Recommendation 1. The panel recommends advising all patients of reproductive age—men and women—of the need to plan a pregnancy and offering preconception counseling whenever necessary (LE 2b, GR B, LA 100%).

The panel recommends regularly evaluating the thoughts of all patients of reproductive age about their feelings about pregnancy, especially women with autoimmune disorders and antiphospholipid syndrome (APS), but also those of patients, including men, with inflammatory joint diseases. In those cases in which a pregnancy is being contemplated, the patient should always be offered preconception counseling. Moreover, to the greatest possible extent, unnecessary delays in conception should be avoided.17,18

The characteristics of this preconception counseling (Table 1), which includes information on the impact of the disease on fertility and pregnancy, as well as on the attitude to adopt in the case of an unforeseen pregnancy, must be adjusted (age, disease, treatment, personal history, obstetric history, etc.) to our patients. This offer should also involve the patient's partner, whenever possible.

This should be done periodically, and it is necessary to insist in that planning a pregnancy is essential to reduce the maternal–fetal risks and ensure its success.

On the other hand, it is important to remember that rheumatic diseases (given their activity or established organic damage) and their treatment can be associated with fertility problems. It has been calculated that approximately 1.5% of the patients with systemic lupus erythematosus (SLE) may have difficulties with infertility,19 due to different causes like, for example, severe flares, moderate-to-severe renal failure with a low glomerular filtration rate (<60mL/min), etc.20 In other autoimmune diseases and vasculitis there is less experience and the results are variable.

Inflammatory diseases of the joints and rheumatoid arthritis (RA), in particular, are under-recognized causes of subfertility and infertility.21,22 Patients with RA have been found to have a lower birth rate, to take longer to become pregnant (more than 1 year in 25% versus 15% in the general population),23 and to recur more to the use of assisted reproduction techniques (9.8% versus 7.6% in the general population).23 In RA patients, the time to pregnancy has been associated with age, nulliparity, inflammatory activity and the use of >7.5mg of prednisone and nonsteroidal anti-inflammatory drugs (NSAID) prior to conception,24 but not to other factors such as having taken methotrexate (MTX) or the duration of the disease.

Some drugs prescribed in rheumatology can also have an influence on fertility. Because NSAID inhibit prostaglandins,22 they can affect implantation25 and ovulation26 in women. In men, on the other hand, there is a risk of oligo/azoospermia because of the use of sulfasalazine. Finally, the utilization of cyclophosphamide may require special management because it provokes potentially irreversible sterility in both sexes (measures for gonadal protection, in vitro fertilization, etc.).

Recommendation 2. The panel suggests evaluating and recommending an effective contraceptive method to be used to avoid an unforeseen pregnancy (LE 1b, GR A, LA 100%).

Aside from certain exceptions (Table 2), inflammatory diseases do not contraindicate pregnancy.18,27–31

We should recommend the utilization of effective contraceptive measures both for men and women, provided pregnancy is not being contemplated, is contraindicated or is being postponed (because of disease activity, initiation of the use of teratogens, etc.).

Combined hormonal contraception is the most efficacious method (Appendix A) (available online),17 especially for stable couples, unless there is a contraindication for the use of estrogens,5 in which case it would be necessary to utilize progestogens alone. However, the panel recommends that each case should be dealt with individually to suggest the contraceptive method that best adapts to the characteristics and circumstances of the patient/couple.

Moreover, in those patients with a high disease activity or significant residual damage (especially to internal organs), perhaps, on an individual basis, the idea of a pregnancy could be reconsidered and definitive methods of sterilization be assessed (Table 2).32–35

In mild-to-moderate flares, if the activity is controlled for at least 3 months with medication compatible with pregnancy, conception can be attempted. Severe flares (lupus nephritis, neuropsychiatric manifestations, severe vasculitis, pulmonary involvement in scleroderma) habitually require intensive treatment with teratogens like cyclophosphamide or mycophenolate mofetil. Thus, in those cases, pregnancy should be postponed at least 1 year until remission is achieved.18

Recommendation 3. The panel recommends that those patients who are candidates for assisted reproduction be provided with information on the available techniques (LE 4, GR D, LA 73%).

Patients with rheumatic diseases and fertility problems are increasingly interested in undergoing assisted reproduction techniques.

Although this subject is in the sphere of and is the responsibility of gynecologists, rheumatologists, as physicians responsible for these patients, should be familiar with the general aspects of these procedures to be able to provide any necessary information.

If there is no contraindication, it is essential not to delay referring patients to the infertility clinic of their center or health area, and to prepare complete reports for these units and become involved in the entire process. For this purpose, each professional must know how these clinics function and how they are managed.

In general, these techniques are safe, although it must be kept in mind that some of them, like ovarian stimulation, increase estrogen levels, which can be accompanied by flares and other complications in patients with SLE or APS. At the present time, we have little evidence on ovarian stimulation in patients with SLE, but it seems to be relatively safe.36–38 However, there is limited information on the thrombotic risk associated with this therapy. Therefore, we should pay special attention to those patients with a high risk of thrombotic events.39

Assisted reproduction techniques should only be considered at a time when the disease is inactive and that they be performed on an individual basis with close monitoring of the patient.

Recommendation 4. Planning a pregnancy should include an evaluation of the obstetric and rheumatic history of the patient, as well as analyses, immunological study, present status of the disease and treatments, comorbidities and possible contraindications for pregnancy (LE 5, GR D, LA 100%).

Recommendation 5. The panel recommends evaluating and reporting the maternal–fetal risk factors of pregnancy on an individual basis and on every aspect of their follow-up (LE 5, GR D, LA 100%).

Recommendation 6. The panel recommends that the patient achieve the best possible control of the inflammatory activity prior to attempting conception, with remission being the desired target, especially in the case of SLE (LE 3, GR C LA 100%).

Pregnancy can change the clinical activity of inflammatory rheumatic diseases and these, in turn, can be risk factors for the progression of the pregnancy. Controlling the clinical activity and the preconception use of agents that are low-risk in terms of the fetus make it possible to reduce maternal–fetal complications. For this reason, it is essential to plan the pregnancy.40,41

As a part of this planning (Table 3), an individual preconception evaluation should be performed, including an obstetric-gynecological history, contraindications of the pregnancy and the risk (and associated factors) of maternal–fetal complications.41–43 These depend on factors related to the mother (age, obstetric history), her disease (clinical activity at the time of conception, certain drugs, existence of irreversible damage, comorbidities or presence of certain autoantibodies) and with the medications utilized prior to and during the pregnancy (Table 4).18,40,41,44,45

In pregnant SLE patients, there is a greater risk of exacerbation of the disease,46–53 including nephropathy, thrombotic events, infections and thrombocytopenia,54–56 as well as preeclampsia,57 eclampsia and hemolysis, elevated liver enzymes and low platelets (HELLP syndrome).56,58 The presence of activity during the 6 months prior to conception increase the risk of flares during the pregnancy and maternal–fetal complications.59–62

There are higher incidences of abortion, neonatal death and premature or low birth weight infants in both in SLE and APS.47,57,59,63

In contrast, some RA patients improve in terms of clinical activity during pregnancy and become worse during the puerperium.29,30 However, the presence of activity at the start of pregnancy has been associated with persistence of activity throughout gestation and an increase in the risk of flares during the puerperium.64 In RA there is also a higher risk of preeclampsia, cesarean section and low birth weight infants,65–68 risks that diminish if disease activity is controlled or is low.69

In general, spondyloarthritis does not negatively interfere with pregnancy, the fetus or breastfeeding. However, a higher rate of cesarean sections, often caused by the disease itself, has been reported.70,71

Patients with systemic sclerosis may have an increased risk of preterm delivery, intrauterine growth restriction and low birth weight.72 Vasculitis does not usually affect the development of pregnancies, but there is an increase in the risk of preterm birth.73

The planning of a pregnancy in patients with SLE and APS should also include a general analysis and testing for lupus anticoagulant and anticardiolipin, anti-β2 glycoprotein, anti-Ro, anti-La and anti-double-strand (ds) DNA antibodies, with components of the complement system.32,74

Another fundamental aspect of planning is for the patient to achieve remission (or, otherwise, on an individual basis, the minimal disease activity possible) with nonteratogens (Table 5) at least 6–12 months before conception.41 For this, treatment must be reevaluated. Agents that are contraindicated during pregnancy (MTX, leflunomide) or considered to be of high risk (cyclophosphamide) should be discontinued and replaced by safe drugs and be maintained for 3–4 months with the patient in clinical remission prior to conception.43 In cases of severe disease, a waiting period of at least 1 year in remission is recommended before pregnancy.18 If the patient is taking an anti-tumor necrosis factor α (TNFα) agent, the possibility of maintaining it until the pregnancy is confirmed or until the end of the second trimester (depending on the patient) can be evaluated. In certain cases, the option of continuing to take it during the entire pregnancy is a decision that must be discussed and agreed upon because of a lack of data.75,76 The level of placental transfer of etanercept and certolizumab pegol is low (see subsequent sections).77,78 If the patient is being treated with rituximab, it must be taken into account that the half-life can be as long as several months and, thus, it should be discontinued between 6 and 12 months prior to conception. For other biological agents, there is very little information, and the need to suspend them or replace them with other medications prior to conception or on the confirmation of the pregnancy is a decision that must made on an individual basis.

In SLE patients, hydroxychloroquine (HCQ) reduces the risk of exacerbations during pregnancy79 and, thus, its use is recommended if the patient is considering pregnancy, because it does not need to be discontinued after conception.79–81 Likewise, some SLE and APS patients should continue to take antiplatelet and/or anticoagulant therapy, even prior to conception (see subsequent sections).44,57,60,63,82–84

Patients must be aware of the treatment they can take during pregnancy and even agree on what to do in the case of flares or serious complications that can put their lives at risk or cause fetal loss. They should also be informed of the risks during the postpartum period and while breastfeeding,18 and what will be involved in follow-up throughout their pregnancy.

Given that a relatively high percentage of pregnancies are not planned,85,86 during the reproductive age, any patient with a rheumatic disease should have preferential access to all of this information.

Recommendation 7. Patients with a high risk—that is, with APS and connective tissue diseases, or with arthritis or spondyloarthritis with moderate-to-high activity or who require corticosteroids or biological agents to control their disease—should be attended to in high-risk obstetric units once pregnancy has been confirmed (LE 5, GR D, LA 100%).

Pregnancy in women with SLE or APS is always a “high-risk” pregnancy because of the increase in maternal–fetal morbidity and mortality.32,42,43,56 In other autoimmune rheumatic diseases, a pregnancy is considered to be “high risk” because of the inflammatory activity and fetal toxicity of many of the treatments employed.18 All of those cases should be referred to high-risk units.

However, in a highly specific group of patients, those who have mild involvement or are under very good medical control, follow-up in the usual consultations can be contemplated.

Recommendation 8. The panel recommends looking for a medical profile as effective and safe as possible for pregnancy, that is individualized for each patient (LE 3, GR B-C, LA 100%).

Knowledge on the safety of medications is one of the cornerstones of an effective and safe obstetric and medical care. Still, we do not have access to enough evidence on all of the drugs to be able to issue robust and explicit recommendations.87 Thus, the prescription of medications during pregnancy should be done with precaution, taking into account a detailed analysis of the risk-benefit in each patient on an individual basis. Table 5 shows the major agents utilized in rheumatology.

Any NSAID should be discontinued upon reaching the third trimester of gestation given the risk of preterm delivery and early closure of the ductus arteriosus.87 The data on the use of cyclooxygenase-2 is very limited, but a recent study seems to show that its utilization increases the risk of fetal malformations, and thus it should be avoided during pregnancy.88 Nonfluorinated corticosteroids (prednisone and prednisolone) can be utilized with caution during pregnancy at the lowest possible doses,89 whereas fluorinated corticosteroids (dexamethasone) are able to cross the placental barrier and, thus, should be administered only at the end of gestation, to favor lung maturation, in the case of risk of preterm birth.87 With respect to synthetic disease-modifying drugs, the United States Food and Drug Administration (FDA) and the Spanish Agency of Medicines and Medical Devices (SAMMD) contraindicate the use of MTX, leflunomide and mycophenolate mofetil during pregnancy. In the case of MTX in men, it has been seen that it can produce azoospermia, although its effects on embryogenesis are now being questioned.90,91

With regard to biological therapies, IgG antibodies are able to cross the placenta from the second trimester on, an occurrence that takes place due to neonatal constant fragment (Fc fragment) receptors.92 We should point out that both etanercept (which has a lower affinity for binding to placental receptors than other anti-TNFα drugs)77 and, especially, certolizumab pegol (which lacks Fc),78 have a low level of placental transfer, a fact that could confer them a better safety profile.

In pregnant women being treated with infliximab and adalimumab, these agents have been detected in umbilical cord blood in the second and third trimester and in the infant until up to 6 weeks after being born.75,76 Thus, in those patients in whom they were maintained during pregnancy, it is recommended that they be discontinued at the end of the second trimester, although at the present time there is no data (in relation to fetal complications) that advise against their use during this entire period.93 Therefore, on an individual basis and in highly justifiable cases (marked disease activity), an agreement can be reached in terms of maintaining them until the end of the pregnancy.

Anti-TNFα agents taken by men at the time of conception have no influence on the fertility or the pregnancy of their partners.94

With respect to rituximab, its use during conception or pregnancy has been associated with preterm births and spontaneous abortions; however, in those studies, the influence of the severity of the underlying disease cannot be ruled out in those cases.95–97 On the other hand, the drug can cross the placental barrier during the second and third trimester and provoke a transient depletion of B cells in the fetus or infant, increasing the risk of infection. However, the long-term effects on the immune system of newborns are unknown. If it had not been discontinued prior to conception, it is advisable to do so as soon as the pregnancy is confirmed.

Finally, we have little data on anakinra, abatacept, tocilizumab, ustekinumab, secukinumab and belimumab.96 Thus, it is recommended that these agents be discontinued as soon as the pregnancy is confirmed, if they had not been prior to conception.

Recommendation 9. The panel recommends close follow-up and control of patients with rheumatic diseases who become pregnant (LE 2a, GR B, LA 100%).

Patients who are pregnant should undergo rigorous obstetric monitoring, as well as a strict control of their underlying disease, preferably in multidisciplinary units that combine the presence of gynecologists with experience in high-risk pregnancies and rheumatologists with broad experience in the planning and control of gestation.

The regularity of visits to their physicians will depend on one hand on the obstetric evaluation and, on the other, on the underlying disease, its activity and the development of flares. In general terms, in a patient with low or virtually no activity, who is stable in clinical terms, the regularity can be every 4–6 weeks during the first 2 trimesters, and be scheduled every 2 weeks starting from 32 to 36 weeks gestation. In the case of disease flares or the development of obstetric complications, the regularity would be determined by the attending physicians. In SLE (depending on the case), check-ups were recommended approximately every 4 weeks by the obstetrician and every 4–6 weeks by the rheumatologist until the 20th week of gestation, every 2 weeks until the 28th week and every week until the end of the pregnancy.50,98–100 Patients with anti-Ro/La antibodies should receive special mention because it is recommended they undergo fetal echocardiography each week between 16 and 26 weeks gestation with measurement of the PR interval and fetal heart rate.56

The evaluation of the patients should be systematic. It ought to include monitoring arterial blood pressure and body weight and a basic physical examination. Analyses should involve a complete blood count with erythrocyte sedimentation rate, routine laboratory tests (glucose, renal and liver function), C-reactive protein (CRP) and urinalysis. In a stable patient, analyses can be performed every 8–12 weeks and more frequently in the case of a flare. The only exception is the urine analysis, which should be carried out in all the check-ups. It is recommended that, in SLE patients, components of the complement system and anti-dsDNA be determined at each visit.74 Usually, in the remainder of the diseases, it is not considered necessary to repeat other autoantibodies. The attempt should be made so that the analyses requested coincide with the timing of the tests routinely called for in obstetrics.

The activity should be evaluated in accordance with routine clinical practice, although taking into consideration that the pregnancy may influence certain parameters used in the evaluation. In the case of RA, the use of the 28-joint Disease Activity Score (DAS28)-CRP is recommended, without the overall patient-reported health status assessment component; in the case of SLE, there are scores adapted for pregnancy.101

The rheumatic diseases most frequently treated in multidisciplinary clinics are RA, spondyloarthritis, APS and SLE. The major recommendations concerning follow-up and monitoring involve these diseases rather than other processes that, because of their incidence or epidemiology, are substantially less common, for example scleroderma, Sjögren's syndrome or systemic vasculitis.14,15

Recommendation 10. In the case of activity or complication, the panel recommends treating each patient on an individual basis, taking into account the type and seriousness of the event, the underlying disease, the trimester of the pregnancy and the available therapeutic options (LE 5, GR D, LA 100%).

In each case, the therapeutic approach should be individualized and agreed upon by the patient and, if necessary, with both the gynecologist and obstetrician.

If a flare occurs in a patient with arthritis, intra-articular injection is safe and effective. The use of NSAID can be considered except in the third trimester. If systemic corticosteroid therapy is required, it is recommended that prednisone, prednisolone and methylprednisolone be administered at the minimum effective doses. If the inflammatory activity persists and it is necessary to add a disease-modifying drug, possible alternatives are HCQ, azathioprine and sulfasalazine.18,102 If the activity persists and the use of biological therapy is proposed, the crossing of the placental barrier must be taken into account; etanercept has a low level of placental transfer, which is minimum in the case of certolizumab pegol18,77,78,102,103 (see preceding sections). It is also necessary to keep in mind the vaccination calendar.

In patients with SLE, it may be necessary to consider the differential diagnosis involving a situation of preeclampsia and a nephritis flare. The presence of other clinical or analytical data on the activity of SLE (extrarenal manifestations of lupus, active urinary sediment, hypocomplementemia and anti-dsDNA antibodies) and normouricemia (versus hyperuricemia in preeclampsia) point to a diagnosis of nephritis.104 In this case, the drugs that should be employed are prednisone and azathioprine.105

If a pregnant woman has cutaneous manifestations of SLE, it will be necessary to decide on topical treatment or local injection of corticosteroids or calcineurin inhibitors, as well as the use of an antimalarial agent, preferably HCQ.

If we detect thrombocytopenia in a patient with SLE, it is essential to rule out preeclampsia, HELLP syndrome or another cause, and it must be confirmed that the low values are a consequence of the underlying disease. In this case, corticosteroids or immunosuppressive agents like azathioprine should be administered. If thrombocytopenia persists or there is evidence of bleeding, intravenous immunoglobulins can be utilized.18,102 If an antimalarial drug or acetylsalicylic acid (ASA) has been prescribed, it should be maintained at low doses.

On the other hand, if the patient tests positive for antiphospholipid antibodies, but does not have symptoms, the option is low-dose ASA or no treatment, provided there are no other additional risk factors. If the patient has a history of repeated abortions (<10 weeks gestation) or of fetal loss (>10 weeks gestation), it is recommended that she receive low-dose ASA together with low-molecular weight heparin (LMWH) at prophylactic doses, since the combination of the 2 drugs is more effective in reducing losses than the administration of ASA alone.106,107 If the patient is receiving anticoagulant therapy with dicoumarol, the latter should be replaced by LMWH at therapeutic doses.108,109 This change should be made before the sixth week of gestation (or even before conception), given that the highest risk of malformations associated with dicoumarol coincides with weeks 6–12.110

In the case, that the patient has SLE or APS and is receiving anticoagulant therapy, the change to oral anticoagulants should be done to heparin prior to conception or, at least, within the 2 weeks after the first missed period, as oral anticoagulants cross the placenta and are associated with embryopathy, congenital malformations and a higher risk of intracranial hemorrhage.111

During pregnancy, the recommended anticoagulant therapy is unfractionated heparin or LMWH, although the latter has the advantage of having a longer plasma half-life and a more predictable dose response, which favors its administration in a single daily dose.111 At the time of delivery, the last dose of LMWH should be administered 24h earlier, and then the patient should receive half of the daily dose. Therapeutic doses of LMWH should be reinitiated 24–72h after delivery, depending on the obstetric procedure and any complications.112

In case the pregnant patient with a rheumatic disease has an infection that requires the utilization of an antibiotic, it is necessary to choose one with a good safety profile regarding pregnancy (Appendix A) (available on the web).113

If the pregnant patient has HELLP syndrome, the best treatment would be to finalize the pregnancy if it is discovered after the 34th week of gestation or if there is deterioration of the maternal or fetal status. Conservative treatment is controversial but should be considered in certain cases prior to 34 weeks gestation.114

Again, if the pregnant patient was previously receiving antiplatelet or anticoagulant therapy due to APS, the decision as to when to discontinue those treatments prior to delivery and reinitiated them afterwards is usually made by the anesthesiologist responsible for the patient. It seems that preoperative antiplatelet therapy does not increase the incidence of major or mild bleeding complications associated with the epidural anesthesia.115 Thus, treatment with low-dose ASA in women with APS could be maintained until the time of delivery or, at least, until a week earlier and reinitiated 24h afterwards.112

With regards to patients receiving LMWH during pregnancy, it is usually recommended that epidural anesthesia be programmed 10–12h after the last dose (if it was prophylactic) or at least 24h after the last dose.112

In the case the patient has not received proper preconception counseling or simply was pregnant when she came to the clinic, the recommendations mentioned above should be adjusted to the situation of the patient and her pregnancy.

Recommendation 11. The panel recommends promoting collaboration among specialties (rheumatology, obstetrics, hematology, etc.) (LE 5, GR D, LA 100%).

The primary care physician should establish direct contact with the rheumatologist in the undesired case in which the pregnancy occurs without the previous knowledge on the part of the latter. It is also recommendable that there be good coordination and communication between the rheumatologist and the obstetrician to carry out the follow-up up of the patient during the pregnancy, as well as with other specialists involved (hematologist, etc.). Aside from the personal relationship among all of the specialists mentioned, the use of the phone for consultation, teleconsultation or e-mail is of great advantage to discuss doubts or solve incidents, all of which is facilitated by the utilization of the electronic health record, which is becoming increasingly widespread.

Whenever possible, it is recommended that the possibility of introducing multidisciplinary units or preferential referral circuits and good coordination among specialties.

Recommendation 12. Having an inflammatory or autoimmune rheumatic disease does not contradict breastfeeding (LE 1, GR A, LA 100%).

For the most part, breast milk from patients with inflammatory or autoimmune diseases is not contraindicated. If the mother wants to nurse her child, care must be taken to use treatments that are not contraindicated during that period.116

On the other hand, patients must be informed during the postpartum that there is a risk of a flare of the disease activity (especially in RA), as well as a risk of thrombosis in other diseases, like SLE.117 These situations may implicate a reevaluation of the therapy.

There is little available evidence on pharmacological safety during breastfeeding (Table 6). Fortunately, not all drugs reach breast milk in significant quantities and the presence of a minimum amount of a drug does not always place the infant at risk.116

Breast milk does not usually interfere with the administration of most of the vaccines required by the mother despite the presence of maternal antibodies in the milk.118 Moreover, it has been observed that breastfeeding increases the effect of certain vaccines like those preventing pneumococcal diseases and Haemophilus influenzae type b (Hib)119 and reduces the incidence of fever after immunization.120

The administration of vaccines to the mother does not generally involve a risk for the infant despite the fact that the production of antibodies is excreted into breast milk. This includes inactivated and even attenuated vaccines since, the virus is not transmitted through breast milk. Should this occur, the concentrations would be very small and would not be associated with infections and, thus, the majority of the vaccines do not suppose a risk for the newborn. An exception are the smallpox and yellow fever vaccines, which have been involved in serious conditions in infants, such as encephalitis, and are therefore absolutely contraindicated.121,122

On the basis of the above information, any decision made during breastfeeding must be discussed with the patient.123

Recommendation 13. Once the pregnancy is over, the usual follow-up of the patient should be undertaken as soon as possible, especially if there have been factors like those mentioned above have been observed, which could indicate a poor prognosis (LE 3, GR C, LA 100%).

It is important that patients with rheumatic diseases return to follow-up as soon after delivery as possible, among other reasons because there is a considerable risk of flares at that time, especially in those patients who have had activity throughout the pregnancy, particularly during the first trimester. Other factors associated with flares are preterm delivery and a low birth weight newborn.124 The frequency of visits will depend on the situation of each patient. The patients should also undergo the usual gynecological and pediatric check-ups.

The evaluation of the disease must be individualized. It should be taken into account that in the immediate postpartum period, aside from the physical changes, patients may have elevated acute-phase reactants. Thus, in the utilization of indicators of activity it is recommendable to employ the CRP, rather than the erythrocyte sedimentation rate.68 All other tests (laboratory analyses, etc.) will be done as usual.

The possible reintroductions or changes in medication will be done depending on the patient's course. This means, for example, that an RA patient in remission whose therapy was interrupted because of the pregnancy, will not need to receive it while she is still in remission.

On the other hand, patients with APS will take LMWH as prophylaxis. If there is a history of thrombosis, therapy will consist of acenocoumarol and/or warfarin, as these drugs are safe during breastfeeding.

Finally, the panel considers that the rheumatologist should be fully involved in the follow-up, regardless of whether the patient had been followed in a high-risk unit or in the usual offices.

Recommendation 14. The newborn does not require special care unless the mother is positive for anti-Ro or anti-La antibodies, has been exposed to biological therapies during the pregnancy or the infant was born with a low birth weight (LE 2b, GR B-C, LA 91%).

Neonatal lupus is the process developed in newborns of mothers with anti-Ro and/or anti-La antibodies, as a consequence of their crossing the placenta, regardless of whether or not there is evidence of SLE, RA or underlying Sjögren's syndrome, or even in the absence of a diagnosed disease.125 Its prevalence can reach 20% and it encompasses manifestations like the skin rash, thrombocytopenia or congenital heart block (CHB). The risk of it developing is related to the antibody titer and not only to their being present.

The risk of CHB is 5% in patients with moderate-to-high titers of anti-Ro antibodies, and is nearly nonexistent with low titers.126 This risk is multiplied approximately 10-fold in the case of women who have previously had a child with neonatal lupus in any of its manifestations.127 Except for CHB, most of the signs of neonatal lupus disappear after clearance of maternal antibodies at the age of 3 to 6 months of life of the newborn. The risk of mortality associated with CHB is approximately 20%, generally due to hydrops fetalis and to myocarditis. The majority of the children who survive require a pacemaker.128

The current recommendations on the management of patients with a high risk include performing weekly fetal echocardiography between 16 and 26 weeks gestation, and every 2 weeks thereafter until week 34.

If there is evidence of progressive CHB and fetal heart failure, the decision should be made to plan the best time for delivery and finalize the pregnancy. No therapeutic option has been found to be efficient in the case of established block. Owing to the low incidence of this complication, it has not been possible to conduct randomized controlled trials.

The administration of fluorinated corticosteroids, which cross the placenta, continues to be recommended in the case of atrioventricular block, pericarditis or another form of myocardial inflammation, although the response is controversial. At the present time, the efficacy of intravenous immunoglobulin therapy has not been demonstrated.129 Recently, 2 important articles reported that the use of HCQ significantly reduces the risk of CHB in anti-Ro or anti-La-positive patients.130,131 More studies on the use of HCQ during pregnancy are needed to determine the possible “protective” effect on these patients.

Infants who have been exposed to anti-TNFα during pregnancy may have a slight increase of mild infections during the first 2 years. Vaccination with non-live vaccines should be carried out in accordance with the established calendar.132 However, due to the reported case of disseminated tuberculosis in a newborn after exposure to an anti-TNFα agent during pregnancy after having been vaccinated with Bacillus Calmette-Guérin vaccine,133 it is recommended that these infants not be vaccinated with live vaccines until they are 6 months old. It is also recommended that analyses be performed during the first weeks to check for the possible development of neutropenia.

The authors declare that no experiments were performed on humans or animals for this study.

The authors declare that no patient data appear in this article.

The authors declare that no patient data appear in this article.