Congenital malformations, stillbirths, and early mortality among the children of atomic bomb survivors: a reanalysis

Of all the data sets pertinent to the estimation of the genetic risks to humans following exposure to ionizing radiation, potentially the most informative is that composed of the cohort of children born to atomic bomb survivors. We present here an analysis of the relationship between parental exposure history and untoward pregnancy outcomes within this cohort, using to the fullest extent possible the recently revised estimates of the doses received by their parents, the so-called DS86 doses. Available for study are 70,073 terminations, but DS86 doses have not been or presently cannot be computed on the parents of 14,770. The frequency of untoward pregnancy outcomes, defined as a pregnancy terminating in a child with a major congenital malformation, and/or stillborn, and/or dying in the first 14 days of life, increases with combined (summed) parental dose, albeit not significantly so. Under a standard linear model, when the sample of observations is restricted to those children whose parents have been assigned the newly established DS86 doses (n = 55,303), ignoring concomitant sources of variation and assuming a neutron RBE of 20, the estimated increase per sievert in the predicted frequency of untoward outcomes is 0.00354 (+/- 0.00343). After adjustment for concomitant sources of variation, the estimated increase per sievert in the proportion of such births is 0.00422 (+/- 0.00342) if the neutron RBE is assumed to be 20. A "one-hit" model with appropriate adjustments for extraneous sources of variation results in an almost identical value, namely, 0.00412 (+/- 0.00364). When the sample is extended to include parents lacking the full array of dose parameters necessary to calculate the DS86 dose, but sufficient for an empirical conversion of the previously employed T65DR dose system to its DS86 equivalent, we find under the linear model that the estimated increase per sievert in untoward pregnancy outcomes is some 31% higher than that published previously, 0.00264 (+/- 0.00277), assuming an RBE of 20, after adjustment for extraneous sources of variation. (Since a dose could not be calculated in 367 of the 70,073 outcomes, the n = 69,706). The corresponding value with the one-hit model is 0.00262 (+/- 0.00294).