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.

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.

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.

IGF-I, Growth, and Body Composition in Preterm Infants up to Term Equivalent Age.

CONTEXT: There are concerns that a higher fat mass in the early life of preterm infants is associated with adverse cardiometabolic outcomes in young adulthood. OBJECTIVE: To investigate the role of IGF-I and growth in determining body composition of preterm infants at term equivalent age. METHODS: An observational study was conducted from August 2015 to August 2018. From birth to term equivalent age, IGF-I levels were measured bi-weekly and growth was assessed weekly. At term equivalent age, body composition was assessed through air displacement plethysmography; 65 infants with a gestational age of 24 to 32 weeks were assessed at term equivalent age, of whom 58 completed body composition measurement. The main outcome measures were fat (free) mass (g) and fat (free) mass percentage at term equivalent age. RESULTS: In the first month of life, each 0.1 nmol/L per week increase in IGF-I was associated with a 465 g (SE 125 g) increase in fat free mass. A greater increase in weight SDS in the first month of life was associated with a higher fat free mass percentage (B 200.9; 95% CI, 12.1-389.6). A higher head circumference SDS was associated with more fat free mass (r = 0.46; 95% CI, 0.21-0.65). However, a greater increase in weight SDS up to term equivalent age was associated with a lower fat free mass percentage (B -55.7, SE 9.4). CONCLUSION: These findings suggest that impaired growth in the first month of life is associated with a less favorable body composition at term equivalent age.

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.

Development of Nationwide Recommendations to Support Prenatal Counseling in Extreme Prematurity.

OBJECTIVES: To develop a nationwide, evidence-based framework to support prenatal counseling in extreme prematurity, focusing on organization, decision-making, content, and style aspects. METHODS: A nationwide multicenter RAND-modified Delphi method study was performed between November 2016 and December 2017 in the Netherlands. Firstly, recommendations were extracted from literature and previous studies. Secondly, an expert panel (n = 21) with experienced parents, obstetricians, and neonatologists rated the recommendations on importance for inclusion in the framework. Thirdly, ratings were discussed in a consensus meeting. The final set of recommendations was approved and transformed into a framework. RESULTS: A total of 101 recommendations on organization, decision-making, content, and style were included in the framework, including tools to support personalization. The most important recommendations regarding organization were to have both parents involved in the counseling with both the neonatologist and obstetrician. The shared decision-making model was recommended for deciding between active support and comfort care. Main recommendations regarding content of conversation were explanation of treatment options, information on survival, risk of permanent consequences, impossibility to predict an individual course, possibility for multiple future decision moments, and a discussion on parental values and standards. It was considered important to avoid jargon, check understanding, and provide a summary. The expert panel, patient organization, and national professional associations (gynecology and pediatrics) approved the framework. CONCLUSIONS: A nationwide, evidence-based framework for prenatal counseling in extreme prematurity was developed. It contains recommendations and tools for personalization in the domains of organization, decision-making, content, and style of prenatal counseling.

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.

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.

Attention deficit hyperactivity disorder and autism spectrum disorder symptoms in school-age children born very preterm.

BACKGROUND: Very preterm (VP) children face a broad range of neurodevelopmental sequelae, including behavioral problems. AIM: To investigate prevalence, pervasiveness and co-occurrence of symptoms of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in school-age children born very preterm. METHODS: Using questionnaire and diagnostic interview data, parent and teacher reported symptoms of ADHD and ASD of 57 VP-children (mean age = 9.2 years) were compared with 57 gender and age matched full-term children using t-tests. Intra-class correlation coefficients quantified parent-teacher agreement. Correlation analysis investigated co-occurrence of ADHD/ASD symptoms. ADHD/ASD measures were aggregated using principal component analysis. Regression analyses investigated the contribution of perinatal risk factors, sex and SES to ADHD/ASD symptoms. RESULTS: VP-children showed higher levels of parent and teacher reported attention problems, social impairment and compromised communication skills. Fair to strong agreement was found between parent and teacher reported ADHD and ASD symptoms, indicating pervasiveness of observed difficulties. Co-occurrence of ADHD and ASD symptoms in VP-children was found. Lower gestational age was associated with higher ADHD and ASD symptom levels, male sex with higher ADHD symptom levels and lower SES with higher ASD symptom levels. CONCLUSION: School-age VP-children show higher levels of ADHD and ASD symptoms, and attention, socialization and communication difficulties in particular. Routinely screening for these problems is recommended in follow-up care.

Sensory processing difficulties in school-age children born very preterm: An exploratory study.

BACKGROUND: Very preterm birth has a detrimental impact on the developing brain, including widespread white matter brain abnormalities that threaten efficient sensory processing. Yet, sensory processing difficulties in very preterm children are scarcely studied, especially at school age. AIMS: To investigate somatosensory registration, multisensory integration and sensory modulation. PARTICIPANTS: 57 very preterm school-age children (mean age=9.2years) were compared to 56 gender and age matched full-term children. METHODS: Group differences on somatosensory registration tasks (Registration of Light Touch, Sensory Discrimination of Touch, Position Sense, Graphestesia), a computerized multisensory integration task, and the parent-reported Sensory Profile were investigated using t-tests and Mann-Whitney U tests. RESULTS: In comparison to full-term children, very preterm children are less accurate on somatosensory registration tasks, including Registration of Light Touch (d=0.34), Position Sense (d=0.31) and Graphestesia (d=0.42) and show more sensory modulation difficulties (d=0.41), including both behavioral hyporesponsivity (d=0.52) and hyperresponsivity (d=0.56) to sensory stimuli. Tactile discrimination and multisensory integration efficiency were not affected in very preterm children. Aspects of sensory processing were only modestly related. CONCLUSION: Very preterm children show sensory processing difficulties regarding somatosensory registration and sensory modulation, and preserved multisensory (audio-visual) integration. Follow-up care for very preterm children should involve screening of sensory processing difficulties at least up to school age.

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.

Sensory modulation in preterm children: Theoretical perspective and systematic review.

BACKGROUND: Neurodevelopmental sequelae in preterm born children are generally considered to result from cerebral white matter damage and noxious effects of environmental factors in the neonatal intensive care unit (NICU). Cerebral white matter damage is associated with sensory processing problems in terms of registration, integration and modulation. However, research into sensory processing problems and, in particular, sensory modulation problems, is scarce in preterm children. AIM: This review aims to integrate available evidence on sensory modulation problems in preterm infants and children (<37 weeks of gestation) and their association with neurocognitive and behavioral problems. METHOD: Relevant studies were extracted from PubMed, EMBASE.com and PsycINFO following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria included assessment of sensory modulation in preterm born children (<37 weeks of gestation) or with prematurity as a risk factor. RESULTS: Eighteen studies were included. Results of this review support the presence of sensory modulation problems in preterm children. Although prematurity may distort various aspects of sensory modulation, the nature and severity of sensory modulation problems differ widely between studies. CONCLUSIONS: Sensory modulation problems may play a key role in understanding neurocognitive and behavioral sequelae in preterm children. Some support is found for a dose-response relationship between both white matter brain injury and length of NICU stay and sensory modulation problems.

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.

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.

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.