Discussion
In this study we described the outcomes of pregnancies in a particular subgroup of patients with SLE without evidence of aPL and history or current nephritis. We aimed to test whether LDASA could have a protective role against APO in this highly selected population without the classic risk factors for pregnancy complications. Thus, the study aimed to address a clinical issue which is raised very frequently in clinical practice and for which the available literature does not provide a clear and definite answer: should we prescribe LDASA to all patients with SLE during pregnancy?
As a matter of the fact, a recent study from the Systemic Lupus International Collaborating Clinics (SLICC) cohort showed that LDASA was prescribed in only 25% of lupus pregnancies despite the presence of traditional risk factors for pre-eclampsia.15
The first important result that emerged from this study is that the incidence of severe obstetric complications in this particular population is low; in particular, pre-eclampsia was observed in 6.1% of patients, an incidence significantly lower than that observed in unselected SLE cohorts and similar to the frequency observed in the general population.16–19 The incidence of pre-eclampsia in our cohort was also lower than that expected in high-risk pregnancies, where it is around 9%.20
The most frequent obstetric complication was preterm delivery, observed in 18.9% of pregnancies; however, severe preterm delivery was reported in a minority of cases. It is important to note that these patients were strictly monitored and most pregnancies were planned, and these aspects could have had an impact on the low number of severe adverse events.
Our results are in line with previous findings on stable patients with SLE without active nephritis or prednisone >20 mg, as in the Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus (PROMISSE) study, where no difference in per cent of LDASA use in patients with and without APO was reported.2 While the study did not restrict to those without aPL or nephritis as in our analysis, the importance of a good control of disease activity was stressed similarly.
The second aspect that emerged from this study is that LDASA does not seem to have a significant impact on the occurrence of obstetric complications in this type of patients; indeed, the frequency of the composite outcome APO and of each adverse outcome is similar in patients on LDASA and not.
This is in line with literature data on the general population showing that the relative risk reduction of pre-eclampsia with LDASA is modest and strongly related to the baseline, individual pre-eclampsia risk.8 21 It may therefore be assumed that the sample size of our study is not sufficient to detect the beneficial effect of LDASA in this type of patient at low risk of complications.
Moreover, a possible bias by indication should be considered; indeed, we can assume that LDASA was probably administered to patients at increased risk of pregnancy complications, at least according to physician judgement.
However, it is interesting to note that pre-eclampsia had a frequency of 2.4% in patients taking LDASA, while those not taking LDASA had 8.3%. Although this difference is not statistically significant, probably due to the low number of observations included, this could suggest a protective effect of LDASA against the hypertensive disorders of pregnancy. On the other hand, chronic hypertension was more frequent, even if not significantly, in the control group than in the LDASA group (5.2% vs 1.2%); this comorbidity represents a well-known major risk factor for pre-eclampsia warranting the intake of LDASA irrespective of the diagnosis of SLE.
Thus, based on these findings, patients with SLE without aPL nor lupus nephritis seem to have a low risk of severe obstetric complications (especially pre-eclampsia) and LDASA treatment does not provide a significant advantage over these complications.
On the other hand, it should also be emphasised that a robust body of evidence showed no significant haemorrhagic risk or fetal risk associated with LDASA use during pregnancy. Thus, in the individual risk–benefit assessment, the potential protection from pregnancy complications seems to outweigh the risk of adverse events.8 22 Unfortunately, we did not assess haemorrhagic complications that occurred in our pregnancies.
This study has some limitations. First of all, it is a retrospective analysis and the physician’s judgement has a strong weight in the study. Indeed, we did not observe any cluster of risk factors in patients who received LDASA, but still it is not possible to reproduce the clinical reasoning made by the physician (or the multidisciplinary team) during preconception counselling.
However, our data derived from the real-life practice of seven European referral centres for pregnancy in SLE and were carefully collected; thus, good standardisation among the centres is expected. The second limitation is related to the small sample size and the resulting small number of obstetric complications, limiting the statistical analysis.
On the other hand, to the best of our knowledge, this is the first study to assess the impact of LDASA in a selected and homogeneous population of patients with SLE with a low-risk profile for obstetric complications.
In conclusion, these data highlight the importance of a careful individual risk assessment for pregnancy complications in patients with SLE, hopefully in the setting of a preconceptional counselling. Moreover, these data encourage a shared decision-making process between patients, rheumatologists and obstetricians, taking into account disease-related and non-disease-related factors.