乌鸦传媒視頻

A multidisciplinary approach is required for the management of conception and pregnancy in patients with any number of medical conditions, from obesity to diabetes to hypertension. Thalassemia, an inherited blood disorder and a common cause of anemia, is no different. As such, the British Society for Hematology (BSH) recently updated its guidelines for the management of conception and pregnancy in the setting of thalassemia, which were published in the British Journal of Hematology.¹

Thalassemia arises from mutations in the 伪, 尾, and 未 globin genes, leading to a spectrum of symptoms ranging from mild anemia to severe, life-threatening conditions that require regular blood transfusions and intensive management of iron overload. Classified by the World Health Organization as a major global health concern, around 1.5% of individuals worldwide carry the 尾-thalassemia trait.² Annually, the global incidence of thalassemia syndromes exceeds 70,000 newborns, while the number of people who carry the thalassemia trait without showing symptoms is estimated to be more than 100 million.^1,3

Thalassemia and pregnancy

The main complications of thalassemia are anemia and iron overload, both of which must be monitored closely and managed aggressively during pregnancy. Additionally, individuals who have had splenectomies, a common treatment for thalassemia, may be at increased risk for thrombotic disease during pregnancy. Similarly, women with skeletal deformities or osteoporosis as a result of thalassemia may be more likely to suffer orthopedic injuries during labor.¹

鈥淎s the thalassemia patients grow older and most now are optimally chelated, they expect to be able to have families,鈥� says the lead author of the newly published guidelines, Farrukh Shah, MBBS, FRCPath, MDRes, MBE, Department of Hematology, Whittington Health, London, U.K. 鈥淐omprehensive guidelines on management of conception and pregnancy in thalassemia patients are really important to support the management of patients through pregnancy, not only in the U.K. but globally, where there is a far larger burden of disease.鈥�

A systematic search of the literature

The BSH Guidelines Committee, General Hematology Task Force, and the General Hematology Sounding Board conducted a comprehensive literature search on thalassemia and pregnancy using PubMed and other databases, with specific filters and terms, updated through 2021. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was applied to determine the quality of evidence and the strength of recommendations.⁴

Recommendations were made for preconception optimization, hypogonadism, antenatal care, intrapartum care, and postnatal care. GRADE 1 recommendations are 鈥渟trong鈥� recommendations; GRADE 2 recommendations are 鈥渨eak.鈥� Ratings of A through D are used to rank the strength of the literature reviewed, with 鈥淎鈥� being the strongest and 鈥淒鈥� being the weakest.

Recommendations for preconception care

GRADE 1 recommendations for preconception care involve genetic counseling (1B), thorough fertility assessments (1B), and effective contraception until optimal health conditions for pregnancy are met (1C).¹ It also includes lifestyle adjustments, such as smoking cessation (1C); optimization of iron chelation therapy (1B); careful management of transfusions with matched blood units (1B); and regular monitoring of cardiac and liver health (1B). Furthermore, infection screening, endocrine function tests, and specific medication adjustments are recommended to prepare for a healthy pregnancy and minimize risks to both mother and child (1B).

Recommendations for people with hypogonadism

Hypogonadism caused by iron deposits in the pituitary gland, gonads, or both is common in patients with thalassemia and may lead to infertility if not managed properly.⁵ GRADE 1 recommendations for males with hypogonadism potentially undergoing spermatogenesis induction include the following:

• Start gonadal assessments at puberty in consultation with a pediatric endocrinologist (1A).
• Monitor response to treatment with gonadotropin for spermatogenesis and adjust the dosage accordingly (1B).
• Recommend assisted conception if natural conception fails to occur after 12 months, especially if the female partner is in her mid-30s or older (1B).
• Replace combined gonadotropin therapy with testosterone therapy if gonadotropin has been unsuccessful after 24 months, unless microsurgical testicular sperm extraction is planned (1C).

Similarly, GRADE 1 recommendations for females requiring ovulation induction include the following:

• Conduct a comprehensive fertility check for couples before initiating ovulation induction therapy (1B).
• Counsel patients on the risks and potential complications (1B).
• Consult a multidisciplinary team after 6 unsuccessful cycles (1B).
• Provide clear counseling on the risks of multiple pregnancies if more than 2 follicles exceed 14 mm at the time of the trigger injection (1B).

Antenatal recommendations

All patients with thalassemia should be evaluated monthly during pregnancy until 28 weeks and then every 2 weeks. Key recommendations include the following:

• Initiate folic acid therapy prior to conception and continue throughout pregnancy (1A).
• Initiate aspirin therapy at 12 weeks鈥� gestation (1A).
• Administer low-molecular-weight heparin (LMWH) thromboprophylaxis and low-dose aspirin to pregnant patients with thalassemia who are splenectomized or have a high platelet count, in the absence of contraindications (1A).
• Administer LMWH during hospital admissions to all pregnant patients with thalassemia (1B).
• Closely monitor the ejection fraction of women with myocardial iron loading during pregnancy and consider chelation therapy for those who experience heart failure (1B).
• Offer desferrioxamine therapy to high-risk patients (T2* < 10 ms) from weeks 20 to 24 of gestation (1B).
• Monitor thyroid function in patients with hypothyroidism (1B).

• Conduct a cardiology evaluation at the beginning of the third trimester for patients with transfusion-dependent thalassemia and a cardiac T2* magnetic resonance imaging greater than 20 milliseconds (ms) (1C).
• Monitor serum fructosamine monthly in patients with diabetes (1C).
• Perform an early viability ultrasound and serial fetal growth scans (1C).

Intrapartum recommendations

These recommendations emphasize the importance of preparedness prior to delivery in pregnant patients with thalassemia. They include the following:

• Minimize blood loss during the third stage of labor (1A).
• Include a late-pregnancy transfusion plan for patients with non-transfusion-dependent thalassemia (1C).

• Notify the multidisciplinary care team on admission (1D).
• Ensure appropriate blood products are available for those with red blood cell antibodies or hemoglobin <100 g/L (1D).
• Note that thalassemia by itself is not an indication for a cesarean delivery (1D).

Postpartum recommendations

• Splenectomized patients should receive LMWH for 6 weeks postpartum (1C).
• Iron burden should be reassessed at 3 months postpartum, although women with myocardial iron overload may need to be evaluated earlier (1C).

Further improving the management of pregnant patients

The authors emphasize the need for a multidisciplinary approach when treating fertility and pregnancy in the setting of thalassemia. 鈥淭he multidisciplinary aspect of the guidelines meant that we really needed rigorous input from endocrinologists who have expertise in male and female infertility, as well as from obstetricians and hematologists,鈥� Dr. Shah told 乌鸦传媒視頻. 鈥淲e were very fortunate in that the Endocrine Society endorsed the guidelines, and that the Royal College of Obstetricians and Gynecologists鈥� guidelines committee reviewed the guidelines and provided excellent feedback.鈥�

Dr. Shah and her colleagues are enthusiastic to have created guidelines that healthcare providers worldwide can use to help patients benefit from recent advances in the treatment of fertility and pregnancy in thalassemia.

鈥淕lobally, these guidelines provide a single document to manage fertility, conception, and pregnancy in this population, and I think they will be an excellent resource for clinical teams,鈥� says Dr. Shah. 鈥淚 hope these guidelines help make the management of conception and pregnancy in thalassemia patients easier and smoother for patients and their clinicians, so that ultimately more patients can achieve parenthood.鈥�

Dr. Shah is hopeful that further advances will be made regarding fertility in patients with thalassemia. 鈥淚 think more research needs to be done to support fertility for patients who may fail spermatogenesis induction or ovulation induction,鈥� she concludes.

Published: June 28, 2024