Aberrant Adiposity and Ectopic Lipid Deposition Characterize the Adult Phenotype of the Preterm Infant

Abstract

Our investigation addresses the hypothesis that disruption of third trimester development by preterm birth alters multiple biological pathways affecting metabolic health in adult life. We compared healthy adult volunteers aged 18 -27 y born at Յ33 wk gestation or at term. We used whole-body MRI, 1 H magnetic resonance spectroscopy (MRS) of liver and muscle, metabonomic profiling of blood and urine, and anthropometric and blood pressure measurements. Preterm subjects had greater (mean difference (95% CI)) total [2.21 L (0.3, 4.1), p ϭ 0.03] and abdominal adipose tissue [internal 0.51 (0.1, 0.9), p ϭ 0.007]; blood pressure [systolic 6.5 mm Hg (2.2, 10.8), p ϭ 0.004; diastolic 5.9 (1.8, 10.1), p ϭ 0.006]; and ectopic lipid (ratio (95% CI)), intrahepatocellular lipid (IHCL) 3.01 (1.78, 5.28) p Ͻ 0.001, and tibialis-intramyocellular lipid (T-IMCL) [1.31 (1.02, 1.69) p ϭ 0.04]. In preterm, compared with term men, there was greater internal adipose tissue [mean (SD); men: preterm 4.0 (1.6), term 2.7 (1.1) liters; women: preterm 2.6 (0.9); term 2.6 (0.5); gender-gestation interaction p ϭ 0.048] and significant differences in the urinary metabolome (elevated methylamines and acetylglycoproteins, lower hippurate). We have identified multiple premorbid biomarkers in ex-preterm young adults, which are most marked in men and indicative of risks to later wellbeing. These data offer insight into biological trajectories affected by preterm birth and/or neonatal care. A round 2% of births in the developed world are below 33 wk gestation. This rate is rising as is survival and Ͼ90% of these infants will go home. Survival free of major impairment is also rising, bringing with it the expectation of life-long health. Preterm birth may be a risk to adult health (1,2). Several groups describe higher blood pressure (3-7). Insulin resistance (8) and poorer reproductive health (9) have also been reported. The biological mediators are unknown.We have previously shown that by term, preterm infants have an altered body composition with significantly greater abdominal adipose tissue (10) and intrahepatocellular lipid (IHCL) (11). There is a high degree of correlation between hypertension, insulin resistance, and abdominal obesity. Abdominal adipose tissue in particular seems to play a major role in the pathogenesis of the metabolic syndrome (12). Increased "ectopic" lipid in liver and muscle as IHCL and soleus and tibialis intramyocellular lipid (S-IMCL and T-IMCL) are also strongly associated with these conditions (13).In this proof-of-concept study, we postulated that disruption of the normal pattern of third trimester development by preterm birth will affect a range of systems affecting metabolic health. We tested the primary hypothesis that young adults born at or below 33 wk gestation would have increased abdominal adiposity in the absence of overt obesity. We also evaluated IHCL, IMCL, fasting glucose and insulin, insulin resistance, serum lipids and serum, and urine metabolomes. METHODSApproval for the study was obtained fro...

Bone and fat mass in relation to postnatal levels of insulin-like growth factors in prematurely born children at 4 y of age

“…The preterm group had a relatively lower lean body mass and increased fat mass compared with the control group after correcting for possible confounders. Increased total and abdominal adipose tissue has also been reported in adult ex-preterm subjects compared with the same in controls (22). In pigs, with IGF-II mutations that induce increased IGF-II levels, more lean body mass is generated; thus, IGF-II seems to influence lean body mass (19).…”

Glucocorticoid Programming in Very Preterm Birth

“…On average, in subjects born very preterm or with VLBW, final height was reduced by 0.5 SD compared to population-specific reference data [51]. Young adults born preterm or with VLBW, despite having a relatively normal body mass index, exhibited a lower lean mass, increased fat content and centralization of fat distribution [11,14,53,54]. …”

Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial

“…18,64 We utilised IHCL content as a mechanistic marker of lipid tolerance, as levels at term correlate with early lipid intake 58 and are higher in very preterm than in full-term infants 18 and young adults. 65 We also monitored liver function using conventional biochemical markers and identified no between-group differences. Overall, our data support the conclusion of a systematic review and meta-analysis that fish oil-based lipid emulsions do not prevent PN-associated cholestasis 31 although the possibility that other formulations, including those with higher fish oil content, may be beneficial is not precluded.…”