Nutritional intake and growth until two years of age in moderate and late preterms.

BACKGROUND AND AIM: Moderate and late preterm infants (MLPTI) (gestational age 32 0/7-36 6/7 weeks), are at risk for suboptimal growth. This study evaluated adherence to nutritional recommendations until 6 months corrected age (CA), growth until 2 years CA, and associations between nutritional intake and growth until 2 years CA. METHODS: We prospectively collected nutritional intakes from 100 MLPTI during the first week of life and at 6 weeks, 3 months, and 6 months CA. Anthropometry was assessed at birth, discharge, term age, and at 6 weeks, 3 months, 6 months, 1 year, and 2 years CA. RESULTS: On day 7, <40% reached nutritional recommendations. Thereafter, >80% reached protein recommendations until 6 months of life, but <60% reached energy recommendations. Weight z-scores increased from -0.44 at term-age to 0.59 at 3 months CA, but declined to -0.53 at 2 years CA on the TNO curves. No significant associations were found between nutritional intake and growth until 2 years CA. CONCLUSION: No associations were demonstrated between nutritional intakes and growth until 2 years CA, despite not reaching recommended intakes. Despite high efforts to optimize growth, MLPTI find their own growth curve in the first 2 years of life. IMPACT: This research is pioneering in identifying how nutrition influences growth in moderate and late preterm infants (MLPTI) up to 2 years corrected age (CA). MLPTI often do not meet the recommended protein and energy intake in their first week of life, suggesting that current guidelines might be too high. No association was demonstrated between nutritional intake and growth of MLPTI in the first 2 years of life. Initially, MLPTI show an increase in weight z-scores from term age up to 3 months CA but experience a decline in weight z-scores at 2 years CA, according to TNO growth charts.

Growth and body composition of infants born moderate-to-late preterm fed a protein- and mineral-enriched postdischarge formula compared with a standard term formula until 6 months corrected age, a randomized controlled trial.

BACKGROUND: Infants born moderate-to-late preterm (i.e., 32 wk-35 wk 6 d gestation) are, analogous to those born very preterm, at risk of later obesity, hypertension, and diabetes. Appropriate early life nutrition is key for ensuring optimal growth and body composition, thereby mitigating potential cardiometabolic risks. OBJECTIVES: We aimed to compare growth and body composition between infants born moderate-to-late preterm fed isocaloric but protein- and mineral-enriched postdischarge formula (PDF) or standard term formula (STF) until 6 mo corrected age (CA; i.e., after term equivalent age [TEA]). METHODS: After enrollment (≤7 d postpartum), infants received PDF if (fortified) mother's own milk (MOM) was insufficient. At TEA, those receiving >25% of intake as formula were randomized to either continue the same PDF (n = 47) or switch to STF (n = 50); those receiving ≥75% of intake as MOM (n = 60) served as references. At TEA and 6 mo CA, we assessed anthropometry and body composition using both dual-energy x-ray absorptiometry (DXA) and air displacement plethysmography (ADP). RESULTS: Feeding groups had similar gestational age (median [25th percentile;75th percentile]: 34.3 [33.5; 35.1] wk), birthweight (mean ± standard deviation [SD]: 2175 ± 412 g), anthropometry, and body composition at TEA. At 6 mo CA, infants fed PDF had slightly, but significantly, greater length (67.6 ± 2.5 and 66.9 ± 2.6 cm, P < 0.05) and larger head circumference (43.9 ± 1.3 and 43.4 ± 1.5 cm, P < 0.05) compared to infants fed STF. Also, infants fed PDF had higher lean mass (LM) and bone mineral content estimated by DXA (4772 ± 675 and 4502 ± 741 g; 140 ± 20 and 131 ± 23 g, respectively; P < 0.05). ADP estimates, however, were not statistically different between feeding groups. CONCLUSIONS: Infants born moderate-to-late preterm demonstrated modest increases in length, head circumference, LM, and bone mineral content when fed PDF compared to STF for 6 mo after TEA. This trial was registered at the International Clinical Trial Registry Platform as NTR5117 and NTR NL4979.

MR Spectroscopy Shows Long Propylene Glycol Half-Life in Neonatal Brain.

INTRODUCTION: Neonatal propylene glycol (PG) clearance is low with long plasma half-life. We hypothesized that neonatal brain PG clearance is diminished and may be related to perinatal asphyxia, infection, or stroke, via different blood-brain barrier permeability. This study aimed to estimate cerebral PG half-life with a clearance model including PG measured with MR spectroscopy (MRS) in neonates that received phenobarbital as the only PG source and to evaluate whether PG clearance was related to intracerebral pathology, for example, perinatal asphyxia, infection, or stroke. METHODS: In this retrospective cohort study, 45 neonates receiving any dose of phenobarbital underwent MRS (short echo time single-voxel MRS at 1.5 T). Cumulative phenobarbital/PG doses were calculated. MRS indications were perinatal asphyxia (n = 22), infection (n = 4), stroke (n = 10), metabolic disease (n = 4), and others (n = 5). RESULTS: Medians (interquartile range) included gestational age 39.4 (3.1) weeks, birth weight 3,146 (1,340) g, and cumulative PG dose 700 (1,120) mg/kg. First-order kinetics with mono-exponential decay showed cerebral PG half-life of 40.7 h and volume of distribution of 1.6 L/kg. Zero-order kinetics showed a rate constant of 0.048 mM/h and a volume of distribution of 2.3 L/kg, but the fit had larger residuals than the first-order model. There were no differences in ΔPG (i.e., PG estimated with clearance model minus PG observed with MRS) in infants with perinatal asphyxia, infection, or stroke. DISCUSSION/CONCLUSION: This study showed a long cerebral PG half-life of 40.7 h in neonates, unrelated to perinatal asphyxia, infection, or stroke. These findings should increase awareness of possible toxic PG concentrations in neonatal brain due to intravenous PG-containing drugs.

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.

Neurodevelopment of children born very preterm and/or with a very low birth weight: 8-Year follow-up of a nutritional RCT.

BACKGROUND: Children born very preterm are at risk for cognitive deficits and motor impairment. Enhanced protein intake immediately after very preterm birth has been associated with favorable growth and improved neurodevelopment. It is unknown whether increased protein intake after discharge from the hospital affects long-term neurodevelopment. OBJECTIVE: The primary objective was to assess neurodevelopment from infancy to 8 years in preterm-born children who received either protein-enriched formula (PDF), standard term formula (TF), or human milk (HM) after discharge. The secondary objective was to assess the correlation between outcomes obtained at 24 months corrected age (CA) and at 8 years. METHODS: This RCT included 152 children born very preterm (gestational age ≤32 weeks) and/or with a very low birth weight (≤1500 g) of whom 102 were randomly assigned to receive PDF (n = 54) or TF (n = 48) from term age to 6 months CA. A control group of infants fed HM (n = 50) was also included. Neurodevelopmental outcomes were assessed at 24 months CA (cognitive and motor functioning; n = 123) and at 8 years (estimated Full Scale Intelligence Quotient, visual-motor skills, verbal memory, attention, and motor functioning; n = 76). RESULTS: The PDF and TF groups were not significantly different in neurodevelopmental outcomes. The HM group had a better cognitive score compared with the PDF group: at 24 months CA 92.9 ± 12.5 vs. 105.2 ± 18.6, P < 0.001 and at 8 years 98.1 ± 11.3 vs. 105.8 ± 9.1, P = 0.017 (P = 0.002 and P = 0.080, respectively, after adjustment for parental educational level). Correlations between outcomes at 24 months CA and 8 years were weak: r = 0.35 and r = 0.37 for cognitive and motor outcomes, respectively. CONCLUSIONS: PDF did not improve long-term neurodevelopmental outcomes as compared with TF. However, these results should be interpreted with caution considering the substantial attrition at follow-up. Furthermore, the correlation between outcomes at different ages was weak, emphasizing the need for long-term follow-up of nutritional intervention studies in preterm-born children.

Early-life growth of preterm infants and its impact on neurodevelopment.

BACKGROUND: Increasing numbers of preterm-born children survive nowadays, and improving long-term health and neurodevelopment is becoming more important. Early-life growth has been linked to neurodevelopmental outcomes. We aimed to study whether this association has changed with time. METHODS: We studied two cohorts of preterm-born children (gestational age ≤32 weeks and/or birth weight ≤1500 g) from 1983 (n = 708) and 2003-2006 (n = 138), respectively. We distinguished four early-life growth patterns at 3 months corrected age: appropriate for gestational age (AGA) with or without growth restriction (AGA GR+/AGA GR-), and small for gestational age (SGA) with or without catch-up growth (SGA CUG+/SGA CUG-). Intelligence quotient (IQ), neuromotor function, and behavior were assessed at ages 19 and 8 years, respectively, for the cohorts. RESULTS: In the 2003-2006 cohort, less children had early-life GR. In both cohorts, SGA CUG- subjects had unfavorable growth trajectories and neurodevelopmental outcomes (IQ ß -6.5, 95% confidence interval (CI) -9.8; -3.2, P < 0.001; neuromotor score ß -1.9%, 95% CI -3.2; -0.6, P = 0.005), while SGA CUG+ subjects were comparable to adequately grown subjects. CONCLUSION: Although the incidence of adverse growth patterns decreased between the cohorts, possibly indicating improvements in care over time, the impact of these growth patterns on neurodevelopmental outcomes was not significantly different. Achieving adequate early-life growth may be crucial for improving neurodevelopmental outcomes, especially for preterms born SGA.

Spectroscopic detection of brain propylene glycol in neonates: Effects of different pharmaceutical formulations of phenobarbital.

BACKGROUND: The first choice for treatment of neonatal convulsions is intravenous phenobarbital, which contains propylene glycol (PG) as a solvent. Although PG is generally considered safe, the dosage can exceed safety thresholds in neonates. High PG levels can cause lactic acidosis. PURPOSE/HYPOTHESIS: To investigate a relationship between brain PG concentration and medication administered to neonates, and to study if a correlation between spectroscopically detected PG and lactate was present. STUDY TYPE: Retrospective. POPULATION: Forty-one neonates who underwent MRI/MRS. FIELD STRENGTH/SEQUENCE: Short echo time single voxel MRS at 1.5T. ASSESSMENT: Spectra were quantified. Concentrations of PG were correlated with medication administered, because intravenously administered phenobarbital solutions contained 10, 25, or 50 mg phenobarbital per ml, all containing 350 mg PG per ml. The interval between medication and MRI/MRS was determined. STATISTICAL TESTS: Chi-square test, Student's t-test, Mann-Whitney U-test and Spearman correlation. RESULTS: Eighteen neonates had brain PG >1 mM (median 3.4 mM, maximum 9.5 mM). All 18 neonates with high brain PG and 14 neonates with low brain PG (<1 mM) received phenobarbital as the only source of PG. Nine neonates did not receive any phenobarbital/PG-containing medication. Neonates with high brain PG more often received 10 mg/ml phenobarbital, resulting in higher PG dose (high vs. low brain PG (median [interquartile range]: 1400 [595] vs. 350 [595] mg/kg, respectively, P < 0.01). In addition, the interval between the last phenobarbital dose and MRI was shorter in the high brain PG group (high vs. low brain PG: 16 [21] vs. 95 [83] hours, respectively, P < 0.001). Within neonates that received phenobarbital, there was no conclusive correlation between spectroscopically detected PG and lactate (Spearman's rho = 0.23, P = 0.10). DATA CONCLUSION: These MRS findings may increase awareness of potentially toxic PG concentrations in the neonatal brain due to intravenous phenobarbital administration and its dependence on the phenobarbital formulation used. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;49:1062-1068.

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.

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 preterm-born 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). Long-term 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 preterm-born 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. This trial was registered at www.trialregister.nl as NTR 2972 (follow-up study [STEP-2 (Study Towards the Effects of Post-discharge Nutrition 2)]) and NTR 55 [original randomized controlled trial (STEP)].

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 ≤1,500g, 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, 15min 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 (ß [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.

Relationship between fat mass measured by dual-energy X-ray absorptiometry and leptin in preterm infants between term age and 6 months' corrected age.

BACKGROUND/AIMS: In term subjects, fat mass (FM) is positively associated with leptin, whereas studies in preterm infants show conflicting results. However, none of these studies measured FM by dual-energy X-ray absorptiometry (DEXA). This study aims to relate FM measured by DEXA in relation to leptin and growth in preterm infants. METHODS: In 139 preterm infants, weight (kg) and length (cm) were measured at birth, term age, and 6 months' corrected age (CA). FM (kg), measured by whole-body DEXA, and leptin (µg/l) were measured at term age and 6 months' CA. RESULTS: At term age and 6 months' CA, FM was associated with leptin (ß = 1.94, 95% CI: 1.51-2.36, and ß = 0.37, 95% CI: 0.26-0.48, respectively; p < 0.001). Gain in weight standard deviation score (SDS) between term age and 6 months' CA was associated with FM and leptin at 6 months' CA (ß = 0.24, 95% CI: 0.18-0.30, and ß = 0.25, 95% CI: 0.16-0.33, respectively; p < 0.001). CONCLUSION: In preterm infants, FM measured by DEXA is associated with leptin, which indicates that leptin is a marker of body FM during the first 6 months after term age. Gain in weight SDS between term age and 6 months' CA results in higher FM and higher leptin at 6 months' CA.

Procollagen type I N-terminal peptide in preterm infants is associated with growth during the first six months post-term.

OBJECTIVE: To identify growth-related collagen and bone parameters in small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) preterm infants during the first six months post-term. In SGA preterm infants, increased growth and decreased bone acquisition, which we demonstrated previously, may be reflected by these markers. DESIGN: Observational study within a randomized controlled trial. PATIENTS: Thirty-three SGA (weight, length or both at birth <-2 SDS) and 98 AGA preterm infants (gestational age [median (IQR)]: 31·1 (1·6) vs 30·3 (2·0) weeks; 72·7% vs 42·9% boys). MEASUREMENTS: Weight (g), length (cm), procollagen type I N-terminal peptide (PINP; µg/l), urinary helical peptide (UHP; µg/mmol creatinine) and alkaline phosphatase (ALP; U/l) expressed as standard deviation scores (SDS) at term age, three and six months post-term. RESULTS: Weight and length gain during the first six months post-term and PINP SDS at term age, three months and six months post-term were higher in SGA compared with AGA infants. UHP SDS and ALP SDS were similar in SGA and AGA infants. PINP SDS and UHP SDS at term age and PINP SDS at three months were associated with subsequent weight and length gain until six months post-term. CONCLUSIONS: Increased growth in SGA compared with AGA preterm infants is reflected by increased collagen type I synthesis during the first six months post-term, suggesting that PINP and UHP correspond with growth in preterm infants. An explanation for decreased bone acquisition of SGA preterm infants may be that increased collagen type I synthesis is not directly followed by increased bone mineralization.

Iron deficiency and anemia in iron-fortified formula and human milk-fed preterm infants until 6 months post-term.

PURPOSE: An iron intake of >2 mg/kg/d is recommended for preterm infants. We hypothesized that human milk (HM)-fed preterm infants require iron supplementation after discharge, whereas iron-fortified formulae (IFF; 0.8-1.0 mg iron/100 ml) may provide sufficient dietary iron until 6 months post-term. METHODS: At term age, 3 and 6 months post-term, ferritin (µg/l) was measured in 92 IFF-fed infants (gestational age (median (interquartile range)) 30.7 (1.4) weeks, birth weight 1,375 (338) gram) and 46 HM-fed infants (gestational age 30.0 (1.7) weeks, birth weight 1,400 (571) gram). Iron intake (mg/kg/d) between term age and 6 months post-term was calculated. RESULTS: Iron was supplemented to 71.7% of HM-fed and 83.7% of IFF-fed infants between term age and 3 months post-term and to 13% of HM-fed and 0% of IFF-fed infants between 3 and 6 months post-term. IFF-fed infants had an iron intake from supplements and formula of 2.66 (1.22) mg/kg/d between term age and 3 months post-term and 1.19 (0.32) mg/kg/d between 3 and 6 months post-term. At 3 and 6 months post-term, the incidence of ferritin <12 µg/l was higher in HM-fed compared to IFF-fed infants (23.8 vs. 7.8% and 26.3 vs. 9.5%, P < 0.02). CONCLUSION: This observational study demonstrates that ferritin <12 µg/l is more prevalent in HM-fed infants until 6 months post-term. This may be due to early cessation of additional iron supplementation. We speculate that additional iron supplementation is not necessary in preterm infants fed IFF (0.8-1.0 mg iron/100 ml), as they achieve ferritin ≥12 µg/l without additional iron supplements between 3 and 6 months post-term.

Higher vitamin D intake in preterm infants fed an isocaloric, protein- and mineral-enriched postdischarge formula is associated with increased bone accretion.

During the first half of infancy, bone accretion in preterm infants fed an isocaloric, protein- and mineral-enriched postdischarge formula (PDF) is higher compared with those fed term formula (TF) or human milk (HM). This may be related to higher protein, calcium, phosphorus, and vitamin D intakes. This study investigated serum calcium, phosphate, and 25-hydroxyvitamin D [25(OH)D] in relation to bone mineral content (BMC) in PDF-, TF-, and HM-fed preterm infants between term age (40 wk postmenstrual age) and 6 mo corrected age (CA). Between term age and 6 mo CA, 52 preterm infants were fed PDF (per 100 mL: 67 kcal, 1.7 g protein, 65 mg calcium, 38 mg phosphorus, 56 IU vitamin D), 41 were fed TF (per 100 mL: 67 kcal, 1.47 g protein, 50 mg calcium, 30 mg phosphorus, 48 IU vitamin D), and 46 were fed HM. Serum calcium, phosphorus, and 25(OH)D were measured at term age and at 3 and 6 mo CA. BMC (g) was measured by whole-body dual-energy X-ray absorptiometry at term age and at 6 mo CA. Between term age and 6 mo CA, intakes of calcium, phosphorus, and vitamin D were significantly higher in PDF- compared with TF-fed infants, and PDF-fed infants reached significantly higher serum 25(OH)D concentrations at 6 mo CA (103 ± 24.3 vs. 92.8 ± 15.5 nmol/L, P = 0.003). Between term age and 6 mo CA, increases in serum 25(OH)D were associated with an increase in BMC (ß = 0.001; 95% CI: 0.00, 0.003; P = 0.046). In conclusion, during the first 6 mo postterm, higher vitamin D intake and greater increase in serum 25(OH)D concentration in PDF-fed preterm infants were associated with increased bone accretion.

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

BACKGROUND/AIMS: 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. METHODS: 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. RESULTS: 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: ß = -1.03, 95% CI -1.65;-0.41, p = 0.001 and ß = -0.78, 95% CI -1.32;-0.23, p = 0.005; insulin: ß = -0.19, 95% CI -0.37;-0.01, p = 0.044 and ß = -0.18, 95% CI -0.35;-0.01, p = 0.035). Nutrient intake was not associated with IGF-I or insulin. CONCLUSIONS: The present study suggests that IGF-I and insulin are important growth regulators in preterm infants until 6 months CA, independent of nutrient intake.

Timing of nutritional interventions in very-low-birth-weight infants: optimal neurodevelopment compared with the onset of the metabolic syndrome.

Recent nutritional research in very-low-birth-weight (VLBW) infants is focused on the prevention of protein malnutrition during the first postnatal weeks. At this early age, nutritional protein fortification depends on amino acid infusion via a central vein because of the immature gastrointestinal tract. In 2010 new guidelines on nutrition were proposed by the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition nutrition committee. In particular, the relative increase in the protein fraction in the nutrition of these infants aims to prevent early postnatal weight loss, to prevent morbidity, and to stimulate neurodevelopment. On the other hand, an increasing number of follow-up studies in VLBW infants indicate that, in particular, those infants who show rapid growth after preterm birth are at risk of metabolic consequences and cardiovascular disease later in life. In this review, we describe the quest to develop a customized diet that offers optimal nutrition at several time points of growth and development during the first year of life. This diet should prevent early malnutrition, enhance neurodevelopment, and limit the increase in total body fat during the first 6 mo. We question whether one type of early diet suffices for normal neurodevelopment with a normal body composition in later life or whether we need several types of diet at various stages of development.

Increased gain in bone mineral content of preterm infants fed an isocaloric, protein-, and mineral-enriched postdischarge formula.

PURPOSE: Preterm infants are at risk for suboptimal bone mineralization. Postnatal bone formation requires optimal nutritional composition. This study evaluated the effect of isocaloric, protein-, and mineral-enriched postdischarge formula (PDF), standard term formula (TF), and human milk (HM) on gain in bone mineral content (BMC) of preterm infants between term age (40 weeks postmenstrual age) and 6 months corrected age (CA). METHODS: Between term age and 6 months CA, 93 preterm infants were randomized to be fed PDF (n = 52) or TF (n = 41) and 46 preterm infants were fed HM. Weight (g) and length (cm) were measured at birth, term age, and 6 months CA. BMC (g) was measured by whole-body dual-energy x-ray absorptiometry at term age and 6 months CA. RESULTS: Gain in BMC (expressed as median with interquartile range) between term age and 6 months CA was higher in PDF-fed infants (102.3 (32.4) g) compared to TF- and HM-fed infants (91.6 (24.5) and 84.5 (33.3) g, respectively), adjusted for gender, gestational age, birthweight, and gain in weight and length. CONCLUSION: Between term age and 6 months CA, isocaloric PDF enhances gain in BMC of preterm infants, independent of gain in weight and length. We speculate that higher gain in BMC during infancy may improve adult bone mass in preterm infants.

Small-for-gestational-age preterm-born infants already have lower bone mass during early infancy.

BACKGROUND: In preterm-born infants, low birth weight and diminished bone accretion deteriorate peak bone mass. Whether low birth weight is already associated with decreased bone mass during infancy is unknown. OBJECTIVE: To study the effect of birth weight on bone accretion between term age (40 weeks postmenstrual age) and six months post-term in preterm-born infants. DESIGN: In 139 preterm-born infants (51% male, gestational age 30.3±1.5 weeks, birth weight 1341±288g) weight and whole-body bone mineral content (BMC, gram) were measured at term age and six months post-term. At birth, infants were small-for-gestational-age (SGA, n=33, weight and/or length<-2 SDS) or appropriate-for-gestational-age (AGA, n=98, weight and length≥-2 SDS). RESULTS: At term age and six months post-term, BMC adjusted for gender and gestational age was lower in SGA than AGA infants (term age: 38.1±9.5 versus 48.6±10.1g, ß=-0.26, 95% CI -0.37; -0.16, p<0.001; six months: 130.1±25.7 versus 145.4±22.9g, ß=-0.16, 95% CI -0.25; -0.08, p<0.001). At six months post-term, BMC remained lower in SGA infants after adjustment for actual weight and length. Between term age and six months post-term, BMC gain adjusted for gender and gestational age was lower in SGA than AGA infants (91.7±22.8 versus 98.2±20.7g; ß=-0.12, 95% CI -0.24; -0.003, p=0.044). BMC gain remained lower in SGA infants after adjustment for weight and length gain. CONCLUSION: The first six months post-term, SGA preterms have lower bone accretion, independent of body size, suggesting that prenatal conditions for bone accretion cannot be replicated postnatally.