scholarly journals Nutritional management in newborn babies receiving therapeutic hypothermia: two retrospective observational studies using propensity score matching

2021 ◽  
Vol 25 (36) ◽  
pp. 1-106
Author(s):  
Chris Gale ◽  
Dusha Jeyakumaran ◽  
Cheryl Battersby ◽  
Kayleigh Ougham ◽  
Shalini Ojha ◽  
...  

Background Therapeutic hypothermia is standard of care for babies with moderate to severe hypoxic–ischaemic encephalopathy. There is limited evidence to inform provision of nutrition during hypothermia. Objectives To assess the association during therapeutic hypothermia between (1) enteral feeding and outcomes, such as necrotising enterocolitis and (2) parenteral nutrition and outcomes, such as late-onset bloodstream infection. Design A retrospective cohort study using data held in the National Neonatal Research Database and applying propensity score methodology to form matched groups for analysis. Setting NHS neonatal units in England, Wales and Scotland. Participants Babies born at ≥ 36 gestational weeks between 1 January 2010 and 31 December 2017 who received therapeutic hypothermia for 72 hours or who died during treatment. Interventions Enteral feeding analysis – babies who were enterally fed during therapeutic hypothermia (intervention) compared with babies who received no enteral feeds during therapeutic hypothermia (control). Parenteral nutrition analysis – babies who received parenteral nutrition during therapeutic hypothermia (intervention) compared with babies who received no parenteral nutrition during therapeutic hypothermia (control). Outcome measures Primary outcomes were severe and pragmatically defined necrotising enterocolitis (enteral feeding analysis) and late-onset bloodstream infection (parenteral nutrition analysis). Secondary outcomes were survival at neonatal discharge, length of neonatal stay, breastfeeding at discharge, onset of breastfeeding, time to first maternal breast milk, hypoglycaemia, number of days with a central line in situ, duration of parenteral nutrition, time to full enteral feeds and growth. Results A total of 6030 babies received therapeutic hypothermia. Thirty-one per cent of babies received enteral feeds and 25% received parenteral nutrition. Seven babies (0.1%) were diagnosed with severe necrotising enterocolitis, and further comparative analyses were not conducted on this outcome. A total of 3236 babies were included in the matched enteral feeding analysis. Pragmatically defined necrotising enterocolitis was rare in both groups (0.5% vs. 1.1%) and was lower in babies who were fed during hypothermia (rate difference –0.5%, 95% confidence interval –1.0% to –0.1%; p = 0.03). Higher survival to discharge (96.0% vs. 90.8%, rate difference 5.2%, 95% confidence interval 3.9% to 6.6%; p < 0.001) and higher breastfeeding at discharge (54.6% vs. 46.7%, rate difference 8.0%, 95% confidence interval 5.1% to 10.8%; p < 0.001) rates were observed in enterally fed babies who also had a shorter neonatal stay (mean difference –2.2 days, 95% confidence interval –3.0 to –1.2 days). A total of 2480 babies were included in the matched parenteral nutrition analysis. Higher levels of late-onset bloodstream infection were seen in babies who received parenteral nutrition (0.3% vs. 0.9%, rate difference 0.6%, 95% confidence interval 0.1% to 1.2%; p = 0.03). Survival was lower in babies who did not receive parenteral nutrition (90.0% vs. 93.1%, rate difference 3.1%, 95% confidence interval 1.5% to 4.7%; p < 0.001). Limitations Propensity score methodology can address imbalances in observed confounders only. Residual confounding by unmeasured or poorly recorded variables cannot be ruled out. We did not analyse by type or volume of enteral or parenteral nutrition. Conclusions Necrotising enterocolitis is rare in babies receiving therapeutic hypothermia, and the introduction of enteral feeding is associated with a lower risk of pragmatically defined necrotising enterocolitis and other beneficial outcomes, including rates of higher survival and breastfeeding at discharge. Receipt of parenteral nutrition during therapeutic hypothermia is associated with a higher rate of late-onset infection but lower mortality. These results support introduction of enteral feeding during therapeutic hypothermia. Future work Randomised trials to assess parenteral nutrition during therapeutic hypothermia. Trial registration Current Controlled Trials ISRCTN474042962. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 36. See the NIHR Journals Library website for further project information.

Author(s):  
James William Harrison Webbe ◽  
Nicholas Longford ◽  
Cheryl Battersby ◽  
Kayleigh Oughham ◽  
Sabita N Uthaya ◽  
...  

ObjectiveTo 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.DesignRetrospective cohort study using propensity matching including 35 maternal, infant and organisational factors to minimise bias and confounding.SettingNational, population-level clinical data obtained for all National Health Service neonatal units in England and Wales.PatientsPreterm neonates born between 30+0 and 32+6 weeks+days.InterventionsThe exposure was parenteral nutrition administered in the first 7 days of postnatal life; the comparator was no parenteral nutrition.Main outcome measuresThe primary outcome was survival to discharge from neonatal care. Secondary outcomes comprised the neonatal core outcome set.Results16 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%).ConclusionsIn 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 numberNCT03767634.


2016 ◽  
Vol 20 (66) ◽  
pp. 1-194 ◽  
Author(s):  
Kate Costeloe ◽  
Ursula Bowler ◽  
Peter Brocklehurst ◽  
Pollyanna Hardy ◽  
Paul Heal ◽  
...  

BackgroundNecrotising enterocolitis (NEC) and late-onset sepsis remain important causes of death and morbidity in preterm babies. Probiotic administration might strengthen intestinal barrier function and provide protection; this is supported by published meta-analyses, but there is a lack of large well-designed trials.ObjectiveTo test the use of the probioticBifidobacterium brevestrain BBG-001 to prevent NEC, late-onset sepsis and death in preterm babies while monitoring probiotic colonisation of participants.DesignDouble-blind, randomised, placebo-controlled trial.SettingRecruitment was carried out in 24 hospitals, and the randomisation programme used a minimisation algorithm. Parents, clinicians and outcome assessors were blinded to the allocation.ParticipantsBabies born between 23 and 30 weeks’ gestation and randomised within 48 hours of birth. Exclusions included life-threatening or any gastrointestinal malformation detected within 48 hours of birth and no realistic chance of survival.InterventionsActive intervention: 1 ml ofB. breveBBG-001 in one-eighth-strength infant formula Neocate®(Nutricia Ltd, Trowbridge, UK), (6.7 × 107to 6.7 × 109colony-forming units) per dose administered enterally. Placebo: 1 ml of one-eighth-strength infant formula Neocate. Started as soon as practicable and continued daily until 36 weeks’ postmenstrual age.Main outcome measuresPrimary outcomes were an episode of bloodstream infection, with any organism other than a skin commensal, in any baby between 72 hours and 46 weeks’ postmenstrual age; an episode of NEC Bell stage ≥ 2 in any baby; and death before discharge from hospital. Secondary outcomes included stool colonisation withB. breve.ResultsIn total, 654 babies were allocated to receive probiotic and 661 to receive placebo over 37 months from July 2010. Five babies were withdrawn; 650 babies from the probiotic group and 660 from the placebo group were included in the primary analysis. Baseline characteristics were well balanced. There was no evidence of benefit for the primary outcomes {sepsis: 11.2% vs. 11.7% [adjusted relative risk (RR) 0.97, 95% confidence interval (CI) 0.73 to 1.29]; NEC Bell stage ≥ 2: 9.4% vs. 10.0% [adjusted RR 0.93, 95% CI 0.68 to 1.27]; and death: 8.3% vs. 8.5% [adjusted RR 0.93, 95% CI 0.67 to 1.30]}.B. brevecolonisation status was available for 1186 (94%) survivors at 2 weeks’ postnatal age, of whom 724 (61%) were positive: 85% of the probiotic group and 37% of the placebo group. There were no differences for subgroup analyses by minimisation criteria and by stool colonisation withB. breveat 2 weeks. No harms associated with the interventions were reported.LimitationsCross-colonisation of the placebo arm could have reduced statistical power and confounded results; analyses suggest that this did not happen.ConclusionsThis is the largest trial to date of a probiotic intervention. It shows no evidence of benefit and does not support routine use of probiotics for preterm infants.Future work recommendationsThe increasing understanding of the pathogenesis of NEC and sepsis will inform the choice of probiotics for testing and better define the target population. Future Phase III trials should incorporate monitoring of the quality and viability of the intervention and colonisation rates of participants; cluster design should be considered.Trial registrationCurrent Controlled Trials ISRCTN05511098 and EudraCT 2006-003445-17.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 66. See the NIHR Journals Library website for further project information.


Author(s):  
Johannes Camp ◽  
Lina Glaubitz ◽  
Tim Filla ◽  
Achim J Kaasch ◽  
Frieder Fuchs ◽  
...  

Abstract Background Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection. The impact of immunosuppressive agents on the outcome of patients with SAB is incompletely understood. Methods Data from two large prospective, international, multicenter cohort studies (INSTINCT and ISAC) between 2006 and 2015 were analyzed. Patients receiving immunosuppressive agents were identified and a 1:1 propensity score (PS) matched analysis was performed to adjust for baseline characteristics of patients. Overall survival and time to SAB-related late complications (SAB relapse, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed by Cox regression and competing risk analyses, respectively. This approach was then repeated for specific immunosuppressive agents (corticosteroids [CSMT] and immunosuppressive agents other than steroids [IMOTS]). Results Of 3,188 analyzed patients, 309 were receiving immunosuppressive treatment according to our definitions and were matched to 309 non-immunosuppressed patients. After PS matching, baseline characteristics were well balanced. In the Cox regression analysis, we observed no significant difference in survival between the two groups (death during follow-up: 105/309 (33.9 %) immunosuppressed patients vs. 94/309 (30.4 %) non-immunosuppressed, hazard ratio 1.20 (95% CI 0.84–1.71). Competing risk analysis showed a cause-specific hazard ratio (CSHR) of 1.81 (95% CI 0.85–3.87) for SAB-related late-complications in patients receiving immunosuppressive agents. CSHR was higher in patients taking IMOTS (3.69; 95% CI 1.41–9.68). Conclusions Immunosuppressive agents were not associated with an overall higher mortality. The risk for SAB-related late complications in patients receiving specific immunosuppressive agents such as IMOTs warrants further investigations.


Author(s):  
M.R. Alturk ◽  
H. Salama ◽  
H. Al Rifai ◽  
M. Al Qubaisi ◽  
S. Alobaidly

BACKGROUND: Early empiric antibiotic exposure appears to negatively influence feeding tolerance in preterm infants. However, the effect of prolonged antibiotic treatment is unknown. The objective of this study was to investigate whether prolonged antibiotics impact the time to full enteral feed in infants less than 29 weeks of gestational age with negative blood cultures. METHODS: Retrospective data for infants less than 29 weeks gestation age were retrieved from the PEARL-Peristat perinatal registry in Qatar. Exclusion criteria were major congenital anomalies, conditions requiring surgery in the first 10 days of life, positive blood cultures in the first 48 hours of life, and death within the first week of life. Antibiotic courses were categorized as prolonged if continued more than 48 hours. The primary outcome was the duration of total parenteral nutrition. RESULTS: Of 199 study infants, 185 (92.9%) underwent antibiotic treatment for >  48 hours despite negative blood cultures. The median duration of parenteral nutrition was not significantly different between the prolonged and short antibiotic groups (25 and 22 days, respectively; p = 0.139). Infants with prolonged antibiotic courses experienced non-significantly higher levels of necrotizing enterocolitis (7.1% and 18.4%, respectively), bronchopulmonary dysplasia (28.6% and 45.4%, respectively), and retinopathy of prematurity (14.3% and 38.4%, respectively). There were no differences in the late-onset sepsis rate (78.6% and 82.1%, respectively) and the in-hospital death rate (7.1% and 7.6%, respectively). CONCLUSIONS: Prolonged antibiotic treatment in infants less than 29 weeks gestation with negative blood cultures has no significant impact on the time to full enteral feed.


2017 ◽  
Vol 117 (7) ◽  
pp. 994-1000 ◽  
Author(s):  
J. Uberos ◽  
E. Aguilera-Rodríguez ◽  
A. Jerez-Calero ◽  
M. Molina-Oya ◽  
A. Molina-Carballo ◽  
...  

AbstractThe aim of the study was to determine whether routine probiotic supplementation (RPS) with Lactobacillus rhamnosus GG (LGG) or Lactobacillus acidophilus +Lactobacillus bifidum is associated with reduced risk of necrotising enterocolitis (NEC)≥Stage II in preterm neonates born at ≤32 weeks’ gestation. We conducted a retrospective cohort study on the effect of probiotic supplementation in very low birth weight infants in our neonatal unit by comparing two periods: before and after supplementation. The incidence of NEC≥Stage II, late-onset sepsis and all-cause mortality was compared for an equal period ‘before’ (Period I) and ‘after’ (Period II) RPS with LGG or L. acidophillus+L. bifidum. Multivariate logistic regression analysis was conducted to adjust for relevant confounders. The study population was composed of 261 neonates (Period I v. II: 134 v. 127) with comparable gestation duration and birth weights. In <32 weeks, we observed a significant reduction in NEC≥Stage II (11·3 v. 4·8 %), late-onset sepsis (16 v. 10·5 %) and mortality (19·4 v. 2·3 %). The benefits in neonates aged ≤27 weeks did not reach statistical significance. RPS with LGG or L. acidophillus+L. bifidum is associated with a reduced risk of NEC≥Stage II, late-onset sepsis and mortality in preterm neonates born at ≤32 weeks’ gestation.


2021 ◽  
Vol 25 (77) ◽  
pp. 1-190
Author(s):  
Kamlesh Khunti ◽  
Simon Griffin ◽  
Alan Brennan ◽  
Helen Dallosso ◽  
Melanie Davies ◽  
...  

Background Type 2 diabetes is a leading cause of mortality globally and accounts for significant health resource expenditure. Increased physical activity can reduce the risk of diabetes. However, the longer-term clinical effectiveness and cost-effectiveness of physical activity interventions in those at high risk of type 2 diabetes is unknown. Objectives To investigate whether or not Walking Away from Diabetes (Walking Away) – a low-resource, 3-hour group-based behavioural intervention designed to promote physical activity through pedometer use in those with prediabetes – leads to sustained increases in physical activity when delivered with and without an integrated mobile health intervention compared with control. Design Three-arm, parallel-group, pragmatic, superiority randomised controlled trial with follow-up conducted at 12 and 48 months. Setting Primary care and the community. Participants Adults whose primary care record included a prediabetic blood glucose measurement recorded within the past 5 years [HbA1c ≥ 42 mmol/mol (6.0%), < 48 mmol/mol (6.5%) mmol/mol; fasting glucose ≥ 5.5 mmol/l, < 7.0 mmol/l; or 2-hour post-challenge glucose ≥ 7.8 mmol/l, < 11.1 mmol/l] were recruited between December 2013 and February 2015. Data collection was completed in July 2019. Interventions Participants were randomised (1 : 1 : 1) using a web-based tool to (1) control (information leaflet), (2) Walking Away with annual group-based support or (3) Walking Away Plus (comprising Walking Away, annual group-based support and a mobile health intervention that provided automated, individually tailored text messages to prompt pedometer use and goal-setting and provide feedback, in addition to biannual telephone calls). Participants and data collectors were not blinded; however, the staff who processed the accelerometer data were blinded to allocation. Main outcome measures The primary outcome was accelerometer-measured ambulatory activity (steps per day) at 48 months. Other objective and self-reported measures of physical activity were also assessed. Results A total of 1366 individuals were randomised (median age 61 years, median body mass index 28.4 kg/m2, median ambulatory activity 6638 steps per day, women 49%, black and minority ethnicity 28%). Accelerometer data were available for 1017 (74%) and 993 (73%) individuals at 12 and 48 months, respectively. The primary outcome assessment at 48 months found no differences in ambulatory activity compared with control in either group (Walking Away Plus: 121 steps per day, 97.5% confidence interval –290 to 532 steps per day; Walking Away: 91 steps per day, 97.5% confidence interval –282 to 463). This was consistent across ethnic groups. At the intermediate 12-month assessment, the Walking Away Plus group had increased their ambulatory activity by 547 (97.5% confidence interval 211 to 882) steps per day compared with control and were 1.61 (97.5% confidence interval 1.05 to 2.45) times more likely to achieve 150 minutes per week of objectively assessed unbouted moderate to vigorous physical activity. In the Walking Away group, there were no differences compared with control at 12 months. Secondary anthropometric, biomechanical and mental health outcomes were unaltered in either intervention study arm compared with control at 12 or 48 months, with the exception of small, but sustained, reductions in body weight in the Walking Away study arm (≈ 1 kg) at the 12- and 48-month follow-ups. Lifetime cost-effectiveness modelling suggested that usual care had the highest probability of being cost-effective at a threshold of £20,000 per quality-adjusted life-year. Of 50 serious adverse events, only one (myocardial infarction) was deemed possibly related to the intervention and led to the withdrawal of the participant from the study. Limitations Loss to follow-up, although the results were unaltered when missing data were replaced using multiple imputation. Conclusions Combining a physical activity intervention with text messaging and telephone support resulted in modest, but clinically meaningful, changes in physical activity at 12 months, but the changes were not sustained at 48 months. Future work Future research is needed to investigate which intervention types, components and features can help to maintain physical activity behaviour change over the longer term. Trial registration Current Controlled Trials ISRCTN83465245. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 77. See the NIHR Journals Library website for further project information.


2020 ◽  
Vol 18 (4) ◽  
pp. 17-28
Author(s):  
A.I. Aminova ◽  
◽  
P.A. Bobkova ◽  
E.I. Belova ◽  
N.V. Zaytseva ◽  
...  

Study objective. To optimize the recommendations on the strategy of enteral feeding for newborn babies with necrotizing enterocolitis (NEC). Patients and methods. A single-centre, observational, prospective, analytical, cohort study of 186 infants aged from 2 days to 2 months (96 boys, 90 girls) with the verified diagnosis of NEC of varied severity, who were treated at the neonatal pathology department of Moscow G.N.Speransky Children’s City Clinical Hospital No 9 in 2016-2018. The patients were divided into 2 groups, depending on disease staging according to the Walsh and Kliegman classification: group I – 124 (66.7%) newborns with mild NEC (stage 1A, B and 2A) and group II – 62 (33.3%) patients with a severe course (stages 2B and 3A, B). Results. As has been found, maternal risk factors for the development of severe forms of NEC in newborns are: maternal age over 40 years (OR = 1.40, 95% CI 0.83–2.17), assisted reproductive technologies (OR = 2.62, 95% CI 1.79–3.66), bad obstetrical-gynaecological history (OR = 1.80, 95% CI 1.03–2.97), infectious diseases during pregnancy (OR = 1.37, 95% CI 0.69–1.90). The ranking of the risk factors present in babies themselves permitted to find a causative relation with such factors as bacteriological contamination of biological media (OR = 2.80, 95% CI 1.3–4.0), bacteremia, viremia (OR = 5.80, 95% CI 2.99–7.13), gestational age 30–32 wks (OR = 2.35, 95% CI 1.01–3.94), which were significant only for mild forms of NEC. A minimal number of severe cases was diagnosed for a combination of breastfeeding and parenteral nutrition (16.7%), development of severe NEC was more often noted when feeding was started within 5 days: breastfeeding (26.3%), formula feeding (33.3 %), mixed breast and formula feeding (5%), or in infants who did not receive feeding due to their severe condition after birth (33%) (р < 0.05). The minimal number of severe NEC cases was found among babies who remained on breast (11.1%) and mixed (11.1%) feeding after the 5th day (р < 0.05), the maximal number – in infants who started from enteral feeding and were transferred to formula feeding (50%). Prolonged enteral feeding was three times more often associated with a severe course of NEC (р < 0.001). Conclusion. As has been found, the frequency of developing severe NEC depends on the character of the first feed after birth. A risk of developing severe forms of NEC decreases in newborns on breast- or mixed feeding, in combination of breast feeding and parenteral nutrition, short courses of enteral pauses, alternation of enteral feeding and enteral pauses. The results might be used in the clinical practice of neonatologists and paediatricians for prevention and management of NEC and its possible complications in newborn infants. Key words: necrotising enterocolitis, enteral pause, enteral nutrition, neonatology, birth weight, gestational age, premature infants


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