Monitoring of Systemic Lupus Erythematosus Pregnancies: A ...

1McDonald, et al: Monitoring in SLE pregnancies

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Monitoring of Systemic Lupus ErythematosusPregnancies: A Systematic Literature ReviewEmily G. McDonald, Lyne Bissonette, Stephanie Ensworth, Natalie Dayan, Ann E. Clarke,Stephanie Keeling, Sasha Bernatsky, and Evelyne Vinet

ABSTRACT. Objective. Few data exist to guide the frequency and type of monitoring in systemic lupus erythe-matosus (SLE) pregnancies. A systematic literature review was performed to address this gap in theliterature.Methods. A systematic review of original articles (1975–2015) was performed using Medline,Embase, and Cochrane Library. We included search terms for SLE, pregnancy, and monitoring. Wealso hand-searched reference lists, review articles, and grey literature for additional relevant articles.Results. The search yielded a total of 1106 articles. After removing 117 duplicates, 929 articles thatwere evidently unrelated to our topic based on title and/or abstract, and 7 that were in a languageother than English or French, 53 articles were included for full-text review. Following a more in-depthreview, 15 were excluded: 6 did not use any measure of SLE activity and 6 did not specifically addressSLE monitoring in pregnancy; 1 case series, 1 review, and 1 metaanalysis were removed. Among the38 included studies, presence of active disease, antiphospholipid (aPL) antibodies positivity, andabnormal uterine and umbilical artery Doppler studies predicted poor pregnancy outcomes. No studiesevaluated an evidence-based approach to the frequency of monitoring. Conclusion. Few existing studies address monitoring for optimal care during SLE pregnancies. Theavailable data imply roles for aPL antibodies measurement (prior to pregnancy and/or during the firsttrimester), uterine and umbilical artery Doppler studies in the second trimester, and following diseaseactivity. Optimal frequency of monitoring is not addressed in the existing literature. (J RheumatolFirst Release July 15 2018; doi:10.3899/jrheum.171023)

Key Indexing Terms: SYSTEMIC LUPUS ERYTHEMATOSUS PREGNANCYMONITORING ADVERSE PREGNANCY OUTCOMES

From the Division of General Internal Medicine, and the Division ofRheumatology, Department of Medicine, McGill University Health Centre,Montréal; Division of Rheumatology, Department of Medicine, Universityof Sherbrooke, Sherbrooke, Québec; Division of Rheumatology, Mary PackArthritis Center, University of British Columbia, Vancouver, BritishColumbia; Division of Rheumatology, Department of Medicine, Universityof Alberta, Edmonton; Division of Rheumatology, Department of Medicine,University of Calgary, Calgary, Alberta, Canada.EV received salary funding from the Fonds de Recherches Santé Québec(FRSQ). EGM received funding from an FRSQ Master’s award and theMcGill Clinician Investigator Program. SK received funding through aCanadian Institutes of Health Research Dissemination Grant.E.G. McDonald, MD, MSc, Division of General Internal Medicine,Department of Medicine, McGill University Health Centre; L. Bissonette,MD, Division of Rheumatology, Department of Medicine, University ofSherbrooke; S. Ensworth, MD, Assistant Professor, Division ofRheumatology, University of British Columbia; N. Dayan, MD, MSc,Division of General Internal Medicine, Department of Medicine, McGillUniversity Health Centre; A.E. Clarke, MD, MSc, Division ofRheumatology, Department of Medicine, University of Calgary; S. Keeling, MD, MSc, Division of Rheumatology, Department of Medicine,University of Alberta; S. Bernatsky, MD, PhD, Division of Rheumatology,Department of Medicine, McGill University Health Centre; E. Vinet, MD,PhD, Division of Rheumatology, Department of Medicine, McGillUniversity Health Centre. Address correspondence to Dr. E. Vinet, Assistant Professor, McGillUniversity Health Centre, 5252 De Maisonneuve West, Montreal, QuébecH4A 3J1, Canada. E-mail: [email protected] Release Article. For details see Reprints and Permissions at jrheum.orgAccepted for publication January 25, 2018.

Systemic lupus erythematosus (SLE) predominantly affectswomen during their reproductive years, occurring in about1/1000 women aged between 15 and 45 years1. SLE isassociated with substantial maternal and fetal morbidityduring pregnancy. Compared with the non-SLE population,SLE has been shown to be associated with an increased riskof preterm birth, cesarean delivery, preeclampsia, low birthweight, intrauterine growth restriction (IUGR), congenitalheart block (CHB), and intrauterine and neonatal death2,3,4,5.Preterm birth is the most common adverse pregnancyoutcome in women with SLE, with incidence ranging from15% to 50% (as opposed to 10% in unaffected women), withincreased risk in women with lupus nephritis or high diseaseactivity. In the general population, preterm birth is the leadingcause of neonatal death and the second most common causeof death (after pneumonia) in children younger than 5 years6. SLE has a waxing and waning course and it has beenshown that if women conceive during a period of diseasequiescence, this will minimize the risk of flare in pregnancy,but will not eliminate it, with rates of flare still rangingbetween 20% and 40% of pregnancies that are conceivedduring a period of remission7,8,9,10. In addition to a greaterfrequency of pregnancy complications, the SLE diseasecourse itself can be negatively affected by pregnancy, with a

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greater number of women developing an SLE flare in theperipartum period11,12,13. SLE pregnancies are considered high risk, beingassociated with higher maternal and fetal morbidity. Althoughthe majority of SLE pregnancies end with live births, activedisease and major organ involvement can affect the outcomesin both mother and fetus. In addition, major fetal issues suchas IUGR and neonatal SLE syndromes make monitoringimperative in SLE pregnancies14. Finally, some symptoms of SLE can be silent, such asrenal flare or thrombocytopenia, emphasizing the need forcloser monitoring in pregnancy; these silent flares can stillincrease the chance of obstetrical complications15. Quality indicators pertaining to reproductive health inSLE have been developed but are limited only to the recom-mendation that anti-SSA/SSB and antiphospholipid (aPL)antibodies be documented in the chart, prior to conception16.Optimal quality indicators remain undefined, and topics tobe addressed include not only laboratory monitoring but alsonewer imaging modalities for monitoring high-riskpregnancies, such as umbilical and uterine artery Dopplerstudies. These are believed to be useful in monitoringpregnancies at high risk of placental insufficiency, whichinclude SLE pregnancies17. Because the issue of how best tofollow disease activity, and how often to monitor for diseaseflares, has not been systematically addressed in the literature,current practice is heterogeneous and not necessarilyevidence-based18. To address this important knowledge gap, a Canadian SLEworking group was established, funded by the CanadianInstitutes of Health Research and endorsed by the CanadianRheumatology Association. One of the aims of this groupwas to determine what investigations are needed to optimallymonitor pregnancy in SLE, in the Canadian context (whichincludes universal healthcare access).

MATERIALS AND METHODSThe systematic literature review was performed according to the PreferredReporting Items for Systematic review and Meta-analysis Protocols(PRISMA-P) 2015 statement19 (Table 1). The review was conducted through 3 search engines: Embase, Medline,and Cochrane. The search was performed on publications between 1975 and2015, without any language restrictions. We used Medical Subject Headingand free text terms adapted for each database to identify original articles.We included search terms for SLE, pregnancy, and monitoring variables. Allterms within each set were combined using the Boolean operator “OR” andthen the 3 sets were combined using “AND.” This was supplemented byhand-searching reference lists, review articles, and grey literature forrelevant articles not identified by the electronic searches, as well as includingrelevant articles published after completion of our review. Exclusion criteriathen included any abstract in a language other than French or English, casereports, case series, and review articles.Study selection. First, titles from the initial search were reviewed by 3individuals (EGM, LB, and EV) to initially include any potential studiesrelated to the study question, and to exclude any duplicates. Second, titlesand abstracts were reviewed to identify relevant studies that met ourinclusion criteria and to exclude case reports and studies unrelated to thesystematic review. Third, 2 reviewers (EGM and LB) independently

reviewed each full-text article for inclusion in the final set of articles, witha third reviewer (EV) settling discrepancies. Two reviewers (EGM and EV)summarized evidence on monitoring of SLE in pregnancy. None of thereviewers were blinded to the authors or journal titles.Data extraction and quality assessment. Relevant data pertaining tomonitoring were extracted from each article as well as general informationsuch as country of the study, type of study, year of publication, and firstauthor. Monitoring was divided into 4 categories: serological tests [whichincluded anti-DNA, antiextractable nuclear antibody, IgG and IgM anticar-diolipin antibodies (aCL), lupus anticoagulant (LAC), and complementlevels]; measures of SLE activity using a validated scoring system [examplesinclude the SLE Disease Activity Index (SLEDAI) and European ConsensusLupus Activity Measure scores; studies that did not use any type of scoringsystem to measure disease activity were not included]; obstetrical Dopplerultrasound monitoring (either uterine or umbilical artery Doppler studies);and other (monitoring variables not falling into one of the above categories).When applicable, we recorded whether the frequency of monitoring wasaddressed, as well as any associations with negative maternal or obstetricaloutcomes. Maternal outcomes were classified as the development ofpreeclampsia, or worsening of SLE disease activity, including lupusnephritis. Obstetrical outcomes were classified as IUGR, spontaneousabortion (prior to 20 weeks of gestational age), small for gestational age(SGA) or low birth weight (SGA and low birth weight were defined withinindividual studies), preterm delivery (prior to 37 weeks gestational age),complete CHB, or intrauterine fetal demise. Relevant data were extracted,synthesized, and presented in tabular format. Risk of bias in individual studies: the Newcastle-Ottawa scale. Final studiesincluded in the systematic review were evaluated for quality of evidence andrisk of bias using the Newcastle-Ottawa scale, which uses a star systemwhereby a study is judged on 3 measures: the selection of the study groups,the comparability of the groups, and how the exposure for case-control (oroutcome of interest for cohort studies) was ascertained.

RESULTSStudy characteristics.A general description of the character-istics of each study is presented in Table 22,9,13,15,20-53including first author, year of publication, study population,and study type, as well as monitoring variables studied. Adescription of the search process, including the reasons forexcluded studies, is shown in Figure 1. In total, 1106 titleswere evaluated from the initial search strategy, of which 117were removed because they were duplicates, and 7 wereremoved because they were in a language other than Frenchor English. Then, on initial review of the title and/or abstracts,929 articles that did not address SLE monitoring inpregnancy and were removed, leaving 53 articles that werereviewed in depth. Upon full review of the 53 articles, it wasfound that 6 more did not address SLE monitoring inpregnancy, 6 did not use any scoring system for SLE diseaseactivity, 1 was a review, 1 was a case series, and 1 was ametaanalysis. These were removed, leaving 38 originalobservational studies for review. Final studies were selectedbased on reporting of adverse obstetrical or maternaloutcomes related to monitoring variables (Figure 1) in SLE.Participant characteristics. The majority of studies evaluatedmonitoring of SLE during pregnancy and immediatelypostpartum. Only a few studies looked specifically at lupusnephritis or focused solely on pregnancies in mothers whowere anti-Ro- and/or La-antibody positive. The study popula-tions were multiethnic, with patients from across the world

2 The Journal of Rheumatology 2018; 45:doi:10.3899/jrheum.171023






Table 1. PRISMA-P checklist for preferred reporting of systematic reviews.

Section and Topic Item No. Checklist Item

Administrative information Title Identification 1a Identify the report as a protocol of a systematic review. Update 1b If the protocol is for an update of a previous systematic review, identify as — This is not an update of a previous

protocol for a systematic review. Registration 2 If registered, provide the name of the registry (such as PROSPERO) and registration number — This systematic review

was not registered. Author Contact 3a Provide name, institutional affiliation, e-mail address of all protocol authors; provide physical mailing address of

corresponding author — Emily Gibson McDonald1, Royal Victoria Hospital, 1001 Decarie St., Montreal, QuebecH4A 3J1, Canada. Evelyne Vinet1, Stephanie Keeling2, Natalie Dayan1, Lyne Bissonette3, Sasha Bernatsky1, StephanieEnsworth4, Ann E. Clarke5. 1McGill University Health Centre, 2University of Alberta, 3University of Laval, 4MaryPack Arthritis Centre, 5University of Calgary.

Contributions 3b Describe contributions of protocol authors and identify the guarantor of the review — Emily McDonald and EvelyneVinet were involved in reading the abstracts, excluding unrelated abstracts, drafting the manuscript including readingarticles in full and collating the data. Lyne Bissonette read and excluded unrelated abstracts. Natalie Dayan wasinvolved in the supervision of Lyne Bissonette. Evelyne Vinet developed the PICO question and the search strategyand supervised Emily McDonald. Stephanie Keeling provided content expertise and supervision of the GRADE recom-mendations. Stephanie Ensworth and Ann E. Clark are part of the Canadian SLE Working Group. Evelyne Vinet isthe guarantor of the manuscript.

Amendments 4 If the protocol represents an amendment of a previously completed or published protocol, identify as such and listchanges; otherwise, state plan for documenting important protocol amendments — This manuscript does not representa protocol amendment.

Support Sources 5a Indicate sources of financial or other support for the review — EV received salary funding from the Fonds de

Recherches Santé Québec (FRSQ). EGM received funding from an FRSQ Master’s award and the McGill ClinicianInvestigator Program. SK received funding through a CIHR Dissemination Event. This work will be used by theCanadian SLE Working Group to develop recommendations for the diagnosis and monitoring of SLE.

Sponsor 5b Provide name for the review funder and/or sponsor — The review was not funded. Role of sponsor 5c Describe roles of funder(s), sponsor(s), and/or institution(s), if any, in developing the protocol — Cochrane Review or funder was involved in the development of the PICO question.Introduction Rationale 6 Describe the rationale for the review in the context of what is already known — Pregnant patients with SLE have

higher rates of adverse obstetrical outcomes and SLE has a high likelihood of flaring in pregnancy, which in termcan lead to worse obstetrical outcomes; there exist few guidelines for the monitoring of pregnancy in SLE; it is knownthat quiescent disease for several months prior to conception is associated with improved outcomes. It is not knownwhat should be monitored throughout pregnancy in terms of blood and urine tests, serologies, ultrasounds, and diseaseactivity and at what frequency.

Objectives 7 Provide an explicit statement of the question(s) the review will address with reference to participants, interventions,comparators, and outcomes (PICO).

P – pregnant SLE patients including all women of child-bearing age. I – laboratory investigations: antiphospholipid antibodies, Ro/SSA and La/SSB antibodies, anti-DNA antibody,

complement levels, ESR, CRP, uric acid; renal function: disease activity, SLEPDAI, SLEDAI, BILAG, SLAM,ECLAM, SRI, CBC differential, lupus activity index, DNA antibodies; other: SLICC, monitoring of the baby, bloodpressure.

C – frequency. O – Preterm birth, preeclampsia/eclampsia, stillbirth, small for gestational age, intrauterine growth restriction,

congenital heart block, fetal heart block, neonatal lupus, stillbirth, miscarriage, SLE flare; gestational hypertension:renal insufficiency, maternal death, thromboembolism event, premature rupture of membranes, prematurelabor/delivery; secondary: gestational diabetes, cesarean delivery.

Methods: For the following section please refer to the Materials and Methods section of the manuscript Eligibility criteria 8 Specify the study characteristics (such as PICO, study design, setting, time frame) and report characteristics (such as

years considered, language, publication status) to be used as criteria for eligibility for the review. Information sources 9 Describe all intended information sources (such as electronic databases, contact with study authors, trial registers, or

other grey literature sources) with planned dates of coverage. Search strategy 10 Present draft of search strategy to be used for at least 1 electronic database, including planned limits, such that it could

be repeated. Study records Data management 11a Describe the mechanism(s) that will be used to manage records and data throughout the review — All records were

managed in an Excel spreadsheet that included author, year, population, exposure, outcomes, and results.



including North America, Europe, Latin America, Asia, andthe Middle East.Monitoring variables characteristics. Of 38 final articlesevaluated, 22/38 (58%) addressed the value of measuringserology, including the measurement of aPL antibodies priorto pregnancy and/or during the first trimester, and 18/38(47%) assessed monitoring for SLE flare with a validatedscoring system, such as the SLEDAI (Figure 2). The utility ofumbilical and/or uterine artery Doppler monitoring forpredicting poor obstetrical outcomes was evaluated in 5/38(13%) articles. Disease activity scoring systems modified toaccount for the physiologic changes of pregnancy wereobserved in 4 articles, such as the SLE in Pregnancy DiseaseActivity Index54 and the Lupus Activity Index in Pregnancy55.Of note, none of them have been formally validated.Outcomes. Findings from each study are summarized andpresented in Table 32,9,13,15,20-53; studies were evaluated forrisk of bias using the Newcastle-Ottawa scale and the qualityof data is presented in Table 42,9,13,15,20-53. Across the studies

included for full review, the presence of active disease(measured by various scoring systems), aPL antibodiespositivity, and abnormal uterine and umbilical artery Dopplerstudies predicted poor pregnancy outcomes. Lowcomplement and thrombocytopenia at the beginning ofpregnancy were also predictors of poor obstetrical outcomes.No studies that assessed the value of serological and diseaseactivity monitoring evaluated an evidence-based approach tothe frequency of monitoring. Studies that addressed uterineand umbilical artery Doppler monitoring discussed thefrequency at which these tests were performed but did notaddress the evidence behind the practice.

DISCUSSIONSummary of findings. In this systematic review examiningmonitoring in SLE pregnancies, 38 articles were included,after an initial screening of 1106 abstracts and 53 articles thatwere reviewed in depth. Final articles addressed themonitoring of SLE-related pregnancy and focused on 3 main



Table 1. Continued.

Section and Topic Item No. Checklist Item

Selection process 11b State the process that will be used for selecting studies (such as 2 independent reviewers) through each phase of thereview (that is, screening, eligibility, and inclusion in metaanalysis) — Three authors were involved in screening theabstracts [2 authors initially — EM and LB, and a third author (EV) was involved if the first 2 authors did not agreeon the eligibility of a study]. Two authors read the articles included for in-depth review and decided on the final exclu-sions (EM and EV).

Data collection process 11c Describe planned method of extracting data from reports (such as piloting forms, done independently, in duplicate),any processes for obtaining and confirming data from investigators — Two authors reviewed the articles included forthe final review and based on an Excel spreadsheet extracted the data and collated it.

Data items 12 List and define all variables for which data will be sought (such as PICO items, funding sources), any pre-planneddata assumptions and simplifications — For variables please refer to the in-depth description of the PICO questionabove where each component of the I and O are described in detail.

Outcomes and 13 List and define all outcomes for which data will be sought, including prioritization of main and additional outcomes, prioritization with rationale – Refer to the PICO question above where all elements of the outcomes are described. Risk of bias in 14 Describe anticipated methods for assessing risk of bias of individual studies, including whether this will be done individual studies at the outcome or study level, or both; state how this information will be used in data synthesis – Studies were evaluated for quality using the Newcastle-Ottawa Scale (described in depth in the body of the thesis). Data synthesis 15a Describe criteria under which study data will be quantitatively synthesized — Preliminary recommendations for

monitoring of pregnancies complicated by lupus are prepared based on GRADE analysis of the data quality (for moredetails please refer to the methods section) of the thesis.

15b If data are appropriate for quantitative synthesis, describe planned summary measures, methods of handling data, andmethods of combining data from studies, including any planned exploration of consistency (such as I2, Kendall’s τ)– Not applicable for this systematic review (relevant for metaanalysis only).

15c Describe any proposed additional analyses (such as sensitivity or subgroup analyses, metaregression) — Not applicablefor this systematic review (relevant for metaanalysis only).

15d If quantitative synthesis is not appropriate, describe the type of summary planned — Not applicable for this systematicreview (relevant for metaanalysis only).

Metabias(es) 16 Specify any planned assessment of metabias(es), such as publication bias across studies, selective reporting within studies – Not applicable for this systematic review (relevant for metaanalysis only).

Confidence in cumulative 17 Describe how the strength of the body of evidence will be assessed (such as GRADE) — This is described in great evidence detail in the methods section of the thesis.

PRISMA-P: Preferred Reporting Items for Systematic Review and Metaanalysis Protocols; GRADE: Grading of Recommendations Assessment, Development,and Evaluation; SLE: systemic lupus erythematosus; CIHR: Canadian Institutes of Health Research; PICO search strategy: Participants — Intervention —Comparison/Comparator — Outcome; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; SLEPDAI: SLE in Pregnancy Disease Activity Index;SLEDAI: Systemic Lupus Erythematosus Disease Activity Index; BILAG: British Isles Lupus Assessment Group index; SLAM: Systemic Lupus ActivityMeasure; ECLAM: European Consensus Lupus Activity Measure; SRI: SLEDAI-2K Responder Index 50; CBC: complete blood count; SLICC: SystemicLupus International Collaborating Clinics.



types of monitoring (blood and urine tests, SLE diseaseactivity monitoring, and uterine or umbilical Dopplerstudies), as well as other types of monitoring. There havebeen no randomized controlled studies on this topic and soall articles were observational studies. The majority of studieswere cohort studies that investigated predictors of poormaternal and fetal outcomes related to measures of SLEactivity (both disease-specific and otherwise) throughoutpregnancy. Studies included SLE women with varyingdegrees of disease activity, with some including only womenwith inactive or mildly active SLE, which might have influ-enced their findings.Possible recommendations. Based on our systematic reviewof the literature, there may be a role for monitoring aPL (LAC

and aCL), dsDNA, complement, and anti-Ro and anti-Laantibodies prior to conception and early in pregnancy.Complement and dsDNA are likely helpful measures whena flare is suspected because these tests were shown innumerous studies that we examined to be predictive of pooroutcomes (20/37 or 54% of studies addressed the predictivevalue of 1 or more of these monitoring variables). Becausepatients with quiescent SLE (i.e., with no or low diseaseactivity) have fewer negative outcomes in pregnancy, if theseautoantibodies and blood tests are measured prior toconception, it might help physicians stratify pregnancy riskin pregnant women and/or women planning a pregnancy.However, dsDNA, for example, does not always correlatewith disease flare and/or activity in all patients and so this is



Table 2. Study characteristics.

Author and Year Study Study Population Monitoring Variables

Al Arfaj 201020 RC Pre- and post-SLE pregnancies Serology, renal, BPAlshohaib 200921 PC Stable class 4 LN Serology, renal, BPBertolaccini 200722 CC SLE vs non-SLE pregnancies Anti-fX11Brucato 200223 PC Anti-Ro–positive pregnancies Serology, disease activityBuyon 20152 PC SLE pregnancies Serology, disease activity, PLT, antihypertensive useClowse 201124 RC SLE pregnancies Serology, disease activityClowse 20139 PC SLE pregnancies Serology, AFP, estradiol, CRP, disease activity, UACortés-Hernández 200225 PC SLE pregnancies Serology, BP, disease activityDaskalakis 200926 PC LN pregnancies Serology, renal, CBCDerksen 199427 PC SLE pregnancies Serology, disease activityFarine 199828 RC SLE pregnancies Disease activity, DopplersSurita 200729 PC SLE pregnancies Renal, disease activityGaballa 201230 PC SLE vs non-SLE pregnancies Serology, disease activity, DopplersGheita 201131 PC SLE pregnancies Serology, disease activity, DopplersLe Thi Huong 200632 PC SLE pregnancies Serology, renal, BP, DopplersIdeguchi 201333 RC SLE pregnancies Serology, fetal cardiac ultrasoundJaeggi 201034 CC Anti-Ro–positive pregnancies SerologyJara 200735 RC SLE vs non-SLE pregnancies Serology, prolactin, disease activityLiu 201215 RC SLE pregnancies Disease activity, presence of LN, thrombocytopeniaMokbel 201336 PC SLE pregnancies Disease activityMolad 200513 PC SLE pregnancies Serology, CBC, chemistry, disease activityMoroni 200237 RC LN pregnancies Renal, BP, serologyPetri 199538 CC SLE vs non-SLE pregnancies AFPSalazar-Páramo 200239 RC SLE vs non-SLE pregnancies Disease activityStagnaro-Green 201140 RC SLE pregnancies HypothyroidismAndrade 200641 RC SLE pregnancies Disease activityClark 200342 RC SLE pregnancies Serology, disease activityMavragani 199843 RC Anti-Ro vs healthy pregnancies Ro/LaOgasawara 199544 PC SLE pregnancies SerologySalomonsson 200245 RC Anti-Ro–positive pregnancies Ro/LaTandon 200446 RC SLE pregnancies RenalLeanos-Miranda 200747 PC SLE pregnancies Anti-PRL antibodies, disease activityMosca 200748 PC SLE pregnancies Serology, C1q antibodies, disease activityZhao 201349 RC New-onset SLE in pregnancy SerologyGiancotti 201150 PC SLE pregnancies DopplersGladman 200251 RC Anti-Ro–positive pregnancies Fetal echocardiogramLockshin 201252 PC Antiphospholipid pregnancies SerologySpence 200653 RC Anti-Ro–positive pregnancies Hypothyroidism

Renal = serum creatinine, urinalysis, urine microscopy, and/or urine protein-to-creatinine ratio. RC: retrospective cohort; PC: prospective cohort; CC: casecontrol; SLE: systemic lupus erythematosus; PRL: prolactin; BP: blood pressure; PLT: platelets; AFP: alpha fetal protein; CRP: C-reactive protein; LN: lupusnephritis; UA: uric acid; CBC: complete blood count.



not universally true, but might still contribute useful infor-mation. In addition, complement levels normally increaseduring pregnancy, which might further complicate its role asa reliable disease activity marker27. The available literature also suggests that laboratorytesting should be combined with evidence of increaseddisease activity index as measured by a validated scoringsystem, such as the SLEDAI, which has also shown to beassociated with poor maternal and obstetrical outcomes innumerous studies included in this systematic review (18/38or 47%). However, no study has directly compared thepredictive value of laboratory or clinical data alone ascompared to SLEDAI (which combines clinical activity aswell as laboratory data).

One expanding area of monitoring in SLE pregnanciesrelates to the role of uterine and umbilical Doppler studies.Absent end-diastolic velocities of the umbilical arterypredict early pregnancy-induced hypertension/preeclamp -sia and fetal or neonatal death in non-SLE pregnancies56,57.Abnormalities demonstrating increased resistive indices,notching of the arteries, or in very severe cases, reversalof end-diastolic flow, are highly predictive of poor fetaloutcomes in SLE pregnancies28,32. This type of monitoringis minimally invasive and could be considered in thesecond and third trimester if the expertise exists in thecenter where the patient’s pregnancy is followed. Thismonitoring could therefore be used at the time of asuspected flare, or at the discretion of the maternal-fetal



Figure 1. Flowchart of the article selection process.



medicine or obstetrical medicine specialist who is involvedin the patient’s care. Four studies looked at alternative or novel tests forpredicting poor outcomes in pregnancy such as anti-C1qantibodies, antiprolactin antibodies, antifactor X11, andalpha-fetal protein. Given that these studies have not beenreproduced, and many of these serological tests are notwidely available, we would not recommend their routine useat this time for monitoring of SLE pregnancies. Regarding other tests, it is reasonable to measure thyroidstimulating hormone levels early in pregnancy, becausehypothyroidism was found to be associated with anincreased risk of prematurity in pregnant women from thegeneral population as well as pregnant women with SLE,and was associated with an increased incidence of completeCHB among the offspring of mothers with anti-Roantibodies40,53. Prior to our study and the meeting of the Canadian SLEWorking Group, guidelines did not exist regarding whatmonitoring variables should be measured in SLE pregnanciesand at what frequency. A systematic review of the literaturerevealed there is no evidence to guide the frequency ofroutine monitoring of complete blood count, chemistry

profile including liver enzymes, and urinalysis (routine ormicroscopy) or urine protein to creatinine levels, duringpregnancy with SLE. There is some evidence for a role formeasuring anti-Ro and anti-La antibodies prior to conceptionand early in SLE-related pregnancy, to risk-stratifypregnancies regarding the development of complete CHB.Similarly, the presence of aPL is predictive of poor outcomes,particularly preeclampsia and fetal loss, and so may bereasonable to measure prior to conception or early inpregnancy. Monitoring SLE disease activity should be done,potentially with a validated scoring system such as theSLEDAI because it relies on assessment of different clinicalaspects of the disease (i.e., clinical manifestations andspecific blood tests). If a flare is suspected, measuring anti-dsDNA antibodies and complement levels may be helpful.Women with SLE should be considered for referral to anexpert in maternal-fetal medicine for fetal monitoring withumbilical artery Doppler studies, given that Doppler abnor-malities are predictive of adverse outcomes; among pregnantpopulations without SLE, this monitoring modality hasimproved fetal outcomes. This systematic review will informguidelines for the type of and frequency of monitoring ofSLE in pregnancy, which are being developed by theCanadian SLE Working Group.



Figure 2. Histogram of the frequency of monitoring variables evaluated in the studies included in the systematic literature review.Serology = anti-DNA, antiextractable nuclear antibody, IgG and IgM anticardiolipin antibodies, lupus anticoagulant, and/orcomplement levels. Disease activity measured using a validated scoring system (examples include the SLEDAI and ECLAMscores; studies that did not use any type of scoring system to measure disease activity were not included). Renal = serum creatinine,urinalysis, urine microscopy and/or urine creatinine-to-protein ratio. Other = variables evaluated by only 1 included study (e.g.,antifactor X11, C1q, and anti-PRL antibodies). AFP: alpha fetal protein; Hypo T4: hypothyroidism; CBC: complete blood count;PLT: platelets; BP: blood pressure; SLEDAI: Systemic Lupus Erythematosus Disease Activity Index; ECLAM: EuropeanConsensus Lupus Activity Measure; PRL: prolactin.





Table

3.Ou

tcome

s rela

ted to

mon

itorin

g vari

ables

.

Autho

r, Yea

r

Cou

ntry,

No. P

atien

ts,

C

riteri

a

C

onclu

sions

No.

Preg

nanc

ies

Al A

rfaj 2

01020

Sa

udi A

rabia,

319 w

omen

,

19

97 A

CR

Any

histo

ry of

LN w

as ass

ociat

ed w

/prem

aturit

y (36

.4% w

/LN

vs 21

.1% w

/o LN

; p 0.

01).

Activ

e LN

was m

ore as

socia

ted

39

6 preg

nanc

ies

w/pre

gnan

cy lo

ss tha

n quie

scent

LN (2

6/44,

59.1%

vs 27

/109,

24.8%

; p <

0.001

) and

more

asso

ciated

w/pr

ematu

rity (

61.1%

v

s 30%

; p =

0.014

).

Pres

ence

of aP

L was

assoc

iated

w/fe

tal lo

ss (12

8 live

birth

s/205

deliv

eries

were

aPL+

, 62.4

% vs

141/1

78 de

liveri

es we

re

aPL

–, 79

.2%; p

= 0.0

04).

S

LE fla

re wa

s asso

ciated

w/fe

tal lo

ss (71

live b

irths

/118 d

elive

ries w

/flare

, 60.2

% vs

198/2

65 pr

egna

ncies

w/o

flare,

74.7%

;

p =

0.004

). Flar

e was

assoc

iated

w/IU

GR (3

8.1%

pregn

ancie

s w/fl

are vs

20.3%

w/o

flare,

p < 0

.003).

H

TN w

as ass

ociat

ed w

/IUGR

(44.6

% HT

N pre

gnan

cies v

s 20.2

% no

n-HTN

; p =

0.01).

HTN

was

assoc

iated

w/pr

ematu

rity

(

48.9%

HTN

preg

nanc

ies vs

21.2%

non-H

TN; p

< 0.0

001).

Alsh

ohaib

2009

21

S

audi

Arab

ia, 20

wom

en,

LN on

biop

sy

20 pr

egna

nt wo

men w

/quies

cent

class

IV L

N. Pr

oteinu

ria in

crease

d sign

ifica

ntly f

rom 32

wee

ks G

A to

34–3

6 wee

ks G

A

2

0 preg

nanc

ies

(p <

0.05).

A

PO oc

curre

d in 6

of 20

patie

nts an

d all w

ere as

socia

ted w

/the d

evelo

pmen

t of a

nti-ds

DNA+

(no p

value

avail

able

for

c

ompa

rison

).An

drade

2006

41

USA,

63 w

omen

and p

regna

ncies

1

997 A

CR

The

SDI s

core

after

pregn

ancy

was

signif

icantl

y high

er tha

n befo

re it (

mean

SDI s

core

befor

e: 0.1

9; me

an SD

I sco

re aft

er:

0

.60, p

< 0.0

001).

D

amag

e acc

rual w

as str

ongly

asso

ciated

w/pr

egna

ncy d

uratio

n, dis

ease

activ

ity, a

nd da

mage

accru

al at

the vi

sit im

media

tely

p

rior to

the p

regna

ncy o

utcom

e (p =

0.00

6, p <

0.00

1 and

p < 0

.001,

respe

ctive

ly), a

nd m

odera

tely a

ssocia

ted w

/total

disea

se

dura

tion (

p = 0.

039).

Berto

laccin

i 200

722

E

nglan

d, 83

preg

nant

19

82 cr

iteria

Pa

tients

w/A

PO w

ere m

ore lik

ely to

have

anti-

fXII

IgG bu

t not

IgM [3

7% vs

4%, O

R 14

(95%

CI 4

.5–43

) and

9% vs

3%,

w

omen

(con

trol 1

23

O

R 2.8

. (95%

CI 0

.6–13

)].

hea

lthy d

elive

ries)

Pati

ents

w/mi

scarri

age a

nd fe

tal de

ath w

ere m

ore lik

ely to

have

anti-

fXII

IgG [3

5% vs

4%; O

R 12

(95%

CI 3

.7–42

) and

40%

vs 4%

, OR

16 (9

5% C

I 4–6

2)].

Bruc

ato 20

0223

Ita

ly, 53

SLE

Ro+ v

s 58 S

LE R

o–

199

7 ACR

T

here

was n

o sign

ifica

nt dif

feren

ce in

APO

betw

een w

omen

w/ a

nd w

/o Ro

antib

odies

(p =

NS fo

r mult

iple c

ompa

rison

s);

C

HB w

as mo

re co

mmon

amon

g Ro+

(no p

value

for c

ompa

rison

; only

2 ca

ses of

CHB

).Bu

yon 2

0152

U

SA an

d Can

ada,

385 w

omen

1997

ACR

F

irst tr

imest

er pre

dictor

s of A

PO in

clude

d LAC

(OR

8.32,

95%

CI 3.

59–1

9.26),

antih

ypert

ensiv

e use

(OR

7.05,

95%

CI

w/SL

E

3

.05–1

6.31),

PGA

score

> 1 (O

R 4.0

2, 95

% CI

1.84

–8.82

), and

plate

let co

unt (

OR 1.

33, 9

5% C

I 1.09

–1.63

per d

ecrea

se of

5

0 × 10

9 cell

s/l).

Clark

2003

42

Ca

nada

, 88 w

omen

and p

regna

ncies

19

97 A

CR

SLE

patie

nts w

/prete

rm de

liveri

es we

re mo

re lik

ely to

be ta

king ≥

10 m

g/day

pred

nison

e duri

ng th

eir pr

egna

ncy (

50.0%

vs

2

2.2%,

p = 0

.028)

and h

ad m

ore aC

L IgG

posit

ivity

(p = 0

023).

T

he m

ean w

eeks

of ge

statio

n was

short

er for

aCL+

IgG

comp

ared t

o the

aCL–

grou

p (34

.9 ± 4

.4 vs

37.5

± 3.2

week

s,

resp

ectiv

ely; p

= 0.0

32). T

here

was n

o diff

erenc

e in s

econ

d trim

ester

disea

se ac

tivity

betw

een t

he te

rm an

d pret

erm gr

oups

(

33.3%

and 3

6.4%

of ea

ch gr

oup h

ad a

SLED

AI of

0).

M

ore w

omen

in th

e term

grou

p rec

eived

no m

edica

tion d

uring

their

preg

nanc

ies co

mpare

d to w

omen

in th

e pret

erm gr

oup

(

20.0%

vs 0.

0%, p

= 0.0

31).

Clow

se 20

1124

U

SA, 2

03 w

omen

, 267

preg

nanc

ies

1997

ACR

T

he pr

esenc

e of a

nti-ds

DNA

in the

seco

nd tr

imest

er wa

s asso

ciated

w/fe

tal lo

ss (11

vs 9,

p = 0

.039)

and p

reterm

birth

(34

vs 46

, p =

0.032

).

Low

C3 i

n the

seco

nd tr

imest

er wa

s asso

ciated

w/fe

tal lo

ss (7/

131 v

s 13/9

2, p =

0.02

1).

High

disea

se ac

tivity

(PGA

≥ 2)

in the

seco

nd tr

imest

er wa

s asso

ciated

w/pr

ematu

rity (

62/19

4 vs 1

8/29,

p = 0.

0003

).Cl

owse

2013

9

US

A, 39

wom

en, 4

0 preg

nanc

ies

199

7 ACR

W

hen m

easu

red at

mid-

gesta

tion (

20–2

8 wee

ks) l

ow es

tradio

l (R

= 0.44

, p =

0.01),

incre

ased f

erritin

(R =

–0.37

, p =

0.05),

or i

ncrea

sed ur

ic ac

id (R

= –0

.43, p

= 0.0

2) ma

y corr

elate

w/pre

matur

ity an

d earl

ier ge

statio

nal a

ge at

deliv

ery.

D

isease

activ

ity di

d not

corre

late w

/prem

aturit

y (me

asured

w/SL

EPDA

I and

PGA)

. Ove

rall, t

he co

hort h

ad lo

w SL

E dise

ase

a

ctivit

y.





Table

3.(C

ontin

ued)

Outco

mes r

elated

to m

onito

ring v

ariab

les.

Autho

r, Yea

r

Cou

ntry,

No. P

atien

ts,

C

riteri

a

C

onclu

sions

No.

Preg

nanc

ies

Corté

s-Hern

ánde

zSp

ain, 6

0 wom

en, 1

03 pr

egna

ncies

19

82 cr

iteria

Amon

g tho

se w/

a hist

ory of

LN,

aCL A

b pos

itivity

was

assoc

iated

w/fe

tal lo

ss: 0/

5 norm

al bir

ths vs

9/11

(82%

) w/a

2002

25fet

allos

s were

aCL A

b+, p

< 0.0

5. HT

N wa

s asso

ciated

w/ A

PO: 0

/5 no

rmal

births

vs 2/

3 (67

%) pr

egna

ncies

w/ A

PO

were

hype

rtens

ive, p

< 0.0

05.

A

mong

all S

LE pr

egna

ncies

, aCL

Ab p

ositiv

ity w

as ass

ociat

ed w

/ APO

: 11/4

3 (26

%) no

rmal

births

vs 11

/25 (4

4%) b

irths

w/ A

PO w

ere aC

L Ab+

, p <

0.05.

HTN

at co

ncep

tion w

as ass

ociat

ed w

/ feta

l loss:

0/43

norm

al bir

ths vs

6/27

(22%

) birt

hs

w/ a

fetal

loss

were

hype

rtens

ive, p

< 0.0

5. Lo

w C3

asso

ciated

w/ f

etal lo

ss: 11

/43 (2

6%) n

ormal

births

vs 12

/27 (4

4%) o

f

birt

hs w

/ APO

had l

ow C

3, p <

0.05

.

Wom

en w

ho fla

red (n

= 34

) tend

ed to

have

a his

tory o

f > 3

flares

/yr up

until

3 mos

PTC

comp

ared t

o tho

se wh

o did

not fl

are

in p

regna

ncy (

n = 67

, p =

0.035

), and

tend

ed to

have

a hig

her m

ean S

LEDA

I in t

he 3

mos P

TC (3

.13 vs

1.64

, p =

0.03).

Dask

alakis

2009

26

Gree

ce, 1

1 wom

en, 1

2 preg

nanc

ies 1

982 c

riteri

a

A

ll pati

ents

w/ L

N on

rena

l biop

sy. R

enal

functi

on de

terior

ated i

n 3/12

(25%

). Pree

clamp

sia oc

curre

d in 3

/12 (2

5%). A

n

APO

was

obser

ved i

n 10/1

2 preg

nanc

ies (8

3%). N

o com

paris

ons w

ere m

ade.

Derks

en 19

9427

The

Neth

erlan

ds, 2

5 wom

en,

1982

ARA

crite

ria

D

isease

activ

ity m

onito

red w

/ SLE

DAI. U

p to 1

4/35 p

regna

ncies

(40%

) man

ifeste

d evid

ence

of di

sease

flare

in pre

gnan

cy.

35 p

regna

ncies

aP

L+ te

nded

to ha

ve fe

wer l

ive bi

rths a

nd m

ore pr

eecla

mpsia

: 10/1

6 (63

%) vs

15/19

(79%

) had

live b

irths

w/ a

PL+ a

nd

4

2% vs

13%

had p

reecla

mpsia

. No p

value

s calc

ulated

.Fa

rine 1

99828

Ca

nada

, 56 w

omen

and

1

982 A

RA cr

iteria

R/A

EDF w

as ass

ociat

ed w

/ APO

. Pree

clamp

sia oc

curre

d in 6

/50 (1

2%) o

f tho

se w/

NED

F vs 4

/6 (67

%) w

/ R/A

EDF (

OR

pre

gnan

cies

1

4, 95

% CI

2.19

–98.1

3; p =

0.00

7).

IUG

R oc

curre

d in 1

2/50 (

24%)

w/ N

EDF v

s 4/6

(67%)

w/ R

/AED

F (OR

6.3,

95%

CI 1.

03–3

8.98;

p = 0.

049).

P

reterm

deliv

ery oc

curre

d in 1

2/50 (

24%)

w/ N

EDF v

s 83%

w/ R

/AED

F (OR

15.8,

95%

CI 1.

68–1

49.17

; p =

0.008

).Ga

balla

2012

30

Egyp

t, 40 w

omen

and p

regna

ncies

1

997 A

CR

The

re wa

s a te

nden

cy fo

r flar

e amo

ng pr

egna

nt SL

E more

than

nonp

regna

nt SL

E: 21

/35 (6

0%) v

s 14/4

0 (37

.5%), p

= 0.0

52.

w

/ SLE

(con

trol 3

5 non

pregn

ant S

LE)

Thos

e who

flare

d were

more

likely

to ha

ve a

SLED

AI >

2 at c

once

ption

: 15/2

5 (60

%) vs

20%,

p = 0

.013.

A

PO w

as ass

ociat

ed w

/ more

seve

re fla

re in

pregn

ancy

: 0/15

full t

erm pr

egna

ncies

vs 7/

16 (4

3.8%)

APO

had a

seve

re fla

re,

p <

0.05.

a

PL po

sitivi

ty wa

s asso

ciated

w/ fe

tal lo

ss: 1/

15 (0

.07%)

term

preg

nanc

ies vs

6/9 (

67%)

fetal

losse

s were

aPL +

ve, p

< 0.0

5.

Acti

ve re

nal d

isease

was

assoc

iated

w/ A

PO: 1

/15 (0

.07%)

term

preg

nanc

ies vs

8/16

(50%

) w/ A

PO ha

d acti

ve re

nal d

isease

at c

once

ption

, p <

0.05.

Gheit

a 201

131

Eg

ypt, 3

6 wom

en an

d preg

nanc

ies

1997

ACR

T

here

was a

high

er SL

EDAI

and S

LICC

in th

ose w

/ APO

and t

he di

fferen

ce re

ache

d sign

ifica

nce f

or the

disea

se ac

tivity

at

the

24th

week

(12.1

3 ± 3.

27 an

d 7.57

± 2.1

8, res

pecti

vely,

p = 0

.005).

U

mbilic

al RI

and P

I were

sign

ifica

ntly h

igher

in tho

se w/

APO

start

ing fr

om th

e 30th

wee

k unti

l full

term

: 0.71

± 0.0

5 vs

0

.66 ±

0.04,

p = 0.

018 f

or RI

and 1

.22 ±

0.26 v

s 0.98

± 0.0

9, p =

0.03

for P

I at 3

0 wee

ks G

A.Gi

anco

tti 20

1150

Ita

ly, 20

wom

en an

d preg

nanc

ies

199

7 ACR

D

opple

r of t

he ut

erine

arter

ies w

as alt

ered i

n 9/20

(45%

) preg

nanc

ies w

/ mea

n RI >

0.79

. Two

of th

ese w

omen

had

s

ponta

neou

s abo

rtion

durin

g the

first

trim

ester

of pre

gnan

cy; th

e othe

r 7 pr

egna

ncies

ende

d w/ p

reterm

deliv

eries.

1

1 wom

en (7

w/ a

ltered

uteri

ne ar

tery U

S Dop

pler a

nd 4

w/ al

tered

fetal

US D

opple

r) ha

d pret

erm de

liveri

es.Gl

adma

n 200

251

Ca

nada

, 105

wom

en,

Anti

-Ro o

r -La

–pos

itive

No c

ase of

CCH

B wa

s obs

erved

in 10

2 preg

nanc

ies w

/o a h

istory

of C

CHB.

Amo

ng 12

preg

nanc

ies w

/ a hi

story

of CC

HB,

118 p

regna

ncies

1 f

etus d

evelo

ped C

CHB.

Resu

lts su

ggest

that

the ri

sks o

f CCH

B w/

o a hi

story

are lo

w.Le

Ti H

uong

2006

32

F

rance

, 84 w

omen

,

199

7 ACR

A

bnorm

al um

bilica

l arte

ry Do

ppler

in th

e sec

ond t

rimest

er pre

dicted

fetal

death

: 3/8

(37.5%

) feta

l dea

ths ha

d an a

bnorm

al

11

6 preg

nanc

ies

umbil

ical a

rtery

Dopp

ler vs

3/92

(3.3%

) live

birth

s (OR

17.8,

95%

CI 2.

84–1

11.68

; p =

0.006

). Notc

hed u

terine

arter

y

Dop

pler p

redict

ed fe

tal de

ath: 5

/8 (62

.5%) f

etal d

eaths

were

abno

rmal

vs 10

/92 (1

0.9%)

of liv

e birt

hs (O

R 13

.67, 9

5% C

I

2.83

–66,

p = 0.

002).

Idegu

chi 2

01333

Jap

an, 4

1 wom

en, 5

5 preg

nanc

ies

199

7 ACR

I

UFD

was a

ssocia

ted w

/ aPL

posit

ivity:

2/8 (

25%)

fetal

death

s vs 1

/42 (2

%) te

rm pr

egna

ncies

were

aPL+

.

IUF

D wa

s asso

ciated

w/ lo

w C3

: 4/8

(50%)

of fe

tal de

aths v

s 6/42

(14%

) had

low

C3.

Jaegg

i 201

034

Can

ada,

40 fe

tuses/

neon

ates

N

/A

All m

others

of ch

ildren

w/ c

ardiac

invo

lveme

nt ha

d mod

erate

to hig

h anti

-Ro a

ntibo

dy le

vels

(> 50

U/m

l) as

comp

ared w

/

w/ C

CHB

comp

ared t

o 146

w/o

o

nly 44

% of

mothe

rs of

healt

hy in

fants

(p < 0

.0001

). In p

rospe

ctive

ly scr

eene

d fetu

ses on

ly, th

e eve

nt rat

e of C

CHB

was

5

% (3

of 59

cases

) for

fetus

es w/

expo

sure

to an

ti-Ro

leve

ls > 5

0 U/m

l, OR

7.8 (0

.4–15

9).Jar

a 200

735

M

exico

, 15 w

omen

and

19

97 A

CR

Elev

ated p

rolac

tin le

vels

corre

lated

w/ M

-SLA

M: r

= 0.4

3, p <

0.01

in pr

egna

ncies

comp

licate

d by p

reterm

birth

.

preg

nanc

ies w

/ SLE





Table

3.(C

ontin

ued)

Outco

mes r

elated

to m

onito

ring v

ariab

les.

Autho

r, Yea

r

Cou

ntry,

No. P

atien

ts,

C

riteri

a

C

onclu

sions

No.

Preg

nanc

ies

Lean

os-M

irand

a

M

exico

, 99 S

LE pr

egna

ncies

199

7 ACR

W

omen

w/ S

LE an

d anti

-PRL

Ab w

ere le

ss lik

ely to

flare

in pr

egna

ncy t

han w

omen

w/o:

2/13

(15.4

%) vs

54/86

(62.8

%),

2007

47

(co

ntrol

151 h

ealth

y preg

nanc

ies)

p =

0.00

4.

Feta

l com

plica

tions

were

more

comm

on am

ong w

omen

w/o

anti-

PRL A

b tha

n wom

en w

/ Ab+

: 57.5

% vs

1/13

(7.7%

),

p =

0.002

.Lo

cksh

in 20

1252

USA

, 144

wom

en an

d preg

nanc

ies

1997

ACR

L

AC w

as the

prim

ary pr

edict

or of

APO

after

12 w

eeks

of ge

statio

n in a

PL-as

socia

ted pr

egna

ncies

. aCL

antib

ody a

nd

a

nti-β

2-GPI

, if L

AC is

not a

lso pr

esent,

did n

ot pre

dict A

PO.

L

AC co

nferre

d an R

R of

12.15

(95%

CI 2

.92–5

0.5) f

or AP

O, p

= 0.00

06.

S

LE co

nferre

d an R

R of

2.16 (

95%

CI 1.

27–3

.68) f

or AP

O, p

= 0.05

.

Prio

r thro

mbos

is co

nferre

d a R

R of

1.9 (9

5% 1.

14–3

.17) f

or AP

O, p

= 0.01

.Li

u 201

215

China

, 105

wom

en, 1

11 pr

egna

ncies

19

97 A

CR

Acti

ve SL

E (S

LEDA

I > 4)

vs qu

iesce

nt SL

E wa

s asso

ciated

w/ th

e foll

owing

:

Prem

aturit

y: 25

/47 (5

3.2%)

vs 3/

34 (8

.8%), p

< 0.0

01

SGA

: 21/4

8 (43

.8%) v

s 3/35

(8.6%

), p <

0.001

P

reecla

mpsia

: 23/5

3 (43

.4%) v

s 2/35

(5.7%

), p <

0.001

F

etal lo

ss: 9/

53 (1

7%) v

s 1/35

(2.9%

), p =

0.047

P

reecla

mpsia

was

a pred

ictor

of pre

gnan

cy lo

ss (O

R 14

.83, 9

5% C

I 3.83

–57.4

1, p <

0.00

1), pr

ematu

rity (

OR 8.

04, 9

5% C

I

2.00

–32.3

4, p =

0.00

3), an

d SLE

flare

in pr

egna

ncy (

OR 8.

92, 9

5% C

I 2.25

–35.4

4, p =

0.00

2).

Thro

mboc

ytope

nia w

as a p

redict

or of

pregn

ancy

loss

(OR

4.43,

95%

CI 1.

12–1

7.6, p

= 0.0

35), a

nd SL

E fla

re in

pregn

ancy

(OR

4.03

, 95%

CI 1

.24–1

7.25,

p = 0.

022).

Mav

ragan

i 199

843

C

hina,

154 R

o+ w

omen

1

997 A

CR

Anti

-Ro p

ositiv

ity w

as no

t asso

ciated

w/ a

n inc

rease

in AP

O be

twee

n SLE

patie

nts 28

/78 (3

5.9%)

vs 31

/71 (4

3.7%)

, p =

NS

(78 S

LE an

d 76 n

on-S

LE)

or b

etwee

n SLE

patie

nts an

d hea

lthy c

ontro

ls 53

/154 (

34.4%

), p =

NS.

vs

142 R

o– (7

1 SLE

)

M

okbe

l 201

336

Egy

pt, 34

wom

en, 3

7 preg

nanc

ies

199

7 ACR

P

lanne

d preg

nanc

y and

SLED

AI at

the b

eginn

ing of

preg

nanc

y were

sign

ifica

ntly a

ssocia

ted w

/ feta

l loss

at un

ivaria

te

ana

lysis.

How

ever,

there

were

no si

gnifi

cant

predic

tors o

f feta

l loss

at bin

ary lo

gistic

regre

ssion

analy

sis. E

ffect

measu

res

n

ot rep

orted

.M

olad 2

00513

Israe

l, 20 w

omen

, 29 p

regna

ncies

1

997 A

CR

In t

his st

udy,

no m

ultiva

riate

mode

ls rea

ched

stati

stica

l sign

ifica

nce.

Increa

sed ds

DNA

(r = 0

.5, p

= 0.03

), prot

einuri

a (r =

0.6,

p = 0

.02), a

nd le

ukop

enia

(r = 0

.6, p

= 0.01

) were

asso

ciated

w/ p

ostpa

rtum

flare

in un

ivaria

te an

alyses

. Incre

ased

p

regest

ation

al SL

EDAI

did n

ot ha

ve a

statis

ticall

y sign

ifica

nt eff

ect o

n risk

for p

ostpa

rtum

flare.

A

PO (i

nclud

ing pr

eecla

mpsia

, IUGR

, and

prem

aturit

y) we

re ass

ociat

ed w

/ low

prege

statio

nal a

lbumi

n (r =

0.5,

p = 0.

01)

a

nd in

crease

d dsD

NA (r

= 0.5

, p =

0.03).

SLED

AI w

as no

t stat

istica

lly as

socia

ted w

/ APO

.M

oroni

2002

37

Italy,

48 w

omen

, 70

1

997 A

CR

Pred

ictors

of fe

tal lo

ss in

multiv

ariate

analy

sis in

clude

d arte

rial h

ypert

ensio

n (OR

6.4,

95%

CI 1.

4–28

.9; p

= 0.05

), prot

einuri

a

preg

nanc

ies w

/LN

(OR1

3.3, 9

5% C

I 2.6–

66.6;

p = 0

.025),

and a

PL (O

R 17

.8, 95

% CI

3.8–

81.4,

p = 0

.01).

T

he pr

esenc

e of a

ny si

gn of

activ

ity of

rena

l dise

ase (p

lasma

crea

tinine

> 1.2

mg/d

l or p

rotein

uria >

0.5 g

/24 h,

w/ u

rinary

red

bloo

d cell

s > 5

cells

/HPF

) at th

e beg

inning

of pr

egna

ncy w

as the

only

predic

tor of

rena

l flar

es. R

enal

flares

occu

rred i

n

1/20

preg

nanc

ies (5

%) w

/ quie

scent

renal

disea

se vs

12/31

preg

nanc

ies (3

9%) w

/ acti

ve re

nal d

isease

(p <

0.01).

Mos

ca 20

0748

Italy

, 19 w

omen

, 21 p

regna

ncies

1

997 A

CR

aPL

was

assoc

iated

w/ A

PO (p

< 0.0

5); no

effec

t mea

sure

report

ed.

A

nti-C

1q an

d anti

-dsDN

A an

tibod

ies w

ere no

t pred

ictive

of A

PO or

of SL

E fla

re (p

= NS)

; no e

ffect

measu

res re

porte

d.Og

asawa

ra 19

9544

Ja

pan,

12 w

omen

and p

regna

ncies

19

82 A

RA

aPL

was

assoc

iated

w/ IU

FD in

a sm

all nu

mber

of wo

men s

tudied

; 6/7

(85.7%

) of a

PL– w

omen

had l

ive bi

rths v

s 2/4

(50%)

of a

PL+ w

omen

. One

aPL–

wom

an ha

d an S

AB. N

o p va

lue av

ailab

le for

comp

ariso

n.Pe

tri 19

9538

U

SA, 5

5 wom

en an

d preg

nanc

ies

198

2 ARA

A

FP w

as hig

her i

n SLE

preg

nanc

ies (1

.425 ±

0.73

vs 1.

169 ±

0.5,

p = 0.

001).

The 4

patie

nts w

/ abn

ormal

AFP (

> 2.3)

were

(contr

ol 10

01 w

omen

w/o

SLE)

more

likely

to ha

ve pr

eterm

deliv

eries

(31.5

vs 36

.3 we

eks,

p = 0.

02) a

nd w

ere m

ore lik

ely to

have

aCL (

p = 0.

03).

Salaz

ar-Pá

ramo

M

exico

, 15 S

LE pr

egna

ncies

199

7 ACR

I

gG aC

L was

assoc

iated

w/ f

etal lo

ss (R

R 7.8

,95%

CI 1

.1–58

; p =

0.01).

2002

39

(co

ntrol

15 no

n-SLE

preg

nanc

ies)

An

ti-ds

DNA

was a

ssocia

ted w

/ feta

l loss

(RR

12, 9

5% C

I 1.7–

86; p

= 0.0

1).

Mild

SLE

flare

was n

ot ass

ociat

ed w

/ APO

, p >

0.05.

S

evere

flare

was

assoc

iated

w/ f

etal lo

ss (R

R 13

.9, 95

% CI

1.7–

100;

p = 0.

01).





Table

3.(C

ontin

ued)

Outco

mes r

elated

to m

onito

ring v

ariab

les.

Autho

r, Yea

r

Cou

ntry,

No. P

atien

ts,

C

riteri

a

C

onclu

sions

No.

Preg

nanc

ies

Salom

onsso

n 200

245

Swed

en, 8

Ro/L

a+ pr

egna

ncies

N

/A

IgG an

ti-Ro

52-kd

antib

odies

could

be de

tected

in al

l moth

ers (9

of 9)

who

gave

birth

to ch

ildren

w/ C

CHB,

as w

ell as

in al

l

w/ C

CHB,

and 2

6 Ro/L

a+ w

/o CC

HB

8

of th

eir af

fected

child

ren. In

moth

ers of

unaff

ected

child

ren, Ig

G an

ti-Ro

52-kd

occu

rred l

ess fr

eque

ntly a

nd at

lowe

r leve

ls

(p <

0.02

).Sp

ence

2006

53

Can

ada,

87 R

o+ w

omen

, 102

preg

nanc

ies

N/A

5/9

(56%)

of ch

ildren

born

to wo

men w

/ anti

-Ro a

nd hy

pothy

roidis

m ha

d CCH

B co

mpare

d to 1

0/78 (

13%)

of ch

ildren

born

t

o wom

en w

/ anti

-Ro a

nd no

rmal

thyroi

d fun

ction

; OR

8.63 (

95%

CI 1.

63–4

8.08;

p = 0.

006).

Stagn

aro-G

reen

USA,

63 w

omen

and p

regna

ncies

1

997 A

CR

Pret

erm de

livery

was

highe

r amo

ng SL

E ca

ses w

/ thyro

id dis

ease

10/15

(67%

) as c

ompa

red to

wom

en w

ho w

ere eu

thyroi

d 20

1140

6/34

(18%

), p <

0.002

.Su

rita 2

00729

N/A

N/A

Ac

tive S

LE w

as ass

ociat

ed w

/ poo

r obs

tetric

al ou

tcome

s. Di

sease

flare

was m

ore co

mmon

in w

omen

w/ r

enal

involv

emen

t

and

was

relate

d to a

grea

ter pr

evale

nce o

f pree

clamp

sia.

Tand

on 20

0446

N

/A

1997

ACR

P

regna

ncy i

n pati

ents

w/ re

nal d

isease

and S

LE w

as no

t asso

ciated

w/ a

more

sign

ifica

nt de

terior

ation

of re

nal f

uncti

on

c

ompa

red to

nonp

regna

nt pa

tients

w/ S

LE an

d ren

al dis

ease

(p = N

S).

Zhao

2013

49

C

hina,

48 w

omen

w/

1

997 A

CR

LN

and s

evere

throm

bocy

topen

ia we

re mo

re co

mmon

ly see

n in n

ew-on

set SL

E du

ring p

regna

ncy t

han i

n pati

ents

w/o

SLE

onset

in pr

egna

ncy,

pre

gnan

cy (6

8.8 vs

35.4%

and 2

5 vs 9

.2%, re

spec

tively

, p <

0.05).

ma

tched

w/ 6

5 wom

en

Com

pared

to L

N pa

tients

w/o

pregn

ancy

(n =

23), L

N pa

tients

w/ p

regna

ncy (

n = 33

) had

more

prom

inent

protei

nuria

and

w/ S

LE an

d not

pregn

ant

nep

hrotic

synd

rome (

p < 0.

05).

ACR:

Ame

rican

Coll

ege o

f Rhe

umato

logy;

SLE:

syste

mic l

upus

eryth

emato

sus;

LN: lu

pus n

ephri

tis; S

DI: S

ystem

ic Lu

pus I

nterna

tiona

l Coll

abora

ting C

linics

/ACR

Dam

age I

ndex

; HTN

: hyp

erten

sion;

IUFD

: intr

auter

ine fe

tal de

ath; C

CHB:

comp

lete c

onge

nital

heart

bloc

k; LA

C: lu

pus a

ntico

agula

nt; aP

L: an

tipho

spho

lipid

antib

odies

; HPF

: high

-powe

r fiel

d; AP

O: ad

verse

preg

nanc

y outc

omes;

GA:

gesta

tiona

l age

; SGA

: sma

ll for

GA; IU

GR: in

traute

rine g

rowth

restri

ction

; PGA

: phy

sician

’s glo

bal a

ssessm

ent; R

/AED

F: rev

ersed

or ab

sent e

nd-di

astoli

c flow

; NED

F: no

tched

end-d

iastol

ic flo

w; SL

ICC:

Syste

mic L

upus

Inter

natio

nal C

ollab

oratin

g Clin

ics; P

TC: p

rior to

conc

eptio

n; PR

L: pr

olacti

n; an

ti-β2

-GPI

: apo

lipop

rotein

H; S

AB: s

ponta

neou

s abo

rtion

; NS:

not s

ignifi

cant;

aCL:

antic

ardiol

ipin a

ntibo

dies;

RI: re

sistan

ce in

dex;

PI: p

ulsati

lity in

dex;

US: u

ltraso

und;

M-S

LAM

: mod

ified

syste

mic l

upus

activ

ity m

easu

remen

t; ARA

: Ame

rican

Rhe

umati

sm A

ssocia

tion;

AFP:

alpha

fetal

prote

in; N

/A: n

ot av

ailab

le;SL

EDAI

: SLE

Dise

ase A

ctivit

y Ind

ex; A

b: an

tibod

y .



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