Richard J Cooke

First year growth of preterm infants fed standard compared to marine oil n−3 supplemented formula

Very low birth weight (VLBW) infants (748–1390 g, n=65) were randomly assigned to receive control or marine oil-supplemented formula when they achieved intakes >454 kJ (110 kcal)/kg/d of a formula designed for VLBW infants. Study formulas with or without marine oil were provided until 79 wk of postconceptional age (PCA), first in a formula designed for preterm infants followed by a formula designed for term infants. Infants were studied at regular intervals through 92 wk PCA. Weight, length, and head circumference were determined by standardized prodedures and normalized to the National Center for Health Statistics figures for growth of infants born at term of the same age and gender. Mean normalized weight, weight-to-length, and head circumference were greatest at 48 wk and decreased thereafter. The decline in normalized weight was greater in infants fed the marine oil-supplemented formula. Beginning at 40 wk, marine oil-supplemented infants compared to controls had significantly poorer Z-scores for weight, length and head circumference. In addition, birth order (negatively) and maternal height (positively) influenced weight and length achievement in infancy as shown previously in infants born at term.

Long-Term Feeding of Formulas High in Linolenic Acid and Marine Oil to Very Low Birth Weight Infants: Phospholipid Fatty Acids

ABSTRACT: Red blood cell (RBC) phospholipids of infants fed human milk compared with formula have more arachidonic acid (AA) and docosahexanoic acid (DHA). The addition of low levels of marine oil to infant formula with 0.6 to 2.0% α-linolenic acid (LLA, 18:3n-3) prevented declines in DHA in formula-fed infants; however, the feeding trials were short (4 to 6 wk), LLA concentrations were low compared with current formulas (3.0 to 5.0% LLA), and the formulas were unstable. Trials with stable formulas were necessary to determine if dietary DHA could maintain phospholipid DHA after discharge from the hospital and, in fact, if it was necessary with higher intakes of LLA. The results of acute (4 wk) and extended (to 79 wk postconception) feeding of such formulas on RBC and plasma phospholipid AA and DHA are reported here. Control formulas were identical to commercially available formulas. Experimental formulas differed only in the addition of small amounts of marine oil. DHA in RBC and plasma phosphatidylethanolamine (PE) declined during four weeks of feeding but not if marine oil provided DHA (0.2% or 0.4%) and plasma phospholipid AA (g/100 g) decreased with time and marine oil feeding. Extended feeding with marine oil accounted for half the DHA in RBC and plasma phosphatidylethanolamine at equilibrium; however, RBC (g/100g) and plasma AA (g/100 g; mg/L plasma) decreased progressively until late infancy and were depressed further by marine oil. We conclude that 1) AA and DHA decline in RBC and plasma phospholipids of preterm infants when only their n-6 and n-3 fatty acid precursors are consumed; and 2) marine oil can maintain cord concentrations of RBC phosphatidylethanolamine DHA but further reduces AA.

Feeding Preterm Infants after Hospital Discharge: Growth and Development at 18 Months of Age

We have shown that preterm infants fed a preterm formula grow better than those fed a standard term infant formula after hospital discharge. The purpose of this follow-up study was to determine whether improved early growth was associated with later growth and development. Preterm infants (≤1750 g birth weight, ≤34 wk gestation) were randomized to be fed either a preterm infant formula (discharge to 6 mo corrected age), or a term formula (discharge to 6 mo), or the preterm (discharge to term) and the term formula (term to 6 mo). Anthropometry was performed at 12 wk and 6, 12, and 18 mo. Mental and psychomotor development were assessed using the Bayley Scales of Infant Development II at 18 mo. Differences in growth observed at 12 wk were maintained at 18 mo. At 18 mo, boys fed the preterm formula were 1.0 kg heavier, 2 cm longer, and had a 1.0 cm greater occipitofrontal circumference than boys fed the term formula. Boys fed the preterm formula were also 600 g heavier and 2 cm longer than girls fed the preterm formula. However, no differences were noted in MDI or PDI between boys fed the preterm formula and boys fed the term formula or between the boys fed preterm formula and girls fed the preterm formula. Overall, boys had significantly lower MDI than girls (mean difference, 6.0;p < 0.01), primarily reflecting lower scores in boys fed the term formula. Thus, early diet has long-term effects on growth but not development at 18 mo of age. Sex remains an important confounding variable when assessing growth and developmental outcome in these high-risk infants.

Body composition of preterm infants during infancy

AIMS To examine body composition in preterm infants. METHODS Body composition was measured by dual energy x-ray absorptiometry (DEXA) at hospital discharge, term, 12 weeks, and at 6 and 12 months corrected age in 125 infants (birthweight ⩽ 1750 g, gestational age ⩽ 34 weeks). RESULTS Body weight derived by DEXA accurately predicted that determined by conventional scales. In both sexes lean mass (LM), fat mass (FM), %FM, bone area (BA), bone mineral mass (BMM), and bone mineral density (BMD) increased rapidly during the study; significant changes were detectable between discharge and term. At 12 months, LM, BA, and BMM, but not FM, %FM, or BMD were greater in boys than in girls. Corrected for age, LM was less than those of the reference term infant; FM and %FM were similar; BMM was greater. Corrected for weight, LM was similar to those of the reference infant, while the FM and %FM of study infants were slightly greater. CONCLUSIONS DEXA accurately measures body mass. Body composition in preterm boys and girls differs. Interpretation of DEXA values may depend on whether age or body weight are regarded as the appropriate reference.

Effect of vegetable and marine oils in preterm infant formulas on blood arachidonic and docosahexaenoic acids

Adding docosahexaenoic acid (DHA) (22:6n-3) to formulas is more effective than increasing formula alpha-linolenic acid (18:3n-3) in maintaining blood phospholipid DHA levels similar to those in breast-fed infants. However, in long-term trials supplementary DHA given as marine oil reduces blood phospholipid arachidonic acid (AA) in preterm infants. This effect is not seen in short-term trials unless the total n-3 intake from marine oil exceeds 0.5% of the total fatty acids. In addition, there is considerable variability among individual preterm infants in blood phospholipid AA and DHA levels that is not dependent on diet. Within dietary treatments, a significant positive correlation between AA and DHA concentrations suggests that factor(s) other than marine oil supplementation affect both AA and DHA status. Docosahexaenoic acid and AA concentrations in plasma phospholipids are significantly correlated with DHA and AA concentrations in red blood cell phospholipids, suggesting that the observed individual differences in DHA and AA within groups represent true differences in fatty acid status. Preterm infants appear to be vulnerable to a poor status of both DHA and AA; further feeding trials are needed to identify the optimal balance of fatty acids for feeding these infants.

Feeding issues in preterm infants.

A major concern for those taking care of preterm infants is to ensure that nutritional intake meets requirements, thereby ensuring that poor nutrition is not rate limiting on outcome. However, establishment of an adequate intake is difficult during early life in the sick infant. Dietary needs also vary, depending on maturity and nutritional and clinical status. Furthermore, measures of outcome are not widely agreed on. This paper will briefly review some of the principles involved and address some of the practical questions that arise on a day to day basis during nutritional care of these high risk infants. Recommended dietary intakes are based on needs for maintenance and growth and the assumption that postnatal growth approximates that in utero at the same post conceptional age.1 However, recommended intakes take time to establish, and, having been established, are commonly interrupted for clinical reasons during the first three to four weeks of life in preterm infants. Figure 1 illustrates this situation more clearly. Embleton et al 2 compared actual and recommended dietary intake (energy 102 kcal/kg/day; protein 3.0 g/kg/day) in a group of preterm infants (⩽ 34 weeks gestation) during the initial hospital stay. By 7 days of age, infants had developed major deficits in energy (∼400 kcal/kg) and protein (13 g/kg), which were not recovered by the time of discharge from hospital; the more immature the infant the greater the deficit at discharge.2 Figure 1 Actual and recommended dietary intake (energy (A) and protein (B)) in a group of preterm infants during the initial hospital stay. *p<0.001. Data taken from Embleton et al.2 It has therefore been suggested that dietary intake must also meet needs for “catch up” growth.3 Whether or not this can be accomplished before hospital discharge remains to be determined, but closer attention must be paid to …

Protein Requirements in Preterm Infants: Effect of Different Levels of Protein Intake on Growth and Body Composition

This study compares growth and body composition in preterm infants (≤1750 g birth weight, ≤34 wk gestation) fed three iso-caloric formulas (80 kcal/100 mL) with different protein concentrations (A = 3.3 g/100 kcal, B = 3.0 g/100 kcal, C = 2.7 g/100 kcal). The study began when full enteral feeding (150 mL/kg/d) was established and lasted until term plus 12 wk corrected age (T + 12 wca). Nutrient intake was closely monitored throughout the study; daily during initial hospital stay and following discharge averaged between each clinic visit. Anthropometry and serum biochemistries were determined weekly during initial stay and at each clinic visit. Body composition was measured after hospital discharge and at T + 12 wca. Seventy-seven infants were recruited. No differences were detected in birth/enrollment characteristics between the groups. Protein intake was closely paralleled by changes in serum urea nitrogen and differed between the groups. Infants in group A were heavier and longer and had greater head circumference at discharge, but this was confounded by a slightly older corrected age in this group. There were no significant anthropometric differences at term or T + 12 wca. No differences were detected in body composition between the groups following discharge or at T + 12 wca. An intake of 3.3 g/100 kcal appears safe and may promote increased growth before initial hospital discharge. After discharge, intakes greater than 2.7 g/100 kcal do not appear to offer clear advantage. Further studies are needed to more precisely define protein requirements in these nutritionally at-risk infants.

Effects of Intrauterine Growth on Intestinal Length in the Human Fetus

Standards for human fetal intestinal length are not well established but have important implications for the care of the preterm and intra-uterine growth-retarded (IUGR) infant. Our purpose was to examine the relationship between intra-uterine growth and intestinal length in the human fetus. One hundred infants were studied. Birth weight and gestational age ranged from 76 to 4,385 g and from 12 to 42 weeks, respectively. Twenty-one infants were noted to be IUGR. Intestinal length (total, small, large) increased (p < 0.0001) with birth weight, gestational age, and crown-heel length but was reduced in IUGR infants. The ratio of body weight to intestinal length increased with gestation but was also reduced in IUGR infants. In conclusion, a reduced functional mass, as suggested by decreased intestinal length or body weight:intestinal length ratio, may contribute to the poor weight sometimes seen in the very-low-birth weight or IUGR infant.

Postnatal growth in infants born between 700 and 1,500 g

Our purpose was to examine postnatal growth in very low birth weight (VLBW) infants (n = 54). A high frequency of intrauterine growth retardation was noted that was corrected by plotting birth weight against crown-heel length and not gestational age. No differences in postnatal growth were noted between infants whose size was appropriate for gestational age (n = 37) and those small for gestational age (n = 17). Overall, growth tended to exceed that previously published. Weight but not length or head gain was less in the smaller (≤ 1,000 g) when compared to the larger (> 1,000 g) VLBW infant. Poorer weight gain could not be related to more “illness” or less nutrient intake in the smaller infants.

Effects of type of dietary protein on acid-base status, protein nutritional status, plasma levels of amino acids, and nutrient balance in the very low birth weight infant.

STUDY OBJECTIVE To determine the effect of the type of dietary protein (3.3 gm/kg per day) on acid-base status, protein nutritional status, plasma amino acid concentrations, and nutrient (nitrogen, fat, mineral, trace element) balance. SUBJECTS Preterm infants (birth weight less than or equal to 1250 gm, gestational age less than or equal to 32 weeks) with no evidence of systemic disease, who had achieved a minimal enteral intake of 110 kcal/kg per day by 21 days of age. INTERVENTIONS Each infant was fed three study formulas that differed only with respect to the ratio of whey to casein (60:40, 35:65, 18:82). Each formula was given for 1 week. At the end each week, blood was drawn and a 48-hour balance was determined. MAIN RESULTS Late metabolic acidosis, uremia, and hyperammonemia were not observed. No differences in pH or serum bicarbonate were noted. Base excess was greater with the casein-predominant formula (18:82 greater than 35:65, 60:40) but remained within normal limits for the preterm infant. Plasma concentrations of threonine (60:40 greater than 35:65 greater than 18:82), phenylalanine, and tyrosine (18:82 greater than 35:65 greater than 60:40) differed. Nitrogen absorption (60:40 less than 35:65, 18:82), nitrogen retention (60:40 less than 35:65, 18:82), fat absorption (60:40, 35:65 greater than 18:82), and phosphorus absorption (60:40 less than 35:65, 18:82) also differed. CONCLUSIONS At an intake of 3.3 gm/kg per day, the type of dietary protein had little effect on metabolic status. Differences in plasma amino acid concentrations and nutrient balance suggest that a formula containing protein with a whey/casein ratio of 35:65 may be preferable to that with a whey/casein ratio of 60:40 or 18:82 for the very low birth weight infant.