Early versus late intravenous nutrition in critically ill term and late preterm babies

Review question: to evaluate the benefits and risks of early (within 72 hours of admission) versus late (after 72 hours of admission) commencement of intravenous nutrition in unwell term babies (those born at 37 weeks of pregnancy or more) and late preterm babies (those born between 34 and 37 weeks of pregnancy).

Background: when very unwell term babies and late preterm babies are unable to tolerate milk feeds due to their illness, it is necessary to give nutrition (such as glucose, amino acids and fat) to these babies via an intravenous drip (a tube that is inserted directly into a vein). Recent studies in sick children and adults suggest that it is better to administer only intravenous glucose initially and to delay giving intravenous amino acids and fat by about a week.

Study characteristics: this review found two small studies that evaluated the effects of early versus late commencement of intravenous amino acids and fat in full term babies. However, relevant results were available from only one study, with evidence up to date as of 5 April 2019.

Key results: late commencement of intravenous nutrition resulted in increased survival during hospital stay and in the first 28 days of birth.The timing of intravenous nutrition was not associated with an increased risk of hospital-acquired blood stream infections, growth and duration of hospital stay. Neurodevelopmental outcomes were not reported. However, the quality of the evidence was considered to be low because the sample size was very small and the results were from only one study.

Conclusions: while there were some benefits of late commencement of intravenous nutrition in term and late preterm babies, the quality of the evidence was low and so our confidence in the results is limited. Further trials are needed which investigate the best time to start intravenous nutrition in unwell newborn babies.

Authors' conclusions: 

Whilst late commencement of PN in term and late preterm infants may have some benefits, the quality of the evidence was low and hence our confidence in the results is limited. Adequately powered RCTs, which evaluate short-term as well as long-term neurodevelopmental outcomes, are needed.

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Background: 

Recently conducted randomised controlled trials (RCTs) suggest that late commencement of parenteral nutrition (PN) may have clinical benefits in critically ill adults and children. However, there is currently limited evidence regarding the optimal timing of commencement of PN in critically ill term and late preterm infants.

Objectives: 

To evaluate the benefits and safety of early versus late PN in critically ill term and late preterm infants.

Search strategy: 

We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (5 April 2019), MEDLINE Ovid (1966 to 5 April 2019), Embase Ovid (1980 to 5 April 2019), EMCare (1995 to 5 April 2019) and MEDLINE via PubMed (1966 to 5 April 2019). We searched for ongoing or recently completed clinical trials, and also searched the grey literature and reference lists of relevant publications.

Selection criteria: 

We included RCTs comparing early versus late initiation of PN in term and late preterm infants. We defined early PN as commencing within 72 hours of admission, and late PN as commencing after 72 hours of admission. Infants born at 37 weeks' gestation or more were defined as term, and infants born between 34 and 36+6 weeks' gestation were defined as late preterm.

Data collection and analysis: 

Two review authors independently selected the trials, extracted the data and assessed the risk of bias. Treatment effects were expressed using risk ratio (RR) and risk difference (RD) for dichotomous outcomes and mean difference (MD) for continuous data. The quality of the evidence was assessed using the GRADE approach.

Main results: 

Two RCTs were eligible for inclusion. Data were only available from a subgroup (including 209 term infants) from one RCT in children (aged from birth to 17 years) conducted in Belgium, the Netherlands and Canada. In that RCT, children with medium to high risk of malnutrition were included if a stay of 24 hours or more in the paediatric intensive care unit (PICU) was expected. Early PN and late PN were defined as initiation of PN within 24 hours and after day 7 of admission to PICU, respectively. The risk of bias for the study was considered to be low for five domains and high for two domains.

The subgroup of term infants that received late PN had significantly lower risk of in-hospital all-cause mortality (RR 0.35, 95% confidence interval (CI) 0.14 to 0.87; RD -0.10, 95% CI -0.18 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) = 10; 1 trial, 209 participants) and neonatal mortality (death from any cause in the first 28 days since birth) (RR 0.29, 95% CI 0.10 to 0.88; RD -0.09, 95% CI -0.16 to -0.01; NNTB = 11; 1 trial, 209 participants).

There were no significant differences in rates of healthcare-associated blood stream infections, growth parameters and duration of hospital stay between the two groups. Neurodevelopmental outcomes were not reported. The quality of evidence was considered to be low for all outcomes, due to imprecision (owing to the small sample size and wide confidence intervals) and high risk of bias in the included studies.

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