Prematurity and programming: contribution of neonatal Intensive Care Unit interventions

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 injury (3) Nutritional and pharmacological protocols for Clinical care (4) Nutritional care in the first two 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 effecting 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.

Birth weight, malnutrition and kidney-associated outcomes—a global concern

“…51 Numerous factors can influence nephrogenesis in premature infants, including growth restriction in utero, interruption of pregnancy with the associated alteration in redox state, adequacy of postnatal nutrition, and pharmacologic interventions after birth. 52 Premature infants that were SGA had fewer nephrons than did infants that were appropriate weight for gestational age (AGA), demonstrating the additional effect of growth restriction on prematurity. 53 Furthermore, premature infants with renal failure (defined as serum creatinine >152.52 μmol/l) have fewer nephrons as compared to those that do not develop renal failure.…”

“…74 A reduced nephron number associated with premature delivery is a likely risk factor for acute kidney injury, although the severity of illness, exposure to nephrotoxic medications, and malnutrition are additionally likely to contribute. 52,75 No defined threshold of creatinine level currently exists to facilitate diagnosis of renal dysfunction in neonates. Consequently, increased awareness among clinicians is required to detect renal injury in affected individuals, to ensure minimization of subsequent renal damage, and to determine the requirement and course of long-term follow-up in premature infants.…”

One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health

“…For example, in India it represents almost 25 to 30% of all births and is a major contributor to perinatal and neonatal morbidity and mortality and to subsequent impaired growth and stunting (Sachdev, 2001). The impact of intrauterine growth retardation and consequent low birth weight on the long term health of the offspring has now been established in large epidemiological studies in humans from different parts of the world and shown in animal models (Barker, 1994; Hales, 1997; Yajnik et al, 1995; Godfrey KM, 1998; Ozanne and Hales, 2002; Whincup et al, 2008; Warner and Ozanne, 2010; Kalhan and Wilson-Costello, 2013). The relationship between fetal growth and its regulation and nutritional, and endocrine interactions between the mother, the placenta and the fetus has been studied extensively (Murphy et al, 2006; Fowden and Forhead, 2009).…”

Premature Birth and Disease Programming. Contribution of Neonatal Intensive Care

“…При этом ряд технологий исключают из про-токолов, если доказаны их побочные или негатив-ные последствия. Так произошло с постнатальным использованием дексаметазона для предотвращения бронхолегочной дисплазии после сообщений о его негативном влиянии на развитие ЦНС [19].…”