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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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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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Individualising care in severe bronchopulmonary dysplasia: a series of N-of-1 trials comparing transpyloric and gastric feeding.
Jensen, EA, Zhang, H, Feng, R, Dysart, K, Nilan, K, Munson, DA, Kirpalani, H
Archives of disease in childhood. Fetal and neonatal edition. 2020;(4):399-404
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Abstract
OBJECTIVE Compare rates of hypoxaemia during transpyloric and gastric feedings in very preterm infants with severe bronchopulmonary dysplasia. DESIGN N-of-1 multiple crossover trials with individual patient and pooled data analyses. SETTING Level IV intensive care nursery. PATIENTS Infants receiving positive airway pressure between 36 and 55 weeks postmenstrual age were enrolled between December 2014-July 2016. INTERVENTION N-of-1 trial consisting of two blocks, each with a 4-day gastric and 4-day transpyloric feeding period assigned in random order. MAIN OUTCOME MEASURES The primary outcome was the frequency of daily intermittent hypoxaemic events (SpO2 ≤80% lasting 10-180 s). Secondary outcomes included the daily proportion of time with an SpO2 ≤80% and mean daily fraction of inspired oxygen. RESULTS Of 15 infants, 13 completed the trial and 2 stopped early for transient worsening in respiratory status during gastric feedings. In the intention-to-treat analyses, transpyloric feedings resulted in increased rates of intermittent hypoxaemia in five infants, greater time per day in hypoxaemia in three infants and more supplemental oxygen use in three infants. One infant received more supplemental oxygen during gastric feedings. The remaining study outcomes were similar between the feeding routes in all other infants. Pooling all data, transpyloric feedings resulted in a higher frequency of intermittent hypoxaemic events (median 7.5/day (IQR 1-23.5) vs 3/day (1-11); adjusted incidence rate ratio 1.8, 95% CI 1.3 to 2.5) and a greater proportion of daily hypoxaemia time (median 0.8% (IQR 0.1-2.3) vs 0.4% (0.07-1.8); adjusted mean difference 1.6, 95% CI 1.1 to 2.5). CONCLUSIONS Transpyloric compared with gastric feedings modestly increased rates of hypoxaemia among study participants. TRIAL REGISTRATION NUMBER NCT02142621.
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Dose-Response Effects of Early Vitamin D Supplementation on Neurodevelopmental and Respiratory Outcomes of Extremely Preterm Infants at 2 Years of Age: A Randomized Trial.
Salas, AA, Woodfin, T, Phillips, V, Peralta-Carcelen, M, Carlo, WA, Ambalavanan, N
Neonatology. 2018;(3):256-262
Abstract
BACKGROUND Many extremely preterm infants have low vitamin D concentrations at birth, but early childhood outcomes after vitamin D supplementation have not been reported. OBJECTIVE To determine a dose-response relationship between increasing doses of enteral vitamin D in the first 28 days after birth and cognitive scores at 2 years of age. METHODS In this phase II double-blind dose-response randomized trial, infants with gestational ages between 23 and 27 weeks were randomly assigned to receive placebo or a vitamin D dose of 200 or 800 IU/day from day 1 of enteral feeding to postnatal day 28. The primary outcome of this follow-up study was Bayley III cognitive score at 22-26 months of age. RESULTS Seventy of 80 survivors had a follow-up evaluation at 2 years of age (88%). There were no significant differences in cognitive scores between supplementation groups (p = 0.47). Cognitive scores did not differ between the higher vitamin D dose group and the placebo group (median difference favoring the 800 IU group: +5 points; 95% CI: -5 to 15; p = 0.23). The linear trend between increasing doses of vitamin D and reduction of neurodevelopmental impairment (placebo group: 54%; 200 IU group: 43%; 800 IU group: 30%; p = 0.08) or language impairment (placebo group: 64%; 200 IU group: 57%; 800 IU group: 45%; p = 0.15) was not statistically significant. Respiratory outcomes at 2 years of age (need for supplemental oxygen or asthma medications) did not differ between groups. CONCLUSION In extremely preterm infants, early vitamin D supplementation did not significantly improve cognitive scores. Though underpowered for clinically meaningful differences in early childhood outcomes, this trial may help determine dosing for further investigation of vitamin D supplementation.
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Nonrandomised interventional study showed that early aggressive nutrition was effective in reducing postnatal growth restriction in preterm infants.
Genoni, G, Binotti, M, Monzani, A, Bernascone, E, Stasi, I, Bona, G, Ferrero, F
Acta paediatrica (Oslo, Norway : 1992). 2017;(10):1589-1595
Abstract
AIM: This study evaluated whether an early aggressive nutrition (EAN) strategy could limit extrauterine growth restriction (EUGR) in a cohort of preterm infants. METHODS This prospective nonrandomised interventional study was carried out in the neonatal intensive care unit of an Italian hospital from January 2013 to December 2015. The prevalence of EUGR was assessed in 100 infants with a gestational age of ≤34 weeks, 50 after the introduction of an EAN regimen in October 2014 and 50 before. RESULTS The prevalence of EUGR at discharge was significantly lower after the introduction of EAN than before for weight (34% vs. 66%), head circumference (22% vs. 42%) and length at discharge (20% vs. 48%). The Z-scores for all measurements were significantly higher after the introduction of EAN. In the EAN group, weight velocity was significantly higher and maximum weight loss and negative changes in the Z-scores from birth to discharge for weight were lower than in the pre-intervention controls. In extremely low birthweight subjects, the weight Z-score and weight velocity were significantly higher in the EAN group than the control group. CONCLUSION The use of EAN at a very early age reduced EUGR and improved auxological outcomes in preterm infants.
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Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial.
Costeloe, K, Hardy, P, Juszczak, E, Wilks, M, Millar, MR, ,
Lancet (London, England). 2016;(10019):649-660
Abstract
BACKGROUND Probiotics may reduce necrotising enterocolitis and late-onset sepsis after preterm birth. However, there has been concern about the rigour and generalisability of some trials and there is no agreement about whether or not they should be used routinely. We aimed to test the effectiveness of the probiotic Bifidobacterium breve BBG-001 to reduce necrotising enterocolitis, late-onset sepsis, and death in preterm infants. METHODS In this multicentre, randomised controlled phase 3 study (the PiPS trial), we recruited infants born between 23 and 30 weeks' gestational age within 48 h of birth from 24 hospitals in southeast England. Infants were randomly assigned (1:1) to probiotic or placebo via a minimisation algorithm randomisation programme. The probiotic intervention was B breve BBG-001 suspended in dilute elemental infant formula given enterally in a daily dose of 8·2 to 9·2 log10 CFU; the placebo was dilute infant formula alone. Clinicians and families were masked to allocation. The primary outcomes were necrotising enterocolitis (Bell stage 2 or 3), blood culture positive sepsis more than 72 h after birth; and death before discharge from hospital. All primary analyses were by intention to treat. This trial is registered with ISRCTN, number 05511098 and EudraCT, number 2006-003445-17. FINDINGS Between July 1, 2010, and July 31, 2013, 1315 infants were recruited; of whom 654 were allocated to probiotic and 661 to placebo. Five infants had consent withdrawn after randomisation, thus 650 were analysed in the probiotic group and 660 in the placebo group. Rates of the primary outcomes did not differ significantly between the probiotic and placebo groups. 61 infants (9%) in the probiotic group had necrotising enterocolitis compared with 66 (10%) in the placebo group (adjusted risk ratio 0·93 (95% CI 0·68-1·27); 73 (11%) infants in the probiotics group had sepsis compared with 77 (12%) in the placebo group (0·97 (0·73-1·29); and 54 (8%) deaths occurred before discharge home in the probiotic group compared with 56 (9%) in the placebo group (0·93 [0·67-1·30]). No probiotic-associated adverse events were reported. INTERPRETATION There is no evidence of benefit for this intervention in this population; this result does not support the routine use of B breve BBG-001 for prevention of necrotising enterocolitis and late-onset sepis in very preterm infants. FUNDING UK National Institute for Health Research Health Technology Assessment programme.
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Delayed primary serial transverse enteroplasty as a novel management strategy for infants with congenital ultra-short bowel syndrome.
Wales, PW, Jancelewicz, T, Romao, RL, Piper, HG, de Silva, NT, Avitzur, Y
Journal of pediatric surgery. 2013;(5):993-9
Abstract
BACKGROUND Congenital ultra-short bowel syndrome (USBS) is a challenging problem with a poor outcome. We report a new management approach for USBS infants that attempts to optimize gut growth potential. METHODS We report five neonates with USBS in whom no correction was performed at primary surgery except placement of a gastrostomy (G) tube. Sham feeds were started with intermittent G-tube clamping to induce bowel dilatation/growth. Serial fluoroscopy was done until bowel caliber reached 5 cm. STEP was performed and continuity established to the colonic remnant. Small bowel length (SBL) and enteral caloric intake were tabulated. RESULTS Patients were born with a mean residual SBL of 19 ± 7.6 cm (14.8% of expected). Median duration of sham feeds prior to STEP was 108 (range 27-232)days. Mean SBL at STEP was 47 ± 12.1cm, which increased post-STEP to 70 ± 12.7 cm (a mean increase of 296% from birth, representing 36.4% ± 13.1% of expected gut length). With a median follow-up time of 20 months (range 8-28), 4/5 achieved >50% enteral calories and have normal liver function. One has undergone liver transplantation. CONCLUSIONS In USBS patients, delayed surgical correction with sham feeds accelerates gut growth, optimizing potential for autologous reconstruction. This approach may offer greater opportunity for intestinal adaptation than traditional options.
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Sodium Alginate (Gaviscon®) does not reduce apnoeas related to gastro-oesophageal reflux in preterm infants.
Corvaglia, L, Spizzichino, M, Zama, D, Aceti, A, Mariani, E, Legnani, E, Faldella, G
Early human development. 2011;(12):775-8
Abstract
BACKGROUND Apnoea of prematurity (AOP) frequently recurs in preterm infants. We have previously shown that a significant but variable proportion of AOP is induced by gastro-oesophageal reflux (GOR). AIM: The aim of this study is to evaluate the efficacy of sodium alginate in reducing the frequency of GOR-related AOP. SUBJECTS Twenty-eight preterm infants with AOP were studied by a six-hour recording of combined multichannel intraluminal impedance and pH monitoring and polysomnography, including two three-hour postprandial periods: sodium alginate was given after one single meal named as drug-given (DG) meal, while the other as drug-free (DF). RESULTS During 165h of registration, 715 apnoeas were recorded, 368 after-DG and 347 after-DF (p=.99); furthermore, 851 GOR episodes were detected, 315 after-DG and 536 after-DF (p=.001). No differences in the number of AOP were found between DG and DF. A significant reduction in the number of acid GORs and in acid exposure was found during DG, while the administration of sodium alginate didn't influence non-acid GOR indexes. The frequency of GOR-related apnoeas didn't differ between DG and DF. DISCUSSION Sodium alginate doesn't reduce the total number of AOP nor GOR-related apnoeas. On the other hand, it reduces acid GOR features, while it had no effect on non-acid GOR indexes.
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Olfactory stimulation prevents apnea in premature newborns.
Marlier, L, Gaugler, C, Messer, J
Pediatrics. 2005;(1):83-8
Abstract
OBJECTIVE Methylxanthines and doxapram are currently used to treat apnea of prematurity but are not fully effective and often present undesirable side effects. The present study examines whether exposure to an odor known to modulate the infant's respiratory rate could reduce the frequency of apneic spells. METHOD Fourteen preterm newborns born at 24 to 28 gestational weeks presenting recurrent apnea despite caffeine and doxapram therapy were exposed to a pleasant odor diffused during 24 hours in the incubator. Efficiency of the olfactory treatment was judged by comparing frequency and severity of apneas occurring during the day of odorization with that observed the day before (baseline) and the day after (posttreatment control). Apnea was defined as any complete cessation of breathing movements for >20 seconds, or less if associated with hypoxia or bradycardia. RESULTS Concerning all types of apneas, a diminution of 36% was observed and seen in 12 of 14 infants. Apneas without bradycardia were reduced (44%) during the day with odorization, and this diminution affected all the infants. The frequency of apnea with moderate bradycardia (heart rate between 70 and 90 beats per minute) was maintained while the frequency of apnea associated with severe bradycardia (heart rate <70 beats per minute) decreased strongly (45%) and affected all the infants. No side effects were observed. CONCLUSION The introduction of a pleasant odor in the incubator is of therapeutic value in the treatment of apneas unresponsive to caffeine and doxapram.
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Erythromycin fails to improve feeding outcome in feeding-intolerant preterm infants.
ElHennawy, AA, Sparks, JW, Armentrout, D, Huseby, V, Berseth, CL
Journal of pediatric gastroenterology and nutrition. 2003;(3):281-6
Abstract
OBJECTIVE Approximately half of extremely low birth weight infants have feeding intolerance, which delays their achievement of full enteral feedings. Erythromycin, a motilin receptor agonist, triggers migrating motor complexes and accelerates gastric emptying in adults with feeding intolerance. Few studies have assessed the efficacy of this drug in preterm infants with established feeding intolerance. This study was designed to assess the efficacy of erythromycin in feeding-intolerant infants, as measured by gastric emptying, maturation of gastrointestinal motor patterns, and time to achieve full enteral feedings. METHODS Subjects were 27 preterm infants who were admitted to the neonatal intensive care unit and who did not achieve full enteral feeding volumes (150 mL/kg/day) within 8 days of the initiation of feedings. In a controlled, randomized, double-blinded clinical trial, infants received intragastric erythromycin or placebo for 8 days without crossover. At study entry, the authors recorded motor activity in the antrum and the duodenum during fasting, in response to intragastric erythromycin (1.5 mg/kg) or placebo, and in response to feeding. Gastric emptying at 20 minutes and transit time from duodenum to anus were determined. Each infant then received erythromycin or placebo for 8 days, and feeding characteristics were prospectively tracked. RESULTS Gastric emptying and characteristics of antroduodenal motor contractions were similar in the two groups, as were the transit times from duodenum to anus. Feeding outcomes were comparable in the two groups. CONCLUSION Intragastric erythromycin does not improve feeding tolerance in preterm infants with established feeding intolerance because it fails to improve gastrointestinal function in the short or long term.