Offspring Birth Weight and Parental Mortality: Prospective Observational Study and Meta-Analysis

The authors have investigated associations between offspring size at birth and parental cardiovascular disease mortality among 12,086 mothers and 6,936 fathers of participants in the British 1958 birth cohort. Birth weight was inversely associated with all-cause mortality and cardiovascular mortality in both mothers and fathers. The adjusted hazard ratio of cardiovascular disease mortality for a 1-standard deviation increase in offspring birth weight in mothers was 0.87 (95% confidence interval (CI): 0.82, 0.93) and in fathers was 0.94 (95% CI: 0.89, 0.99). The association was not specific for cardiovascular disease. In fathers, similar weak associations with violent and accidental deaths, stomach cancer, and alcohol- and smoking-related outcomes were found. Weak associations for these outcomes were also found for mothers, but the magnitude of the association with cardiovascular disease was greater than with any other outcomes. In a meta-analysis pooling results from this study with six others, the adjusted hazard ratio of cardiovascular disease mortality among mothers was 0.75 (95% CI: 0.67, 0.84) and that among fathers was 0.93 (95% CI: 0.91, 0.95), with evidence that the difference in effect between mothers and fathers was not due to chance (p < 0.001). The weak association of offspring birth weight with cardiovascular disease in fathers may be due to residual confounding by factors such as socioeconomic position and smoking that they share with the offspring's mother and that would therefore be associated with low offspring birth weight as well as adverse outcomes in the father. The stronger association in mothers is consistent with intergenerational effects on intrauterine growth and with the fetal origins hypothesis.