|Year : 2016 | Volume
| Issue : 6 | Page : 135-138
Lupus pregnancies: An Indian perspective
Mithun C Mohan1, Vinod Ravindran2
1 Department of Internal Medicine, Starcare Hospital, Muscat, Sultanate of Oman, Kerala, India
2 Centre for Rheumatology; Department of Rheumatology, National Hospital, Calicut, Kerala, India
|Date of Web Publication||22-Nov-2016|
Centre for Rheumatology, Calicut - 673 009, Kerala
Source of Support: None, Conflict of Interest: None
There are several challenges to a successful pregnancy outcome in patients with lupus in India including unplanned pregnancies, myths and false beliefs related to lupus pregnancies and poor access to dedicated care. Pregnant lupus patients are best managed by a multidisciplinary team consisting of rheumatologist, obstetrician, and other relevant specialists. In this narrative review, we have appraised available literature on the outcomes of pregnancy among lupus patients in India, highlight the lacunae in the care of such patients, and also present perspective of this issue based on our own experience.
Keywords: Fetal loss, high-risk pregnancy, immunosuppression, preeclampsia, preterm
|How to cite this article:|
Mohan MC, Ravindran V. Lupus pregnancies: An Indian perspective. Indian J Rheumatol 2016;11, Suppl S2:135-8
| Introduction|| |
Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder which predominantly affects women of the childbearing age group, and pregnancies in the affected individuals pose a major challenge to all those involved in its management.  As in SLE fertility normally remains unaffected, clinicians are likely to encounter many scenarios in the context of pregnancies. The emotional trauma suffered by women who have experienced multiple pregnancy losses make it even more complex.  Due to the current availability of better therapeutic options, patients with lupus are experiencing better disease control and better quality of life; therefore, merely a diagnosis of SLE is no longer a contraindication for pregnancy though chances of pregnancy-related morbidity exist.  Pregnancy outcomes are more likely to be favorable if pregnancy is attempted when disease is in remission or when disease activity is adequately controlled before conception.  In this narrative review, we have focused on the available literature on the outcomes of pregnancy among lupus patients in India and also present perspective of this issue based on our own experience.
| Lupus Pregnancies: Indian Literature|| |
In 1999, one of the earliest retrospective reports from India on the maternal and fetal outcomes among pregnant lupus patients reported the obstetric and fetal outcome of 15 lupus pregnancies in 1985-1997 and compared them with 45 parity-matched normal pregnancies.  Eleven women were in remission while four patients had active disease at the time of conception. Only two patients (with history of renal lupus) had a flare during the antenatal period, these low rates of flare were attributed to good disease control at time of conception and during pregnancy in a majority. Compared to controls, babies born to mothers with lupus had lower gestational age, lower birth weight, and there was higher incidence of intrauterine growth retardation (IUGR). However, preterm deliveries and mode of deliveries (cesarean section versus instrumentation) were comparable in cases and controls. Importantly, there were two stillbirths in the lupus group; one was in a patient who had disease flare with active lupus nephritis and another in lupus patient with inactive disease but had hyperpyrexia due to malarial infection. In summary, in this small study, lupus flare was uncommon, but incidence of IUGR reported was higher. The former was attributed to the use of prednisolone during the pregnancy.
Subsequently, a study in 2005 reported a retrospective review of records of 33 pregnancies occurring after the onset of lupus in 17 women attending the rheumatology clinic of a tertiary care center in India; however, only four of them had institution-based multidisciplinary care.  Majority (21/33) were unplanned pregnancies; however, in 19/33, the disease was well controlled at the time of conception. There were 15 live births (45%), 12 spontaneous abortions (36%) and 6 pregnancies (18%) were terminated due to high disease activity in the mothers, and there were 4 pregnancies with IUGR. Nine pregnancies were associated with a flare of disease. Irrespective of whether the disease was well controlled or not at conception, both groups had a flare in lupus (11 in 19 and 7 in 8, respectively). This study was small and it is difficult to make valid conclusions from it, however, relatively high fetal wastage underscored the lack of access to multidisciplinary care.
Closely following in 2005 was another report of 52 pregnancies in 31 women with lupus.  This was essentially a chart review of nearly 13 years (retrospective in the first 11 years). Twenty-one pregnancies occurred in patients with active (mild with mainly cutaneous and arthritis) and 31 in patients with inactive lupus. Surprisingly, though all patients were counseled not to become pregnant unless their disease has been in remission for at least 6 months, of the 41 pregnancies (21 with major organ involvement and 20 with minor), 23 were unplanned. Eleven of the 52 pregnancies were medically terminated (three due to active disease and one as the patients was on cyclophosphamide). Of the remaining 41 pregnancies, there were 24 live births (58.5%). The live births were more frequent when pregnancy occurred while lupus was inactive (82.6%) compared to when it was active (27.7%). There were 12 spontaneous abortions (29%), which were also more frequent in active lupus (10/18 vs. 2/28). There was one maternal death, regarding which the authors have provided no further details. Flare was noted in three pregnancies and preeclampsia in four. This study also highlighted the high rates of fetomaternal morbidity and mortality and lower live birth rates even in a tertiary care center.
In 2010, a retrospective questionnaire-based survey comparing menstrual irregularities and pregnancy outcomes of patients with SLE (n = 210) and rheumatoid arthritis (RA) (n = 210) showed that before the onset of disease, the frequency of live births (73% vs. 81%) as well as first trimester spontaneous abortions (19% vs. 14%) among women with SLE or RA, respectively, were comparable.  After disease onset, there were 121 pregnancies in SLE. Live births were only 22% (27/121). Complicated live births (defined by the authors as cesarean section, preterm, IUGR, or low birth weight [LBW]) occurred in 30/121 (25%) SLE pregnancies. Pregnancy loss (spontaneous abortions) occurred in 64/121 (53%). Proportion of the second-trimester pregnancy loss also rose in patient with SLE to 34%. Other interesting observations made in this study were a), reduced mean family size (1.44 1.35) compared to Indian national average of 2.7 alluding both to a possible reduced fertility and increased pregnancy risk and b), even before the onset of SLE those patients were at over 1.5 times higher risk of pregnancy losses. 
Recently in 2011, a study reported another decades experience from tertiary care center and compared it to their previous experience. , A total of 71 pregnancies (35 prospectively and 36 retrospectively) in 35 women with lupus were studied between 1998 and 2009. There were 47/71 (66%) live births; however, spontaneous abortions (33%), preterm deliveries (30%), perinatal loss (13%), and cesarean section (18%) were substantial though less when compared to authors' own previous experience of 15 pregnancies in women with lupus.  Remarkably, all women conceived during the disease quiescence period, and 82% pregnancies followed preconception counseling. Another interesting observation was that all those 35 prospectively followed pregnancies resulted in live births.
Since mid-2010, for recurrent pregnancy losses in patients with lupus, senior author of this review has worked on a multidisciplinary approach which focuses on avoidance of "routine" investigations and involves working with group of colleagues from across specialties (not confined to same institute or geographical area). It values the natural maternal instinct regarding pregnancy and recognizes it to be a compliment to the clinician driven care. This prospective approach first reported 14 patients in 2012 and recently in 2016 a total of 53 patients. ,
These patients with SLE fulfilling the ACR classification criteria had at least one previous adverse obstetric outcome (maternal; preterm labor, preeclampsia, or previous medical termination of pregnancy [MTP] in view of SLE flare, fetal; miscarriage, IUGR, preterm birth, LBW, intrauterine death, or stillbirth). All patients had in-depth preconception counseling and were prospectively followed throughout the pregnancy as per the protocol with multidisciplinary team input. Briefly, the protocol comprised prenatal counseling, prenatal drug and disease status review, risk stratification, periodic antenatal visits for the monitoring of pregnancy (including with obstetric ultrasounds) and disease, two-dimensional echocardiogram at weeks 18 and 32 if Ro/La were positive, and postnatal disease and drug review and contraception advice. , Therapeutic changes were made as necessary at each stage. , Patients were given a helpline number to contact the rheumatologist directly if they had any concern, and obstetricians who were not in same institutions were kept in regular touch with periodic phone calls and formal letters.
In these 53 patients, the previous poor obstetric outcomes were: Miscarriages in 30, MTP in 9, preterm labor with IUGR in 9, intrauterine death and stillbirth in 2 each, and preeclampsia in 1. Nine patients had secondary APS, and 14 had both or either Ro/La positive. Nine had lupus nephritis at least 6 months ago.  There were 44 live births (85%). Of these 44 live births, 10 were low birth weight; 28 were delivered either by instrumentation or cesarean section. Sixteen patients (30%) had lupus flare (nine mild, five moderate, and two severe based on SLEPDAI). Only eight patients had miscarriages.  This study although small shows that it is possible for lupus patients with recurrent pregnancy losses to have favorable pregnancy outcome provided that the management protocol includes preconception counseling, regular assessments of disease activity, antenatal care, and a multidisciplinary approach of obstetrician working in close concert with the rheumatologist and other relevant specialists.
| Lupus pregnancies: Felt needs and potential solutions|| |
It is clear from a critical appraisal of the aforementioned studies that the studies on the outcome of pregnancies among lupus patients from India are small, single centered, and retrospective in nature either a review of records or based on questionnaire. The later therefore, being subject to recall bias. Apart from the logistical issues, there may be several local issues creating a barrier in achieving an "acceptable outcome" and its measurement.  Like lupus, the need for dedicated units catering for pregnancy in other autoimmune diseases has also been felt but does not appear to be in place as a formal set up even in the large teaching institutions.  Lack of adequate numbers of trained rheumatologists is a major issue, especially considering that the projected numbers of such individuals would still fall short in foreseeable future.  Staggering patient load in both obstetrics and rheumatology may also affect reallocation of already restricted resources to the care of pregnant patients with autoimmune rheumatic diseases. One can consider several current lacunae in the care of lupus pregnancies [Box 1 [Additional file 1]] in India.
A multidisciplinary team involving rheumatologist, physician, obstetrician, etc., is highly desirable, but we feel that rheumatologist should strive to give leadership to such teams due to their wide overall knowledge about lupus as a disease to identify complications early and to prevent adverse outcomes in these patients.
It is generally recognized that the development of rheumatology as a specialty in India requires curricular reforms, capacity building, patient education, and political support.  Never the less, it is imperative that the existing rheumatologists start taking in interest in the lupus pregnancies and where possible try build a team by empowering and educating not only the relevant clinicians but also the patients and encourage them in being an active part of the patient counseling and support. 
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Lateef A, Petri M. Management of pregnancy in systemic lupus erythematosus. Nat Rev Rheumatol 2012;8:710-8.
Kavanaugh A, Cush JJ, Ahmed MS, Bermas BL, Chakravarty E, Chambers C, et al.
Proceedings from the American College of Rheumatology Reproductive Health Summit: The management of fertility, pregnancy, and lactation in women with autoimmune and systemic inflammatory diseases. Arthritis Care Res (Hoboken) 2015;67:313-25.
Aggarwal N, Sawhney H, Vasishta K, Chopra S, Bambery P. Pregnancy in patients with systemic lupus erythematosus. Aust N Z J Obstet Gynaecol 1999;39:28-30.
Gupta A, Agarwal A, Handa R. Pregnancy in Indian patients with systemic lupus erythematosus. Lupus 2005;14:926-7.
Chandran V, Aggarwal A, Misra R. Active disease during pregnancy is associated with poor foetal outcome in Indian patients with systemic lupus erythematosus. Rheumatol Int 2005;26:152-6.
Gupta R, Deepanjali S, Kumar A, Dadhwal V, Agarwal SK, Pandey RM, et al.
A comparative study of pregnancy outcomes and menstrual irregularities in northern Indian patients with systemic lupus erythematosus and rheumatoid arthritis. Rheumatol Int 2010;30:1581-5.
Aggarwal N, Raveendran A, Suri V, Chopra S, Sikka P, Sharma A. Pregnancy outcome in systemic lupus erythematosus: Asia′s largest single centre study. Arch Gynecol Obstet 2011;284:281-5.
Ravindran V, Balakrishnan KP, Divakaran M. Pregnancy outcome in lupus patients with previous adverse outcomes: Experience with protocol-based, multidisciplinary care from Kerala, South India. Rheumatology (Oxford) 2012;51:i134.
Ravindran V, Bhadran S, Reshma V. Pregnancy outcome in lupus patients with previous adverse outcomes: Experience with protocol-based, multidisciplinary care from Kerala, South India. Indian J Rheumatol 2016;11:S56.
Ravindran V. Rheumatology outcome measures in principle and practice in India: So near and yet so far. Indian J Rheumatol 2013;8:8-10.
Ravindran V. Systemic vasculitis and pregnancy. In: Sharma SK, Sawhney S, editors. Rheumatic Diseases in Women & Children. 1 st
ed. New-Delhi: Jaypee Brothers Medical Publishers (P) Ltd.; 2013. p. 44-9.
Misra DP, Agarwal V, Negi VS. Rheumatology in India: A bird′s eye view on organization, epidemiology, training programs and publications. J Korean Med Sci 2016;31:1013-9.
Handa R. Rheumatology in India - Quo vadis? Nat Rev Rheumatol 2015;11:183-8.