Early introduction of lipids to parenterally-fed preterm infants

Premature babies who are not yet ready to digest and absorb full milk feeds are given lipids through a vein to improve their nutrition. The issue of how early the lipids should be introduced to be advantageous while causing no harm is a matter of debate. The review found that, while no side effects were reported, there was no statistically significant benefit of introducing lipids before five days of age. Long term effects of early introduction of lipids in premature babies have not been reported.

Authors' conclusions: 

No statistically significant effects of 'early introduction' of lipids on short term nutritional or other clinical outcomes, either benefits or adverse effects, were demonstrated in the studies reviewed. Based on the currently available evidence, 'early' initiation of lipids (≤ 5 days after birth) can not be recommended for short term growth or to prevent morbidity and mortality in preterm infants.

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Background: 

Lipids are essential components of parenteral nutrition for preterm infants. Parenteral lipids can be administered through a peripheral vein, and their early introduction offers the potential advantages of increasing energy intake and providing essential fatty acids and fat soluble vitamins. Concerns have been raised about potential adverse effects including chronic lung disease (CLD), increase in pulmonary vascular resistance, impaired pulmonary gas diffusion, bilirubin toxicity, sepsis and free radical stress.

Objectives: 

To determine the safety and efficacy of 'early' (≤ 5 days after birth) introduction of lipids to parenterally fed preterm infants.

Search strategy: 

Eligible studies were identified by searching MEDLINE (December 2004), EMBASE 1980 - 2004, Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2004) and CINAHL (December 1982 - December 2004). Abstracts of the Society for Pediatric Research were hand searched from 1980 to 2004 inclusive. No language restrictions were applied.

Selection criteria: 

All randomised or quasi randomised controlled trials comparing 'early' versus 'no early' introduction of lipids to preterm infants.

Data collection and analysis: 

Data were sought regarding effects on growth and risk of CLD or death, other respiratory morbidities including duration of respiratory support, duration of supplemental oxygen, the need for home oxygen, pneumothorax (PTX), pulmonary haemorrhage and pulmonary interstitial emphysema (PIE), ≥ stage 2 necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), sepsis, intraventricular haemorrhage (IVH), clinically significant thrombocytopenia and significant jaundice. Methodological quality of eligible studies was assessed according to allocation concealment, blinding of intervention, blinding of outcome assessment and completeness of follow up. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. For categorical data the Typical relative risk (RR), Typical risk difference (RD) and number needed to treat (NNT) with 95% confidence intervals (CI) were calculated. Continuous data were analysed using weighted mean difference (WMD).

Main results: 

Five studies (n = 397) were included in the review. All studies compared the effectiveness and safety of 'early' introduction versus 'no early' introduction of lipids in preterm infants. The timing of introduction of 'early lipids' ranged from < 12 hours after birth to day five of life. The timing of introduction of lipids in the 'no early' lipid group ranged from day six after birth to day 14 after birth. The initial dose ranged from 0.5 - 1 g/kg/day with gradual daily increments up to a maximum of 2.5 - 3.5 g/kg/day.
For the primary outcomes (growth, death and CLD), there was no statistically significant difference between the 'early' lipid and 'no early' lipid groups.
Days to regain birth weight: [WMD 0.59 (95% CI -2.41, 3.58); two trials; N = 71].
Rate of weight gain (g/day) during period of hospital stay: [MD -2.40 (95% CI -5.30, 0.50); one trial; N = 129]
Death (irrespective of time): [Typical RR 1.04 (95% CI 0.69, 1.56); Typical RD 0.01 (95% CI -0.07, 0.08); five trials; N = 397]
Neonatal deaths: [Typical RR 1.35 (95% CI 0.78, 2.34); Typical RD 0.05 (95% CI -0.04, 0.13); four trials; N = 268].
CLD: [Typical RR 1.10 (95% CI 0.81, 1.49); Typical RD 0.04 (95% CI -0.09, 0.17); two trials; N = 193].

For the secondary outcomes of other respiratory morbidities including duration of respiratory support, duration of supplemental oxygen, PTX, pulmonary haemorrhage, PIE, NEC, ROP, PDA, sepsis, IVH and significant jaundice, there were no statistically significant differences between 'early' and 'no early' lipid groups.

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