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Background: The ideal quantity of dietary protein for formula-fed low birth weight infants is still a matter of debate. Protein intake must be sufficient to achieve normal growth without leading to negative effects such as acidosis, uremia, and elevated levels of circulating amino acids., Objectives: To determine whether higher (≥ 3.0 g/kg/d) versus lower (< 3.0 g/kg/d) protein intake during the initial hospital stay of formula-fed preterm infants or low birth weight infants (< 2.5 kilograms) results in improved growth and neurodevelopmental outcomes without evidence of short- or long-term morbidity. Specific objectives were to examine the following comparisons of interventions and to conduct subgroup analyses if possible. 1. Low protein intake if the amount was less than 3.0 g/kg/d. 2. High protein intake if the amount was equal to or greater than 3.0 g/kg/d but less than 4.0 g/kg/d. 3. Very high protein intake if the amount was equal to or greater than 4.0 g/kg/d., Search Methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8), in the Cochrane Library (August 2, 2019); OVID MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R) (to August 2, 2019); MEDLINE via PubMed (to August 2, 2019) for the previous year; and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (to August 2, 2019). We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-randomized trials., Selection Criteria: We included RCTs contrasting levels of formula protein intake as low (< 3.0 g/kg/d), high (≥ 3.0 g/kg/d but < 4.0 g/kg/d), or very high (≥ 4.0 g/kg/d) in formula-fed hospitalized neonates weighing less than 2.5 kilograms. We excluded studies if infants received partial parenteral nutrition during the study period, or if infants were fed formula as a supplement to human milk., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane and the GRADE approach to assess the certainty of evidence., Main Results: We identified six eligible trials that enrolled 218 infants through searches updated to August 2, 2019. Five studies compared low (< 3 g/kg/d) versus high (3.0 to 4.0 g/kg/d) protein intake using formulas that kept other nutrients constant. The trials were small (n = 139), and almost all had methodological limitations; the most frequent uncertainty was about attrition. Low-certainty evidence suggests improved weight gain (mean difference [MD] 2.36 g/kg/d, 95% confidence interval [CI] 1.31 to 3.40) and higher nitrogen accretion in infants receiving formula with higher protein content (3.0 to 4.0 g/kg/d) versus lower protein content (< 3 g/kg/d), while other nutrients were kept constant. No significant differences were seen in rates of necrotizing enterocolitis, sepsis, or diarrhea. We are uncertain whether high versus low protein intake affects head growth (MD 0.37 cm/week, 95% CI 0.16 to 0.58; n = 18) and length gain (MD 0.16 cm/week, 95% CI -0.02 to 0.34; n = 48), but sample sizes were small for these comparisons. One study compared high (3.0 to 4.0 g/kg/d) versus very high (≥ 4 g/kg/d) protein intake (average intakes were 3.6 and 4.1 g/kg/d) during and after an initial hospital stay (n = 77). Moderate-certainty evidence shows no significant differences in weight gain or length gain to discharge, term, and 12 weeks corrected age from very high protein intake (4.1 versus 3.6 g/kg/d). Three of the 24 infants receiving very high protein intake developed uremia., Authors' Conclusions: Higher protein intake (≥ 3.0 g/kg/d but < 4.0 g/kg/d) from formula accelerates weight gain. However, limited information is available regarding the impact of higher formula protein intake on long-term outcomes such as neurodevelopment. Research is needed to investigate the safety and effectiveness of protein intake ≥ 4.0 g/kg/d., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The ideal quantity of dietary protein for formula-fed low birth weight infants is still a matter of debate. Protein intake must be sufficient to achieve normal growth without negative effects such as acidosis, uremia, and elevated levels of circulating amino acids., Objectives: To determine whether higher (≥ 3.0 g/kg/d) versus lower (< 3.0 g/kg/d) protein intake during the initial hospital stay of formula-fed preterm infants or low birth weight infants (< 2.5 kilograms) results in improved growth and neurodevelopmental outcomes without evidence of short- and long-term morbidity.To examine the following distinctions in protein intake. 1. Low protein intake if the amount was less than 3.0 g/kg/d. 2. High protein intake if the amount was equal to or greater than 3.0 g/kg/d but less than 4.0 g/kg/d. 3. Very high protein intake if the amount was equal to or greater than 4.0 g/kg/d.If the reviewed studies combined alterations of protein and energy, subgroup analyses were to be carried out for the planned categories of protein intake according to the following predefined energy intake categories. 1. Low energy intake: less than 105 kcal/kg/d. 2. Medium energy intake: greater than or equal to 105 kcal/kg/d and less than or equal to 135 kcal/kg/d. 3. High energy intake: greater than 135 kcal/kg/d.As the Ziegler-Fomon reference fetus estimates different protein requirements for infants based on birth weight, subgroup analyses were to be undertaken for the following birth weight categories. 1. < 800 grams. 2. 800 to 1199 grams. 3. 1200 to 1799 grams. 4. 1800 to 2499 grams., Search Methods: The standard search methods of the Cochrane Neonatal Review Group were used. MEDLINE, CINAHL, PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library) were searched., Selection Criteria: Randomized controlled trials contrasting levels of formula protein intake as low (< 3.0 g/kg/d), high (≥ 3.0 g/kg/d but < 4.0 g/kg/d), or very high (≥ 4.0 g/kg/d) in formula-fed hospitalized neonates weighing less than 2.5 kilograms were included. Studies were excluded if infants received partial parenteral nutrition during the study period or were fed formula as a supplement to human milk. Studies in which nutrients other than protein also varied were added in a post-facto analysis., Data Collection and Analysis: The standard methods of the Cochrane Neonatal Review Group were used., Main Results: Five studies compared low versus high protein intake. Improved weight gain and higher nitrogen accretion were demonstrated in infants receiving formula with higher protein content while other nutrients were kept constant. No significant differences were seen in rates of necrotizing enterocolitis, sepsis, or diarrhea.One study compared high versus very high protein intake during and after an initial hospital stay. Very high protein intake promoted improved gain in length at term, but differences did not remain significant at 12 weeks corrected age. Three of the 24 infants receiving very high protein intake developed uremia.A post-facto analysis revealed further improvement in all growth parameters in infants receiving formula with higher protein content. No significant difference in the concentration of plasma phenylalanine was noted between high and low protein intake groups. However, one study (Goldman 1969) documented a significantly increased incidence of low intelligence quotient (IQ) scores among infants of birth weight less than 1300 grams who received a very high protein intake (6 to 7.2 g/kg)., Authors' Conclusions: Higher protein intake (≥ 3.0 g/kg/d but < 4.0 g/kg/d) from formula accelerates weight gain. However, limited information is available regarding the impact of higher formula protein intake on long-term outcomes such as neurodevelopmental abnormalities. Available evidence is not adequate to permit specific recommendations regarding the provision of very high protein intake (> 4.0 g/kg/d) from formula during the initial hospital stay or after discharge.

Background: The ideal quantity of dietary protein for formula-fed low birth weight infants < 2.5 kilograms is still a matter of controversy and debate. In premature infants, the protein intake must be sufficient to achieve normal growth without negative effects such as acidosis, uremia, and elevated levels of circulating amino acids (e.g. phenylalanine levels). This systematic review evaluates the benefits and risks of higher (>= 3.0 g/kg/day) versus lower (< 3.0 g/kg/day) protein intakes during the initial hospital stay of formula-fed preterm infants < 2.5 kilograms., Objectives: To determine whether higher (>= 3.0 g/kg/day) versus lower (< 3.0 g/kg/day) protein intakes during the initial hospital stay of formula-fed preterm infants < 2.5 kilograms result in improved growth and neurodevelopmental outcomes without evidence of short and long-term morbidity., Search Strategy: Two review authors searched MEDLINE (1966 - May 2005), CINAHL (1982 - May 2005), PubMed (1966 - May 2005), EMBASE (1980 - May 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2005), abstracts, conferences and symposia proceedings from Society of Pediatric Research, and American Academy of Pediatrics. Cross references were reviewed independently for additional relevant titles and abstracts for articles up to fifty years old., Selection Criteria: Randomized controlled trials contrasting levels of formula protein intakes as low (< 3.0 g/kg/day), high (=> 3.0 g/kg/day but < 4.0 g/kg/day), or very high protein intake (=> 4.0 g/kg/day) during hospitalization of neonates less than 2.5 kilograms at birth who were formula-fed. Studies were not included if infants received partial parenteral nutrition during the study period or were fed formula as a supplement to human milk. Given the small number of studies that met all inclusion criteria, studies in which nutrients other than protein also varied (> 10% relative difference) were added in a post-facto analysis., Data Collection and Analysis: Two review authors used standard methods of the Cochrane Collaboration and of the Cochrane Neonatal Review Group to independently assess trial eligibility and quality, and extracted data. In a 3-arm trial where two groups fell within the same predesignated protein intake group, weighted means and pooled standard deviations were calculated., Main Results: The literature search identified 37 studies, of which five met all the inclusion criteria. All five studies compared low (< 3.0 g/kg/day) to high protein intakes (=> 3.0 g/kg/day but < 4.0 g/kg/day). The overall analysis revealed an improved weight gain (WMD 2.36 g/kg/day, 95% CI 1.31, 3.40) and higher nitrogen accretion (WMD 143.7 mg/kg/day, 95% CI 128.7, 158.8) in infants receiving formula with higher protein content while other nutrients were kept constant. None of the studies reported IQ or Bayley scores at 18 months or later. No significant differences were seen in rates of necrotizing enterocolitis, sepsis or diarrhea. Of three studies included in the post-facto analysis, only one could be included in the meta-analysis. The post-facto analysis revealed further improvement in all growth parameters in infants receiving formula with higher protein content (weight gain: WMD 2.53 g/kg/day, 95% CI 1.62, 3.45, linear growth: WMD 0.16 cm/week, 95% CI 0.03, 0.30, and head growth: WMD 0.23, 95% CI 0.12, 0.35). There was no significant difference (WMD 0.25, 95% CI -0.20, 0.70) in the concentration of plasma phenylalanine between the high and low protein intake groups. One study (Goldman 1969) in the post-facto analysis documented a significantly increased incidence of low IQ scores, below 90, in infants of birth weight less than 1300 grams who received a very high protein intake (6 to 7.2 g/kg/day)., Authors' Conclusions: This systematic review suggests that higher protein intake (=> 3.0 g/kg/day but < 4.0 g/kg/day) from formula accelerates weight gain. Based on increased nitrogen accretion rates, this most likely indicates an increase in lean body mass. Although accelerated weight gain is considered to be a positive effect, increase in other outcome measures examined may represent a negative or ambivalent effect. These include elevated blood urea nitrogen levels and increased metabolic acidosis. Limited information was available regarding the impact of higher formula protein intakes on long term outcomes such as neurodevelopmental abnormalities. As determined in this review, existing research literature on this topic is not adequate to make specific recommendations regarding the provision of very high protein intake (> 4.0 g/kg/day) from formula.

Nine hundred and eighty-six children (519 boys, 467 girls) who had chickenpox at least 1 year previously were examined for the presence of scars resulting from this disease. Ninety-six (18.5%) boys and 88 (18.8%) girls had chickenpox scars, giving rise to an overall prevalence of 18.7%. The scars were found on the face in 75 (40.8%), neck 2 (1.1%), shoulders 8 (4.3%), upper limbs 15 (8.2%), anterior thorax 50 (27.2%), abdomen 106 (57.6%), back 65 (35.3%), buttocks 9 (4.9%), and lower limbs 12 (6.5%) affected children. The mean number of scars in the 184 children was 2.8 (standard deviation 1.9). The scars were hyperpigmented in 32, hypopigmented in 160, depressed in 38, and hypertrophic in 32 children. Keloids were noted in two children.