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Published on: January 7, 2020
Prematurity and programming: contribution of neonatal Intensive Care Unit interventions
S C Kalhan1, D Wilson-Costello2
11 Department of Molecular Medicine, Cleveland Clinic, Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
Insights
Premature birth and neonatal interventions may program long-term health by affecting one-carbon metabolism. Accelerated infant growth further compounds these risks for non-communicable diseases.
Area of Science:
- Neonatology
- Developmental programming
- Metabolic health
Background:
- Improved survival rates for premature infants are leading to more adults with potential long-term health risks.
- Limited data exist on the link between neonatal events and adult non-communicable diseases.
Purpose of the Study:
- To explore how intrauterine growth restriction, prematurity, and neonatal interventions may program adult non-communicable diseases.
- To investigate the role of one-carbon metabolism in these programming effects.
Main Methods:
- Review of clinical and experimental data on redox injury, nutritional interventions, and glucocorticoid effects.
- Analysis of factors correlating with insulin sensitivity in older age.
Main Results:
- Premature birth is a major contributor to later insulin sensitivity issues, compounded by infant weight gain.
- Perturbations in one-carbon metabolism are implicated in developmental programming.
Conclusions:
- Neonatal interventions and premature birth may program long-term health via one-carbon metabolism.
- These effects can be additive to intrauterine growth restriction and influenced by early infant growth.
Abstract:
Contemporary clinical practice for the care of the prematurely born babies has markedly improved their rates of survival so that most of these babies are expected to grow up to live a healthy functional life. Since the clinical follow-up is of short duration (years), only limited data are available to relate non-communicable diseases in adult life to events and interventions in the neonatal period. The major events that could have a programming effect include: (1) intrauterine growth restriction; (2) interruption of pregnancy with change in redox and reactive oxygen species (ROS) injury; (3) nutritional and pharmacological protocols for clinical care; and (4) nutritional care in the first 2 years resulting in accelerated weight gain. The available data are discussed in the context of perturbations in one carbon (methyl transfer) metabolism and its possible programming effects. Although direct evidence for genomic methylation is not available, clinical and experimental data on impact of redox and ROS, of low protein intake, excess methionine load and vitamin A, on methyl transfers are reviewed. The consequences of antenatal and postnatal administration of glucocorticoids are presented. Analysis of the correlates of insulin sensitivity at older age, suggests that premature birth is the major contributor, and is compounded by gain in weight during infancy. We speculate that premature interruption of pregnancy and neonatal interventions by affecting one carbon metabolism may cause programming effects on the immature baby. These can be additive to the effects of intrauterine environment (growth restriction) and are compounded by accelerated growth in early infancy.
