Estimation of the reference values and decision limits for growth hormone in newborns using dried blood spots.

OBJECTIVES: Severe deficiency of growth hormone (GHD) of the newborn is a rare but potentially life-threatening disease. GH measured during the first week of life, using dried blood spots (DBS), may offer several advantages. Aim of the study was to estimate the reference values for GH in newborns by a new analytical method using DBS. METHODS: Using a new developed analytical method, GH was estimated from DBS of 1,036 healthy newborns attending the Neonatology Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan in the period July-October 2021. Reference values for GH deficiency were estimated by the Harrell-Davis bootstrap method, with 90 %CI calculated by the bias-corrected and accelerated bootstrap method. RESULTS: All GH measurements required 33 analytical sessions (8 months) with a CV% for calibration curve slopes equal to 6.9 %. Intermediate precision evaluated by measurement of low (3 µg/L) and high (10 µg/L) quality controls was, respectively, 14 and 6.5 %. GH reference values, estimated at percentiles 1.0st, 2.5th and 5.0th, and their 90 %CI, were, respectively, 4.5 µg/L (90 %CI 3.8-5.1), 5.9 µg/L (90 %CI 5.4-6.4) and 7.0 µg/L (90 %CI 6.7-7.3). GH levels were not associated with sex, standard deviation scores, birth weight, gestational age, type of delivery or mother's variables (age, smoking habit, gestational diabetes). CONCLUSIONS: Validation data suggest that this method can be used to measured GH in newborns using DBS. The reference values estimated in this study are in accordance with previous published works using ELISA and may help confirming the clinical suspicion of neonatal GHD.

Dose-dependent impact of human milk feeding on tidal breathing flow-volume loop parameters across the first 2 years of life in extremely low-birth-weight infants: a cohort study.

The purpose of this study is to test the hypothesis that higher consumption of human milk (HM) in preterm infants with birth weight (BW) <1000 g is associated with improved lung function in a dose-dependent manner over the first 2 years of corrected age (CA). This retrospective study at an academic medical center included infants with BW <1000g. They had lung function assessment by the tidal breathing flow-volume loop (TBFVL) follow-up visits at 0-3-, 3-6-, 6-12-, 12-18-, and 18-24-month CA. One hundred eighty infants were included in the study with a mean (SD) gestational age 26.5 (1.90) weeks and BW 772.4 (147.0) g, 50% were female, and 60% developed BPD. 62.8% of infants received HM during the NICU stay. According to a general linear model (including GA, being small for GA (SGA), sex, human milk percentage, sepsis, and BPD), on average, each week of GA resulted in a higher tPTEF/tE of 1.24 (p = 0.039) and being SGA in a lower tPTEF/tE of 5.75 (p = 0.013) at 0-3-month CA. A higher percentage of human milk out of the total enteral intake was associated with better tPTEF/tE z-scores at 0-3 months (p = 0.004) and 18-24 months of CA (p = 0.041). BPD diagnosis was associated with a relevantly worse tPTEF/tE z-score at 6-12 months of CA (p = 0.003). CONCLUSION: Preterm infants with higher consumption of HM had significantly less airway obstruction across the first 2 years, suggesting that human milk may contribute in a dose-dependent manner to improve lung function in early childhood in former preterm infants born ELBW. WHAT IS KNOWN: • Human milk feeding reduces the risk of prematurity-related morbidities, including necrotizing enterocolitis, sepsis, lower respiratory tract infections, and BPD. Both exclusive and partial human milk feeding appear to be associated with a lower risk of BPD in preterm infants. WHAT IS NEW: • This cohort study of 180 preterm infants with birth weight < 1000 g found that exposure to human milk during hospitalization improves airway obstruction markers tPTEF/tE z-score over the first 2 years of corrected age in a dose-dependent manner.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) I-Cognitive Function and Metabolic Risk.

Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials, n = 1410; adjusted relative risk (aRR) 0.88 [95% CI 0.68, 1.13]; p = 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials, n = 438; aRR 0.94 [0.76, 1.17]; p = 0.59). However, supplementation reduced motor impairment in toddlers (13 trials, n = 1406; aRR 0.76 [0.60, 0.97]; p = 0.03), and improved motor scores overall (13 trials, n = 1406; adjusted mean difference 1.57 [0.14, 2.99]; p = 0.03) and in girls not boys (p = 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth.

Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m2: adjusted mean difference (aMD) -0.11[95% CI -0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.

Effect of human milk and other neonatal variables on lung function at three months corrected age.

OBJECTIVE: To evaluate the impact of human milk and different neonatal variables on tidal breathing flow-volume loop (TBFVL) parameters within three months' corrected age (CA) in infants born ≤32 wks or weighing <1500 g. METHODS: We retrospectively studied 121 infants with gestational age (GA) ≤ 32 weeks or birth weight (BW) <1500 gr who had lung function assessment within three months' CA by TBFVL analysis between June 2009 and April 2018. We investigated the impact of GA, gender, being Small for GA (SGA), sepsis, days of mechanical ventilation (MV) and human milk feeding (HMF) on later respiratory function, both in the entire group and according to BW ( ≤1000 g and >1000 g). RESULTS: The mean(SD) z-score for tidal volume (Vt) and time to peak expiratory flow to expiratory time (tPTEF/tE) were respectively -4.3 (2.5) and -0.8 (2.0) for the overall population with no significant differences between infants <1000 g or ≥1000 g. The mean(SD) Vt standardized for body weight was 6.2(2.0) ml/kg. Being female was associated with better Vt/Kg, whereas longer MV or being born SGA were associated with worst tPTEF/tE. For infants with BW < 1000 gr, tPTEF/tE was positively associated with HMF. CONCLUSION: An early TBFVL assessment within three months' CA already reveals lung function alteration in preterm infants. Being female is associated with better Vt/Kg, while longer duration of MV or being born SGA negatively affect tPTEF/tE. The positive association between HMF and better tPTEF/tE in infants with BW <1000 g has emerged, which deserves further investigation.

How does gestational age affect growth and body composition of preterm twins?

BACKGROUND: Twins experience altered growth compared to singletons. The primary aim of this study was to compare growth and body composition (BC) of twin and singleton preterm infants from birth to 3 months according to gestational age (GA). Secondary aims were to evaluate the effect of chorionicity and mode of feeding on twins' BC. METHODS: Anthropometric measurements and BC were performed at term and 3 months in preterm infants (GA < 37 weeks). Infants were categorized as: extremely, very, moderate and late preterm infants. Chorionicity was assigned as monochorionic, dichorionic or multichorionic. Mode of feeding was recorded as any human milk feeding vs formula feeding. RESULTS: Five hundred and seventy-six preterm infants were included (223 twins). Late-preterm twins were lighter and shorter at each study point; fat-free mass (FFM) was lower in these infants at each study point, compared to singletons. No differences were found between twins and singleton on the other category. Multichorionic infants had an FFM deficit compared to monochorionic and dichorionic at term, whereas no differences were found at 3 months. FFM at term was negatively associated with being twin and formula-fed. CONCLUSIONS: Twins and singletons born before 34 weeks' GA showed similar anthropometry and BC. Conversely, twin late-preterm infants showed different growth and BC compared to singletons.

Human milk protein vs. formula protein and their use in preterm infants.

PURPOSE OF REVIEW: We review the current available evidence on the metabolic fate of human milk proteins and their potential clinical implications for growth and body composition development vs. those of formula proteins in preterm infants. RECENT FINDINGS: The decreased content of human milk protein in preterm mothers throughout lactation might contribute to the reduced growth reported in exclusively human milk-fed infants compared with that of formula-fed infants. Recent studies have demonstrated that preterm infants are capable of degrading human milk proteins regardless of their degree of prematurity or postnatal age, with limited contribution from milk proteases to protein digestion. The nitrogen balance of fortified human milk-fed preterm infants is higher than that of formula-fed preterm infants. Moreover, the growth of human milk-fed preterm infants appears to be accompanied by fat-free mass deposition. SUMMARY: Provided that adequate protein and energy intakes are delivered, human milk enhances protein use rather than oxidation as well as promotes tissue growth, leading to preferential fat-free mass deposition and contributing to the recovery of the body composition in preterm infants. Human milk feeding should be supported and promoted for all preterm mother-infant pairs.

Complementary Feeding Practices in a Cohort of Italian Late Preterm Infants.

Limited data are available on complementary feeding in preterm infants, who show increased nutritional needs and are at risk of altered postnatal growth. The aim of this study was to investigate the timing and content of complementary feeding in a cohort of late preterm infants. We conducted a prospective, observational study, including mothers who had given birth to infants admitted to level I or II of care with a gestational age between 34 and 36 weeks. Mothers were contacted at 3, 6 and 12 months after delivery by phone calls and were asked about their infant's mode of feeding and the timing and schedule of the introduction of different solid foods types. A total of 49 mothers and 57 infants completed the study. The mean postnatal age of the introduction of complementary foods was 5.7 ± 0.7 months. Low energy and/or low protein-dense foods were first introduced in most infants. Fruit as the first type of complementary food in the infant's diet was associated with a 1.6-month advance in initiating complementary feeding. The present findings provide further insight into complementary feeding practices in late preterm infants and underline the need for specific recommendations addressing this vulnerable population.

Can Basic Characteristics Estimate Body Composition in Early Infancy?

OBJECTIVES: Increasing evidence demonstrates that body composition in early life contributes to the programming of health later in life in both full-term and preterm infants. Given the important role of body composition, the increased availability of easy, noninvasive, and accurate techniques for its assessment has been recommended. The aim of the present study was to identify basic characteristics and anthropometric measurements that best correlate with body composition in infants. METHODS: Anthropometric measurements and body composition assessed by air-displacement plethysmography were assessed either at birth or at term-corrected age in 1239 infants (654 full-term, 585 preterm). The associations of sex, GA (gestational age), and weight with FFM (fat-free mass) and FM (fat mass) adjusted by length (g/cm) were investigated by multiple linear regression models. Bland-Altman tests were performed, and an equation for calculating FFM was determined. RESULTS: Preterm infants exhibited increased FM and reduced FFM compared with full-term infants (477.6 ±â€Š204 vs 259.7 ±â€Š147 g and 2583 ±â€Š494 vs 2770 ±â€Š364 g, respectively). GA, male sex, and weight were positively associated with FFM (r = 0.806, P < 0.0001; 6.1 g of average bias). GA and male sex were negatively associated with FM, whereas weight was positively associated with FM (r = 0.641, P < 0.0001; 4.9 g of average bias). CONCLUSIONS: The assessment of body composition represents the criterion standard. When body composition assessment is not feasible, the equation based on sex, GA, and anthropometric measurements can be useful in predicting body composition in both full-term and preterm infants.

Seven Years Cognitive Functioning and Early Assessment in Extremely Low Birth Weight Children.

Infants born preterm are at high risk for the onset of cognitive dysfunctions at school age. The aim of this study was to investigate the association between early neurodevelopmental assessment and the risk of adverse cognitive outcome in extremely low birth weight children. We enrolled all newborns (January 2002 - April 2007) consecutively admitted to our Institution, with a birthweight < 1000 g. Exclusion criteria were genetic abnormalities, severe neurofunctional impairment, and/or neurosensory disabilities. Ninety-nine children were assessed at 1 year of corrected age using the Griffiths Mental Development Scales Revised. The same children were re-assessed at school age through the Wechsler Intelligence Scale for Children. Children with impaired Griffiths General Quotient (i.e., <1 SD) at 1 year of corrected age showed a significantly lower Full Scale Intelligence Quotient at 7 years of chronological age when compared to children who scored in the normal range at 1 year (p < 0.01). Considering the Griffiths Sub-quotients separately, a poor score in the Performance or in the Personal-Social Sub-quotients at 1 year was associated with significantly worse cognitive outcomes both in the Verbal and in the Performance Intelligence Quotients at 7 years (p < 0.01 and p < 0.05, respectively). A score <1 SD in the Locomotor or in the Eye and Hand Coordination Sub-quotients were specifically associated with poorer Performance or Verbal Intelligence Quotients, respectively (p < 0.05). Our findings suggest that a poor score on the Griffiths Scales at 1 year is associated with a higher risk of cognitive impairment at school age. Larger confirmation studies are needed.

Learning Disabilities in Extremely Low Birth Weight Children and Neurodevelopmental Profiles at Preschool Age.

At school age extremely low birth weight (ELBW) and extremely low gestational age (ELGAN) children are more likely to show Learning Disabilities (LDs) and difficulties in emotional regulation. The aim of this study was to investigate the incidence of LDs at school age and to detect neurodevelopmental indicators of risk for LDs at preschool ages in a cohort of ELBW/ELGAN children with broadly average intelligence. All consecutively newborns 2001-2006 admitted to the same Institution entered the study. Inclusion criteria were BW < 1000 g and/or GA < 28 weeks. Exclusion criteria were severe cerebral injuries, neurosensory disabilities, genetic abnormalities, and/or a Developmental Quotient below normal limits (< 1 SD) at 6 years. The presence of learning disabilities at school age was investigated through a parent-report questionnaire at children's age range 9-10 years. Neurodevelopmental profiles were assessed through the Griffiths Mental Development Scales at 1 and 2 years of corrected age and at 3, 4, 5, and 6 years of chronological age and were analyzed comparing two groups of children: those with LDs and those without. At school age 24 on 102 (23.5%) of our ELBW/ELGAN children met criteria for LDs in one or more areas, with 70.8% comorbidity with emotional/attention difficulties. Children with LDs scored significantly lower in the Griffiths Locomotor and Language subscales at 2 years of corrected age and in the Personal-social, Performance and Practical Reasoning subscales at 5 years of chronological age. Our findings suggest that, among the early developmental indicators of adverse school outcome, there is a poor motor experimentation, language delay, and personal-social immaturity. Cognitive rigidity and poor ability to manage practical situations also affect academic attainment. Timely detection of these early indicators of risk is crucial to assist the transition to school.

Neurofunctional assessment at term equivalent age can predict 3-year neurodevelopmental outcomes in very low birth weight infants.

AIM: Preterm infants are at high risk of developing motor delay, learning difficulties and behavioural problems and the availability of valid neurodevelopmental assessments is a major clinical issue. This study evaluated the relationship between preterm infants' neurofunctional assessment at term equivalent age and neurodevelopment outcome at three years of chronological age. METHODS: Neurofunctional assessment was performed in 70 very low birth weight infants at term equivalent age and neurodevelopmental outcome was assessed at three years of chronological age with the Griffiths Mental Development Scale - Extended Revised. RESULTS: At term equivalent age, 81% of the children had normal neurofunctional scores and 82.5% of those showed normal neurodevelopmental outcome at three years. Of the 19% who had impaired development at term equivalent age, 38.5% had neurodevelopmental delay at three years. Impaired neurofunctional status was associated with an increased risk of developmental delay in the global quotient (odds ratio 12.1) and locomotor sub-quotient (odds ratio 18.35) compared with normal neurofunctional status. Infants with sepsis or necrotising enterocolitis also faced a higher risk of neurodevelopmental delay. CONCLUSION: Neurofunctional assessment performed at term equivalent age appeared to provide early identification of preterm infants at risk of neurodevelopmental delay at three years of chronological age.

Formula-fed infants have significantly higher fat-free mass content in their bodies than breastfed babies.

AIM: Early nutrition may affect body composition development. This study assessed body composition changes in healthy term infants in the first four months of life, comparing the results for breastfed and formula-fed babies. METHODS: A longitudinal, observational study was conducted with healthy term infants, who had a birth weight of more than 2500 g and were aged up to 3 weeks at enrolment. Infants were either exclusively breastfed or formula-fed. Growth and body composition were assessed by air-displacement plethysmography at enrolment and 4 months. RESULTS: A total of 158 infants were enrolled (72 exclusively breastfed and 86 exclusively formula-fed). Body composition was similar between the two feeding groups at enrolment, but fat-free mass (4831 ± 538 g vs 4641 ± 461 g; p = 0.036) at 4 months and the fat-free mass changes between enrolment and 4 months (80.3 ± 16.4% vs 67.6 ± 18.4%; p < 0.001) were higher in formula-fed infants than breastfed ones. CONCLUSIONS: Our findings suggest that formula-fed infants show different body composition development during the first 4 months of life to breastfed ones, with higher fat-free mass content.

Implementation of nutritional strategies decreases postnatal growth restriction in preterm infants.

BACKGROUND: Prevention of postnatal growth restriction of very preterm infants still represents a challenge for neonatologists. As standard feeding regimens have proven to be inadequate. Improved feeding strategies are needed to promote growth. Aim of the present study was to evaluate whether a set of nutritional strategies could limit the postnatal growth restriction of a cohort of preterm infants. METHODOLOGY/PRINCIPAL FINDINGS: We performed a prospective non randomized interventional cohort study. Growth and body composition were assessed in 102 very low birth weight infants after the introduction of a set of nutritional practice changes. 69 very low birth weight infants who had received nutrition according to the standard nutritional feeding strategy served as a historical control group. Weight was assessed daily, length and head circumference weekly. Body composition at term corrected age was assessed using an air displacement plethysmography system. The cumulative parenteral energy and protein intakes during the first 7 days of life were higher in the intervention group than in the historical group (530 ± 81 vs 300 ± 93 kcal/kg, p<0.001 and 21 ± 2.9 vs 15 ± 3.2 g/kg, p<0.01). During weaning from parenteral nutrition, the intervention group received higher parental/enteral energy and protein intakes than the historical control group (1380 ± 58 vs 1090 ± 70 kcal/kg; 52.6 ± 7 vs 42.3 ± 10 g/kg, p<0.01). Enteral energy (kcal/kg/d) and protein (g/kg/d) intakes in the intervention group were higher than in the historical group (130 ± 11 vs 100 ± 13; 3.5 ± 0.5 vs 2.2 ± 0.6, p<0.01). The negative changes in z score from birth to discharge for weight and head circumference were significantly lower in the intervention group as compared to the historical group. No difference in fat mass percentage between the intervention and the historical groups was found. CONCLUSIONS: The optimization and the individualization of nutritional intervention promote postnatal growth of preterm infants without any effect on percentage of fat mass.

Growth and fat-free mass gain in preterm infants after discharge: a randomized controlled trial.

OBJECTIVE: To investigate whether the consumption of a nutrient-enriched formula after hospital discharge determines different growth and weight gain composition in preterm infants according to intra- and extrauterine growth pattern. METHODS: Two hundred seven preterm infants were randomized at term-corrected age to receive treatment A (term formula) or B (nutrient-enriched formula) up to 6 months of corrected age, using 2 computer-generated randomization lists, 1 for adequate for gestational age (AGA) and 1 for small for gestational age (SGA) infants. Infants were weaned according to our clinical practice after 6 months' corrected age. Anthropometric parameters and body composition by an air displacement plethysmography system were assessed at term and 1, 3, and 6 months' corrected age. Anthropometric parameters were also assessed at 12 months. RESULTS: Protein intakes were higher in infants receiving treatment B than in infants receiving treatment A at each study point. There were no differences between the feeding groups in weight and length SD scores in either the AGA and SGA group through the study. The mean head circumference values were higher in AGA infants receiving treatment B than in AGA infants receiving treatment A at 6 and 12 months, whereas at 6 months, the percentage of fat mass was lower. No difference in body composition was detected among SGA infants through the study. CONCLUSIONS: This randomized controlled trial demonstrates the beneficial effect of the consumption of a nutrient-enriched formula after hospital discharge by AGA infants both in terms of head circumference growth and fat-free mass gain.

Effect of nutrition on growth and body composition in infants born preterm.

The optimization of the nutritional management of preterm infants has gained importance due to the increased survival of these vulnerable infants. In fact, the achievement of an adequate growth has been associated with a favourable neurodevelopment outcome. Nevertheless, preterm infants still develop severe nutrient deficiencies during the first few weeks of life so that they are frequently growth restricted upon discharge. In addition, preterm infants have been found to show an increased and aberrant adiposity at term-corrected age. The development of strategies immediately after birth has been found to produce excellent results in terms of growth without having any detrimental effect on body composition at term-corrected age. Continuing to monitor growth and body composition changes in relation to different nutrition interventions is essential as growth pattern and body composition appear to have a long term effect on health outcomes.

Postnatal catch-up fat after late preterm birth.

BACKGROUND: Late preterm birth accounts for 70% of preterm births. The aim of the study was to investigate the postnatal weight gain and weight gain composition changes in a cohort of late preterm infants. METHODS: A total of 49 late preterm infants (mean birth weight 2,496 ± 330 g and gestational age 35.2 ± 0.7 wks) underwent growth and body composition assessment by an air displacement plethysmography system on the fifth day of life, at term, and at 1 and 3 mo of corrected age. The reference group was composed of 40 healthy, full-term, breast-fed infants. RESULTS: The late preterm infants showed a Δ fat mass gain between birth and term-corrected age equal to 182%. As compared with full-term infants, at term and 1 mo of corrected age mean weight (3,396 ± 390 vs. 3,074 ± 409 g and 4,521 ± 398 vs. 4,235 ± 673 g, respectively) and percentage of fat mass (16.1 ± 4.6 vs. 8.9 ± 2.9 and 22.6 ± 4.2 vs. 17.4 ± 4.0, respectively) were significantly higher in late preterm infants, whereas no difference among groups was found at 3 mo. CONCLUSION: Rapid postnatal catch-up fat was found in these infants. Further studies are needed to investigate whether this short-term increase in fat mass may modulate the risk of chronic diseases or represent an adaptive mechanism to extrauterine life.

Evaluation of air-displacement plethysmography for body composition assessment in preterm infants.

BACKGROUND: Adiposity may contribute to the future risk of disease. The aim of this study was to evaluate the accuracy and reliability of an air-displacement plethysmography (ADP) system to estimate percentage fat mass (%FM) in preterm infants and to evaluate interdevice reliability in infants. METHODS: A total of 70 preterm and 9 full-term infants were assessed. The accuracy of ADP measurements was assessed by determining reference %FM values using H(2)(18)O dilution measurement. RESULTS: Mean %FM by ADP was 5.67 ± 1.84 and mean %FM by H(2)18O dilution was 5.99 ± 2.56. Regression analysis showed that %FM by ADP was associated with %FM by H(2)(18)O dilution (R2 = 0.63, SE of estimate (SEE) = 1.65, P = 0.006). Bland-Altman analysis showed no bias (r = -0.48, P = 0.16) and 95% limits of agreement were -3.40 to 2.76 %FM. There was no difference in mean interdevice reliability %FM values (8.97 vs. 8.55 %FM) between ADP 1 and 2. Regression analysis indicated a low SEE (1.14% FM) and high R2 (0.91); 95% limits of agreement were -1.87 to 2.71 %FM. The regression line did not differ significantly from the line of identity. CONCLUSION: ADP is a noninvasive, reliable, and accurate technique to measure preterm infants' body composition in both research and clinical settings.

Tolerance and safety evaluation in a large cohort of healthy infants fed an innovative prebiotic formula: a randomized controlled trial.

BACKGROUND: the addition of oligosaccharides to infant formula has been shown to mimic some of the beneficial effects of human milk. The aim of the study was to assess the tolerance and safety of a formula containing an innovative mixture of oligosaccharides in early infancy. METHODOLOGY/PRINCIPAL FINDINGS: this study was performed as a multi-center, randomized, double-blind, placebo-controlled trial including healthy term infants. Infants were recruited before the age of 8 weeks, either having started with formula feeding or being fully breast-fed (breastfeeding group). Formula-fed infants were randomized to feeding with a regular formula containing a mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group). Growth, tolerance and adverse events were assessed at 8, 16, 24 and 52 weeks of age. The prebiotic and control groups showed similar mean weight, length and head circumference, skin fold thicknesses, arm circumference gains and stool frequency at each study point. As far as the anthropometric parameters are concerned, the prebiotic group and the control group did not attain the values shown by the breastfeeding group at any study point. The skin fold thicknesses assessed in the breastfeeding group at 8 weeks were strikingly larger than those in formula fed infants, whereas at 52 weeks were strikingly smaller. The stool consistency in the prebiotic group was softer than in the control group at 8, 16 and 24 weeks (p<0.001) and closer to that of the breastfeeding group. There was no difference in the incidence of adverse events between the two formula groups. CONCLUSIONS: our findings demonstrate the tolerability and the long term safety of a formula containing an innovative mixture of oligosaccharides in a large cohort of healthy infants. TRIAL REGISTRATION: drks-neu.uniklinik-freiburg.de DRKS 00000201.