Glomerular Disease and Pregnancy

Nephrologists are routinely involved in the care of pregnant women with glomerulonephritis. Prepregnancy counseling is vital to inform women of the potential risks of pregnancy and to reduce those risks by optimizing clinical status and medications. In general, for all glomerulonephritides, the best pregnancy outcomes are achieved when the disease is in remission and the woman has preserved renal function with no proteinuria or hypertension. Each glomerulonephritis has specific considerations, for example in lupus nephritis, mycophenolate is teratogenic and must be stopped at least 6 weeks before conception, hydroxychloroquine is recommended for all pregnant women, and flares are frequently encountered and must be treated appropriately. De novo glomerulonephritis should be considered when significant proteinuria is found early in pregnancy or an acute kidney injury with active urine is encountered. Biopsy can be safely undertaken in the first trimester. Treatment is often with corticosteroids, azathioprine, and/or tacrolimus. Rituximab is increasingly used for severe disease. Women with glomerulonephritis should ideally be managed in a joint renal-obstetric clinic. This review details the approach to the care of women with glomerulonephritis from prepregnancy counseling, through antenatal care and delivery, to the postpartum period. Special attention is given to medications and treatment of glomerulonephritis in pregnancy. Nephrologists are routinely involved in the care of pregnant women with glomerulonephritis. Prepregnancy counseling is vital to inform women of the potential risks of pregnancy and to reduce those risks by optimizing clinical status and medications. In general, for all glomerulonephritides, the best pregnancy outcomes are achieved when the disease is in remission and the woman has preserved renal function with no proteinuria or hypertension. Each glomerulonephritis has specific considerations, for example in lupus nephritis, mycophenolate is teratogenic and must be stopped at least 6 weeks before conception, hydroxychloroquine is recommended for all pregnant women, and flares are frequently encountered and must be treated appropriately. De novo glomerulonephritis should be considered when significant proteinuria is found early in pregnancy or an acute kidney injury with active urine is encountered. Biopsy can be safely undertaken in the first trimester. Treatment is often with corticosteroids, azathioprine, and/or tacrolimus. Rituximab is increasingly used for severe disease. Women with glomerulonephritis should ideally be managed in a joint renal-obstetric clinic. This review details the approach to the care of women with glomerulonephritis from prepregnancy counseling, through antenatal care and delivery, to the postpartum period. Special attention is given to medications and treatment of glomerulonephritis in pregnancy. Clinical Summary•Prepregnancy counseling is important for all women with glomerulonephritis who are considering pregnancy.•It is vital that, where possible, any glomerulonephritis is in remission before pregnancy.•Mycophenolate is teratogenic. Azathioprine, calcineurin inhibitors, and steroids are all safe in pregnancy.•Women with glomerulonephritis should ideally be managed in a joint renal-obstetric clinic. •Prepregnancy counseling is important for all women with glomerulonephritis who are considering pregnancy.•It is vital that, where possible, any glomerulonephritis is in remission before pregnancy.•Mycophenolate is teratogenic. Azathioprine, calcineurin inhibitors, and steroids are all safe in pregnancy.•Women with glomerulonephritis should ideally be managed in a joint renal-obstetric clinic. Historically, women with glomerulonephritis (with the notable exception of lupus nephritis) rarely got pregnant – mostly at the behest of their doctors. Improvements in both medical care and fertility technology mean pregnancy is a feasible option for more and more women, and as a result, nephrologists need to be proficient in issues such as fertility, teratogenicity, and pregnancy. Choice of initial and maintenance immunosuppressive therapies, use of adjunctive therapies such as antihypertensives, use of contraceptives, and even timing of biopsy will all need to be given special consideration in women of child-bearing age. Pregnancies should be planned in advance with therapies modified to facilitate successful conception, pregnancy, and delivery. Ideally, all women should receive prepregnancy counseling with a specialist obstetric nephrologist or obstetric physician.1Wiles K. Lightstone L. Glomerular disease in women.Kidney Int Rep. 2018; 3: 258-270Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar However, we recognize this service is not available everywhere and often it will be their usual nephrologist providing this service.1Wiles K. Lightstone L. Glomerular disease in women.Kidney Int Rep. 2018; 3: 258-270Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar The aim of this review is to discuss the management of women with glomerulonephritis before pregnancy, antenatally and postnatally. The best maternal and fetal outcomes in women with a history of glomerulonephritis are in those with preserved renal function, minimal proteinuria, and no hypertension. Therefore, the main priorities are early diagnosis and effective treatment. The potential impact of the treatment on future fertility should be discussed with all women of child-bearing age. Where treatments are equally effective (eg, mycophenolate mofetil vs cyclophosphamide for induction treatment of lupus nephritis),2Appel G.B. Contreras G. Dooley M.A. et al.Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis.J Am Soc Nephrol. 2009; 20: 1103-1112Crossref PubMed Scopus (781) Google Scholar the fertility-preserving treatment should be considered. If a fertility-affecting treatment must be used, steps to protect fertility should be discussed (eg, low-dose cyclophosphamide, gonadotrophin antagonists,3Somers E.C. Marder W. Christman G.M. Ognenovski V. McCune W.J. Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus.Arthritis Rheum. 2005; 52: 2761-2767Crossref PubMed Scopus (230) Google Scholar involvement of fertility specialists and/or freezing embryos).4Elizur S.E. Chian R.-C. Holzer H.E.G. Gidoni Y. Tulandi T. Tan S.L. Cryopreservation of oocytes in a young woman with severe and symptomatic endometriosis: a new indication for fertility preservation.Fertil Steril. 2009; 91: 293.e1-293.e3Abstract Full Text Full Text PDF Scopus (58) Google Scholar Women receiving treatments where pregnancy is contraindicated (eg, cyclophosphamide, mycophenolate, methotrexate) must be informed of the risk and be advised to use effective contraception. Long-acting, reversible contraception is ideal (eg, Mirena coil or Nexplanon) as they are safe and extremely effective. The progesterone-only pill is also an acceptable choice.1Wiles K. Lightstone L. Glomerular disease in women.Kidney Int Rep. 2018; 3: 258-270Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Estrogen-containing contraceptives are associated with increased risks of venous thromboembolism, arterial disease, hypertension, and breast and cervical cancer, which mean they are an inappropriate choice of contraception for many women with glomerular disease. There are also concerns they may be associated with disease flares in lupus nephritis.5Wiles K.S. Nelson-Piercy C. Bramham K. Reproductive health and pregnancy in women with chronic kidney disease.Nat Rev Nephrol. 2018; 14: 165-184Crossref PubMed Scopus (53) Google Scholar Condoms, with typical use, have a 19% failure rate per year and cannot be recommended as acceptable contraception.1Wiles K. Lightstone L. Glomerular disease in women.Kidney Int Rep. 2018; 3: 258-270Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Prepregnancy counseling offers a number of unique opportunities including reviewing the diagnosis and activity, medications, and potential impacts of pregnancy on the disease and the disease on pregnancy. This allows women to make an informed choice before pursuing pregnancy.5Wiles K.S. Nelson-Piercy C. Bramham K. Reproductive health and pregnancy in women with chronic kidney disease.Nat Rev Nephrol. 2018; 14: 165-184Crossref PubMed Scopus (53) Google Scholar Where a prepregnancy consultation has not taken place many of these discussions around risks, impact on disease and likely pregnancy course will take place at the first antenatal appointment when it might be too late to optimize disease status, stop teratogenic medications, or prevent an ill-timed or unintended pregnancy. Reviewing the patient's diagnosis and disease activity is vital for accurate and informed prepregnancy counseling. For all glomerulonephritides, pregnancy outcomes depend on disease activity before pregnancy, presence and degree of proteinuria, presence of hypertension, and degree of renal function.6Wiles K. Webster P. Seed P. et al.The impact of chronic kidney disease stages 3-5 on pregnancy outcomes.Nephrol Dial Transplant. 2020; (In press)Crossref Scopus (20) Google Scholar To ensure the best maternal and fetal outcomes, any induction treatment should be completed and the patient be stable on pregnancy-safe maintenance immunosuppression or off treatment for at least 6 months before conception.7Moroni G. Doria A. Giglio E. et al.Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study.J Autoimmun. 2016; 74: 6-12Crossref PubMed Scopus (76) Google Scholar Pregnancy-safe medications should not be reduced or withdrawn immediately before or after conception as the overall aim is to maintain remission. Women with active disease should postpone pregnancy until their disease is quiescent. Where disease is unlikely to be controlled, a full discussion about the risks of pregnancy should be undertaken. Occasionally, a biopsy is undertaken at this stage to facilitate informed decision-making.1Wiles K. Lightstone L. Glomerular disease in women.Kidney Int Rep. 2018; 3: 258-270Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Women should be informed; they are likely to have a more medicalized pregnancy and delivery. Usually, they need obstetrician-led care (as opposed to midwife led), extra appointments, and scans during pregnancy and may need to deliver in a hospital setting. Women (and doctors) often worry about medications and pregnancy. As well as reviewing and optimizing the patient's medications, prepregnancy counseling is the ideal time to reassure women as to which of their medications are safe in pregnancy and breastfeeding and the risks to themselves and to their pregnancy if stopped. In the authors' experience, acknowledging and discussing womens' anxieties about medications in pregnancy results in less fear and less inappropriate medication cessation during pregnancy. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers are commonly used to as renal protective agents in glomerulonephritis – however, second/third trimester exposure is associated with what can be a lethal embryopathy. ACE inhibitors can be continued until women fall pregnant and stopped once the pregnancy is confirmed and no later than 6 weeks gestation. Women with irregular menstrual periods need to perform regular pregnancy tests to ensure early pregnancy diagnosis.8Diav-Citrin O. Shechtman S. Halberstadt Y. et al.Pregnancy outcome after in utero exposure to angiotensin converting enzyme inhibitors or angiotensin receptor blockers.Reprod Toxicol. 2011; 31: 540-545Crossref PubMed Scopus (63) Google Scholar Angiotensin receptor blockers should be stopped before conception. Occasionally, ACE inhibitors are stopped in anticipation of pregnancy to allow an assessment of baseline proteinuria. This can be advantageous later in pregnancy if the cause of increasing proteinuria is unknown and preeclampsia is being considered. Azathioprine,9Nørgård B. Pedersen L. Fonager K. Rasmussen S.N. Sørensen H.T. Azathioprine, mercaptopurine and birth outcome: a population- based cohort study.Aliment Pharmacol Ther. 2003; 17: 827-834Crossref PubMed Scopus (130) Google Scholar tacrolimus,10Kainz A. Harabacz I. Cowlrick I.S. Gadgil S.D. Hagiwara D. Review of the course and outcome of 100 pregnancies in 84 women treated with tacrolimus.Transplantation. 2000; 70: 1718-1721Crossref PubMed Scopus (203) Google Scholar cyclosporine,11Bar Oz B. Hackman R. Einarson T. Koren G. Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis.Transplantation. 2001; 71: 1051-1055Crossref PubMed Scopus (359) Google Scholar and hydroxychloroquine7Moroni G. Doria A. Giglio E. et al.Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study.J Autoimmun. 2016; 74: 6-12Crossref PubMed Scopus (76) Google Scholar are all considered safe in pregnancy and breastfeeding. Rituximab12Chakravarty E.F. Murray E.R. Kelman A. Farmer P. Pregnancy outcomes after maternal exposure to rituximab.Blood. 2011; 117: 1499-1506Crossref PubMed Scopus (389) Google Scholar and steroids13Blom K. Odutayo A. Bramham K. Hladunewich M.A. Pregnancy and glomerular disease: a systematic review of the literature with management guidelines.Clin J Am Soc Nephrol. 2017; 12: 1862-1872Crossref PubMed Scopus (74) Google Scholar can be given after consideration of the risks and benefits (discussed in the following). The risk of preeclampsia should be assessed, and where appropriate, a plan should be made to start low-dose aspirin (75-150 mg) in pregnancy.14Bujold E. Roberge S. Lacasse Y. et al.Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a metaanalysis.Obstet Gynecol. 2010; 116: 402-414Crossref PubMed Scopus (827) Google Scholar,15National GA. Hypertension in pregnancy: diagnosis and management.Google Scholar Women with CKD, hypertension, and autoimmune diseases such as systemic lupus erythematosus (SLE) or antiphospholipid syndrome should all receive aspirin prophylaxis.15National GA. Hypertension in pregnancy: diagnosis and management.Google Scholar The authors would recommend prophylaxis to all women with glomerulonephritis with the exception of childhood nephrotic syndrome that has been in remission for many years. Women with significant proteinuria(>250 mg/mmol), hypoalbuminemia (<20-25 g/L),16Hladunewich M.A. Bramham K. Jim B. Maynard S. Managing glomerular disease in pregnancy.Nephrol Dial Transpl. 2017; 32: i48-i56Crossref PubMed Scopus (10) Google Scholar or increased thrombotic risk17Royal College of Obstetricians & GynaecologistsReducing the risk of venous thromboembolism during pregnancy and the puerperium.Green Top Guideline. 2015; (Available at: https://www.rcog.org.uk/globalassets/documents/guidelines/gtg-37a.pdf. Accessed January 4, 2020.)Google Scholar (eg, prior venous thromboembolism, venous thromboembolism in first degree relative, obesity, age >35 years) will need prophylactic low-molecular-weight heparin during pregnancy. Both low-dose aspirin and low-molecular-weight heparin are safe in pregnancy.18Wiles K. Chappell L. Clark K. et al.Clinical practice guideline on pregnancy and renal disease.BMC Nephrol. 2019; 20: 401Crossref PubMed Scopus (58) Google Scholar Many women with glomerulonephritis will require management of hypertension before and during pregnancy (whether preexisting, pregnancy-induced hypertension or preeclampsia). A blood pressure of 135/85 mmHg is targeted.15National GA. Hypertension in pregnancy: diagnosis and management.Google Scholar,18Wiles K. Chappell L. Clark K. et al.Clinical practice guideline on pregnancy and renal disease.BMC Nephrol. 2019; 20: 401Crossref PubMed Scopus (58) Google Scholar Labetalol and nifedipine are commonly used antihypertensives in pregnancy, either is an appropriate first choice.19Lowe S.A. Bowyer L. Lust K. et al.The SOMANZ guideline for the management of hypertensive disorders of pregnancy.Aust N Z J Obstet Gynaecol. 2015; 55: e1-e29https://doi.org/10.1111/ajo.12399Crossref PubMed Scopus (160) Google Scholar Prepregnancy counseling is also an ideal time to discuss other general issues, for example if the patient is not planning pregnancy (yet or ever), they should be using long-acting, reversible contraception. They should also take folic acid 4 mg for 3 months before conception.20Greenberg J.A. Bell S.J. Guan Y. Yu Y.H. Folic acid supplementation and pregnancy: more than just neural tube defect prevention.Rev Obstet Gynecol. 2011; 4: 52PubMed Google Scholar Prepregnancy counseling should also address disease-specific considerations for the individual glomerular disease; the impact of the glomerulonephritis on pregnancy, the impact of pregnancy on their glomerulonephritis, medications, and other special considerations – refer to disease-specific sections under antenatal care in the following. Where possible, women with glomerulonephritis should attend a combined renal-obstetric clinic antenatally. They need regular blood pressure, urine protein:creatinine ratios (24-hour urine protein collections are not required), and blood tests (minimum 4 weekly). Serial growth scans from 24 to 28 weeks of gestation are indicated if they have active glomerulonephritis or CKD. As mentioned previously, they should be on aspirin and venous thromboembolism prophylaxis (if indicated), their blood pressure should be strictly controlled, and they should be on pregnancy-safe medications.18Wiles K. Chappell L. Clark K. et al.Clinical practice guideline on pregnancy and renal disease.BMC Nephrol. 2019; 20: 401Crossref PubMed Scopus (58) Google Scholar Treatment of active glomerulonephritides during pregnancy, de novo disease, a flare, or relapse, is difficult. Treatment will depend on severity and glomerular disease subtype (refer to disease-specific sections below). Occasionally, the diagnosis is unknown, but treatment is required; in these cases, we favor tacrolimus over high-dose steroids as this would effectively, and likely more safely, treat minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis as well as lupus nephritis.21Webster P. Wardle A. Bramham K. Webster L. Nelson-Piercy C. Lightstone L. Tacrolimus is an effective treatment for lupus nephritis in pregnancy.Lupus. 2014; 23: 1192-1196Crossref PubMed Scopus (54) Google Scholar Treatment of severe flares and life- or organ-threatening disease is hugely challenging and fraught with anxiety. In these scenarios, depending on the stage of pregnancy, termination or premature delivery should be considered and discussed with the patient. Preeclampsia is commonly encountered in women with glomerulonephritis. Preeclampsia is a clinical diagnosis, and a renal biopsy is rarely appropriate (the classic histopathological lesion is endothelial swelling “endotheliosis”).22Stillman I.E. Karumanchi S.A. The glomerular injury of preeclampsia.J Am Soc Nephrol. 2007; 18: 2281-2284Crossref PubMed Scopus (225) Google Scholar Nephrologists may be asked to help differentiate it from a flare of an underlying glomerulonephritis, a notoriously difficult task.23Umans J.G. Obstetric nephrology: preeclampsia—the nephrologist’s perspective.Clin J Am Soc Nephrol. 2012; 7: 2107-2113Crossref PubMed Scopus (14) Google Scholar In some cases, serum markers may be useful; low complement levels may indicate a lupus flare or high titers of antiphospholipase A2 receptor antibodies may support a diagnosis of membranous nephropathy instead of preeclampsia. In women without CKD, the antiangiogenic factors soluble fms-like tyrosine kinase 1 and placental growth factor are likely to be useful in this situation in the future. They can be measured in serum/plasma and levels greater or lower than the manufacturer’s specific cutoffs can help to diagnosed preeclampsia. They are not yet in widespread clinical practice.24Duhig K.E. Myers J. Seed P.T. et al.Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial.Lancet. 2019; 393: 1807-1818Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar, 25Agrawal S. Cerdeira A.S. Redman C. et al.Meta-analysis and systematic review to assess the role of soluble fms-like tyrosine kinase-1 and placenta growth factor ratio in prediction of preeclampsia.Hypertension. 2018; 71: 306-316Crossref PubMed Scopus (102) Google Scholar, 26Bramham K. Seed P.T. Lightstone L. et al.Diagnostic and predictive biomarkers for pre-eclampsia in patients with established hypertension and chronic kidney disease.Kidney Int. 2016; 89: 874-885Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar Preeclampsia can be associated with fluid overload, acute kidney injury, and oliguria. Fluid restriction/avoidance of intravenous fluids is generally recommended in preeclampsia, despite oliguria, owing to the risk of iatrogenic pulmonary edema. Diuretics are only recommended if there is pulmonary edema.18Wiles K. Chappell L. Clark K. et al.Clinical practice guideline on pregnancy and renal disease.BMC Nephrol. 2019; 20: 401Crossref PubMed Scopus (58) Google Scholar,19Lowe S.A. Bowyer L. Lust K. et al.The SOMANZ guideline for the management of hypertensive disorders of pregnancy.Aust N Z J Obstet Gynaecol. 2015; 55: e1-e29https://doi.org/10.1111/ajo.12399Crossref PubMed Scopus (160) Google Scholar,27National GA. Intrapartum care for women with existing medical conditions or obstetric complications and their babies.Google Scholar Lupus nephritis commonly occurs in women of child-bearing age, so issues surrounding fertility and pregnancy have long been recognized as important. As a result, there are robust data on lupus nephritis and pregnancy to inform management and prepregnancy counseling. A large 2017 meta-analysis showed an increased risk of miscarriage (relative risk [RR] 1.51), prematurity (RR 3.05), small for gestational age (RR 1.59), preeclampsia (RR 1.91), hypertension (RR 1.99), and caesarean section (RR 1.85) in those with SLE compared with those without SLE. There was an increased likelihood of live birth (RR 1.38) in those without SLE.28Bundhun P.K. Soogund M.Z. Huang F. Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: a meta-analysis of studies published between years 2001–2016.J Autoimmun. 2017; 79: 17-27Crossref PubMed Scopus (114) Google Scholar A multicentre study of 71 pregnancies by Moroni et al7Moroni G. Doria A. Giglio E. et al.Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study.J Autoimmun. 2016; 74: 6-12Crossref PubMed Scopus (76) Google Scholar,29Moroni G. Doria A. Giglio E. et al.Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study.J Autoimmun. 2016; 74: 194-200Crossref PubMed Scopus (61) Google Scholarin which 61 women were with lupus nephritis, 56 in remission and 15 with ongoing mild activity reported an 8.4% fetal loss, 28.2% prematurity, and 16.4% small for gestational age; 19.7% had a renal flare, 8.4% preeclampsia, and 2% hemolysis, elevated liver enzymes, and low platelets syndrome. Predicting who will have an adverse pregnancy outcome can be difficult. The study by Moroni et al7Moroni G. Doria A. Giglio E. et al.Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study.J Autoimmun. 2016; 74: 6-12Crossref PubMed Scopus (76) Google Scholar found that presence of antiphospholipid antibodies and arterial hypertension is associated with fetal loss. Baseline proteinuria (odds ratio [OR] 2.74), Systemic Lupus Erythematous Disease Activity Index score (a composite marker of lupus activity) (OR 1.18), active nephritis (OR 17.7), hypertension (OR 18.9), and history of renal flares (OR 5.25) all predicted prematurity as did increasing proteinuria and Systemic Lupus Erythematous Disease Activity Index score during pregnancy. The prospective Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus study (which excluded those with proteinuria >1000 mg/24 h and creatinine >1.2 mg/dL) found the single biggest risk factor for an adverse outcome was the presence of lupus anticoagulant; however, being non-white or Hispanic and hypertensive greatly increased risk even if lupus anticoagulant negative. Given that lupus nephritis is much more common in non-white women and hypertension is very common in lupus nephritis, many women with prior lupus nephritis should be considered as having high risk of adverse pregnancy outcomes. However, most women with quiescent lupus, without significant renal impairment or proteinuria, will have good pregnancy outcomes.30Buyon J.P. Kim M.Y. Guerra M.M. et al.Predictors of pregnancy outcomes in patients with lupus: a cohort study.Ann Intern Med. 2015; 163: 153Crossref PubMed Scopus (298) Google Scholar For most women with quiescent lupus nephritis, pregnancy does not significantly affect their estimated glomerular filtration rate (eGFR). A single-center retrospective study comparing pregnancies in women with SLE with and without lupus nephritis found no difference in eGFR between the groups at 39 months after delivery.31Bramham K. Hunt B.J. Bewley S. et al.Pregnancy outcomes in systemic lupus erythematosus with and without previous nephritis.J Rheumatol. 2011; 38: 1906-1913Crossref PubMed Scopus (101) Google Scholar At 1-year postpartum, patients with renal flares in the cohort of Moroni et al29Moroni G. Doria A. Giglio E. et al.Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study.J Autoimmun. 2016; 74: 194-200Crossref PubMed Scopus (61) Google Scholar had a normal creatinine level (65.12 ± 14.08 μmol/L). In women with known lupus nephritis, their medications should be optimized to facilitate pregnancy planning. Methotrexate and mycophenolate are contraindicated in pregnancy and should be stopped at least 6 weeks before conception to avoid teratogenicity and to ensure there is no increase in disease activity once stopped/changed to an alternative medication such as azathioprine.32Lightstone L. Hladunewich M.A. Lupus nephritis and pregnancy: concerns and management.Semin Nephrol. 2017; 37: 347-353Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar,33Flint J. Panchal S. Hurrell A. et al.BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding—Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids.Rheumatology. 2016; 55: 1693-1697Crossref PubMed Scopus (293) Google Scholar If a woman conceives while taking mycophenolate, the risks should be discussed. First trimester exposure to mycophenolate is associated with congenital malformations (microtia, external auditory canal atresia, orofacial clefts, cardiovascular malformations, and digital hypoplasia) and high rates of miscarriage.32Lightstone L. Hladunewich M.A. Lupus nephritis and pregnancy: concerns and management.Semin Nephrol. 2017; 37: 347-353Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Management options include termination of pregnancy or immediate switch to pregnancy-safe medications. Usually mycophenolate is switched to azathioprine before pregnancy or, where appropriate, immunosuppression is stopped. A thiopurine methyltransferase level should be checked before azathioprine is started, so an appropriate starting dose can be chosen. Myelosuppression is more common in those with no or low levels of thiopurine methyltransferase activity, so a lower starting dose is usually chosen. The maximum dose to use in pregnancy is 2 mg/kg/d.32Lightstone L. Hladunewich M.A. Lupus nephritis and pregnancy: concerns and management.Semin Nephrol. 2017; 37: 347-353Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Prednisolone is safe in pregnancy but is associated with diabetes, hypertension, and weight gain; ideally, they should be taking ≤ 7.5 mg/d.32Lightstone L. Hladunewich M.A. Lupus nephritis and pregnancy: concerns and management.Semin Nephrol. 2017; 37: 347-353Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar,34Knight C. Nelson-Piercy C. Management of systemic lupus erythematosus during pregnancy: challenges and solutions.Open Access Rheumatol Res Rev. 2017; 9: 37-53Crossref PubMed Scopus (51) Google Scholar,35Stojan G. Petri M. The risk benefit ratio of glucocorticoids in SLE: have things changed over the past 40 years?.Curr Treat Options Rheumatol. 2017; 3: 164-172Crossref PubMed Google Scholar Rituximab crosses the placenta. Rituximab exposure in the second and third trimesters lead to cord levels equal to or higher than maternal levels and neonatal B cell depletion. Long-term effects on the developing immune system are unknown.32Lightstone L. Hladunewich M.A. Lupus nephritis and pregnancy: concerns and management.Semin Nephrol. 2017; 37: 347-353Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar,36Andreoli L. Bertsias G.K. Agmon-Levin N. et al.EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.Ann Rheum Dis. 2017; 76: 476-485Crossref PubMed Scopus (406) Google Scholar The baby should not have live vaccinations for 6 months after rituximab.32Lightstone L. Hladunewich M.A. Lupus nephritis and pregnancy: concerns and management.Semin Nephrol. 2017; 37: 347-353Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar If rituximab is bein