Background: Research over the past decade has suggested that prenatal and early postnatal nutrition influence the risk of developing chronic degenerative diseases up to 60 years later. We now present evidence that risk of death from infectious diseases in young adulthood is similarly programmed by early life events.
Methods: In three rural Gambian villages, affected by a marked annual seasonality in diet and disease, we have kept detailed demographic, anthropometric and health records since 1949. Fate was known with certainty for 3,162 individuals (2,059 alive/1,103 dead, most dying in childhood). For this case-control analysis of antecedent predictors of premature mortality, all adult deaths (n = 61) were paired with two randomly selected controls matched for sex and year of birth.
Results: Mean age at death was 25 (SD: 8) years. Adult death was associated with a profound bias in month of birth with 49 cases born in the nutritionally-debilitating hungry season (Jul-Dec) versus 12 in the harvest season (Jan-Jun). Relative to harvest season the hazard ratio for early death in hungry-season births rose from 3.7 (for deaths >14.5 years, P = 0.000013) to 10.3 (for deaths >25 years, P = 0.00002). Anthropometric and haematological status at 18 months of age was identical in cases and controls, indicating an earlier origin to the defect. Most deaths for which cause was known had a definite or possible infectious aetiology; none were from degenerative diseases of affluence.
Conclusions: Early life exposures, correlated with season of birth, strongly influence susceptibility to fatal infections in young adulthood. The evidence suggests that nutritionally-mediated intrauterine growth retardation may permanently impair the development of immune function.
PIP: This paper presents the influence of prenatal and early postnatal nutrition on the risk of developing chronic degenerative diseases during late adulthood. Investigation of the thrifty phenotype hypothesis using 1949 birth records in three rural Gambian villages illustrates the severity of seasonality in diet and disease patterns. A database of 3162 individuals--2059 survivors and 1103 fatalities--was examined. Using a case-control analysis of antecedent predictors of premature mortality, all deaths were paired with two randomly selected controls matched for sex and year. Results revealed that the mean age at death was 25 years, with 49 adult death cases occurring in the nutritionally debilitating hungry season compared to 12 cases occurring during the harvest season. In relation to the harvest season, the hazard ratio rose from 3.7 (for deaths at age 14.5 years; p = 0.000013) to 10.3 (for deaths at age 25 years; p = 0.00002). Both the anthropometric and hematological status at 18 months was similar in cases and controls, with most deaths caused by a definite or possible infectious etiology without evidence of degenerative disease cause. This study concludes that early life exposures correlated with season of birth significantly influence the susceptibility to fatal infections in young adulthood. This also suggests that nutritionally mediated intrauterine growth retardation could permanently impair the development of immune function.