The long-term renal and cardiovascular consequences of prematurity

Infants born prematurely at <37 weeks' gestation account for over 80% of infants weighing <2,500 g at birth-low birth weight (LBW) infants. This designation remains the surrogate marker for developmental origins of adult disease. Landmark studies spanning four decades have shown that individuals born with a LBW are more likely to develop cardiovascular and renal disease in later life, which is believed to be related to 'developmental programming' of such adult disease during vulnerable periods of growth in utero and in the early postnatal period. There has long been ambiguity regarding the distinction between infants with intrauterine growth restriction and preterm infants since both show a low nephron endowment that is associated with subsequent hypertension and chronic kidney disease. Knowledge is growing specific to the preterm infant and the developmental associations of being born preterm with the interruption of normal organogenesis relative to the vascular tree and kidney. Both systems develop by branching morphogenesis and interruptions lead to considerable deficits in their structure and function. These developmental aberrations can lead to endothelial dysfunction, hypertension, proteinuria and metabolic abnormalities that persist throughout life. This Review will examine the effect of preterm birth on the development of cardiovascular and kidney disease in later life and will also discuss potential early interventions to alter the progression of disease

Maternal adaptations and inheritance in the transgenerational programming of adult disease

Adverse exposures in utero have long been linked with an increased susceptibility to adult cardio-renal and metabolic diseases. Clear gender differences exist, whereby growth-restricted females, although exhibiting some phenotypic modifications, are often protected from overt disease outcomes. One of the greatest physiological challenges facing the female gender, however, is that of pregnancy; yet little research has focused on the outcomes associated with this, as a potential ‘second-hit’ for those who were small at birth. We review the limited evidence suggesting that pregnancy may unmask cardio-renal and metabolic disease states and the consequences for long-term maternal health in females who were born small. Additionally, a growing area of research in this programming field is in the transgenerational transmission of low birth weight and disease susceptibility. Pathways for transmission might include an abnormal adaptation to pregnancy by the growth-restricted mother and/or inheritance via the parental germline. Strategies to optimise the pregnancy environment and/or prevent the consequences of inheritance of programmed deficits and dysfunction are of critical importance for future generations