Body composition in preterm infants: a systematic review on measurement methods.

BACKGROUND: There are several methods to measure body composition in preterm infants. Yet, there is no agreement on which method should be preferred. METHODS: PubMed, Embase.com, Wiley/Cochrane Library, and Google Scholar were searched for studies that reported on the predictive value or validity of body composition measurements in preterms, up to 6 months corrected age. RESULTS: Nineteen out of 1884 identified studies were included. Predictive equations based on weight and length indices, body area circumferences, skinfold thickness, bioelectrical impedance, and ultrasound did not show agreement with body composition measured with air displacement plethysmography (ADP), dual-energy x-ray absorptiometry (DXA), magnetic resonance imaging (MRI), or isotope dilution. ADP agreed well with fat mass density measured by isotope dilution (bias -0.002 g/ml, limits of agreement ±0.012 g/ml, n = 14). Fat mass percentage measured with ADP did not agree well with fat mass percentage measured by isotope dilution (limits of agreement up to ±5.8%) and the bias between measurements was up to 2.2%. DXA, MRI, and isotope dilution were not compared to another reference method in preterms. CONCLUSIONS: DXA, ADP, and isotope dilution methods are considered trustworthy validated techniques. Nevertheless, this review showed that these methods may not yield comparable results. IMPACT: Based on validation studies that were conducted in a limited number of study subjects, weight and length indices, body area circumferences, skinfold thickness, bioelectrical impedance, and ultrasound seem to be a poor representation of body composition in preterm infants. DXA, ADP, and isotope dilution methods are considered trustworthy and validated techniques. Nevertheless, these methods may not yield comparable results.

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.

A comparative study using dual-energy X-ray absorptiometry, air displacement plethysmography, and skinfolds to assess fat mass in preterms at term equivalent age.

The aim of this study was to compare whole body composition, generated by air displacement plethysmography (ADP) and dual-energy X-ray absorptiometry (DXA), and to evaluate the potential predictive value of the sum of skinfolds (∑SFT) for whole body composition, in preterm infants at term equivalent age. A convenience sample of sixty-five preterm infants with a mean (SD) gestational age of 29 (1.6) weeks was studied at term equivalent age. Fat mass measured by DXA and ADP were compared and the ability of the ∑SFT to predict whole body fat mass was investigated. There was poor agreement between fat mass percentage measured with ADP compared with DXA (limits of agreement: - 4.8% and 13.7%). A previously modeled predictive equation with the ∑SFT as a predictor for absolute fat mass could not be validated. Corrected for confounders, the ∑SFT explained 42% (ADP, p = 0.001) and 75% (DXA, p = 0.001) of the variance in fat mass percentage.Conclusions: The ∑SFT was not able to accurately predict fat mass and ADP and DXA did not show comparable results. It remains to be elucidated whether or not DXA provides more accurate assessment of whole body fat mass than ADP in preterm infants.Trial registration: NTR5311 What is Known: • Diverse methods are used to assess fat mass in preterm infants. What is New: • This study showed that there is poor agreement between dual-energy X-ray absorptiometry, air displacement plethysmography, and skinfold thickness measurements. • Our results affirm the need for consensus guidelines on how to measure fat mass in preterm infants, to improve the assimilation of data from different studies and the implementation of the findings from those studies.

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.

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.

Reference curves of birth weight, length, and head circumference for gestational ages in Yogyakarta, Indonesia.

BACKGROUND: The birth weight reference curve to estimate the newborns at risk in need of assessment and monitoring has been established. The previous reference curves from Indonesia, approximately 8 years ago, were based on the data collected from teaching hospitals only with limited gestational ages. The aims of the study were to update the reference curves for birth weight, supine length and head circumference for Indonesia, and to compare birth weight curves of boys and girls, first child and later children, and the ones in the previous studies. METHODS: Data were extracted from the Maternal-Perinatal database between 1998-2007. Only live singletons with recorded gestational ages of 26 to 42 weeks and the exact time of admission to the neonatal facilities delivered or referred within 24 h of age to Sardjito Hospital, five district hospitals and five health centers in Yogyakarta Special Territory were included. Newborns with severely ill conditions, congenital anomaly and chromosomal abnormality were excluded. Smoothening of the curves was accomplished using a third-order polynomial equation. RESULTS: Our study included 54,599 singleton live births. Growth curves were constructed for boys (53.3%) and girls (46.7%) for birth weight, supine length, and head circumference. At term, mean birth weight for each gestational age of boys was significantly higher than that of girls. While mean birth weight for each gestational age of first-born-children, on the other hand was significantly lower than that of later-born-children. The mean birth weight was lower than that of Lubchenco's study. Compared with the previous Indonesian study by Alisyahbana, no differences were observed for the aterm infants, but lower mean birth weight was observed in preterm infants. CONCLUSIONS: Updated neonatal reference curves for birth weight, supine length and head circumference are important to classify high risk newborns in specific area and to identify newborns requiring attention.

Dietary proteins and IGF I levels in preterm infants: determinants of growth, body composition, and neurodevelopment.

It has been demonstrated that a high-protein diet in preterm born infants during the first weeks of life may enable a growth rate equal to that seen in utero and may also result in a better long-term neurodevelopmental outcome. This diet may limit immediate postnatal growth retardation and may hence lower the risk of increased fat deposition after birth leading to the metabolic syndrome in later life. Insulin-like growth factor I (IGF I) has proven to play an important role in early postnatal growth of preterm infants, but also seems to have a persisting influence on body composition in childhood. Furthermore, increased IGF I concentrations in preterm infants have been associated with improved neurodevelopmental outcome. This review will elaborate on the role of dietary proteins and IGF I on growth, body composition, and neurodevelopment of preterm infants. Possible causal pathways will be explored and areas for future research will be proposed.

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.

A crucial role for white matter alterations in interference control problems of very preterm children.

BACKGROUND: Attention problems are among the most prominent behavioral deficits reported in very preterm children (below 32 wk of gestation) at school age. In this study, we aimed to elucidate the brain abnormalities underlying attention problems in very preterm children by investigating the role of abnormalities in white and gray brain matter during interference control, using functional magnetic resonance imaging (fMRI)-guided probabilistic diffusion tensor tractography. METHODS: Twenty-nine very preterm children (mean (SD) age: 8.6 (0.3) y), and 47 term controls (mean (SD) age: 8.7 (0.5) y), performed a fMRI version of the Eriksen Flanker task measuring interference control. RESULTS: Very preterm children showed slower reaction times than term controls when interfering stimuli were presented, indicating poorer interference control. Very preterm children and term controls did not differ in mean activation of the cortical regions involved in interference control. However, impaired fractional anisotropy (FA) was found in very preterm children in specifically those fiber tracts that innervate the cortical regions involved in interference control. Lower FA was related to poorer interference control in very preterm children. CONCLUSION: White matter alterations have a crucial role in the interference control problems of very preterm children at school age.

Neurodevelopmental outcome during the first year of life in preterm infants after supplementation of a prebiotic mixture in the neonatal period: a follow-up study.

AIM: The study aimed to determine the effect of enteral supplementation of a prebiotic mixture (neutral and acidic oligosaccharides) in the neonatal period on neurodevelopmental outcome in preterm infants with a gestational age of less than 32 weeks and/or birth weight of less than 1,500 g in the first year of life. METHODS: Neurodevelopmental outcome consisted of tone and motility according to Touwen, motor ability according to the Alberta Infant Motor Scale, as well as vision and hearing were evaluated at 0, 3, 6, and 12 months corrected age (CA). To adjust for potential confounders, data were analyzed by multinomial or logistic regression. RESULTS: In total, 93 of 101 infants (92%) participated in the study (prebiotic mixture group [n = 48] and placebo group [n = 45]). Incidence of suspect and abnormal neurodevelopmental outcome and delayed motor ability was not different in the prebiotic mixture and placebo group at 0, 3, 6, and 12 months (CA). Infants with 1 or more neonatal infections or more had a higher incidence of abnormal neurodevelopmental outcome (OR: 20.73; 95% CI: 1.31-328.46; p = 0.03) at 6 months CA. CONCLUSION: Short-term enteral supplementation of a prebiotic mixture in the neonatal period had no effect on neurodevelopmental outcome in preterm infants in the first year of life. However, serious neonatal infections in preterm infants were associated with adverse neurodevelopmental outcome at 6 months, but not at 12 months.

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.

Associations between Bronchopulmonary Dysplasia, Insulin-like Growth Factor I and Nutrition.

Insulin-like growth factor I (IGF-I) has been suggested as an important factor in the pathogenesis of bronchopulmonary dysplasia (BPD). In turn, nutrition has been associated with IGF-I levels and could be of importance in the pathogenesis of BPD. This study aimed to explore the association between nutrition, the IGF-I axis and the occurrence of BPD. Eighty-six preterm infants (44 male, mean gestational age: 29.0 weeks (standard deviation: 1.7 weeks)) were enrolled in an observational study. Serum IGF-I (µg/L) and insulin-like growth factor binding protein 3 (IGFBP-3; mg/L) were measured at birth and at 2, 4 and 6 weeks postnatal age. BPD was diagnosed at 36 weeks postmenstrual age. Twenty-nine infants were diagnosed with BPD. For every µg/L per week increase in IGF-I, the odds of BPD decreased (0.68, 95% CI 0.48-0.96, corrected for gestational age). The change in IGF-I in µg/L/week, gestational age in weeks and a week of predominant donor human milk feeding were associated with the occurrence of BPD in the multivariable analysis (respectively, OR 0.63 (0.43-0.92), OR 0.44 (0.26-0.76) and 7.6 (1.2-50.4)). IGFBP-3 was not associated with the occurrence of BPD in the multivariable analysis. In conclusion, a slow increase in IGF-I levels and a lower gestational age increase the odds of BPD. Donor human milk might increase the odds of BPD and should be further explored.

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.

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.

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.

The crucial role of the predictability of motor response in visuomotor deficits in very preterm children at school age.

AIM: We aimed to clarify the underpinnings of widespread visuomotor deficits in very preterm children. METHOD: Fifty-eight very preterm children (26 males, 32 females; mean [SD] age 7 y 6 mo [5 mo], gestational age 29.2 wks [1.6]; birthweight 1237 g [336]), recruited from a tertiary level neonatal intensive care unit, and 64 age-matched, comparison children born at term (28 males, 36 females; mean age [SD] 7 y 8 mo [7 mo]) participated. IQ was measured using a short form of the Wechsler Intelligence Scale for Children (3rd edition). A research diagnosis of developmental coordination disorder (DCD) was defined as a score below the 15th centile on the Movement Assessment Battery for Children. Visuomotor performance was assessed using a computerized task, in which children followed a predictable (structured condition) or an unpredictable (non-structured condition) trail on a touch screen using their index finger. RESULTS: Forty-six per cent of the very preterm children had a research diagnosis of DCD, compared with 16% of children born at term (p<0.001, odds ratio 4.69 [95% CI 2.01-10.99]). No group difference in visuomotor performance was present for the structured condition. In the non-structured condition, children born very preterm with and without a research diagnosis of DCD had poorer visuomotor performance than those born at term. INTERPRETATION: The predictability of the required motor response plays a crucial role in visuomotor deficits in very preterm children, regardless of DCD status.

Effect of non-human neutral and acidic oligosaccharides on allergic and infectious diseases in preterm infants.

UNLABELLED: Short-term supplementation of non-human neutral and acidic oligosaccharides during the first postnatal weeks may enhance the maturation of the immune response in preterm infants and may lead to less allergic and infectious diseases during the first year of life. In a randomized controlled trial, 113 preterm infants (gestational age <32 weeks and/or birth weight <1500 g) were allocated to receive enteral neutral and acidic oligosaccharide supplementation or placebo between days 3 and 30 of life. The median age at follow-up was not different in both groups: 12 months corrected age (interquartile range [IQR], 11-15) in the prebiotic mixture group and 12 months corrected age in the placebo group (IQR, 10-19), respectively. In addition, baseline patient, maternal, and environmental characteristics were not different between the prebiotic mixture (n = 48) and placebo (n = 46) group. Incidence of allergic and infectious diseases was assessed by validated questionnaires. In total, 94/98 (96 %) of the eligible, surviving infants participated in this follow-up study. The incidence of atopic dermatitis (odds ratio [OR], 0.80; 95 % confidence interval [CI], 0.24-2.67), bronchial hyper-reactivity (OR, 1.04; 95 % CI, 0.38-2.87) and infections of the upper respiratory (OR, 0.95; 95 % CI, 0.37-2.44), lower respiratory (OR, 1.03; 95 % CI, 0.37-2.88), and gastrointestinal (OR, 1.77; 95 % CI, 0.55-5.73) tract was not different between the groups. Adjustment for potential confounding factors did not change the results of the primary analysis. CONCLUSION: Short-term enteral supplementation of non-human neutral and acidic oligosaccharides during the neonatal period in preterm infants does not decrease the incidence of allergic and infectious diseases during the first year of life.

Attention problems of very preterm children compared with age-matched term controls at school-age.

OBJECTIVES: To clarify the severity, specificity, and neurocognitive underpinnings of attention problems in very preterm children. STUDY DESIGN: A sample of 66 preterm (<32 weeks gestation), mean (SD) age 7.5 (0.4) years, and 66 age-matched term controls participated. Symptoms of inattention were assessed using parent and teacher-rated questionnaires, and neurocognitive measures included speed and consistency in speed of information processing, lapses of attention (tau), alerting, orienting, and executive attention, as well as verbal and visuospatial working memory. Group differences were investigated using ANOVA, and Sobel tests were used to clarify the mediating role of neurocognitive impairments on attention problems. RESULTS: There was a large decrease in visuospatial working memory abilities (P < .001, d = .87), and medium increases in tau (P = .002, d = 0.55) as well as parent and teacher ratings of inattention (range d = 0.40-0.56) in very preterm children compared with term peers. Tau and visuospatial working memory were significant predictors of parent (R(2) = .161, P < .001 and R(2) = .071, P = .001; respectively) and teacher (R(2) = .152, P < .001 and R(2) = .064, P = .002; respectively) ratings of inattention, and completely explained the effects of very preterm birth on attention problems. CONCLUSIONS: Increased lapses of attention and poorer visuospatial working memory fully account for the attention problems in very premature children at school-age.

Effects of neonatal enteral glutamine supplementation on cognitive, motor and behavioural outcomes in very preterm and/or very low birth weight children at school age.

In very preterm ( < 32 weeks of gestation) and/or very low birth weight (VLBW, < 1500 g birth weight) children, serious neonatal infections are among the main causes of poor developmental outcomes later in childhood. The amino acid glutamine has been shown to reduce the incidence of serious neonatal infections in very preterm and/or VLBW children, while developmental effects beyond 24 months are unknown. We determined the cognitive, motor and behavioural outcomes at school age of a cohort of sixty-four very preterm and/or VLBW children (aged 7·5 (sd 0·4) years) who participated in a randomised placebo-controlled trial using enteral glutamine between day 3 and day 30 of life. Cognitive and motor outcomes were studied using the Wechsler Intelligence Scale for Children-III, the Movement Assessment Battery for Children (MABC), the Attention Network Test and a visual working memory task. Behavioural outcomes were evaluated using parent- and teacher-rated questionnaires. Intelligence quotient, processing speed, attentional functioning, working memory and parent- and teacher-rated behavioural outcomes were not different between children treated with glutamine or placebo; only visuomotor abilities as measured by the Ball Skills scale of the MABC (P = 0·002; d = 0·67) were poorer in the glutamine group. This effect persisted after taking into account the beneficial effects of lower serious neonatal infections rates in children treated with glutamine (P = 0·005). In conclusion, glutamine supplementation between day 3 and day 30 of life had neither beneficial nor detrimental effects on long-term cognitive, motor and behavioural outcomes of very preterm and/or VLBW children at school age, although visuomotor abilities were poorer in children that received glutamine.

Effect of neutral and acidic oligosaccharides on fecal IL-8 and fecal calprotectin in preterm infants.

The gastrointestinal inflammatory response may play a role in the susceptibility of preterm infants for infections. We previously reported a trend toward lower endogenous infection morbidity after enteral supplementation of neutral and acidic oligosaccharides (SC GOS/LC FOS/AOS). We hypothesize that enteral supplementation of prebiotics may decrease infectious morbidity by reducing intestinal inflammation. Therefore, we aimed to determine the effect of enteral supplementation of prebiotics on intestinal inflammation, as measured by fecal IL-8 (f-IL-8) and calprotectin (f-calprotectin), in preterm infants. In a randomized controlled trial, infants with a GA <32 wk and/or birth weight <1,500 g received enteral supplementation of prebiotics or placebo (maltodextrin) between d 3 and 30 of life. F-IL-8 and f-calprotectin was assessed at baseline, d 7, 14, and 30 of life. In total, 113 infants were included. Baseline patient and nutritional characteristics were not different in the SC GOS/LC FOS/AOS (n = 55) and the placebo group (n = 58). Enteral supplementation of prebiotics had no effect on f-IL-8 and f-calprotectin. F-IL-8 and f-calprotectin were strongly correlated at all time points (p < 0.001). In conclusion, enteral supplementation of prebiotics (SC GOS/LC FOS/AOS) does not affect f-IL-8 and f-calprotectin levels in preterm infants.