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1.
Using Nature to Nurture: Breast Milk Analysis and Fortification to Improve Growth and Neurodevelopmental Outcomes in Preterm Infants.
Ottolini, KM, Schulz, EV, Limperopoulos, C, Andescavage, N
Nutrients. 2021;(12)
Abstract
Premature infants are born prior to a critical window of rapid placental nutrient transfer and fetal growth-particularly brain development-that occurs during the third trimester of pregnancy. Subsequently, a large proportion of preterm neonates experience extrauterine growth failure and associated neurodevelopmental impairments. Human milk (maternal or donor breast milk) is the recommended source of enteral nutrition for preterm infants, but requires additional fortification of macronutrient, micronutrient, and energy content to meet the nutritional demands of the preterm infant in attempts at replicating in utero nutrient accretion and growth rates. Traditional standardized fortification practices that add a fixed amount of multicomponent fortifier based on assumed breast milk composition do not take into account the considerable variations in breast milk content or individual neonatal metabolism. Emerging methods of individualized fortification-including targeted and adjusted fortification-show promise in improving postnatal growth and neurodevelopmental outcomes in preterm infants.
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Clinical Results of the Implementation of a Breast Milk Bank in Premature Infants (under 37 Weeks) at the Hospital Universitario del Valle 2018-2020.
Torres-Muñoz, J, Jimenez-Fernandez, CA, Murillo-Alvarado, J, Torres-Figueroa, S, Castro, JP
Nutrients. 2021;(7)
Abstract
Breast milk is widely recognized as the best source of nutrition for both full term and premature babies. We aimed to identify clinical results of the implementation of a breast milk bank for premature infants under 37 weeks in a level III hospital. 722 neonates under 37 weeks, hospitalized in the Neonatal intensive care unit (ICU), who received human breast milk from the institution's milk bank 57% (n = 412) vs. mixed or artificial 32% (n = 229), at day 7 of life. An exploratory data analysis was carried out. Measures of central tendency and dispersion were used, strength of association of odds ratio (OR) and its confidence intervals (95% confidence interval (CI)). 88.5% had already received human milk before day 7 of life. Those who received human milk, due to their clinical condition, had 4 times a greater chance of being intubated (OR 4.05; 95% CI 1.80-9.11). Starting before day 7 of life decreases the opportunity to develop necrotizing enterocolitis by 82% (adjusted odds ratio (ORa) 0.18; 95% CI 0.03-0.97), intraventricular hemorrhage by 85% (ORa 0.15; 95% CI 0.06-0.45) and sepsis by 77% (ORa 0.23; 95% CI 0.15-0.33). Receiving human milk reduces the probability of complications related to prematurity, evidencing the importance that breast milk banks play in clinical practice.
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Early Enteral Feeding Improves Tolerance of Parenteral Nutrition in Preterm Newborns.
Boscarino, G, Conti, MG, Di Chiara, M, Bianchi, M, Onestà, E, Faccioli, F, Deli, G, Repole, P, Oliva, S, Cresi, F, et al
Nutrients. 2021;(11)
Abstract
(1) Background: The tolerance of preterm newborns for the high nutritional intakes given by parenteral nutrition (PN) is still debated because of the risk of metabolic complications. Despite enteral nutrition (EN) being the preferred route of nutrition, an exclusive enteral feeding is not always possible, as in preterm newborns, the gut is immature and less tolerant of EN. We aimed to study the impact of a minimal enteral feeding (MEF) on the possible early metabolic complications of PN in a cohort of preterms with gestational age at birth GA ≤ 29 + 6/7 weeks of postmenstrual age. (2) Methods: We divided the study sample in two cohorts: 1) Late-Feeding (cohort 1), newborns who received MEF starting from the 8th day of age, and (2) Early-Feeding (cohort 2), newborns who received MEF, consisting of the administration of at least 4-5 mL/kg/day by the enteral route, in the first 7 days of age. The primary outcome of the study was the rate of at least one metabolic complication, including hyperglycemia, hypertriglyceridemia, or metabolic acidosis. (3) Results: We enrolled 80 newborns (Late-Feeding cohort 51 vs. Early-Feeding cohort 29). The rate of all metabolic complications was statistically higher in the Late-Feeding cohort compared to the Early-Feeding cohort. Binary logistic regression analysis showed that late administration of MEF negatively influenced the rate of all metabolic complications. (4) Conclusions: Early minimal administration of EN is associated with less frequent PN-related metabolic side effects and a higher rate of survival in critically ill newborns.
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Preventing Brain Injury in the Preterm Infant-Current Controversies and Potential Therapies.
Yates, N, Gunn, AJ, Bennet, L, Dhillon, SK, Davidson, JO
International journal of molecular sciences. 2021;(4)
Abstract
Preterm birth is associated with a high risk of morbidity and mortality including brain damage and cerebral palsy. The development of brain injury in the preterm infant may be influenced by many factors including perinatal asphyxia, infection/inflammation, chronic hypoxia and exposure to treatments such as mechanical ventilation and corticosteroids. There are currently very limited treatment options available. In clinical trials, magnesium sulfate has been associated with a small, significant reduction in the risk of cerebral palsy and gross motor dysfunction in early childhood but no effect on the combined outcome of death or disability, and longer-term follow up to date has not shown improved neurological outcomes in school-age children. Recombinant erythropoietin has shown neuroprotective potential in preclinical studies but two large randomized trials, in extremely preterm infants, of treatment started within 24 or 48 h of birth showed no effect on the risk of severe neurodevelopmental impairment or death at 2 years of age. Preclinical studies have highlighted a number of promising neuroprotective treatments, such as therapeutic hypothermia, melatonin, human amnion epithelial cells, umbilical cord blood and vitamin D supplementation, which may be useful at reducing brain damage in preterm infants. Moreover, refinements of clinical care of preterm infants have the potential to influence later neurological outcomes, including the administration of antenatal and postnatal corticosteroids and more accurate identification and targeted treatment of seizures.
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5.
Lactoferrin Supplementation to Prevent Late-Onset Sepsis in Preterm Infants: A Meta-Analysis.
Razak, A, Hussain, A
American journal of perinatology. 2021;(3):283-290
Abstract
OBJECTIVE This study aimed to systematically review and meta-analyze the role of lactoferrin supplementation to prevent late-onset sepsis (LOS) in preterm infants. STUDY DESIGN Database search include PubMed, Web of Science, and Cochrane central for randomized clinical trial (RCTs). The Cochrane Grading of Recommendations Assessment, Development, and Evaluation methodology was used for summarizing the results. RESULTS Ten RCTs involving 3,679 infants were included. Lactoferrin supplementation with or without probiotics decreased all LOS (relative risk [RR]: 0.56; 95% confidence interval [CI]: 0.36-0.86; I 2 = 58%; 10 studies; 3,470 subjects; level of evidence [LOE]: low) significantly. Similarly, lactoferrin supplementation without probiotics decreased all LOS (RR: 0.43; 95% CI: 0.29-0.62; I 2 = 0%; 8 studies; 1,209 subjects; LOE: moderate) significantly. Lactoferrin supplementation did not significantly reduce necrotizing enterocolitis (RR: 0.62; 95% CI: 0.29-1.33; I 2 = 43%; 6 studies; 3,079 subjects; LOE: low), all-cause mortality (RR: 0.74; 95% CI: 0.36-1.53; I 2 = 53%; 8 studies; 3,395 subjects; LOE: very low), bronchopulmonary dysplasia (RR: 1; 95% CI: 0.90-1.13; I 2 = 0%; 4 studies; 2,570 subjects; LOE: moderate), and threshold retinopathy of prematurity eligible for surgical treatment (RR: 0.61; 95% CI: 0.25-1.51; I 2 = 74%; 2 studies; 2,481 subjects; LOE: very low). CONCLUSION Low to moderate quality evidence suggests that lactoferrin supplementation reduces LOS in preterm infants. Further research is needed to improve the certainty in the evidence.
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The Use of Postnatal Weight Gain Algorithms to Predict Severe or Type 1 Retinopathy of Prematurity: A Systematic Review and Meta-analysis.
Athikarisamy, S, Desai, S, Patole, S, Rao, S, Simmer, K, Lam, GC
JAMA network open. 2021;(11):e2135879
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Abstract
IMPORTANCE The currently recommended method for screening for retinopathy of prematurity (ROP) is binocular indirect ophthalmoscopy, which requires frequent eye examinations entailing a heavy clinical workload. Weight gain-based algorithms have the potential to minimize the need for binocular indirect ophthalmoscopy and have been evaluated in different setups with variable results to predict type 1 or severe ROP. OBJECTIVE To synthesize evidence regarding the ability of postnatal weight gain-based algorithms to predict type 1 or severe ROP. DATA SOURCES PubMed, MEDLINE, Embase, and the Cochrane Library databases were searched to identify studies published between January 2000 and August 2021. STUDY SELECTION Prospective and retrospective studies evaluating the ability of these algorithms to predict type 1 or severe ROP were included. DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted data. This meta-analysis was performed according to the Cochrane guidelines and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. MAIN OUTCOMES AND MEASURES Ability of algorithms to predict type 1 or sever ROP was measured using statistical indices (pooled sensitivity, specificity, and summary area under the receiver operating characteristic curves, as well as pooled negative likelihood ratios and positive likelihood ratios and diagnostic odds ratios). RESULTS A total of 61 studies (>37 000 infants) were included in the meta-analysis. The pooled estimates for sensitivity and specificity, respectively, were 0.89 (95% CI, 0.85-0.92) and 0.57 (95% CI, 0.51-0.63) for WINROP (Weight, IGF-1 [insulinlike growth factor 1], Neonatal, ROP), 1.00 (95% CI, 0.88-1.00) and 0.60 (95% CI, 0.15-0.93) for G-ROP (Postnatal Growth and ROP), 0.95 (95% CI, 0.71-0.99) and 0.52 (95% CI, 0.36-0.68) for CHOP ROP (Children's Hospital of Philadelphia ROP), 0.99 (95% CI, 0.73-1.00) and 0.49 (95% CI, 0.03-0.74) for ROPScore, 0.98 (95% CI, 0.94-0.99) and 0.35 (95% CI, 0.22-0.51) for CO-ROP (Colorado ROP). The original PINT (Premature Infants in Need of Transfusion) ROP study reported a sensitivity of 0.98 (95% CI, 0.91-0.99) and a specificity of 0.36 (95% CI, 0.30-0.42). The pooled negative likelihood ratios were 0.19 (95% CI, 0.13-0.27) for WINROP, 0.0 (95% CI, 0.00-0.32) for G-ROP, 0.10 (95% CI, 0.02-0.53) for CHOP ROP, 0.03 (95% CI, 0.00-0.77) for ROPScore, and 0.07 (95% CI, 0.03-0.16) for CO-ROP. The pooled positive likelihood ratios were 2.1 (95% CI, 1.8-2.4) for WINROP, 2.5 (95% CI, 0.7-9.1) for G-ROP, 2.0 (95% CI, 1.5-2.6) for CHOP ROP, 1.9 (95% CI, 1.1-3.3) for ROPScore, and 1.5 (95% CI, 1.2-1.9) for CO-ROP. CONCLUSIONS AND RELEVANCE This study suggests that weight gain-based algorithms have adequate sensitivity and negative likelihood ratios to provide reasonable certainty in ruling out type 1 ROP or severe ROP. Given the implications of missing even a single case of severe ROP, algorithms with very high sensitivity (close to 100%) and low negative likelihood ratios (close to zero) need to be chosen to safely reduce the number of unnecessary examinations in infants at lower risk of severe ROP.
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Oropharyngeal Colostrum Positively Modulates the Inflammatory Response in Preterm Neonates.
Martín-Álvarez, E, Diaz-Castro, J, Peña-Caballero, M, Serrano-López, L, Moreno-Fernández, J, Sánchez-Martínez, B, Martín-Peregrina, F, Alonso-Moya, M, Maldonado-Lozano, J, Hurtado-Suazo, JA, et al
Nutrients. 2020;(2)
Abstract
During the first days of life, premature infants have physiological difficulties swallowing, thereby missing out on the benefits of breastfeeding. The aim of this study is to assess the effects of oropharyngeal mother's milk administration in the inflammatory signaling of extremely premature infants. Neonates (n = 100) (<32 week's gestation and/or <1500 g) were divided into two groups: mother's milk group (n = 48), receiving 0.2 mL of oropharyngeal mother's milk every 4 h for the first 15 days of life, and a control group (n = 52), not receiving oropharyngeal mother's milk. Serum concentrations of interleukin (IL) IL-6, IL-8, IL-10, IL-1ra, tumor necrosis factor alpha (TNF-α), and interferón gamma (IFN-γ) were assessed at 1, 3, 15, and 30 days of postnatal life. Maternal and neonatal outcomes were collected. The rate of common neonatal morbidities in both groups was similar. The mother's milk group achieved full enteral feeding earlier, and showed a decrease in Il-6 on days 15 and 30, in IL-8 on day 30, and in TNF-α and INF-γ on day 15, as well as an increase in IL-1ra on days 3 and 15 and in IL-10 on day 30. Oropharyngeal mother's milk administration for 15 days decreases the pro-inflammatory state of preterm neonates and provides full enteral nutrition earlier, which could have a positive influence on the development of the immune system and inflammatory response, thereby positively influencing other developmental outcomes.
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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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Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants.
Pammi, M, Suresh, G
The Cochrane database of systematic reviews. 2020;(3):CD007137
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Abstract
BACKGROUND Lactoferrin, a normal component of human colostrum and milk, can enhance host defenses and may be effective for prevention of sepsis and necrotizing enterocolitis (NEC) in preterm neonates. OBJECTIVES To assess the safety and effectiveness of lactoferrin supplementation to enteral feeds for prevention of sepsis and NEC in preterm neonates. Secondarily, we assessed the effects of lactoferrin supplementation to enteral feeds on the duration of positive-pressure ventilation, development of chronic lung disease (CLD) or periventricular leukomalacia (PVL), length of hospital stay to discharge among survivors, and adverse neurological outcomes at two years of age or later. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to update our search. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 9), MEDLINE via PubMed (1966 to 20 January 2020), PREMEDLINE (1996 to 20 January 2020), Embase (1980 to 20 January 2020), and CINAHL (1982 to 20 January 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. SELECTION CRITERIA In our search, we included randomized controlled trials (RCTs) evaluating enteral lactoferrin supplementation at any dose or duration to prevent sepsis or NEC in preterm neonates. DATA COLLECTION AND ANALYSIS We used the standard methods of Cochrane Neonatal and the GRADE approach to assess the certainty of evidence. MAIN RESULTS Meta-analysis of data from twelve randomized controlled trials showed that lactoferrin supplementation to enteral feeds decreased late-onset sepsis (typical RR 0.82, 95% CI 0.74 to 0.91; typical RD -0.04, 95% CI, -0.06, -0.02; NNTB 25, 95% CI 17 to 50; 12 studies, 5425 participants, low-certainty evidence) and decreased length of hospital stay (MD -2.38, 95% CI, -4.67, -0.09; 3 studies, 1079 participants, low-certainty evidence). Sensitivity analysis including only good methodological certainty studies suggested a decrease in late-onset sepsis with enteral lactoferrin supplementation (typical RR 0.87, 95% CI, 0.78, 0.97; typical RD -0.03, 95% CI, -0.05, -0.0; 9 studies, 4702 participants, low-certainty evidence). There were no differences in NEC stage II or III (typical RR 1.10, 95% CI, 0.86, 1.41; typical RD -0.00, 95% CI, -0.02, 0.01; 7 studies, 4874 participants; low-certainty evidence) or 'all-cause mortality' (typical RR 0.90, 95% CI 0.69, 1.17; typical RD -0.00, 95% CI, -0.01, 0.01; 11 studies, 5510 participants; moderate-certainty evidence). One study reported no differences in neurodevelopmental testing by Mullen's or Bayley III at 24 months of age after enteral lactoferrin supplementation (one study, 292 participants, low-certainty evidence). Lactoferrin supplementation to enteral feeds with probiotics decreased late-onset sepsis (RR 0.25, 95% CI 0.14 to 0.46; RD -0.13, 95% CI -0.18 to -0.08; NNTB 8, 95% CI 6 to 13; 3 studies, 564 participants; low-certainty evidence) and NEC stage II or III (RR 0.04, 95% CI 0.00 to 0.62; RD -0.05, 95% CI -0.08 to -0.03; NNTB 20, 95% CI 12.5 to 33.3; 1 study, 496 participants; very low-certainty evidence), but not 'all-cause mortality' (very low-certainty evidence). Lactoferrin supplementation to enteral feeds with or without probiotics had no effect on CLD, duration of mechanical ventilation or threshold retinopathy of prematurity (low-certainty evidence). Investigators reported no adverse effects in the included studies. AUTHORS' CONCLUSIONS We found low-certainty evidence from studies of good methodological quality that lactoferrin supplementation of enteral feeds decreases late-onset sepsis but not NEC ≥ stage II or 'all cause mortality' or neurodevelopmental outcomes at 24 months of age in preterm infants without adverse effects. Low- to very low-certainty evidence suggests that lactoferrin supplementation of enteral feeds in combination with probiotics decreases late-onset sepsis and NEC ≥ stage II in preterm infants without adverse effects, however, there were few included studies of poor methodological quality. The presence of publication bias and small studies of poor methodology that may inflate the effect size make recommendations for clinical practice difficult.
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Early application of caffeine improves white matter development in very preterm infants.
Liu, S, Zhang, X, Liu, Y, Yuan, X, Yang, L, Zhang, R, Zhang, X, Wang, X, Xu, F, Zhu, C
Respiratory physiology & neurobiology. 2020;:103495
Abstract
The aim of this study was to evaluate the effect of early prophylactic caffeine treatment on white matter development in very preterm infants using cerebral magnetic resonance imaging. A total of 194 preterm infants (≤32 weeks gestational age) were randomly assigned to the caffeine (n = 96) or placebo (n = 93) treatment group and administered with either caffeine or placebo within 72 h after birth. Cerebral magnetic resonance imaging, including diffuse tensor imaging examination, was performed at 34-36 weeks of corrected gestational age, and the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured. In total, 160 infants were included in the final analysis, including 80 cases in the placebo group and 80 cases in the caffeine group. There were fewer instances of apnea of prematurity and shorter assisted ventilation times for infants in the caffeine group compared to the placebo group (p < 0.05). Infants in the caffeine group had significantly higher FA values in white matter, including the posterior limb of the internal capsule, the corpus callosum, the frontal, occipital, and parietal white matter, the cerebellum, and the cerebral peduncle, compared to infants in the placebo group. ADC values in the above white matter areas were significantly reduced in the caffeine group. However, there were no significant differences regarding the FA and ADC in the gray matter between the two groups. These results demonstrate that early administration of caffeine improves white matter micro-structural development in preterm infants, but with no significant effect on short-term complications related to prematurity.