Pregnancy implications for systemic lupus erythematosus and the antiphospholipid syndrome

doi:10.1016/j.jaut.2011.11.010

Journal of Autoimmunity

Volume 38, Issues 2–3, May 2012, Pages J197-J208

https://doi.org/10.1016/j.jaut.2011.11.010 Get rights and content

Abstract

Multidisciplinary approach and patient counselling have been the key points in the improvement of the management of pregnancy in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Most of these women can have successful pregnancy when thoroughly informed and instructed on several different issues. Disease activity should be in stable remission prior to pregnancy in order to reduce the chance for flare during pregnancy. To this purpose, medications must be modulated: “safe” drugs should be continued throughout pregnancy, embryotoxic/foetotoxic drugs should be withdrawn timely, and beneficial drugs such as low dose aspirin and heparin should be added for prophylaxis of maternal and foetal outcome, especially in the presence of antiphospholipid antibodies. The safety profile of anti-rheumatic drugs during pregnancy and breastfeeding should be kept constantly updated, as new data from inadvertent exposure accumulates and new drugs (especially biological agents) are available. Patients may carry autoantibodies that can negatively affect the baby, being neonatal lupus the prototypical case of passively acquired autoimmunity. Research has been greatly active in this field and more information on risk stratification and management are now available for counselling. The effect of both autoantibodies and drug exposure has been evaluated in the offspring: some concerns about learning disabilities have been raised, but these are treatable conditions that are likely to be overcome.

To counsel a woman with SLE/APS during childbearing age means also to deal with contraception. Despite the “preferred choice” – combined oral contraceptive – may not be suitable for most of the patients, other options are available and should be offered and discussed with the patient. Fertility is not generally affected in SLE/APS patients, but those cases who require assisted reproduction techniques should be carefully evaluated and managed.

Highlights

► Patients with SLE and APS can have successful pregnancies when properly assisted. ► Multidisciplinary approach and pre-gestational counselling are key points to favourable outcome. ► Optimal timing: pregnancy should start during stable remission of maternal disease. ► Teratogenic drugs should be withdrawn, while “safe” drugs should be continued throughout pregnancy. ► Autoantibodies that may negatively affect pregnancy outcome should be screened in each patient.

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a remitting and relapsing trend. SLE mainly affects young females during their reproductive years, therefore pregnancy is a topic of major interest. In early times, pregnancy was discouraged in women affected by SLE, because it was reported that the disease could become more aggressive during pregnancy, putting both the mother and the foetus at high risk. In the last 30 years, the management of the disease has greatly improved, and the approach to pregnancy along with it. SLE patients can successfully carry out a pregnancy, as long as timing and management of gestation are planned in close contact with doctors. In fact, pregnancy should be still considered a high risk period during the course of SLE, with a large number of potential complications that can influence maternal and foetal health. In particular, many SLE patients carry antiphospholipid antibodies (aPL), which are well-known risk factors for thrombotic events and pregnancy morbidity [1]. The antiphospholipid syndrome (APS) may present also as a primary form (PAPS), without any underlying systemic autoimmune disease such as SLE. Such patients are at risk for either a first obstetric failure or a recurrence of pregnancy loss.

In any case, preconception counselling is essential in order to estimate the chance of both foetal and maternal problems, related to either disease activity, serologic profile or organ involvement as contraindication to pregnancy. In addition, the checklist must include some epidemiologic items that are relevant to any pregnancy (age, smoking, arterial hypertension, diabetes mellitus, previous obstetric history, previous thrombosis) [2]. The counselling and the follow-up during and after pregnancy should be preferably performed by a multidisciplinary team joined by rheumatologists, obstetricians, neonatologists and also other medical specialties (nephrology, neurology, cardiology, haematology, etc.) when indicated [3].

When talking about her productive plans, any patient will ask the following questions: “Will my baby be healthy?”, “Will my disease worsen during pregnancy?”, “Will medications harm my baby?”. Therefore, the following issues must be discussed with a patient who desires a pregnancy:

•
Disease activity during pregnancy and post-partum period and its possible effects on foetal outcome;
•
Obstetrical maternal complications;
•
Autoantibodies able to interfere with pregnancy outcome (in particular aPL and anti-Ro/SSA and anti-La/SSB antibodies);
•
Drugs compatible or not with pregnancy, drugs to be added during pregnancy.

Section snippets

Lupus flares during pregnancy

An important aspect of pregnancy in lupus patients is the risk of the occurrence of disease flares.

It is not simple to quantify the incidence of such complications because many clinical studies were performed using individual definitions of flare. In recent times, many efforts were done to create a “pregnancy-version” of existing activity indexes, such as ECLAM, SLEDAI, SLAM and LAI, aiming at making studies more comparable [4]. The literature reports discordant results from prospective,

Definition of APS and aPL

The antiphospholipid syndrome (APS) is a systemic autoimmune disorder defined by the occurrence of venous and arterial thromboses, often multiple, and pregnancy morbidity (abortions, foetal deaths, premature births), in the presence of antiphospholipid antibodies (aPL) [1]. APS can be found in patients having neither clinical nor laboratory evidence of another definite autoimmune condition (primary APS) or it may be associated with other diseases, mainly systemic lupus erythematosus (SLE). aPL

Compatibility of drugs with pregnancy

One of the critical issue in the management of a pregnancy in SLE/APS patients is to choose the right medication to treat the mother without harming the foetus. The pregnancy categories used by the United States Food and Drug Administration (FDA) are often not very helpful for the clinician for various reasons. Warnings may come from evidence that is mostly based on animal data, or restrictions may be generated by the lack of information in humans, rather than by a demonstrated teratogenicity.

Contraception, fertility and assisted reproduction

Speaking of contraception with SLE/APS patients goes beyond the simple need of avoiding unwanted pregnancies. Several conditions may require an effective contraception: early stage of the disease, very active disease, severe organ involvement or damage, use of embryotoxic/fetotoxic drugs. Therefore, contraceptive counselling is essential in the rheumatologic practice, but in the “real life” most women do not receive any information about this issue [110], [111]. A common misconception among

The offspring of SLE/APS patients

A major source of anxiety for women with SLE/APS who wish to become pregnant is the possible impact of maternal disease and medications on the offspring, in terms of physical and mental development of the child. Older and recent studies have focused on several different aspects of the issue: physical growth, neuropsychological development, effect of drugs on the infant’s immune system, and development of autoimmune features in children [132], [133].

First of all, it should be emphasized that

Concluding remarks

SLE and APS are chronic systemic diseases that affect young women during their childbearing age. Great improvement has been done in the past few decades in the approach to pregnancy. Maternal counselling is the key point. Women should be aware that pregnancy is possible and can be satisfactorily managed in terms of both maternal and neonatal outcome. To this purpose, some “minimal requirements” are needed: i) optimal timing: pregnancy should start in a period of stable remission of maternal

Acknowledgements

Dr. Andreoli is supported by the project “Dote Ricercatore e Dote Ricerca Applicata ai sensi dell’accordo regionale per lo sviluppo del capitale umano nel sistema universitario Lombardo sottoscritto tra Regione Lombardia e Università Lombarde il 20-10-2009” (Università degli Studi di Brescia).

References (153)

S. Miyakis et al.
International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)
J Thromb Haemost
(2006)
G. Moroni et al.
Pregnancy in lupus nephritis
Am J Kidney Dis
(2002)
M.E. Clowse et al.
A national study of the complications of lupus in pregnancy
Am J Obstet Gynecol
(2008)
M.J. Johnson et al.
Evaluation of preterm delivery in a systemic lupus erythematosus pregnancy clinic
Obstet Gynecol
(1995)
M.S. Magid et al.
Placental pathology in systemic lupus erythematosus: a prospective study
Am J Obstet Gynecol
(1998)
E.T. Jaeggi et al.
Prolongation of the atrioventricular conduction in fetuses exposed to maternal anti-Ro/SSA and anti-La/SSB antibodies did not predict progressive heart block. A prospective observational study on the effects of maternal antibodies on 165 fetuses
J Am Coll Cardiol
(2011)
D.M. Friedman et al.
Prospective evaluation of fetuses with autoimmune-associated congenital heart block followed in the PR interval and dexamethasone evaluation (PRIDE) study
Am J Cardiol
(2009)
M. Biggioggero et al.
The geoepidemiology of the antiphospholipid syndrome
Autoimmun Rev
(2010)
H.J. Out et al.
Histopathological findings in placentae from patients with intra-uterine fetal death and anti-phospholipid antibodies
Eur J Obstet Gynecol Reprod Biol
(1991)
C. Agostinis et al.
In vivo distribution of beta2glycoprotein I under various pathophysiological conditions
Blood
(2011)

J.M. Thurman et al.

A novel inhibitor of the alternative complement pathway prevents antiphospholipid antibody-induced pregnancy loss in mice

Mol Immunol

(2005)

I. Cavazzana et al.

Complement activation in antiphospholipid syndrome: a clue for an inflammatory process?

J Autoimmun

(2007)

R.T. Urbanus et al.

Antiphospholipid syndrome and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study

Lancet Neurol

(2009)

J.R. Hutson et al.

The transfer of 6-mercaptopurine in the dually perfused human placenta

Reprod Toxicol

(2011 Nov)

N.Y. Lee et al.

6-Mercaptopurine transport by equilibrative nucleoside transporters in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBTs

J Pharm Sci

(2011)

G. Ruiz-Irastorza et al.

Lupus and pregnancy: integrating clues from the bench and bedside

Eur J Clin Invest

(2011)

M. Ostensen et al.

Pregnancy and reproduction in autoimmune rheumatic diseases

Rheumatology (Oxford)

(2011)

A. Doria et al.

Challenges of lupus pregnancies

Rheumatology

(2008)

E. Imbasciati et al.

Pregnancy in women with pre-existing lupus nephritis: predictors of fetal and maternal outcome

Nephrol Dial Transplant

(2009)

M.E. Clowse et al.

The impact of increased lupus activity on obstetrical outcomes

Arthritis Rheum

(2005)

M.E. Clowse et al.

The clinical utility of measuring complement and anti-dsDNA antibodies during pregnancy in patients with systemic lupus erythematosus

J Rheumatol

(2011)

F.Z. Rahman et al.

Pregnancy outcome in lupus nephropathy

Arch Gynecol Obstet

(2005)

E. Oviasu et al.

The outcome of pregnancy in women with lupus nephritis

Lupus

(1991)

K. Bramham et al.

Pregnancy outcomes in systemic lupus erythematosus with and without previous nephritis

J Rheumatol

(2011)

A. Smyth et al.

A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis

Clin J Am Soc Nephrol

(2010)

A. Tandon et al.

The effect of pregnancy on lupus nephritis

Arthritis Rheum

(2004)

G. Ruiz-Irastorza et al.

Heart disease, pregnancy and systemic autoimmune diseases

M. Bonnin et al.

Severe pulmonary hypertension during pregnancy. Mode of delivery and anesthetic management of 15 consecutive cases

Anesthesiology

(2005)

J.E. Salmon et al.

Mutations in complement regolatory proteins predispose to preeclampsia: a genetic analysis of the PROMISSE cohort

PLoS Med

(2011)

E. Vinet et al.

Decreased live births in women with systemic lupus erythematosus

Arthritis Care Res (Hoboken)

(2011)

M.E. Clowse et al.

Early risk factors for pregnancy loss in lupus

Obstet Gynecol

(2006)

S. Yan Yuen et al.

Pregnancy outcome in systemic lupus erythematosus (SLE) is improving: results from a case control study and literature review

Open Rheumatol J

(2008)

C.A. Clark et al.

Preterm deliveries in women with systemic lupus erythematosus

J Rheumatol

(2003)

A. Stagnaro-Green et al.

Thyroid disease in pregnant women with systemic lupus erythematosus: increased preterm delivery

Lupus

(2011)

D. Le Thi Houng et al.

The second trimester Doppler ultrasound examination is the best predictor of late pregnancy outcome in systemic lupus erythematosus and/or the antiphospholipid syndrome

Rheumatology (Oxford)

(2006)

G. Castellino et al.

Uterine artery Doppler in predicting pregnancy outcome in women with connective tissue disorders

Rheumatology (Oxford)

(2006)

E. Silverman et al.

Non-cardiac manifestations of neonatal lupus erythematosus

Scand J Immunol

(2010)

J.S. Prendville et al.

Central nervous system involvement in neonatal lupus erythematosus

Ped Dermatol

(2003)

M. Motta et al.

Cerebral ultrasound abnormalities in infants born to mothers with autoimmune disease

Arch Dis Child Fetal Neonatal

(2011)

L.K. Hornberger et al.

Spectrum of cardiac involvement in neonatal lupus

Scand J Immunol

(2010)

G. Guettrot-Imbert et al.

A new presentation of neonatal lupus: 5 cases of isolated mild endocardial fibroelastosis associated with maternal anti-SSA/Ro and anti-SSB/La antibodies

J Rheumatol

(2011)

A. Brucato et al.

Pregnancy outcomes in patients with autoimmune diseases and anti-Ro/SSA antibodies

Clin Rev Allergy Immunol

(2011)

A. Ambrosi et al.

Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern

Ann Rheum Dis

(2011)

C. Llanos et al.

Recurrence rates of cardiac manifestations associated with neonatal lupus and maternal/fetal risk factors

Arthritis Rheum

(2009)

P.M. Izmirly et al.

Cutaneous manifestations of neonatal lupus and risk of subsequent congenital heart block

Arthritis Rheum

(2010)

S. Salomonsson et al.

Autoantibodies associated with congenital heart block

Scand J Immunol

(2010)

L. Strandberg et al.

Antibodies to amino acid 200–239 (p200) of Ro52 as serological markers for the risk of developing congenital heart block

Clin Exp Immunol

(2008)

L.S. Strandberg et al.

Maternal MHC regulates generation of pathogenic autoantibodies and fetal MHC-encoded genes determine susceptibility in congenital heart block

J Immunol

(2010)

R.M. Clancy et al.

Identification of candidate loci at 6p21 and 21q22 in a genome-wide association study of cardiac manifestations of neonatal lupus

Arthritis Rheum

(2010)

A. Brucato et al.

Passively acquired anti-SSA/Ro antibodies are required for congenital heart block following ovodonation but maternal genes are not

Arhtritis Rheum

(2010)

Cited by (71)

Immunologic causes and thrombophilia in recurrent pregnancy loss
2021, Fertility and Sterility
Citation Excerpt :
Planning embryo transfers according to the clinical stability of the autoimmune disease could minimize pregnancy risks. An emphasis on preconception counseling and strict disease control in the months prior to conception are essential for managing the desire for pregnancy (notably by ART) and autoimmune diseases (17). Routine metabolic screening of all RPL patients is not yet recommended, but this classic recommendation may change in the future.
Certain miscarriages result from immunologic factors, but there is no clear identification of the precise causes of recurrent pregnancy loss (RPL). Miscarriages and RPL can arise from a disruption of maternal–fetal immune homeostasis. Remodeling of the maternal uterine spiral arteries is one of the key steps for normal growth and development of the fetus. An adequate oxygen supply is necessary for correct placentation, and it is accomplished by proper vascular changes. The development of fetal tissues creates a potential immunologic problem since the fetus can express paternal antigens and, in some cases, antigens of a gamete donor. The maternal immune system actively responds to fetal antigens, and dysregulation of this crosstalk could partly explain pregnancy complications such as miscarriages and RPL. RPL resulting from thrombophilia is primarily due to acquired thrombophilia, and therefore screening and treatment should be focused on antiphospholipid antibody syndrome.
In utero exposure to Azathioprine in autoimmune disease. Where do we stand?
2020, Autoimmunity Reviews
Azathioprine (AZA), an oral immunosuppressant, is safe during pregnancy. Some reports suggested different impairments in the offspring of mothers with autoimmune diseases (AI) exposed in utero to AZA. These observations are available from retrospective studies or case reports. However, data with respect to the long-term safety in the antenatally exposed child are still lacking. The aim of this study is to summarize the current knowledge in this field and to focus on the need for a prospective study on this population. We performed a PubMed search using several search terms.
The actual data show that although the risk of congenital anomalies in offspring, as well as the infertility risk, are similar to those found in general population, there is a higher incidence of prematurity, of lower weight at birth and an intra-uterine delay of development. There is also an increased risk of materno- fetal infections, especially cytomegalovirus infection. Some authors raise the interrogations about neurocognitive impairment. Even though the adverse outcomes might well be a consequence of maternal illness and disease activity, interest has been raised about a contribution of this drug. However, the interferences between the external agent (in utero exposure to AZA), with the host (child genetic susceptibility, immune system anomalies, emotional status), environment (public health, social context, availability of health care), economic, social, and behavioral conditions, cultural patterns, are complex and represent confounding factors.
In conclusion, it is necessary to perform studies on the medium and long-term outcome of children born by mothers with autoimmune diseases, treated with AZA, in order to show the safety of AZA exposure. Only large-scale population studies with long-term follow-up will allow to formally conclude in this field.
- •
  There is no study on a significant number of subjects concerning the medium and long-term outcome of children born by mothers with autoimmune disease treated with AZA.
- •
  As AZA use is related to underlying disease and disease activity and many confounders interfere with AZA treatment, there is a major difficulty to distinguish between the influence of the disease itself on the risk of adverse birth outcome and potential AZA effects in offspring at medium and long term.
- •
  Data need to be implemented with large, multicenter studies.
Safety issues and recommendations for successful pregnancy outcome in systemic lupus erythematosus
2018, Journal of Autoimmunity
Citation Excerpt :
Potential maternal and obstetric complications should be explained. In terms of treatment of APS, maternal risk factors, prior thrombosis, prior pregnancy loss, current organ damage, and disease activity should all be taken into account to better manage these patients for both the thrombotic and obstetric risk assessment [27,69]. The PROMISSE (Predictors of pRegnancy Outcome: biomarkers in antiphospholipid antibody Syndrome and Systemic lupus Erythematosus) [40] was a prospective multicenter observational study that studied women with aPL and/or SLE (either inactive or mild/moderate active disease) compared to controls.
Systemic lupus erythematosus (SLE) primarily affects women of childbearing age. One of the major changes in SLE focuses on the timing of a successful pregnancy. In the past, pregnancy was strongly discouraged in SLE, especially in the presence of risk factors such as nephritis, use of immunosuppressive therapies, or positivity of specific autoantibodies such as anti-phospholipids and anti-Ro/SSA, La/SSBA. Thanks to our better knowledge on the disease and management, pregnancy success rates in SLE patients have significantly improved care by the a multidisciplinary team which fosters a successful pregnancy with minimal complications for the mother and fetus when the disease is inactive or in remission. This approach is based on a counseling phase before pregnancy, to assess SLE activity phase, specific medications, risk factors, and continues through pregnancy and lactation with significantly improved pregnancy outcomes. Further, we can now better define the risk of disease flares during pregnancy based on a better understanding of the changes in maternal immunity and its relationship with SLE-associated autoimmunity and chronic inflammation. There is wide consensus that women with SLE can have successful pregnancies as long as conception is planned in a phase of inactive disease, and when the patient is closely managed by a rheumatologist, high-risk OB/GYN, neonatologist, and other medical specialists as indicated. Preconception counseling is essential to assess the risk of both fetal and maternal complications as well as identify life-threatening contraindications. Particular attention should be used in those SLE cases that have nephritis, APS or positivity for aPL, pulmonary hypertension, and positive anti-Ro/SSA or anti-La/SSB antibodies. In conclusion, the use of specific guidelines on the management of SLE before and during pregnancy and lactation, and a better understanding of the use of immunosuppressive therapies have significantly increased pregnancy success.
Obstetric Manifestations of the Antiphospholipid Syndrome
2017, Handbook of Systemic Autoimmune Diseases
The serious impact of the obstetric manifestations related to antiphospholipid syndrome (APS) can be understood by the fact that the disease was first described in patients with obstetric morbidity, in particular midtrimester foetal losses. The definition of obstetric APS includes different pathological manifestations: recurrent early pregnancy loss, foetal death, early severe preeclampsia, placental insufficiency, and/or intrauterine growth restriction and HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome. Nevertheless, the association between pregnancy loss or other pregnancy complications and antiphospholipid antibodies has yet not been completely defined. A very important aspect to consider in the management of patients with obstetric APS is the risk stratification: not all the clinical and the serological settings confer the same risk and consequently a tailored therapeutic approach is required. Success is the result of a careful surveillance conducted by a multidisciplinary team (obstetricians, rheumatologists, and neonatologists).
A clinical decision support system for prediction of pregnancy outcome in pregnant women with systemic lupus erythematosus
2017, International Journal of Medical Informatics
Pregnancy among systemic lupus erythematosus (SLE)-affected women is highly associated with poor obstetric outcomes. Predicting the risk of foetal outcome is essential for maximizing the success of pregnancy. This study aimed to develop a clinical decision support system (CDSS) to predict pregnancy outcomes among SLE-affected pregnant women.
We performed a retrospective analysis of 149 pregnant women with SLE, who were followed at Shariati Hospital (104 pregnancies) and a specialized clinic (45 pregnancies) from 1982 to 2014. We selected significant features (p < 0.10) using a binary logistic regression model performed in IBM SPSS (version 20). Afterward, we trained several artificial neural networks (multi-layer perceptron [MLP] and radial basis function [RBF]) to predict the pregnancy outcome. In order to evaluate and select the most effective network, we used the confusion matrix and the receiver operating characteristic (ROC) curve. We finally developed a CDSS based on the most accurate network. MATLAB 2013b software was applied to design the neural networks and develop the CDSS.
Initially, 45 potential variables were analysed by the binary logistic regression and 16 effective features were selected as the inputs of neural networks (P-value < 0.1). The accuracy (90.9%), sensitivity (80.0%), and specificity (94.1%) of the test data for the MLP network were achieved. These measures for the RBF network were 71.4%, 53.3%, and 79.4%, respectively. Having applied a 10-fold cross-validation method, the accuracy for the networks showed 75.16% accuracy for RBF and 90.6% accuracy for MLP. Therefore, the MLP network was selected as the most accurate network for prediction of pregnancy outcome.
The developed CDSS based on the MLP network can help physicians to predict pregnancy outcomes in women with SLE.
A comprehensive review of the clinical approach to pregnancy and systemic lupus erythematosus
2016, Journal of Autoimmunity
Citation Excerpt :
However, whether these complications should be attributed to Belimumab, or to the assumption of concomitant drugs or active disease itself is not clarified yet [132]. The current suggestion is to interrupt this medication about 4 months before conception [5], switching to an immunosuppressant compatible with pregnancy. The suspension has to be applied also to Rituximab (RTX), another biological DMARD that has been used in SLE/APS patients with refractory disease.
Nowadays, most of the young women affected by Systemic Lupus Erythematosus (SLE) can carry out one or more pregnancies thanks to the improvement in treatment and the consequent reduction in morbidity and mortality. Pregnancy outcome in these women has also greatly improved in the last decades. A correct timing for pregnancy (tailored on disease activity and established during a preconception counselling), together with a tight monitoring during the three trimesters and the post-partum period (to timely identify and treat possible obstetric complications or maternal disease flares), as well as the concept of multidisciplinary management, are currently milestones of the management of pregnancy in SLE patients. Nevertheless, the increasing knowledge on the compatibility of drugs with pregnancy has allowed a better treatment of these patients, by choosing medications that control maternal disease activity without harming the foetus. However, particular attention and strict monitoring should be dedicated to SLE pregnant women in particular clinical settings: patients with lupus nephritis and patients with aPL positivity or Antiphospholipid syndrome, who are at higher risk for maternal and foetal complications, but also patients with anti-Ro/SSA and/or anti-La/SSB antibodies, because of the risk of neonatal lupus. A discussion on family planning, as well as counselling on contraception, should be part of the everyday-practice for physicians caring for SLE women during their reproductive age. Another issue is the possible reduction of fertility in these women, that can be due to different reasons. Consequently, the request for assisted reproduction techniques has been increasing in the last years, so that rheumatologists and gynaecologists should be prepared to counsel SLE patients also in this particular setting.

View all citing articles on Scopus

View full text

Pregnancy implications for systemic lupus erythematosus and the antiphospholipid syndrome

Abstract

Highlights

Introduction

Section snippets

Lupus flares during pregnancy

Definition of APS and aPL

Compatibility of drugs with pregnancy

Contraception, fertility and assisted reproduction

The offspring of SLE/APS patients

Concluding remarks

Acknowledgements

J Thromb Haemost

Am J Kidney Dis

Am J Obstet Gynecol

Obstet Gynecol

Am J Obstet Gynecol

J Am Coll Cardiol

Am J Cardiol

Autoimmun Rev

Eur J Obstet Gynecol Reprod Biol

Blood

Mol Immunol

J Autoimmun

Lancet Neurol

Reprod Toxicol

J Pharm Sci

Lupus and pregnancy: integrating clues from the bench and bedside

Eur J Clin Invest

Pregnancy and reproduction in autoimmune rheumatic diseases

Rheumatology (Oxford)

Challenges of lupus pregnancies

Rheumatology

Pregnancy in women with pre-existing lupus nephritis: predictors of fetal and maternal outcome

Nephrol Dial Transplant

The impact of increased lupus activity on obstetrical outcomes

Arthritis Rheum

The clinical utility of measuring complement and anti-dsDNA antibodies during pregnancy in patients with systemic lupus erythematosus

J Rheumatol

Pregnancy outcome in lupus nephropathy

Arch Gynecol Obstet

The outcome of pregnancy in women with lupus nephritis

Lupus

Pregnancy outcomes in systemic lupus erythematosus with and without previous nephritis

J Rheumatol

A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis

Clin J Am Soc Nephrol

The effect of pregnancy on lupus nephritis

Arthritis Rheum

Heart disease, pregnancy and systemic autoimmune diseases

Severe pulmonary hypertension during pregnancy. Mode of delivery and anesthetic management of 15 consecutive cases

Anesthesiology

Mutations in complement regolatory proteins predispose to preeclampsia: a genetic analysis of the PROMISSE cohort

PLoS Med

Decreased live births in women with systemic lupus erythematosus

Arthritis Care Res (Hoboken)

Early risk factors for pregnancy loss in lupus

Obstet Gynecol

Pregnancy outcome in systemic lupus erythematosus (SLE) is improving: results from a case control study and literature review

Open Rheumatol J

Preterm deliveries in women with systemic lupus erythematosus

J Rheumatol

Thyroid disease in pregnant women with systemic lupus erythematosus: increased preterm delivery

Lupus

The second trimester Doppler ultrasound examination is the best predictor of late pregnancy outcome in systemic lupus erythematosus and/or the antiphospholipid syndrome

Rheumatology (Oxford)

Uterine artery Doppler in predicting pregnancy outcome in women with connective tissue disorders

Rheumatology (Oxford)

Non-cardiac manifestations of neonatal lupus erythematosus

Scand J Immunol

Central nervous system involvement in neonatal lupus erythematosus

Ped Dermatol

Cerebral ultrasound abnormalities in infants born to mothers with autoimmune disease

Arch Dis Child Fetal Neonatal

Spectrum of cardiac involvement in neonatal lupus

Scand J Immunol

A new presentation of neonatal lupus: 5 cases of isolated mild endocardial fibroelastosis associated with maternal anti-SSA/Ro and anti-SSB/La antibodies

J Rheumatol

Pregnancy outcomes in patients with autoimmune diseases and anti-Ro/SSA antibodies

Clin Rev Allergy Immunol