The goal of nutritional management of very low birthweight infants [VLBW] is the achievement of postnatal growth at a rate approximating the intrauterine growth of a normal fetus at a similar post-conceptional age (<xref ref-type="bibr" rid="bib001">1</xref>). In reality, however, the growth of these infants lags considerably after birth (<xref ref-type="bibr" rid="bib002">2</xref>) for a variety of reasons including our inability to provide the needed nutrients. Nutritional support of these infants has become an integral part of their care and this assumes more importance since the incidence of prematurity has increased in recent years (<xref ref-type="bibr" rid="bib003">3</xref>) resulting in an ever increasing number of infants that challenge both neonatologists and nutritionists. This is further confounded by the increase in post neonatal morbidities including poor growth, neurodevelopmental delay, hearing, vision loss and cerebral palsy.Data from the NICHD Neonatal Research Network demonstrates the differences between normal intrauterine growth and the observed rate of growth of VLBW infants (<xref ref-type="bibr" rid="bib002">2</xref>). Three cohorts of infants, 24–25, 26–27 and 28–29 weeks of gestation were compared to intrauterine growth (<xref ref-type="bibr" rid="bib004">4</xref>). All groups initially lost weight and birthweight was regained by approximately 2.5 weeks; however, by 32 weeks postmenstrual age, the growth curves for all three groups was below the 10th percentile for <italic>in utero</italic> growth. The weight differences represented 35–41% of the average weight of a 32 week fetus thus creating <italic>extrauterine growth restriction</italic>. Reasons for poor growth include delayed commencement of total parenteral nutrition, intolerance to glucose and lipids, feeding practices and the feeding of unfortified human milk or term infant formulas. However, in recent years, there has been a substantial increase in nutrient intakes of the VLBW infant during the early neonatal period, largely as a consequence of early parental nutrition (<xref ref-type="bibr" rid="bib005">5</xref>–<xref ref-type="bibr" rid="bib006">6</xref>). Nonetheless, the nutrient intakes received by VLBW infants are lower than nutrient intakes by the fetus and this deficit may persist beyond the early nutritional period past hospital discharge. There is considerable evidence that the early growth deficit has long-lasting effects including short stature and poor neurodevelopmental outcome (<xref ref-type="bibr" rid="bib007">7</xref>). These considerations have led to the concept of <bold><italic>“aggressive nutrition of the VLBW infant.”</italic></bold>Aggressive nutrition conceptually would mean that the transition from <italic>in utero</italic> to <italic>ex-utero</italic> life should proceed with minimal metabolic stress and growth deficit. However, given the current state of affairs, our best approach could be to minimize the interruption without adverse metabolic cost.</sec><sec id="sec002"><title>Strategies to promote growth

JNNFI

Journal of Neonatology

0973-21870973-2179

National Neonatology Forum

jn-20-3-012

Commentaries

Early nutritional support of the very low birthweight infant in the NICU

Bhatia

Jatinder

Professor and Chief Section of Neonatology, Vice Chair for Clinical Research

Department of Pediatrics, Medical College of Georgia, Augusta, GA, USA. E-mail: jatindeb@mail.mcg.edu

7–92006

203272274

The goal of nutritional management of very low birthweight infants [VLBW] is the achievement of postnatal growth at a rate approximating the intrauterine growth of a normal fetus at a similar post-conceptional age (<xref ref-type="bibr" rid="bib001">1</xref>). In reality, however, the growth of these infants lags considerably after birth (<xref ref-type="bibr" rid="bib002">2</xref>) for a variety of reasons including our inability to provide the needed nutrients. Nutritional support of these infants has become an integral part of their care and this assumes more importance since the incidence of prematurity has increased in recent years (<xref ref-type="bibr" rid="bib003">3</xref>) resulting in an ever increasing number of infants that challenge both neonatologists and nutritionists. This is further confounded by the increase in post neonatal morbidities including poor growth, neurodevelopmental delay, hearing, vision loss and cerebral palsy.Data from the NICHD Neonatal Research Network demonstrates the differences between normal intrauterine growth and the observed rate of growth of VLBW infants (<xref ref-type="bibr" rid="bib002">2</xref>). Three cohorts of infants, 24–25, 26–27 and 28–29 weeks of gestation were compared to intrauterine growth (<xref ref-type="bibr" rid="bib004">4</xref>). All groups initially lost weight and birthweight was regained by approximately 2.5 weeks; however, by 32 weeks postmenstrual age, the growth curves for all three groups was below the 10th percentile for <italic>in utero</italic> growth. The weight differences represented 35–41% of the average weight of a 32 week fetus thus creating <italic>extrauterine growth restriction</italic>. Reasons for poor growth include delayed commencement of total parenteral nutrition, intolerance to glucose and lipids, feeding practices and the feeding of unfortified human milk or term infant formulas. However, in recent years, there has been a substantial increase in nutrient intakes of the VLBW infant during the early neonatal period, largely as a consequence of early parental nutrition (<xref ref-type="bibr" rid="bib005">5</xref>–<xref ref-type="bibr" rid="bib006">6</xref>). Nonetheless, the nutrient intakes received by VLBW infants are lower than nutrient intakes by the fetus and this deficit may persist beyond the early nutritional period past hospital discharge. There is considerable evidence that the early growth deficit has long-lasting effects including short stature and poor neurodevelopmental outcome (<xref ref-type="bibr" rid="bib007">7</xref>). These considerations have led to the concept of <bold><italic>“aggressive nutrition of the VLBW infant.”</italic></bold>Aggressive nutrition conceptually would mean that the transition from <italic>in utero</italic> to <italic>ex-utero</italic> life should proceed with minimal metabolic stress and growth deficit. However, given the current state of affairs, our best approach could be to minimize the interruption without adverse metabolic cost.</sec><sec id="sec002"><title>Strategies to promote growth

Initiation of parenteral nutrition: Several controlled studies have demonstrated the efficacy and safety of amino acids initiated within the first 24 hours of age (8–12). Amino acid intakes up to 3 g/kg/d are well tolerated. Glucose infusion rates should maintain euglycemia. However, VLBW infants are often intolerant to higher glucose intakes and glucose delivery can be limiting. Several strategies have been used to ameliorate the hyperglycemia: decrease glucose delivery; administer amino acids which decrease glucose concentrations presumably by enhancing endogenous insulin production; initiation of exogenous insulin which may have an added benefit of reducing hyperkalemia. The latter approach has been questioned because of resultant lactic acidosis noted in one study (13). Lipids when administered satisfy both essential fatty acid requirements and serve as an efficient energy source. VLBW infants can be intolerant to large amounts of lipids and need to be monitored for tolerance [measuring triglycerides] as lipids are increased in a step wise fashion to 3 g/kg/d.

Initiation and advancement of enteral feeds: Because of the availability and tolerance of parenteral nutrition, many clinicians often delay the initiation of enteral nutrition because of the fear of developing Necrotizing enterocolitis. It should be noted that swallowed amniotic fluid provides the third trimester fetus approximately 25% of the protein intake of a term breast fed infant (14). Since it is well known that intraluminal nutrition is important for gastrointestinal integrity, enteral nutrition should be started as soon as feasible given that the GI tract is already used to receiving nutrients.

There are numerous studies demonstrating that feeding early has advantages in establishing complete enteral nutrition, decreased incidence of cholestasis and better glucose homeostasis. Feeding regimens of 20 mL/kg/d for smaller preterm infants and 30 mL/kg/d for larger premature infants have been well tolerated. Postnatal growth needs to be monitored closely especially when chronic lung disease is also present because of the increased energy expenditure associated with increased work of breathing.

The aggressive early nutrition approach has been demonstrated to result in: earlier achievement of positive nitrogen balance; nearly normal amino acid profiles; higher energy intakes; less hyperglycemia; no differences in BUN, triglycerides, ammonia or bicarbonate concentrations; improved growth and fewer infants less than the 10^th percentile at 36 weeks postconceptional age.

The suggested guidelines are as follows:

Early initiation and advancement of parenteral nutrition

Early initiation of enteral feeds with human milk or premature infant formulas

Appropriate fortification of human milk

Infants less than 1800 g be fed a premature infant formula or human milk fortified appropriately

Transition to 22 kcal/oz formula at >1800 g with all growth parameters at or above 25^th percentile and infant is gaining 15–40 g/d

If fed human milk, continue fortification unless infant can tolerate larger volumes and is a larger premature infant [32–34 weeks] Transition from 22 kcal to 20 kcal/oz term formula beyond 6 months if all parameters are above the 25^th percentile

There is evidence that low birthweight infants are at risk for developing cardiovascular disease, hypertension, insulin resistance and obesity raising the issue of long term “nutritional programming” (15,16). Further, Fewtrell et al (17) recently demonstrated that at age 13 to 16 years, insulin resistance as measured by proinsulin concentration [32/33 split] was greater in preterm infants fed a preterm formula than a low-nutrient formula. In another study, in a cohort of infants being followed longitudinally, brachial artery flow-mediated endothelium-dependent dilatation in adolescence was greater in a cohort of infants who as infants gained weight in the first two weeks of life compared to those whose weight gain was below the sample mean (18). However, these data need to be put into proper perspective since the NICHD data in a large cohort demonstrated uniform growth lag in the cohorts of small premature infants. Until more optimal strategies are developed, striving towards the best possible gain without adverse metabolic effects may be appropriate (19).

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