What are the age‑specific reference ranges for routine hematology and basic chemistry laboratory values in pediatric patients, from neonates through adolescents?

Age-Specific Pediatric Blood Parameter Reference Ranges

Laboratories must use age-specific, analyzer-specific, and reagent-specific reference ranges when interpreting pediatric blood parameters, as applying adult reference ranges to children will misclassify approximately 30% of healthy children as abnormal. 1, 2

Critical Principles for Pediatric Laboratory Interpretation

The concept of "developmental hemostasis" applies broadly to pediatric laboratory values—physiological differences in blood parameters evolve dramatically with age from the neonatal period through adolescence. 1 This creates three essential requirements:

• Use standardized age groupings: neonates, 1 month to 1 year, 1-5 years, 6-10 years, and 11-16 years, which reflect statistically different physiological states 1, 2
• Match analyzer and reagent systems: Only use published reference ranges established with the identical analyzer and reagent system used in your laboratory, as both reagent-specific and analyzer-specific differences significantly impact results 1
• Never extrapolate adult ranges: Population-specific, reagent-specific, and analyzer-specific differences have all been demonstrated to cause systematic misdiagnosis 1

Hematology Reference Ranges by Age Group

Neonatal Period (Birth to 28 Days)

Hemoglobin and Hematocrit values in neonates depend on both gestational age (GA) and postnatal age (PNA), requiring mathematical modeling for accurate interpretation. 3

• Hemoglobin concentration and hematocrit must be interpreted using quadratic functions that incorporate both GA (22-42 weeks) and PNA (0-28 days) as independent variables 3
• Fetal hemoglobin (HbF) predominates during this period, making hemoglobin electrophoresis patterns completely different from older children 4
• Critical pitfall: Hemoglobin A2 measurement should never be performed for definitive thalassemia diagnosis until 6 months of age, when hemoglobin patterns have stabilized 4

Infants (1 Month to 1 Year)

Reference intervals for 1-year-old children show no significant sex differences, allowing combined reference ranges for both boys and girls at this age. 5

• Hematology parameters at 1 year of age can be established using community-based healthy children as reference populations 5
• Iron status varies significantly based on feeding method during the first 6 months: formula-fed infants show higher iron, ferritin, and transferrin saturation compared to breastfed infants 5
• Further studies are required to better delineate changes within the <1-year-old age group, as this represents a period of rapid physiological transition 1

Children (1-5 Years, 6-10 Years)

Using adult reference ranges for the APTT assay in 1-5 year olds would incorrectly classify approximately 30% of healthy children as abnormal. 1

• Reticulocyte parameters (CHr/Ret-He, Delta-He, IRF) and hypochromic RBC percentages require age-specific reference ranges in children 6 months to 18 years 6
• Reticulocyte hemoglobin content (CHr) shows no significant gender variation across all pediatric age groups (median 30.8 ± 1.7 pg) 6
• Red blood cell parameters exhibit an increasing trend with age, while leukocytes, lymphocytes, basophils, and platelets show a slight decrease with age 7

School-Age Children (6-12 Years)

In the 6-12 year age range, specific partitioning requirements exist for different parameters:

• Hematocrit and MCV require both age and sex partitioning 7
• Hemoglobin and erythrocyte counts require age partitioning only 7
• MCH, MCHC, platelets, and white blood cell counts remain stable across this age span and do not require partitioning 7

Adolescents (11-16 Years)

Sex-specific differences emerge prominently during adolescence:

• Delta-He, immature reticulocyte fraction (IRF), and percentage of hypochromic red blood cells (%Hypo) show statistically significant gender differences in the 12-17 years group 6
• This age group represents the transition toward adult reference ranges but still requires pediatric-specific values 1

Clinical Chemistry Reference Ranges

Common biochemistry analytes show age-dependent variations that require mathematical modeling using power variables in age, with modification by sex when appropriate. 8

• Reference intervals for 30 common biochemistry analytes have been established across 5 different analyzer types for children 30 days to <18 years of age 8
• Variations between analyzer types for most analytes fall within allowable total error limits, enabling some degree of harmonization 8
• Age-specific reference limits can be reported as mathematical functions of age and/or sex, allowing incorporation into laboratory information systems 8

Hemoglobin-Specific Clinical Thresholds

Beyond reference ranges, specific clinical thresholds guide transfusion decisions:

• Restrictive transfusion threshold of <70 g/L is appropriate for most stable, non-bleeding children 2
• Maintain hemoglobin >70 g/L even in conditions with limited oxygen delivery (septic shock, traumatic brain injury, post-cardiac surgery) 2
• Blood products in children should be prescribed by volume: 10 ml/kg of RBC transfusion increases hemoglobin by approximately 20 g/L 2

Critical Pitfalls to Avoid

The most common error is using adult reference ranges or published ranges from different analyzer/reagent systems, leading to systematic misdiagnosis. 1, 2

• Reagent-specific differences can reverse age-related patterns: APTT reference ranges decrease with age using PTT-A reagent but increase with age using Cephascreen reagent from the same manufacturer 1
• Misdiagnosis triggers unnecessary repeat testing, mixing studies, factor assays, and can lead to surgery cancellation, additional consultations, and long-term psychological impact on families 1
• If published data for your specific analyzer/reagent system are unavailable, consider referring samples to a laboratory that can provide age-appropriate reference ranges 1

Special Considerations for Premature Infants

Validated reference values for premature neonates, particularly very low-birth-weight infants, require urgent attention as neonatal care advances. 1

• The issue of validated reference values for all hemostatic proteins and assays in premature neonates deserves structured, age-related research 1
• New devices and techniques for hemostasis assessment must be approached with age-specific validation studies 1

When Laboratory Cannot Provide Age-Appropriate Ranges

If your laboratory cannot generate its own reference ranges and lacks published ranges for your specific analyzer/reagent system:

• Exercise extreme caution when performing and interpreting studies in children 1
• Strongly consider referral to a specialized pediatric laboratory that maintains population-, reagent-, and analyzer-specific reference ranges 1
• Never attempt to "adjust" adult ranges or use ranges from different systems, as this approach lacks scientific validity 1