A Critical Review on Obstetric Follow-up ofWomen Affected by Systemic Lupus Erythematosus

Pastore, Danilo Eduardo Abib; Costa, Maria Laura; Parpinelli, Mary Angela; Surita, Fernanda Garanhani

doi:10.1055/s-0038-1625951

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Revista Brasileira de Ginecologia e Obstetrícia

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Brasil

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Review Article • Rev. Bras. Ginecol. Obstet. 40 (04) • Apr 2018 • https://doi.org/10.1055/s-0038-1625951 copy

A Critical Review on Obstetric Follow-up ofWomen Affected by Systemic Lupus Erythematosus

Uma Revisão Crítica Sobre o Acompanhamento Obstétrico de Mulheres com Lúpus Eritematoso Sistêmico

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

To review the existing recommendations on the prenatal care of women with systemic lupus erythematosus (SLE), based on currently available scientific evidence.

Methods

An integrative review was performed by two independent researchers, based on the literature available in the MEDLINE (via PubMed), EMBASE and The Cochrane Library databases, using the medical subject headings (MeSH) terms “systemic lupus erythematosus” AND “high-risk pregnancy” OR “prenatal care.” Studies published in English between 2007 and 2017 were included; experimental studies and case reports were excluded. In cases of disagreement regarding the inclusion of studies, a third senior researcher was consulted. Forty titles were initially identified; four duplicates were excluded. After reading the abstracts, 7 were further excluded and 29 were selected for a full-text evaluation.

Results

Systemic lupus erythematosus flares, preeclampsia, gestation loss, preterm birth, fetal growth restriction and neonatal lupus syndromes (mainly congenital heartblock) were the major complications described. The multidisciplinary team should adopt a specific monitoring, with particular therapeutic protocols. There are safe and effective drug options that should be prescribed for a good control of SLE activity.

Conclusion

Pregnant women with SLE present an increased risk for maternal complications, pregnancy loss and other adverse outcomes. The disease activity may worsen and, thereby, increase the risk of other maternal-fetal complications. Thus, maintaining an adequate control of disease activity and treating flares quickly should be a central goal during prenatal care.

Keywords:
systemic lupus erythematosus; pregnancy; prenatal care; maternal outcomes; fetal outcomes

Criterion	Clinical criteria
Acute cutaneous lupus	Lupus malar rash (do not count if malar discoid); bullous lupus; toxic epidermal necrolysis variant of SLE; maculopapular lupus rash; photosensitive lupus rash (in the absence of dermatomyositis);OR subacute cutaneous lupus (nonindurated psoriasiform and/or annular polycyclic lesions that resolve without scarring, although occasionally with postinflammatory dyspigmentation or telangiectasias)
Chronic cutaneous lupus	Classic discoid rash; localized (above the neck); generalized (above and below the neck); hypertrophic (verrucous) lupus; lupus panniculitis (profundus); mucosal lupus; lupus erythematosus tumidus; chilblains lupus; OR discoid lupus/lichen planus overlap
Nonscarring alopecia	Diffuse thinning or hair fragility with visible broken hairs (in the absence of other causes, such as alopecia areata, drugs, iron deficiency, and androgenic alopecia)
Oral or nasal ulcers	Palate, buccal, tongue, OR nasal ulcers (in the absence of other causes, such as vasculitis, Behçet disease, infection [herpesvirus], inflammatory bowel disease, reactive arthritis, and acidic foods)
Joint disease	Synovitis involving two or more joints, characterized by swelling or effusion OR tenderness in two or more joints and at least 30 minutes of morning stiffness
Serositis	Typical pleurisy for more than one day, pleural effusions, or pleural rub, ORtypical pericardial pain (pain with recumbency improved by sitting forward) for more than one day, pericardial effusion, pericardial rub, or pericarditis by electrocardiography in the absence of other causes, such as infection, uremia, and Dressler's syndrome
Renal	Urine protein-to-creatinine ratio (or 24-hour urine protein) representing 500 mg protein/24 hours, OR red blood cell casts
Neurologic	Seizures; psychosis; mononeuritis multiplex (in the absence of other known causes, such as primary vasculitis); myelitis; peripheral or cranial neuropathy (in the absence of other known causes, such as primary vasculitis, infection, and diabetes mellitus); OR acute confusional state (in the absence of other causes, including toxic/metabolic, uremia, drugs)
Hemolytic anemia	Hemolytic anemia
Leukopenia or lymphopenia	Leukopenia (< 4,000/mm³ at least once) (in the absence of other known causes, such as Felty syndrome, drugs, and portal hypertension), OR lymphopenia (< 1,000/mm³ at least once) (in the absence of other known causes, such as glucocorticoids, drugs, and infection)
Thrombocytopenia	Thrombocytopenia (< 100,000/mm³) at least once in the absence of other known causes, such as drugs, portal hypertension, and thrombotic thrombocytopenic purpura
Immunologic criteria
ANA	ANA level above laboratory reference range
Anti-dsDNA	Anti-dsDNA antibody level above laboratory reference range (or > 2-fold the reference range if tested by ELISA)
Anti-Sm	Presence of antibody to Sm nuclear antigen
Antiphospholipid	Antiphospholipid antibody positivity as determined by any of the following: Positive test result for lupus anticoagulant; false-positive test result for rapid plasma reagin; medium- or high-titer anticardiolipin antibody level (IgA, IgG, or IgM); or positive test result for anti-β 2-glycoprotein I (IgA, IgG, or IgM)
Low complement	Low C3; low C4; OR low CH50
Direct Coombs test	Direct Coombs test in the absence of hemolytic anemia

Original Articles
Author, Year (Country)	Study Design	Population Description	Main Results
Zhan et al. (2017)¹¹11 Zhan Z, Yang Y, Zhan Y, Chen D, Liang L, Yang X. Fetal outcomes and associated factors of adverse outcomes of pregnancy in southern Chinese women with systemic lupus erythematosus. PLoS One 2017;12(04):e0176457. Doi: 10.1371/journal.pone.0176457 https://doi.org/10.1371/journal.pone.017... (China)	Retrospective observational study	251 SLE patients with 263 pregnancies assisted at the First Affiliated Hospital of Sun Yat-Sen University, from 2001 to 2015.	APOs occurred in 70.0% of pregnancies, in which pregnancy loss in 28.5%; PTB in 21.3%; IUGR in 12.2%; and fetal distress in 8.0%. The use of antimalarial medications was associated with lower risk for APOs (OR 0.3, 95% CI 0.1–0.7, p= 0.01). Fetal umbilical artery Doppler in the third trimester showed higher resistance among SLE patients with APOs than the ones without APOs (2.9 ± 0.9 versus 2.4 ± 0.5, p= 0.001).
Simard et al. (2017)¹²12 Simard JF, Arkema EV, Nguyen C, et al. Early-onset preeclampsia in lupus pregnancy. Paediatr Perinat Epidemiol 2017;31(01):29-36. Doi: 10.1111/ppe.12332 https://doi.org/10.1111/ppe.12332... (Sweden)	Retrospective observational study	742 births to women with SLE and 10,484 births to non-SLE women from the Swedish Lupus Linkage (SLINK) cohort, with at least one pregnancy/birth in the Medical Birth Register, from 2001 to 2012.	Among births to women with SLE, there were 32 (4.3%) diagnoses of early-onset PE, and among births to non-SLE women, there were 55 (0.5%). SLE was associated with an increased risk of early onset PE (RR 7.8, 95% CI 4.8–12.9, all pregnancies). The association remained similar upon restriction to women without pregestational hypertension.
Chiu et al. (2016)¹³13 Chiu TF, Chuang YW, Lin CL, et al. Long-term outcomes of systemic lupus erythematous patients after pregnancy: a Nationwide Population- Based Cohort Study. PLoS One 2016;11(12):e0167946. Doi: 10.1371/journal.pone.0167946 https://doi.org/10.1371/journal.pone.016... (Taiwan)	Retrospective cohort study	Records of pregnant (1,526) and non-pregnant (2,932) women with SLE, and pregnant (3,052) and non-pregnant (3,052) women without SLE obtained from the Taiwan National Health Insurance Research Dataset, from 1997 to 2010.	Pregnant patients with SLE exhibited significantly increased risk of ESRD after adjusting for other confounders, like immunosuppressant and parity (HR = 3.19, 95% CI: 1.35 ± 7.52 for pregnant non-SLE; and HR = 2.77, 95% CI: 1.24 ± 6.15 for nonpregnant non-SLE patients). No significant differences in the ESRD incidence were observed in pregnant and nonpregnant SLE patients. Pregnant SLE patients exhibited better clinical condition at the baseline and a significantly lower risk of overall mortality than nonpregnant SLE patients.
Hussein Aly et al. (2016)¹⁴14 Hussein Aly EA, Riyad RM, Mokbel AN. Pregnancy outcome in patients with systemic lupus erythematosus: a single center study in the High Risk Pregnancy unit. Middle East Fertil Soc J 2016;21:168-174. Doi: 10.1016/j.mefs.2015.12.003 https://doi.org/10.1016/j.mefs.2015.12.0... (Egypt)	Prospective observational study	91 pregnancies (84 women) with SLE attending the antenatal clinic at the high-risk pregnancy unit at Cairo University Hospitals, from 2010 to 2015.	The most common manifestations of SLE were cutaneous (93%), articular (92%), lupus nephritis (53%), hypertension (39%) and secondary APS (38%). Incidence rates: abortion 15%, FGR 32%, PTB 13%, PE 12%, fetal death 8%, neonatal admission ICU 15%, LBW 22%, SLE antenatal flares 44%. There was association between hypertension and abortion (p= 0.04), PE (p= 0.0001) and SLE flares (p= 0.0001). Lupus nephritis and hypertension were predictors of PE (p= 0.01 and p= 0.002 respectively) and SLE flares (p= 0.048 and p= 0.003 respectively).
Tedeschi et al. (2016)¹⁵15 Tedeschi SK, Guan H, Fine A, Costenbader KH, Bermas B. Organspecific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes. Clin Rheumatol 2016;35(07):1725-1732. Doi: 10.1007/s10067-016-3270-5 https://doi.org/10.1007/s10067-016-3270-... (USA)	Retrospective observational study	114 SLE pregnant women referred to Brigham and Women's Hospital Lupus Center (Harvard Medical School), from 1990 to 2013.	Most pregnancies resulted in a live term delivery (76.5%). Factors significantly associated with adverse pregnancy outcomes were Nephritis (OR 3.6, 95% CI 1.0–12.8), cytopenias (OR 3.9, 95% CI 1.3–11.4), and serositis (OR 5.9, 95% CI 1.0–34.0).
Buyon et al. (2015)¹⁶16 Buyon JP, Kim MY, Guerra MM, et al. Predictors of pregnancy outcomes in patients with lupus: a Cohort Study. Ann Intern Med 2015;163(03):153-163. Doi: 10.7326/M14-2235 https://doi.org/10.7326/M14-2235... (USA, Canada)	Prospective cohort study	385 patients (49% non-Hispanic white; 31% with prior nephritis) with SLE in the PROMISSE study, from 2003 to 2012	APOs occurred in 19.0% (95% CI, 15.2% to 23.2%) of pregnancies; fetal death in 4%, neonatal death in 1%, PTB in 9%, and SGA neonate in 10%. Severe flares in the second and third trimesters occurred in 2.5% and 3.0%, respectively. Baseline predictors of APOs included presence of LAC (OR 8.32; CI 3.59 to 19.26), antihypertensive use (OR 7.05; CI 3.05 to 16.31]), and platelet count (OR 1.33; CI, 1.09 to 1.63 per decrease of 50 × 109 cells/L). Non-Hispanic white race was protective (OR 0.45; CI, 0.24 to 0.84). Maternal flares, higher disease activity, and smaller increases in C3 level later in pregnancy also predicted APOs. Among women without baseline risk factors, the APO rate was 7.8%. For those who were either LAC-positive or were LAC-negative but nonwhite or Hispanic and using antihypertensives, the APO rate was 58.0% and the fetal or neonatal mortality was 22.0%.
Chen et al. (2015)¹⁷17 Chen S, Sun X, Wu B, Lian X. Pregnancy in women with systemic lupus erythematosus: a retrospective study of 83 pregnancies at a single centre. Int J Environ Res Public Health 2015;12(08): 9876-9888. Doi: 10.3390/ijerph120809876 https://doi.org/10.3390/ijerph120809876... (China)	Retrospective observational study	83 pregnancies in 80 women with SLE attended at the Zhangzhou Affiliated Hospital of Fujian Medical University, from 2008 to 2013.	The sample was divided into three groups: group A (patients in remission for > 6 months before pregnancy, proteinuria < 0.5 g per day, without renal failure and discontinuation of cytotoxic drugs for > one year); group B (patients with SLE disease activity in the six months before pregnancy); group C (patients with new onset SLE during pregnancy). In group A, 76.47% pregnancies achieved full-term deliveries and 80.39% achieved live born infants. In group B and C, the outcome was poor. Among 62 patients (64 pregnancies) diagnosed as SLE before pregnancy, SLE flares occurred in 27 (42.19%) pregnancies. SLE disease activity in the six months before pregnancy was significantly associated with lupus flare (OR 5.00, 95% CI 1.14–21.87, p= 0.03) and fetal loss. New onset lupus during pregnancy was independently associated with obstetric complications (OR 7.22, 95% CI 2.14–24.38, p= 0.001).
Jakobsen et al. (2015)¹⁸18 Jakobsen IM, Helmig RB, Stengaard-Pedersen K. Maternal and foetal outcomes in pregnant systemic lupus erythematosus patients: an incident cohort from a stable referral population followed during 1990-2010. Scand J Rheumatol 2015;44(05): 377-384. Doi: 10.3109/03009742.2015.1013982 https://doi.org/10.3109/03009742.2015.10... (Denmark)	Retrospective observational study	84 pregnancies in 39 women diagnosed with SLE referred to a Danish University Hospital during 1990–2010 (registered at the Danish National Registry)	SLE flares developed in 46.4%, PE in 8.3%, and HELLP syndrome in 4.8% of cases. Significantly higher rates of premature delivery (p= 0.0032), C-section (p= 0.015), hypertension (p= 0.025), and IUGR (p= 0.003) were found. Disease activity (p= 0.021) increased the risk of prematurity 3-fold. Two NLS and one congenital heart block were described. Birth weight and length were significantly lower in the SLE cohort.
Tedeschi et al. (2015)¹⁹19 Tedeschi SK, Massarotti E, Guan H, Fine A, Bermas BL, Costenbader KH. Specific systemic lupus erythematosus disease manifestations in the six months prior to conception are associated with similar disease manifestations during pregnancy. Lupus 2015;24 (12):1283-1292. Doi: 10.1177/0961203315586455 https://doi.org/10.1177/0961203315586455... (USA)	Retrospective observational study	147 pregnancies among 113 women followed at the Brigham and Women's Lupus Center (Harvard Medical School), between 1990 and 2013.	Among women with organ-specific lupus activity during the 6 months before conception, the crude odds for the same type of activity during pregnancy was 7.7- to 32.5-fold higher compared with women without that type of activity immediately before conception.
Madazli et al. (2014)²⁰20 Madazli R, YukselMA, OnculM, Imamoglu M, Yilmaz H. Obstetric outcomes and prognostic factors of lupus pregnancies. Arch Gynecol Obstet 2014;289(01):49-53. Doi: 10.1007/s00404-013-2935-4 https://doi.org/10.1007/s00404-013-2935-... (Turkey)	Retrospective observational study	65 consecutive cases of SLE and pregnancy referred to a University Hospital, from 2002 to 2011.	Disease flare-up occurred in 7.7% of patients. Mean GA at delivery was 36.6 ± 4.2 and mean birth weight was 2,706 ± 927 g. Stillbirth, FGR, PE and PTB rates were 4.6, 18.5, 9.2 and 27.6%, respectively. Cases with uterine artery Doppler abnormalities had significantly poorer obstetric outcomes.
Fatemi et al. (2013)²¹21 Fatemi A, Fard RM, Sayedbonakdar Z, Farajzadegan Z, Saber M. The role of lupus nephritis in development of adverse maternal and fetal outcomes during pregnancy. Int J Prev Med 2013;4(09): 1004-1010 (Iran)	Retrospective observational study	72 pregnancies in 65 patients attending at Lupus Clinic in Isfahan University of Medical Sciences between 1998 and 2012.	No woman with LN experienced preterm Labor or stillbirth. 16 pregnancies either ended in abortion or experienced PE of which seven had LN. Lupus nephritis and positive ANA were related to PE, whereas age of SLE development was associated with preterm labor. LN was associated with PE and SLE flare.
Gaballa et al. (2012)²²22 Gaballa HA, El-Shahawy EED, Atta DS, Gerbash EF. Clinical and serological risk factors of systemic lupus erythematosus outcomes during pregnancy. Egyp Rheumatol. 2012;34:159-165. Doi: 10.1016/j.ejr.2012.04.004 https://doi.org/10.1016/j.ejr.2012.04.00... (Egypt)	Case-control study	40 SLE pregnant women from inpatient and outpatient clinics of the rheumatology & rehabilitation and Ob&Gyn Departments of Zagazig University Hospitals; another 35 non-pregnant SLE patients attending rheumatology outpatient clinics were taken as a control group. The study was conducted from 2008 to 2010	Pregnant women comprised group A and non-pregnant women comprised group B. SLEDAI was increased in both groups, more in group A. Lupus flares were increased during pregnancy as it occurred in 62.5% of group A compared with 37.14% in group B. Severe flares were more frequent in group A. Gestational hypertension and SLEDAI showing disease activity were risk factors for poor maternal outcome. Fetal outcome included full term 37.5%, PTB 25%, FGR 22.5%, stillbirth 12.5%, abortion 7.5% and congenital heart block 2.5%. Factors associated with poor fetal outcome were severe flares and active renal disease. Full term pregnancy was more common in patients with no flares.
Surita et al. (2007)²³23 Surita FG, ParpinelliMA, Yonehara E, Krupa F, Cecatti JG. Systemic lupus erythematosus and pregnancy: clinical evolution, maternal and perinatal outcomes and placental findings. Sao Paulo Med J 2007;125(02):91-95. Doi: 10.1590/S1516-31802007000200005 https://doi.org/10.1590/S1516-3180200700... (Brazil)	Observational cohort study	67 women with lupus (76 pregnancies) who received care at a tertiary clinic for high-risk pregnancies, at Universidade do Estado de Campinas, Brazil, between 1995 and 2002.	Flare-ups occurred in 85.3% of cases, especially when there was renal involvement (being the most significant). This was related to greater numbers of women with PE and poor perinatal outcome. In cases when there was active disease, IUGR was more common. The placental weight was significantly lower in the women with renal involvement. Flare-ups and renal involvement in lupus patients during pregnancy are associated with increased maternal and perinatal complications.
Review Articles
Author, Year	Type of Review	Main Results	Conclusions and Recommendations
Knight and Nelson-Piercy (2017)²⁴24 Knight CL, Nelson-Piercy C. Management of systemic lupus erythematosus during pregnancy: challenges and solutions. Open Access Rheumatol 2017;9:37-53. Doi: 10.2147/OARRR.S87828 https://doi.org/10.2147/OARRR.S87828...	Narrative review	SLE provides challenges in prepregnancy, antenatal, intrapartum, and postpartum periods for the medical, obstetric, and midwifery teams. Women are at risk of lupus flares, worsening renal impairment, onset of or worsening hypertension, PE, miscarriage, FGR, PTB, and/or neonatal lupus syndrome.	In pregnancy, early referral for hospital-coordinated care, involvement of obstetricians and rheumatologists, an individual management plan, regular reviews, and early recognition of flares and complications are all important. A C-section may be required in certain obstetric contexts (e.g., preterm delivery for maternal and/or fetal well-being), but vaginal birth should be the aim for the majority of women. Postnatally, an ongoing individual management plan remains important.
Lateef and Petri (2017)²⁵25 Lateef A, Petri M. Systemic lupus erythematosus and pregnancy. Rheum Dis Clin North Am 2017;43(02):215-226. Doi: 10.1016/j.rdc.2016.12.009 https://doi.org/10.1016/j.rdc.2016.12.00...	Narrative review	Outcomes for pregnancy in the setting of SLE have considerably improved but the maternal and fetal risks remain high. Disease flares, PE, pregnancy loss, PTB, FGR and neonatal lupus syndromes (especially heart block) remain the main complications.	Specific monitoring and treatment protocols need to be used for situations such as presence of specific antibodies (antiphospholipid antibodies and anti-SSA/SSB). Safe and effective treatment options exist and should be used to control disease activity during pregnancy. Close monitoring and judicious use of medications are the key to achieve optimal outcomes.
Ostensen (2017)²⁶26 ØstensenM. Preconception Counseling. Rheum Dis Clin North Am 2017;43(02):189-199. Doi: 10.1016/j.rdc.2016.12.003 https://doi.org/10.1016/j.rdc.2016.12.00...	Narrative review	Ideal conditions for pregnancy are conception at a stage of remission or minimal disease activity while on stable, pregnancy-compatible medication.	Points discussed during preconception counseling should be shared with all doctors and health professionals involved in the care of a pregnant patient. Address family planning in all patients of fertile age. Physicians should actively offer information on reproduction issues to all patients. Address medication concerns and the benefits of optimal disease control in pregnancy with all patients.
Moroni and Ponticelli (2016)²⁷27 Moroni G, Ponticelli C. Pregnancy in women with systemic lupus erythematosus (SLE). Eur J InternMed 2016;32:7-12. Doi: 10.1016/j.ejim.2016.04.005 https://doi.org/10.1016/j.ejim.2016.04.0...	Narrative review	Pregnancy is not contraindicated in women with SLE. However, pregnant patients with lupus nephritis may run increased risk of PE and PTB. The maternal and fetal outcome are strongly correlated with lupus activity, kidney function and the presence of aPL antibodies.	Ideally, a woman should plan a pregnancy only until her lupus has been under control for at least 6 months.
Yamamoto and Aoki (2016)²⁸28 Yamamoto Y, Aoki S. Systemic lupus erythematosus: strategies to improve pregnancy outcomes. Int J Womens Health 2016; 8:265-272. Doi: 10.2147/IJWH.S9015 https://doi.org/10.2147/IJWH.S9015...	Narrative review	Maternal and fetal risks are higher in females with SLE than in the general population. However, with appropriate management of the disease, sufferers may have a relatively uncomplicated pregnancy course.	Factors such as appropriate preconception counseling and medication adjustment, strict disease control prior to pregnancy, intensive surveillance during and after pregnancy by both the obstetrician and rheumatologist, and appropriate interventions play a key role.
Jesus et al. (2015)²⁹29 de Jesus GR, Mendoza-Pinto C, de Jesus NR, et al. Understanding andmanaging pregnancy in patients with lupus. Autoimmune Dis 2015;2015:943490	Narrative review	The risk of flares depends on the level of maternal disease activity in the 6–12 months before conception and is higher in women with repeated flares before conception, in those who discontinue useful medications and in women with active glomerulonephritis at conception.	It is a challenge to differentiate lupus nephritis from PE and, in this context, the angiogenic and antiangiogenic cytokines are promising. Prenatal care of pregnant patients with SLE requires close collaboration between rheumatologist and obstetrician. Planning pregnancy is essential to increase the probability of success.
Singh and Chowdhary (2015)³⁰30 Singh AG, Chowdhary VR. Pregnancy-related issues in women with systemic lupus erythematosus. Int J RheumDis 2015;18(02): 172-181. Doi: 10.1111/1756-185X.12524 https://doi.org/10.1111/1756-185X.12524...	Narrative review	Established risk factors for adverse pregnancy outcomes include active disease within 6 months prior to conception and during pregnancy, active nephritis, maternal hypertension, antiphospholipid antibodies and hypocomplementemia.	Certain aspects such as prevention of PTB, treatment of congenital heart block due to neonatal lupus and recurrent pregnancy loss despite best management, remains challenging. Pregnant patients with SLE should be followed in a high-risk obstetric clinic, and care should be closely coordinated between the obstetrician and rheumatologist.
Lateef and Petri (2013)³¹31 Lateef A, PetriM.Managing lupus patients during pregnancy. Best Pract Res Clin Rheumatol 2013;27(03):435-447. Doi: 10.1016/j.berh.2013.07.005 https://doi.org/10.1016/j.berh.2013.07.0...	Narrative review	Although live births are achieved in the majority of the pregnancies in women with SLE, active disease and major organ involvement can negatively affect the outcomes. Disease flares during SLE pregnancy pose the unique issue of recognition and differentiation between physiologic changes and disease state. Similarly, PE and lupus nephritis may lead to diagnostic confusion.	A multidisciplinary approach, with close monitoring, is essential for optimal outcomes. Safe treatment options exist and should be appropriately used for disease activity during pregnancy.
Lateef and Petri (2012)³²32 Lateef A, Petri M. Management of pregnancy in systemic lupus erythematosus. Nat Rev Rheumatol 2012;8(12):710-718. Doi: 10.1038/nrrheum.2012.133 https://doi.org/10.1038/nrrheum.2012.133...	Narrative review	Maternal and fetal mortality and morbidity are considerably increased among pregnancies with SLE, compared with the general population. Active maternal disease, renal involvement, specific autoantibody subsets and advanced organ damage are predictors of poor outcome.	Multidisciplinary care, close monitoring, high-risk surveillance, and judicious use of medications are essential to achieve good outcomes.
Stanhope et al. (2012)³³33 Stanhope TJ, White WM, Moder KG, Smyth A, Garovic VD. Obstetric nephrology: lupus and lupus nephritis in pregnancy. Clin J Am Soc Nephrol 2012;7(12):2089-2099. Doi: 10.2215/CJN.12441211 https://doi.org/10.2215/CJN.12441211...	Narrative review	Renal involvement in the form of either active LN at the time of conception, or a LN new onset or flare during pregnancy increases the risks of PTD, PE, maternal mortality, fetal/neonatal demise, and FGR.	The major goal of immunosuppressive therapy in pregnancy is control of disease activity with medications that are relatively safe for a growing fetus. Therefore, the use of mycophenolate mofetil, due to increasing evidence supporting its teratogenicity, is contraindicated during pregnancy.
Baer et al. (2011)³⁴34 Baer AN, Witter FR, Petri M. Lupus and pregnancy. Obstet Gynecol Surv 2011;66(10):639-653. Doi: 10.1097/OGX.0b013e318239e1ee https://doi.org/10.1097/OGX.0b013e318239...	Narrative review	The frequency of pregnancy loss in lupus has dropped to a level commensurate with that of the general population. The outcomes of lupus pregnancies are better if conception is delayed until the disease has been inactive for at least 6 months, and the medication regimen has been adjusted in advance.	Monitoring should include baseline and monthly laboratory tests, serial ultrasonography, fetal surveillance tests, and fetal m-mode echocardiography for mothers with SSA (Ro) or SSB (La) antibodies. If hydroxychloroquine was in use before conception, it should be maintained throughout pregnancy. If a woman with SLE has antiphospholipid antibodies, prophylactic treatment with aspirin and/or low-molecular weight heparin is indicated to prevent fetal loss. Lupus flares during pregnancy are generally treated with hydroxychloroquine, low-dose prednisone, pulse intravenous methylprednisolone, and azathioprine. High-dose prednisone and cyclophosphamide are reserved for severe lupus complications.
Ruiz-Irastorza and Khamashta (2011)³⁵35 Ruiz-Irastorza G, KhamashtaMA. Lupus and pregnancy: integrating clues from the bench and bedside. Eur J Clin Invest 2011;41 (06):672-678. Doi: 10.1111/j.1365-2362.2010.02443.x https://doi.org/10.1111/j.1365-2362.2010...	Narrative review	Women with severe active disease or a high degree of irreversible damage, such as those with symptomatic pulmonary hypertension, heart failure, severe restrictive pulmonary disease or severe chronic renal failure should best avoid pregnancy.	Adequate pregnancy care of women with SLE rests on three pillars: a coordinated medical-obstetrical care, an agreed and well-defined management protocol and a good neonatal unit. Pregnancy should be planned following a preconceptional visit for counselling.
Buyon (2009)³⁶36 Buyon JP. Updates on lupus and pregnancy. Bull NYU Hosp Jt Dis 2009;67(03):271-275	Narrative review	Flare rates are generally low for patients who are clinically stable at conception. For patients who have never had renal disease, there is no firm evidence that they will develop active renal disease simply due to being pregnant. For women with anti-SSA antibodies, the risk of having a child with congenital heart block is 2%, which rises to a recurrence rate of 18%.	For patients with aPL antibodies detected in the first trimester of pregnancy, the lupus anticoagulant is the strongest predictor of serious pregnancy complications.
Doria et al. (2008)³⁷37 Doria A, Tincani A, Lockshin M. Challenges of lupus pregnancies. Rheumatology (Oxford) 2008;47(Suppl 3):iii9-iii12. Doi: 10.1093/rheumatology/ken151 https://doi.org/10.1093/rheumatology/ken...	Narrative review	Most SLE patients experience uncomplicated pregnancies. One of the major risks for SLE mothers is the occurrence of a disease flare during pregnancy. Another major risk of SLE relapse during pregnancy is glomerulonephritis, especially if active at the time of conception.	To reduce the risk of maternal and fetal complications, pregnancies must be planned when SLE is inactive and must be closely and appropriately monitored. Specific blood tests predict some pregnancy complications.
Clowse (2007)³⁸38 Clowse ME. Lupus activity in pregnancy. Rheum Dis Clin North Am 2007;33(02):237-252, v	Narrative review	Pregnancy in a woman with SLE can be complicated by lupus activity and pregnancy mishaps. Recent studies found an increase in lupus activity during pregnancy, possibly worsened by hormonal shifts required to maintain pregnancy. An elevated risk for poor pregnancy outcomes, such as stillbirth, preterm birth, low birth weight and preeclampsia, is related to an increased lupus activity.	A rheumatologist and a high-risk obstetrician are best equipped to care for women with lupus who become pregnant. Careful planning and treatment may be required to achieve success of gestation.
Witter (2007)³⁹39 Witter FR. Management of the high-risk lupus pregnant patient. Rheum Dis Clin North Am 2007;33(02):253-265, v-vi	Narrative review	Interactions between SLE and pregnancy include the overall activity of lupus and pregnancy outcome, the effect of lupus nephritis on pregnancy, the effect of pregnancy on the progression of lupus nephritis, and the differentiation of hypertension related to lupus nephritis from PE.	A live birth can be achieved by close coordination of care between the patient's rheumatologist, obstetrician, and, in the case of renal involvement, her nephrologist.

Preconception visit checklist	Contraindications to pregnancy
Age?	Severe lupus flare within the previous 6 months
Any previous pregnancy?	Severe restrictive lung disease (FVC < 1 L)
Previous pregnancy complications?	Heart failure
Presence of severe irreversible damage?	Chronic renal failure (Cr > 28 mg/dL)
Recent or current lupus activity?	Stroke within the previous 6 months
Presence of antiphospholipid antibodies/syndrome?	Previous severe preeclampsia or HELLP syndrome despite therapy with aspirin and heparin
Other chronic medical conditions? (Hypertension, diabetes, etc.)	Severe pulmonary hypertension (estimated systolic PAP > 50 mm Hg or symptomatic)
Current treatment: any “forbidden” drugs? (including cyclophosphamide, methotrexate, mycophenolate, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, diuretics and statins)
Positivity of anti-SSA /anti-SSB?
Smoking?

Score	Descriptor	Modified for pregnancy	Considerations
8	Seizure	Yes	(r/o eclampsia)
8	Psychosis	No
8	Organic brain syndrome	No
8	Visual disturbance	No	(hypertension is already considered an exclusion in SELENA-SLEDAI and SLEDAI)
8	Cranial nerve disorder	Yes	(r/o Bell palsy)
8	Lupus headache	Yes	(r/o Bell palsy)
8	CVA	Yes	(r/o eclampsia)
8	Vasculitis	Yes	(consider palmar erythema)
4	Arthritis	Yes	(consider bland knee effusions)
4	Myositis	No
4	Urinary casts	No
4	Hematuria	Yes	(r/o cystitis and vaginal RBC reflective of placental problems)
4	Proteinuria	Yes	(r/o eclampsia)
4	Pyuria	Yes	(r/o infection)
2	Rash	Yes	(consider chloasma)
2	Alopecia	Yes	(consider normal postpartum alopecia)
2	Mucosal Ulcers	No
2	Pleurisy	Yes	(hyperventilation may be secondary to progesterone, dyspnea secondary to enlarging uterus)
2	Pericarditis	No
2	Low complement	Yes	(complements normally rise during pregnancy)
2	Increased DNA binding	No
1	Thrombocytopenia	Yes	(r/o preeclampsia, HELLP syndrome, incidental thrombocytopenia of pregnancy)
1	Leukopenia	Yes	(consider normal rise of leukocyte count during pregnancy)
1	Fever	No

Federação Brasileira das Sociedades de Ginecologia e Obstetrícia Av. Brigadeiro Luís Antônio, 3421, sala 903 - Jardim Paulista, 01401-001 São Paulo SP - Brasil, Tel. (55 11) 5573-4919 - Rio de Janeiro - RJ - Brazil
E-mail: editorial.office@febrasgo.org.br

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[1] Address for correspondence Fernanda Garanhani Surita, MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Universidade Estadual de Campinas - Unicamp, Rua Alexander Fleming, 101, Campinas, SP, 13083-881, Brazil (e-mail: surita@unicamp.br).

1.	Erythema malar.
2.	Discoid lupus.
3.	Photosensitivity.
4.	Oral ulcers.
5.	Arthritis.
6.	Serositis (pleuritis or pericarditis).
7.	Nephropathy (persistent proteinuria greater than 0.5 g/day and/or glomerular hematuria).
8.	Neurological disorders (convulsion or psychosis).
9.	Hematologic disorders (hemolytic anemia, leucopenia, thrombocytopenia).
10.	Immune disorder (presence of LE cells, anti-DNA or anti-Sm antibodies, false positive VDRL test, anticardiolipin IgG or IgM antibodies, lupus anticoagulant).
11.	Antinuclear antibody (ANA).