GRAPHICAL ABSTRACT

INTRODUCTION

Although timely blood transfusion can substantially reduce hemorrhage-related mortality in settings with increased institutional deliveries [1], obstetric hemorrhage continues to be a primary contributor to maternal mortality globally [2]. While transfusion is a critical component of hemorrhage management, its widespread use has raised concerns regarding overuse, complications associated with allogeneic blood, and constraints related to blood supply. These concerns have driven increasing attention toward patient blood management (PBM), a multimodal strategy that encompasses optimization of hemoglobin (Hb) levels, pharmacologic and surgical techniques to minimize blood loss, and the use of alternatives to allogeneic transfusion. PBM has been shown to reduce unnecessary transfusions and improve clinical outcomes and is increasingly being adopted as a standard component of obstetric care in several countries [3–5].

Jehovah’s Witnesses (JW), who categorically refuse blood transfusions on religious grounds, can serve as an exemplary clinical model for evaluating the effectiveness of PBM in obstetric care. Pregnancies in JW women have traditionally been considered high risk for obstetric hemorrhage, not because of underlying physiological factors, but because transfusion refusal substantially limits therapeutic options in the event of massive bleeding [6,7]. Globally, the JW community comprises approximately 8.7 million to 9.0 million members, accounting for about 0.2% of the world’s population [8], including an estimated 100 000 individuals in Korea [9]. Based on national demographic data, the number of JW deliveries can be broadly estimated at several hundred per year, although official statistics are unavailable, and these estimates do not account for age distribution or fertility patterns within the JW population. Nevertheless, these figures suggest that JW women represent a small but consistently present subgroup within obstetric practice. In real-world clinical settings, however, JW women may experience limited access to appropriate obstetric care or even denial of services due to concerns regarding transfusion refusal and the relative rarity of this patient population. These challenges are particularly consequential during obstetric emergencies, in which refusal of transfusion can markedly increase the risk of maternal death due to hemorrhage. Previous studies conducted in the United States and the Netherlands in the early 2000s reported that women who refused transfusion faced a 44-fold to 130-fold increased risk of maternal death, primarily attributable to obstetric hemorrhage [6,10]. These findings highlighted the clinical vulnerability of this population and emphasized the importance of multidisciplinary planning involving senior clinicians [3,4].

With the development and implementation of PBM strategies, increasing evidence suggests that safe obstetric care for JW women is achievable [7,11]. Nevertheless, large-scale data examining obstetric outcomes in JW women managed under structured PBM protocols remain limited, particularly within Asian populations. Many previous studies have been confined to small case series or comparisons with national demographic data, thereby providing limited insight into institution-level outcomes. Accordingly, the objective of this study was to evaluate obstetric outcomes, particularly hemorrhagic-related morbidity, in JW women compared to matched non-JW women at a single center with an established PBM program. This approach positions JW women not only as a clinically high-risk group but also as a representative population for assessing the effectiveness of PBM strategies in contemporary obstetric care.

METHODS

Study Population

This was a retrospective matched cohort study. We reviewed the electronic medical records of consecutive JW and non-JW women with singleton pregnancies who delivered between January 2018 and December 2023 at Soonchunhyang University Seoul Hospital, a single PBM-based, transfusion-free center for JW patients. At the initial antenatal visit or prior to delivery, JW patients completed informed consent documentation explicitly indicating refusal of blood transfusion and specifying acceptable blood products or alternatives. This information was systematically recorded in the hospital’s electronic medical record system. During the 6-year study period, a total of 2492 deliveries were recorded, of which 222 (8.9%) were identified as JW. Women with multiple gestations (i.e., twin or higher-order pregnancies), gestational age <23+0 weeks, or therapeutic termination were excluded. Specifically, 49 cases of multiple gestations and 47 cases with gestational age <23+0 weeks or therapeutic termination were excluded. After these exclusions, 205 JW women remained eligible and were included without restriction for baseline obstetric risk. For comparison, non-JW women were selected at a 1:3 ratio using propensity score matching (PSM) based on obstetric hemorrhagic risk factors, including maternal age, gestational age at delivery, parity, mode of delivery, previous uterine operation, complex placental disorder, hypertensive disorder, and diabetes mellitus during pregnancy [12–14].

At our institution, standardized PBM protocols are applied to all pregnant women, irrespective of religious status, by attending physicians trained in transfusion-free management. These protocols include routine measurement of complete blood count and serum ferritin levels preconceptionally and during the first and second trimesters, with intravenous (IV) iron administered after the second trimester in cases of unresolved iron deficiency anemia (Supplemental Material 1). Intraoperative management protocols involve routine use of uterotonics, early administration of tranexamic acid, uterine tamponade, and interventional radiology, together with access to blood alternatives such as fibrinogen concentrate and prothrombin complex. Cell salvage was made available for selected high-risk patients.

Variables and Outcomes

The exposure variable was the maternal group, defined as JW or non-JW women (control group).

The primary outcomes were obstetric morbidities related to postpartum hemorrhage and the PBM strategies used to manage it. These outcomes included severe postpartum anemia, uterine atony, blood loss ≥1000 mL at cesarean section, placental abruption, retained placenta, postpartum wound infection, and maternal death. Severe postpartum anemia was defined as the lowest Hb level <7.0 g/dL during the hospital stay after delivery. Uterine atony was defined by the presence of the diagnostic code “uterine atony during labor (International Classification of Diseases, 10th revision [ICD-10] code O62.2)” or “postpartum hemorrhage due to uterine atony (ICD-10 codes O72.0 or O72.1)” recorded during the delivery hospitalization. The amount of blood loss was recorded only for cesarean deliveries; therefore, analyses of blood loss in this study were limited to cesarean section cases. Other obstetric outcomes included rates of emergency cesarean section and preterm birth (delivery before 37 completed weeks of gestation), length of hospital stay, neonatal outcomes (gender, birth weight, Apgar score, and intrauterine fetal death), Hb levels during pregnancy and postpartum (day 1 and 3 after delivery), and IV iron administration during antenatal and postnatal periods. A high-risk subgroup, defined as patients requiring blood transfusion or blood substitutes, included cases of uterine atony, severe postpartum anemia, complex placental disorders, placental abruption, and hemolysis/elevated liver enzymes/low platelet count (HELLP) syndrome [2]. Hemorrhage management within this subgroup was analyzed, including IV iron administration, blood transfusion, uterine artery embolization, and cesarean hysterectomy.

The covariates included maternal age, pre-pregnancy body mass index (BMI), parity, gestational age at delivery, mode of delivery, previous uterine operation, complex placental disorders, hypertensive disorders, and diabetes mellitus. Hypertensive disorders included gestational hypertension, preeclampsia diagnosed at >20 weeks of gestation, and chronic hypertension. Diabetes mellitus included gestational diabetes mellitus diagnosed at >20 weeks of gestation and pregestational diabetes. Complex placental disorders included placenta accreta spectrum, placenta previa, and low-lying placenta. Previous uterine operations included cesarean section and myomectomy.

Statistical Analysis

PSM was performed at a 1:3 ratio (JW: non-JW) using a greedy nearest-neighbor algorithm with a 0.1 standard deviations caliper to minimize selection bias. Matching variables included maternal age, gestational age at delivery, parity, previous uterine surgery, complex placental disorders, hypertensive disorders, and diabetes mellitus. Covariate balance was assessed using absolute standardized differences.

Categorical variables were expressed as counts (%) and compared using the chi-square or Fisher exact test, with rare outcomes (e.g., severe anemia, placental disorders, hemolysis/elevated liver enzymes/low platelet count syndrome) primarily analyzed using the Fisher exact test. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported, with the Haldane–Anscombe correction applied when zero cell counts occurred. Continuous variables were summarized as medians with interquartile ranges (IQRs) and compared using the Mann–Whitney U-test. A p-value <0.05 was considered statistically significant. All analyses were performed using R version 4.2.3 (R Foundation for Statistical Computing, Vienna, Austria) and Rex-Pro version 3.6.3 (RexSoft Inc., Seoul, Korea).

Ethics Statement

This study was approved by the Institutional Review Board (IRB) of Soonchunhyang University Seoul Hospital (IRB approval No. 2025-01-009). Electronic medical records were accessed for research purposes between February 6, 2025, and February 10, 2025, following IRB approval. The requirement for informed consent was waived by the IRB due to the retrospective nature of the study and the use of de-identified data. All methods were conducted in accordance with relevant guidelines and regulations, including the Declaration of Helsinki.

RESULTS

Clinical and Obstetric Characteristics

After 1:3 PSM, 601 (26.4%) of 2270 non-JW women were matched to 205 JW women (Figure 1). Baseline characteristics were well balanced between the 2 groups (Supplemental Material 2). Table 1 summarizes the clinical and obstetric characteristics of the matched cohorts. The median maternal age was 34 years in both groups (JW: 34 [30–38] vs. non-JW: 34 [31–36] years). Hypertensive disorders occurred in 6.7% of pregnancies, and diabetes mellitus occurred in 4.2%, with no significant differences between groups. JW women had a significantly lower pre-pregnancy BMI than non-JW women (20.4 [18.5–23.2] vs. 21.1 [19.4–23.5], p=0.004).

Regarding Hb and IV iron use (Table 2), JW women had significantly higher first-trimester Hb levels than non-JW women (12.6±1.1 vs. 11.8±3.4 g/dL, p=0.012). Hb levels in both groups remained stable throughout pregnancy, with no significant declines or intergroup differences during the second and third trimesters. Antepartum IV iron was administered more frequently in JW women (7.3 vs. 2.8%, p=0.008). Postpartum IV iron use was comparable between groups (11.8 vs. 13.2%, p=0.697). Antepartum supplementation primarily consisted of ferric carboxymaltose (500 mg/dose), whereas postpartum therapy typically involved iron sucrose (200 mg administered in 1 to 2 doses).

Obstetric Outcomes

Gestational age at delivery, rates of preterm birth, cesarean delivery (elective and emergency), length of hospitalization, and obstetric complications, including placental abruption, retained placenta, postpartum wound infection, and maternal death, did not differ significantly between the groups (Table 3). Median blood loss during cesarean section was greater in non-JW women than in JW women (500 [400–600] vs. 500 [300–500] mL, p=0.010). Rates of blood loss ≥1000 mL at cesarean section (3.0 vs. 8.6%, p=0.072) and severe postpartum anemia (Hb <7 g/dL) (0.5 vs. 1.5%, p=0.466) were lower in JW women; however, these differences did not reach statistical significance. Neonatal outcomes, including birth weight, gender, Apgar scores, and intrauterine fetal death, were similar between groups.

Hemorrhage Management in the High-risk Subgroup

The incidence of high-risk cases requiring blood transfusion or blood substitutes was 10.2% (21/205) in JW women and 11.1% (67/601) in non-JW women (p=0.796) (Table 4). Uterine atony was the most frequent cause of hemorrhage in both groups. Severe postpartum anemia was observed in 1 JW woman (0.5%) and 9 non-JW women (1.5%); although the risk appeared lower in JW women, this difference did not reach statistical significance (OR, 0.32; 95% CI, 0.01 to 2.35; p=0.466), likely reflecting the limited number of events. Management strategies for high-risk cases in non-JW women included blood transfusion (n=7, 10.4%), uterine artery embolization (n=2), cesarean hysterectomy (n=1), and IV iron therapy (n=23, 34.3%). Among JW women, 8 (38.1%) received IV iron therapy alone. Cell salvage was prepared for selected JW patients [15] but was not used. Despite the absence of transfusion in JW women, rates of severe postpartum anemia, length of hospital stay, and obstetric complications were comparable to those observed in non-JW women. However, statistical power was limited by the small sample size of high-risk cases; thus, these findings should be interpreted with caution.

DISCUSSION

This study shows that the use of PBM strategies in obstetric care does not appear to increase the risk of hemorrhagic morbidity in JW women under general clinical circumstances when compared with non-JW women. Among non-JW women considered high-risk for transfusion, 10.4% (7/67) required transfusion, accounting for 1.2% (7/601) of all non-JW women; this proportion is consistent with a recent finding (1.8%) reported from Korea [16]. In contrast, 10.2% (21/205) of JW women with similar high-risk conditions were successfully managed without transfusion, with no cases requiring intensive care or resulting in severe adverse maternal morbidity. Collectively, these findings suggest that structured PBM protocols may enable safe obstetric care even in women who categorically refuse blood transfusion.

Previous studies have examined obstetric outcomes in JW women with mixed findings. Earlier investigations reported higher maternal mortality and hemorrhagic morbidity among JW women compared with non-JW women, emphasizing the need for heightened caution [6,10,17]. In contrast, more recent studies have suggested that with broader acceptance of certain blood alternatives [11,18] and when deliveries are managed by experienced clinicians, mortality and morbidity are not significantly higher in JW women than in non-JW women [7,11]. Our findings are consistent with these later reports, demonstrating no significant differences in hemorrhage-related morbidity between groups. Maternal mortality could not be evaluated as a primary outcome in the present study, given Korea’s very low maternal mortality rate and the limited sample size (<1000 cases). However, a key strength of this study lies in its large, propensity score–matched cohort managed by a single obstetric team under a structured PBM protocol. To our knowledge, this is the first large-scale matched cohort study in an Asian population focusing specifically on hemorrhage-related morbidity and transfusion-restricted obstetric management. The study design also provided an indirect framework for evaluating PBM effectiveness, as JW women—who categorically refused transfusion—were necessarily managed under mandatory transfusion-free PBM protocols, whereas non-JW women received PBM-based care with transfusion available as an option.

As shown in Table 2 and Table 4, group-level differences in PBM-related practices were observed, including antenatal hemoglobin optimization, IV iron use, and first-line management strategies for postpartum hemorrhage. JW women also exhibited higher Hb levels in early pregnancy and more frequent IV iron supplementation, reflecting proactive preventive anemia management [19]. These findings may indicate greater attention to hemostasis and earlier interventions in JW women [20]. However, these differences should be interpreted with caution, as underestimation of blood loss cannot be entirely excluded. Given that the incidence of severe postpartum anemia (Hb <7 g/dL) and blood loss >1000 mL during cesarean section did not differ significantly between groups, actual blood loss was likely comparable. Similar observations have been reported in previous studies, in which estimated blood loss during cesarean section and operative vaginal delivery was lower in JW women than in matched cohorts, although these differences were not statistically significant [11]. Taken together, these results may reflect heightened awareness among JW women and their physicians, leading to proactive anemia management, strict adherence to PBM protocols, and earlier intraoperative interventions, thereby contributing to comparable outcomes despite the absence of transfusion.

The implications of this study extend beyond the JW population. Despite evidence indicating that obstetric outcomes in JW women are not necessarily worse when PBM strategies are applied, many institutions and clinicians continue to avoid or decline care for JW patients. In Korea, there is currently no formal designation of transfusion-free delivery centers or an established referral system, and even basic data regarding the number of women requiring bloodless obstetric care or the availability of such services are lacking. In our experience, women presenting to our transfusion-free center often traveled from distant regions, not because of increased obstetric risk, but because they were unable to identify local maternity centers willing or able to provide transfusion-free care. This situation places the burden of seeking appropriate care on patients themselves and highlights structural gaps in access within the healthcare system. Countries such as the United Kingdom and Australia have implemented comprehensive guidelines for the management of patients who refuse transfusion [3,4]. Nevertheless, limitations in legal frameworks and the absence of standardized medical guidelines to support clinicians in ethically complex, life-threatening situations without transfusion remain substantial challenges. Combined with the inherent unpredictability of obstetric hemorrhage, these factors impose a significant burden on healthcare providers and contribute to reluctance in treating JW patients. Furthermore, the limited number of institutions experienced in transfusion-free management restricts access to obstetric care for JW women, potentially increasing the risk of hemorrhagic morbidity [20]. Ensuring universal access will require the development of centers capable of safely managing patients for whom transfusion is not an option, along with clearly defined referral pathways and broader integration of PBM into routine obstetric practice.

The significance of PBM is not limited to religious minorities. Transfusion may also be restricted by systemic factors, including blood shortages [9], rising cesarean section rates, and the decline of local delivery infrastructure. In Korea, the cesarean section rate reached 61.6% in 2022 [21], and the closure of maternity units has contributed to long-distance transfers and delays in emergency obstetric care [22]. Moreover, concerns regarding blood supply instability are increasing as a result of demographic changes, including population aging and a shrinking donor pool. At the same time, the growing proportion of pregnancies among women of advanced maternal age is expected to further increase transfusion demand in obstetric practice. Consequently, limited access to timely transfusion may occur not only for religious reasons but also due to structural and demographic barriers. In addition, increased transfusion rates for peripartum women have been reported in obstetrics, with a substantial proportion of these transfusions considered inappropriate [23]. In this context, PBM plays a critical role in improving the quality of care and maternal safety in diverse clinical cases. Advances in hemostatic agents, surgical techniques, uterotonics, and antenatal anemia prevention [19], along with the increasing acceptance of blood alternatives among JW women [16], further strengthen the feasibility of transfusion-restricted management. As more women deliver under circumstances in which transfusion may be delayed or unavailable, systematic application of PBM principles will be essential for safeguarding maternal safety [24].

This study therefore carries broader significance beyond the JW population. Clinical strategies originally developed to address the constraints of transfusion refusal in JW women have generated knowledge that is applicable more widely in obstetric practice, indicating that adverse outcomes are not inevitable in transfusion-restricted settings. Furthermore, these findings emphasize that enhancing patient safety through PBM while respecting patient autonomy constitutes an essential component of patient-centered, evidence-based obstetric care. At the policy level, designation of PBM-capable delivery centers, systematic national surveillance of transfusion-restricted cases, and establishment of referral networks will be essential to strengthen preparedness and ensure equitable access to safe obstetric care. Ultimately, integrating PBM into routine obstetric practice may reduce transfusion-related risks, conserve scarce blood resources, and improve both clinical and public health outcomes across diverse maternal populations [25].

This study has several limitations. First, it was a retrospective study conducted at a single institution, which may limit the generalizability of the findings. Second, rare outcomes such as maternal mortality may have been underrepresented due to the sample size and study design. Third, compliance with individual components of PBM could not be fully assessed in this retrospective dataset, which may limit interpretation of differences in PBM implementation between groups. Finally, most participants were classified as low to moderate risk, with high-risk conditions such as multiple gestation and maternal coagulopathy either excluded from the study or rarely observed.

In conclusion, this retrospective matched cohort study conducted at a PBM-based center observed no significant differences in hemorrhage-related obstetric outcomes between JW and non-JW women. These findings suggest that delivery can be safely managed in transfusion-restricted settings when PBM is systematically applied. While blood transfusion remains an essential component of obstetric care, PBM provides a robust framework for enhancing maternal safety when transfusion is not an option. Broader implementation of PBM may improve maternal outcomes, reduce dependence on transfusion, and address ongoing challenges related to blood safety and supply.

Supplemental Materials

Notes

Conflict of Interest

The authors have no conflicts of interest associated with the material presented in this paper.

Funding

This work was supported by the Soonchunhyang University Research Fund (2025-0012).

Acknowledgements

We thank the staff of the transfusion-free center and the Jehovah’s Witness women who participated in this study. We also thank Jin-Hwan Kim, MPH, PhD, for his valuable advice on this study.

Author Contributions

Conceptualization: Oh JW, Kwon SS, Yoon SY. Data curation: Oh JW, Kwon SS, Yoon SY, Lee JJ, Choi KY. Formal analysis: Kwon SS. Funding acquisition: Kwon SS. Methodology: Kwon SS. Project administration: Oh JW, Kwon SS, Yoon SY. Visualization: Oh JW. Writing – original draft: Oh JW, Kwon SS, Yoon SY. Writing – review & editing: Oh JW, Kwon SS, Yoon SY, Lee JJ, Choi KY.

Figure 1

Flow chart illustrating the establishment of the study population. JW, Jehovah’s Witnesses.

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References

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