Disease burden in offspring is associated with changing paternal demographics in the United States

Background: Average paternal age in the United States has increased substantially in the last few decades. Children of advanced age fathers have a higher incidence of early onset cancer and neuropsychiatric disease.

Objectives: To quantify the number of population adjusted cases of early-onset cancer and neuropsychiatric disease in children attributable to increasing paternal age in the United States.

Methods: Paternal age in the United States from 1972 to 2015 was collected using the National Vital Statistics System (NVSS). Population attributable fraction and paternal age-specific cumulative incidence rates of several cancers and neuropsychiatric disorders were obtained from peer-reviewed publications. Paternal age-specific birth rates were correlated with paternal age-specific cumulative incidence rates to determine the number of attributable cases of disease caused by advancing age of fathers in the United States.

Results: The 2015 birth cohort in the United States is estimated to expect 9.2% more cases of acute lymphoblastic leukemia (ALL) diagnosed before 16 years of age (157 additional cases), 13.2% more cases of embryonal tumors in children <5 years of age (209 additional cases), and 13.0% more cases of breast cancer in females younger than 40 years old (424 additional cases) compared to the 1972 birth cohort. We can estimate to expect 10.5% more cases of schizophrenia diagnosed before 21 years of age (2864 additional cases), 6.3% more cases of autism spectrum disorder (ASD) in adolescents <17 years of age (2934 additional cases), 4.5% more cases of anorexia nervosa (AN) in females 8-30 years old (620 additional cases), and 9.2% more cases of bipolar disorder in young patients 16-25 years old (252 additional cases) in the 2015 birth cohort compared to the 1972 birth cohort.

Conclusion: Increasing paternal age in the United States is associated with a substantial increase in the number of cases of early-onset cancer and neuropsychiatric disease in offspring.