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Outcomes in relation to early parenteral nutrition use in preterm neonates born between 30 and 33 weeks' gestation: a propensity score matched observational study.
Webbe, JWH, Longford, N, Battersby, C, Oughham, K, Uthaya, SN, Modi, N, Gale, C
Archives of disease in childhood. Fetal and neonatal edition. 2022;(2):131-136
Abstract
OBJECTIVE To evaluate whether in preterm neonates parenteral nutrition use in the first 7 postnatal days, compared with no parenteral nutrition use, is associated with differences in survival and other important morbidities. Randomised trials in critically ill older children show that harms, such as nosocomial infection, outweigh benefits of early parenteral nutrition administration; there is a paucity of similar data in neonates. DESIGN Retrospective cohort study using propensity matching including 35 maternal, infant and organisational factors to minimise bias and confounding. SETTING National, population-level clinical data obtained for all National Health Service neonatal units in England and Wales. PATIENTS Preterm neonates born between 30+0 and 32+6 weeks+days. INTERVENTIONS The exposure was parenteral nutrition administered in the first 7 days of postnatal life; the comparator was no parenteral nutrition. MAIN OUTCOME MEASURES The primary outcome was survival to discharge from neonatal care. Secondary outcomes comprised the neonatal core outcome set. RESULTS 16 292 neonates were compared in propensity score matched analyses. Compared with matched neonates not given parenteral nutrition in the first postnatal week, neonates who received parenteral nutrition had higher survival at discharge (absolute rate increase 0.91%; 95% CI 0.53% to 1.30%), but higher rates of necrotising enterocolitis (absolute rate increase 4.6%), bronchopulmonary dysplasia (absolute rate increase 3.9%), late-onset sepsis (absolute rate increase 1.5%) and need for surgical procedures (absolute rate increase 0.92%). CONCLUSIONS In neonates born between 30+0 and 32+6 weeks' gestation, those given parenteral nutrition in the first postnatal week had a higher rate of survival but higher rates of important neonatal morbidities. Clinician equipoise in this area should be resolved by prospective randomised trials. TRIAL REGISTRATION NUMBER NCT03767634.
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Early versus later initiation of parenteral nutrition for very preterm infants: a propensity score-matched observational study.
Uthaya, S, Longford, N, Battersby, C, Oughham, K, Lanoue, J, Modi, N
Archives of disease in childhood. Fetal and neonatal edition. 2022;(2):137-142
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Abstract
OBJECTIVE To evaluate the impact of timing of initiation of parenteral nutrition (PN) after birth in very preterm infants. DESIGN Propensity-matched analysis of data from the UK National Neonatal Research Database. PATIENTS 65 033 babies <31 weeks gestation admitted to neonatal units in England and Wales between 2008 and 2019. INTERVENTIONS PN initiated in the first 2 days (early) versus after the second postnatal day (late). Babies who died in the first 2 days without receiving PN were analysed as 'late'. MAIN OUTCOME MEASURES The main outcome measure was morbidity-free survival to discharge. The secondary outcomes were survival to discharge, growth and other core neonatal outcomes. FINDINGS No difference was found in the primary outcome (absolute rate difference (ARD) between early and late 0.50%, 95% CI -0.45 to 1.45, p=0.29). The early group had higher rates of survival to discharge (ARD 3.3%, 95% CI 2.7 to 3.8, p<0.001), late-onset sepsis (ARD 0.84%, 95% CI 0.48 to 1.2, p<0.001), bronchopulmonary dysplasia (ARD 1.24%, 95% CI 0.30 to 2.17, p=0.01), treated retinopathy of prematurity (ARD 0.50%, 95% CI 0.17 to 0.84, p<0.001), surgical procedures (ARD 0.80%, 95% CI 0.20 to 1.40, p=0.01) and greater drop in weight z-score between birth and discharge (absolute difference 0.019, 95% CI 0.003 to 0.035, p=0.02). Of 4.9% of babies who died in the first 2 days, 3.4% were in the late group and not exposed to PN. CONCLUSIONS Residual confounding and survival bias cannot be excluded and justify the need for a randomised controlled trial powered to detect differences in important functional outcomes.
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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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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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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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Assessment of Neonatal Intensive Care Unit Practices and Preterm Newborn Gut Microbiota and 2-Year Neurodevelopmental Outcomes.
Rozé, JC, Ancel, PY, Marchand-Martin, L, Rousseau, C, Montassier, E, Monot, C, Le Roux, K, Butin, M, Resche-Rigon, M, Aires, J, et al
JAMA network open. 2020;(9):e2018119
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Abstract
IMPORTANCE In very preterm newborns, gut microbiota is highly variable with major dysbiosis. Its association with short-term health is widely studied, but the association with long-term outcomes remains unknown. OBJECTIVE To investigate in preterm newborns the associations among practice strategies in neonatal intensive care units (NICUs), gut microbiota, and outcomes at 2 years. DESIGN, SETTING, AND PARTICIPANTS EPIFLORE is a prospective observational cohort study that includes a stool sample collection during the fourth week after birth. Preterm newborns of less than 32 weeks of gestational age (GA) born in 2011 were included from 24 NICUs as part of the French nationwide population-based cohort, EPIPAGE 2. Data were collected from May 2011 to December 2011 and analyzed from September 2016 to December 2018. EXPOSURES Eight NICU strategies concerning sedation, ventilation, skin-to-skin practice, antibiotherapy, ductus arteriosus, and breastfeeding were assessed. A NICU was considered favorable to a practice if the percentage of that practice in the NICU was more than the expected percentage. MAIN OUTCOMES AND MEASURES Gut microbiota was analyzed by 16S ribosomal RNA gene sequencing and characterized by a clustering-based method. The 2-year outcome was defined by death or neurodevelopmental delay using a Global Ages and Stages questionnaire score. RESULTS Of 577 newborns included in the study, the mean (SD) GA was 28.3 (2.0) weeks, and 303 (52.5%) were male. Collected gut microbiota was grouped into 5 discrete clusters. A sixth cluster included nonamplifiable samples owing to low bacterial load. Cluster 4 (driven by Enterococcus [n = 63]), cluster 5 (driven by Staphylococcus [n = 52]), and cluster 6 (n = 93) were significantly associated with lower mean (SD) GA (26.7 [1.8] weeks and 26.8 [1.9] weeks, respectively) and cluster 3 (driven by Escherichia/Shigella [n = 61]) with higher mean (SD) GA (29.4 [1.6] weeks; P = .001). Cluster 3 was considered the reference. After adjustment for confounders, no assisted ventilation at day 1 was associated with a decreased risk of belonging to cluster 5 or cluster 6 (adjusted odds ratio [AOR], 0.21 [95% CI, 0.06-0.78] and 0.19 [95% CI, 0.06-0.62], respectively) when sedation (AOR, 10.55 [95% CI, 2.28-48.87] and 4.62 [1.32-16.18], respectively) and low volume of enteral nutrition (AOR, 10.48 [95% CI, 2.48-44.29] and 7.28 [95% CI, 2.03-26.18], respectively) was associated with an increased risk. Skin-to-skin practice was associated with a decreased risk of being in cluster 5 (AOR, 0.14 [95% CI, 0.04-0.48]). Moreover, clusters 4, 5, 6 were significantly associated with 2-year nonoptimal outcome (AOR, 6.17 [95% CI, 1.46-26.0]; AOR, 4.53 [95% CI, 1.02-20.1]; and AOR, 5.42 [95% CI, 1.36-21.6], respectively). CONCLUSIONS AND RELEVANCE Gut microbiota of very preterm newborns at week 4 is associated with NICU practices and 2-year outcomes. Microbiota could be a noninvasive biomarker of immaturity.
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Impact of different stages of intrauterine inflammation on outcome of preterm neonates: Gestational age-dependent and -independent effect.
Pietrasanta, C, Pugni, L, Merlo, D, Acaia, B, Consonni, D, Ronchi, A, Ossola, MW, Ghirardi, B, Bottino, I, Cribiù, FM, et al
PloS one. 2019;(2):e0211484
Abstract
OBJECTIVE To investigate the impact of different stages of intrauterine inflammation (IUI) on neonatal outcomes, before and after adjusting for gestational age (GA) and other perinatal confounders. METHODS This was an observational, prospective, single-center cohort study including all eligible neonates with GA < 35 weeks and/or birth weight ≤ 1500 g born at a 3rd level Neonatal Intensive Care Unit between 2011 and 2014. Pathological patterns of placenta, membranes and cord were classified according to Redline's criteria. Multivariable linear and logistic regression models were applied, either including or not GA among the covariates. RESULTS Of the 807 enrolled neonates, 134 (16.6%) had signs of IUI: among these, 54.5% showed just histological chorioamnionitis (HCA), 25.4% had HCA + funisitis (FUN) stage 1, and 20.1% had HCA + FUN stage 2-3. At univariate analysis, HCA increased the risk for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia, while FUN (any stage) had a deleterious impact on all outcomes investigated. After adjustment for covariates not including GA, HCA was a risk factor only for ROP (OR = 2.8, CI: 1-7.8), while FUN (any stage) was still associated with increased ORs for all outcomes (p <0.01). Upon inclusion of GA in the regression model, the results differed remarkably. HCA was associated with lower risk for mechanical ventilation (OR = 0.3, CI: 0.1-0.7) and need for surfactant (OR = 0.5, CI: 0.2-0.9), while FUN (any stage) worsened clinical conditions at birth (p <0.05), increased the risk for early-onset sepsis (p <0.01), and increased the length of mechanical ventilation (FUN stage 2-3 only, RC = 6.5 days, CI: 2-11). No other outcome was affected. CONCLUSIONS IUI, especially FUN, negatively impact most neonatal morbidities, but its effect is partially reverted adjusting for GA. Considered that GA is an intermediate variable interposed between prenatal causes of prematurity and outcomes, the appropriateness of adjusting for GA may be questionable.
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Physiological instability after respiratory pauses in preterm infants.
Marshall, AP, Lim, K, Ali, SK, Gale, TJ, Dargaville, PA
Pediatric pulmonology. 2019;(11):1712-1721
Abstract
BACKGROUND The factors influencing the severity of apnea-related hypoxemia and bradycardia are incompletely characterized, especially in infants receiving noninvasive respiratory support. OBJECTIVES To identify the frequency and predictors of physiological instability (hypoxemia-oxygen saturation (SpO2 ) <80%, or bradycardia-heart rate (HR) < 100 bpm) following respiratory pauses in infants receiving noninvasive respiratory support. METHODS Respiratory pause duration, derived from capsule pneumography, was measured in 30 preterm infants of gestation 30 (24-32) weeks [median (interquartile range)] receiving noninvasive respiratory support and supplemental oxygen. For identified pauses of 5 to 29 seconds duration, we measured the magnitude and duration of SpO2 and HR reductions over a period starting at the pause onset and ending 60 seconds after resumption of breathing. Temporally clustered pauses (<60 seconds separation) were analyzed separately. The relative contribution of respiratory pauses to overall physiological instability was determined, and predictors of instability were sought in regression analysis, including demographic, clinical and situational variables as inputs. RESULTS In total, 17 105 isolated and 9180 clustered pauses were identified. Hypoxemia and bradycardia were more likely after longer duration and temporally-clustered pauses. However, the majority of such episodes occurred after 5 to 9 second pauses given their numerical preponderance, and short-lived pauses made a substantial contribution to physiological instability overall. Birth gestation, hemoglobin concentration, form of respiratory support, caffeine treatment, respiratory pause duration and temporal clustering were identified as predictors of instability. CONCLUSIONS Brief respiratory pauses, especially when clustered, contribute substantially to hypoxemia and bradycardia in preterm infants.
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Maternal milk feedings reduce sepsis, necrotizing enterocolitis and improve outcomes of premature infants.
Cortez, J, Makker, K, Kraemer, DF, Neu, J, Sharma, R, Hudak, ML
Journal of perinatology : official journal of the California Perinatal Association. 2018;(1):71-74
Abstract
OBJECTIVE Human milk (donor milk (DM) and/or maternal milk (MM)) feedings protect against late onset sepsis (LOS), necrotizing enterocolitis (NEC) and death. However, DM lacks many anti-infective components of MM. Therefore, we studied exclusive MM feedings to evaluate the full effect of human milk on infectious and other outcomes in premature infants. STUDY DESIGN All infants born before 33 weeks postmenstrual age (PMA) who received exclusive (>95%) MM or exclusive preterm formula (PF) were included in this prospective investigation. RESULTS Sixty-three infants (53%) received MM and 55 infants (47%) received PF. Both groups had similar baseline characteristics. Infants in the MM group achieved full enteral nutrition sooner (14±8 vs 19±15 days, P<0.03) and required a shorter duration of central venous lines (14±10 vs 22±21, P<0.005). Fewer infants in the MM group developed LOS (9 vs 19, P<0.05) and pneumonia (8 vs 16, P<0.05) than PF infants. Only one MM and five PF infants developed NEC (Bell stage ⩾II). Logistic regression analysis using PMA and prolonged rupture of membranes as covariates demonstrated an increased rate of NEC (odds ratio=8.85, CI=1.01 to 25.17, P=0.048) in PF infants. Periventricular leukomalacia (PVL) was more common in PF (4 vs 0, P=0.04) than in MM infants. CONCLUSION Feedings of MM advanced more rapidly and were associated with fewer infections than PF. A possible protective effect of MM against PVL, not previously described, may be related to its immune and anti-inflammatory components.
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Effects of caffeine on the preterm brain: An observational study.
Dix, LML, van Bel, F, Baerts, W, Lemmers, PMA
Early human development. 2018;:17-20
Abstract
BACKGROUND AND AIM Caffeine improves neurodevelopmental outcome of preterm infants. This study analyses the effects of caffeine on the neonatal brain. We hypothesized that caffeine has a neuroprotective effect through an increase in oxygen metabolism; reflected by increased cerebral oxygen extraction, electrical function, and perfusion. METHODS Preterm infants <32 weeks gestation (GA) receiving their primary dose caffeine-base (10 mg/kg) were included. Ten minutes of stable monitoring were selected before, during, and every hour up to 6 h after caffeine. Near-infrared spectroscopy monitored regional cerebral oxygenation (rScO2) and extraction (FTOE). Amplitude-integrated electroencephalogram (aEEG) monitored minimum, mean and maximum amplitudes. Spontaneous activity transients (SAT) rate and the interval between SATs (ISI) were calculated. Mean arterial blood pressure (MABP), heart rate (HR) and arterial oxygen saturation (SaO2) were monitored. Arterial pCO2's were collected before and 4 h after caffeine. Brain perfusion was assessed 1 h before and 3 h after caffeine by Doppler-measured resistance-index (RI), peak systolic velocity (PSV) and end-diastolic velocity (EDV), in the anterior cerebral artery (ACA) and internal carotid artery (ICA). Results were presented in mean ± SD. RESULTS 34 infants, mean GA 28.8 ± 2.1 wk, were included. rScO2 significantly decreased from 69 ± 11 to 63 ± 12 1 h after caffeine, and recovered at 6 h (66 ± 10). FTOE increased correspondingly. MABP and HR increased significantly. PSV in the ACA decreased slightly. Other Doppler variables, aEEG parameters, and SaO2 were unaffected. CONCLUSION Caffeine increases oxygen extraction, suggesting a (transient) stimulating effect on brain metabolism. However, no substantial changes were found in brain perfusion and in electrical brain activity.