Size at birth as a predictor of mortality in adulthood: a follow-up of 350 000 person-years

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Abstract
Background Small body size at birth, as a marker of an adverse intrauterine environment, has recently emerged as an important risk factor for death from cardiovascular disease. Our aim was to study the relationship between small size at birth and all-cause and non-cardiovascular mortality, which has been poorly documented. Methods We studied 13 830 individuals born between 1924 and 1944 in Helsinki, Finland, at term as singletons. Dates and primary causes of death between 1971 and 1998 were obtained from the Finnish National Death Register. Results 1668 men and 671 women died during the follow-up at the mean age of 56.0 (range 26.7–74.9) years. Lower birthweight was associated with increased all-cause mortality in females (Odds ratio (OR) for 1 kg decrease in birthweight 1.25, 95% CI 1.05–1.49; P = 0.01) but not in males (OR 1.08; 0.96–1.19; P = 0.2; P for sex–birthweight interaction = 0.09). Similarly, short length at birth was a predictor of all-cause mortality in females (OR for 1 cm decrease 1.10; 1.05–1.15; P < 0.0001) but not in males (OR 1.01; 0.98–1.02; P = 0.4; P for sex–length at birth interaction = 0.002). Low birthweight and short length at birth predicted premature death in adulthood (n = 654) was associated with lower birthweight (OR for 1 kg decrease 1.33; 1.12–1.59; P = 0.001), and length (OR 1.05; 1.00–1.10; P = 0.03), and in females death from cardiovascular disease (n = 179) was associated with short length at birth (OR 1.11; 1.02–1.20; P = 0.02). In females death from non-cardiovascular diseases was predicted by low birthweight (OR 1.25; 1.01–1.54; P = 0.04) and short length at birth (OR 1.09; 1.03–1.15; P = 0.003) (n = 475), but not in males (n = 975; P for interaction = 0.02 and 0.004, respectively). Cancer-related death was associated with higher birthweight (OR for 1 kg decrease 0.76; 0.61–0.95; P = 0.02) and ponderal index (OR for 1 kg/m3 increase 0.95; 0.91–0.99; P = 0.01) in males (n = 361) but not in females (n = 269). Conclusions Small size at birth is associated with increased all-cause mortality at all ages among adult women but only with premature death in adult men. Among women death from both cardiovascular and non-cardiovascular causes is associated with small body size at birth. Among men an association between small birthsize and later cardiovascular disease is counterbalanced by an association between large body size at birth and later cancer.