Introduction: Hemochromatosis, a disorder of iron overload, poses theoretical risks in pregnancy due to iron-mediated oxidative stress, which is implicated in pathologies like pre-eclampsia. However, clinical data, particularly from large, diverse cohorts, is limited. Previous studies have been hampered by the inclusion of unspecified hemochromatosis codes, which may dilute true associations. This study aims to evaluate maternal and obstetric outcomes in a cohort of pregnant patients focused on hereditary and transfusion-associated hemochromatosis, identified using specific ICD-10 codes, to provide a clearer understanding of the associated risks.

Methods: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) from 2017 to 2022. We identified delivery hospitalizations for women aged 15-50. The exposure was defined by ICD-10 codes for hereditary hemochromatosis (E83.110) and hemochromatosis due to red blood cell transfusions (E83.111). Cases with unspecified (E83.119) or other (E83.118) hemochromatosis codes were excluded. A 1:4 propensity score matching was performed to create a comparable control group without hemochromatosis, balancing for age, race, insurance, hospital characteristics, and comorbidities (obesity, diabetes, hypertension). Outcomes included preeclampsia, cesarean delivery, blood transfusion, liver complications, and anemia. Survey-weighted logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). STATA 19.5 was used for analysis.

Results: We identified 185 delivery hospitalizations with focused hemochromatosis (168 hereditary, 17 transfusion-associated) matched to 740 controls. The hemochromatosis group had significantly higher odds of preeclampsia/eclampsia (8.1% vs 4.2%; OR 2.02, 95% CI 1.05-3.87) and significant comorbidities, including a fourteen-fold increased risk of liver complications (OR 14.51, 95% CI 2.72-143.73) and a seven-fold increased risk of requiring blood transfusion (OR 7.52, 95% CI 2.22-28.83). Anemia was diagnosed in 96.8% of hemochromatosis cases versus 60.5% of controls (OR 19.45, 95% CI 8.59-44.04, p<0.0001). This extremely high prevalence of anemia in an iron overload state is notable. The cohort included patients with transfusion-associated hemochromatosis, whose underlying conditions are themselves causes of severe anemia; this may skew the overall anemia prevalence. Furthermore, the standard management for hemochromatosis involves therapeutic phlebotomy. This treatment is typically performed prior to pregnancy and paused during gestation, which can result in a patient having a pre-existing, coded diagnosis of iatrogenic anemia upon conception. Regarding secondary outcomes, these pregnancies were associated with significantly longer hospital stays (3.3 vs 2.5 days; Rate Ratio 1.32, p<0.0001) and higher total charges ($30,921 vs $23,768; Rate Ratio 1.30, p=0.0002).

Conclusions: In this large, nationwide analysis focused on specific subtypes of hemochromatosis, we found that pregnant women with hereditary and transfusion-associated hemochromatosis have significantly increased risks of adverse maternal outcomes, including preeclampsia, liver complications, and the need for blood transfusion. The near-universal diagnosis of co-occurring anemia highlights the complex pathophysiology and management of these patients, where anemia may be iatrogenic (due to phlebotomy) or a feature of the underlying disease leading to iron overload. These findings underscore the importance of specialized, multidisciplinary care for this high-risk obstetric population. Further studies are warranted to differentiate outcomes between hemochromatosis subtypes and to establish optimal management strategies during pregnancy.

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2025
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