A randomized controlled trial of prenatal nutritional supplementation in New York City. Prenatal food supplementation fortified with multiple micronutrients increases birth length: a randomized controlled trial in rural Burkina Faso. Supplementation with human milk protein improves growth of small premature infants fed human milk. Growth, nutrient retention, and metabolic response in low birth weight infants fed varying intakes of protein and energy. Protein requirements in preterm infants: effect of different levels of protein intake on growth and body composition. Effect of protein/energy ratio on growth and behavior of premature infants: preliminary findings. Moderate nutrient supplementation of mother's milk for preterm infants supports adequate bone mass and short-term growth: a randomized, controlled trial. Protein-energy oral supplementation in malnourished nursing-home residents. A controlled trial. Effects of maternal multiple micronutrient supplementation on fetal growth: a double-blind randomized controlled trial in rural Burkina Faso. Effect of varying protein intake on energy balance, protein balance and estimated weight gain composition in premature infants.
This randomized controlled trial of nutritional supplementation in pregnancy, in a poor black urban population in the United States, aimed to increase the birth weight and influence the postnatal development of the offspring of mothers at high risk of having low birth weight infants. The execution of the research design and adherence to the treatment regimen among the experimental population appeared adequate for a reasonable test of the treatments. At birth, the only significant favorable effect of supplementation observed was the prevention of depressed birth weight among the offspring of mothers who smoked heavily. With balanced protein-calorie supplementation, length of gestation was increased, the proportion of low-birth-weight infants reduced, and mean birth weight raised by 41 gm (not statistically significant). With high protein supplementation, there was an excess of very early premature births and associated neonatal deaths, and there was significant growth retardation up to 37 weeks of gestation. At 1 year of age, significant effects of high protein supplement were found on three psychological measures: visual habituation, visual dishabituation, and mean length of free play episodes. These measures were unrelated to measures of growth at birth and at 1 year of age. There were no detectable residual adverse effects of high protein supplementation at 1 year of age. Prenatal multiple micronutrient (MMN) or balanced energy and protein supplementation has a limited effect on birth size of the offspring.
                The objective was to determine whether a prenatal MMN-fortified food supplement (FFS) improves anthropometric measures at birth compared with supplementation with an MMN pill alone.
                We conducted a nonblinded, individually randomized controlled trial in 1296 pregnant women in 2 villages in rural Burkina Faso. Supplements were provided on a daily basis, and compliance was closely verified by using a community-based network of home visitors.
                Anthropometric measures at birth were available for analysis for 87% of the 1175 live singleton deliveries enrolled. After adjustment for gestational age at birth, the FFS group had a significantly higher birth length (+4.6 mm; P = 0.001). FFS supplementation resulted in a modestly higher birth weight (+31 g; P = 0.197). Subgroup analyses showed clinically important treatment effects on birth length (+12.0 mm; P = 0.005) and on birth weight (+111 g; P = 0.133) for underweight [body mass index (in kg/m(2)) <18.5] pregnant women. Women with early pregnancy anemia who received FFS gave birth to longer newborns (+7.3 mm; P = 0.002) than did those who received MMN supplementation.
                The provision of FFS to pregnant women resulted in higher birth length than did MMN supplementation. For women with a suboptimal prepregnancy nutritional status, MMN supplementation should be complemented with a balanced energy and protein supplement to produce a clinical effect on birth size. The trial was registered at clinicaltrials.gov as NCT00909974. We investigated the influence of human milk protein and medium-chain triglyceride supplementations of human milk feedings on the growth of very low birth weight infants during their first weeks of life. A group of 44 preterm infants with birth weights of less than 1,520 g and a mean gestational age of 30.3 weeks was randomly divided into four groups to receive plain human milk or human milk supplemented with human milk protein (0.9 g/dL), with medium-chain triglycerides (1 g/dL), or with both. The medium-chain triglyceride oil supplementation did not influence the growth of these infants. The infants given supplementary protein gained weight faster during weeks 4 to 6 than those without (18.5 +/- 0.7 v 15.1 +/- 0.6 g/kg/d; mean +/- SEM; P = .001). After 4 weeks of age the infants given supplementary protein had a mean weight gain equal to the mean intrauterine rate, in contrast to the infants of the other groups, who grew more slowly until age 6 weeks. Furthermore, we found a correlation between serum albumin concentration and weight gain during the seventh week of life (P = .018). The length growth velocity for the infants with protein supplementation was 0.99 +/- 0.06 cm/wk (mean +/- SEM) and for those without 0.83 +/- 0.05 cm/wk (P = .043). There was no difference in growth of head circumference between the groups. We conclude that human milk protein supplementation improves the growth of small premature infants fed human milk, and that the protein concentration of bank milk is insufficient for their adequate growth. Growth, nutrient retention, and metabolic response were determined in low birth weight (LBW) infants fed daily protein and energy intakes, respectively, of 2.8 gm/kg and 119 kcal/kg (group 1), 3.8 gm/kg and 120 kcal/kg (group 2), and 3.9 gm/kg and 142 kcal/kg (group 3). The mean rates of both weight gain and nitrogen retention in group 1 were somewhat greater than intrauterine rates; plasma concentrations of transthyretin and albumin also were acceptable. Thus the lower protein intake appeared to be adequate. On the other hand, the rates of weight gain and nitrogen retention in groups 2 and 3 were greater than those in group 1, supporting the efficacy of the higher protein intake with respect to growth. However, blood urea nitrogen and plasma amino acid concentrations also were higher in groups 2 and 3; both were higher in group 2 than in group 3, reflecting the positive effect of the higher energy intake on protein utilization. This observation, combined with data from an earlier study, indicates that protein intakes in excess of 3 gm/100 kcal will not be utilized completely. Energy expenditure in group 3 was greater than in group 1 but not group 2, raising the possibility that protein intakes not utilized completely contribute to diet-induced thermogenesis. The higher energy intake in group 3 vs group 2 did not affect rate of weight gain significantly, but energy storage in group 3, and hence fat accretion, was greater than that of other groups. In all groups the ratio of protein accretion to fat accretion reflected dietary proportions of protein and energy. This study compares growth and body composition in preterm infants (< or =1750 g birth weight, < or =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. Premature infants weighing less than 1550 gm at birth were randomly assigned to receive one of three formulas identical in composition except for protein content (2.2, 2.7, and 3.2 gm.100 kcal-1) to determine the effects on growth, protein nutritional status, and behavior. Data collected for 2 weeks from the time of achieving an enteral energy intake of 100 kcal.kg-1.day-1 included measurements of weight, length, head circumference, and skin-fold thickness, and concentrations of plasma amino acids, serum total protein, prealbumin, retinol-binding protein, and urea nitrogen. In a subset of infants, behavior was assessed at the end of the feeding study with the Neonatal Behavior Assessment Scale. Except for the concentrations of plasma amino acids, there were no significant differences in growth or in other biochemical measurements among the three groups, but there were significant differences in the orientation, habituation, and stability clusters of the behavior assessment. Further, there were significant correlations between the plasma amino acid values and the behavioral clusters. These preliminary data suggest a relationship between protein intake in the neonatal period and behavioral outcome at the end of the feeding period in the absence of differences in growth and gross markers of protein nutritional status. The behavioral items noted to differ among the groups may indicate later cognitive outcome; detailed studies about behavioral responses to neonatal dietary intakes and later outcome seem indicated. Our objectives were 1) to determine whether moderate nutrient supplementation of mother's milk (MM) for preterm infants, in the form of a new multinutrient fortifier (MNF), would improve short-term growth and bone mineral content (BMC) when compared with supplementation with calcium and phosphorus alone; and 2) to investigate whether moderate calcium and phosphorus intakes, in the form of calcium glycerophosphate (CaGP), resulted in a BMC similar to that of term corrected infants. Twenty-five preterm infants fed MM were randomly assigned to receive either MM+MNF or MM+CaGP. A third group of infants fed preterm formula (PTF) served as a comparison group. Whole-body BMC and lean and fat mass were determined by dual-energy X-ray absorptiometry (DXA) at full-term age. Nitrogen retention and calcium, phosphorus, and zinc intakes were determined by using mass balance techniques. Nitrogen retention was significantly lower in the MM+CaGP group than in the PTF group as were both weight and length gain (weight gain: 16.6 +/- 1.6, 14.2 +/- 2.0, and 16.1 +/- 2.9 g x kg(-1) x d(-1); length gain: 1.1 +/- 0.2, 0.9 +/- 0.2, and 1.1 +/- 0.3 cm/wk for the MM+MNF, MM+CaGP, and PTF groups, respectively). Biochemical indexes of mineral status and bone turnover were normal. Conservative amounts of calcium and phosphorus, as CaGP, resulted in adequate BMC. Moderate amounts of protein, calcium, and phosphorus plus trace elements added to MM in the form of an MNF resulted in improved linear growth but did not provide any advantages to BMC when compared with supplementation with calcium and phosphorus alone. To validate a nutritional intervention programme for elderly people living in nursing homes.
                In a prospective, randomized, controlled study of 88 residents, we determined nutritional status at day 0 and day 60 using a record of dietary intake, anthropometry, hand-grip strength and mini-nutritional assessment. Dietary intake, grip strength and body weight were also recorded at day 30. We divided subjects into four groups according to their mini-nutritional assessment score. Those with a score 24 received no oral supplementation. Those at risk of malnutrition (with a score of 17-23.5) were randomized to oral supplementation. Those with a score <17 received oral supplementation. We recorded the amount of oral supplements consumed daily.
                Compliance with oral supplementation was good, and daily intake averaged about 400 kcal. The total energy intake on day 60 was significantly higher in both of the groups that received supplements. Following supplementation, most subjects at risk of malnutrition improved their mini-nutritional assessment score and increased their weight (by 1.4 +/- 0.5 kg). Neither the mini-nutritional assessment score nor weight improved in subjects at risk of malnutrition who did not receive supplements. Supplementation in the malnourished group resulted in a mean mini-nutritional assessment score increase (from 13.9 +/- 2.6 to 17.1 +/- 3.9) and a mean weight gain of 1.5 +/- 0.4 kg.
                Oral nutritional supplements are well accepted and result in increased daily protein and energy intake, body weight and nutritional status in most malnourished patients and in those at risk of malnutrition. Intrauterine growth retardation is a major predictor of child health in developing countries.
                We tested whether providing pregnant women with the UNICEF/WHO/UNU international multiple micronutrient preparation (UNIMMAP), rather than iron and folic acid alone, improved fetal growth and its correlates.
                An intention-to-treat, double-blind, randomized controlled trial including 1426 pregnancies was carried out in rural Burkina Faso. Tablet intake was directly observed.
                Pregnancy outcome was known in 96.3% of the participants. After adjustment for gestational age at delivery, both birth weight (52 g; 95% CI: 4, 100; P = 0.035) and birth length (3.6 mm; 95% CI: 0.8, 6.3; P = 0.012) were significantly higher in the UNIMMAP group. UNIMMAP had a differential effect by percentiles of birth weight and length distributions: the risk of large-for-gestational-age infants was higher in the UNIMMAP group (OR: 1.58; 95% CI: 1.04, 2.38; P = 0.03), although the risk of low birth weight remained unchanged. The effect of UNIMMAP on birth size was modified by maternal body mass index at enrollment and could be more important in multiparous women and women taking sulfadoxine-pyrimethamine. Unexpectedly, the risk of perinatal death was marginally significantly increased in the UNIMMAP group (OR: 1.78; 95% CI: 0.95, 3.32; P = 0.07), and this seemed to affect mainly primiparous women (OR: 3.44; 95% CI: 1.1, 10.7; P for interaction = 0.11).
                Maternal UNIMMAP modestly but significantly increased fetal growth. The resulting benefit on infant growth and survival needs to be assessed. The possible lack of benefit and potential harm in primiparous women should be further investigated. This trial was registered at clinicaltrials.gov as NCT00642408. We studied the effect of varying only protein intake on energy balance, protein balance and estimated weight gain composition in premature infants fed either a formula with a protein content of 2.0 g/100 ml (F2) or a protein content of 1.5 g/100 ml (F1.5).
                Premature infants were randomly allocated to receive F1.5 or F2. Weight gain composition was estimated from protein and energy balances. Energy expenditure was measured with doubly labelled water.
                F1.5, n = 8; gestational age 32 +/- 3 weeks, birth weight 1716 +/- 560 g. F2, n = 8; gestational age 32 +/- 3 weeks, birth weight 1544 +/- 488 g.
                Infants fed F2 showed a significantly higher protein accretion (P = 0.003) and weight gain (P = 0.011) when compared to the infants fed F1.5. There were no differences in the energy balance. The estimated weight gain composition was different between both groups.
                The F2 fed infants had an estimated weight gain composition comparable to the reported intrauterine values, while the F1.5 fed infants showed a weight gain composition more comparable to the reported values of the full term infant. The impact of nutrient composition in premature infant formulas on body composition and growth is discussed.
This review provides encouraging evidence that antenatal nutritional advice with the aim of increasing energy and protein intake in the general obstetric population appears to be effective in reducing the risk of preterm birth, increasing head circumference at birth and increasing protein intake, there was no evidence of benefit or adverse effect for any other outcome reported.
Balanced energy and protein supplementation seems to improve fetal growth, and may reduce the risk of stillbirth and infants born small-for-gestational age. High-protein supplementation does not seem to be beneficial and may be harmful to the fetus. Balanced-protein supplementation alone had no significant effects on perinatal outcomes.
The results of this review should be interpreted with caution, the risk of bias was either unclear or high for at least one category examined in several of the included trials and the quality of the evidence was low for several important outcomes. Also the anthropometric characteristics of the general obstetric population is changing, therefore, those developing interventions aimed at altering energy and protein intake should ensure that only those women likely to benefit are included. Large, well designed randomised trials are needed to assess the effects of increasing energy and protein intake during pregnancy in women whose intake is below recommended levels.