The central premise of the review is that improved survival has created a new clinical population with new needs. Advances in transfusion regimens, iron chelation drugs that bind excess iron and allow the body to excrete it, and coordinated multidisciplinary care have dramatically extended life expectancy for people with transfusion-dependent beta-thalassemia. Many women now survive well into their reproductive years and beyond, and their reproductive potential has improved in parallel. Pregnancy, once a rare event in this population, has become increasingly feasible, although the authors are emphatic that it remains a high-risk condition that demands specialized management rather than routine obstetric care. The review is designed as a practical roadmap for hematologists, obstetricians, endocrinologists, cardiologists, and primary care providers who may encounter these patients only occasionally but must coordinate their care intensively.

The foundation of a safe pregnancy, according to the review, is laid long before conception. The authors call for comprehensive preconception evaluation by a multidisciplinary team, covering cardiac function, iron overload, endocrine disorders, liver disease, kidney function, fertility, and genetic risk. Each of these domains reflects a distinct vulnerability created by the disease and its treatment. Chronic anemia forces the heart to work harder, and accumulated iron can stiffen and weaken the cardiac muscle directly. The endocrine axis is particularly fragile: iron deposition in the pituitary gland, gonads, thyroid, and pancreas can impair hormone production, and many women with the condition require hormonal support to ovulate at all. Liver disease and reduced kidney reserve add further layers of risk. Genetic counseling is also essential, because beta-thalassemia is inherited in an autosomal recessive pattern, meaning that the carrier status of the partner determines whether each pregnancy carries a risk of affected offspring.

Cardiac assessment emerges as perhaps the most consequential element of the preconception workup. Myocardial iron overload, detectable with cardiovascular magnetic resonance imaging, is the leading cause of mortality in people with transfusion-dependent thalassemia, and pregnancy places substantial additional hemodynamic demands on the heart, with blood volume increasing by roughly forty to fifty percent and cardiac output rising accordingly. The review emphasizes that women with significant myocardial iron require particularly careful planning, and that early identification and treatment of iron overload and cardiac disease remain essential for optimizing outcomes. In practice, this means that the cardiac evaluation is not a one-time gatekeeping exercise but a recurring process that continues throughout pregnancy, with periodic cardiac assessment recommended for all patients as gestation progresses.

Once pregnancy is established, the review recommends maintaining pre-transfusion hemoglobin levels at ten grams per deciliter or higher, a more aggressive target than the thresholds typically used in non-pregnant patients with the condition. The rationale is physiological: the fetus depends entirely on maternal oxygen delivery, and the expanded plasma volume of pregnancy dilutes the maternal red cell mass. More frequent transfusions are usually required to hit the target, which in turn accelerates iron accumulation, creating a delicate balancing act between protecting fetal oxygenation and limiting maternal iron burden. The authors also recommend regular fetal growth surveillance, because placental insufficiency and intrauterine growth restriction are recognized complications in this population, alongside screening for gestational diabetes, which is more common in women with thalassemia-related endocrine dysfunction and iron overload, and individualized thromboprophylaxis for patients judged to be at high risk of venous thromboembolism.

Iron chelation policy during pregnancy is one of the most nuanced areas the review addresses. The standard oral and oral-agent chelators, deferiprone and deferasirox, are not established as safe in pregnancy, and the general recommendation is that chelation therapy should be discontinued once conception is confirmed. However, the authors note an important exception for women with severe cardiac or hepatic iron overload. For these patients, deferoxamine, an older chelator administered by continuous subcutaneous or intravenous infusion that does not cross the placenta appreciably, may be considered from the second trimester onward. In women with significant myocardial iron, deferoxamine has been used from approximately twenty weeks of gestation, or earlier when clinically indicated. This individualized approach reflects a risk-benefit calculation: the danger of untreated cardiac iron, which can precipitate heart failure during the hemodynamic stress of late pregnancy and delivery, can outweigh the theoretical fetal risks of exposure in selected cases.

The review also maps out the peripartum and postpartum terrain, which carries its own distinct hazards. Women with thalassemia-related endocrine dysfunction may face impaired uterine contractility and increased bleeding risk, while splenectomy, performed in some patients to reduce transfusion requirements, is associated with a higher risk of thromboembolic events, making individualized thromboprophylaxis particularly important in that subgroup. Cesarean delivery may be indicated for obstetric reasons, but it is not mandated by the disease itself. After delivery, the resumption of chelation must be coordinated with infant feeding choices, since chelators are excreted in breast milk, and the maternal transfusion schedule and iron monitoring must be re-established promptly. The authors stress that adherence to evidence-based recommendations across this entire continuum substantially reduces maternal and fetal complications.

What makes the review notable is its synthesis of forty discrete recommendations into a coherent care pathway, effectively converting scattered international guidance into a single clinical reference. The authors systematically reviewed publications including clinical practice guidelines, systematic reviews, meta-analyses, and original studies to identify evidence across preconception counseling, maternal assessment, antenatal care, transfusion strategy, chelation, fetal surveillance, delivery, and postpartum management. This breadth matters because care for these women is inherently fragmented: a hematologist manages transfusions and iron, an endocrinologist manages hormonal induction of ovulation and diabetes risk, a cardiologist tracks cardiac iron and function, and an obstetrician manages fetal surveillance and delivery. The review’s contribution is to bind those threads together and to make explicit where evidence is strong and where recommendations rest on expert consensus rather than randomized trials, a distinction that is important in a field where pregnancy is too rare and too risky for large controlled studies.

The implications extend beyond individual clinics. As survival in transfusion-dependent beta-thalassemia continues to improve worldwide, particularly in the Mediterranean, Middle East, and South and Southeast Asia where the disease is most prevalent, the number of women reaching reproductive age and seeking pregnancy will only grow. Health systems that have historically focused on pediatric transfusion care will need to build adult and reproductive services, including fertility preservation and assisted reproduction, since spontaneous conception is often impossible in women with iron-induced hypothalamic-pituitary damage. The review’s emphasis on early identification and treatment of iron overload, cardiac disease, and endocrine dysfunction is, in effect, an argument for lifelong preventive care beginning in childhood, so that women who wish to become pregnant arrive at that decision with organs as protected as possible.

For patients and families, the message is one of cautious, conditional optimism. Pregnancy in women with transfusion-dependent beta-thalassemia is still classified as high risk, and the review does not minimize the vigilance it demands: pre-transfusion hemoglobin held at or above ten grams per deciliter, periodic cardiac evaluation, gestational diabetes screening, fetal growth monitoring, and carefully individualized decisions about chelation. But the central finding is unambiguous. With comprehensive preconception planning, multidisciplinary management, regular monitoring, and adherence to the evidence-based recommendations now assembled in one place, favorable maternal and fetal outcomes are achievable. What was once dismissed as medically impossible has become a realistic goal, provided that the pregnancy is planned, monitored, and supported by a team that understands both the disease and the profound physiological transformations of gestation.

Subject of Research: Management of pregnancy in women with transfusion-dependent beta-thalassemia

Article Title: Management of pregnancy in women with transfusion-dependent β-thalassemia: An evidence-based narrative review with clinical recommendations

Article References: Miri-Aliabad, G., & Dahmardeh, T. (2026). Management of pregnancy in women with transfusion-dependent β-thalassemia: An evidence-based narrative review with clinical recommendations. Annals of Hematology. https://doi.org/10.1007/s00277-026-07309-1

Image Credits: AI Generated

DOI: 10.1007/s00277-026-07309-1

Keywords: beta-thalassemia, transfusion-dependent thalassemia, pregnancy, blood transfusion, iron overload, iron chelation, deferoxamine, preconception care, fertility, gestational diabetes, genetic counseling, maternal-fetal outcomes