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Consequences of using chronological age versus corrected age when testing cognitive and motor development in infancy and intelligence quotient at school age for children born preterm.
Gould, JF, Fuss, BG, Roberts, RM, Collins, CT, Makrides, M
PloS one. 2021;(9):e0256824
Abstract
BACKGROUND Children born preterm (<37 weeks' gestation) have an increased risk of poor neurodevelopment, including lower intelligence quotient (IQ) scores compared with their term-born counterparts. OBJECTIVE To explore the differences in psychometric scores for cognition and motor skills when they are age-standardized according to chronological age instead of corrected age for children born preterm. METHODS We assessed = 554 children born <33 weeks' gestation with the Bayley Scales of Infant Development, 2nd edition (mental and motor scores) at 18 months and the Weschler Abbreviated Scale of Intelligence (IQ score) at seven years of age. Scores were standardized according to chronological age and corrected age and differences between mean chronological and corrected scores were compared, along with the proportion of children whose scores could be classified as impaired. RESULTS When scores were standardized according to chronological age instead of corrected age there was a large significant difference of 17.3 points on the mental scale (79.5 vs. 96.8, respectively) and 11.8 points on the motor scale (84.8 vs. 96.6, respectively) at 18 months. By seven years, the difference in IQ scores remained, although of a smaller magnitude at 1.9 points between mean chronological and corrected age scoring (97.2 vs. 99.1, respectively). CONCLUSION Consistent with previous literature, outcome assessments for preterm infants consistently differed according to use of chronological or corrected age to standardized scores. Cognitive scores were impacted more severely than motor scores, and differences were more substantial in early childhood than later in childhood. For clinical purposes, correction for preterm birth is only likely to have an impact during early childhood, however assessments for research purposes should continue to correct into childhood to account for the persistent bias due to preterm birth.
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Metabolic Bone Disease of Prematurity: Risk Factors and Associated Short-Term Outcomes.
Avila-Alvarez, A, Urisarri, A, Fuentes-Carballal, J, Mandiá, N, Sucasas-Alonso, A, Couce, ML
Nutrients. 2020;(12)
Abstract
Despite the importance of early recognition of metabolic bone disease (MBD) of prematurity, there is still significant variability in screening practices across institutions. We conducted an observational study of infants born at ≤32 weeks of gestation with a birth weight of ≤1500 g (n = 218) to identify clinical factors associated with biochemical indicators of MBD. Bone mineral status was assessed by measuring alkaline phosphatase and phosphate levels between weeks 3 and 5 of life. Two comparisons were performed after classifying infants as either MBD (cases) or non-MBD (controls), and as either high or low risk for MBD, as determined based on the results of MBD screening. In total, 27 infants (12.3%) were classified as cases and 96 (44%) as high-risk. Compared with controls, MBD infants had a significantly lower gestational age and birth weight, and a longer duration of parenteral nutrition and hospital stay. Respiratory outcomes were significantly poorer in high- versus low-risk infants. Multivariate logistic regression showed that birth weight was the only independent risk factor for MBD (odds ratio [OR]/100 g, 0.811; confidence interval [CI95%], 0.656-0.992; p = 0.045) and that birth weight (OR/100 g, 0.853; CI95%, 0.731-0.991; p = 0.039) and red blood cell transfusion (OR, 2.661; CI95%, 1.308-5.467; p = 0.007) were independent risk factors for high risk of MBD. Our findings provide evidence of risk factors for MBD that could help clinicians to individualize perinatal management. The association of red blood cell transfusion with MBD is a novel finding that may be related to iron overload and that merits further study.
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Effects of a nutrient-dense formula compared with a post-discharge formula on post-discharge growth of preterm very low birth weight infants with extrauterine growth retardation: a multicentre randomised study in China.
Yu, MX, Zhuang, SQ, Gao, XY, Tong, XM, Yue, SJ, Shi, LP, Chen, DM, Liang, K
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2020;(4):557-565
Abstract
BACKGROUND Post-discharge optimal growth and nutritional intake have beneficial effects for neurodevelopment in preterm very low birth weight infants (VLBWIs) with extrauterine growth retardation (EUGR). The present study aimed to compare the effects of a nutrient-dense formula (NDF) to a post-discharge formula (PDF) on post-discharge growth of preterm VLBWIs with EUGR. METHODS Forty-eight preterm VLBWIs with EUGR at discharge were randomised to receive NDF (100 kcal per 100 mL; 2.6 g protein per 100 mL) or PDF (74 kcal per 100 mL; 1.95 g protein per 100 mL) for 1-6 months until body weight reached the 50th percentile on growth charts with corrected age. Volume, nutrient intake, anthropometry and biochemistry data were collected. RESULTS Volume intake was lower in the NDF group than the PDF group during the first 2 months of feeding (P = 0.039 and 0.018, respectively).There were no significant differences in volume intake during months 2-6 of feeding. Energy, protein, carbohydrate and fat intake were higher in the NDF group during months 1-6 of feeding. There were no significant differences in weight, length, and head circumference Z-scores during months 1-6 between the two groups. The △length Z-score from discharge to month 6 was significantly higher in the NDF group than the PDF group (P = 0.043). No differences existed between the two groups with respect to biochemistry. CONCLUSIONS After discharge, preterm VLBWIs with EUGR fed a NDF gain anthropometric parameter Z-scores similar to those for a PDF within 6 months of follow-up. A NDF leading to gain in length requires further follow-up.
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Early Caffeine Administration and Neurodevelopmental Outcomes in Preterm Infants.
Lodha, A, Entz, R, Synnes, A, Creighton, D, Yusuf, K, Lapointe, A, Yang, J, Shah, PS, ,
Pediatrics. 2019;(1)
Abstract
BACKGROUND Although caffeine use for apnea of prematurity is well studied, the long-term safety and benefit of routine early caffeine administration has not been explored. Our objective was to determine the association between early (within 2 days of birth) versus late caffeine exposure and neurodevelopmental outcomes in preterm infants. METHODS Infants of <29 weeks' gestation born between April 2009 and September 2011 and admitted to Canadian Neonatal Network units and then assessed at Canadian Neonatal Follow-up Network centers were studied. Neonates who received caffeine were divided into early- (received within 2 days of birth) and late-caffeine (received after 2 days of birth) groups. The primary outcome was significant neurodevelopmental impairment, defined as cerebral palsy, or a Bayley Scales of Infant and Toddler Development, Third Edition composite score of <70 on any component, hearing aid or cochlear implant, or bilateral visual impairment at 18 to 24 months' corrected age. RESULTS Of 2108 neonates who were eligible, 1545 were in the early-caffeine group and 563 were in the late-caffeine group. Rates of bronchopulmonary dysplasia, patent ductus arteriosus, and severe neurologic injury were lower in the early-caffeine group than in the late-caffeine group. Significant neurodevelopmental impairment (adjusted odds ratio 0.68 [95% confidence interval 0.50-0.94]) and odds of Bayley Scales of Infant and Toddler Development, Third Edition cognitive scores of <85 (adjusted odds ratio 0.67 [95% confidence interval 0.47-0.95]) were lower in the early-caffeine group than in the late-caffeine group. Propensity score-based matched-pair analyses revealed lower odds of cerebral palsy and hearing impairment only. CONCLUSIONS Early caffeine therapy is associated with better neurodevelopmental outcomes compared with late caffeine therapy in preterm infants born at <29 weeks' gestation.
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Neurodevelopmental Outcomes of Preterm Infants With Retinopathy of Prematurity by Treatment.
Natarajan, G, Shankaran, S, Nolen, TL, Sridhar, A, Kennedy, KA, Hintz, SR, Phelps, DL, DeMauro, SB, Carlo, WA, Gantz, MG, et al
Pediatrics. 2019;(2)
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Abstract
OBJECTIVE Among extremely preterm infants, we evaluated whether bevacizumab therapy compared with surgery for retinopathy of prematurity (ROP) is associated with adverse outcomes in early childhood. METHODS This study was a retrospective analysis of prospectively collected data on preterm (22-26 + 6/7 weeks' gestational age) infants admitted to the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers who received bevacizumab or surgery exclusively for ROP. The primary outcome was death or severe neurodevelopmental impairment (NDI) at 18 to 26 months' corrected age (Bayley Scales of Infant and Toddler Development, Third Edition cognitive or motor composite score <70, Gross Motor Functional Classification Scale level ≥2, bilateral blindness or hearing impairment). RESULTS The cohort (N = 405; 214 [53%] boys; median [interquartile range] gestational age: 24.6 [23.9-25.3] weeks) included 181 (45%) infants who received bevacizumab and 224 (55%) who underwent ROP surgery. Infants treated with bevacizumab had a lower median (interquartile range) birth weight (640 [541-709] vs 660 [572.5-750] g; P = .02) and longer durations of conventional ventilation (35 [21-58] vs 33 [18-49] days; P = .04) and supplemental oxygen (112 [94-120] vs 105 [84.5-120] days; P = .01). Death or severe NDI (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.94 to 2.14) and severe NDI (aOR 1.14; 95% CI 0.76 to 1.70) did not differ between groups. Odds of death (aOR 2.54 [95% CI 1.42 to 4.55]; P = .002), a cognitive score <85 (aOR 1.78 [95% CI 1.09 to 2.91]; P = .02), and a Gross Motor Functional Classification Scale level ≥2 (aOR 1.73 [95% CI 1.04 to 2.88]; P = .04) were significantly higher with bevacizumab therapy. CONCLUSIONS In this multicenter cohort of preterm infants, ROP treatment modality was not associated with differences in death or NDI, but the bevacizumab group had higher mortality and poor cognitive outcomes in early childhood. These data reveal the need for a rigorous appraisal of ROP therapy.
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Improved Outcomes in Preterm Infants Fed a Nonacidified Liquid Human Milk Fortifier: A Prospective Randomized Clinical Trial.
Schanler, RJ, Groh-Wargo, SL, Barrett-Reis, B, White, RD, Ahmad, KA, Oliver, J, Baggs, G, Williams, L, Adamkin, D
The Journal of pediatrics. 2018;:31-37.e2
Abstract
OBJECTIVE To compare growth, feeding tolerance, and clinical and biochemical evaluations in human milk-fed preterm infants randomized to receive either an acidified or a nonacidified liquid human milk fortifier. STUDY DESIGN This prospective, controlled, parallel, multicenter growth and tolerance study included 164 preterm infants (≤32 weeks of gestation, birth weight 700-1500 g) who were randomized to acidified or nonacidified liquid human milk fortifier from study day 1, the first day of fortification, through study day 29 or until hospital discharge. RESULTS There was no difference in the primary outcome of weight gain from study days 1 to 29 (acidified liquid human milk fortifier, 16.4 ± 0.4 g/kg/day; nonacidified liquid human milk fortifier, 16.9 ± 0.4 g/kg/day). However, in both the intention-to-treat and the protocol evaluable analyses, infants fed nonacidified liquid human milk fortifier had significantly greater weight gain from study days 1 to 15 (17.9 g/kg/day vs 15.2 g/kg/day; P = .001). Infants fed with acidified liquid human milk fortifier received more protein (4.26 vs g/kg/day 4.11 g/kg/day, P = .0099) yet had lower blood urea nitrogen values (P = .010). The group fed acidified liquid human milk fortifier had more vomiting (10.3% vs 2.4%; P = .018), gastric residuals (12.8% vs 3.7%; P = .022), and metabolic acidosis (27% vs 5%; P < .001) in the intention-to-treat analysis and more abdominal distension (14.0% vs 1.7%; P = .015) in the protocol evaluable analysis. CONCLUSIONS Infants fed an acidified liquid human milk fortifier had higher rates of metabolic acidosis and poor feeding tolerance compared with infants fed a nonacidified liquid human milk fortifier. Initial weight gain was poorer with the acidified liquid human milk fortifier. TRIAL REGISTRATION ClinicalTrials.gov: NCT02307760.
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Splanchnic-Cerebral Oxygenation Ratio Decreases during Enteral Feedings in Anemic Preterm Infants: Observations under Near-Infrared Spectroscopy.
Braski, K, Weaver-Lewis, K, Loertscher, M, Ding, Q, Sheng, X, Baserga, M
Neonatology. 2018;(1):75-80
Abstract
BACKGROUND Anemia is common in premature infants. Due to risks with red blood cell transfusions, many anemic infants are not transfused. The implications of this pathophysiologic status, especially at times of increased metabolic demand (enteral feedings), is not well understood. Near-infrared spectroscopy (NIRS) allows for the noninvasive determination of regional oxygen saturations (rSO2) in tissues such as the brain and mesentery, giving insight into their oxygen sufficiency. OBJECTIVE We tested the hypothesis that during enteral feedings very low birth weight (VLBW) infants with a hematocrit ≤28% will experience a decrease in splanchnic rSO2 and splanchnic-cerebral oxygenation ratio (SCOR). METHODS This prospective, observational, 2-centered study included VLBW infants receiving full enteral feedings with a hematocrit ≤28%. Cerebral and splanchnic rSO2 were monitored via NIRS for 24 h. Average values were calculated for periods immediately preceding, during, and after each feeding. SCOR was calculated from these values (rSO2 splanchnic/rSO2 cerebral), and data were analyzed using a linear mixed effect model. RESULTS Fifty neonates with a median gestational age of 28 weeks (range 23-32), a birth weight of 1,118 ± 284 g (mean ± SD), and a hematocrit of 26 ± 2% (mean ± SD) were studied. During feedings, SCOR decreased significantly from baseline (0.72 ± 0.17 to 0.69 ± 0.17, p = 0.043). With feedings, there was a trend of decreased splanchnic rSO2 (47 ± 11 to 45 ± 10, p = 0.057) and no change in cerebral rSO2 (66 ± 8 to 66 ± 7, p = 0.597). CONCLUSIONS VLBW infants with a hematocrit ≤28% had a decrease in SCOR and a trend towards decreased splanchnic rSO2 with enteral feedings.
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Body Composition following Necrotising Enterocolitis in Preterm Infants.
Binder, C, Longford, N, Gale, C, Modi, N, Uthaya, S
Neonatology. 2018;(3):242-248
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BACKGROUND The optimal nutritional regimen for preterm infants, including those that develop necrotising enterocolitis (NEC), is unknown. OBJECTIVE The objective here was to evaluate body composition at term in infants following NEC, in comparison with healthy infants. The primary outcome measure was non-adipose tissue mass (non-ATM). METHODS We compared body composition assessed by magnetic resonance imaging at term in infants born <31 weeks of gestational age that participated in NEON, a trial comparing incremental versus immediate delivery of parenteral amino acids on non-ATM, and SMOF versus intralipid on intrahepatocellular lipid content. There were no differences in the primary outcomes. We compared infants that received surgery for NEC (NEC-surgical), infants with medically managed NEC (NEC-medical), and infants without NEC (reference). RESULTS A total of 133 infants were included (8 NEC-surgical; 15 NEC-medical; 110 reference). In comparison with the reference group, infants in the NEC-surgical and NEC-medical groups were significantly lighter [adjusted mean difference (95% CI) NEC-surgical: -630 g (-1,010, -210), p = 0.003; NEC-medical: -440 g (-760, -110), p = 0.009] and the total adipose tissue volume (ATV) was significantly lower [NEC-surgical: -360 cm3 (-516, -204), p < 0.001; NEC-medical: -127 cm3 (-251, -4); p = 0.043]. There were no significant differences in non-ATM [adjusted mean difference (95% CI) NEC-surgical: -46 g (-281, 189), p = 0.70; NEC-medical: -122 g (-308, 63), p = 0.20]. CONCLUSION The lower weight at term in preterm infants following surgically and medically managed NEC, in comparison to preterm infants that did not develop the disease, was secondary to a reduction in ATV. This suggests that the nutritional regimen received was adequate to preserve non-ATM but not to support the normal third-trimester deposition of adipose tissue in preterm infants.
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Dietary Protein Intake, Breast Feeding and Growth in Human Milk Fed Preterm Infants.
Tonkin, E, Miller, J, Makrides, M, McPhee, AJ, Morris, SA, Gibson, RA, Collins, CT
International journal of environmental research and public health. 2018;(6)
Abstract
Protein intakes of preterm infants are frequently below recommendations, but few studies report accurate intakes due to the difficulty of analysing human milk clinically. This observational analysis from a randomised trial of infants born.
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Impact of homogenization of pasteurized human milk on gastric digestion in the preterm infant: A randomized controlled trial.
de Oliveira, SC, Bellanger, A, Ménard, O, Pladys, P, Le Gouar, Y, Henry, G, Dirson, E, Rousseau, F, Carrière, F, Dupont, D, et al
Clinical nutrition ESPEN. 2017;:1-11
Abstract
BACKGROUND & AIMS It has been suggested that homogenization of Holder-pasteurized human milk (PHM) could improve fat absorption and weight gain in preterm infants, but the impact on the PHM digestive kinetics has never been studied. Our objective was to determine the impact of PHM homogenization on gastric digestion in preterm infants. METHODS In a randomized controlled trial, eight hospitalized tube-fed preterm infants were their own control to compare the gastric digestion of PHM and of homogenized PHM (PHHM). PHM was obtained from donors and, for half of it, was homogenized by ultrasonication. Over a six-day sequence, gastric aspirates were collected twice a day, before and 35, 60 or 90 min after the start of PHM or PHHM ingestion. The impact of homogenization on PHM digestive kinetics and disintegration was tested using a general linear mixed model. Results were expressed as means ± SD. RESULTS Homogenization leaded to a six-fold increase in the specific surface (P < 0.01) of lipid droplets. The types of aggregates formed during digestion were different between PHM and PHHM, but the lipid fraction kept its initial structure all over the gastric digestion (native globules in PHM vs. blend of droplets in PHHM). Homogenization increased the gastric lipolysis level (P < 0.01), particularly at 35 and 60 min (22 and 24% higher for PHHM, respectively). Homogenization enhanced the proteolysis of serum albumin (P < 0.05) and reduced the meal emptying rate (P < 0.001, half-time estimated at 30 min for PHM and 38 min for PHHM). The postprandial gastric pH was not affected (4.7 ± 0.9 at 90 min). CONCLUSIONS Homogenization of PHM increased the gastric lipolysis level. This could be a potential strategy to improve fat absorption, and thus growth and development in infants fed with PHM; however, its gastrointestinal tolerance needs to be investigated further. This trial was registered at clinicaltrials.gov as NCT02112331.