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