Karen Edmond, MBBS, MSc, PhD, Rajiv Bahl, MD, PhD
World Health Organization 2006
Findings of the review
What to feed
Choice of milk
Breastfeeding or mother’s own expressed milk. There is strong and consistent evidence that feeding mother’s own milk to pre-term infants of any gestation is associated with a lower incidence of infections and necrotising enterocolitis, and improved neurodevelopmental outcome as compared with formula feeding. Feeding unsupplemented mother’s own milk to pre-term infants <1500 g resulted in slower weight and length gains, but the implications of this slower growth are unclear and there is not enough evidence to assess if it increased the risk of malnutrition. Long-term beneficial effects of breastfeeding on blood pressure, serum lipid profile or pro-insulin levels have also been reported for pre-term infants. There are limited data on most outcomes in term LBW infants; the available data suggest that improved infection and neurodevelopmental outcomes associated with feeding mother’s milk in pre-term infants are also seen in this group.
Donor human milk. The available data indicate that feeding with donor human milk rather than standard or pre-term infant formula to LBW infants of <32 weeks gestation reduces the incidence of necrotising enterocolitis. The data are insufficient to conclude if there are neurodevelopmental advantages. Growth is slower in the short term in the infants fed donor human milk, but there are insufficient data to assess the effects on long-term growth outcomes. It should be noted that many of the identified studies used drip milk (i.e. breastmilk that drips from the opposite breast while breastfeeding) rather than the recommended expressed donor milk. Although there is limited evidence, it can be assumed that the findings are similar in infants of 32–36 weeks gestation. There are no data on outcomes in the subgroup of term LBW infants.
Pre-term infant formula. Infants of <32 weeks gestational age who were fed preterm infant formula had higher psychomotor developmental scores at 18 months of age than those fed standard infant formula. Although there was no overall effect observed in these children at 7½–8 years of age, the verbal intelligence quotient (IQ) scores were higher in the pre-term infant formula group among boys. Pre-term formula increases growth during the neonatal period but this is not sustained during later infancy and childhood. No long-term benefits (e.g. blood pressure, serum lipid profile or pro-insulin) have been found. There are insufficient data to draw any conclusions for pre-term infants of 32–36 weeks gestational age or for term LBW infants.
Optimal duration of exclusive breastfeeding
Overall there is no evidence to recommend a different duration of exclusive breastfeeding for pre-term or term LBW infants than for infants who are not low birth weight. Limited available data from industrialized countries suggest that early supplementation of breastfeeding (at about 3 months of age) with a high calorie diet in pre-term infants may marginally increase linear growth and haemoglobin levels. No data are available for other key outcomes. Among term LBW infants, the available evidence from two trials suggests that exclusive breastfeeding for 6 months, compared with 4 months, had no deleterious impact on neurodevelopment, growth, or haemoglobin levels, if it was accompanied by iron supplementation.
Human milk supplementation
Vitamin D. There is some evidence of reduced linear growth and increased risk of rickets in babies with a birth weight <1500 g fed unsupplemented human milk. There seems to be no consistent benefit of increasing the intake of vitamin D from the usually recommended 400 IU per day. There are no clinical trial data on the effect of vitamin D on key clinical outcomes in infants with a birth weight >1500 g. Phosphorus and calcium. There is some evidence that phosphorus and calcium supplementation reduces the risk of metabolic bone disease in pre-term infants and leads to short-term increases in bone mineralization in infants with a birth weight of <1500 g. There are no data on the effect of phosphorus and calcium supplementation on key clinical outcomes in infants with a birth weight >1500 g.
Iron. Iron supplementation, started at 6–8 weeks of age in LBW infants, is effective in preventing anaemia during infancy. There is some evidence that anaemia is common in LBW infants fed unsupplemented human milk even at 8 weeks of age. There is also some evidence to suggest that iron supplementation, started at 2 weeks of age, may prevent this early anaemia in infants with birth weights <1500 g. However, there are insufficient data on the safety of iron supplementation during the first two months of life. There are no data on the effects of iron supplementation on mortality, common childhood illnesses or neurodevelopment in LBW infants.
Vitamin A. No conclusions can be made about the benefits of early vitamin A supplementation of LBW infants. Findings from a single large trial suggest that vitamin A (50,000 IU in one or two divided doses) during the first days of life may have a survival advantage, particularly in infants with birth weights <2000 g.
Zinc. There are no data on the effect of zinc on key clinical outcomes in pre-term infants. Data from two trials in developing countries suggest that term LBW infants in developing countries may have lower mortality and morbidity if they receive zinc supplementation. There seems to be little evidence that zinc supplementation in these infants improves neurodevelopment or affects growth.
Multicomponent fortifier. In infants of <32 weeks gestation, there is evidence that use of multicomponent fortifier leads to short-term increases in weight gain, linear growth, head growth and bone mineralization. There are insufficient data to evaluate the long-term neurodevelopmental and growth outcomes, although there appears to be no effect on growth beyond one year of age. Use of multicomponent fortifiers does not appear to be associated with increased risk of mortality or necrotizing enterocolitis, although the small number of infants and the large amount of missing data in the studies reduce confidence in this conclusion. Also, in the largest trial undertaken there was a significant increase in the incidence of infection among infants receiving the fortifier. There are no data examining the efficacy of multicomponent fortifier in infants of 32–36 weeks gestation or in term LBW infants.
How to feed
Cup feeding compared with bottle feeding. In pre-term infants, cup feeding leads to higher rates of full (exclusive or predominant) breastfeeding, compared with bottle feeding at the time of discharge from hospital. Cup feeding was also associated with greater physiological stability, e.g. lower risk of bradycardia or desaturation, than bottle feeding. No data are available for term LBW infants. When cup feeding is correctly done, i.e. with the infant upright and the milk is not poured into the mouth, there is no evidence that there is an increased risk of aspiration.
Nasogastric compared with orogastric feeding. Physiological data show that nasogastric tubes increase airway impedance and the work of breathing in very preterm infants, which is supported by clinical data showing an increased incidence of apnoea and desaturation.
Bolus compared with continuous intragastric feeding. Bolus feeding refers to a calculated amount of feed given intermittently every 1–4 hours by a nasogastric or orogastric tube. In infants of <32 weeks gestation, there is some evidence that bolus feeding can reduce the time to full enteral feeding, but no conclusions can be made about other advantages or disadvantages. A disadvantage of continuous feeding of expressed breastmilk is that fat can separate and stick to the syringe and tubes. There are physiological data which show that duodenal motor responses and gastric emptying is enhanced in infants of 32–35 weeks gestation given continuous intragastric feeding. There are no trial data comparing clinical outcomes associated with continuous or bolus intragastric feeding in infants of 32–36 weeks gestation or in term LBW infants.
Initiation of ‘maintenance’ enteral feeding. Data are available only from two controlled studies conducted in the 1960s. One of these studies showed that infants <2250 g at birth had higher mortality if given full maintenance enteral fluids starting within 2 hours of birth as compared to those given small enteral feeds starting 12–16 hours after birth. Findings from the other study in infants of <32 weeks gestation indicated that infants given IV fluids on the first day of life had lower mortality than those who received nasogastric feeds of glucose in water or those who received no feeds or fluids. No firm conclusions can be drawn from these studies. However, it appears that very pre-term infants may benefit from avoidance of full enteral feeds on the first day of life.
Progression of enteral feeding. In infants of <32 weeks gestation, faster rates of increase in feeding volumes (20–35 ml/kg/day compared with 10–20 ml/kg/day) may decrease the time to full enteral feeds and may increase weight gain. There is limited information regarding safety (broad confidence intervals for incidence of necrotising enterocolitis) and the effect on length of hospital stay. There are limited data from which to draw any conclusions about fast rates of advancement of feeding rates in infants with 32–36 weeks gestation or in term LBW infants. However, these infants are more likely to tolerate rapid feeding regimens even better than smaller more immature infants.
Demand or scheduled feeding. Demand feeding may be feasible for some infants with 32–36 weeks gestation and may reduce the length of hospitalization. No data are available for infants of <32 weeks gestation and term LBW infants.
Thermal care and support for breastfeeding
Maternal involvement in care and feeding of LBW infants. Substantial benefits in terms of improved breastfeeding rates and early discharge from hospital were reported when mothers participated in the care and feeding of their LBW infants in neonatal units.
Time of discharge from hospital. Several RCTs indicate that there are no adverse outcomes of early discharge, including no differences in weight gain, short-term complications and hospital readmissions, if the infants are discharged when the following criteria are met: the infant can breastfeed and maintain body temperature in an open crib, shows no evidence of clinical illness and is not losing weight, and the mother demonstrates satisfactory care-giving skills.
Kangaroo mother care (KMC). In clinically stable pre-term infants with a birth weight of <2000 g, there is evidence that KMC is at least as effective as conventional care in reducing mortality. KMC may reduce infections and improve exclusive breastfeeding rates and weight gain. There are insufficient data regarding the effect of KMC in infants with birth weights <1500 g because many of these infants were excluded from the available studies as they were not considered to be clinically stable. There is preliminary evidence from resource-poor settings that KMC may be effective even in clinically unstable LBW infants including those with birth weights <1500 g. There are no data regarding the effect of KMC in term LBW infants.
Non-nutritive sucking. Non-nutritive sucking may decrease the length of hospital stay in pre-term infants but has no effect on growth outcomes in preterm infants who weigh less than 1800 g at birth. Encouraging the infant to suck on the ‘emptied’ breast, after expression of breast milk, may result in improved breastfeeding rates at discharge and at follow-up.
Breastfeeding counselling. There are few data on the effect of breastfeeding counselling among pre-term infants of <32 weeks gestation. Among pre-term infants of 32–36 weeks gestation and term LBW infants, breastfeeding counselling improves the rates of exclusive breastfeeding at 3 months. This finding is consistent with the results of a meta-analysis of 20 intervention trials in term normal birth weight infants.
Drug therapy for enhancing lactation. The available evidence suggests that metoclopramide or domperidone increases breastmilk volume in mothers of infants of <32 weeks gestation, particularly those who were having difficulty in maintaining milk production. There are no data regarding efficacy in the mothers of infants of 32–36 weeks gestation or for term LBW infants.
Blood glucose monitoring. There are no studies reporting the effects of regular blood glucose monitoring on subsequent outcomes. Limited observational data indicate that recurrent and/or prolonged blood glucose levels of <2.6 mmol/l (<45 mg/dl) are likely to be associated with poorer neurodevelopment in later life.
Growth monitoring. There is evidence that exact mimicry of fetal growth is not possible even in well-resourced neonatal care units in developed countries. Catch-up growth occurs after very discrepant rates of neonatal growth and is less likely to be complete in the smallest infants. The optimal timing of catch-up growth is uncertain. It is unclear if lack of rapid catch-up is associated with a higher malnutrition risk. Rapid catch-up does not appear to improve neurodevelopment. On the other hand, rapid catch-up after the first year of life may be associated with increased cardiovascular risk in later life. Although monitoring the growth of LBW infants is considered essential for appropriate management, there are no data examining the effects of growth monitoring on key clinical outcomes of LBW infants.
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