Follow-up of a randomized trial on postdischarge nutrition in preterm-born children at age 8 y

Background: Early nutritional interventions may modulate health risks in preterm-born infants. Previously, we showed that pretermborn infants fed an isocaloric protein- and mineral-enriched postdischarge formula (PDF) from term age to 6-mo corrected age (CA) gained more lean mass than did those fed term formula (TF). Longterm follow-up of randomized nutritional trials is important to test the hypothesis that short-term positive effects on health are sustainable. Objective: The aim of this follow-up study was to compare body size, body composition, and metabolic health at age 8 y in pretermborn children who were randomly assigned to receive either PDF or TF from term age until 6-mo CA. Design: A total of 79 of 152 children (52%) from the original randomized controlled trial were enrolled for follow-up at age 8 y. Weight, height, and head circumference were measured by using standard methods. Body composition, including fat mass, lean mass, bone mineral content, and bone mineral density, was determined by dual-energy X-ray absorptiometry. Blood pressure was measured in the supine position by using an automatic device. Metabolic variables, including glucose, insulin, insulin-like growth factor I, triglycerides, cholesterol, cortisol, and leptin, were measured after an overnight fast. Nutritional habits at age 8 y were assessed by using a 3-d nutritional diary. Results: At age 8 y, no differences were found in body size, body composition, bone variables, and metabolic health variables when comparing children fed PDF with those fed TF. Adjustment for known and possible confounders did not change these results. Conclusions: In this follow-up study in preterm-born children, we showed that the favorable effects of PDF at 6-mo CA either were not maintained or could not be confirmed because of attrition at the age of 8 y. We suggest that future research should focus on nutritional interventions in the pre- and postdischarge period as a continuum rather than as separate entities

Growth in preterm infants until six months postterm: the role of insulin and IGF-I

Since insulin-like growth factor type I (IGF-I) and insulin regulate growth in term infants, they were studied in relation to nutrient intake and growth until 6 months corrected age (CA) in preterm infants. In 138 preterm infants (51% male, gestational age (expressed as median (IQR)) 30.6 (1.9) weeks, birth weight 1,368 (389) g) weight SDS, length SDS, IGF-I, and insulin were measured at term age, 3 and 6 months CA. IGF-I and insulin at term age were associated with weight SDS and length SDS at term age and 3 months CA. IGF-I and insulin at 3 months CA were associated with weight SDS and length SDS at 3 and 6 months CA. IGF-I and insulin at term age were negatively associated with gain in weight SDS and gain in length SDS between term age and 6 months CA (IGF-I: β = -1.03, 95% CI -1.65;-0.41, p = 0.001 and β = -0.78, 95% CI -1.32;-0.23, p = 0.005; insulin: β = -0.19, 95% CI -0.37;-0.01, p = 0.044 and β = -0.18, 95% CI -0.35;-0.01, p = 0.035). Nutrient intake was not associated with IGF-I or insulin. The present study suggests that IGF-I and insulin are important growth regulators in preterm infants until 6 months CA, independent of nutrient intak

Post term dietary-induced changes in DHA and AA status relate to gains in weight, length, and head circumference in preterm infants

Preterms need supplementation with docosahexaenoic (DHA) and arachidonic (AA) acids to prevent steep postnatal declines. Associations between growth and erythrocyte (RBC) DHA and AA were studied in 139 preterms (51% male, gestational age 30.3 +/- 1.5 weeks, birth weight 1341 +/- 288 g) fed human milk with breast milk fortifier or preterm formula until term, followed by postdischarge formula (PDF: n=52, 0.4% DHA, 0.4% AA), term formula (TF; n=41, 0.2% DHA, 0.2% AA), or human milk (HM; n=46). At six months, PDF resulted in higher RBC-DHA than TF and HM, while RBC-AA was higher than TF, but similar to HM. There were no between-group differences in growth between term and six months. RHC-DHA related positively with gain in weight and length and negatively with gain in head circumference. RBC-AA related positively with gain in head circumference and negatively with gain in weight and length. In conclusion, PDF with higher DHA and AA than TF may promote postnatal growth of preterms. (C) 2011 Elsevier Ltd. All rights reserved

Improving long-term health outcomes of preterm infants: how to implement the findings of nutritional intervention studies into daily clinical practice

Preterm-born children are at risk for later neurodevelopmental problems and cardiometabolic diseases; early-life growth restriction and suboptimal neonatal nutrition have been recognized as risk factors. Prevention of these long-term sequelae has been the focus of intervention studies. High supplies of protein and energy during the first weeks of life (i.e., energy > 100 kcal kg−1 day−1 and a protein-to-energy ratio > 3 g/100 kcal) were found to improve both early growth and later neurodevelopmental outcome. Discontinuation of this high-energy diet is advised beyond 32–34 weeks postconceptional age to prevent excess fat mass and possible later cardiometabolic diseases. After discharge, nutrition with a higher protein-to-energy ratio (i.e., > 2.5–3.0 g/100 kcal) may improve growth and body composition in the short term. Conclusion: Preterm infants in their first weeks of life require a high-protein high-energy diet, starting shortly after birth. Subsequent adjustments in nutritional composition, aimed at achieving optimal body composition and minimizing the long-term cardiometabolic risks without jeopardizing the developing brain, should be guided by the growth pattern. The long-term impact of this strategy needs to be studied.What is Known:• Preterm infants are at risk for nutritional deficiencies and extrauterine growth restriction.• Extrauterine growth restriction and suboptimal nutrition are risk factors for neurodevelopmental problems and cardiometabolic disease in later life.What is New:• Postnatally, a shorter duration of high-energy nutrition may prevent excess fat mass accretion and its associated cardiometabolic risks and an early switch to a protein-enriched diet should be considered from 32-34 weeks postconceptional age.• In case of formula feeding, re-evaluate the need for the continuation of a protein-enriched diet, based on the infant’s growth pattern

Salt sensitivity of blood pressure at age 8 years in children born preterm

Preterm birth and low birth weight have been associated with an increased risk of hypertension; postnatal growth and dietary salt intake may contribute to these associations. In adults, the change of blood pressure (BP) in response to modifications in salt intake, i.e., salt sensitivity of BP, has been independently associated with cardiovascular disease. Little is known about salt sensitivity in children. We hypothesize that it may partly explain the association between preterm birth and higher BP in later life. We assessed salt sensitivity of BP at age 8 years in 63 preterm-born children, and explored its association with postnatal growth, sodium intake, and body composition from infancy onwards. BP was measured at baseline and after a 7-day high-salt diet. The difference in mean arterial pressure (MAP) was calculated; salt sensitivity was defined as an increase in MAP of ≥5%. Ten children (16%) showed salt sensitivity of BP, which was associated with neonatal growth restriction as well as with lower fat mass and BMI from infancy onwards. At age 8 years, children classified as salt sensitive had a lower weight-for-age SD-score (-1.5 ± 1.3 vs. -0.6 ± 1.1) and BMI (13.8 ± 1.7 vs. 15.5 ± 1.8 kg/m2) compared to their salt resistant counterparts. Sodium intake was not associated with (salt sensitivity of) BP. Salt sensitivity of BP was demonstrated in preterm-born children at age 8 years and may contribute to the development of cardiovascular disease at later age. Long-term follow-up studies are necessary to assess reproducibility of our findings and to explore clustering with other cardiovascular risk factors

Leptin and IGF-1 in relation to body composition and bone mineralization of preterm-born children from infancy to 8 years

Objective: Preterm birth has been associated with altered body composition, especially increased fat mass (FM) and decreased bone mineralization, and leptin and IGF-1 have been suggested to be involved in the regulation of both. We aimed to study the interplay between leptin, IGF-1, FM and bone mineralization measured in infancy and childhood of children born preterm. Design: Observational study. Patients/subjects: Seventy-nine (40 boys) preterm-born children (gestational age ≤32 weeks and/or birth weight ≤1500 g) aged 8 years. Measurements: Serum leptin and IGF-1 were measured at term age, at 3- and 6-month corrected age (CA), and 8 years. Body composition (fat and lean mass) and bone parameters (bone area, mineral content and density) were measured by Dual-energy X-ray Absorptiometry (DXA) at term age, 6-month CA and 8 years. Results: Leptin was positively associated with FM at all time points and with bone parameters at term age and 6-month CA. IGF-1 was associated with body composition and bone density at most of the time points. Explained variation in bone mineralization increased significantly by adding bone area (BA) and height to the models. Conclusions: During infancy and childhood, leptin and IGF-1 were associated with body composition in preterm-born children. In addition, leptin was associated with bone parameters in early infancy, but not in childhood. It is hypothesized that a complicated interplay between multiple pathways, which most likely changes over time, is involved in regulation of body composition and bone mineralization of preterm-born infants

Salt sensitivity of blood pressure at age 8 years in children born preterm

Preterm birth and low birth weight have been associated with an increased risk of hypertension; postnatal growth and dietary salt intake may contribute to these associations. In adults, the change of blood pressure (BP) in response to modifications in salt intake, i.e., salt sensitivity of BP, has been independently associated with cardiovascular disease. Little is known about salt sensitivity in children. We hypothesize that it may partly explain the association between preterm birth and higher BP in later life. We assessed salt sensitivity of BP at age 8 years in 63 preterm-born children, and explored its association with postnatal growth, sodium intake, and body composition from infancy onwards. BP was measured at baseline and after a 7-day high-salt diet. The difference in mean arterial pressure (MAP) was calculated; salt sensitivity was defined as an increase in MAP of ≥5%. Ten children (16%) showed salt sensitivity of BP, which was associated with neonatal growth restriction as well as with lower fat mass and BMI from infancy onwards. At age 8 years, children classified as salt sensitive had a lower weight-for-age SD-score (-1.5 ± 1.3 vs. -0.6 ± 1.1) and BMI (13.8 ± 1.7 vs. 15.5 ± 1.8 kg/m2) compared to their salt resistant counterparts. Sodium intake was not associated with (salt sensitivity of) BP. Salt sensitivity of BP was demonstrated in preterm-born children at age 8 years and may contribute to the development of cardiovascular disease at later age. Long-term follow-up studies are necessary to assess reproducibility of our findings and to explore clustering with other cardiovascular risk factors

Addressing nutritional needs in preterm infants to promote long-term health

The number of infants who are born (extremely) preterm and survive into adulthood is still increasing. Therefore, long-term consequences of preterm birth and possibilities to positively influence outcomes increasingly gain attention. Early nutrition and growth are thought to be important contributors in determining long-term health, especially with respect to cardiometabolic diseases and neurodevelopment. Adequate parenteral feeding of preterm infants immediately after birth, with a rapid replacement by enteral nutrition, preferably with fortified mother’s own milk, is considered of utmost importance. This can help to prevent extra-uterine growth restriction and to promote both short- and long-term health and development

Birth weight and postnatal growth in preterm born children are associated with cortisol in early infancy, but not at age 8 years

Background Preterm birth has been associated with altered hypothalamic-pituitary-adrenal (HPA-) axis activity as well as cardiometabolic diseases and neurodevelopmental impairments later in life. We assessed cortisol from term age to age 8 y in children born preterm, to explore the development of HPA-axis activity in association with intrauterine and early-postnatal growth until 6 mo. corrected age. Methods In 152 children born at a gestational age ≤32 wks. and/or with a birth weight ≤1,500 g, random serum cortisol was assessed at term age (n = 150), 3 mo. (n = 145) and 6 mo. corrected age (n = 144), and age 8 y (n = 59). Salivary cortisol was assessed at age 8 y (n = 75): prior to bedtime, at awakening, 15 min after awakening, and before lunch. Cortisol was analyzed in association with birth weight-standard deviation score (SDS), being born small for gestational age (SGA), and combinations of intrauterine and postnatal growth: appropriate for gestational age (AGA) with or without growth restriction (AGA GR+ or AGA GR−) at 6 mo. corrected age, and SGA with or without catch-up growth (SGA CUG+ or SGA CUG−) at 6 mo. corrected age. Cross-sectional associations at all time points were analyzed using linear regression, and longitudinal associations were analyzed using generalized estimating equations. Results Longitudinally, birth weight-SDS was associated with cortisol (β [95%CI]): lower cortisol over time was seen in infants with a birth weight ≤−2 SDS (−50.69 [−94.27; −7.11], p = 0.02), infants born SGA (−29.70 [−60.58; 1.19], p = 0.06), AGA GR+ infants (−55.10 [−106.02; −4.17], p = 0.03) and SGA CUG− infants (−61.91 [−104.73; −19.10], p = 0.01). In cross-sectional analyses at age 8 y, no associations were found between either serum or salivary cortisol and birth weight-SDS, SGA-status, or growth from birth to 6 mo. corrected age. Conclusion In children born preterm, poor intrauterine and postnatal growth were associated with lower cortisol in early infancy, but not at age 8 y. Even though HPA-axis activity no longer differed between groups at age 8 y, or differences could not be confirmed due to attrition, it is unknown whether the differences found in early infancy could attribute to increased health risks later in life