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To determine whether reduced serum or plasma protein and micronutrient levels are common in children infected with the human immunodeficiency virus (HIV) and whether these levels are different in children with growth retardation compared to those with normal growth.

Children with perinatally acquired HIV infection and their HIV-uninfected siblings who were followed up in the Intensive Primary Care Clinic at the Johns Hopkins Children's Center

None listed.

Recruitment

Children with perinatally acquired HIV infection and their HIV-uninfected siblings who were followed up in the Intensive Primary Care Clinic at the Johns Hopkins Children's Center.  

Design

Case-control study. 

Blinding used

Assumed for laboratory measures.

Statistical Analysis

• Differences in mean growth and laboratory analyses were assessed by analysis of variance with Duncan pairwise comparison
• Chi-square analysis was used to identify differences in the frequency of micronutrient deficiencies between groups
• Energy and nutrient intake from 24-hour weighed food intake was compared with 24-hour dietary recall by means of paired T-test.

 

Timing of Measurements

During a 24-hour stay in the Pediatric Clinical Research Unit, blood samples were taken, growth measurements obtained and dietary intake assessed.

Dependent Variables

Blood work conducted by the pathology department of the Johns Hopkins Hospital:

• Serum total protein: Biuret method
• Albumin: Doumas bromcresol green dye-binding reaction
• Prealbumin: Methylometry
• Plasma zinc and selenium: Atomic absorption spectroscopy
• Serum vitamin A: High-performance liquid chromatography

Dietary intake assessed by 24-hour weighed food intake during the child's stay in the Pediatric Clinical Research Unit and also by 24-hour dietary recall of the previous day's dietary intake at home as provided by the parent and the child. Nutrient analysis was conducted using the Nutritionist IV software package (version 4.1, 1996). Nutrient levels were compared with the RDAs for each child according to his or her age. Caretakers were asked to report any micronutrient supplementation before the study.

• Dietary energy
• Dietary protein
• Dietary zinc
• Dietary selenium
• Dietary vitamin A.

Independent Variables

 Three comparison groups:

• HIV-infected with growth retardation defined as height or weight for age or weight for height Z-score of -1.5 or less based on National Center for Health Statistics growth standards (HIV+Gr)
• HIV-infected with normal growth defined as height and weight for age and weight for height Z-score greater than -1.5 based on NCHS standards (HIV+)
• HIV-uninfected with normal growth as defined above (HIV-).

Control Variables

• CD4 cell number: The two groups of HIV-infected children were distributed similarly among the CDC classification system (1994 system)
• Mean CD4 lymphocyte number was lower in the HIV+Gr group, but was not statistically significant.

• Initial N: 38 (21 boys; 17 girls)
• Attrition (final N): None
• Age
  • HIV+Gr: 7.2±2.2 years (mean ± standard deviation)
  • HIV+: 6.8±1.5 years
  • HIV-: 7.1±2.8 years
• Ethnicity: Not given
• Other relevant demographics
  • Disease information
    • All were afebrile and free of acute infection at the time of study
    • CD4 cell number
    • HIV+GR: 331±545
    • HIV+: 652±549.
• Anthropometrics
  • Height-for-age Z-score
    • HIV+Gr: -1.6±1.2^b
    • HIV+: -0.7±0.8
    • HIV-: 0.5±0.9^c.
  • Weight-for-age Z-score
    • HIV+Gr: -1.5±0.6^c
    • HIV+: -0.4±1.1
    • HIV-: 0.1±0.8^d.
  • Weight-for-height Z-score
    • HIV+Gr: -0.5±1.1
    • HIV+: 0.1±0.8
    • HIV-: 0.3±0.8.
• Location: Intensive Primary Care Clinic at the Johns Hopkins Children's Center, Baltimore, MD.

^b Significantly lower than HIV+ and HIV- (P<0.05)
^c Significantly greater than HIV+Gr and HIV+ (P<0.05)
^d Definition of this superscript was not given.

 Table Two: Plasma and Micronutrient Levels in Serum and Plasma

Variables	HIV+Gr	HIV+	HIV-	Normal Range
Serum Total Protein (g/L)	80±7y	86±10y	71±3	60-82
Albumin (g/L)	45±3	45±4	45±2	35-53
Prealbumin (g/L)	0.19±0.03	0.17±0.03	0.18±0.04	0.13±0.27 (-?)
Plasma zinc (umol/L)	13.0±2.8	12.7±1.7	13.0±1.7	8.4-23.0
Plasma Selenium (umol/L)	1.37±0.16	1.35±0.11	1.43±0.16	1.14-2.15
Serum Vitamin A (umol/L)	1.78±0.42z	1.47±0.35	1.40±0.35	1.05-3.32

^y Significantly different from HIV- (P<0.05)
^z Significantly different from HIV+ and HIV- (P<0.05).

Dietary Energy Intake Assessed by 24-Hour Weighed Diet (WD) and 24-Hour Dietary Recall (DR): Percentage RDA for Age

	24-Hour Weighed Diet	24-Hour Dietary Recall
HIV+Gr (N=9)	103±25	116±23x
HIV+ (N=18)	94±23	85±28
HIV- (N=10)	92±13	96±26

^x Mean is significantly different from the mean for HIV+ group (P<0.05).

Dietary Protein Intake Assessed by 24-Hour Weighed Diet (WD) and 24-Hour Dietary Recall (DR): Percentage RDA for Age

	24-Hour Weighed Diet	24-Hour Dietary Recall
HIV+Gr (N=9)	212±63	322±106y,z
HIV+ (N=18)	224±71	232±80
HIV- (N=10)	188±41	220±99

^y Mean is significantly different from the mean for HIV+ and HIV- groups (P<0.05)
^z Dietary recall is significantly different from kilocalorie count (P<0.02).

Other Findings

• Mean energy intake approximated the RDA for energy
• Mean protein intake exceeded the RDA for protein
• Only mean zinc intake was less than two-thirds of the RDA
• There were no significant differences between groups in the frequency for any nutrient studied.

• Abnormal serum or plasma protein or micronutrient levels were uncommon in this cohort of HIV-infected children, even in children with growth retardation
• These findings suggest that routine monitoring of the level of proteins and micronutrients studied is unnecessary in the absence of specific clinical indicators of deficiency.

Government:

NIH

This reviewer has concerns regarding the authors' second conclusion statement regarding routine monitoring. The children were afebrile and free of acute infection at the time of study. It is well known that fever and infection alters metabolism and can also negatively influence micronutrient status. These changes, due to the presence of infection, may occur before clinical signs of a nutrient deficiency occur. So, based upon the reviewers experience, it seems that monitoring would be warranted in the case of a child who is undergoing an opportunistic infection.

It was not clear to the reviewer why the subjects were admitted to the Pediatric Clinical Research Unit and the length of admit was not mentioned. It was unclear whether the children were admitted for study purposes or if the child was admitted and then enrolled in the study.

• Body composition analyses is mentioned in the methods section, but then is not mentioned in the results or discussion
• The basis of free of acute infection is not given. Measurement of markers of inflammation may have been beneficial in addition to clinical symptoms of infection.
• There is no indication as to whether the investigators used fasting or non-fasting blood draws. Non-fasting blood collections will impact plasma zinc values.
• Limitations: The nutrient requirements of HIV-infected children may well be different from those of uninfected children, however and the nutrient intake demonstrated in our study may be insufficient for optimal growth and nutritional status. This is really the only limitation that is mentioned.
• Sources of funding were not disclosed.