Inconsistent medication recommendations for immune-mediated inflammatory diseases across pregnancy, lactation, and...

Immune-mediated inflammatory diseases (IMIDs) often affect women of childbearing age. Since active inflammatory disease is related with impaired reproductive outcomes, effective disease control is crucial. Clinical guidelines aim to support evidence-based shared decision-making. However, inconsistencies between guidelines across specialties may cause confusion, undermine adherence and lead to adverse health outcomes. This study aimed to assess consistency within and across perinatal IMID guidelines in gastroenterology, rheumatology and dermatology regarding medication use during pregnancy, lactation and among prospective fathers, and to identify medications with insufficient safety data.

A review was conducted in August 2025 using most recent versions of leading international guidelines (N = 11), published between 2015 and 2025. Guideline recommendations for IMID medications were categorized by two independent authors. Data-analysis examined the prevalence and type of consistency, trimester-specific consistency, most common recommendation per medication and the agreement on preconception discontinuation timing.

Within medical specialties, guideline consistency for individual medications was highest for gastroenterology (61/74, 82.4%), followed by rheumatology (165/220, 75.0%) and dermatology (57/94, 60.6%). Across specialties, agreement was greatest between gastroenterology and rheumatology (pregnancy 86.2%, lactation 81.2%, paternal 88.5%) and lowest between gastroenterology and dermatology (pregnancy 51.3%, lactation 40.6%, paternal 47.1%). Trimester-specific recommendations were consistent across guidelines in 33.3% (2/6) of the cases. Agreement on preconception discontinuation timing was 41.7% (5/12) for maternal cases and 66.7% (2/3) for paternal exposure. At least one inconsistency was found in 75.0% of within-guideline and 87.5% of across-guideline comparisons. At medication-class level, most inconsistencies stemmed from insufficient safety data reporting (59.5%), particularly for small molecules (28.6%), immunomodulators (26.1%) and interleukin inhibitors (34.1%).

Inconsistencies between guidelines, both within and across specialties, were frequent and pose challenges for reproductive decision-making in IMID patients. The lack of safety data in reproductive contexts contributed to guideline inconsistencies and revealed the need to prioritize future research on recently marketed pharmacotherapeutic classes, such as small molecules (JAK-inhibitors, PDE4-modulators) and interleukin inhibitors. In the future, guidelines should be updated regularly, include explicit recommendations, integrate reproductive contexts, and adopt unambiguous language, standardized categories and uniform methodological frameworks.