First global guideline of the World Health Organization on pregnancy care in sickle cell disease: Balancing maternal equity and ethical accountability

Authors

  • Varsha Ratan GaikwadDepartment of Pharmacy, Sandip University, Nashik, India 
  • Akshay H. ShahDepartment of Pharmacology, Anand Pharmacy College, Anand, Gujarat, India

    • DOI:

    Keywords

    ethical accountability, pregnancy guidelines, sickle cell disease

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    Correspondence

    Ambika Nand Jha
    Email: nandjha99@gmail.com

    Publication history

    Received: 28 June 2025
    Accepted: 24 Sep 2025
    Published online: 30 Sep 2025

    Funding

    None

    Ethical approval

    Not applicable 

    Trial registration number

    Not applicable

    Copyright

    © The Author(s) 2025; all rights reserved. 
    Published by Bangladesh Medical University (former Bangabandhu Sheikh Mujib Medical University).
    Key messages
    The WHO’s first global guideline on sickle cell disease in pregnancy (2025) provides both clinical clarity and ethical accountability, offering a pathway toward safe, equitable, and dignified maternal care, especially in resource-limited settings. However, the challenges of turning the recommendations into actions need political will and strategic investments. 
    The June 2025 release of the World Health Organisation (WHO)’s first global guideline on managing sickle cell disease (SCD) in pregnancy marks a milestone in maternal and public health [1]. As an inherited haemoglobinopathy, SCD imposes physiological, psychological, and social burdens on women of reproductive age. Yet maternal health frameworks have long lacked clinically comprehensive and ethically grounded guidance. This new WHO guideline is not only a scientific advancement—it is an ethical imperative. SCD affects more than 7.7 million people globally, primarily in sub-Saharan Africa, the Middle East, South Asia, and the Caribbean. Improved childhood survival has led to more women with SCD reaching reproductive age, who face a four- to eleven-fold higher risk of maternal mortality compared to their peers. They are also at increased risk for severe anaemia, pre-eclampsia, thromboembolic events, infections, and adverse fetal outcomes such as growth restriction, preterm birth, and stillbirth. Existing guidance has largely been based on high-income contexts, with limited relevance to low- and middle-income countries (LMICs), where the disease burden is highest. 
     
    The WHO guideline addresses this critical gap with over 20 evidence-based recommendations tailored for resource-constrained settings. It combines clinical science with a focus on equity, improving pharmacological management: up to 5 mg of folic acid is advised in non-malaria regions, and 400 µg in areas receiving sulfadoxine-pyrimethamine. Routine iron supplementation is discouraged unless deficiency is confirmed. Prophylactic transfusions are recommended for women with severe or frequent crises, subject to careful risk-benefit evaluation.
     
    Importantly, the guideline revises the traditional recommendation to avoid hydroxycarbamide (hydroxyurea) during pregnancy. It now supports use after the first trimester under a shared decision-making model—prioritising autonomy and individualised risk-benefit dialogue [2]. Pain management, which has historically been neglected, is emphasised through personalised plans that may include paracetamol, NSAIDs, and opioids, based on gestational age and clinical history. Hospitalised patients should receive fluid balance management, prophylactic anticoagulation, and structured fetal monitoring with growth scans every four weeks from 24 to 32 weeks, and every three weeks thereafter.
     
    Delivery planning is individualised. Vaginal delivery is preferred unless medically contraindicated. The timing of delivery should balance maternal and fetal risk while centring informed maternal choice [3]. Postnatal care includes surveillance for thrombosis, newborn screening, contraception counselling, breastfeeding support, and timely re-initiation of hydroxyurea when clinically appropriate. The integration of SCD-specific services into reproductive healthcare ensures continuity throughout the life course.
     
    The guideline’s ethical foundation is as important as its clinical content. WHO explicitly calls for stigma-free, respectful, and culturally competent care. Women with SCD often face systemic bias, pain dismissal, and delayed interventions. By emphasising shared decision-making, patient dignity, and provider training, the guideline affirms reproductive justice as a core value. To support implementation, a concise Table 1 summarising the WHO 2025 guideline’s key clinical interventions, ethical principles, and system-level requirements is presented below. This framework clarifies the intersection between medical evidence, patient rights, and health system capacity, facilitating practical translation into care pathways. Nonetheless, implementation barriers persist. Many LMICs lack safe blood supplies, diagnostics, multidisciplinary teams, and routine antenatal monitoring. The WHO guideline must be viewed not only as a clinical roadmap but as a call for systemic reform. Investments in training, supply chains, and health infrastructure are essential [1].

    Categories

    Number (%)

    Sex

     

       Male

    36 (60.0)

       Female

    24 (40.0)

    Age in yearsa

    8.8 (4.2)

       Education

     

       Pre-school

    20 (33.3)

       Elementary school

    24 (40.0)

       Junior high school

    16 (26.7)

    Cancer diagnoses

     

       Acute lymphoblastic leukemia

    33 (55)

       Retinoblastoma

    5 (8.3)

       Acute myeloid leukemia

    4 (6.7)

       Non-Hodgkins lymphoma

    4 (6.7)

       Osteosarcoma

    3 (5)

       Hepatoblastoma

    2 (3.3)

       Lymphoma

    2 (3.3)

       Neuroblastoma

    2 (3.3)

       Medulloblastoma

    1 (1.7)

       Neurofibroma

    1 (1.7)

       Ovarian tumour

    1 (1.7)

       Pancreatic cancer

    1 (1.7)

       Rhabdomyosarcoma

    1 (1.7)

    aMean (standard deviation)

    Categories

    Number (%)

    Sex

     

       Male

    36 (60.0)

       Female

    24 (40.0)

    Age in yearsa

    8.8 (4.2)

    Education

     

       Pre-school

    20 (33.3)

       Elementary school

    24 (40.0)

       Junior high school

    16 (26.7)

    Cancer diagnoses

     

    Acute lymphoblastic leukemia

    33 (55)

    Retinoblastoma

    5 (8.3)

    Acute myeloid leukemia

    4 (6.7)

    Non-Hodgkins lymphoma

    4 (6.7)

    Osteosarcoma

    3 (5)

    Hepatoblastoma

    2 (3.3)

    Lymphoma

    2 (3.3)

    Neuroblastoma

    2 (3.3)

    Medulloblastoma

    1 (1.7)

    Neurofibroma

    1 (1.7)

    Ovarian tumour

    1 (1.7)

    Pancreatic cancer

    1 (1.7)

    Rhabdomyosarcoma

    1 (1.7)

    aMean (standard deviation)

    Table 1 Summarising the World Health Organization 2025 guideline’s key clinical interventions, ethical principles, and system-level requirements

    Category

    Key Factors

    Weight

    Strengths

    Strong management support, skilled workforce, compliance with legal regulations

    0.338

    Weaknesses

    Logistical complexity, inadequate segregation, financial constraints

    0.13

    Opportunities

    Industry collaboration, environmental policies, new technology

    0.094

    Threats

    Limited space, lack of coordination, high investment risk

    0.329

    Pain level

    Number (%)

    P

    Pre

    Post 1

    Post 2

    Mean (SD)a pain score

    4.7 (1.9)

    2.7 (1.6)

    0.8 (1.1)

    <0.001

    Pain categories

    		    

       No pain (0)

    -

    1 (1.7)

    31 (51.7)

    <0.001

       Mild pain (1-3)

    15 (25.0)

    43 (70.0)

    27 (45.0)

    		 

       Moderete pain (4-6)

    37 (61.7)

    15 (25.0)

    2 (3.3)

    		 

       Severe pain (7-10)

    8 (13.3)

    2 (3.3)

    -

    		 

    aPain scores according to the visual analogue scale ranging from 0 to 10; SD indicates standard deviation

    Clinical focus area

    Key WHO recommendations

    Public health and ethical rationale

    Antenatal pharmacological care

    • Daily folic acid: 5 mg (non-malaria zones); 400 µg with  sulfadoxine–pyrimethamine 
    • Iron only if deficiency documented 
    • Prophylactic transfusion for women with prior severe crises

    • Prevents adverse effects of excess folate 
    • Preserves antimalarial efficacy 
    • Minimizes crisis recurrence while balancing transfusion risks

    Hydroxycarbamide use

    • May continue/reinitiate after first trimester 
    • Shared decision-making approach

    • Promotes autonomy and individualized care 
    • Moves beyond outdated blanket contraindications

    Pain management strategy

    • Individualized pain plans 
    • Paracetamol, NSAIDs, opioids as per gestational stage/history

    • Counters undertreatment of SCD pain 
    • Respects patient preferences, reduces stigma, avoids misuse

    Inpatient management protocols

    • Careful fluid monitoring 
    • Thromboprophylaxis unless contraindicated 
    • Serial fetal scans: 24 wks (4-weekly to 32 wks), then 3-weekly

    • Prevents pulmonary edema 
    • Reduces thromboembolic risk 
    • Enables early detection of fetal growth restriction

    Labour and delivery planning

    • Vaginal birth preferred unless contraindicated 
    • Birth timing based on maternal–fetal risk and maternal preference

    • Reduces unnecessary cesarean sections 
    • Promotes safe, dignified, patient-centered delivery

    Postnatal and interpregnancy care

    • Monitor thrombotic complications 
    • Newborn SCD screening 
    • Breastfeeding support, contraception, early hydroxyurea reintegration

    • Ensures maternal–newborn continuity of care 
    • Supports safe reproductive planning 
    • Promotes long-term disease control and parenting goals

    Health system strengthening

    • Invest in diagnostics, safe blood access, multidisciplinary teams, antenatal infrastructure

    • Addresses systemic inequities 
    • Calls for sustainable policy action in LMICs

    Global health equity and research inclusion

    • Frame SCD in pregnancy as maternal equity issue 
    • Include pregnant/lactating women in SCD trials

    • Corrects historical research exclusion 
    • Advances reproductive justice and global accountability

    This guideline also marks a paradigm shift. As the first in WHO’s forthcoming series on noncommunicable diseases (NCDs) during pregnancy, it recognises chronic illness—long overlooked—as a significant contributor to maternal mortality [4, 5]. Future guidance on diabetes, cardiovascular disease, mental health, and respiratory conditions should adopt this equity-focused model.
     
    Finally, it closes a long-standing ethical gap: excluding pregnant and lactating women with SCD from clinical trials. Their inclusion in future therapeutic studies is vital for ensuring safe, effective, and fair care.
     
    In conclusion, WHO’s guideline on SCD in pregnancy is more than just a clinical protocol; it is a transformative blueprint for maternal health equity. Rooted in autonomy, dignity, and inclusion, it sets a new global standard. The challenge now is to turn these recommendations into action, particularly in high-burden settings. With political will and strategic investment, it can become a cornerstone of safe and equitable motherhood for women living with SCD.
    Acknowledgements
    None
    Author contributions
    Manuscript drafting and revising it critically: ANJ, VRG, AHS. Approval of the final version of the manuscript: ANJ, VRG, AHS. Guarantor of accuracy and integrity of the work: ANJ, VRG, AHS.
    Conflict of interest
    We do not have any conflict of interest.
    Data availability statement
    Not applicable
    Supplementary file
    None
      References
      1. World Health Organization. WHO issues first global guideline to improve pregnancy care for women with sickle cell disease ;Geneva: World Health Organization; 2025 Jun 19. Available from: https://www.who.int/news/item/19-06-2025-who-issues-first-global-guideline-to-improve-pregnancy-care-for-women-with-sickle-cell-disease [Accessed on 28 Sep 2025]
      2. GBD 2021 Sickle cell disease collaborators. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: A systematic analysis from the Global Burden of Disease Study 2021. Lancet Haematol. 2023 Aug;10(8):e585-e599. doi: https://doi.org/10.1016/S2352-3026(23)00118-7
      3. WHO recommendations on the management of sickle-cell disease during pregnancy, childbirth and the interpregnancy period. Geneva: World Health Organization; 2025. Available from: https://www.who.int/publications/i/item/9789240109124 [Accessed on 28 Sep 2025]
      4. Centers for Disease Control and Prevention (CDC). Women with sickle cell disease and prenatal care; Atlanta (GA): CDC; 2024 Jun 4. Available from: https://www.cdc.gov/sickle-cell/communication-resources/women-with-sickle-cell-disease-and-prenatal-care.html [Accessed on 28 Sep 2025]
      5. Inácio P. Women with SCD at higher risk of complications during pregnancy ;Sickle Cell Anemia News. 2025 Mar 6. Available from: https://sicklecellanemianews.com/news/women-scd-higher-risk-pregnancy-complications-study/ [Accessed on 28 Sep 2025]