Original Article

Journal of Perinatology (2006) 26, S27–S30. doi:10.1038/sj.jp.7211469

Postdischarge nutritional therapy

D H Adamkin1

1University of Louisville, Louisville, Kentucky, USA

Correspondence: Professor DH Adamkin, University of Louisville, 571 South Floyd Street, Suite 342, Louisville, Kentucky 40202. E-mail: david.adamkin@louisville.edu

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Abstract

Nutrient-enriched diets for preterm infants after hospital discharge (preterm formula or postdischarge formula (PDF)) results in improved growth and these differences appear to persist beyond the period of nutrient intervention. The PDF diet effect is greatest in males, possibly reflecting their higher growth rates. The critical growth epoch appears to be the first 2 months post-term, suggesting a finite period and therefore opportunity for enhanced growth. Whether the observed growth effects persist further or have consequences for other aspects of health or development requires further investigation.

Keywords:

premature, nutrition

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Introduction

The recommended goal of nutrition support for very low birth weight (VLBW) infants (<1500 g birth weight (BW)) from birth to term is to match the in utero growth rates of the normally growing fetus. 1 However, this goal is rarely achieved in the VLBW infant and , in fact, growth failure is more extreme in the very very low birth weight (VVLBW) infant (<1000 g BW; VVLBW). In a recent study of 200 VVLBW infants, we found that 66 to 85% fell below the 10th percentile at discharge when stratified into three cohorts of 800 to 1000 g, 600 to 800 g and <600 g, respectively.2

Growth faltering immediately after birth, including postnatal weight loss of 10 to 18% and time to return to birth weight (RTBW) of approximately 14 to 18 days, is partially responsible for the development of extrauterine growth retardation (EUGR). Actually, many VLBW infants grow at rates similar to a fetus of comparable postconceptional age after RTBW. It is early growth delay, coupled with a lack of catch-up growth, that produces EUGR, particularly in VVLBW infants.2, 3

Figure 1, from the NICHD Neonatal Research Network demonstrates the differences between normal intrauterine growth and the observed rates of postnatal growth in the NICHD study.3 For each gestational age category, the postnatal study growth curve was shifted to the right of the reference curve. Therefore, this 'growth deficiency' is common in VLBW infants.

Figure 1.
Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

Mean body weight versus gestational age in weeks for all study infants who had gestational ages at birth of between 24 and 29 weeks. (Reproduced with permission from Pediatrics 104: 280–289, Copyright © 1999 by the AAP).

Full figure and legend (52K)

Aggressive nutritional management during hospitalization can decrease the degree of initial postnatal weight loss and promote earlier onset and more rapid rates of postnatal growth in VLBW infants.4, 5 However, at discharge weights of 1800 to 2000 g, VLBW infants typically have low body stores of nutrients,6 inadequate bone mineralization,7 and an accumulated protein and energy deficit of approximately 20 g/kg and 1400 kcal/kg, respectively.2, 8

Although considerable attention has been directed toward improving the nutrition of hospitalized VLBW infants with nutrient-enriched formulae and multinutrient fortifiers for human milk, it is only recently that attention has been paid to nutritional support of these infants after hospital discharge. Long-term data show that the neonatal period is critical in terms of the effects of nutrition on later health and developmental outcomes.9, 10, 11, 12 The first year of life may provide an important opportunity for human somatic and brain growth to compensate for earlier deprivation. A key question is whether VLBW infants have special nutritional requirements in the postdischarge period and, in more biologic terms, whether this period of nutrition is also critical for later health and development, particularly since it is common for human milk fortifiers to be stopped and/or term infant formulae to be substituted at an arbitrary time point, at hospital discharge.

However, although children born preterm remain, on average, shorter and lighter than children born at term, there is no evidence that nutrition during the period of hospitalization has any long-term effects on growth. Thus, despite major differences in neonatal growth rates seen in infants receiving different diets for the first few weeks of life,13 these differences do not persist into childhood.14 Whether nutrition during the period after hospital discharge influences longer-term growth, or whether, in more biological terms, the postdischarge period is a critical one for programming the growth trajectory or other aspects of health, is a separate issue.

Available data suggest that as population, preterm infants are in a state of suboptimal nutrition at the time of discharge from the hospital and beyond. It is likely that improving this situation would be beneficial both in the short-term and also potentially for longer-term health and development.

The effects of nutrition after hospital discharge

Nutrient-enriched formula for preterm infants after hospital discharge (postdischarge formula (PDF)) is generally intermediate in composition between preterm and term formulae. When compared to term formula, PDF contains an increased amount of protein with sufficient additional energy to permit utilization. Postdischarge formula also contains extra calcium, phosphorous and zinc, all of which are necessary to promote linear growth. Additional vitamins and trace elements are included to support the projected increased growth.

A pilot study of 32 preterm infants performed 13 years ago was the first to show that those randomized to receive the PDF up to 9 months post-term showed significantly greater weight and length gains and had higher bone mineral content in the distal radius that infants who received a standard term infant formula (TF).15

Three recent studies add additional insight into the role for PDF, suggesting benefits may be related to birth weight,16 gender,16, 17, 18 and/or a 'window of opportunity' when supplemental nutrients can promote 'catch-up' and subsequent growth even after discontinuation of PDF.13, 14 Two of the reports also raise the possibility that postdischarge nutrition may benefit long-term development.17, 18

Two hundred and eighty-four preterm infants received either TF or PDF for the first 9 months post-term. At 9 months post-term, PDF infants were significantly heavier (mean difference 370 g) and longer (1.1 cm) than TF infants, and the length difference persisted to 18 months post-term. Differences between diet groups were significantly greater in boys, who had a length advantage of 1.5 cm at 18 months if they received PDF. There was no evidence that the PDF had made infants fat; their mean weight centile was still below the 50th centile and skin-fold thicknesses were not increased. Head circumference and developmental outcome at 9 or 18 months did not differ significantly between groups, although PDF infants had a 2.8 point advantage (0.25 s.d.) in Bayley mental development score (the study was powered to detect a larger (0.3 s.d.) difference).17

Carver et al.16 found growth was improved in preterm infants fed a PDF after hospital discharge up to 12 months corrected age, with the significant differences in weight, length, and/or head circumference most marked for smaller infants (BW <1250 g) and male infants. The differences in growth produced by PDF occurred quite early and then did not increase appreciable over time, suggesting that the benefit of PDF with respect to catch-up occurred soon after discharge. The benefits persisted throughout the period of observation and, for infants with birth weight <1250 g, growth in head circumference was the most beneficial effect.

Another study looked at the use of preterm formula (PTF) after discharge.18 One hundred and twenty-nine preterm infants were randomly assigned to one of three dietary regimes until 6 months post-term: TF, PTF or PTF until term then TF to 6 months. Males fed PTF after discharge showed significantly greater weight and length gain and larger head circumference by 6 months post-term than those fed TF throughout. Infants fed PTF took on average 180 ml/kg, resulting in a protein intake of around 4 g/kg/day. Those fed TF increased to around 220 ml/kg/day, but their protein intake did not match that of the PTF group. At 18 months post-term, boys previously fed PTF were on average 1 kg heavier, 1 cm longer and had 1 cm greater head circumference that those fed TF. Body composition measurements made using dual X-ray absorptiometry (DXA) suggested that the additional weight gain was composed predominantly of lean tissue rather than fat.19 There were no significant differences in neurodevelopment measured using the Bayley Scales of Infant Development at 18 months.

However, Decurtis et al.20 and the Cochrane Database21 conclude that the evidence is limited that feeding preterm infants after hospital discharge with a calorie and protein-enriched formula (compared to a standard term formula) leads to a higher rate of linear growth and weight gain.21 The 33 patient Decurtis trial20 is a 2-month study and is among the six trials15, 16, 18, 20, 22 meeting inclusion in the Cochrane analysis. Based on these six studies they recommend that follow-up of infants participating in the trials might provide further data on the effect of the intervention and growth through later childhood and on later neuro developmental outcomes, also concluded that large randomized controlled trials are needed.21

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Conclusions

Randomized studies demonstrate that the use of either PTF or PDF after discharge in preterm infants result in improved growth, with differences in weight and length persisting beyond the period of intervention in two studies. Such findings raise the hypothesis that nutrition during the postdischarge period may have longer-term effects on the growth trajectory. Evidence from three randomized trials suggests that the effect of a nutrient-enriched postdischarge diet is greatest in boys, possibly reflecting their higher growth rates and protein requirements. Whether the observed growth effects persist, or have consequences for other aspects of health or development requires further investigation.

Two of the studies clearly demonstrate the advantage in growth is apparent quite early, suggesting a finite period, 'critical growth epoch' (the first 1 to 2 months post-terms) during which catch-up growth in response to higher nutrient intake is most likely to occur.16, 18

Heird suggests more attention be paid to nutrition postdischarge as part of a strategy to address requirements for catch-up growth. He notes this is problematic because there seems to be this finite period – perhaps as brief as a few weeks during which response to increased nutrient intake occurs.23

However, continuation of the nutrient-enriched formula for some time beyond the first 2 months post-term is necessary to assure the early advantage provided by the PTF persists. Perhaps VVLBW infants with EUGR at discharge plus microcephaly, or oxygen-dependence or poor recent growth rates before discharge might be candidates for discharge on PTF.

In humans, the importance of nutrition in early life is now well known, and the term 'programming' has been proposed to emphasize that early nutrition should be considered not simply in terms of providing immediate nutritional needs but also because of certain biologic effects that may have lasting or lifelong significance.9, 10, 11 Epidemiologic data also suggest that small size both at birth and at 1 year of age is associated with higher rates of diabetes, hypertension, cardiovascular diseases and stroke later in life.24, 25 The American Academy of Pediatrics has recognized the importance of the postdischarge period and recommends PDF in the first 9 months in these infants.26

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References

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