complication of a pregnancy is scleroderma renal crisis: despite the fact that ACE inhibitors are associated with congenital abnormalities and are relatively contraindicated in pregnancy, in this case their use is recommended. In order to avoid complications, pregnancies in SSc should be planned when the disease is stable, and should be avoided in rapidly progressing diffuse SSc as such patients are at a greater risk for developing serious cardiopulmonary and renal problems early in the disease. HCQ, intravenous immunoglobulins (if blood pressure is not high and renal function is normal) and low doses of steroids may be safely used. In case of rapid worsening of disease activity, elective termination in the first trimester and an induced pre-term birth in the last trimester may be suggested. In order to minimize risks, a multidisciplinary team should assist scleroderma patients to suggest the best timing for a pregnancy and to tailor adequate supportive treatment during the pregnancy.
Url:
DOI: 10.1093/rheumatology/ken174
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ISTEX:F5C7FD016721CE0E484271800E381FFD4AE293E8Le document en format XML
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Miniati</name><affiliation><mods:affiliation>Department of Biomedicine, Section of Rheumatology and Department of Gynecology, Perinatology and Human Reproduction, AOUC, Florence, Italy.</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: irene.miniati@unifi.it</mods:affiliation></affiliation></author><author><name sortKey="Guiducci, S" sort="Guiducci, S" uniqKey="Guiducci S" first="S." last="Guiducci">S. Guiducci</name><affiliation><mods:affiliation>Department of Biomedicine, Section of Rheumatology and Department of Gynecology, Perinatology and Human Reproduction, AOUC, Florence, Italy.</mods:affiliation></affiliation></author><author><name sortKey="Mecacci, F" sort="Mecacci, F" uniqKey="Mecacci F" first="F." last="Mecacci">F. 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Retrospective studies clearly show an increased frequency of pre-term births and small full-term infants but the frequency of miscarriage and neonatal survival rate did not differ from healthy controls. The worst life-threatening complication of a pregnancy is scleroderma renal crisis: despite the fact that ACE inhibitors are associated with congenital abnormalities and are relatively contraindicated in pregnancy, in this case their use is recommended. In order to avoid complications, pregnancies in SSc should be planned when the disease is stable, and should be avoided in rapidly progressing diffuse SSc as such patients are at a greater risk for developing serious cardiopulmonary and renal problems early in the disease. HCQ, intravenous immunoglobulins (if blood pressure is not high and renal function is normal) and low doses of steroids may be safely used. In case of rapid worsening of disease activity, elective termination in the first trimester and an induced pre-term birth in the last trimester may be suggested. In order to minimize risks, a multidisciplinary team should assist scleroderma patients to suggest the best timing for a pregnancy and to tailor adequate supportive treatment during the pregnancy.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>I. Miniati</name><affiliations><json:string>Department of Biomedicine, Section of Rheumatology and Department of Gynecology, Perinatology and Human Reproduction, AOUC, Florence, Italy.</json:string><json:string>E-mail: irene.miniati@unifi.it</json:string></affiliations></json:item><json:item><name>S. Guiducci</name><affiliations><json:string>Department of Biomedicine, Section of Rheumatology and Department of Gynecology, Perinatology and Human Reproduction, AOUC, Florence, Italy.</json:string></affiliations></json:item><json:item><name>F. 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In case of rapid worsening of disease activity, elective termination in the first trimester and an induced pre-term birth in the last trimester may be suggested. 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<front>
<journal-meta>
<journal-id journal-id-type="hwp">rheumatology</journal-id>
<journal-id journal-id-type="publisher-id">brheum</journal-id>
<journal-title>Rheumatology</journal-title>
<issn pub-type="ppub">1462-0324</issn>
<issn pub-type="epub">1462-0332</issn>
<publisher>
<publisher-name>Oxford University Press</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.1093/rheumatology/ken174</article-id>
<article-id pub-id-type="publisher-id">ken174</article-id>
<article-categories>
<subj-group>
<subject>Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Pregnancy in systemic sclerosis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Miniati</surname><given-names>I.</given-names></name>
<xref ref-type="aff" rid="AFF1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Guiducci</surname><given-names>S.</given-names></name>
<xref ref-type="aff" rid="AFF1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Mecacci</surname><given-names>F.</given-names></name>
<xref ref-type="aff" rid="AFF1"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Mello</surname><given-names>G.</given-names></name>
<xref ref-type="aff" rid="AFF1"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Matucci-Cerinic</surname><given-names>M.</given-names></name>
<xref ref-type="aff" rid="AFF1"><sup>1</sup></xref>
</contrib>
</contrib-group>
<aff id="AFF1"><sup>1</sup>Department of Biomedicine, Section of Rheumatology and <sup>2</sup>Department of Gynecology, Perinatology and Human Reproduction, AOUC, Florence, Italy.</aff>
<author-notes>
<corresp>Correspondence to: I. Miniati, Department of Biomedicine, Section of Rheumatology, AOUC Florence, viale Pieraccini 18, 50139 Florence, Italy. E-mail: <email>irene.miniati@unifi.it</email></corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>6</month>
<year>2008</year>
</pub-date>
<volume>47</volume>
<issue>suppl_3</issue>
<issue-title>Pregnancy in the Rheumatic Diseases</issue-title>
<fpage>iii16</fpage>
<lpage>iii18</lpage>
<history>
<date date-type="received">
<day>19</day>
<month>3</month>
<year>2008</year>
</date>
<date date-type="accepted">
<day>2</day>
<month>4</month>
<year>2008</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</copyright-statement>
<copyright-year>2008</copyright-year>
</permissions>
<abstract>
<p>While in the past, pregnant SSc patients were thought to be at high risk for poor fetal and maternal outcome, at present, careful planning, close monitoring and appropriate therapy allows these patients to have a successful pregnancy. Retrospective studies clearly show an increased frequency of pre-term births and small full-term infants but the frequency of miscarriage and neonatal survival rate did not differ from healthy controls. The worst life-threatening complication of a pregnancy is scleroderma renal crisis: despite the fact that ACE inhibitors are associated with congenital abnormalities and are relatively contraindicated in pregnancy, in this case their use is recommended. In order to avoid complications, pregnancies in SSc should be planned when the disease is stable, and should be avoided in rapidly progressing diffuse SSc as such patients are at a greater risk for developing serious cardiopulmonary and renal problems early in the disease. HCQ, intravenous immunoglobulins (if blood pressure is not high and renal function is normal) and low doses of steroids may be safely used. In case of rapid worsening of disease activity, elective termination in the first trimester and an induced pre-term birth in the last trimester may be suggested. In order to minimize risks, a multidisciplinary team should assist scleroderma patients to suggest the best timing for a pregnancy and to tailor adequate supportive treatment during the pregnancy.</p>
</abstract>
<kwd-group><kwd>Scleroderma and related disorders</kwd><kwd>Pregnancy</kwd></kwd-group>
</article-meta>
</front>
<body>
<sec sec-type="intro"><title>Introduction</title>
<p>Systemic sclerosis (SSc) is a CTD that affects women of childbearing age at least five times more than men [<xref ref-type="bibr" rid="B1">1</xref>].</p>
<p>For a long time, SSc has been considered a strict contraindication for pregnancy, because patients were thought to be at high risk for poor fetal and maternal outcome, including maternal death [<xref ref-type="bibr" rid="B2">2</xref>]. Individual case reports and case series, in which outcomes of both pregnancy and disease were poor in women with SSc, have been reported [<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B4">4</xref>]. This experience has led physicians to recommend that SSc patients avoid pregnancy or have elective terminations if pregnancy occurs.</p>
<p>At present, most physicians agree that SSc women have a high likelihood of successful pregnancy if careful planning, close monitoring and appropriate therapy are performed. In fact, retrospective case–control studies [<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B6">6</xref>] showed less ominous outcomes. However, an increased frequency of pre-term births and small full-term infants, compared with controls, was observed [<xref ref-type="bibr" rid="B5">5</xref>, <xref ref-type="bibr" rid="B6">6</xref>].</p>
<p>The disease subset, according to LeRoy <italic>et al</italic>.'s classification [<xref ref-type="bibr" rid="B7">7</xref>], may influence the pregnancy outcome. In fact, the only prospective study published in 1999 by Steen and Medsger [<xref ref-type="bibr" rid="B8">8</xref>] reported 29% of pre-term births and all but one of the infants survived; the frequency of miscarriage was significantly increased in long-standing diffuse systemic sclerosis (dSSc). The results of this study are summarized in <xref ref-type="table" rid="T1">Table 1</xref>.
<table-wrap id="T1"><label>T<sc>able</sc> 1.</label><caption><p>Pregnancy outcomes in 91 SSc patients, prospective study [<xref ref-type="bibr" rid="B8">8</xref>]</p></caption>
<table frame="hsides">
<thead align="left">
<tr>
<th>Disease</th>
<th>Limited</th>
<th>Diffuse</th></tr></thead>
<tbody align="left">
<tr>
<td>Pregnancies, <italic>n</italic></td>
<td>41</td>
<td>50</td></tr>
<tr>
<td>Miscarriages (%)</td>
<td>14.6</td>
<td>14 (late dSSc = 42)</td></tr>
<tr>
<td>Pre-term delivery (%)</td>
<td>22</td>
<td>28</td></tr>
<tr>
<td>Live birth (%)</td>
<td>84</td>
<td>77</td></tr></tbody></table></table-wrap></p>
<p>Symptoms related to SSc, particularly RP, improved during pregnancy, but oesophageal reflux worsened. After pregnancy, some women with diffuse SSc had increased skin thickening [<xref ref-type="bibr" rid="B8">8</xref>].</p>
<p>Steen and Medsger [<xref ref-type="bibr" rid="B8">8</xref>] concluded that women with SSc have acceptable pregnancy outcomes compared with those affected by other rheumatic disease and that infertility was not a frequent problem. Thus, the pregnancy risks for SSc women or their infants are limited, but it is suggested that a well-timed pregnancy with careful obstetric monitoring will maximize the likelihood of a successful outcome [<xref ref-type="bibr" rid="B9">9</xref>].</p>
<p>In a retrospective analysis of 59 pregnancies of 17 mothers with SSc, the effect of disease on pregnancy outcome was variable. There was no adverse effect on fertility. While there was an apparent decrease in fertility in the limited SSc, this was not seen in the diffuse variety. There was a decreased incidence of live birth after the onset of disease as compared prior with the onset of disease. Fetal wastage after the onset of disease was contributed equally by spontaneous abortions as well as induced terminations of pregnancies. The presence of aCLs was not related to adverse outcome [<xref ref-type="bibr" rid="B9">9</xref>].</p>
<p>The presence of aPLs, which is more common in SLE, increases the risk for fetal and maternal complications in pregnancy: deep venous thrombosis and pulmonary embolism, stroke and hepatic infarction may occur during pregnancy and the first 6 weeks post-partum [<xref ref-type="bibr" rid="B10">10</xref>].</p></sec>
<sec><title>Does pregnancy jeopardize the vascular tone control and the function of internal organs?</title>
<p>RP usually improves during pregnancy, particularly with the increased cardiac output in the second half of pregnancy [<xref ref-type="bibr" rid="B8">8</xref>]. Gastro-oesophageal reflux worsens in SSc patients [<xref ref-type="bibr" rid="B8">8</xref>], but is also a quite common symptom in healthy pregnancies, particularly during third trimester as the uterus enlarges. Mallory–Weiss syndrome in SSc patients with oesophageal disease, who vomit during early or late pregnancy, has also been described [<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>]. This can be associated with life-threatening bleeding and recurrent vomiting that needs prompt treatment and hospitalization for these patients. Skin thickening has been shown to increase during post-partum in diffuse SSc [<xref ref-type="bibr" rid="B8">8</xref>].</p>
<p>The greatest danger in pregnant SSc women is the occurrence of renal crisis, secondary to acute-onset severe hypertension that can be life-threatening for both mother and child. It can be confused with pre-eclampsia and HELLP syndrome (H = haemolysis, E = elevated, L = liver enzymes, L = low, P = platelets), but in contrast to pre-eclampsia, delivering the fetus does not affect the hypertension or renal dysfunction. Elevation of blood pressure in these patients, even mild, should be considered potentially very serious. However, pregnancy itself does not seem to increase the risk of renal crisis [<xref ref-type="bibr" rid="B13">13</xref>]. We know that renal crisis is more common in patients with early diffuse SSc, within 5 yrs from symptom onset and with the presence of anti-topoisomerase and anti-RNA polymerase III antibodies and exposure to high doses of corticosteroids [<xref ref-type="bibr" rid="B8">8</xref>]. Pre-eclampsia rate does not seem to be increased in SSc patients [<xref ref-type="bibr" rid="B14">14</xref>].</p></sec>
<sec><title>How to manage a pregnancy in SSc patients?</title>
<p>Pregnancy in SSc may be uneventful, with both good maternal and fetal outcomes. SSc is a multisystem disease and complications do occur; however, careful antenatal evaluations, discussion of potential problems and participation in a high-risk obstetric monitoring programme is mandatory to optimize the best outcome. Because women with diffuse SSc are at greater risk for developing serious cardiopulmonary and renal problems early in the disease, they should be encouraged to delay pregnancy until the disease stabilizes. All patients who become pregnant during this high-risk time should be monitored extremely carefully. Although there are some suggestions that there are increases in infertility and miscarriages before disease onset, recent studies show that these issues probably do not have major impact for women with established SSc who plan to become pregnant. The high risk of premature and small infants may be minimized with specialized obstetric and neonatal care. The only threat for SSc pregnant women is scleroderma renal crisis, which, unlike blood pressure elevation in non-scleroderma pregnancies, must be treated promptly and aggressively with ACE inhibitors. Although ACE inhibitors are normally contraindicated in pregnancy, especially during the third trimester and since they have been associated with infant kidney dysfunction, it is essential to control hypertension and the associated renal crisis in pregnant SSc patients [<xref ref-type="bibr" rid="B15">15</xref>], which is potentially life saving. Furthermore, with a careful management, a history of renal crisis, at present, does not represent a contraindication to future pregnancy providing that the disease has been stable for several years prior to pregnancy [<xref ref-type="bibr" rid="B10">10</xref>]. In these patients, a trial off ACE inhibitors before pregnancy has been suggested to see if the blood pressure may be controlled with other medications. Patients may be put back on ACE inhibitors in case other medications do not manage to control blood pressure [<xref ref-type="bibr" rid="B16">16</xref>].</p>
<p>Other pregnancy problems may not be unique to SSc, but because it is a chronic illness, any complication carries higher risks for both mother and child. It is important for the maternal disease to be stabilized before pregnancy in order to reduce the risk of maternal and fetal complications. Pregnancy may not be suggested in patients with severe visceral involvement; the presence of severe cardiomyopathy (ejection fraction <30%), pulmonary hypertension, severe restrictive lung disease (forced vital capacity <50%), renal insufficiency are associated with an adverse outcome of pregnancy [<xref ref-type="bibr" rid="B16">16</xref>].</p>
<p>However, a careful planning, a close monitoring and an aggressive management should allow women with SSc to have a high likelihood of a successful pregnancy. The risk of therapies chosen to treat the pregnant patient with a relapse is high. Low-dose prednisone did not show an increased risk for oral cleft [<xref ref-type="bibr" rid="B17">17</xref>] or association with development of renal crisis [<xref ref-type="bibr" rid="B18">18</xref>]. Histamine blockers and proton pump inhibitors may be used for the treatment of oesophageal reflux, nausea and vomiting. In a multicentre, prospective, controlled study, the rate of major anomalies was not increased with proton pump inhibitors, indicating that they do not represent a major teratogenic risk in humans [<xref ref-type="bibr" rid="B19">19</xref>]. Chloroquine and HCQ, at recommended doses, are not associated with birth defects; in addition, no visual or hearing impairment in children at follow-up has been observed [<xref ref-type="bibr" rid="B20">20</xref>]. Intravenous immunoglobulin therapy that has shown a significant effect in controlling skin and joint involvement in SSc [<xref ref-type="bibr" rid="B21">21</xref>] may be allowed during pregnancy; although significant amounts cross the placenta, no adverse effects on the fetus or neonate have been reported [<xref ref-type="bibr" rid="B22">22</xref>]. Cyclophosphamide is contraindicated in pregnancy: besides the risk of impaired fertility, a 16–22% risk of congenital anomalies after first trimester exposure has been reported [<xref ref-type="bibr" rid="B22">22</xref>].</p></sec>
<sec><title>The worst scenario</title>
<p>A problem that a physician may experience in a pregnant SSc woman may be the acceleration and progression of skin involvement and the rapid deterioration of the function of internal organs. This is the worst scenario that may push the physician—depending on the week of pregnancy and after a thorough consultation with the mother—to the following different choices:
<list list-type="roman-lower">
<list-item><p>During the first trimester, to favour elective termination in order to allow an aggressive treatment, noxious to the fetus, to slow disease progression.</p></list-item>
<list-item><p>During the third trimester, to favour an induced pre-term birth and start promptly aggressive treatment.</p></list-item>
<list-item><p>In any phase of pregnancy, to just treat symptomatically with allowed drugs (calcium channel blockers, HCQ, intravenous immunoglobulins, proton pump inhibitors, steroids, etc.) trying to get the patient to the time when a pre-term birth is allowed and only treat aggressively afterwards.</p></list-item>
</list>
</p>
<p>This scenario is a challenge for the physician. However, any suggestion must be shared with the mother and the choice and the final word always remain hers.</p></sec>
<sec sec-type="conclusions"><title>Conclusions</title>
<p>Today, in SSc women, still in the early phase of the disease or even in advanced phases with a good function of internal organs, pregnancy is a reality that may allow the birth of healthy babies. A multidisciplinary team is, however, needed to give the best advice to the patient and to tailor an adequate supportive treatment during the pregnancy. In these conditions, risks are minimized and a successful and uneventful pregnancy is possible in SSc women.</p>
<p><inline-graphic xlink:href="ken174b1"></inline-graphic></p>
<p><italic>Disclosure statement</italic>: The authors have declared no conflicts of interest.</p></sec>
</body>
<back>
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</article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Pregnancy in systemic sclerosis</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Pregnancy in systemic sclerosis</title></titleInfo><name type="personal" displayLabel="corresp"><namePart type="given">I.</namePart><namePart type="family">Miniati</namePart><affiliation>Department of Biomedicine, Section of Rheumatology and Department of Gynecology, Perinatology and Human Reproduction, AOUC, Florence, Italy.</affiliation><affiliation>E-mail: irene.miniati@unifi.it</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S.</namePart><namePart type="family">Guiducci</namePart><affiliation>Department of Biomedicine, Section of Rheumatology and Department of Gynecology, Perinatology and Human Reproduction, AOUC, Florence, Italy.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">F.</namePart><namePart type="family">Mecacci</namePart><affiliation>Department of Biomedicine, Section of Rheumatology and Department of Gynecology, Perinatology and Human Reproduction, AOUC, Florence, Italy.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G.</namePart><namePart type="family">Mello</namePart><affiliation>Department of Biomedicine, Section of Rheumatology and Department of Gynecology, Perinatology and Human Reproduction, AOUC, Florence, Italy.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M.</namePart><namePart type="family">Matucci-Cerinic</namePart><affiliation>Department of Biomedicine, Section of Rheumatology and Department of Gynecology, Perinatology and Human Reproduction, AOUC, Florence, Italy.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2008-06</dateIssued><dateCreated encoding="w3cdtf">2008-04-02</dateCreated><copyrightDate encoding="w3cdtf">2008</copyrightDate></originInfo><abstract>While in the past, pregnant SSc patients were thought to be at high risk for poor fetal and maternal outcome, at present, careful planning, close monitoring and appropriate therapy allows these patients to have a successful pregnancy. Retrospective studies clearly show an increased frequency of pre-term births and small full-term infants but the frequency of miscarriage and neonatal survival rate did not differ from healthy controls. The worst life-threatening complication of a pregnancy is scleroderma renal crisis: despite the fact that ACE inhibitors are associated with congenital abnormalities and are relatively contraindicated in pregnancy, in this case their use is recommended. In order to avoid complications, pregnancies in SSc should be planned when the disease is stable, and should be avoided in rapidly progressing diffuse SSc as such patients are at a greater risk for developing serious cardiopulmonary and renal problems early in the disease. HCQ, intravenous immunoglobulins (if blood pressure is not high and renal function is normal) and low doses of steroids may be safely used. In case of rapid worsening of disease activity, elective termination in the first trimester and an induced pre-term birth in the last trimester may be suggested. 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type="ark">ark:/67375/HXZ-4JNL5871-0</identifier><identifier type="DOI">10.1093/rheumatology/ken174</identifier><identifier type="ArticleID">ken174</identifier><accessCondition type="use and reproduction" contentType="copyright">© The Author 2008. 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