Feeding the Small for Gestational Age Infant Feeding the Small for Gestational Age Infant What s the right strategy? Infants born small-for-gestational age (SGA) are at higher risk for adult diseases. Metabolic and cardiovascular risk may be modulated by nutrition in early infancy Poor postnatal growth is linked to decreased cognitive function Low birth weight in combination with catch-up growth predicts the occurrence of the metabolic syndrome in men at late middle age Colle, et al. Pediatrics, 1976 Forsen et al, Ann Intern Med, 2000 Eriksson et al, BMJ, 2001 Eriksson et al, Diabetologia, 2003 Fagerberg et al, J Intern Med, 2004 Eriksson et al, Diabetologia, 2006 Ecklund et al, J Clin Endocrionol Metab, 2007 1
Low birth weight in combination with catch-up growth predicts the occurrence of the metabolic syndrome in men at late middle age This group were all SGA Figure 1. The prevalence of the metabolic syndrome at age 58 years by tertiles of the ratio of weight at age 18 years/birth weight in 396 Caucasian men. Fagerberg et al, 2004 2
Catch-up Growth in Exclusively Breast fed SGA babies Growth occurs in sequence Normalization of lean mass occurs by 4 months of age Normalization of bone mineral content occurs by 12 months of age Fat mass still reduced at 12 months of age Catch-up Growth in Formula Fed SGA babies Early catch up of fat mass Associated with elevated levels of IGF-1 and low levels of adiponectin (risk factors for later development of obesity and insulin resistance) 3
Infants 37weeks gestation recruited from 5 hospitals in the UK Birth weight <10 percentile Randomized to receive standard infant formula (n=147; n=83 age 6-8 years) or nutrient enriched formula until 9 months of age (n=152;n=70 age 6-8) Reference group were breast fed infants (n=175; n=97 age 6-8) Formula Composition 4
Does faster growth lead to higher blood pressure? Standard (n=83) Nutrient Enriched (n=70) P value Diastolic 61.3 64.8 0.01 MAP 76.9 79.9 0.03 Systolic 100.5 102.5 0.2 Adjusted for age, sex, socioeconomic status, z score for weight and height Faster early weight gain programmed higher later blood pressure in all 3 groups. Which Milk Should Be Fed to the SGA Infant? Neurodevelopmental Considerations Infants who were breastfed exclusively for >12 weeks scored 5.0 points (range, 0.7-9.30) greater on the Wechsler Preschool and Primary Scales than those breastfed for <12 weeks. Rao et al, Acta Paediatr, 2002. Mean scores on the Bayley Mental Development Index and Psychomotor Development Index were 8.2 points greater and 5.8 points greater, respectively at 18 months of age in term SGA infants whose mothers chose to breastfeed compared to those whose mothers chose to formula feed. Morley et al, Arch Dis Child, 1988 Which Milk Should Be Fed to the SGA Infant? Outcomes of Trials In an RCT of term SGA infants who received a 76 kcal/100 ml enriched formula had a significantly lower Psychomotor Development Index (99.5 vs 102.0) scores at 9 months than infants fed the standard term formula. Morley et al, Pediatrics, 2004 Available data suggest that the benefits of feeding mother's milk to SGA infants, such as feed tolerance, infection, NEC, and neurodevelopment, are similar to those for preterm infants. 5
Which Milk Should Be Fed to the SGA Infant? The ideal postnatal growth rate for SGA infants is not known. A fetus grows in utero at a rate of at least 15-20 g/kg/day. To attain this rate, the SGA infant would need approximately 110-135 kcal/kg/day with additional energy for catch-up growth. The current goal of current nutritional management is to achieve a postnatal growth rate similar to normal intrauterine growth. However, postnatal growth failure and associated poor neurodevelopmental outcomes occur commonly in SGA infants. Which Milk Should Be Fed to the SGA Infant? The slower the rate of intrauterine growth, the less likely the infant will exhibit catch-up growth. Less-affected and healthier SGA infants are more likely to respond to nutritional intervention and exhibit catch-up growth during the first 6 months. the lower the gestational age, the longer it takes to achieve final catch-up growth and the worse the long-term prognosis. Which Milk Should Be Fed to the SGA Infant? Catch-up growth may need to be gradual: not too much and not too fast. If an infant is SGA at birth and subsequently has a discharge weight AGA, this represents early postnatal catch-up growth and may be a risk factor for metabolic syndrome in adult life. Healthy catch-up growth is paralleled by an increase in linear growth and lean body mass, and unhealthy catch-up growth is associated with an increase in fat mass, central adiposity, and insulin resistance. 6
Which Milk Should Be Fed to the SGA Infant? Population studies show that the majority of SGA infants achieve catch-up growth during the first 2 years of life, and a failure to show early compensatory growth in that time period predicts permanently decreased growth. Hediger et al, Pediatrics, 1998 What are the gaps and the limitations? Difficulties in the translation of data from high-income to low-income countries Lack of good and well-powered prospective randomized studies Lack of knowledge of the extent to which infant weight gain may be programmed in utero Lack of knowledge of the genetic determinants of infant and childhood growth What are the gaps and the limitations? The unknown extent to which surrogate markers of the metabolic syndrome may sufficiently predict the development of type 2 diabetes or obesity What are the roles of macro and micronutrients What is the balance between short-term advantage and long term risks of postnatal overnutrition 7