Postpartum challenges in women with systemic autoimmune diseases

Introduction

The postpartum period represents a clinically challenging phase for women with systemic autoimmune diseases (SAD), yet it remains less extensively investigated than pregnancy (1, 2).

Women affected by SAD are at increased risk of postpartum disease flares, thrombotic events, infections, and treatment-related challenges (3–6). Abrupt immunological and hormonal changes occurring after delivery, together with treatment modifications during pregnancy and breastfeeding, may contribute to disease reactivation and clinical instability (7). Therefore, conditions such as SLE, antiphospholipid syndrome (APS), inflammatory arthritis (IA), and other connective tissue diseases are associated with heterogeneous but clinically relevant postpartum risks.

Current literature has predominantly focused on pregnancy-related outcomes, whereas data on the postpartum period remain fragmented, sometimes controversial, and are often derived from small cohorts or retrospective studies. As a result, postpartum management is frequently extrapolated from pregnancy recommendations, despite the distinct clinical and immunological features of this phase.

This Mini Review aims to summarize the available evidence on postpartum complications in women with SAD, with a specific focus on disease flares, thrombotic and infectious complications, and therapeutic management during breastfeeding.

Biological and clinical determinants of postpartum vulnerability

The postpartum period is characterized by immunological, hormonal, and clinical changes that may predispose women with SAD to disease reactivation and other complications. After delivery, the immunological adaptations that promote fetal tolerance during pregnancy rapidly reverse, resulting in a shift toward a more pro-inflammatory immune profile (8). This immune “rebound,” together with the abrupt decline in estrogen and progesterone levels, has been implicated in the increased risk of disease flares observed in the early postpartum phase.

This increased vulnerability appears to be most pronounced within the first 6–12 weeks after delivery, although an elevated risk of disease reactivation and maternal complications may persist for several months postpartum, depending on baseline disease activity, treatment modifications, and breastfeeding-related factors.

In addition to biological mechanisms, clinical factors play a relevant role in postpartum vulnerability. During pregnancy, immunosuppressive and immunomodulatory therapies may be modified, reduced, or temporarily discontinued because of safety concerns, and in the postpartum period, the re-initiation or escalation of treatment may be delayed by breastfeeding considerations, uncertainty regarding drug safety, or limited access to specialized care (3, 9). These factors may result in suboptimal disease control during a critical window.

Furthermore, the postpartum period is associated with an increase in thrombotic and infectious risk, which may be amplified in patients with SAD (5). Endothelial activation, coagulation changes, and residual pregnancy-related hypercoagulability persist after delivery, particularly in the presence of antiphospholipid antibodies (aPL) and/or additional cardiovascular risk factors. At the same time, immune dysregulation and immunosuppressive treatments may increase susceptibility to infections (3).

Taken together, the convergence of immunological rebound, hormonal withdrawal, and treatment-related challenges creates a clinical phase that is distinct from pregnancy and requires dedicated attention.

Postpartum disease flares

The postpartum period is associated with an increased risk of disease flares across several SAD (6, 10). The timing and severity of postpartum disease reactivation vary according to the underlying condition, disease activity before conception, and therapeutic management during and after pregnancy. Most flares occur within the first weeks to months after delivery, a timeframe that overlaps with profound immunological changes and frequent treatment adjustments.

Systemic lupus erythematosus and antiphospholipid syndrome

Women with SLE represent one of the best-studied populations among SAD with regard to postpartum outcomes. Several studies have shown that the postpartum period is associated with an increased risk of disease flares in women with SLE (4, 11). Indeed, epidemiological data indicate that approximately 35%–70% of women with SLE may experience a disease flare during pregnancy or after birth, with a substantial proportion of flares occurring after delivery (12).

Prospective studies have reported heterogeneous postpartum flare rates. Real-world cohorts indicate that approximately 20%–40% of women with SLE experience mild to moderate disease flares during the first year postpartum, even after relatively stable pregnancies (4). In contrast, data derived from highly selected populations with well controlled disease, such as those enrolled in the PROMISSE study, suggest a substantially lower frequency of low frequency of moderate-to-severe flares, underscoring the protective role of sustained disease remission across the reproductive continuum (13). Postpartum flares in SLE may involve both serological and clinical manifestations, including arthritis, cutaneous disease, and hematologic abnormalities, while severe organ-threatening flares appear less frequent than mild-to-moderate manifestations, but remain clinically relevant (11).

Importantly, disease activity before conception and during pregnancy has been identified as a major predictor of postpartum relapse (4, 11).

In addition to inflammatory flares, women with SLE are at increased risk of postpartum thrombotic complications compared with the general population (5).

In APS, postpartum morbidity is driven predominantly by thrombotic rather than inflammatory complications. The risk of venous and arterial thrombosis remains elevated during the puerperium, especially in women with prior thrombotic events or persistent aPL positivity (14).

Evidence from systematic reviews and multicenter cohorts indicates that women with primary APS or confirmed aPL positivity remain at increased risk of maternal thrombotic complications beyond delivery, particularly in the presence of high-risk aPL profiles or a history of thrombosis (15, 16).

Therefore, careful anticoagulation management beyond delivery is required, with appropriate risk stratification and individualized treatment decisions extending into the postpartum period, as highlighted by the European League Against Rheumatism (EULAR) recommendations (17, 18).

Inflammatory arthritis

Women with IA, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA), are known to experience significant disease activity fluctuations across the reproductive period (19–23). While pregnancy has traditionally been associated with clinical improvement in RA, this effect is heterogeneous and not universal, as highlighted by a systematic review and meta-analysis showing that a substantial proportion of women do not achieve disease remission during gestation (19).

In contrast, the postpartum period is consistently associated with an increased risk of disease flares in women with IA. Several prospective and observational studies have reported postpartum flare rates of approximately 30%–40% in women with RA, often following relative disease quiescence during pregnancy (19, 24). These flares predominantly involve articular manifestations and may significantly impact maternal function and quality of life during a period of increased physical and psychosocial demands.

Real-world data further support the high vulnerability of patients with IA in the postpartum period. In a prospective cohort from a tertiary referral center including women with SAD, IA showed the highest rates of postpartum disease flares (41.7%), with joint involvement representing the most frequent type of postpartum complication (6). Importantly, higher disease activity before conception and during pregnancy was associated with an increased risk of postpartum flares, reinforcing the concept that sustained disease control across during all reproductive phases is critical.

Postpartum disease reactivation in IA may be further exacerbated by treatment-related factors. Discontinuation or dose reduction of disease-modifying antirheumatic drugs (DMARDs) during pregnancy, together with delayed treatment escalation in the postpartum period due to breastfeeding concerns, may contribute to suboptimal disease control (9). Despite increasing evidence supporting the compatibility of several biologic and conventional DMARDs with breastfeeding (25), gaps in knowledge and inconsistent counseling remain common, potentially delaying appropriate therapeutic interventions.

Other systemic autoimmune diseases

Beyond SLE, APS and IA, the postpartum period represents a clinically relevant and often underrecognized phase for women affected by other SAD, including systemic sclerosis, idiopathic inflammatory myopathies, Sjögren's syndrome, undifferentiated connective tissue disease, and systemic vasculitis. Although available evidence is limited and largely derived from small cohorts or retrospective studies, postpartum disease reactivation has been reported across different disease entities (10, 26).

In systemic sclerosis, disease activity is generally considered stable during pregnancy; however, postpartum worsening of vascular manifestations, such as Raynaud's phenomenon and digital ischemia, has been described. These changes are likely related to hormonal fluctuations and alterations in vascular tone occurring after delivery (27).

Similarly, women with idiopathic inflammatory myopathies may experience postpartum flares characterized by increased muscle weakness and elevated muscle enzymes, particularly in cases where immunosuppressive therapy was reduced or discontinued during pregnancy (10, 28).

Women with primary Sjögren's syndrome and undifferentiated connective tissue disease may show a heterogeneous postpartum clinical course, ranging from mild constitutional symptoms to more pronounced systemic involvement (29, 30). In these conditions, the postpartum period may also pose diagnostic and management challenges, as symptoms such as fatigue, arthralgia, or sicca manifestations can overlap with physiological postpartum changes.

Systemic vasculitis represent a particularly challenging group, given the potential severity of disease flares in the postpartum period. Case series and observational data suggest that disease reactivation may occur shortly after delivery, especially in patients with a history of active disease before conception or in those requiring treatment de-escalation during pregnancy (31, 32). Close clinical monitoring and early reintroduction or adjustment of immunosuppressive therapy are therefore essential to reduce the risk of severe maternal complications.

Maternal complications beyond disease activity

Thrombotic and cardiovascular complications

The postpartum period is characterized by a physiological prothrombotic state, driven by persistent hypercoagulability, endothelial activation, and reduced fibrinolysis, which may persist for several weeks after delivery. In women with SAD, this intrinsic risk may be further amplified by disease-related factors, including systemic inflammation, endothelial dysfunction, and the presence of aPL (5, 8, 26).

Venous thromboembolism (VTE) represents one of the most relevant maternal complications in the postpartum period. Population-based studies have shown an increased risk of postpartum VTE in women with autoimmune diseases compared with the general obstetric population (5). This risk appears particularly pronounced in patients with SLE and APS, but may also extend to other SAD characterized by vascular involvement or chronic inflammation (14, 31).

In addition to disease-related factors, obstetric and peripartum variables may substantially contribute to thrombotic risk. Cesarean delivery, prolonged immobilization, postpartum hemorrhage, and infections may act as additional triggers in susceptible patients (33, 34). Moreover, the discontinuation or dose reduction of anticoagulant or antiplatelet therapy around the time of delivery may further increase vulnerability during the early postpartum phase (14).

The puerperium represents the period of highest thrombotic risk across the entire reproductive course. In the general obstetric population, the risk of VTE has been estimated to be up to 20–60 times higher during the first 6 weeks postpartum compared with non-pregnant women of reproductive age, with the highest incidence occurring within the first 2 weeks after delivery (33–35). In women with SAD, this baseline risk is further amplified by disease-related factors, including systemic inflammation, endothelial dysfunction, and the presence of aPL, resulting in a substantially increased absolute and relative thrombotic risk (5, 14, 26).

Population-based studies have consistently shown that autoimmune diseases are independently associated with a higher incidence of postpartum VTE compared with the general obstetric population (5).

Despite the recognized thrombotic risk, evidence specifically guiding postpartum thromboprophylaxis in women with SAD remains limited, particularly in patients without established APS but with additional risk factors (17, 25).

Accordingly, several international guidelines, including those from the American College of Obstetricians and Gynecologists (35), the Society for Maternal-Fetal Medicine (36), the Royal College of Obstetricians and Gynaecologists (37), and the American College of Chest Physicians (38), recommend risk-stratified approaches to postpartum thromboprophylaxis. These recommendations emphasize individualized assessment incorporating obstetric factors, prior thrombotic history, autoimmune disease status, and additional cardiovascular risk factors, rather than a uniform prophylactic strategy.

Beyond venous events, emerging data suggest that the postpartum period may also be associated with an increased burden of cardiovascular complications in women with SAD, potentially related to persistent inflammation, vascular dysfunction, and metabolic changes occurring after pregnancy (8, 26). This cardiovascular vulnerability may be further amplified by endothelial dysfunction and pregnancy-related vascular stress, particularly in women with pre-existing cardiovascular risk factors or severe disease phenotypes. Importantly, these complications should not be considered isolated events, but rather part of a broader spectrum of postpartum morbidity in women with SAD. The coexistence of inflammatory activity, vascular dysfunction, obstetric factors, and treatment-related issues may result in overlapping and mutually reinforcing risks during the early postpartum period. This complexity highlights the need for a comprehensive postpartum assessment that extends beyond disease activity alone and incorporates cardiovascular and thrombotic risk evaluation. This paradigm reflects a broader shift toward personalized VTE prevention as an integral component of comprehensive cardiovascular risk management during pregnancy and the postpartum period, particularly in women with SAD.

Infectious complications

The postpartum period is associated with an increased susceptibility to infections, related to factors such as physiological immune modulation and tissue trauma during delivery. In women with SAD, this vulnerability may be further enhanced by underlying immune dysregulation and by the need to resume or intensify immunosuppressive therapy after delivery (3, 8, 26).

Postpartum infections may include puerperal infections, surgical site infections following cesarean delivery, urinary tract infections, and, less commonly, severe systemic infections. Available data suggest that women with SAD experience a higher infectious burden compared with the general postpartum population, although robust disease-specific estimates are lacking (3, 26). The risk may be particularly relevant in patients exposed to glucocorticoids, conventional immunosuppressants, or biologic agents, especially when treatment escalation is required in the context of postpartum disease reactivation.

An additional challenge in the postpartum setting is the potential clinical overlap between infection and disease flare. Symptoms such as fever, fatigue, musculoskeletal pain, and elevated inflammatory markers may complicate differential diagnosis, potentially leading to delays in appropriate management. This diagnostic uncertainty is further amplified in the early postpartum period, when physiological inflammatory changes and recovery from delivery may mimic or mask pathological processes (7, 8).

Mental health and quality of life

Mental health and quality of life represent critical yet underexplored dimensions of the postpartum period in women with SAD. While postpartum psychological distress is relatively common in the general population, patients with autoimmune conditions may be particularly vulnerable due to the combined impact of chronic disease, immune-mediated inflammation, physical recovery after delivery, and the demands of newborn care (3, 8).

Postpartum depression and anxiety may be influenced by both psychosocial and biological factors. Inflammatory pathways have been implicated in the pathogenesis of mood disorders, and persistent immune activation in SAD may contribute to affective symptoms in the postpartum period (7, 8). In addition, concerns related to disease flares, medication safety during breastfeeding, and fear of long-term disease progression may further increase psychological burden (39).

Fatigue is one of the most prevalent and disabling symptoms reported by women with SAD, and distinguishing pathological fatigue related to disease activity or systemic inflammation from physiological postpartum exhaustion represents a clinical challenge. This distinction is further complicated by sleep deprivation, anemia, and the physical and emotional demands of early motherhood, which may substantially impair functional status and overall quality of life (3, 26).

Therapeutic challenges in the postpartum period

The postpartum period represents a critical therapeutic window for women with SAD, and clinical decision-making during this phase is often complex, as treatment strategies must consider the timing of therapy re-initiation, drug safety during lactation, and the heterogeneity of disease-specific risks. Despite the availability of international recommendations (17, 25), real-life management frequently requires individualized approaches.

Timing of treatment re-initiation

One of the main challenges in the postpartum management of SAD is determining the optimal timing for restarting or intensifying immunosuppressive therapy. Early postpartum re-initiation of therapy may reduce the risk of flares and prevent cumulative organ damage, especially in conditions such as SLE and IA (4, 19, 24).

However, evidence guiding the timing of treatment resumption remains limited and is largely based on observational studies and expert opinion (10, 26). In clinical practice, therapeutic decisions are often influenced by disease severity, prior flare history, breastfeeding intentions, and patient preferences.

Drug safety and breastfeeding

Breastfeeding represents an additional point to consider in postpartum therapeutic decision-making.

Importantly, infant feeding choices should ideally be discussed during the prenatal period, allowing timely selection or adjustment of maternal therapies compatible with breastfeeding. Early counseling facilitates continuity of effective treatment after delivery and may reduce unnecessary treatment interruptions during a high-risk phase for disease reactivation.

While an increasing number of antirheumatic and immunosuppressive drugs are considered compatible with lactation, misconceptions regarding drug safety often lead to unnecessary treatment discontinuation or avoidance (9, 25), potentially exposing women to an increased risk of postpartum flares (3, 26).

In women with SLE, several observational studies have shown that concerns about medication safety are among the main reasons for delayed breastfeeding initiation, early discontinuation, or complete avoidance of breastfeeding, despite the availability of compatible therapies (40–42). Lower breastfeeding rates and shorter duration have been reported in SLE women compared with the general obstetric population, highlighting the clinical impact of counseling and therapeutic decisions in the postpartum period.

Current evidence supports the use of several conventional synthetic disease-modifying antirheumatic drugs, low-dose glucocorticoids, and selected biologic agents during breastfeeding (9, 25). However, data on newer targeted therapies remain scarce, and long-term infant outcomes are insufficiently studied. As a result, clinicians may adopt overly cautious approaches, emphasizing the need for clear communication, shared decision-making, and up-to-date knowledge of available safety data.

Knowledge gaps and future directions

Despite increasing attention to postpartum outcomes in women with SAD, significant gaps remain in both clinical research and care delivery. First, most studies focus on pregnancy per se, with limited dedicated postpartum follow-up, resulting in a scarcity of prospective data on long-term maternal outcomes and standardized endpoints across disease entities.

Second, current evidence rarely incorporates patient-reported outcomes specific to the postpartum period, such as quality of life, psychological well-being, and functional status. In addition, validated instruments tailored to capture these outcomes in the context of autoimmune disease postpartum are lacking, hindering both clinical practice and research comparisons.

Third, there is a need for structured care pathways and multidisciplinary models that seamlessly integrate postpartum care into broader reproductive health services. International surveys of care delivery highlight that, even in expert centers, approaches to monitoring and treatment during and after pregnancy vary widely, and formal protocols for postpartum care are often absent or inconsistently applied (43). This organizational gap likely contributes to fragmented care and may delay therapeutic decision-making or support access.

Finally, qualitative research on patient experiences underscores that women with autoimmune diseases continue to report unmet informational and support needs related to family planning, pregnancy, lactation, and postpartum care, suggesting that evidence gaps translate into real-world challenges for affected patients (44). Addressing these gaps will require collaborative, patient-centered research agendas, innovative clinical trials with meaningful endpoints, and implementation studies designed to evaluate integrated care models across diverse healthcare settings.

The main postpartum challenges and remaining unmet needs across systemic autoimmune diseases are summarized in Table 1.

Table 1. Key postpartum challenges and unmet needs in systemic autoimmune diseases.

Discussion

The postpartum period represents a critical phase in the reproductive course of women with SAD, characterized by complex immunological and clinical changes.

Beyond the risk of disease flares, this period is characterized by a broad spectrum of maternal complications, including thrombotic events, infections, and a substantial physical and psychological burden. Available evidence suggests that postpartum morbidity is influenced not only by disease activity before and during pregnancy, but also by therapeutic adjustments, breastfeeding-related decisions, and the organization of follow-up care after delivery.

Despite growing awareness, postpartum outcomes remain insufficiently investigated. Most studies primarily focus on pregnancy, with limited postpartum follow-up and marked heterogeneity in study design, outcome measures, and disease-specific endpoints.

Moreover, gaps between clinical recommendations and real-world practice, together with fragmented postpartum care and limited multidisciplinary coordination, may contribute to delays in therapeutic decision-making and suboptimal disease control. These organizational challenges highlight the need for structured postpartum care pathways integrated into reproductive health services.

Future research should prioritize postpartum-specific follow-up, evaluating multidisciplinary care models tailored to this critical phase. Recognizing the postpartum period as an integral component of reproductive health is essential to improve long-term maternal outcomes and the quality of care for women with SAD.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Footnotes

Edited by: Klara Rosta, Medical University of Vienna, Austria

Reviewed by: Elisabeth D'Costa, Universitätsklinik für Gynäkologie und Geburtshilfe Innsbruck, Austria