Elsevier

Journal of Autoimmunity

Volume 74, November 2016, Pages 6-12
Journal of Autoimmunity

Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study

https://doi.org/10.1016/j.jaut.2016.07.010Get rights and content

Highlights

  • Fetal prognosis of SLE pregnancies is improved but is still worse than in healthy women.

  • In our cohort, antiphospholipid antibodies and arterial hypertension are the predictors of fetal loss.

  • Nowadays pre term delivery is the most frequent complication in lupus nephritis pregnancies.

  • SLE and lupus nephritis activity and arterial hypertension predict pre term delivery.

  • SLE mothers treated with hydroxychloquine have low risk of SFGA babies.

Abstract

The aim of this multicenter study was to assess the present risk of fetal complications and the inherent risk factors in pregnant women with lupus nephritis.

Seventy-one pregnancies in 61women (59 Caucasians and 2 Asians) with lupus nephritis were prospectively followed between October 2006 and December 2013. All patients received a counselling visit within 3 months before the beginning of pregnancy and were followed by a multidisciplinary team. At baseline mild active nephritis was present in 15 cases (21.1%).

Six pregnancies (8.4%) resulted in fetal loss. Arterial hypertension at baseline (P = 0.003), positivity for lupus anticoagulant (P = 0.001), anticardiolipin IgG antibodies (P = 0.007), antibeta2 IgG (P = 0.018) and the triple positivity for antiphospholipid antibodies (P = 0.004) predicted fetal loss.

Twenty pregnancies (28.2%) ended pre-term and 12 newborns (16.4%) were small for gestational age. Among the characteristics at baseline, high SLE disease activity index (SLEDAI) score (P = 0.027), proteinuria (P = 0.045), history of renal flares (P = 0.004), arterial hypertension (P = 0.009) and active lupus nephritis (P = 0.000) increased the probability of preterm delivery. Odds for preterm delivery increased by 60% for each quarterly unit increase in SLEDAI and by 15% for each quarterly increase in proteinuria by 1 g per day. The probability of having a small for gestational age baby was reduced by 85% in women who received hydroxychloroquine therapy (P = 0.023).

In this study, the rate of fetal loss was low and mainly associated with the presence of antiphospholipid antibodies. Preterm delivery remains a frequent complication of pregnancies in lupus. SLE and lupus nephritis activity are the main risk factors for premature birth. Arterial hypertension predicted both fetal loss and preterm delivery.

Based on our results the key for a successful pregnancy in lupus nephritis is a multidisciplinary approach with close medical, obstetric and neonatal monitoring. This entails: a) a preconception evaluation to establish and inform women about pregnancy risks; b) planning pregnancy during inactive lupus nephritis, maintained inactive with the lowest possible dosage of allowed drugs; c) adequate treatment of known risk factors (arterial hypertension, antiphospholipid and antibodies); d) close monitoring during and after pregnancy to rapidly identify and treat SLE flares and obstetric complications.

Introduction

For many years, pregnancy has been discouraged in women with lupus and renal disease due to the high risk of maternal and fetal complications [1], [2], [3], [4]. However, pregnancy outcome has improved dramatically over time and today pregnancy is no longer considered contraindicated for many women with lupus nephritis. A number of studies have shown that maternal outcome is relatively safe if renal disease is inactive and kidney function is preserved [5], [6], [7]. The risk of fetal loss has decreased over the past 40 years as well. The rate of fetal loss in lupus pregnancy was on average 43% in 1960–1965 and was reduced to about 17% in 2000–2003 [8]. Improved renal prognosis, preconception counselling, and intensive perinatal monitoring contributed to improved fetal outcome. Nonetheless, the rate of fetal loss is still higher than in pregnancies of healthy women. Moreover, lupus can complicate pregnancy with an increased risk of stillbirths, premature deliveries, intrauterine growth retardations and heart problems in the newborn [2], [5], [9], [10]. A systematic review of 37 studies, that included 2751 pregnancy outcomes in 1842 women with lupus nephritis, reported an induced abortion rate of 5.9%. Apart from induced abortion, fetal complications included miscarriages (16.0%), stillbirth (3.6%), neonatal deaths (2.5%), and intrauterine growth retardation (12.7%). The unsuccessful pregnancy rate was 23.4%, and premature birth rate was 39.4% [11].

A number of predictors of fetal complications has been identified. Lupus activity at conception or during pregnancy [12] and renal activity in particular [13], [14], [15] were the strongest predictors. Independently of clinical activity, hypocomplementemia or anti-dsDNA antibodies positivity in the second trimester are associated with a higher rate of pregnancy loss and preterm birth [16], [17]. Another important risk factor for fetal outcome is represented by antiphospholipid antibodies (aPL) positivity [18], [19], [20], [21], [22]. Women with a combination of high clinical activity and serological markers of SLE are a higher risk of poor pregnancy outcome. The risk is more elevated in the presence of triple aPL positivity and hypocomplementemia [23].

Nonetheless, the present knowledge of the rate and predictors of fetal complications in lupus nephritis is based on retrospective data collected over a long period of time, during which, the treatments of lupus nephritis were heterogeneous, pre-conception counselling was used sporadically, and many patients became pregnant during a period of lupus activity [5], [9], [10], [24], [25].

We report here the results of a multicenter, prospective, observational study designed by “The Pregnancy Study Group” of the Italian Society of Nephrology. The aim of the study was to assess the actual rate of maternal and fetal complications and the risk factors for these events in pregnant women with a history of lupus nephritis closely monitored by a multidisciplinary team. The results of maternal complications have been reported in a previous paper [26].

Section snippets

Patients

The complete protocol of the study has been reported elsewhere [26]. In brief, patients with lupus nephritis that became pregnant between October 2006 and December 2013 and who met the following criteria were enrolled in this study: i) SLE diagnosis according to the ACR criteria [27]; ii) lupus nephritis diagnosed either by renal biopsy or on clinical ground; iii) a counselling visit within 3 months before the beginning of pregnancy; iv) signed informed consent.

The protocol was not submitted to

Results

Seventy-one pregnancies in 61women (59 Caucasians and 2 Asians) with lupus nephritis were included in this prospective study. There were two twin pregnancies, so that we collected information on 73 fetal outcomes.

The mean age of the patients at conception was 32.7 ± 4.5 years (median 32.9 years). Their body mass index was 22.53 ± 3.81. The duration of SLE and of lupus nephritis were respectively 130.4 ± 73.1 months (median 120) and 100.8 ± 72.4 months (median 80.5). The diagnosis of lupus

Discussion

In this paper we analyzed the risk of fetal complications in women with lupus nephritis who became pregnant during a time frame of seven years, received pre-pregnancy counselling and were prospectively followed by a team of experts.

We observed fetal loss in 8.2% of offspring, preterm delivery in 28.2%, and 18.4% of newborns were SGA. Compared to retrospective studies, this rate of fetal loss is one of the lowest reported. Even in studies published after 2000, fetal loss ranged between 13 and

Conclusions and recommendations

In this paper we present the results of a multicenter study in which pregnant women with lupus nephritis were prospectively followed by a team of different specialists. Such an approach obtained a low rate of fetal loss. Preterm delivery and small for gestational age newborns remained important issues, particularly for patients with arterial hypertension, a history of repeated flares or for those with signs of lupus activity at and during pregnancy. However, the short-term complications in

Founding source

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Competing interests

None.

Acknowledgments

We gratefully acknowledge the following Medical Doctors for their contribution enrolling patients into the study: Fausta Catapano Nefrologia, Ospedale Policlinico Sant’Orsola-Malpighi, Bologna; Antonio del Giudice Nefrologia, Fondazione Casa Sollievo della Sofferenza, San Giovanni Rotondo Foggia; Cristina Izzo Nefrologia, Azienda Ospedaliera Universitaria Maggiore della Carita’ Novara; Gianfranca Cabiddu Azienda Ospedaliera Brotzu, Cagliari, Italy.

We gratefully acknowledge Dr Claudio Ponticelli

References (69)

  • J.P. Hayslett et al.

    Effect of pregnancy in patients with lupus nephropathy

    Kidney Int.

    (1980)
  • A. Coomarasamy et al.

    Aspirin for prevention of preeclampsia in women with historical risk factors: a systematic review

    Obstet. Gynecol.

    (2003)
  • G. Mintz et al.

    Prospective study of pregnancy in systemic lupus erythematosus. Results of a multidisciplinary approach

    J. Rheumatol.

    (1986)
  • E. Oviasu et al.

    The outcome of pregnancy in women with lupus nephritis

    Lupus

    (1991)
  • D.K. Packham et al.

    Lupus nephritis and pregnancy

    Q. J. Med.

    (1992)
  • E. Imbasciati et al.

    Lupus nephropathy and pregnancy. A study of 26 pregnanciesin patients with systemic lupus erythematosus and nephritis

    Nephron

    (1984)
  • D.L. Huong et al.

    Renal involvement in systemic lupus erythematosus. A study of 180 patients from a single center

    Med. Baltim.

    (1999)
  • M. Abu-Shakra et al.

    Mortality studies in systemic lupus erythematosus. Results from a single center. I. Causes of death

    J. Rheumatol.

    (1995)
  • C.A. Clark et al.

    Decrease in pregnancy loss rates in patients with systemic lupus erythematosus over a 40-year period

    J. Rheumatol.

    (2005)
  • D.L. Huong et al.

    Pregnancy in past or present lupus nephritis: a study of 32 pregnancies from a single centre

    Ann. Rheum. Dis.

    (2001)
  • E. Imbasciati et al.

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

    Nephrol. Dial. Transpl.

    (2009)
  • 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)
  • J. Liu et al.

    Pregnancy in women with systemic lupus erythematosus: a retrospective study of 111 pregnancies in Chinese women

    J. Matern. Fetal Neonatal. Med.

    (2012)
  • M.A. Saavedra et al.

    Impact of previous lupus nephritis on maternal and fetal outcomes during pregnancy

    Clin. Rheumatol.

    (2012)
  • S.J. Wagner et al.

    Maternal and foetal outcomes in pregnant patients with active lupus nephritis

    Lupus

    (2009)
  • M.E. Clowse et al.

    Early risk factors for pregnancy loss in lupus

    Obstet. Gynecol.

    (2006)
  • 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)
  • M.E. Clowse et al.

    Predictors of preterm birth in patients with mild systemic lupus erythematosus

    Ann. Rheum. Dis.

    (2013)
  • R.A. Levy et al.

    Antiphospholipid antibodies and antiphospholipid syndrome during pregnancy: diagnostic concepts

    Front. Immunol.

    (2015)
  • M.D. Lockshin et al.

    Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies

    Arthritis Rheum.

    (2012)
  • S. De Carolis et al.

    Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome

    Lupus

    (2012)
  • F. Carmona et al.

    Class III-IV proliferative lupus nephritis and pregnancy: a study of 42 cases

    Am. J. Reprod. Immunol.

    (2005)
  • J.H. Koh et al.

    Pregnancy and patients with preexisting lupus nephritis: 15 years of experience at a single center in Korea

    Lupus

    (2015)
  • G. Moroni et al.

    Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study

    J. Autoimmun.

    (2016)
  • Cited by (90)

    • Glomerular diseases in pregnancy: pragmatic recommendations for clinical management

      2023, Kidney International
      Citation Excerpt :

      Conversely, with respect to kidney function, women with a GD and normal kidney function before pregnancy do not have a clearly increased risk of kidney function impairment during or after pregnancy, even in the long-term, compared with nonpregnant women with a GD. This finding has been documented particularly in women with IgAN39,40 and LN.41,42 The frequency of kidney function testing is not clearly established in pregnant women with a GD.

    View all citing articles on Scopus
    1

    Gabriella Moroni and Andrea Doria: equally contributing first authors.

    2

    Marta Mosca and Pietro Ravani: equally contributing senior authors.

    View full text