Atopic dermatitis is a relapsing inflammatory dermatosis characterized by epidermal barrier dysfunction, pruritus, type 2 immune activation and impaired quality of life. Pregnancy-associated immunological and hormonal changes may aggravate pre-existing disease or precipitate new eczematous manifestations. Poor control may lead to sleep disturbance, excoriation, secondary infection, psychological distress and substantial treatment burden. Effective maternal disease control is therefore important, but therapeutic choices are complicated by placental exposure, pregnancy-related pharmacokinetic changes and the lack of randomized studies in pregnant populations [1–3]. Standard AD treatment guidance for the general adult population cannot be transferred uncritically to pregnancy. Treatments with strong efficacy outside pregnancy, including methotrexate, mycophenolate mofetil and oral Janus kinase inhibitors, may be unacceptable during gestation. Conversely, large pregnancy pharmacoepidemiological datasets support commonly used topical corticosteroids, although the underlying evidence is not limited to women with AD. Newer biologics have expanded therapeutic possibilities, but evidence remains limited and inconsistent across molecules and trimesters of exposure [2–6]. This review examines the comparative therapeutic usefulness and maternal-fetal safety of available treatment modalities, distinguishes direct AD pregnancy evidence from broader pregnancy datasets, and identifies uncertainties relevant to prescribing and shared decision-making. 2. Objectives The primary objective was to compare reported maternal and fetal outcomes among pregnant patients exposed to therapies used for AD. Secondary objectives were to summarize treatment effectiveness during pregnancy, compare evidence across major treatment classes, examine trimester and dose considerations, and identify research gaps associated with targeted agents.

3.1 Review design and eligibility This systematic review considered original human studies evaluating treatment of AD during pregnancy. Eligible evidence included pregnancy cohorts, case series and pregnancy-exposure reports addressing barrier care, topical anti-inflammatory therapy, phototherapy, conventional systemic treatment or targeted biologic therapy. Systematic reviews, expert consensus documents and clinical guidelines were consulted for contextual interpretation but were not counted as independent primary studies. 3.2 Search strategy and information sources Search concepts combined terms related to “atopic dermatitis”, “atopic eczema”, “pregnancy”, “pregnant”, “topical corticosteroids”, “tacrolimus”, “pimecrolimus”, “narrowband UVB”, “cyclosporine”, “azathioprine”, “dupilumab”, “tralokinumab”, “lebrikizumab”, “JAK inhibitors”, “birth outcomes” and “congenital malformations”. Bibliographic information was cross-checked using PubMed/MEDLINE-indexed records, publisher full-text sources and references of contemporary guidelines. Publications available through 30 June 2026 were considered. 3.3 Data extraction and synthesis Extracted items included study design, exposure definition, sample size, comparator, eczema outcomes, pregnancy end points and numerical effect estimates. Adjusted estimates were preferred for comparative cohorts. Case reports and case series were interpreted as signal-detection evidence rather than absolute risk estimates. Because treatment exposures, comparators and outcome definitions varied markedly across studies, a narrative synthesis was undertaken. 3.4 Assessment of validity and certainty Potential threats to validity were considered according to observational-study principles, including confounding by indication, disease severity, selection of completed pregnancies, exposure misclassification, differential outcome ascertainment and overlap among published cases. Certainty was assessed qualitatively in light of sample size, directness, precision and consistency.

4.1 Study selection A total of 872 records were identified through database searching, and no additional records were identified through registers. After removal of 176 duplicate records and 11 records removed for other reasons, 685 records remained for title and abstract screening. Of these, 603 records were excluded and 82 reports were sought for retrieval. Thirteen reports were not retrieved; therefore, 69 full-text reports were assessed for eligibility. Following full-text assessment, 61 reports were excluded for the following reasons: review articles or meta-analyses (n = 14), conference abstracts or case reports (n = 10), insufficient pregnancy-specific treatment or safety data (n = 12), mixed or non-AD populations (n = 9), overlapping cohorts (n = 8), and non-English or inaccessible full texts (n = 8). Finally, 8 studies, represented by 8 reports, were included in the qualitative synthesis (Figure 1). 4.2 Characteristics of the evidence The evidence base was highly asymmetric. Large population-based pregnancy cohorts were available for topical corticosteroids, whereas most direct AD-specific pregnancy evidence for novel systemic agents consisted of case series, case reports and registry-based observational studies. The largest assessed dupilumab propensity-matched cohort included pregnant patients with several type 2 inflammatory diagnoses rather than exclusively AD [4,7]. Table 1 summarizes the principal numerical findings from identifiable pregnancy-exposure studies. Study / design Exposure and comparator Key numerical findings Interpretive consideration Andersson et al., 2021; nationwide matched cohort [4] 60,497 topical corticosteroid exposed; 241,986 matched unexposed SGA 9.4% vs 9.4%; RR 1.00 (95% CI 0.98–1.03) Strong pregnancy safety data; dermatologic indications mixed Preuß et al., 2025; propensity-matched EHR cohort [7] 293 dupilumab exposed vs 293 matched controls Any adverse pregnancy outcome HR 0.53 (95% CI 0.33–0.84); premature obstetric labour HR 0.11 (0.03–0.45) Type 2 inflammatory conditions, not solely AD; residual confounding Chopra et al., 2025; review of exposure reports [8] 68 women; 69 dupilumab-exposed pregnancies 58 live births; 11 spontaneous abortions; 0 congenital defects reported Secondary synthesis with overlapping and selectively reported cases Sánchez-García et al., 2025; meta-analysis [9] 15 observational studies; 115 pregnant women Mean reported dupilumab exposure 27.52 weeks; 58/73 live births in reporting subset Secondary synthesis; heterogeneous follow-up and outcomes 4.3 Emollients, barrier care and non-pharmacological treatment Regular emollient use is recommended for all pregnant patients with AD and can reduce xerosis, itch and dependence on anti-inflammatory medication. Bland products with minimal fragrance and irritants are preferred. Wet-wrap therapy may improve short-term control during severe flares, but caution is required because occlusion can increase topical drug penetration and infection risk. These approaches are best regarded as baseline care rather than alternatives to anti-inflammatory treatment when disease is active [2,3]. 4.4 Topical corticosteroids Topical corticosteroids remain the most extensively studied anti-inflammatory treatment for AD during pregnancy. Appropriate potency should be selected according to site and severity, while prolonged extensive use of very potent agents should be avoided. In a nationwide Danish cohort of 1,052,975 eligible singleton live-birth pregnancies, 60,497 topical corticosteroid-exposed pregnancies were propensity matched to 241,986 unexposed pregnancies. Small-for-gestational-age infants occurred in 9.4% of both groups (RR 1.00, 95% CI 0.98–1.03), providing reassuring evidence against a major increase in fetal growth restriction under observed prescribing patterns [4]. These data provide robust reassurance regarding fetal growth outcomes, although filled prescriptions may not fully represent actual drug use and the underlying population included dermatologic conditions beyond AD. When clinically needed, topical corticosteroids should not be withheld solely because of pregnancy, but the lowest effective regimen compatible with disease control remains preferable [2–4]. 4.5 Topical calcineurin inhibitors Topical tacrolimus and pimecrolimus offer steroid-sparing treatment for sensitive sites such as the face and intertriginous regions. Their systemic absorption is usually low when used on limited areas, and pregnancy guidance permits conditional use for localized resistant lesions. However, large AD-specific prospective fetal-outcome studies are lacking, and their safety profile cannot be inferred directly from systemic tacrolimus use in transplant recipients, whose pharmacokinetics and comorbidities differ substantially [2,3]. 4.6 Phototherapy Narrow-band ultraviolet B (NB-UVB) is the preferred non-systemic escalation option when topical therapy is inadequate, particularly in patients with extensive disease. It does not directly expose the fetus to ionizing radiation and is regarded as compatible with pregnancy in contemporary guidance. Folate monitoring should be considered during repeated courses, and facial shielding may help limit melasma. Psoralen plus UVA (PUVA), because it involves systemic psoralen exposure, should be avoided during pregnancy [2,3]. 4.7 Cyclosporine and other conventional systemic agents Cyclosporine is the most consistently supported conventional systemic option for severe, refractory AD in pregnancy, particularly after failure of optimized topical therapy and, where feasible, phototherapy. Most pregnancy experience derives from transplant recipients rather than AD-specific cohorts, but existing evidence does not indicate a major teratogenic signal. Hypertension, renal dysfunction and prematurity remain important monitoring concerns, and blood pressure, renal function and maternal clinical status should be assessed jointly by dermatology and obstetric teams [2,3,10]. Azathioprine may be considered selectively, especially when effective treatment had been established before conception, but direct evidence for initiation in AD during pregnancy is limited. Short systemic corticosteroid courses may occasionally be used as rescue treatment; however, prolonged use is discouraged because maternal metabolic, infectious and hypertensive complications may outweigh short-term benefit. Methotrexate and mycophenolate mofetil are contraindicated in pregnancy [2,3,10]. 4.8 Dupilumab and emerging biologics Dupilumab blocks the shared IL-4/IL-13 receptor signalling pathway and is highly effective in non-pregnant moderate-to-severe AD, but pregnancy-specific evidence remains observational. In a 2025 propensity-matched electronic health record study, 293 dupilumab-exposed pregnancies were matched to 293 controls with type 2 inflammatory conditions, and no increase in adverse pregnancy outcomes was observed (HR 0.53, 95% CI 0.33–0.84) [7]. This apparent reduction should not be interpreted as a protective pharmacologic effect because residual confounding and disease heterogeneity remain plausible explanations. Earlier syntheses reported 58 live births and 11 spontaneous abortions among 69 dupilumab-exposed pregnancies, with no congenital defects observed among reported births [8]. A broader synthesis included 115 pregnant women across 15 observational studies [9]. These reports may contain overlapping cases and cannot be summed as unique exposures. Current evidence is encouraging but insufficient for routine initiation of dupilumab during pregnancy, and data remain very limited for newer biologics such as tralokinumab, lebrikizumab and nemolizumab [2,3,11,12]. 4.9 Janus kinase inhibitors and contraindicated treatments Oral JAK inhibitors used for AD, including upadacitinib, abrocitinib and baricitinib, should not be used during pregnancy. Reproductive risk and limited human data likewise preclude use of methotrexate and mycophenolate mofetil. Treatment planning before conception is therefore essential for women of childbearing age who are receiving or considering these agents [2,3]. Table 2 provides a comparative clinical interpretation of the available treatment options. Treatment Expected AD benefit Pregnancy evidence Practice implication Emollients / barrier care Essential background symptom control High clinical familiarity; minimal systemic exposure Recommended for all severities Topical corticosteroids Effective for inflammatory flares Large matched obstetric safety cohort Preferred anti-inflammatory first line Topical calcineurin inhibitors Useful steroid-sparing localized control Indirect and limited direct pregnancy data Conditional use for sensitive areas NB-UVB phototherapy Useful for extensive uncontrolled AD Fetal exposure considered negligible; pregnancy AD trials sparse Reasonable second-line escalation Cyclosporine Systemic control of severe refractory disease Mainly indirect pregnancy observational evidence Specialist option with BP/renal monitoring Azathioprine Selected systemic maintenance Indirect pregnancy evidence; sparse AD-specific studies Consider continuation case by case Short oral corticosteroid course Rapid temporary flare suppression Maternal metabolic and obstetric concerns Avoid routine use; rescue only Dupilumab High efficacy outside pregnancy Emerging observational pregnancy cohorts Individualized specialist assessment Other biologics Effective for some non-pregnant patients Very limited pregnancy exposure data Not routinely recommended JAK inhibitors / methotrexate / mycophenolate May be highly efficacious outside pregnancy Reproductive risk or insufficient safe exposure evidence Avoid or contraindicated during pregnancy 4.10 Maternal and fetal outcome dimensions Maternal outcomes of interest include pruritus control, sleep, infection, depressive symptoms and drug toxicity, along with pregnancy-specific complications such as hypertension, gestational diabetes and preeclampsia. Fetal outcomes require differentiation between miscarriage, structural malformation, fetal growth restriction, prematurity and neonatal outcomes. Small observational series, particularly for biologics, are useful for signal detection but cannot exclude uncommon risks. The timing of exposure is important because transplacental transfer of IgG-based biologics increases later in gestation [7–9,11].

A practical evidence hierarchy emerges from the available literature. Emollients and topical corticosteroids are the best-supported first-line options; topical calcineurin inhibitors and NB-UVB provide steroid-sparing or non-systemic escalation; cyclosporine can be considered for severe uncontrolled disease under specialist monitoring; and biologic evidence, although encouraging, remains limited and insufficient for routine use. This hierarchy reflects the balance of disease control and maternal-fetal safety as supported by current evidence, rather than a direct head-to-head comparison of efficacy among pregnant patients. The large matched cohort evaluating topical corticosteroid exposure is especially informative because it provides robust pregnancy safety data. For dupilumab, emerging comparative evidence is clinically important, but disease-indication heterogeneity and residual confounding remain key concerns. A hazard ratio below one for adverse pregnancy outcomes should not be misinterpreted as proof of protective treatment effect. Clinical decisions should instead weigh the harms of uncontrolled maternal disease against treatment-related uncertainties and should incorporate gestational age, disease severity, prior treatment response, comorbidities and follow-up feasibility. 5.1 Methodological limitations The primary evidence remains largely nonrandomized. AD-only pregnancy cohorts are scarce for several therapies, efficacy is not consistently quantified using standardized scores, and observational datasets may miss medication adherence, spontaneous pregnancy losses or long-term neonatal outcomes. Case reports preferentially capture unusual or favorable exposures, and secondary reviews of dupilumab may include overlapping pregnancies. These limitations preclude a defensible cross-treatment quantitative ranking. 5.2 Research priorities Prospective registries should record indication-specific severity scores, trimester and cumulative exposure, co-therapies, baseline obstetric risk, miscarriage, fetal growth, preterm birth, neonatal infection and longer-term developmental outcomes. Newer biologics require independently replicated comparator studies, and severe AD systemic treatment requires pragmatic evaluation against the risks of uncontrolled disease. Standardized follow-up would substantially improve confidence in treatment-related safety estimates.

In pregnancy-associated atopic dermatitis, foundational barrier care and appropriately used topical corticosteroids provide the most defensible balance of effectiveness and established fetal safety evidence. Topical calcineurin inhibitors and NB-UVB are useful escalation approaches, and cyclosporine remains the most acceptable systemic option for severe treatment-resistant disease when careful maternal monitoring is feasible. Dupilumab observational cohorts have not identified a clear excess of major adverse outcomes, but currently available evidence is not sufficient to establish definitive safety or justify routine initiation during pregnancy. Systemic JAK inhibitors, methotrexate and mycophenolate mofetil should be avoided. Multidisciplinary, individualized treatment remains essential.

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