Case-control study of perinatal factors and hepatoblastoma in children with an extremely low birthweight.

Abstract

There is a significant association between hepatoblastoma and low birthweight. A case-control study was conducted to reveal risk factors for hepatoblastoma in children of extremely low birthweight (< 1,000 g). Prenatal and postnatal histories, including parental histories, of 12 hepatoblastoma cases and 75 birthweight-matched controls were compared. The gestational age of the hepatoblastoma cases (23-32 weeks: median 25 weeks), tended to be lower than that of the controls (23-36 weeks; median, 27 weeks; P = 0.072). The time for an infant's bodyweight to return to the same level as the birthweight also tended to be longer in hepatoblastoma cases than in controls (P = 0.055). All hepatoblastoma cases received oxygen therapy for a period of 4-508 days (median 114 days), which was significantly longer than the 0-366 days (median 62 days) in the controls (P = 0.022). Furosemide was given to all hepatoblastoma cases and was used for a significantly longer period in these infants (6460 days; median 89 days) than in the controls (0-241 days; median 44 days P = 0.027). A univariate Cox regression demonstrated that the time taken to regain bodyweight at birth and the duration of both oxygen therapy and furosemide treatment were significantly associated with the development of hepatoblastoma (hazard ratio (HR)= 1.044, P= 0.013; HR = 1.006, P= 0.001; and HR = 1.007, P= 0.001, respectively). Although there were significant correlations between the factors, a multivariate Cox regression analysis identified the duration of oxygen therapy as a significant independent risk factor (HR = 1.006, P = 0.001). Oxygen therapy and furosemide treatment, along with the rate of growth, are risk factors for the development of hepatoblastoma in children of extremely low birthweight, and the duration of oxygen therapy is the most important factor in predicting the development of hepatoblastoma. Further studies are necessary to determine the real reasons for the development of hepatoblastoma and to protect children of low birthweight from the development of cancer.