Do Women with Thalassemia Have an Increased Risk of Small for Gestational Age Infants?
Yes, women with β-thalassemia major are approximately 70% more likely to deliver small for gestational age (SGA) infants compared to women without thalassemia.
Evidence from Population-Based Studies
The most recent and highest quality evidence comes from a 2025 US population-based study analyzing over 3 million pregnancies, which found that mothers with β-thalassemia major had a 68% increased risk of delivering SGA neonates (adjusted OR 1.68,95% CI 1.07-2.62) 1. This represents the strongest evidence available from a non-endemic region using rigorous matching methodology.
Mechanisms and Contributing Factors
The increased SGA risk in thalassemia pregnancies stems from multiple pathophysiologic mechanisms:
Iron overload effects: Cardiac and hepatic iron deposition can compromise placental perfusion and fetal growth, particularly when severe iron overload exists before conception 2, 3
Increased transfusion requirements: Blood consumption typically increases during pregnancy to maintain hemoglobin around 10 g/dL, which combined with interruption of chelation therapy, significantly worsens iron overload and may compromise fetal growth 2
Chronic anemia and hypoxia: Even with optimal transfusion, chronic tissue hypoxia affects placental function and fetal development 4
Endocrine dysfunction: Hypogonadotropic hypogonadism and other endocrinopathies common in thalassemia patients may affect pregnancy outcomes 3, 5
Clinical Context and Additional Risks
Beyond SGA, women with thalassemia face substantially elevated risks for other adverse outcomes:
Preterm delivery: 3-fold higher incidence than background population, with increased rates of both preterm and very preterm delivery 5, 2
Fetal loss: Spontaneous miscarriage and fetal loss occur in 9-33.3% of thalassemia pregnancies 2, 3
Obstetric complications: Frequent gestational diabetes, preeclampsia, and hypertension 2, 3
Cesarean delivery: 30% increased likelihood (adjusted OR 1.30,95% CI 1.03-1.63), with rates ranging from 24-100% in various series due to fetopelvic disproportion, osteoporosis, or maternal complications 1, 2
Critical Management Considerations
Pre-conception assessment is mandatory and should include cardiac MRI (T2*) to assess iron loading, echocardiography for chamber dimensions and function, and comprehensive evaluation of liver iron burden 6, 2. Women with severe cardiac or hepatic iron overload require intensified chelation before attempting pregnancy 6.
During pregnancy, maintain hemoglobin at approximately 10 g/dL through transfusion therapy, though this paradoxically worsens iron overload when chelation is discontinued 6, 2. Consider restarting deferoxamine chelation toward the end of the second trimester in patients with severe iron overload threatening maternal cardiac function 6, 2.
Thromboprophylaxis with heparin or low-molecular-weight heparin is essential, particularly in splenectomized patients and those with thalassemia intermedia 6, 2.
Common Pitfalls to Avoid
The most critical error is failing to perform comprehensive pre-pregnancy cardiac assessment, as cardiac complications during pregnancy range from 1.1-15.6% and heart disease accounts for approximately 70% of deaths in transfusion-dependent thalassemia patients 2, 3.
Another common mistake is inadequate fetal surveillance—given the 70% increased SGA risk, serial growth ultrasounds in the third trimester are warranted, though specific intervals are not defined in guidelines 1.
Pregnancy in thalassemia requires management by a multidisciplinary team at an expert center, as favorable outcomes depend on continuous preconception, antenatal, and postpartum assessment 2, 7, 4.