On-going public health surveillance efforts are critical for understanding of the impact and outcomes of thalassemias. California implemented newborn screening (NBS) for beta thalassemia in 1990 and for alpha thalassemia and hemoglobin H (HbH) in 1999; over 99% of all live births are screened. This program has identified hundreds of newborns with these life-threatening disorders, and has led to improved care and outcomes. However the impact of immigration and state-to-state migration of high-risk populations is unknown, and this limits understanding of the prevalence of thalassemia in California.
The National Heart, Lung and Blood Institute (NHLBI)-funded and Centers for Disease Control and Prevention (CDC)-directed Registry and Surveillance System for Hemoglobinopathies (RuSH) cooperative agreement collected and linked population-based surveillance data in seven states from a variety of data sources for years 2004-2008. In California, these data included case reports of patients from large specialty treatment centers – Children’s Hospital Los Angeles and UCSF Benioff Children’s Hospital Oakland. In a subsequent CDC cooperative agreement, Public Health Research, Epidemiology and Surveillance in Hemoglobinopathies (PHRESH), California collected additional case reports from four treatment centers: University of California (UC) Davis Medical Center, UC Irvine Medical Center, UC San Francisco Medical Center and UC San Diego Rady Children’s Hospital. We linked reported cases born 1990-2008 to NBS hemoglobinopathy registry thalassemia cases using date of birth, sex, diagnosis and name.
There were 273 treatment center reported cases born during the NBS time frame (i.e., 1990-2008 for beta thalassemia, 1999-2008 for alpha thalassemia), including 113 HbH, 46 beta thalassemia major, 20 HbH/Constant Spring, 17 beta thalassemia intermedia, 26 other beta thalassemia, 3 alpha thalassemia major and 48 cases with unknown or unreported genotype. Of the 225 with known genotype, 62% were definite links to the NBS registry, an additional 16% were likely matches (same date of birth, sex and genotype with no other match for that registry case, but different surname) and 21% had no match in the registry. Treatment center reported cases with known genotype not in the NBS registry were more likely to be older (45% unlinked in the oldest age group vs. 12% unlinked in the youngest group) and for 4% (n = 8) of linked cases the treatment center diagnosis differed significantly from the NBS diagnosis. Among the 48 reported cases with unknown genotype, only nine linked to registry cases. Without confirmatory testing, it is unknown whether these cases have thalassemia trait or benign forms of hemoglobin disorders (e.g., Hemoglobin EE) or any form of blood disorder, so interpretation of the lack of linkage among these cases is difficult. Table 1 shows proportions of cases linked (definite and likely matches) and unlinked with the registry by genotype and year. Linked cases from these six treatment centers represented 23% of all NBS registry thalassemia cases for the relevant time period.
While California’s strong NBS program is effectively capturing incidence of thalassemias at birth, these data show a high number of cases born out of state or otherwise undiagnosed that may represent migration to the state of high risk populations. These data also do not capture the number of NBS-identified infants who moved out of state during this time period. On-going population-based surveillance for thalassemia is important to monitor changes in prevalence and outcomes among those affected, and informs development of standards of care, policy and advocacy efforts.
This work was supported by the CDC and the NHLBI, cooperative agreement numbers U50DD000568 and U50DD001008.
|Treatment Center Reported Genotype/Diagnosis||Years Screening Begun||Total Eligible Treatment Center Cases||Linked to NBS Registry||1990-1994||1995-1999||2000-2004||2005-2008|
|Hemoglobin H/Constant Spr.||1999||20||16||--||1||1||2|
|α thalassemia major||1999||3||3||--||0||0||0|
|β thalassemia major||1990||46||27||7||9||2||1|
|β thalassemia intermedia||1990||17||7||2||4||2||2|
|β thalassemia other||1990||26||19||1||2||1||3|
|Total Known Genotype||225||177||10||19||10||9|
|Total Reported Cases||273||186||14||29||27||17|
Disclosures No relevant conflicts of interest to declare.
- © 2014 by The American Society of Hematology