The Effect of Comprehensive Care and Degree of Iron Overload on Maternal and Fetal Outcomes in Pregnancies of Transfusion-Dependent Beta-Thalassemia Patients

Iron overload resulting in hypogonadotrophic hypogonadism is the major cause of infertility in patients with beta-Thalassemia Major (bTM). However, in patients who are able to achieve pregnancy, the effects of iron overload and comprehensive care by hematologists specialized in Hemoglobinopathies on maternal-fetal outcomes have not been well-documented. We hypothesize that in patients with transfusion-dependent bTM, lack of comprehensive care prior to conception or elevated ferritin is associated with poor maternal-fetal outcomes and increased rates of antepartum complications.

A retrospective review was conducted on transfusion-dependent bTM patients who delivered at the Mount Sinai Hospital (MSH), a quaternary referral, high risk obstetrics care institution in Central Ontario, Canada, between 2000 and 2010 based on the Antenatal Database, Delivery Database, electronic and paper-based medical records. Patients were jointly managed by a maternal-fetal medicine specialist and hematologist specialized in hemoglobinopathies. All forms of chelation were discontinued during pregnancy. We analyzed the maternal-fetal outcomes and antepartum complications based on the presence or absence of comprehensive care prior to pregnancy by the Red Blood Cell Disorders (RBCD) Clinic at the University Health Network, a hemoglobinopathy comprehensive care centre from the same catchment area as MSH. Components of comprehensive care include regular monitoring of iron burden, screening and treatment of target organ damage from iron overload, genetic counseling from physicians, and psychosocial counseling from a social worker. We also analyzed the relationship between the pre-pregnancy ferritin levels and birth weight, gestational age, and any antepartum complications.

We identified 40 singleton deliveries and 3 twin deliveries by 42 patients (40 bTM, 1 Thalassemia Intermedia, 1 Hemoglobin E/beta-Thalassemia). There were no maternal or fetal deaths. The 3 twin pregnancies were excluded from analysis due to being a potential confounder in maternal and fetal outcomes. Mean maternal age at delivery was 33.11 years (95% CI 31.77, 34.45 years). Mean gestational age at delivery was 38.29 weeks (95% CI 37.41, 39.17 weeks) with six (15%) pre-term births (<37 weeks). Fourteen deliveries (35%) were by Caesarian section and 26 were vaginal deliveries. Six (15%) were low birth weight (<2500 g) and 2 (5%) were small for gestational age. Ten of the 39 patients analyzed (11 deliveries) received comprehensive care at RBCD clinic prior to their pregnancies. There was no significant difference in maternal-fetal outcomes or antepartum complications between patients who received comprehensive care prior to conception and those who did not. However, patients who received comprehensive care were significantly younger and had lower parity (P = 0.0072 and 0.0276 respectively). In the 19 deliveries where pre-pregnancy ferritin was available, there was no association between pre-pregnancy ferritin and fetal birth weight, gestational age, or any antepartum complications.

There was no association between pre-pregnancy ferritin level and maternal-fetal outcomes. Presence of comprehensive care prior to conception did not appear to significantly change the maternal-fetal outcomes in transfusion-dependent beta-Thalassemia patients. We speculate that the lack of difference may be due to a higher proportion of primigravida in the comprehensive care group acting as a potential confounder, given that primigravida in general have higher rates of adverse pregnancy outcome. In addition, patients with higher parity may have less severe complications from iron overload, and consequently are less likely to be referred to a comprehensive care center. Limitations include small sample size and single center study. Further prospective observational studies with larger sample size are required to evaluate whether a) introduction of uniform comprehensive care to all women with bTM in child-bearing age will improve pregnancy outcomes; b) ferritin or liver iron concentration is useful in predicting antepartum complications in bTM patients.

Kuo:Novartis Canada: Research Funding.